Protocol Index	

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OP RESEARCH PRO00037983 NCT05899608 WITH CARBOPLATIN AUC = 6 / ABRAXANE ZHANG	

Types:      Research Oncology Treatment
Synonyms:  SMT112-3003 - HARMONI-3

Cycle 1	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation. 
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion. Additionally, within 10 minutes post first infusion of ivonescimab/pembrolizumab on C1D1.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HIV 1/2 ANTIGEN/ANTIBODY, FOURTH GENERATION, WITH REFLEXES	Interval: --	Occurrences: --		  	SYPHILIS TREPONEMA SCREEN WITH RPR CONFIRMATION (REVERSE ALGORITHM)	Interval: --	Occurrences: --		  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	If the patient develops a Grade GREATER than or EQUAL to 3 irAE or infusion-related reaction, additional blood samples may be taken. For patients who develop infusion-related reaction, ADA sample should be collected at the end of infusion, if possible.
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Nursing Orders
  	ONC NURSING COMMUNICATION 59	Interval: --	Occurrences: --	Comments:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr  GREATER than 1.4
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 90 Minutes		  	CARBOplatin (PARAplatin) in sodium chloride 0.9% 150 mL chemo IVPB	AUC: 6 Use AUC	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 120 Minutes	Instructions:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr GREATER than 1.4.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	CARBOPLATIN 10 MG/ML INTRAVENOUS SOLUTION	Medications	 	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	150 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	150 mL	No	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Days 8,15	Perform every 7 days x2		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose						Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 2	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	If the patient develops a Grade GREATER than or EQUAL to 3 irAE or infusion-related reaction, additional blood samples may be taken. For patients who develop infusion-related reaction, ADA sample should be collected at the end of infusion, if possible.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Nursing Orders
  	ONC NURSING COMMUNICATION 59	Interval: --	Occurrences: --	Comments:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr  GREATER than 1.4
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 90 Minutes		  	CARBOplatin (PARAplatin) in sodium chloride 0.9% 150 mL chemo IVPB	AUC: 6 Use AUC	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 120 Minutes	Instructions:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr GREATER than 1.4.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	CARBOPLATIN 10 MG/ML INTRAVENOUS SOLUTION	Medications	 	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	150 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	150 mL	No	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Days 8,15	Perform every 7 days x2		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose						Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 3	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Nursing Orders
  	ONC NURSING COMMUNICATION 59	Interval: --	Occurrences: --	Comments:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr  GREATER than 1.4
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 90 Minutes		  	CARBOplatin (PARAplatin) in sodium chloride 0.9% 150 mL chemo IVPB	AUC: 6 Use AUC	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 120 Minutes	Instructions:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr GREATER than 1.4.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	CARBOPLATIN 10 MG/ML INTRAVENOUS SOLUTION	Medications	 	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	150 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	150 mL	No	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Days 8,15	Perform every 7 days x2		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose						Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 4	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Nursing Orders
  	ONC NURSING COMMUNICATION 59	Interval: --	Occurrences: --	Comments:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr  GREATER than 1.4
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 90 Minutes		  	CARBOplatin (PARAplatin) in sodium chloride 0.9% 150 mL chemo IVPB	AUC: 6 Use AUC	Route: intravenous	once over 30 Minutes for 1 dose			Offset: 120 Minutes	Instructions:	Use minimum serum creatinine 0.7 mg/dL for Carboplatin AUC dosing. HOLD and notify provider if SCr increase by GREATER than or EQUAL to 0.5 mg/dL from baseline or SCr GREATER than 1.4.	Ingredients:	Name	Type	Dose	Selected	Adds Vol.	CARBOPLATIN 10 MG/ML INTRAVENOUS SOLUTION	Medications	 	Main Ingredient	Yes	SODIUM CHLORIDE 0.9 % INTRAVENOUS SOLUTION	QS Base	150 mL	Yes	Yes	DEXTROSE 5 % IN WATER (D5W) INTRAVENOUS SOLUTION	QS Base	150 mL	No	Yes				Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled				Days 8,15	Perform every 7 days x2		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	MEASURE WEIGHT	Interval: --	Occurrences: --		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Chemotherapy
  	NAB-PACLItaxel (ABRAXANE) chemo infusion 100 mg/m2 (Treatment Plan)	Dose: 100 mg/m2	Route: intravenous	once over 30 Minutes for 1 dose						Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 5	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 6	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	If the patient develops a Grade GREATER than or EQUAL to 3 irAE or infusion-related reaction, additional blood samples may be taken. For patients who develop infusion-related reaction, ADA sample should be collected at the end of infusion, if possible.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 7	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 8,9	Repeat 2 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 10	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 11,12	Repeat 2 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 13	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	If the patient develops a Grade GREATER than or EQUAL to 3 irAE or infusion-related reaction, additional blood samples may be taken. For patients who develop infusion-related reaction, ADA sample should be collected at the end of infusion, if possible.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 14,15	Repeat 2 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 16	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 17 to 19	Repeat 3 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 20	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 21	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --	Comments:	If the patient develops a Grade GREATER than or EQUAL to 3 irAE or infusion-related reaction, additional blood samples may be taken. For patients who develop infusion-related reaction, ADA sample should be collected at the end of infusion, if possible.
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 22,23	Repeat 2 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 24	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 25 to 27	Repeat 3 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 28	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 29 to 31	Repeat 3 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 32	Repeat 1 time	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycles 33,34	Repeat 2 times	Cycle length: 21 days	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
Cycle 35	Repeat 1 time	Cycle length: 1 day	Day 1	Perform every 1 day x1		Appointment Requests
  	INFUSION APPOINTMENT REQUEST	Interval: --	Occurrences: --			Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 20	Interval: --	Occurrences: --	Comments:	Patient will be randomized in a 1:1 ratio to the following 2 treatment groups: 
• Group A: ivonescimab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by ivonescimab maintenance (31 cycles). 
• Group B: pembrolizumab + carboplatin + either paclitaxel or nab-paclitaxel Q3W for 4 cycles followed by pembrolizumab maintenance (31 cycles).
			Line Care
  	sodium chloride 0.9% flush 20 mL	Dose: 20 mL	Route: intravenous	PRN	Start: S					Line Care
  	sodium chloride 0.9 % infusion 250 mL	Dose: 250 mL	Route: intravenous	once @ 30 mL/hr for 1 dose	Start: S			Instructions:	To keep vein open.			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
On ivonescimab/pembrolizumab administration days, vital signs will be assessed within 30 minutes pre-infusion and within 10 minutes of the end of infusion. 
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Provider Communication
  	ONC PROVIDER COMMUNICATION 3	Interval: --	Occurrences: --	Comments:	Bone scan: Order as appropriate to confirm complete response (CR) or when progression of bone metastases is suspected.
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Outpatient Electrolyte Replacement Protocol
  	TREATMENT CONDITIONS 39	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Potassium level LESS than 3.5 mEq/L; 
3. Recent pre-infusion labs.   

Dosing is based on lab value.
o Serum potassium less than 3.0mEq/L, give 40mEq KCL IV or PO and contact MD/NP. 
o Serum potassium 3.0 to 3.2mEq/L, give 40mEq KCL IV or PO. 
o Serum potassium 3.3 to 3.4mEq/L, give 20mEq KCL IV or PO. 
o Serum potassium 3.5 mEq/L or greater, do not give potassium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
		  	TREATMENT CONDITIONS 40 	Interval: --	Occurrences: --	Comments:	The protocol applies only if the following is met. 
1. SCr LESS than 1.5; 
2. Magnesium level LESS than 1.6 mg/dL; 
3. Recent pre-infusion labs. 

Dosing is based on lab value. 
o Serum Magnesium less than 1.0 mg/dL, give 2 gram magnesium sulfate IV and contact MD/NP. 
o Serum Magnesium 1.0 to 1.2 mg/dL, give 2 gram magnesium sulfate IV. 
o Serum Magnesium 1.3 to 1.5 mg/dL, give 1 gram magnesium sulfate IV. 
o Serum Magnesium 1.6 mg/dL or greater, do not give magnesium replacement. 

If patient meets criteria, order THERAPY PLAN called "Outpatient Electrolyte Replacement". 
Sign electrolyte replacement order as Per protocol: cosign required.
			Pre-Medications
  	ondansetron (ZOFRAN) IV 16 mg	Dose: 16 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	fosaprepitant (EMEND) IVPB 150 mg	Dose: 150 mg	Route: intravenous	once over 30 Minutes for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.		  	dexAMETHasone (DECADRON) IV 10 mg	Dose: 10 mg	Route: intravenous	once for 1 dose	Start: S			Instructions:	Administer 30 mins prior to infusion.			Biologicals
  	INV-Ivonescimab/Pembrolizumab infusion (HARMONI3/Pro00037983/Zhang) 1 each	Dose: 1 each	Route: intravenous	once over 60 Minutes for 1 dose			Offset: 30 Minutes			Nursing Orders
  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Within 10 minutes post ivonescimab/pembrolizumab Infusion.
			Hematology & Oncology Hypersensitivity Reaction Standing Order
  	ONC NURSING COMMUNICATION 82	Interval: --	Occurrences: --	Comments:	Grade 1 - MILD Symptoms (cutaneous and subcutaneous symptoms only - itching, flushing, periorbital edema, rash, or runny nose)
1. Stop the infusion.
2. Place the patient on continuous monitoring.
3. Obtain vital signs.
4. Administer Normal Saline at 50 mL per hour using a new bag and new intravenous tubing.
5. If greater than or equal to 30 minutes since the last dose of Diphenhydramine, administer Diphenhydramine 25 mg intravenous once.
6. If less than 30 minutes since the last dose of Diphenhydramine, administer Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
7. Notify the treating physician.
8. If no improvement after 15 minutes, advance level of care to Grade 2 (Moderate) or Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Grade 2 - MODERATE Symptoms (cardiovascular, respiratory, or gastrointestinal symptoms - shortness of breath, wheezing, nausea, vomiting, dizziness, diaphoresis, throat or chest tightness, abdominal or back pain)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
6. Administer Normal Saline at 150 mL per hour using a new bag and new intravenous tubing.
7. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous), Cetirizine 10 mg orally and Famotidine 20 mg intravenous once.
8. If no improvement after 15 minutes, advance level of care to Grade 3 (Severe).
9. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	ONC NURSING COMMUNICATION 83	Interval: --	Occurrences: --	Comments:	Grade 3 – SEVERE Symptoms (hypoxia, hypotension, or neurologic compromise – cyanosis or O2 saturation less than 92%, hypotension with systolic blood pressure less than 90 mmHg, confusion, collapse, loss of consciousness, or incontinence)
1. Stop the infusion.
2. Notify the CERT team and treating physician immediately.
3. Place the patient on continuous monitoring.
4. Obtain vital signs.
5. If heart rate is less than 50 or greater than 120, or blood pressure is less than 90/50 mmHg, place patient in reclined or flattened position.
6. Administer Oxygen at 2 L per minute via nasal cannula. Titrate to maintain O2 saturation of greater than or equal to 92%.
7. Administer Normal Saline at 1000 mL intravenous bolus using a new bag and new intravenous tubing.
8. Administer Hydrocortisone 100 mg intravenous (if patient has allergy to Hydrocortisone, please administer Dexamethasone 4 mg intravenous) and Famotidine 20 mg intravenous once.
9. Administer Epinephrine (1:1000) 0.3 mg subcutaneous.
10. Assess vital signs every 15 minutes until resolution of symptoms or otherwise ordered by covering physician.
		  	diphenhydrAMINE (BENADRYL) injection 25 mg	Dose: 25 mg	Route: intravenous	PRN	Start: S				  	cetirizine (ZyrTEC) tablet 10 mg	Dose: 10 mg	Route: oral	once PRN	Start: S				  	famotidine (PEPCID) injection 20 mg	Dose: 20 mg	Route: intravenous	PRN	Start: S				  	hydrocortisone sodium succinate (Solu-CORTEF) injection 100 mg	Dose: 100 mg	Route: intravenous	PRN					  	dexAMETHasone (DECADRON) IV 4 mg	Dose: 4 mg	Route: intravenous	PRN					  	epINEPHrine (ADRENALIN) 1 mg/1 mL injection 0.3 mg	Dose: 0.3 mg	Route: subcutaneous	PRN	Start: S					Discharge Nursing Orders
  	ONC NURSING COMMUNICATION 76	Interval: --	Occurrences: --	Comments:	Discontinue IV.
			Discharge Nursing Orders
☑	sodium chloride 0.9 % flush 20 mL	Dose: 20 mL	Route: intravenous	PRN					☑	HEParin, porcine (PF) injection 500 Units	Dose: 500 Units	Route: intra-catheter	once PRN	Start: S			Instructions:	Concentration: 100 units/mL. Heparin flush for Implanted Vascular Access Device maintenance.			Discharge Nursing Orders
  	alteplase (CATHFLO) for NON Quinton and NON Hemodialysis Catheters 2 mg	Dose: 2 mg	Route: intra-catheter	once PRN	Start: S			Instructions:	HOLD and notify provider if Platelets LESS than 50.  Instill dose into occluded catheter. Do not force solution into
catheter. After a 30-minute dwell time, assess catheter function by attempting
to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood in
patients greater than or equal to 10 kg to remove Cathflo Activase and
residual clots. Gently irrigate the catheter with NS. If catheter remains
nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell
time: 120 minutes) and reassess function. If catheter function is not restored,
a second dose may be instilled					
EOT	Repeat 1 time	Cycle length: 29 days	Day 1	Perform every 1 day x1		Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Physical examination: Symptomatic and targeted when clinically indicated
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	ECOG performance status
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Vital signs: Blood pressure, heart rate, respiratory rate, temperature and oxygen saturation.
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication/concomitant therapy
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
		  	ONC NURSING COMMUNICATION 22	Interval: --	Occurrences: --	Comments:	Health-related quality of life (HRQoL) assessments: EQ-5D, EORTC QLQ C30, EORTC QLQ LC13
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	As clinically indicated
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	URIC ACID LEVEL	Interval: --	Occurrences: --		  	GGT	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	CREATINE KINASE, TOTAL (CPK)	Interval: --	Occurrences: --		  	TRIGLYCERIDES	Interval: --	Occurrences: --		  	CHOLESTEROL	Interval: --	Occurrences: --		  	C-REACTIVE PROTEIN	Interval: --	Occurrences: --		  	AMYLASE LEVEL	Interval: --	Occurrences: --		  	LIPASE LEVEL	Interval: --	Occurrences: --			Labs
  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --			Labs
  	TSH AND FREE T4	Interval: --	Occurrences: --			Labs
  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS B CORE ANTIBODY IGM	Interval: --	Occurrences: --	Comments:	As clinically indicated for patients with known or active hepatitis B. If applicable, subsequent testing per standard of care (e.g. hepatitis virus DNA levels) for
assessment of active hepatitis.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	HCV RNA test if the antibody test is positive. As clinically indicated.
			Labs
  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	If the patient shows proteinuria of 2+ or higher on urine dipstick or routine analysis, a 24-hour urine collection should be provided for further analysis
			Provider Communication
  	ONC PROVIDER COMMUNICATION 4	Interval: --	Occurrences: --	Comments:	Place separate order for 24-hour Urinalysis as needed.
			Labs
  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	Serum or urine pregnancy test: Women of childbearing age
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --		  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --					
Safety Follow-up (30 +7 days)	Repeat 1 time	Cycle length: 90 days	Day 1	Perform every 1 day x1		Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
			Imaging
☑	CT HEAD W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI BRAIN W CONTRAST	Interval: --	Occurrences: --	Comments:	CT or MRI brain with contrast : Performed if metastases at baseline or clinically indicated. Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☑	CT CHEST W CONTRAST ABDOMEN W CONTRAST PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI CHEST W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI ABDOMEN W WO CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
		☐	MRI PELVIS W CONTRAST	Interval: --	Occurrences: --	Comments:	CT scan or MRI chest, abdomen and pelvis with contrast: Imaging will not be adjusted for delays in treatment cycles and will be performed per calendar schedule (days on study). Enhanced if not contraindicated.
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --					
Safety Follow-up (90 ±7 days)	Repeat 1 time	Cycle length: 336 days	Day 1	Perform every 1 day x1		Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
			Labs
  	RESEARCH STUDY SPECIMEN	Interval: --	Occurrences: --					
Follow-up (every 12 weeks)	Repeat 1 time	Cycle length: 90 days	Day 1	Perform every 1 day x1		Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	AE/SAE evaluation
					
Survival Follow-up (every 90±14 days)	Repeat 1 time	Cycle length: 90 days	Day 1	Perform every 1 day x1		Provider Communication
  	ONC PROVIDER COMMUNICATION	Interval: --	Occurrences: --	Comments:	Please refer to Study Protocol for any questions or discrepancies. See Schedule of Events Calendar for sequence of diagnostic tests, examinations, and treatment administration: See Safety Parameters-for Toxicity Management and Dose Modification Guidelines: Protocol Access hyperlink  SMT112-3003_Zhang
		  	ONC PROVIDER COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Dose Modifications and Management for Ivonescimab/Pembrolizumab Treatment: Refer to Section 5.4.2.4: Dose Modifications for Ivonescimab/Pembrolizumab for Potential VEGF-related Adverse Events
Protocol Access Hyperlink : SMT112-3003_Zhang
			Nursing Orders
  	ONC NURSING COMMUNICATION 25	Interval: --	Occurrences: --	Comments:	Survival status
		  	ONC NURSING COMMUNICATION 30	Interval: --	Occurrences: --	Comments:	Additional anticancer therapy