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OP RESEARCH PRO00037866 / DB-1303-O-3002 NIRAVATH SCREENING	

Types:      Research Oncology Treatment
Synonyms:  PRE-SCREENING, METASTATIC BREAST CANCER , BASELINE

Screening	Repeat 1 time	Cycle length: 28 days	Day -28	Perform every 1 day x1			Research tolerance: -0/+0 days	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:  DB-1303-O-3002_Niravath
			Nursing Orders
  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Tissue screening informed consent must be signed before tumor tissue screening assessments.
		  	ONC NURSING COMMUNICATION 2	Interval: --	Occurrences: --	Comments:	Signed Informed Consent Form(s) - Main informed consent form must be signed before initiating all other screening assessments. If a procedure was completed as standard of care within 28 days of dosing prior to consent, this is permitted and does not need to be repeated. If the procedures to be repeated in C1D1 are performed within 7 days (3 days for safety laboratories) before C1D1 and the subject's condition has not changed, there is no need to repeat at C1D1, unless a specific procedure requires a narrower time window
		  	ONC NURSING COMMUNICATION 5	Interval: --	Occurrences: --	Comments:	Review of eligibility criteria
		  	ONC NURSING COMMUNICATION 6	Interval: --	Occurrences: --	Comments:	Medical, surgical, and cancer histories, including demographic information: including clinically significant diseases, surgeries, cancer history (including prior cancer therapies and procedures), reproductive status, smoking history, and use of alcohol and drugs of abuse will be recorded at screening. Demographic data, including date of birth (or age), sex, and self-reported race or ethnicity, will also be recorded. Medical history will include a directed series of questions.
		  	ONC NURSING COMMUNICATION 8	Interval: --	Occurrences: --	Comments:	Complete physical examination: A complete physical examination will include, at a minimum, assessments of the head, eyes, ears, nose, and throat, and the cardiovascular, dermatologic, musculoskeletal, respiratory, gastrointestinal, genitourinary, and neurologic systems. As part of the tumor assessment, physical examinations should include the evaluation of the presence and degree of enlarged lymph nodes, hepatomegaly, and splenomegaly.
		  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Tumor assessment: The same CT or MRI method of assessment should be used to characterize each identified and reported lesion at baseline, during the study and follow-up. Subjects who discontinue study treatment early for reasons other than disease progression will continue to undergo tumor assessments following the original schedule until the start of new systemic anticancer therapy, disease progression, death, lost to follow-up, or withdrawal of consent, whichever occurs first. Requirements and details for tumor assessments are provided in Section 8.1.1.
		  	ONC NURSING COMMUNICATION 12	Interval: --	Occurrences: --	Comments:	Ophthalmologic assessment: include visual acuity testing, and slit lamp examination at the SCN and EOT, and as clinically indicated during treatment
		  	ONC NURSING COMMUNICATION 15	Interval: --	Occurrences: --	Comments:	Concomitant medication
		  	ONC NURSING COMMUNICATION 14	Interval: --	Occurrences: --	Comments:	Tumor sample (for HER2 status):  A mandatory FFPE tumor sample must be provided, preferably obtained at the time of metastatic disease or later (most recent pre-randomization tumor sample).
		  	ONC NURSING COMMUNICATION 16	Interval: --	Occurrences: --	Comments:	Adverse events: collection of all AEs regardless of attribution should begin from the time of signing of the ICF until Safety FU visit. Only ongoing or new AEs related to study drug should be collected during the Long-term FU period. All AE/SAE and AESI that are ongoing at the Safety FU visit, whether related to study treatment, will be followed up in the follow-up period until recovery or return to baseline or become stable assessed by investigator, or death or lost to follow-up
		  	VITAL SIGNS - T/P/R/BP	Interval: --	Occurrences: --	Comments:	Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be assessed.
Blood pressure and pulse measurements will be assessed seated position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (e.g., television, cell phones).
		  	HEIGHT AND WEIGHT	Interval: --	Occurrences: --	Comments:	Initial infusion dose for each subject will be calculated based on the subject's weight at screening. If the subject's weight has changed by = ± 10%, the subject's dose will be recalculated based on the subject's updated weight.
		  	PULSE OXIMETRY	Interval: --	Occurrences: --	Comments:	If the SpO2 of SCN is performed within 3 days before C1D1 and the subject's condition has not changed, there is no need to repeat the SpO2 of C1D1.
			Nursing Orders
  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	At screening, ECGs will be obtained in triplicate. Subsequent ECGs will be performed in triplicate only if an abnormality is noted. When performed in triplicate, 3 individual ECG tracings should be obtained in succession within 10 minutes after being in a supine/semi-recumbent position for 5 minutes.
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	At screening, ECGs will be obtained in triplicate. Subsequent ECGs will be performed in triplicate only if an abnormality is noted. When performed in triplicate, 3 individual ECG tracings should be obtained in succession within 10 minutes after being in a supine/semi-recumbent position for 5 minutes.
		  	ECG 12-LEAD	Interval: --	Occurrences: --	Comments:	At screening, ECGs will be obtained in triplicate. Subsequent ECGs will be performed in triplicate only if an abnormality is noted. When performed in triplicate, 3 individual ECG tracings should be obtained in succession within 10 minutes after being in a supine/semi-recumbent position for 5 minutes.
		  	CT CHEST WO CONTRAST	Interval: --	Occurrences: --	Comments:	A non-contrast HRCT scan of the chest is preferred if feasible, otherwise a non-contrast CT is acceptable. The HRCT/CT chest scan will be performed for all subjects, in addition to standard CT/MRI scans of chest/abdomen/pelvis for tumor assessments. If both an HRCT/CT of the chest for assessment of ILD/pneumonitis and a diagnostic IV contrast enhanced chest CT scan for tumor response assessment (as part of chest-abdomen-pelvis imaging) are to be acquired in the same imaging session, HRCT/CT should be performed first. HRCT scans are acquired on study as and when ILD/pneumonitis is suspected/as clinically indicated.
		  	TRANSTHORACIC ECHOCARDIOGRAM COMPLETE W CONT STRAIN 3D IF NEEDED	Interval: --	Occurrences: --	Comments:	ECHO: perform either ECHO or MUGA to measure LVEF.
		  	NM X GATED BLOOD POOL SINGLE (MUGA RESTING)	Interval: --	Occurrences: --	Comments:	MUGA: perform either ECHO or MUGA to measure LVEF.
		  	SPIROMETRY	Interval: --	Occurrences: --	Comments:	Should include spirometry (minimum requirement of: FVC [L], FVC % predicted, FEV1 [L], FEV1 % predicted, FEV1/FVC %). DLCO will be performed (when feasible), but for subjects with prior severe and/or clinically significant pulmonary disorders, DLCO is a requirement
			Labs
  	TROPONIN	Interval: --	Occurrences: --	Comments:	Perform ONLY at LabCorp, Quest, or HM ECC sites.  Blood samples for troponin (preferably high-sensitivity troponin-T) analysis should also be collected at screening, at EOT and if at any time a subject reports signs or symptoms suggesting congestive heart failure, myocardial infarction, or other causes of myocyte necrosis. If ECG is abnormal, follow institutional guidelines.
		  	TROPONIN T	Interval: --	Occurrences: --	Comments:	Blood samples for troponin (preferably high-sensitivity troponin-T) analysis should also be collected at screening, at EOT and if at any time a subject reports signs or symptoms suggesting congestive heart failure, myocardial infarction, or other causes of myocyte necrosis. If ECG is abnormal, follow institutional guidelines.
		  	HIV 1/2 ANTIGEN/ANTIBODY, FOURTH GENERATION, WITH REFLEXES	Interval: --	Occurrences: --	Comments:	All patients will be tested for HIV locally prior to the inclusion into the study and if not in contradiction with local legislation; individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count GREATER than or EQUAL to 200/µL, and have an undetectable viral load
		  	HEPATITIS B SURFACE ANTIGEN	Interval: --	Occurrences: --	Comments:	If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available.
Patients with active HBV must have the following: 
o HBV DNA LESS than 500 IU/mL obtained within 28 days prior to initiation of study treatment. 
o Received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment (per local standard of care) for the length of the study. 
o If HBV DNA increases to GREATER than or EQUAL to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed.
		  	HEPATITIS B SURFACE ANTIBODY	Interval: --	Occurrences: --	Comments:	If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available.
Patients with active HBV must have the following: 
o HBV DNA LESS than 500 IU/mL obtained within 28 days prior to initiation of study treatment. 
o Received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment (per local standard of care) for the length of the study. 
o If HBV DNA increases to GREATER than or EQUAL to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed.
		  	HEPATITIS B CORE ANTIBODY TOTAL	Interval: --	Occurrences: --	Comments:	If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available.
Patients with active HBV must have the following: 
o HBV DNA LESS than 500 IU/mL obtained within 28 days prior to initiation of study treatment. 
o Received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment (per local standard of care) for the length of the study. 
o If HBV DNA increases to GREATER than or EQUAL to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed.
		  	HEPATITIS B VIRUS (HBV), QUANTITATIVE PCR	Interval: --	Occurrences: --	Comments:	If a participant has a positive HbsAg test and/or a positive total HbcAb test at screening, quantitative HbsAg and an HBV DNA test should be performed at screening. If local quantitative HbsAg test is not available, a qualitative HbsAg followed by quantitative HBV DNA can be performed as an alternative. Study treatment and procedures may proceed while HBV DNA is being processed, but results should be reviewed by the investigator as soon as they are available.
Patients with active HBV must have the following: 
o HBV DNA LESS than 500 IU/mL obtained within 28 days prior to initiation of study treatment. 
o Received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment (per local standard of care) for the length of the study. 
o If HBV DNA increases to GREATER than or EQUAL to 500 IU/mL, consultation with a hepatologist or gastroenterologist with specialty in HBV is recommended. The Medical Monitor is available to advise as needed.
		  	HEPATITIS C ANTIBODY	Interval: --	Occurrences: --	Comments:	If a patient has a positive HCV antibody test at screening, an HCV RNA test must also be performed to determine if the patient has an active HCV infection. Patients with a positive HCV antibody test at screening will undergo additional quantitative HCV RNA testing and must be tested locally at timepoints indicated.
				Day -7	Perform every 1 day x1			Research tolerance: -0/+0 days	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:  DB-1303-O-3002_Niravath
			Nursing Orders
  	ONC NURSING COMMUNICATION 10	Interval: --	Occurrences: --	Comments:	ECOG Performance Status
			Labs
  	CBC WITH PLATELET AND DIFFERENTIAL	Interval: --	Occurrences: --		  	ABSOLUTE NEUTROPHIL COUNT	Interval: --	Occurrences: --		  	COMPREHENSIVE METABOLIC PANEL	Interval: --	Occurrences: --		  	MAGNESIUM LEVEL	Interval: --	Occurrences: --		  	PHOSPHORUS LEVEL	Interval: --	Occurrences: --		  	LDH	Interval: --	Occurrences: --		  	PROTHROMBIN TIME WITH INR	Interval: --	Occurrences: --		  	PARTIAL THROMBOPLASTIN TIME (PTT)	Interval: --	Occurrences: --		  	URINALYSIS, AUTOMATED WITH MICROSCOPY	Interval: --	Occurrences: --	Comments:	including dipstick (pH, specific gravity, glucose, protein, ketones, and blood) and microscopic examination (sediment, RBCs, WBCs, casts, crystals, epithelial cells, and bacteria)
If urinary protein is GREATER than or EQUAL to 2+ on dipstick, then a 24-hour urine collection is required to check the total urinary protein. If there is an explanation for the positive dipstick result (e.g., menses), it should be recorded, and there is no need to perform further laboratory assessments. 
Urine dipstick for proteinuria must be LESS than 2+ within 7 days prior to initiation of study treatment. Patients discovered to have GREATER than or EQUAL to 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate LESS than 1 g of protein in 24 hours.
		  	HCG QUALITATIVE, SERUM SCREEN	Interval: --	Occurrences: --	Comments:	For female subjects of childbearing potential, a serum ß-HCG pregnancy test should be performed during the SCN (within 7 days prior to randomization) If the serum ß-HCG pregnancy test of SCN is performed within 3 days before C1D1, there is no need to repeat the urine pregnancy test of C1D1. Any positive urine pregnancy test result must be confirmed immediately using a serum test.