Study to Evaluate Sacituzumab Govitecan in Combination With Talazoparib in Patients With Metastatic Breast Cancer.

Inclusion Criteria:

• Adult (≥ 18 years of age).

• Histologically confirmed stage IV (metastatic) breast cancer.

• Participants must have biopsy proven ER negative (ER-), PR negative (PR-), HER2negative, invasive breast cancer, by AJCC 7th edition staging. ER, PR, and HER2positivity would be determined per institutional (local) guidelines.

• Pre- and postmenopausal women are eligible.

• ECOG performance status = 0-1

• Measurable disease as per RECIST Version 1.1.

• Ability to understand and the willingness to sign a written informed consentdocument. Patient has signed the Informed Consent (ICF) prior to any screeningprocedures being performed and is able to comply with protocol requirements.

• At least 2 weeks beyond treatment (chemotherapy, targeted therapy, immunotherapy,and/or radiation therapy) or major surgery and recovered from all acute toxicities (adverse events from prior anti-cancer agents need to be grade 1 or lower; grade 2alopecia or peripheral neuropathy is permitted).

• At least 2 weeks beyond corticosteroids (however, low dose corticosteroids <20 mgprednisone or equivalent daily are permitted).

• Patient has adequate bone marrow and organ function as defined by the followinglaboratory values at screening:

• Absolute neutrophil count ≥1.5 × 109/L

• Platelets ≥100 × 109/L

• Hemoglobin ≥10.0 g/dL

• INR ≤1.5

• creatinine clearance ≥60 mL/min

• In the absence of liver metastases, alanine aminotransferase (ALT) andaspartate aminotransferase (AST) <2.5 x ULN. If the patient has livermetastases, ALT and AST <5 x ULN

• Total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients withwell-documented Gilbert's Syndrome.

• Fasting plasma glucose <140 mg/dL / 7.7 mmol/L and Glycosylated Hemoglobin (HbA1c) ≤ 8% (both criteria must be met).

Exclusion Criteria:

• Participants who have had anti-cancer therapy including targeted therapy orchemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycinC) prior to entering the study, or those who have not recovered from adverse events (clinically significant grade 2 or higher adverse events; grade 2 alopecia orperipheral neuropathy is permitted) due to prior anti-cancer agents.

• Participants who have received prior irinotecan or ADC backbone with SN-38 ortopoisomerase-1 inhibitor.

• Participants with progressive CNS metastatic disease. Patients with stable CNSmetastasis would be eligible, provided mets radiologically stable for at least onemonth, and patient is not actively taking steroids (more than 20 mg of prednisone orequivalent dose).

• Current use of strong CYP3A inhibitors/inducers, or P-gp inhibitors within 7 daysprior to randomization. For a list of strong CYP3A inhibitors/inducers and P-gpinhibitors, refer to Appendix C.

• Uncontrolled inter-current illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements. Patient has impairment of gastrointestinal (GI) function orGI disease that may significantly alter the absorption of the study drugs (e.g.,ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorptionsyndrome, or small bowel resection).

• Clinically significant, uncontrolled heart disease and/or cardiac repolarizationabnormality including any of the following:

• History of angina pectoris, symptomatic pericarditis, coronary artery bypassgraft (CABG) or myocardial infarction within 6 months prior to study entry.

• Documented cardiomyopathy.

• History of cardiac failure, significant/symptomatic bradycardia, Long QTsyndrome, family history of idiopathic sudden death or congenital long QTsyndrome or any of the following:

• Known risk to prolong the QT interval or induce Torsade's de Pointes.

• Uncorrected hypomagnesemia or hypokalemia.

• Systolic Blood Pressure (SBP) >160 mmHg or <90 mmHg.

• Bradycardia (heart rate <50 at rest), by ECG or pulse.

• On screening, inability to determine the QTcF interval on the ECG (i.e.:unreadable or not interpretable) or QTcF >450 screening ECG.

• HIV-positive participants on combination antiretroviral therapy are ineligible.These participants are at increased risk of lethal infections when treated withmarrow-suppressive therapy. Appropriate studies will be undertaken in participantsreceiving combination antiretroviral therapy when indicated.

• Pregnant women are excluded from this study because the safety of study medicationsis not established in pregnant women.

• Women of child-bearing potential, defined as all women physiologically capable ofbecoming pregnant, or fertile men, unless they are using highly effective methods ofcontraception throughout the study and after study drug discontinuation (till 8weeks in women and six months in males, post-study). Male patient should not donatesperm while on treatment and up to 6 months after last dose. Women are consideredpost-menopausal and not of child bearing potential if they have had 12 months ofnatural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. ageappropriate, history of vasomotor symptoms) or have had surgical bilateraloophorectomy (with or without hysterectomy) or tubal ligation at least six weeksago. In the case of oophorectomy alone, only when the reproductive status of thewoman has been confirmed by follow up hormone level assessment is she considered notof child bearing potential. Highly effective contraception methods include:

• Total abstinence when this is in line with the preferred and usual lifestyle ofthe patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods ofcontraception.

• Female sterilization (have had surgical bilateral oophorectomy with or withouthysterectomy), total hysterectomy, or tubal ligation at least six weeks beforetaking study treatment. In case of oophorectomy alone, only when thereproductive status of the woman has been confirmed by follow up hormone levelassessment

• Use of oral, injected or implanted hormonal methods of contraception orplacement of an intrauterine device (IUD) or intrauterine system (IUS), orother forms of hormonal contraception that have comparable efficacy (failurerate <1%), for example hormone vaginal ring or transdermal hormonecontraception.

• In case of use of oral contraception, women should have been stable on the samepill for a minimum of 3 months before taking study treatment. Note: While oralcontraceptives are allowed, they should be used in conjunction with a barriermethod of contraception due to unknown effect of drug-drug interaction.