A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer

Inclusion Criteria:

1. Females or males age ≥ 18 years (at time of signing informed consent)
2. Parts 1 and 2 only: Histologically confirmed metastatic or recurrent or locallyadvanced triple-negative breast cancer (estrogen receptor (ER) ≤10%; progesteronereceptor (PR) ≤10%; and HER2 negative by immunohistochemistry (IHC) or fluorescent insitu hybridization (FISH) Expansion only: Histologically confirmed metastatic or recurrent, or locally advancedtriple-negative breast cancer as defined by the most recent American Society ofClinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
3. Patient is not a candidate for endocrine based therapy, based on Investigatorjudgement
4. Have a history of progressive disease despite prior therapy
5. Part 1: Have had at least 1 prior cytotoxic chemotherapy. Part 2: Have had no more than 2 prior chemotherapy-inclusive regimens for locallyadvanced or metastatic disease, unless approved by the Sponsor (no limit on priortargeted anticancer therapies such as mechanistic target or rapamycin (mTOR) or CDK4/6inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonalantibodies against CTL4 or VEGF.) Expansion Cohort A (combination treatment in post-TROP2-ADC patients): Have receivedTROP2-ADC therapy for unresectable locally advanced or metastatic disease. Expansion Cohort B (ZEN003694 monotherapy): Have had at least 1 prior systemic therapyfor locally advanced or metastatic disease which may or may not have included aTROP2-ADC. Expansion Cohort C (combination treatment in TROP2-ADC-naive patients): Have had atleast 1 prior systemic therapy for locally advanced or metastatic disease and who havenot received prior TROP2-ADC therapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Part 2 and Expansion only: Measurable disease per RECIST version 1.1

Exclusion Criteria:

1. Documented germline mutations of BRCA1 or BRCA2
2. Parts 1 and 2 only: Evidence of disease progression during platinum treatment eitherin the neoadjuvant or in the metastatic setting. For patients receiving platinum inthe neoadjuvant setting, at least 6 months must have elapsed between the last dose ofplatinum-based treatment and enrollment
3. Part 2 only: Patients with inflammatory breast cancer
4. Current or anticipated use of medications known to be strong inhibitors or inducers ofCYP3A4 or substrates of CYP1A2 with narrow therapeutic windows. Strong inhibitors,inducers or substrates must be discontinued at least 7 days prior to the firstadministration of study drug.
5. Current or anticipated use within 7 days prior to the first administration of studydrug, or during the study, of strong P-gp inhibitors.
6. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxabanotamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Lowmolecular weight heparin is allowed
7. Prior anticancer therapy (chemotherapy, radiation, hormone therapy, immunotherapy orinvestigational agent) within 3 weeks from the start of study drug (except fornitrosoureas and mitomycin C within 6 weeks from start of study drug)
8. Parts 1 and 2 only: Radiation to >25% of the bone marrow
9. Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug
10. Have previously received an investigational BET inhibitor (including previousparticipation in studies with the Sponsor's drug, ZEN003694); except for patients inExpansion Cohort B who received ZEN003694 monotherapy and are eligible to cross-overto combination treatment
11. Prior treatment with a PARP inhibitor
12. QTcF interval > 470 msec
13. Insufficient recovery (i.e., has not recovered to at least Grade 1) from priortreatment-related toxicities except for alopecia, fatigue and Grade 2 neuropathy
14. Non-healing wound, ulcer or bone fracture (not including a pathological bone fracturecaused by a pre-existing pathological bone lesion)
15. Parts 1 and 2 only: Brain metastases not adequately treated and clinically stable (atthe discretion of the Investigator) for at least 3 months prior to the start of studytreatment, unless a shorter interval is approved by the Sponsor's Medical Monitor Expansion only: Progressive, symptomatic, or untreated brain metastases. CNSmetastases treated definitively with surgery and/or radiation must be radiographicallystable based on imaging at least 3 months after definitive treatment. CNS metastasesrequiring steroid doses equivalent to prednisone doses >10 mg daily or an increase insteroid doses due to CNS disease prior to consent are not eligible
16. Expansion only: Disease initially diagnosed with expression of estrogen receptor (ER)or progesterone receptor (PR) as ≥5%
17. Expansion only: Patients treated with prior endocrine therapy