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Purpose

This is a two-part open label, non-randomized, Phase 2, study of ZEN003694 in combination with Talazoparib in patients with TNBC without germline mutations of BRCA1 or BRCA2. Part 1 is a dose escalation and Part 2 is a Simon 2-Stage design. There are 3 expansion cohorts: Expansion Cohort A (combination treatment in post-TROP2-ADC patients), Expansion Cohort B (ZEN003694 monotherapy), and Expansion Cohort C (combination treatment in TROP2-ADC-naive patients).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 locally advanced triple-negative breast cancer (estrogen receptor (ER) ≤10%; progesterone receptor (PR) ≤10%; and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) Expansion only: Histologically confirmed metastatic or recurrent, or locally advanced triple-negative breast cancer as defined by the most recent American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. 3. Patient is not a candidate for endocrine based therapy, based on Investigator judgement 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 locally advanced or metastatic disease, unless approved by the Sponsor (no limit on prior targeted anticancer therapies such as mechanistic target or rapamycin (mTOR) or CDK4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against CTL4 or VEGF.) Expansion Cohort A (combination treatment in post-TROP2-ADC patients): Have received TROP2-ADC therapy for unresectable locally advanced or metastatic disease. Expansion Cohort B (ZEN003694 monotherapy): Have had at least 1 prior systemic therapy for locally advanced or metastatic disease which may or may not have included a TROP2-ADC. Expansion Cohort C (combination treatment in TROP2-ADC-naive patients): Have had at least 1 prior systemic therapy for locally advanced or metastatic disease and who have not 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 either in the neoadjuvant or in the metastatic setting. For patients receiving platinum in the neoadjuvant setting, at least 6 months must have elapsed between the last dose of platinum-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 of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows. Strong inhibitors, inducers or substrates must be discontinued at least 7 days prior to the first administration of study drug. 5. Current or anticipated use within 7 days prior to the first administration of study drug, or during the study, of strong P-gp inhibitors. 6. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed 7. Prior anticancer therapy (chemotherapy, radiation, hormone therapy, immunotherapy or investigational agent) within 3 weeks from the start of study drug (except for nitrosoureas 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 previous participation in studies with the Sponsor's drug, ZEN003694); except for patients in Expansion Cohort B who received ZEN003694 monotherapy and are eligible to cross-over to 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 prior treatment-related toxicities except for alopecia, fatigue and Grade 2 neuropathy 14. Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture caused by a pre-existing pathological bone lesion) 15. Parts 1 and 2 only: Brain metastases not adequately treated and clinically stable (at the discretion of the Investigator) for at least 3 months prior to the start of study treatment, unless a shorter interval is approved by the Sponsor's Medical Monitor Expansion only: Progressive, symptomatic, or untreated brain metastases. CNS metastases treated definitively with surgery and/or radiation must be radiographically stable based on imaging at least 3 months after definitive treatment. CNS metastases requiring steroid doses equivalent to prednisone doses >10 mg daily or an increase in steroid 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Masking Description
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 and Part 2 		ZEN003694 will be administered PO QD with Talazoparib PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
  • Drug: ZEN003694
    PO QD
    Other names:
    • ZEN-3694
  • Drug: Talazoparib
    PO QD
    Other names:
    • Talzenna
Experimental
Expansion Cohort A - Combination Treatment in post-TROP2-ADC patients 		ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
  • Drug: ZEN003694
    PO QD
    Other names:
    • ZEN-3694
  • Drug: Talazoparib
    PO QD
    Other names:
    • Talzenna
Experimental
Expansion Cohort B - ZEN003694 Monotherapy 		ZEN003694 will be administered PO QD as monotherapy at the RP2D in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 PO QD with Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
  • Drug: ZEN003694
    PO QD
    Other names:
    • ZEN-3694
Experimental
Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patients 		ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.
  • Drug: ZEN003694
    PO QD
    Other names:
    • ZEN-3694
  • Drug: Talazoparib
    PO QD
    Other names:
    • Talzenna

More Details

Status
Active, not recruiting
Sponsor
Zenith Epigenetics

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.