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

  • STATUS
    Recruiting
  • End date
    May 27, 2024
  • participants needed
    179
  • sponsor
    Zenith Epigenetics
Updated on 4 October 2022
cancer
estrogen
measurable disease
breast cancer
progesterone
metastasis
immunohistochemistry
HER2
triple negative breast cancer
progesterone receptor
erbb2
estrogen receptor
BRCA1
BRCA2
vascular endothelial growth factor
triple-negative breast cancer
talazoparib

Summary

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).

Details
Condition Triple Negative Breast Cancer
Treatment Talazoparib, ZEN003694
Clinical Study IdentifierNCT03901469
SponsorZenith Epigenetics
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Females or males age ≥ 18 years (at time of signing informed consent)
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
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Society of Clinical Oncology/College of American Pathologists (ASCO/CAP)
guidelines
Patient is not a candidate for endocrine based therapy, based on Investigator judgement
Have a history of progressive disease despite prior therapy
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
Part 2 and Expansion only: Measurable disease per RECIST version 1.1

Exclusion Criteria

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
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)
Documented germline mutations of BRCA1 or BRCA2
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
Part 2 only: Patients with inflammatory breast cancer
Current or anticipated use within 7 days prior to the first administration of study drug, or during the study, of strong P-gp inhibitors
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
Parts 1 and 2 only: Radiation to >25% of the bone marrow
Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug
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
Prior treatment with a PARP inhibitor
QTcF interval > 470 msec
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
Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture caused by a pre-existing pathological bone lesion)
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
Expansion only: Disease initially diagnosed with expression of estrogen receptor (ER) or progesterone receptor (PR) as ≥5%
Expansion only: Patients treated with prior endocrine therapy
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