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PARP Inhibitor

ZEN003694 + Talazoparib for Triple Negative Breast Cancer (TNBC Trial)

Phase 2
Waitlist Available
Research Sponsored by Zenith Epigenetics
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Have received TROP2-ADC therapy for unresectable locally advanced or metastatic disease (Expansion Cohort A)
Must not have
Radiation to >25% of the bone marrow (Parts 1 and 2 only)
Prior anticancer therapy within 3 weeks from the start of study drug (except for nitrosoureas and mitomycin C within 6 weeks from start of study drug)
Timeline
Screening 3 weeks
Treatment Varies
Follow Up from screening up to 18 months
Awards & highlights

Summary

This trial is testing a new drug, ZEN003694, in combination with an existing drug, Talazoparib, in patients with Triple-Negative Breast Cancer (TNBC) who do not have BRCA1 or BRCA2 mutations. The trial has two parts: a dose escalation part to find the best dose of the new drug, and a Simon 2-Stage design part to test how well the combination works. There are three expansion cohorts testing different aspects of the combination.

Who is the study for?
Adults with triple-negative breast cancer (TNBC) that's advanced or returned and doesn't have BRCA1/2 mutations. They must have tried chemotherapy before, can't be candidates for hormone therapy, and should not have certain blood clotting medication use or untreated brain metastases. Specific cohorts include those who've had TROP2-ADC treatment or are naive to it.Check my eligibility
What is being tested?
The trial is testing ZEN003694 alone and combined with Talazoparib in TNBC patients. It has two parts: dose escalation to find safe levels, followed by a Simon 2-Stage design to assess effectiveness. There are three groups based on prior treatments like TROP2-ADC.See study design
What are the potential side effects?
Potential side effects aren't detailed here but may include typical reactions to cancer drugs such as nausea, fatigue, blood count changes, risk of infection, liver function issues, and possibly others specific to the study drugs' profiles.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am fully active or restricted in physically strenuous activity but can do light work.
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I have received TROP2-ADC therapy for my advanced or metastatic disease.
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My breast cancer is triple-negative and has spread or come back.
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I have undergone at least one chemotherapy treatment.
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My condition worsened despite previous treatments.
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I have undergone at least one round of chemotherapy.
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I've had treatment for advanced cancer but not with TROP2-ADC.
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My breast cancer is triple-negative and not responsive to hormones or HER2 treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I have not had radiation to more than 25% of my bone marrow.
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I haven't had cancer treatment in the last 3 weeks, or 6 weeks for specific drugs.
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I have been treated with a PARP inhibitor before.
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I have a genetic mutation in BRCA1 or BRCA2.
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I am taking oral blood thinners that target Factor Xa or Factor IIa.
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I have brain metastases that are getting worse, causing symptoms, or untreated.
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I have a wound, ulcer, or bone fracture that is not healing.
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My brain metastases have been stable and untreated for at least 3 months.
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My cancer got worse during platinum-based treatment.
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I have not had bone-targeted radionuclide therapy in the last 6 weeks.
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I am taking or will take medication that strongly affects certain liver enzymes.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~from screening up to 18 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and from screening up to 18 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Expansion Cohort A: Objective response rate (ORR) by RECIST v1.1 (CR or PR)
Part 1 and Part 2: Incidence of treatment-related adverse events (AE) and treatment-related serious adverse events (SAE)
Part 1: Incidence of dose-limiting toxicities (DLT)
+1 more
Secondary outcome measures
Part 1, Expansion Cohorts A and C: Clinical benefit rate (CBR)
Part 1, Part 2, Expansion Cohorts A and C: Evaluate median progression-free survival
Part 1, Part 2, and Expansion Cohort C: Objective response rate (ORR)
+8 more

Side effects data

From 2019 Phase 1 & 2 trial • 75 Patients • NCT02711956
75%
Visual impairment
25%
Haematuria
25%
Fatigue
25%
Weight decreased
25%
Enterococcal bacteraemia
25%
Pathological fracture
100%
80%
60%
40%
20%
0%
Study treatment Arm
DE A+B 36 mg ZEN003694 + Enzalutamide
DE/DC A+B 48 mg ZEN003694 + Enzalutamide
DE A+B 60 mg ZEN003694 + Enzalutamide
DE A+B 72 mg ZEN003694 + Enzalutamide
DE/DC A+B 96 mg ZEN003694 + Enzalutamide
DE A+B 120 mg ZEN003694 + Enzalutamide
DE A+B 144 mg ZEN003694 + Enzalutamide

Trial Design

4Treatment groups
Experimental Treatment
Group I: Part 1 and Part 2Experimental Treatment2 Interventions
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.
Group II: Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patientsExperimental Treatment2 Interventions
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.
Group III: Expansion Cohort B - ZEN003694 MonotherapyExperimental Treatment1 Intervention
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.
Group IV: Expansion Cohort A - Combination Treatment in post-TROP2-ADC patientsExperimental Treatment2 Interventions
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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
ZEN003694
2016
Completed Phase 2
~120
Talazoparib
2021
Completed Phase 2
~2770

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Breast cancer treatments often target specific molecular pathways to inhibit cancer cell growth and survival. BET inhibitors like ZEN003694 work by blocking the BET family of proteins, which are involved in regulating gene expression that promotes cancer cell proliferation. PARP inhibitors such as Talazoparib prevent the repair of DNA damage in cancer cells, leading to cell death, particularly in cells deficient in homologous recombination repair mechanisms. These targeted therapies are crucial for breast cancer patients as they offer more personalized treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.
Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.

Find a Location

Who is running the clinical trial?

Zenith EpigeneticsLead Sponsor
9 Previous Clinical Trials
497 Total Patients Enrolled
PfizerIndustry Sponsor
4,595 Previous Clinical Trials
12,868,655 Total Patients Enrolled
114 Trials studying Breast Cancer
36,195 Patients Enrolled for Breast Cancer
Newsoara Biopharma Co., Ltd.Industry Sponsor
7 Previous Clinical Trials
1,003 Total Patients Enrolled

Media Library

Talazoparib (PARP Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03901469 — Phase 2
Breast Cancer Research Study Groups: Expansion Cohort A - Combination Treatment in post-TROP2-ADC patients, Part 1 and Part 2, Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patients, Expansion Cohort B - ZEN003694 Monotherapy
Breast Cancer Clinical Trial 2023: Talazoparib Highlights & Side Effects. Trial Name: NCT03901469 — Phase 2
Talazoparib (PARP Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03901469 — Phase 2
~19 spots leftby Jul 2025