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

NCT ID: NCT03901469

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-26
• Study Completion Date: 2024-03-07

Brief 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).

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ZEN003694

Intervention Type: DRUG

PO QD

Talazoparib

Intervention Type: DRUG

PO QD

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.

Group Type: EXPERIMENTAL

ZEN003694

Intervention Type: DRUG

PO QD

Talazoparib

Intervention Type: DRUG

PO QD

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.

Group Type: EXPERIMENTAL

ZEN003694

Intervention Type: DRUG

PO QD

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.

Group Type: EXPERIMENTAL

ZEN003694

Intervention Type: DRUG

PO QD

Talazoparib

Intervention Type: DRUG

PO QD

Interventions

ZEN003694

PO QD

Intervention Type: DRUG

Talazoparib

PO QD

Intervention Type: DRUG

Other Intervention Names

ZEN-3694; Talzenna

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Newsoara Biopharma Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zenith Epigenetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Tennessee Oncology (Sarah Cannon)

Nashville, Tennessee, United States

MD Anderson

Houston, Texas, United States

Institut Jules Bordet

Anderlecht, , Belgium

UZ Leuven

Leuven, , Belgium

The First Affiliated Hosptial of Bengbu Medical College

Bengbu, Anhui, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Hunan Cancer Hospital

Changsha, Hunan, China

Affliated Hospital of Jining Medical University

Jining, Shandong, China

The Second People's Hospital of Neijiang

Neijiang, Sichuan, China

Tianjing Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

START Madrid

Madrid, , Spain

Countries

United States; Belgium; China; Spain

References

Kharenko OA, Patel RG, Calosing C, van der Horst EH. Combination of ZEN-3694 with CDK4/6 inhibitors reverses acquired resistance to CDK4/6 inhibitors in ER-positive breast cancer. Cancer Gene Ther. 2022 Jun;29(6):859-869. doi: 10.1038/s41417-021-00375-9. Epub 2021 Aug 12.

Reference Type: DERIVED

PMID: 34385584 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-003906-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ZEN003694-004

Identifier Type: -

Identifier Source: org_study_id