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

NCT03901469 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ZEN003694-0042018-003906-26
• Study Type: interventional
• Target: 115
• Locations: 4 countries
• Sites: 19

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

Keywords

TNBC; ZEN003694; ZEN-3694; Talazoparib; Breast Cancer; PARPi; poly ADP ribose polymerase; bromodomain; BETi

Outcome Measures

Primary Outcomes (4)

• Part 1 and Part 2: Number of Participants With Treatment-related Adverse Events (AE) and Treatment-related Serious Adverse Events (SAE)

  Cycle 1 Day 1 to 30 days post last dose (each cycle is 28 days) up to 22 months

• Part 1: Number of Participants With Dose-limiting Toxicities (DLT)

  Determination of DLT will be made during the first 28 days of treatment (i.e., Cycle 1) in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably or definitely related to study drug.

  Cycle 1, Up to 1 month

• Part 2: Clinical Benefit Rate (CBR)

  Percentage of patients with a best overall response of confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST v1.1

  From screening up to 18 months

• Expansion Cohort A: Objective Response Rate (ORR) by RECIST v1.1 (CR or PR)

  Percentage of participants with a confirmed complete response (CR) or partial response (PR) by RECIST 1.1

  From screening up to 18 months

Secondary Outcomes (12)

• Part 1, Expansion Cohorts A and C: Clinical Benefit Rate (CBR)

  From screening up to 18 months

• Part 1, Part 2, and Expansion Cohort C: Objective Response Rate (ORR)

  From screening up to 18 months

• Part 2, Expansion Cohorts A and C: Safety Profile of ZEN003694 in Combination With Talazoparib.

  From screening up to 18 months

• Part 1, Part 2, Expansion Cohorts A & C: Evaluate Median Progression-free Survival

  From screening up to 18 months

• Part 2, Expansion Cohorts A and C: Evaluate Duration of Response (DOR)

  From screening up to 18 months

Study Arms (4)

Part 1 and Part 2

EXPERIMENTAL

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; Drug: Talazoparib

Expansion Cohort A - Combination Treatment in post-TROP2-ADC patients

EXPERIMENTAL

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; Drug: Talazoparib

Expansion Cohort B - ZEN003694 Monotherapy

EXPERIMENTAL

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

Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patients

EXPERIMENTAL

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; Drug: Talazoparib

Interventions

ZEN003694 DRUG

PO QD

Also known as: ZEN-3694

Expansion Cohort A - Combination Treatment in post-TROP2-ADC patients; Expansion Cohort B - ZEN003694 Monotherapy; Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patients; Part 1 and Part 2

Talazoparib DRUG

PO QD

Also known as: Talzenna

Expansion Cohort A - Combination Treatment in post-TROP2-ADC patients; Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patients; Part 1 and Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Part 2 and Expansion only: Measurable disease per RECIST version 1.1

You may not qualify if:

• 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 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.
• 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
• 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)
• 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

Sponsors & Collaborators

• Zenith Epigenetics: lead
• Pfizer: collaborator
• Newsoara Biopharma Co., Ltd.: collaborator

Study Sites (19)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66203, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology (Sarah Cannon)

Nashville, Tennessee, 37203, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Institut Jules Bordet

Anderlecht, 1070, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

The First Affiliated Hosptial of Bengbu Medical College

Bengbu, Anhui, 233000, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

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

Guangzhou, Guangdong, 510289, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

Location

Affliated Hospital of Jining Medical University

Jining, Shandong, 272000, China

Location

The Second People's Hospital of Neijiang

Neijiang, Sichuan, 641100, China

Location

Tianjing Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

Location

START Madrid

Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 34385584 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Zenith Study Team
• Organization: Zenith Epigenetics

ZEN003694-004@zenithepigenetics.com

587-390-7865

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: April 3, 2019
• Study Start: June 26, 2019
• Primary Completion: March 7, 2024
• Study Completion: March 7, 2024
• Last Updated: October 7, 2025
• Results First Posted: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (8); CN (7); BE (2)