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Triple Negative Breast CancerPhase 2TNBCNCT03901469

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

A Phase 2 study testing ZEN003694 and Talazoparib in people with Triple Negative Breast Cancer, run by Zenith Epigenetics at 19 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
ZEN003694 and Talazoparib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
19 sitesin 4 countries
Study dates
26 Jun 2019to 7 Mar 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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
  • 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

Trial locations and contacts

19 sites in 4 countries.

19 sites in 4 countries

United States8 sites

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • MD Anderson

    Houston, Texas, 77030

  • Tennessee Oncology (Sarah Cannon)

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Kansas Cancer Center

    Westwood, Kansas, 66203

Other trials in United States

China7 sites

  • The First Affiliated Hosptial of Bengbu Medical College

    Bengbu, Anhui, 233000

  • Hunan Cancer Hospital

    Changsha, Hunan, 410000

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

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

    Guangzhou, Guangdong, 510289

  • Affliated Hospital of Jining Medical University

    Jining, Shandong, 272000

  • The Second People's Hospital of Neijiang

    Neijiang, Sichuan, 641100

  • Tianjing Medical University Cancer Institute & Hospital

    Tianjin, Tianjin Municipality, 300060

Other trials in China

Belgium2 sites

  • Institut Jules Bordet

    Anderlecht, 1070

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Spain2 sites

  • Vall d'Hebron Institute of Oncology (VHIO)

    Barcelona, 08035

  • START Madrid

    Madrid, 28050

Other trials in Spain

About this study

Official title: A Phase 2b Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer

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).

Being tested
ZEN003694, Talazoparib
Keywords
TNBC, ZEN003694, ZEN-3694, Talazoparib, Breast Cancer, PARPi, poly ADP ribose polymerase, bromodomain, BETi
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZEN003694Drug

    Also called ZEN-3694

    PO QD

  • TalazoparibDrug

    Also called Talzenna

    PO QD

Study groups in NCT03901469
Study groupRoleWhat they receive
Part 1 and Part 2ExperimentalZEN003694 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.
Receives: Drug: ZEN003694; Drug: Talazoparib
Expansion Cohort A - Combination Treatment in post-TROP2-ADC patientsExperimentalZEN003694 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.
Receives: Drug: ZEN003694; Drug: Talazoparib
Expansion Cohort B - ZEN003694 MonotherapyExperimentalZEN003694 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.
Receives: Drug: ZEN003694
Expansion Cohort C - Combination Treatment in TROP2-ADC-naïve patientsExperimentalZEN003694 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.
Receives: Drug: ZEN003694; Drug: Talazoparib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

  2. 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.

    Measured: Cycle 1, Up to 1 month

  3. 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

    Measured: From screening up to 18 months

  4. 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

    Measured: From screening up to 18 months

Secondary outcomes (12)

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

    Percentage of participants with a confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST 1.1

    Measured: From screening up to 18 months

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

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

    Measured: From screening up to 18 months

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

    Incidence of Treatment-related Adverse Events (AE) and Treatment-related Serious Adverse Events (SAE) in Part 2, Expansion Cohorts A and C

    Measured: From screening up to 18 months

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

    Median progression-free survival is the time from randomization to documented disease progression or death

    Measured: From screening up to 18 months

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

    For subjects with a confirmed response of PR or CR, duration of response is measured from the date of the first response until the time that overall disease progression (radiographic progressive disease or clinical deterioration) or death is documented.

    Measured: From screening up to 18 months

  6. Part 1 and Part 2: Measure the Pharmacokinetic Parameter (PK) of Cmax of ZEN003694 and ZEN003791 (Active Metabolite)

    Cmax is defined as the maximum or peak plasma concentration of drug (calculated from samples taken over a 4-hour or 8-hour time period). Cmax(0-8h) was calculated for Cycle 1, Day 1. Cmax(0-4h) was calculated for Cycle 2, Day 1. Pre-dose is time 0 for calculations.

    Measured: Part 1: Cycle 1 Day 1: Pre-dose, 15 min, 30 min, 1 hour, 2 hour, 4 hour, 6 hour, and 8 hours post-dose. Parts 1 & 2: Cycle 2 Day 1: Pre-dose, 1 hour, 2 hour, and 4 hours post-dose. (cycles are 28 days)

  7. Part 1 and Part 2: Measure the Pharmacokinetic (PK) Parameter of Combined AUC(0-4h or 0-8h) of ZEN003694 and ZEN003791 (Active Metabolite)

    AUC(0-4h or 0-8h) is defined as the area under the curve (plasma concentration of drug calculated from samples taken over a 4-hour or 8-hour time period). AUC(0-8h) was calculated for Cycle 1, Day 1. AUC(0-4h) was calculated for Cycle 2, Day 1. Pre-dose is time 0 for calculations.

    Measured: Part 1: Cycle 1 Day 1: Pre-dose, 15 min, 30 min, 1 hour, 2 hour, 4 hour, 6 hour, and 8 hours post-dose. Parts 1 & 2: Cycle 2 Day 1: Pre-dose, 1 hour, 2 hour, and 4 hours post-dose. (cycles are 28 days)

  8. Part 1 & 2: Measure Plasma Concentrations of Talazoparib.

    Plasma concentrations of talazoparib will be measured.

    Measured: Part 1: Cycle 1 Day 15: Pre-dose; Parts 1& 2 Cycle 2 Day 1: Pre-dose; Cycle 2 Day 15: Pre-dose (each cycle is 28 days)

  9. Expansion Cohorts A, B, and C: Measure Plasma Concentrations of ZEN003694 and the Active Metabolite ZEN003791.

    Plasma concentrations of ZEN003694 and the active metabolite ZEN003791 will be measured.

    Measured: Cycle 2 Day 1: Pre-dose, 1 hour, 2 hours, and 4 hours post-dose; Cycle 2 Day 15: Pre-dose (each cycle is 28 days)

  10. Expansion Cohorts A and C: Measure Plasma Concentrations of Talazoparib.

    Plasma concentrations of talazoparib will be measured.

    Measured: Cycle 2 Day 1: Pre-dose, Cycle 2 Day 15: Pre-dose (each cycle is 28 days)

  11. Part 2, Expansion Cohorts A and C: Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by EORTC QLQ-C30 for Overall Duration

    European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

    Measured: Screening and Day 1 of every 28-day Cycle, up to 18 months (Overall Duration)

  12. Part 2, Expansion Cohorts A and C: Change From Baseline in Breast Symptoms Scale as Assessed by the EORTC-QLQ-BR23

    European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much), higher scores=high level of symptom/problems.

    Measured: Screening and Day 1 of every 28-day Cycle, up to 18 months (Overall Duration)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2019
  2. Study start26 Jun 2019
  3. Primary completion7 Mar 2024
  4. Study completion7 Mar 2024

Why it stopped: Parts 1 and 2 and Expansion Cohort C were completed. Expansion Cohorts A and B were discontinued based on results from an interim futility analysis and not due to safety concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
115 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03901469
Sponsor's protocol ID
ZEN003694-004
Other IDs
2018-003906-26, 2018
Acronym
TNBC
Status last verified
Sep 2025
First submitted
22 Mar 2019
Last updated
7 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34385584

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZEN003694 and Talazoparib in people with Triple Negative Breast Cancer, run by Zenith Epigenetics at 19 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States, China, Belgium, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 and Part 2: Number of Participants With Treatment-related Adverse Events (AE) and Treatment-related Serious Adverse Events (SAE) (time frame: Cycle 1 Day 1 to 30 days post last dose (each cycle is 28 days) up to 22 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03901469, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2025.

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