Testing the Addition of Anti-Cancer Drug, ZEN003694 (ZEN-3694) and PD-1 Inhibitor (Pembrolizumab), to Standard Chemotherapy (Nab-Paclitaxel) Treatment in Patients With Advanced Triple-Negative Breast Cancer
A Phase 1b Trial of ZEN003694 (ZEN-3694) With Pembrolizumab and Nab-Paclitaxel in Patients With Metastatic Triple-Negative Breast Cancer
4 other identifiers
interventional
57
1 country
6
Brief Summary
This phase Ib trial tests the safety and tolerability of ZEN003694 in combination with an immunotherapy drug called pembrolizumab and the usual chemotherapy approach with nab-paclitaxel for the treatment of patients with triple negative-negative breast cancer that has spread to other parts of the body (advanced). Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Immunotherapy with monoclonal antibodies, such as pembrolizumab may help the body's immune system attach the cancer and may interfere with the ability of tumor cells to grow and spread. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Combination therapy with ZEN003694 pembrolizumab immunotherapy and nab-paclitaxel chemotherapy may help shrink or stabilize cancer for longer than chemotherapy alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2023
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2022
CompletedFirst Posted
Study publicly available on registry
June 21, 2022
CompletedStudy Start
First participant enrolled
May 18, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
May 13, 2026
April 1, 2026
3.9 years
June 16, 2022
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Maximum tolerated dose (MTD) of ZEN003694 (ZEN-3694) used in combination with pembrolizumab and nab-paclitaxel
A Bayesian optimal interval design will be used to identify the MTD.
Up to 28 days from start of treatment
Recommended phase 2 dose (RP2D) of ZEN003694 (ZEN-3694) used in combination with pembrolizumab and nab-paclitaxel
Will be for adverse events consistent with a dose-limiting toxicity definition.
Up to 28 days from start of treatment
Incidence of adverse events
Toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. Toxicities will be summarized by maximum grade and by treatment dose level. Incidence rate of each toxicity will be reported with 95% exact confidence intervals.
Up to 3 years from treatment start date
Secondary Outcomes (8)
Pharmacokinetics profile of the combination of ZEN003694 (ZEN-3694), pembrolizumab and nab-paclitaxel
Pre-dose & 2 hours (h) post-dose on cycle 0 day 1 (C0D1), C2D15, C4D1, & C6D8; pre-dose & 0.5h post-dose on C1D1; pre-dose & 0.5, 1, 2, 4, 6, 8 & 24h post-dose on C1D15
Recommended phase 2 dose (RP2D)
Up to 3 years
Overall response rate
From start of the treatment until disease progression/ recurrence, or for up to 3 years
PFS
From the time of study enrollment until the identification of disease progression or death, or for up to 3 years
Overall survival
From the time of study enrollment until death due to any cause, or for up to 3 years
- +3 more secondary outcomes
Other Outcomes (1)
Potential biomarker indicators of response and resistance to the triplet combination
Baseline up to on-treatment and post-treatment biopsies
Study Arms (2)
Dose Escalation (ZEN003694, nab-paclitaxel, pembrolizumab)
EXPERIMENTALPatients receive ZEN003694 PO QD on days 1-21, nab-paclitaxel IV over 30 minutes on day 1, 8, and 15, and pembrolizumab IV over 30 minutes every 21 days of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity with a maximum of 35 doses of pembrolizumab administered. Patients also undergo CT or MRI scan and collection of blood samples throughout the trial.
Dose Expansion (ZEN003694, nab-paclitaxel, pembrolizumab)
EXPERIMENTALPatients receive ZEN003694 PO QD on days 1-7 prior to combination therapy. Patients then receive ZEN003694 PO QD on days 1-21, nab-paclitaxel IV over 30 minutes on days 1, 8, and 15, and pembrolizumab IV over 30 minutes every 21 days of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity with a maximum of 35 doses of pembrolizumab administered. Patients also undergo biopsies on study, and CT or MRI scans and collection of blood samples throughout the trial.
Interventions
Given PO
Undergo CT
Undergo MRI
Given IV
Given IV
Undergo collection of blood samples
Undergo biopsy
Eligibility Criteria
You may qualify if:
- Participants must have a histologically or cytologically confirmed diagnosis of TNBC based on standard criteria for the disease:
- Estrogen receptor (ER) and progesterone receptor (PR) \< 10% by immunohistochemistry (IHC), and HER2-negative (per current American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guidelines)
- Patients who have not had ER, PR and HER2 testing and thus, ER, PR and HER2 status is unknown, are not eligible
- Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
- Participants must have disease that is unresectable locally advanced or metastatic
- DOSE ESCALATION COHORT: Known PD-L1 status is not required prior to study enrollment. Central PD-L1 testing (on archival tumor tissue) will occur retrospectively
- DOSE ESCALATION COHORT: Any number of prior lines of therapy are allowed in the metastatic setting. Prior immune checkpoint inhibitor allowed in any setting
- DOSE ESCALATION COHORT: Evaluable or measurable disease per RECIST 1.1 criteria
- DOSE EXPANSION COHORT: PD-L1 status must be negative. Standard local testing with any PD-L1 antibody that has been validated in a Clinical Laboratory Improvement Act (CLIA)- certified environment will be acceptable for including patients on trial. Primary or metastatic samples may be tested for PD-L1 status. Central confirmation will occur retrospectively. For patients in whom a baseline research tumor tissue biopsy is not performed (e.g. site of disease is not safely accessible), archival tissue should be provided for central confirmatory PD-L1 testing
- DOSE EXPANSION COHORT: 0-1 prior lines of systemic therapy in the metastatic setting
- DOSE EXPANSION COHORT: Participants must have measurable disease per RECIST 1.1 criteria
- DOSE EXPANSION COHORT: Participants must have disease that is amenable to biopsy as judged by the treating investigator and must be willing to undergo pre- and on-treatment tumor biopsies, if safely accessible
- Age \>= 18 years
- Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with nab-paclitaxel and pembrolizumab (MK-3475) in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- +25 more criteria
You may not qualify if:
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694), nab-paclitaxel, or pembrolizumab
- Patients with uncontrolled intercurrent illness
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Any gastrointestinal (GI) disorder that may affect absorption of oral medications in the opinion of the treating investigator, such as malabsorption syndrome or major bowel or stomach resection
- Pregnant women are excluded from this study because ZEN003694 (a BETi agent) and MK-3475 have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to MK-3475 and nab-paclitaxel
- Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
- DOSE EXPANSION COHORT: Prior exposure to immune checkpoint inhibitors in the metastatic setting. PD-1 or PD-L1 inhibitors in the neo-/adjuvant setting are allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to development of metastatic disease
- DOSE EXPANSION COHORT: Prior exposure to taxane-based therapy in the metastatic setting. Taxane in the neo-/adjuvant setting is allowed if at least 12 months have elapsed since the end of adjuvant systemic treatment to development of metastatic disease
- Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 (ZEN-3694). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients receiving any medications or substances that are 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
- Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694)
- Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694)
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI)
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has a known history of active tuberculosis (TB)
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Boston Medical Center
Boston, Massachusetts, 02118, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ana C Garrido-Castro
Dana-Farber - Harvard Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2022
First Posted
June 21, 2022
Study Start
May 18, 2023
Primary Completion (Estimated)
March 31, 2027
Study Completion (Estimated)
March 31, 2027
Last Updated
May 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.