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OncoMatch/Clinical Trials/NCT05422794

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

Is NCT05422794 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments including Pembrolizumab and BET Bromodomain Inhibitor ZEN-3694 for anatomic stage iii breast cancer ajcc v8.

Phase 1RecruitingNational Cancer Institute (NCI)NCT05422794Data as of May 2026

Treatment: BET Bromodomain Inhibitor ZEN-3694 · Nab-paclitaxel · PembrolizumabThis 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.

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Extracted eligibility criteria

Cancer type

Breast Carcinoma

Triple-Negative Breast Cancer

Biomarker criteria

Required: ESR1 expression < 10% by IHC (< 10% by immunohistochemistry (IHC))

Estrogen receptor (ER) and progesterone receptor (PR) < 10% by immunohistochemistry (IHC)

Required: PR (PGR) expression < 10% by IHC (< 10% by immunohistochemistry (IHC))

Estrogen receptor (ER) and progesterone receptor (PR) < 10% by immunohistochemistry (IHC)

Required: HER2 (ERBB2) HER2-negative (HER2-negative (per current ASCO/CAP guidelines))

HER2-negative (per current American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guidelines)

Required: PD-L1 (CD274) negative (negative)

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.

Disease stage

Required: Stage III, IV (AJCC v8)

disease that is unresectable locally advanced or metastatic

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Cannot have received: ZEN003694 (BET inhibitor) (ZEN003694)

Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor

Cannot have received: immune checkpoint inhibitor

Exception: DOSE EXPANSION COHORT: 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 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

Cannot have received: taxane

Exception: DOSE EXPANSION COHORT: 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

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

Lab requirements

Blood counts

Absolute neutrophil count ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L

Kidney function

Serum or plasma creatinine ≤ 1.5 x ULN OR GFR ≥ 60 mL/min (CKD-EPI estimation)

Liver function

Total bilirubin ≤ 1.5 x ULN (or ≤ 2.0 x ULN in patients with documented Gilbert's Syndrome); AST/ALT ≤ 3.0 x ULN or ≤ 5.0 x ULN for participants with documented liver metastases

Cardiac function

New York Heart Association Functional Classification of class 2B or better

Absolute neutrophil count ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L; Total bilirubin ≤ 1.5 x ULN (or ≤ 2.0 x ULN in patients with documented Gilbert's Syndrome); AST/ALT ≤ 3.0 x ULN or ≤ 5.0 x ULN for participants with documented liver metastases; Serum or plasma creatinine ≤ 1.5 x ULN OR GFR ≥ 60 mL/min; New York Heart Association Functional Classification of class 2B or better

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Boston Medical Center · Boston, Massachusetts
  • Dana-Farber Cancer Institute · Boston, Massachusetts
  • NYU Langone Hospital - Long Island · Mineola, New York
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone · New York, New York
  • Ohio State University Comprehensive Cancer Center · Columbus, Ohio

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