OncoMatch/Clinical Trials/NCT05327010
Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
Is NCT05327010 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including BET Bromodomain Inhibitor ZEN-3694 and Talazoparib for advanced malignant solid neoplasm.
Treatment: BET Bromodomain Inhibitor ZEN-3694 · Talazoparib — This phase II trial tests whether ZEN003694 (ZEN-3694) in combination with talazoparib works to shrink tumors in patients with solid tumors that are unlikely to be cured or controlled with treatment and that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Another aim of this study is to find out if, and how, patients' genes influence their response to this specific drug combination. For this part of the study, investigators will run tests using samples of patients' tumor tissue and blood that will be collected during the study. ZEN-3694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that overproduce BET protein. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Genes are pieces of the DNA code that individuals inherit from their parents. Some genes work to protect against cancer by correcting damage that can occur in the DNA when cells divide. BRCA1 and BRCA2 are two examples of these types of genes, and they are called tumor-suppressor genes. For example, if a person has a mutation in a BRCA1/2 gene they have a greatly increased risk of developing breast and ovarian cancer because their cells may no longer be able to completely repair damaged DNA. It is the accumulation of DNA damage which causes a cell to change into a cancerous cell. Other genes are also involved in this process, and these are called DNA damage repair genes. The KRAS mutation is a change in a protein in normal cells. Normally KRAS serves as an information hub for signals in the cell that lead to cell growth, but when there is a mutation in KRAS it signals too much and cells grow without being told to, which causes cancer. Combination therapy with ZEN-3694 and talazoparib may be effective at slowing or stopping tumor growth in patients with advanced cancer.
Check if I qualifyExtracted eligibility criteria
Cancer type
Tumor Agnostic
Biomarker criteria
Required: BRCA1 germline or somatic mutation
Cohort 1 must have (i) a germline or somatic mutation in BRCA1
Required: BRCA2 germline or somatic mutation
Cohort 1 must have (i) a germline or somatic mutation in BRCA2
Required: BARD1 germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: BARD1
Required: FANCA germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: FANCA
Required: BRIP1 germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: BRIP1
Required: PALB2 germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: PALB2
Required: RAD51 germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: RAD51
Required: RAD51C germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: RAD51C
Required: RAD51D germline or somatic mutation
Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: RAD51D
Required: KRAS mutation
Cohort 4 must have KRAS mutated advanced solid tumors
Allowed: KRAS G12C
Patients with KRAS G12C mutations must have already had KRAS G12C targeted therapy (e.g., sotorasib) previously
Disease stage
Metastatic disease required
metastatic or unresectable and ... at least one measurable disease site, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: PARP inhibitor
must have received prior PARPi monotherapy or PARPi combination-therapy
Cannot have received: ZEN003694 (ZEN-3694) or investigational BET inhibitor (ZEN003694, ZEN-3694)
Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
Lab requirements
Blood counts
Absolute neutrophil count >= 1,500/mcL; Platelets >= 150,000/mcL; Hemoglobin >= 10.0 g/dL (no blood transfusions in the preceding 28 days)
Kidney function
Creatinine <= 1.5 x institutional ULN OR GFR >= 60 mL/min/1.73 m^2 for subjects with creatinine levels > 1.5 x institutional ULN, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
Liver function
Total bilirubin <= 1.5 x institutional ULN OR direct bilirubin = ULN for subjects with total bilirubin levels > 1.5 x ULN; AST/ALT <= 2.5 x institutional ULN
Cardiac function
NYHA class 2B or better
Absolute neutrophil count >= 1,500/mcL; Platelets >= 150,000/mcL; Hemoglobin >= 10.0 g/dL (no blood transfusions in the preceding 28 days); Total bilirubin <= 1.5 x institutional ULN OR direct bilirubin = ULN for subjects with total bilirubin levels > 1.5 x ULN; AST/ALT <= 2.5 x institutional ULN; Creatinine <= 1.5 x institutional ULN OR GFR >= 60 mL/min/1.73 m^2 ... NYHA class 2B or better
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- City of Hope Comprehensive Cancer Center · Duarte, California
- City of Hope at Irvine Lennar · Irvine, California
- UC San Diego Moores Cancer Center · La Jolla, California
- Keck Medicine of USC Koreatown · Los Angeles, California
- Los Angeles General Medical Center · Los Angeles, California
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