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 (Sep 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
Treatments studied
Targeted therapy
Other
Cancer type
Tumor Agnostic
Biomarker criteria
Required: BARD1 mutation
Required: BRCA1 mutation
Required: BRCA2 mutation
Required: BRIP1 mutation
Required: FANCA mutation
Required: KRAS mutation
Required: PALB2 mutation
Required: RAD51 mutation
Required: RAD51C mutation
Required: RAD51D mutation
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: systemic therapy — advanced/metastatic
Patients must have received at least one line of systemic therapy in the advanced/metastatic setting
Must have received: PARP inhibitor
Cohort 1: must have received prior PARPi monotherapy or PARPi combination-therapy
Must have received: PARP inhibitor
Cohort 2: must have received prior PARPi monotherapy or PARPi combination therapy
Must have received: PARP inhibitor
Cohort 3: must be patients who have had PR/CR on prior PARPi monotherapy or PARPi combination treatment
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 ULN OR GFR >= 60 mL/min/1.73 m^2 for subjects with creatinine > 1.5 x 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 ULN OR direct bilirubin = ULN for subjects with total bilirubin > 1.5 x ULN; AST/ALT <= 2.5 x 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 ULN OR direct bilirubin = ULN for subjects with total bilirubin > 1.5 x ULN; AST/ALT <= 2.5 x ULN; Creatinine <= 1.5 x ULN OR GFR >= 60 mL/min/1.73 m^2 for subjects with creatinine > 1.5 x ULN, unless data exists supporting safe use at lower kidney function values, no lower than 30 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
Showing up to 5 US sites.
See all sites on ClinicalTrials.gov →Frequently asked questions
Is NCT05327010 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior ZEN003694 (ZEN-3694) or investigational BET inhibitor disqualifies patients from enrollment.
Does this trial require BARD1?
Yes, BARD1 mutation is a required biomarker for enrollment.
Does this trial require BRCA1?
Yes, BRCA1 mutation is a required biomarker for enrollment.
Does this trial require BRCA2?
Yes, BRCA2 mutation is a required biomarker for enrollment.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualify