ComBET Trial: ZEN-3694 and Talazoparib for Advanced Solid Tumors
This study, called the ComBET Trial, is testing a combination of two anti-cancer drugs, ZEN-3694 and talazoparib, for people with advanced solid tumors. These are cancers that have spread or cannot be removed by surgery, and for which standard treatments are no longer working. Researchers want to see if this drug combination can shrink tumors. They are also studying how a person's genes might affect their response to these drugs. ZEN-3694 works by targeting a protein called BET, which can help tumor cells grow. The study aims to enroll 88 participants and is looking for people aged 18 and older with specific types of tumors that can be biopsied. The main goal is to measure how many patients experience tumor shrinkage.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It plans to enroll 88 participants.
- What's involved
- You would take ZEN-3694 and talazoparib by mouth daily in 28-day cycles. You would also undergo diagnostic imaging, blood tests, and tumor biopsies throughout the study.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint, objective response rate, is measured from the start of treatment to the first response.
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NCT05327010
Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
Recruiting
PHASE2Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~88 participants
Updated 2026-08-20 on ClinicalTrials.gov
What's tested:BET Bromodomain Inhibitor ZEN-3694Biopsy ProcedureBiospecimen CollectionDiagnostic Imaging TestingTalazoparib
At a glance
Recruiting sites
22 of 36 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective response rate (ORR)
Measured over From initiation of treatment to first response
Conditions
NCT05327010
Where you'd take part
This study runs at 36 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
City of Hope at Irvine Lennar
Irvine, Californiastudy coordinator listed
Recruiting
City of Hope Comprehensive Cancer Center
Duarte, Californiastudy coordinator listed
Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgiastudy coordinator listed
Recruiting
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Marylandstudy coordinator listed
Recruiting
Northwestern University
Chicago, Illinoisstudy coordinator listed
Recruiting
Ochsner Medical Center Jefferson
New Orleans, Louisianastudy coordinator listed
Recruiting
UC San Diego Medical Center - Hillcrest
San Diego, Californiastudy coordinator listed
Recruiting
UC San Diego Moores Cancer Center
La Jolla, Californiastudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Timothy A Yap · PRINCIPAL_INVESTIGATOR · University of Texas MD Anderson Cancer Center LAO
Who to contact
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Eligibility criteria
Inclusion
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Patients must have a tumor lesion that can be biopsied with 'low' or 'minimal' risk and at least one measurable disease site, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
Note: Tumor lesions that are situated in a previously irradiated area may or may not be considered measurable
Patients in cohorts 1, 2, and 4 should have at least one relevant mutation. Patients enrolled in cohorts 1-3 do not require that PARP inhibitor (i) be the immediate prior therapy to be eligible for the trial. Patients should sign a screening consent that will allow the review of local next generation sequencing (NGS) or equivalent Clinical Laboratory Improvement Amendment (CLIA)-certified assay results by MD Anderson's Precision Oncology Decision Support (PODS) team to ensure that the mutations are actionable. No variants of uncertain significance (VUS) will be allowed
Patients in Cohort 1 must have (i) a germline or somatic mutation in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination-therapy
Patients in Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: BARD1; FANCA; BRIP1; PALB2; RAD51; RAD51C; RAD51D, with no evidence of mutations in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination therapy
Patients in Cohort 3 must be (i) patients who have had PR/CR on prior PARPi monotherapy or PARPi combination treatment; and (ii) patients with no evidence of BRCA1 or BRCA2 mutations or any of the relevant DDR aberrations listed in cohort 2. Patients with ovarian cancer should not have progressed on platinum-therapy within six months of therapy
Patients in Cohort 4 must have KRAS mutated advanced solid tumors. Prior treatments with KRAS inhibitors are permitted. Patients with KRAS G12C mutations must have already had KRAS G12C targeted therapy (e.g., sotorasib) previously
Patients must have received at least one line of systemic therapy in the advanced/metastatic setting. Subjects with diseases without known effective options, and subjects who have declined standard of care therapy prior to study introduction, are also eligible. Patients with ovarian cancer in cohort 3 should not have progressed on platinum within six months of therapy
Age \>= 18 years
Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with talazoparib in patients \< 18 years of age, children are excluded from this study
Patients must be greater than 4 weeks (6 weeks for nitrosoureas or mitomycin C) beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation. Patients must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities =\< grade 1) with the exception of alopecia or anorexia
Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
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 upper limit of normal (ULN) OR direct bilirubin = ULN for subjects with total bilirubin levels \> 1.5 x ULN
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
Creatinine 1.5 x =\< institutional ULN OR glomerular filtration rate (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
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable viral load while on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable. Patients with known symptomatic brain metastases requiring steroids are excluded. Of note, patients who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout. Follow-up brain imaging after central nervous system (CNS)-directed therapy must show no evidence of progression and patient should be clinically stable for at least 1 month. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. However, patients with concurrent malignancy that is progressing or requiring active treatment are excluded
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be of class 2B or better
The effects of the combination ZEN003694 (ZEN-3694) and talazoparib on the developing human fetus are unknown. For this reason, and because BET inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 7 months after completion of study drug administration
Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (\>/= 1 year before screening), total hysterectomy, or menopause (defined as 12 consecutive months of amenorrhea)
Ability to understand and the willingness to sign a written informed consent document
Exclusion
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or talazoparib
Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or P-gp, strong inhibitors of BCRP, sensitive substrates of CYP1A2, proton-pump-inhibitors (H2 antagonists are allowed), and herbal medications/preparations (vitamins are allowed) 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 with uncontrolled intercurrent illness
Patients with psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is a BET inhibiting agent with 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 prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 month following the last dose of the study drug. These potential risks may also apply to other agents used in this study
Patients who are involved in the planning and/or conduct of the study
Patients who are unable or unwilling to swallow pills
Active infection requiring intravenous (IV) antibiotics, or other uncontrolled intercurrent illness requiring hospitalization
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 with radiation to \> 25% of the bone marrow
Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694) or talazoparib
Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
Patients with cerebrovascular accident (CVA), myocardial infarction, or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib
Patients with impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 (ZEN-3694) or talazoparib
Patients that have had major surgery other than diagnostic surgery, dental surgery, or stenting within 4 weeks prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib
What this trial measures
- Objective response rate (ORR)From initiation of treatment to first response
Systemically assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. ORR = complete response + partial response. Complete response is defined as the disappearance of all target or non-target lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target or non-target lesions.