Actively Recruiting
Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
88
Participants Needed
36
Research Sites
267 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed metastatic or unresectable malignancy with no effective standard treatment available
- Presence of at least one measurable tumor lesion that can be biopsied safely
- Patients must have relevant mutations depending on cohort (e.g., BRCA1/2, DNA damage repair genes, or KRAS mutation) as confirmed by genetic testing
- At least one prior systemic therapy for advanced or metastatic disease received
- Age 18 years or older
- At least 4 weeks since last chemotherapy or investigational therapy and recovered from side effects (except hair loss or appetite loss)
- ECOG performance status of 0 to 2 or Karnofsky score 60% or higher
- Adequate blood counts and organ function as specified
- Controlled HIV, hepatitis B, and hepatitis C infections under defined conditions
- Patients with treated and stable brain metastases meeting defined criteria
- Patients with prior or concurrent malignancies not expected to interfere with study
- Cardiac function classified as New York Heart Association class 2B or better
- Agreement to use effective contraception for men and women of childbearing potential
- Women of child-bearing potential must have a negative pregnancy test
- Ability and willingness to provide informed consent
You will not qualify if you...
- Receiving other investigational agents
- History of allergic reaction to ZEN-3694 or talazoparib or similar compounds
- Use of medications that strongly affect CYP3A4, P-gp, or BCRP enzymes or certain other drug interactions unless stopped 7 days before treatment
- Uncontrolled illnesses or infections requiring hospitalization
- Psychiatric or social conditions limiting study compliance
- Pregnant or breastfeeding women
- Involvement in study planning or conduct
- Inability or unwillingness to swallow pills
- Use of factor Xa or IIa inhibitors except low molecular weight heparin
- Radiation to more than 25% of bone marrow
- Use of bone-targeted radionuclides within 6 weeks before study
- Prior treatment with ZEN-3694 or other BET inhibitors
- Recent cerebrovascular events or unstable heart conditions within 6 months
- Gastrointestinal conditions affecting drug absorption
- Major surgery within 4 weeks before study start except minor procedures or stenting
- Symptomatic brain metastases requiring steroids or carcinomatous meningitis
- Concurrent malignancy requiring active treatment or progressing disease
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 36 locations
1
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
Actively Recruiting
2
City of Hope at Irvine Lennar
Irvine, California, United States, 92618
Actively Recruiting
3
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Actively Recruiting
4
Keck Medicine of USC Koreatown
Los Angeles, California, United States, 90020
Active, Not Recruiting
5
Los Angeles General Medical Center
Los Angeles, California, United States, 90033
Active, Not Recruiting
6
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Active, Not Recruiting
7
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, United States, 92663
Active, Not Recruiting
8
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Active, Not Recruiting
9
UC San Diego Medical Center - Hillcrest
San Diego, California, United States, 92103
Actively Recruiting
10
UCHealth University of Colorado Hospital
Aurora, Colorado, United States, 80045
Actively Recruiting
11
Yale University
New Haven, Connecticut, United States, 06520
Active, Not Recruiting
12
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, United States, 06611
Active, Not Recruiting
13
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States, 32610
Active, Not Recruiting
14
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Actively Recruiting
15
Northwestern University
Chicago, Illinois, United States, 60611
Actively Recruiting
16
University of Kansas Clinical Research Center
Fairway, Kansas, United States, 66205
Actively Recruiting
17
University of Kansas Cancer Center
Kansas City, Kansas, United States, 66160
Actively Recruiting
18
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, United States, 66210
Actively Recruiting
19
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States, 66211
Actively Recruiting
20
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States, 66205
Actively Recruiting
21
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States, 40536
Actively Recruiting
22
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States, 70121
Actively Recruiting
23
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, United States, 20892
Actively Recruiting
24
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Active, Not Recruiting
25
University of Kansas Cancer Center - North
Kansas City, Missouri, United States, 64154
Actively Recruiting
26
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, United States, 64064
Actively Recruiting
27
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, United States, 64116
Suspended
28
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Actively Recruiting
29
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
30
University of Texas at Austin
Austin, Texas, United States, 78712
Active, Not Recruiting
31
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0565
Actively Recruiting
32
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
33
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Actively Recruiting
34
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
Active, Not Recruiting
35
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Actively Recruiting
36
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States, 23298
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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