New drug cocktail aims to shrink Hard-to-Treat tumors

NCT ID NCT05327010

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Aug 21, 2026 · Updated 11 times

Summary

This study tests whether a combination of two drugs (ZEN003694 and talazoparib) can shrink tumors in people with advanced solid cancers that have stopped responding to standard treatments. About 88 adults will take part. Researchers will also look at participants' genes to see if they affect how well the treatment works.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 88 people

The number the study aims to enrol. It can still change while the study runs.

Started

Nov 2022

Expected to finish

Dec 2027

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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 Criteria: * 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

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Conditions

The condition(s) this trial relates to.

cancer metastatic malignant neoplasm neoplasm Neoplasm Metastasis

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced malignant solid neoplasm Metastatic malignant solid neoplasm Unresectable malignant solid neoplasm

How to take part

Only the study team decides who joins. These are the ways to reach them.

The study's own enquiry address

This study publishes an address for enquiries. See it below .
The places running it

23 sites. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Show contact details

Locations

City of Hope Comprehensive Cancer Center
RECRUITING

Duarte, California, 91010, United States

Contact Email: •••••@•••••
City of Hope at Irvine Lennar
RECRUITING

Irvine, California, 92618, United States
Emory University Hospital/Winship Cancer Institute
RECRUITING

Atlanta, Georgia, 30322, United States
Huntsman Cancer Institute/University of Utah
ACTIVE_NOT_RECRUITING

Salt Lake City, Utah, 84112, United States
Keck Medicine of USC Koreatown
ACTIVE_NOT_RECRUITING

Los Angeles, California, 90020, United States
Los Angeles General Medical Center
ACTIVE_NOT_RECRUITING

Los Angeles, California, 90033, United States
National Cancer Institute Developmental Therapeutics Clinic
RECRUITING

Bethesda, Maryland, 20892, United States
National Institutes of Health Clinical Center
ACTIVE_NOT_RECRUITING

Bethesda, Maryland, 20892, United States
Northwestern University
RECRUITING

Chicago, Illinois, 60611, United States

Contact Email: •••••@•••••
Ochsner Medical Center Jefferson
RECRUITING

New Orleans, Louisiana, 70121, United States
Smilow Cancer Hospital Care Center-Trumbull
ACTIVE_NOT_RECRUITING

Trumbull, Connecticut, 06611, United States
UC San Diego Medical Center - Hillcrest
RECRUITING

San Diego, California, 92103, United States
UC San Diego Moores Cancer Center
RECRUITING

La Jolla, California, 92093, United States

Contact Email: •••••@•••••
UCHealth University of Colorado Hospital
ACTIVE_NOT_RECRUITING

Aurora, Colorado, 80045, United States
UF Health Cancer Institute - Gainesville
ACTIVE_NOT_RECRUITING

Gainesville, Florida, 32610, United States
UNC Lineberger Comprehensive Cancer Center
RECRUITING

Chapel Hill, North Carolina, 27599, United States

Contact Email: •••••@•••••
UPMC Hillman Cancer Center
RECRUITING

Pittsburgh, Pennsylvania, 15232, United States
USC / Norris Comprehensive Cancer Center
ACTIVE_NOT_RECRUITING

Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
ACTIVE_NOT_RECRUITING

Newport Beach, California, 92663, United States
UT MD Anderson Cancer Center
RECRUITING

Houston, Texas, 77030, United States
University of California Davis Comprehensive Cancer Center
ACTIVE_NOT_RECRUITING

Sacramento, California, 95817, United States
University of Kansas Cancer Center
RECRUITING

Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center - Lee's Summit
RECRUITING

Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center - North
RECRUITING

Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center at North Kansas City Hospital
SUSPENDED

North Kansas City, Missouri, 64116, United States
University of Kansas Cancer Center-Overland Park
RECRUITING

Overland Park, Kansas, 66210, United States
University of Kansas Clinical Research Center
RECRUITING

Fairway, Kansas, 66205, United States
University of Kansas Hospital-Indian Creek Campus
RECRUITING

Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
RECRUITING

Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
RECRUITING

Lexington, Kentucky, 40536, United States
University of Texas Health Science Center at San Antonio
WITHDRAWN

San Antonio, Texas, 78229, United States
University of Texas Medical Branch
RECRUITING

Galveston, Texas, 77555-0565, United States

Contact Email: •••••@•••••
University of Texas at Austin
ACTIVE_NOT_RECRUITING

Austin, Texas, 78712, United States
University of Virginia Cancer Center
RECRUITING

Charlottesville, Virginia, 22908, United States

Contact Email: •••••@•••••
VCU Massey Comprehensive Cancer Center
RECRUITING

Richmond, Virginia, 23298, United States
Yale University
ACTIVE_NOT_RECRUITING

New Haven, Connecticut, 06520, United States

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