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Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors | Clinical Trials | Clareo Health

RECRUITINGPHASE1

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4/6 Inhibitor Abemaciclib in Patients With NUT Carcinoma, Breast Cancer and Other Solid Tumors

NCT05372640•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase I trial tests the safety, side effects, and best dose of ZEN003694 when given together with abemaciclib in treating patients with NUT carcinoma, breast cancer or other solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). ZEN003694 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. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ZEN003694 and abemaciclib may help shrink or stabilize cancer in patients with NUT carcinoma, breast cancer or other solid tumors.

Detailed Description

PRIMARY OBJECTIVE: I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BET bromodomain inhibitor ZEN-3694 (ZEN003694) and abemaciclib. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Determine the preliminary rates of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), time to response (TTR) and duration of response (DoR) for the combination of ZEN003694 and abemaciclib in participants utilizing Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. III. Evaluate the pharmacokinetic (PK) profile of the combination. EXPLORATORY OBJECTIVE: I. Explore potential biomarker indicators of response and resistance in tumor tissue and blood samples. OUTLINE: This is a dose-escalation study of BET bromodomain inhibitor ZEN-3694 followed by a dose expansion study. Patients receive ZEN003694 orally (PO) once daily (QD) on days 1-28 or 5 days on and 2 days off of each cycle, and abemaciclib PO twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo imaging evaluation, blood sample collection and tumor biopsy throughout the study. After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

Eligibility

Age

12 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants 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
•Dose Escalation Cohort Only: Participants must have evaluable disease or measurable disease per RECIST 1.1 criteria
•Dose Expansion Cohort Only:
•* Participants must have a diagnosis of NUT carcinoma (NC) based on standard criteria for the disease, with diagnostic testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory:
•* Ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) testing, OR
•* Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, OR
•* Detection of the NUT gene translocation as determined by either deoxyribonucleic acid (DNA) next-generation sequencing (NGS) or ribonucleic acid (RNA) sequencing.
•* Participants must have measurable disease per RECIST 1.1 criteria
•Any number of prior lines of therapy in the metastatic setting are allowed, including prior BET inhibitor therapy and prior CDK4/6 inhibitor therapy
•Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] grade =\< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy
+26 more criteria

Exclusion Criteria

•Participants who have had cytotoxic chemotherapy, immunotherapy, or other investigational therapy within 2 weeks prior to entering the study. There is a two-week required washout period for previous BET inhibitor therapy
•Participants who have had radiotherapy within at least 2 weeks prior to entering the study. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed
•Participants who have had major surgery within 3 weeks prior to entering the study
•Participants who have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 1 week (whichever is shorter) of study entry
•Patients who are receiving any other investigational agents
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or abemaciclib
•Patients requiring medications or substances that are strong inhibitors or strong inducers of CYP3A4 or CYP3A enzymes are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 and abemaciclib. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. 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, including but not limited to: ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (e.g. estimated creatinine clearance \< 30ml/min), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea that, in the judgment of the investigator, would preclude participation in this study
•Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. As proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids may alter the pharmacokinetics of ZEN003694 by reducing ZEN003694 exposure, patients receiving proton pump inhibitors are ineligible. If H2 blockers or other acid reducing agents are used concomitantly with ZEN003694, a staggered dosing schedule should be used. 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
•Pregnant women are excluded from this study because ZEN003694 is a BETi 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, breastfeeding should be discontinued if the mother is treated with ZEN003694. These potential risks may also apply to other agents used in this study
+7 more criteria

Locations (7)

Keck Medicine of USC Koreatown

Los Angeles, California, United States

Los Angeles General Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

August 10, 2023

Primary Completion Date

June 1, 2026

Completion Date

June 1, 2026

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Breast CarcinomaMetastatic Malignant Solid NeoplasmMetastatic NUT CarcinomaUnresectable Breast CarcinomaUnresectable Malignant Solid NeoplasmUnresectable NUT Carcinoma

Interventions

Abemaciclib

DRUG

BET Bromodomain Inhibitor ZEN-3694

DRUG

Biopsy Procedure

PROCEDURE

Biospecimen Collection

PROCEDURE

Diagnostic Imaging Testing

PROCEDURE

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

Inclusion Criteria

Exclusion Criteria

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

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