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Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors

Phase Ib/II Study of ZEN003694 and Entinostat in Advanced and Refractory Solid Tumors

NCT05053971•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase I/II trial tests the safety, side effects, and best dose of entinostat and ZEN003694 in treating patients with solid tumors that have spread to other places in the body (advanced) or does not respond to treatment (refractory). Entinostat is in a class of drugs called histone deacetylase (HDAC) inhibitors. It may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 over produce BET protein. This trial aims to test the safety of combination therapy with entinostat and ZEN003694 in treating patients with advanced or refractory solid tumors.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of BET bromodomain inhibitor ZEN-3694 (ZEN003694) and entinostat in combination in patients with advanced and refractory solid tumors based on dose limiting toxicities (DLTs) of the combination of ZEN003694 and entinostat. (Phase I) II. To determine the overall response rate (ORR) of ZEN003694 and entinostat in advanced/progressive pancreatic cancer. (Phase II) SECONDARY OBJECTIVES: I. To describe the safety profile of ZEN003694 and entinostat in advanced and refractory solid tumors. (Phase I) II. To determine the progression-free survival (PFS), duration of response (DOR), and overall survival (OS) of ZEN003694 and entinostat in this patient population. (Phase I) III. To describe the safety profile of ZEN003694 and entinostat in advanced/progressive pancreatic cancer. (Phase II) IV. To determine the progression-free survival (PFS), duration of response (DOR), and overall survival (OS) of ZEN003694 and entinostat in this patient population. (Phase II) V. To assess the effect of ZEN003694 and entinostat therapy on apoptosis, as measured by an apoptosis multiplex immunoassay. (Phase I Daily Dosing of ZEN003694) EXPLORATORY OBJECTIVES: I. To assess the effect of ZEN003694 and entinostat therapy on c-MYC and YAP1 as measured by apoptosis immunofluorescence assay. (Phase I Daily Dosing of ZEN003694) II. To assess the effect of ZEN003694 and entinostat therapy on c-MYC and YAP1 as measured by ribonucleic acid (RNA) and protein expression. (Phase I Daily Dosing of ZEN003694) III. To assess the effect of ZEN003694 and entinostat therapy on tumor burden and gene expression patterns as measured by RNA sequencing (RNASeq) on circulating tumor deoxyribonucleic acid (DNA) (ctDNA) specimens. (Phase I Daily Dosing of ZEN003694) OUTLINE: This is a phase I, dose-escalation study of ZEN003694 in combination with entinostat followed by a phase II study. PHASE I RUN-IN PERIOD (DAILY DOSING) (NO LONGER USED PER AMENDMENT DATED JUNE 12, 2025): Patients receive ZEN003694 orally (PO) once daily (QD) during days -14 to 1. Patients also undergo core needle biopsy within 30 days prior to starting therapy. PHASE I \& II COMBINATION TREATMENT (DAILY DOSING) (NO LONGER USED PER AMENDMENT DATED JUNE 12, 2025): Patients receive entinostat PO QW on days 1, 8, 15, and 22, and ZEN003694 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo core needle biopsy on day 1 of cycle 1, and on day 1 of cycle 14. PHASE I and PHASE II (INTERMITTENT DOSING): Patients receive entinostat PO on days 1, 8, 15, and 22 of each cycle and ZEN003694 PO QD on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) throughout the study. After completion of study treatment, patients are followed for 30 days.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have a) advanced or refractory solid tumor and must meet standard requirements for treatment
•For patients in Phase 2: Patients must have locally advanced, unresectable OR metastatic pancreatic cancer refractory to standard therapy
•For patients with solid tumors, they must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
•For patients with solid tumors, they must have received at least one standard of care regimen for metastatic disease
•Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694, alone or in combination with entinostat, in patients \< 18 years of age, children are excluded from this study
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
•Hemoglobin \>= 9.0 g/dL (measured within 14 days prior to administration of study treatment)
•Absolute neutrophil count (ANC) \>= 1,500/mcL (measured within 14 days prior to administration of study treatment)
•Platelets \>= 100,000/mcL (measured within 14 days prior to administration of study treatment)
•Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (measured within 14 days prior to administration of study treatment)
+10 more criteria

Exclusion Criteria

•Patients who have had any anti-cancer therapy within 30 days (or 5 half-lives, whichever is shorter) prior to the first dose of the investigational products
•Patients who have received radiation therapy within 21 days prior to the first dose of the investigational products
•Patients who have a diagnosis of NK cell lymphoma
•Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia, or stable chronic grade 2 toxicities that do not overlap with presumed toxicities of entinostat or ZEN003694
•Patients who are receiving any other investigational agents
•Patients with known untreated or symptomatic brain or leptomeningeal metastases are excluded. Patients with previously treated CNS metastasis may be included provided that they have stable CNS disease for at least 4 weeks (confirmed by imaging) without symptoms and are off corticosteroids (above physiologic dose) for that indication
•Patients with significant malabsorption or nausea and vomiting that would interfere with oral therapies
•Patients with bleeding diathesis or clinically significant bleeding within the prior 6 months
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat (e.g. medications that have a benzamide structure (tiapride, remoxipride, clebopride) or ZEN003694
•Patients receiving any medications or substances that are strong inhibitors or strong inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 and substrates of CYP1A2 must be discontinued at least 7 days prior to the first dose of ZEN003694. 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
+14 more criteria

Locations (3)

Yale University

New Haven, Connecticut, United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Key Dates

Start Date

November 16, 2022

Primary Completion Date

July 1, 2026

Completion Date

July 1, 2026

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Advanced Malignant Solid NeoplasmLocally Advanced Pancreatic CarcinomaMetastatic Pancreatic CarcinomaRefractory Malignant Solid NeoplasmRefractory Pancreatic CarcinomaStage II Pancreatic Cancer AJCC v8Stage III Pancreatic Cancer AJCC v8Stage IV Pancreatic Cancer AJCC v8Unresectable Pancreatic Carcinoma

Interventions

BET Bromodomain Inhibitor ZEN-3694

DRUG

Computed Tomography

PROCEDURE

Core Biopsy

PROCEDURE

Entinostat

DRUG

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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 A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors

Inclusion Criteria

Exclusion Criteria

Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations

IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors

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

Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial

Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer