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Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCLC) With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer (CRC) | Clinical Trials | Clareo Health

COMPLETEDPHASE1/PHASE2

Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCLC) With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer (CRC)

A Phase 1b/2, Open-label, Dose Escalation Study of Entinostat in Combination With Pembrolizumab in Patients With Non-small Cell Lung Cancer, With Expansion Cohorts in Patients With Non-small Cell Lung Cancer, Melanoma, and Mismatch Repair-Proficient Colorectal Cancer

NCT02437136•Syndax Pharmaceuticals

View on ClinicalTrials.gov

Summary

The purpose of this study is to determine the safety and tolerability of entinostat used in combination with pembrolizumab in participants with NSCLC. Additionally, the purpose of the study is to assess how effective entinostat and pembrolizumab are in combination in participants with NSCLC, Melanoma, and Mismatch-Repair Proficient CRC.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants with NSCLC:
•1. Has histologically- or pathologically-confirmed recurrent/metastatic NSCLC.
•2. If has adenocarcinoma, required to have previously been tested for anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, with results available for collection in this study, and, if positive, has been treated with prior epidermal growth factor receptor (EGFR) or ALK therapy.
•3. Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Additional requirements related to prior treatments applied and may have been dependent on mutational status.
•4. Participants with NSCLC enrolled in Cohort 1 of the Expansion Phase should not have been previously treated with a PD-1/PD-L1-blocking antibody.
•Participants in Expansion Phase, Cohorts 2 (NSCLC) and 3 (Melanoma):
•5. Previously treated with a PD-1/PD-L1-blocking antibody and experienced documented, unequivocal radiographic progression of disease by irRECIST, or similar criteria during or within 12 weeks after last dose of such treatment. Participants must have received at least 6 weeks of PD-1/PD-L1 therapy for Cohort 2 and at least 8 weeks of PD-1/PD-L1 therapy for Cohort 3.
•Participants with Melanoma:
•6. In addition to having been previously treated with a PD-1/PD-L1-blocking antibody, has a histologically- or cytologically-confirmed diagnosis of unresectable or metastatic melanoma and experienced unequivocal progressive disease during treatment with a Serine/threonine-protein kinase B-Raf (BRAF) inhibitor if BRAF V600 mutation-positive. Treatment with BRAF inhibitor may occur after treatment with the checkpoint inhibitor.
•Participants in Expansion Phase, Cohort 4 (CRC):
+14 more criteria

Exclusion Criteria

•1. Diagnosis of immunodeficiency or receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
•2. Active autoimmune disease that has required systemic treatment in past 2 years (that is, with disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
•3. History of interstitial lung disease (ILD).
•4. Allergy to benzamide or inactive components of entinostat.
•5. History of allergies to any active or inactive ingredients of pembrolizumab or severe hypersensitivity (≥Grade 3) to pembrolizumab.
•6. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
•* Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval \> 470 milliseconds (msec).
•* Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, or uncontrolled systemic infection.
•* Another known additional malignancy that is progressing or requires active treatment (excluding adequately treated basal cell carcinoma, squamous cell of the skin, cervical intraepithelial neoplasia \[CIN\]/cervical carcinoma in situ or melanoma in situ, or ductal carinoma in situ of the breast). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
•* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
+17 more criteria

Locations (11)

Yale University

New Haven, Connecticut, United States

Emory University

Atlanta, Georgia, United States

University of Maryland, Marlene and Stewart Greenbaum Cancer Center

Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Dana Farber Cancer Institution

Boston, Massachusetts, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

St Luke's University Health Network

Easton, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Key Dates

Start Date

August 26, 2015

Primary Completion Date

September 29, 2022

Completion Date

September 29, 2022

Last Updated

March 20, 2025

Enrollment

191

ACTUAL participants

Conditions

Non-Small Cell Lung CancerMelanomaMismatch Repair-Proficient Colorectal Cancer

Interventions

entinostat

DRUG

pembrolizumab

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, 2025Data 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

Ph1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCLC) With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer (CRC)

Inclusion Criteria

Exclusion Criteria

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