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)

Conditions

• Melanoma
• Mismatch Repair-Proficient Colorectal Cancer
• Non-Small Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• entinostat — DRUG
  An orally available histone deacetylases inhibitor (HDACs)
• pembrolizumab — DRUG
  A selective humanized monoclonal antibody (mAb)

Study Details

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.

Key Dates

Start date

Aug 26, 2015

Status verified

Mar 2025

Primary completion

Sep 29, 2022

Completion

Sep 29, 2022

Study Design

Enrollment

191 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1b (Dose Escalation): Entinostat 3 mg Weekly + Pembrolizumab
  Participants with NSCLC will receive entinostat 3 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks (Day 1 of each 21-day cycle).
• Experimental: Phase 1b (Dose Escalation): Entinostat 5 mg Weekly + Pembrolizumab
  Participants with NSCLC will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
• Experimental: Phase 1b (Dose Confirmation): Entinostat 5 mg Weekly + Pembrolizumab
  Participants with NSCLC will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
• Experimental: Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab
  Participants with NSCLC with squamous cell or adenocarcinoma histology who had not been treated with a programmed cell death receptor-1 (PD-1)- or programmed cell death ligand-1 (PD-L1)-blocking antibody, will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
• Experimental: Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab
  Participants with NSCLC (any histology) who has previously been treated with and unequivocally progressed on either a PD-1- or PD-L1-blocking antibody, will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
• Experimental: Phase 2, Cohort 3: Entinostat 5 mg Weekly + Pembrolizumab
  Participants with melanoma who has previously been treated with and unequivocally progressed on either a PD-1- or PD-L1-blocking antibody, will receive entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).
• Experimental: Phase 2, Cohort 4: Entinostat 5 mg Weekly + Pembrolizumab
  Participants with CRC (mismatch repair-proficient) who had not been previously treated with a PD-1- or PD-L1-blocking antibody, received entinostat 5 mg administered orally weekly (Days 1, 8, and 15 of each 21-day cycle) along with pembrolizumab 200 mg via IV infusion once every 3 weeks (Day 1 of each 21-day cycle).

Primary Outcome Measure

Phase 2: Objective Response Rate (ORR), as Assessed Using Immune Response RECIST (irRECIST) [ Time Frame: From date of randomization to date of progression (up to 765 days) ]

Locations (11)

Related coverage on Hipa.ai

• Pembrolizumab/Entinostat Combo Shows 22.2% ORR in NSCLC
  Pembrolizumab · Mar 20, 2025 · ClinicalTrials.gov

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