Trial results for the Phase 1b/2 study (NCT02437136) investigating entinostat in combination with pembrolizumab were posted on ClinicalTrials.gov on 2025-03-20. The study, which included participants with non-small cell lung cancer (NSCLC), melanoma, and colorectal cancer (CRC), reported an objective response rate (ORR) of up to 22.2% in one NSCLC cohort.
Background
The study aimed to determine the safety and tolerability of entinostat combined with pembrolizumab, and to assess the effectiveness of this combination in participants with non-small cell lung cancer (NSCLC), melanoma, and mismatch repair-proficient colorectal cancer (CRC).
Trial design
The Phase 1b/2 study (NCT02437136) was a dose-escalation study with expansion cohorts, enrolling 191 participants. The trial investigated the combination of entinostat and pembrolizumab in patients with non-small cell lung cancer, melanoma, and mismatch repair-proficient colorectal cancer. The study's purpose included assessing the safety and tolerability of the combination, as well as its effectiveness.
Key results
The trial reported objective response rates (ORR) and clinical benefit rates (CBR) across various cohorts, as assessed using Immune Response RECIST (irRECIST) and Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). All cohorts received entinostat 5 mg weekly + pembrolizumab.
For Objective Response Rate (ORR) as assessed using irRECIST (percentage of participants):
- Phase 2, Cohort 1: 22.2
- Phase 2, Cohort 2: 9.2
- Phase 2, Cohort 3: 18.9
- Phase 2, Cohort 4: 5.4
For Clinical Benefit Rate (CBR) as assessed using irRECIST (percentage of participants):
- Phase 2, Cohort 1: 33.3
- Phase 2, Cohort 2: 14.5
- Phase 2, Cohort 3: 35.8
- Phase 2, Cohort 4: 8.1
For Clinical Benefit Rate (CBR) as assessed using RECIST 1.1 (percentage of participants):
- Phase 2, Cohort 1: 22.2
- Phase 2, Cohort 2: 14.5
- Phase 2, Cohort 3: 30.2
- Phase 2, Cohort 4: 2.7
What this means
The results from this Phase 1b/2 study indicate that the combination of entinostat and pembrolizumab elicited varied objective response rates and clinical benefit rates across different cancer types and cohorts. The highest ORR of 22.2% was observed in Phase 2, Cohort 1. These early-phase findings provide initial insights into the potential activity of this combination therapy in difficult-to-treat cancers like NSCLC, melanoma, and CRC, warranting further investigation into specific patient populations or dosing strategies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02437136, titled "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)," were posted on 2025-03-20 on clinicaltrials.gov.