Trial results for a Phase 2 study (NCT03978624) investigating pembrolizumab alone and in combination with entinostat in bladder cancer were posted on ClinicalTrials.gov on 2025-10-07. The study observed mean changes in CD8 T cell immune gene signature of 1.11 Z-score for pembrolizumab and 1.01 Z-score for the combination.
Background
Pembrolizumab (Keytruda) is an established immunotherapy. This study investigated its use in bladder cancer, specifically in a 'window of opportunity' setting for patients deemed ineligible for or refusing cisplatin-based neoadjuvant chemotherapy.
Trial design
The Phase 2 'Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer' (NCT03978624) was an open-label platform study. It enrolled 20 participants with muscle-invasive bladder cancer (MIBC) who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy, or were planning trimodality therapy. The study's primary objective was to assess changes to immunogenomic markers after treatment with pembrolizumab alone and in combination with entinostat.
Key results
Key results from the study focused on changes in immunogenomic markers and the frequency of adverse events. For the outcome 'Changes in CD8 T Cell Immune Gene Signature in the Pembrolizumab + Entinostat Group and the Pembrolizumab Group':
- In the Pembrolizumab group, the mean change was 1.11 Z-score (Standard Deviation: 1.39).
- In the Pembrolizumab Plus Entinostat group, the mean change was 1.01 Z-score (Standard Deviation: 1.12).
Regarding the 'Frequency and Severity of Attributed Adverse Events as Assessed by CTCAE v5.0':
- In the Pembrolizumab group, participant counts for different attributed adverse events were 1, 2, 1, 1, and 1.
- In the Pembrolizumab Plus Entinostat group, participant counts for different attributed adverse events were 0, 2, 0, 0, and 1.
What this means
The results indicate that both pembrolizumab alone and in combination with entinostat led to positive mean changes in the CD8 T cell immune gene signature in participants with bladder cancer. While both treatment arms showed an increase in this immunogenomic marker, the mean change was slightly higher in the pembrolizumab monotherapy group compared to the combination. The observed adverse event counts provide initial safety insights within this small patient cohort, but further analysis would be needed for definitive conclusions on comparative safety profiles.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03978624, titled 'Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer,' were posted on 2025-10-07 on clinicaltrials.gov.