Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer

Summary

Participation Requirements

Description

This study will investigate immunogenomic changes with pembrolizumab alone and in combination with a selective class I histone deacetylase (HDAC) inhibitor (entinostat). The study will enroll 20 subjects with a confirmed diagnosis of MIBC (cT2-T4aN0M0) who are ineligible for (based on consensus crit...

This study will investigate immunogenomic changes with pembrolizumab alone and in combination with a selective class I histone deacetylase (HDAC) inhibitor (entinostat). The study will enroll 20 subjects with a confirmed diagnosis of MIBC (cT2-T4aN0M0) who are ineligible for (based on consensus criteria)[1] or refuse neoadjuvant cisplatin-based chemotherapy. Subjects must consent to having tissue collected for research purposes during the scheduled surgery prior to study entry. After screening and enrollment, blood and archived transurethral resection of the bladder tumor (TURBT) tumor tissue will be collected from each subject for baseline analyses. Subjects will then start on clinical trial treatment followed by radical cystectomy. Subjects will be administered pembrolizumab alone 200 mg IV on day 1 and day 22 (Arm 1) or pembrolizumab on day 1 and day 22 and entinostat 5 mg given orally on day 1, day 8 and day 15 (Arm 2). Blood and tumor will then be collected from each subject at the time of cystectomy (within 10 weeks after initiation of protocol therapy). The investigators do not anticipate delays in surgery due to the planned schedule of the preoperative treatment administration for the purposes of this study and based on the phase II ENCORE 601 trial (pembrolizumab and entinostat in melanoma) which reported an acceptable safety profile. Phase I data identified grade 1/2 fatigue as the most common entinostat-related toxicity, with neutropenia and anemia only occurring at doses exceeding those proposed for this study. Safety stopping rules for drug-related toxicity will dictate whether the trial should be halted if subjects are experiencing drug-related toxicity that delays or interferes with standard of care procedures.

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