A Phase I/IB, Open Label, Dose Finding Study to Evaluate Safety, Pharmacodynamics and Efficacy of Pembrolizumab in Combination With Vorinostat in Patients With Advanced Prostate, Renal or Urothelial Carcinoma.

ABSTRACT:

Background

Immunosuppressive factors such as regulatory T cells and myeloid-derived suppressive cells (MDSCs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have immunomodulatory effects. Thus, we conducted a Phase Ib clinical study with the HDAC inhibitor vorinostat and the PD-1 inhibitor pembrolizumab in patients (pts) with metastatic urothelial (UC), renal (RCC) and prostate (PCA) carcinoma.

Methods

The phase I portion consisted of two dose levels of vorinostat (100 and 200 mg, PO daily 2 weeks ON and 1 week OFF) and a fixed dose of pembrolizumab (200 mg IV every 21 days). Patients (pts) were assigned to three cohorts: Cohort A (previously treated, anti-PD1/PD-L1 naïve UC and RCC), Cohort B (previously treated, anti-PD1/PD-

SUBMITTER: Pili R 

PROVIDER: S-EPMC11947755 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature