2406P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma of the penis: Subgroup analysis of the PEVOsq basket trial

Advanced penile squamous cell carcinoma (PSCC) is a rare disease, with limited treatment options and poor prognosis. Although PD-1 blockade demonstrated some activity in PSCC patients (pts), response rate is modest. Preclinical data suggests that vorinostat (V), an HDAC inhibitor, might improve immunotherapy efficacy by modulating the epigenome. PEVOsq is an open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of pembrolizumab (P) in combination with V in pts with recurrent and/or metastatic squamous carcinomas. Pts had to be PD1/PD-L1 antagonist-naïve with no restriction in terms of prior lines of treatments. P dose was 200 mg Q3W IV, and V 400 mg QD PO. Sample size was determined using an A’Hern design with the following hypotheses (alpha=10%, power=85%, p0=5%, p1=30%). Primary endpoint was objective response rate (ORR) according to RECIST 1.1 Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Among 112 included pts, 11 pts with penis cancer were evaluable for safety and efficacy. Median age was 71 years old [range: 39-82]. Median number of prior lines of therapies was 1 [range: 0-2]. Two pts (18.2%) had an objective response. Median PFS and OS were 2.4 [95%CI: 0.5-4.1] and 4.4 months [95%CI: 1.6-11.0], respectively. Five (45.5%) pts developed G3/4 treatment related adverse events. P and V were stopped for toxicity in 10.0% and 27.3% of pts, respectively. 54.5% of pts had a dose-reduced of V for toxicity including hematotoxicity, gastrointestinal toxicity, asthenia, and creatinine increase. Results according to PDL1, MSI, TMB and HPV will be presented at the meeting. P combined with V produced limited efficacy in advanced PSCC pts and was associated with substantial toxicity.