923P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic head & neck squamous cell carcinoma – subgroup analysis of the PEVOsq basket trial

Targeting the PD1/PD-L1 axis in head and neck squamous cell carcinoma (HNSCC) patients improves survival. However, only a minority of patients (pts) respond to treatment. 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. A’Hern design with the following hypotheses (alpha=5%, power=90%, p0=10%, p1=35%). 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, 27 and 26 HNSCC pts were evaluable for safety and efficacy. Median age was 59 years old [range: 18-77]. Median number of prior lines of therapies was 0 [range: 0-1]. Five pts (19.2%, [95%CI: 6.6-39.4]) had an objective response. Median DOR was 3.2 months [95%CI: 1.3-NR]. Median PFS and OS were 4.1 [95%CI: 1.5-4.4] and 9.2 months [95%CI: 6.8-14.4], respectively. Ten pts (37.0%) developed G3/4 treatment related adverse events. P and V were stopped for toxicity in 3.8% and 30.8% of pts, respectively. 40.7% 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 encouraging antitumor activity in HNSCC pts independant of PD-L1 expression, although the V dose had to be reduced in a substantial proportion of pts.