758P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic vulvar and vaginal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial

Vulvar and vaginal squamous cell carcinoma (VVSCC) are rare, representing 4% of gynecologic cancers. At recurrent/metastatic stage systemic treatments are limited without gold-standard, chemotherapy response rate is poor. Immunotherapy has been approved for some metastatic SCC. Translational analyzes suggest that SCC share common molecular features as epigenetic. Modulating the epigenome might improve the efficacy of immunotherapy. Combining pembrolizumab (P) to an epidrug vorinostat (V) has been proposed in the PEVO basket trial. We described here the VVSCC cohort. PEVOsq is an open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of P combined to V in patients with recurrent/metastatic SCC of the cervix, head and neck, anus, vulva/vagina, penis, and lung. Patients had to be PD1/PD-L1 antagonist-naïve. There was no selection based on PD-L1 expression, HPV status, or number 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=5%, power=90%, p0=5%, p1=30%). The primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS). Among 112 included patients, 17 had a VVSCC metastatic/recurrent cancer. Median age was 63 years old [range: 40-85], 14 (82.4%) had a metastatic disease and 3 (17.6%) a locally advanced relapse. Lung 50.0%) and lymph nodes (78.6%) were the major metastatic sites. Inclusion in PEVOsq was the first-line treatment for most of patients, with a median number of prior treatment lines of 0 [range: 0-1]. Three patients out of 16 evaluable patients (18.8%) had an OR: 1 (6.3%) CR and 2 (12.5%) PR. Median PFS was 1.3 months [95%CI: 1.1-4.3]. Median OS was 17.5 months [95%CI: 2.3-NR]. Four patients (23.5%) had a G3/4 treatment related AE. Results according to PDL1, MSI, TMB and HPV will be presented at the meeting. P combined with V is safe and produce encouraging efficacy in VVSCC patients.