Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure GC: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, Nanostring, Samsung, Celltrion, Ellipsis, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Mylan. CLT: Roche, Seattle Genetics, Rakuten, Nanobiotix, MSD, BMS, Merck Serono, AstraZeneca, GlaxoSmithKline, Novartis, Celgene. XF: Roche, Janssen, BMS, Leo Pharma, Amgen Research. LC: Leo Pharma, Amgen. JG: Roche, Leo Pharma. IP: employee and equity holder in Oncompass Medicine Ltd. RD, PF, and AD are employees of Oncompass Medicine Ltd. All other authors have declared no conflicts of interest.