Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial

Background: Immune checkpoint inhibitors (ICI) targeting Programmed death-1 (PD-1) have shown their efficacy in advanced MSI/dMMR (microsatellite instability/deficient mismatch repair) tumors. The MSI/dMMR status predicts clinical response to ICI. The promising results evaluating ICI in localized MSI/dMMR tumors in neoadjuvant setting need to be confirmed in MSI/dMMR solid tumors. The aim of the IMHOTEP trial is to assess the efficacy of neoadjuvant anti-PD-1 treatment in MSI/dMMR tumors regarding the pathological complete response rate.Methods: This study is a prospective, multicenter, phase II study including 120 patients with localized MSI/dMMR carcinomas suitable for curative surgery. A single dose of pembrolizumab will be adminis-tered before the surgery planned 6 weeks later. Primary objective is to evaluate the efficacy of neoad-juvant pembrolizumab according to pathological complete tumor response. Secondary objectives are to assess safety, recurrence-free survival and overall survival. Ancillary studies will assess molecular and immunological biomarkers predicting response/resistance to ICI. First patient was enrolled in December 2021.Discussion: The IMHOTEP trial will be one of the first clinical trial investigating perioperative ICI in local-ized MSI/dMMR in a tumor agnostic setting. Assessing neoadjuvant anti-PD-1 is mandatory to improve MSI/dMMR patient's outcomes. The translational program will explore potential biomarker to improve our understanding of immune escape and response in this ICI neoadjuvant setting.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

The IMHOTEP trial aims to assess the efficacy of neoadjuvant anti-PD-1 treatment in localized MSI/dMMR tumors and explore molecular and immunological biomarkers predicting response to immune checkpoint inhibitors. This trial is significant in improving the outcomes of MSI/dMMR patients.