Immunotherapy in MSI/dMMR tumors in the perioperative setting: The IMHOTEP trial
- Creators
- Coutzac, Clélia
- Bibeau, Frédéric
- Ben Abdelghani, Méher
- Aparicio, Thomas
- Cohen, Romain
- Coquan, Élodie
- Dubreuil, Olivier
- Evesque, Ludovic
- Ghiringhelli, François
- Kim, Stefano
- Lesourd, Samuel
- Neuzillet, Cindy
- Phelip, Jean Marc
- Piessen, Guillaume
- Rochigneux, Philippe
- Samalin, Emmanuelle
- Soularue, Émilie
- Touchefeu, Yann
- Tougeron, David
- Zaanan, Aziz
- de la Fouchardière, Christelle
- Others:
- Département cancer environnement (Centre Léon Bérard - Lyon) ; Centre Léon Bérard [Lyon]
- Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) ; Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Service d'Anatomie pathologique [CHRU Besançon] ; Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
- Centre Paul Strauss ; CRLCC Paul Strauss
- Hopital Saint-Louis [AP-HP] (AP-HP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC) ; Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
- Groupe Hospitalier Diaconesses Croix Saint-Simon
- Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)
- Service d'oncogénétique [Centre georges-François Leclerc] ; Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL) ; UNICANCER-UNICANCER
- Centre Eugène Marquis (CRLCC)
- Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
- Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)
- Hôpital Claude Huriez [Lille] ; CHU Lille
- Centre de Recherche en Cancérologie de Marseille (CRCM) ; Aix Marseille Université (AMU)-Institut Paoli-Calmettes ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Institut Paoli-Calmettes ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
- Institut du Cancer de Montpellier (ICM)
- Institut Mutualiste de Montsouris (IMM)
- Nantes Université (Nantes Univ)
- Centre hospitalier universitaire de Poitiers (CHU Poitiers)
- Hôpital Européen Georges Pompidou [APHP] (HEGP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
- Amgen; Bristol-Myers Squibb, BMS; Pfizer; AstraZeneca; Bayer; Roche; Sanofi; Meso Scale Diagnostics, MSD; Les Laboratories Pierre Fabre; MSD France; Ministère des Affaires Sociales et de la Santé; Institut National Du Cancer, INCa: PHRC-K 2019 Inca-DGOS_14333, PRT-K 2020–15324; Servier; Institut Servier
- CC declares a consulting and advisory board for Amgen, Servier, and received honoria from Servier, Amgen. TA received honoraria from Servier, Pierre fabre, Amgen, AstraZeneca and declares consulting for Bioven, Servier, SIRTEC, MSD. RC received honoraria from MSD Oncology, Pierre Fabre, and Bristol-Myers Squibb, declares consulting from Exeliom Biosciences, Enterome Bioscience and received research funding from Servier Institute. OD received honoraria from Amgen, Sanofi, Merck Serono, MSD, Servier, Ipsen, Keocyt and declares consulting for Merck Serono, Sanofi, MSD, AstraZeneca, Novartis. LE declares consulting for BMS and Servier. FG declares research grant from Roche, AstraZeneca and consulting for Astrazenca, Roche, Sanofi, BMS, MSD, Merck-Serono, Amgen. EL declares consulting for Roche, Servier, Ipsen, Bayer, BTG, MSD. CN received honoraria from Amgen, AstraZeneca, Baxter, Bristol-Myers Squibb, Fresenius Kabi, Incyte Biosciences, Merck, MSD, Mylan, Novartis, Nutricia, Pierre Fabre, Roche, Sanofi, Servier and research funding from Roche. ES received honoraria from Servier, Amgen, Merck Serono, MSD, Pierre Fabre Oncology BMS, Sanofi, Research funding from Bayer, and declares consulting for Pierre Fabre Oncology. YT declares honoraria from MSD, Astra Zeneca, Bayer, Amgen, Servier, Ipsen, Pierre Fabre, AAA and consulting for Merck. DT received honoraria from Amgen, Roche, Sanofi, Bristol-Myers Squibb, Merck Serono, MSD, Bristol-Myers Squibb, Servier/Pfizer, Ipsen, research funding from AstraZeneca, SERVIER, Roche, MSD, BTG, and declares consulting for Sanofi, MSD, Pierre Fabre, and AstraZeneca. A.Z. declares consulting and/or advisory boards for Amgen, Lilly, Merck, Roche, Sanofi, Servier, Baxter, MSD, Pierre Fabre, Havas Life, Alira Health, Zymeworks, and Daiichi. CDLF received honoraria from Amgen, Astra- Zeneca, Bayer, Bristol-Myers Squibb, Eisai, Incyte Biosciences, Ipsen, Lilly, Merck Serono, MSD, Pierre Fabre Oncologie, Pfizer, Roche, Sanofi-Aventis, Servier. FB, MBZ, SK, EC, PR and ES declares no conflicts of interests.
- This study is supported by a grant from the French Ministry of Health and the French National Cancer Institute (PHRC-K 2019 Inca-DGOS_14333 and PRT-K 2020–15324). It is also carried out with the support of MSD France. The opinions expressed in this article are those of the authors and do not necessarily reflect those of MSD France.
Description
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 administered before the surgery planned 6 weeks later. Primary objective is to evaluate the efficacy of neoadjuvant 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 localized 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.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-03837196
- URN
- urn:oai:HAL:hal-03837196v1
- Origin repository
- UNICA