[Localized MSI/dMMR gastric cancer patients, perioperative immunotherapy instead of chemotherapy: The GERCOR NEONIPIGA phase II study is opened to recruitment].

Abstract

INTRODUCTION:

Perioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi).

AIM:

The GERCOR NEONIPIGA single-arm phase II study (NCT04006262; EUDRACT 2018-004712-22) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumab in neoadjuvant setting, then nivolumab alone after surgery for patients with resectable MSI/dMMR gastric cancer.

MATERIAL AND METHODS:

Main inclusion criteria are: gastric and oesogastric junction adenocarcinoma (GOA), T2-T4, all N stage and M0, MSI/dMMR. Patients will be treated with nivolumab 240mg Q2W, 6 infusions, and ipilimumab 1mg/kg Q6W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoadjuvant treatment and postoperative ECOG performance status 0-1, will be treated with adjuvant nivolumab 480mg Q4W, 9 infusions.

RESULTS:

The primary endpoint is pathological complete response rate (pCR-R). Based on a Fleming design, with α=5% and β=20%, 27 patients have to be evaluated (H0=5%; H1=20%). Secondary endpoints include disease-free survival, overall survival and safety.

CONCLUSION:

This study is planned to include 32 patients to evaluate the pCR-R with the combination of nivolumab and ipilimumab in neoadjuvant setting for MSI/dMMR localized GOA. The MSI/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might mark a turning point in the management of localized MSI/dMMR GOA patients.

• Authors: Romain Cohen, Thomas Pudlarz, Marie-Line Garcia-Larnicol, Dewi Vernerey, Xavier Dray, Léa Clavel, Marine Jary, Guillaume Piessen, Aziz Zaanan, Thomas Aparicio, Christophe Louvet, Christophe Tournigand, Benoist Chibaudel, David Tougeron, Rosine Guimbaud, Jaafar Benouna, Antoine Adenis, Harry Sokol, Christophe Borg, Alex Duval, Magali Svrcek, Thierry André
• Journal: Bulletin du cancer (Bull Cancer) Vol. 107 Issue 4 Pg. 438-446 (Apr 2020) ISSN: 1769-6917 [Electronic] France
• Vernacular Title: Patients atteints d’un cancer gastrique localisé MSI/dMMR, pas de chimiothérapie mais une immunothérapie périopératoire : l’essai de phase II GERCOR NEONIPIGA vient d’être ouvert au recrutement.
• PMID: 32057467 (Publication Type: Clinical Trial Protocol, Journal Article)
• Copyright: Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents, Immunological
• Ipilimumab
• Nivolumab

Topics

• Adenocarcinoma (drug therapy, genetics, pathology, surgery)
• Antineoplastic Agents, Immunological (therapeutic use)
• Chemotherapy, Adjuvant
• Clinical Trials, Phase II as Topic
• DNA Mismatch Repair
• Disease-Free Survival
• Humans
• Ipilimumab (therapeutic use)
• Microsatellite Instability
• Multicenter Studies as Topic
• Neoadjuvant Therapy (methods)
• Nivolumab (therapeutic use)
• Patient Selection
• Perioperative Care
• Phenotype
• Stomach Neoplasms (drug therapy, genetics, pathology, surgery)
• Treatment Outcome