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

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 microsotellite 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; EUORACT 2018-00471222) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumob 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 MO, MSI/dMMR. Patients will be treated with nivolumab 240 mg Q2 W, 6 infusions, and ipilimumob 1 mg/kg Q6 W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoodjuvant treatment and postoperative ECOG performance status 0-1, will be treated with adjuvant nivolumab 480 mg Q4 W, 9 infusions. Results > The primary endpoint is pathological complete response rate (pCR-R). Based on Fleming design, with alpha = 5% and beta = 20%, 27 patients hove to be evaluated (HO = 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 MSl/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might murk o turning point in the management of localized MSI/dMMR GOA patients.