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.
Keywords: Cancer de l’estomac; Gastric cancer; Instabilité des microsatellites; Ipilimumab; Lynch syndrome; Microsatellite instability; Nivolumab; Syndrome de Lynch.