Romain Cohen1, Thomas Pudlarz2, Marie-Line Garcia-Larnicol3, Dewi Vernerey4, Xavier Dray5, Léa Clavel6, Marine Jary7, Guillaume Piessen8, Aziz Zaanan9, Thomas Aparicio10, Christophe Louvet11, Christophe Tournigand12, Benoist Chibaudel13, David Tougeron14, Rosine Guimbaud15, Jaafar Benouna16, Antoine Adenis17, Harry Sokol18, Christophe Borg19, Alex Duval20, Magali Svrcek21, Thierry André22. 1. AP-HP, Sorbonne Université, hôpital Saint-Antoine, department of medical oncology, 75012 Paris, France. Electronic address: romain.cohen@aphp.fr. 2. AP-HP, hôpital Saint-Antoine, Department of medical oncology, 75012 Paris, France. 3. GERCOR (Groupe Coopérateur Multidisciplinaire en Oncologie), Paris, France. 4. University Hospital of Besançon, Methodology and Quality of Life Unit in Oncology, 25000 Besançon, France; University Bourgogne Franche-Comté, interactions Hôte-Greffon-Tumeur/Ingénierie cellulaire et génique, EFS BFC, UMR1098, Inserm, 25000 Besançon, France. 5. AP-HP, Sorbonne Université, hôpital Saint-Antoine, department of endoscopy, 75012 Paris, France. 6. Hôpital privé Jean-Mermoz, gastro-enterology and digestive oncology department, Lyon, France. 7. University Bourgogne Franche-Comté, interactions Hôte-Greffon-Tumeur/Ingénierie cellulaire et génique, EFS BFC, UMR1098, Inserm, 25000 Besançon, France; CHU de Jean-Minjoz, Medical oncology department, 3, boulevard Alexander-Fleming, 25000 Besançon, France. 8. Hôpital Claude-Huriez, service de chirurgie digestive et oncologique, 59000 Lille, France. 9. Paris Descartes University, Sorbonne Paris Cité, Georges-Pompidou European Hospital, Department of Digestive Oncology, Paris, France. 10. AP-HP, université de Paris, Hôpital Saint-Louis, Gastro-enterology and digestive oncology department, Paris, France. 11. Institut mutualiste Montsouris, medical oncology department, 75014 Paris, France. 12. AP-HP, Henri-Mondor Hospital, Medical Oncology Department, Créteil, France. 13. Hôpital Franco-Britannique, Fondation Cognacq-Jay, Medical Oncology, Levallois-Perret, France. 14. Poitiers University Hospital, Department of Gastroenterology, Poitiers, France. 15. CHU de Toulouse-IUCT Rangueil-Larrey, Digestive Medical Oncology department, Toulouse, France. 16. University Hospital of Nantes, Digestive Oncology, Nantes, France. 17. ICM Val d'Aurelle, medical oncology department, Montpellier, France. 18. AP-HP, Sorbonne Université, Centre de Recherche Saint-Antoine, CRSA, Hôpital Saint-Antoine, gastroenterology department, Inserm, 75012 Paris, France. 19. University Bourgogne Franche-Comté, interactions Hôte-Greffon-Tumeur/Ingénierie cellulaire et génique, EFS BFC, UMR1098, Inserm, 25000 Besançon, France; Hôpital privé Jean-Mermoz, gastro-enterology and digestive oncology department, Lyon, France. 20. Sorbonne Université, centre de recherche Saint-Antoine, équipe Instabilité des microsatellites et cancer, équipe labellisée par la Ligue nationale contre le cancer et SIRIC CURAMUS, Inserm UMRS 938, 75012 Paris, France. 21. AP-HP, Sorbonne Université, hôpital Saint-Antoine, department of pathology, 75012 Paris, France. 22. AP-HP, Sorbonne Université, hôpital Saint-Antoine, department of medical oncology, 75012 Paris, France.
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.
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
Authors: J Schumacher; P Malfertheiner; M Venerito; T Stolze; S Franke; J Haybaeck; M Moehler; P P Grimminger; H Lang; W Roth; I Gockel; N Kreuser; H Bläker; C Wittekind; F Lordick; M Vieth; L Veits; O Waidmann; P Lingohr; U Peitz; C Schildberg; M Kruschewski; N Vassos; E Goni; C J Bruns; K Ridwelski; S Wolff; H Lippert Journal: J Cancer Res Clin Oncol Date: 2022-02-25 Impact factor: 4.553