Multicenter phase 2 study of tremelimab plus durvalumab as neoadjuvant or non-operative management for MSI-H G/GEJ adenocarcinoma

In patients with resctable gastric/gastroesophageal junction adenocarcinoma (GAC/GEJAC), dMMR/MSI-H status confers improved survival, but limited benefit from chemotherapy. Immunotherapy may eliminate the need of chemotherapy or surgery for these patients. The multicenter phase 2 INFINITY study in Italy evaluated in cohort 1 (May 2021- February 2022) the activity and safety of tremelimumab plus durvalumab (T300/D) as neoadjuvant treatment for dMMR/MSI-H, resectable GAC/GEJAC, followed by surgery. Pathologic complete response and major pathologic response were seen in 60% and 80%, respectively. The 24-month disease-specific survival rate was 85% and overall survival rate was 92%. In cohort 2 (January 2023-December 2023) 18 patients received T300D; 13 patients had clinical complete response and did not undergo surgery. At 11.5 months median follow-up, one patient had local regrowth and underwent salvage surgery. The 12-month gastrectomy-free survival was 64.2%. The authors conclude that INFINITY provided promising activity results of a chemo-free T300/D combination regimen as pre-operative treatment in dMMR/MSI-H GAC/GEJAC, and the first available feasibility results of a non-operative management strategy in this disease setting.