Multicenter phase 2 trial of nivolumab plus ipilimumab for advanced dMMR/MSI-H noncolorectal cancers

Cohort D of the nonrandomized phase 2 MOST-CIRCUIT trial, at 17 centers in Australia and New Zealand, evaluated nivolumab plus ipilimumab, every three weeks for four doses, followed by nivolumab every four weeks for 96 weeks or until disease progression or unacceptable toxicity, in patients with advanced dMMR/MSI-H noncolorectal cancers. The co-primary endpoints were objective response rate (ORR) and progression-free survival rate at 6 months (PFS-6). Overall, 52 patients representing 17 tumor types were included, with the most common tumor type being endometrial cancer (n=26; 50%) and 27 patients (52%) being pretreated for metastatic disease. The median follow-up was 10.7 months (range 6.2-38). ORR was 63% (95% CI 50-75) with the median duration of response not being reached and 79% of response being ongoing. The PFS-6 was 71% for the overall cohort and 69% of patients with endometrial cancer. Median PFS and OS were not reached. Overall, 12 patients (23%) experienced a grade 3-4 immune-related adverse event. The authors conclude that nivolumab plus ipilimumab showed significant activity in dMMR/MSI-H noncolorectal cancer.