Multicenter phase 2 trial of dual CTLA-4 and PD-1 blockade in rare cancers: final results from NCI/SWOG S1609

NCI/SWOG S1609 was a signal seeking trial of dual CTLA-4 and PD-1 blockade with ipilimumab plus nivolumab in 53 cohorts of rare cancer patients. Overall, 798 previously treated patients were enrolled, and 727 eligible patients received treatment. In 24 of 53 cohorts (45%) clinical activity was observed, defined as 2 or more patients with confirmed response. Median objective response rate was 12% (range 0-75), median clinical benefit rate was 27% (0-75), median 2-year progression-free survival was 10% (0-75), and median 3-year overall survival was 23% (0-100). PFS at 6 months correlated moderately was 1-year and 3-year OS. Altogether, 82 patients (11%) had an iPFS of ≥ 2 years. Immune-related toxicity rates were comparable to prior studies. Adverse events led to treatment discontinuation in 102 patients (14%). Patients alive at 6 months who discontinued treatment due to immune-related toxicity had longer OS than those who discontinued treatment for other reasons. The authors conclude that patients with multiple refractory rare cancers derived meaningful benefit from ipilimumab plus nivolumab.