A Randomized Phase 2 Study Of Nivolumab Monotherapy Or Nivolumab Combined with Ipilimumab In Patients with Advanced Gastrointestinal Stromal Tumors

Purpose: Most GISTs are driven by KIT/PDGFRa mutations. TKI benefit is progressively less after imatinib failure. This phase II trial analyzed the efficacy of nivolumab (N) or nivolumab + ipilimumab (N + I) in refractory GIST patients. Patients And Methods: Advanced/metastatic GIST patients refractory to at least imatinib were randomized 1:1 in a noncomparative, parallel group, unblinded Phase 2 trial of N (240mg Q2wks) or N + I (240 mg Q2wks + 1mg/kg Q6wks). The primary endpoint was the ORR of N alone or N+I by RECIST 1.1 in the ITT population. Results: 36 patients with a median of 3 (1-6) prior lines of therapies were enrolled. 10/19(52.6%) patients had SD for a CBR of 52.6 % in the N arm and the median PFS was 11.7 wks (95% CI, 7.0, 17.4). In the N+I arm, 1/16(6.7%) patients had a CR and 4/16(25.0%) had SD for a CBR of 31.3% and a median PFS of 8.3wks (95% CI, 5.6, 22.2). The 4 and 6 month PFS were 42.1% and 26.3%, respectively for N and 31.3% and 18.8%, respectively for N+I. The most common adverse events (AEs) attributed to N and N+I were fatigue: 13.9% and 22.2%, respectively. There were 9 total attributable grade 3-4 AEs. Conclusions: The primary endpoint of RR>15% was not observed for N or N + I. In a heavily pretreated GIST population, responses and long term disease control with both N and N+I were observed. No new safety signals have been observed.