A randomized phase 2 study of nivolumab monotherapy versus nivolumab combined with ipilimumab in patients with metastatic or unresectable gastrointestinal stromal tumor (GIST).

Abstract

55 Background: The therapy with tyrosine kinase inhibitors changed the prognosis of patients with advanced GIST. Unfortunately, most of the tumors become resistant to therapy and patients succumb to the disease. New therapies for this patient population are needed. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST progressing on at least imatinib were enrolled on a randomized, parallel group, unblinded phase 2 trial of either nivolumab(nivo) (240 mg Q2wks) or nivo (240 mg Q2wks) with ipilimumab(ipi) (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate (ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Patients were randomized 1:1 and the response was assessed every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: To date, 14 patients (median # of prior therapies: 4) have started on trial and 8 remain on treatment. In the nivo only arm, 3/7 patient had SD for a CBR of 42.8 %. The median PFS of the nivo arm was 8 weeks. In the nivo + ipi arm, 1/5(20%) patients had a PR and 1/5 have SD for a CBR of 40%; 2 patients were censored. The median PFS of the nivo + ipi arm was 8.43 weeks. 1 patient in the nivo arm had grade 3 fatigue and 1 patient in the nivo + ipi arm had grade 3 diarrhea. Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, durable responses and disease control were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.