In a randomized, unblinded, phase 2 trial in which investigators assessed the safety and efficacy of nivolumab monotherapy and nivolumab-ipilimumab combination treatment in advanced gastrointestinal stromal tumor (GIST), patients in both groups demonstrated positive responses to treatment. However, both groups failed to achieve the primary endpoint, which was an overall response rate of >15%.

In the nivolumab group, progression-free survival was 42.1% at 4 months and 26.3% at 6 months; the median progression-free survival was 11.7 weeks. In the combination treatment group, progression-free survival rates at 4 and 6 months were 31.3% and 18.8%, respectively, and the median progression-free survival was 8.3 weeks.

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Patients in the nivolumab group demonstrated a clinical benefit rate of 52.6%, whereas patients in the nivolumab plus ipilimumab group exhibited a 31.3% clinical benefit rate.

The safety profiles of these tyrosine kinase inhibitor (TKI) treatments included 9 grade 3 or 4 adverse events. The most common adverse event was fatigue, reported by 13.9% of individuals in the nivolumab group and 22.2% in the combination group.

Study Methods

Researchers initially enrolled 36 patients with advanced or metastatic GIST who were no longer responding to the first-line TKI treatment, imatinib. These patients were refractory to a median of 3 prior lines of TKI therapy, with a range between 1 and 6. The investigators randomly divided the patients, with 19 in the nivolumab only group and 16 in the nivolumab and ipilimumab group.

The individuals in the nivolumab only group received 250 mg every 2 weeks, while the individuals in the combination treatment group received 250 mg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks.  

The authors concluded, “In a heavily pretreated GIST population, responses and long-term disease control with both [nivolumab] and [nivolumab plus ipilimumab] were observed.” Therefore, nivolumab monotherapy and nivolumab with ipilimumab could be fourth-line or beyond fourth-line TKI treatments for patients with advanced refractory GIST.


Singh AS, Hecht JR, Rosen L, et al. A randomized phase 2 study of nivolumab monotherapy or nivolumab combined with ipilimumab in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res. Published online August 18, 2021. doi:10.1158/1078-0432.CCR-21-0878