Randomized phase 2 trial of ipilimumab-nivolumab versus standard of care for non-clear cell renal cell carcinoma

Non-clear cell renal cell cancers (nccRCCs) are a heterogeneous group of more than 20 different entities. Tyrosine kinase inhibitors with or without immune checkpoint inhibitors are considered as a standard of care (SOC), but optimal treatment is not yet defined. The multinational randomized phase 2 SUNNIFORECAST trial compared ipilimumab plus nivolumab versus SOC for previously untreated locally advanced or metastatic nccRCC. The 12-months OS rate (primary endpoint) was 78% with ipilimumab-nivolumab versus 68% with SOC (p=0.026), median OS was 33.2 months versus 25.2 months (HR 0.81; p=0.163); the median progression-free survival was 5.4 months versus 5.7 months; and objective response rate was 32.8% versus 19.3%. Exploratory analysis showed a significant OS advantage with ipilimumab-nivolumab over SOC in patients with PD-L1 combined positive score ≥1 (HR 0.56; 95% CI 0.37-0.86). Treatment discontinuation due to toxicity occurred in 17% of patients with ipilimumab-nivolumab and 9% of patients with SOC. The authors conclude that these results underline a relevant clinical benefit of ipilimumab-nivolumab for previously untreated advanced nccRCC compared to current SOC.