A phase 3 trial compared nivolumab plus ipilimumab with sunitinib in previously untreated advanced clear-cell renal-cell carcinoma. The study enrolled 1096 patients, with 550 assigned to nivolumab plus ipilimumab and 546 to sunitinib. The primary endpoints were overall survival, objective response rate, and progression-free survival. Nivolumab plus ipilimumab showed significantly higher overall survival (75% at 18 months vs. 60% with sunitinib) and objective response rate (42% vs. 27%) compared to sunitinib. Median progression-free survival was 11.6 months with nivolumab plus ipilimumab versus 8.4 months with sunitinib. Treatment-related adverse events were common, with 93% of patients in the nivolumab plus ipilimumab group and 97% in the sunitinib group experiencing at least one adverse event. Grade 3 or 4 events occurred in 46% and 63% of patients, respectively. Nivolumab plus ipilimumab was associated with a lower risk of death compared to sunitinib, with a hazard ratio of 0.63. The combination therapy showed significant benefits in overall survival and objective response rate in intermediate- and poor-risk patients. The trial was funded by Bristol-Myers Squibb and Ono Pharmaceutical. The results suggest that nivolumab plus ipilimumab is a more effective treatment option for previously untreated advanced clear-cell renal-cell carcinoma compared to sunitinib.A phase 3 trial compared nivolumab plus ipilimumab with sunitinib in previously untreated advanced clear-cell renal-cell carcinoma. The study enrolled 1096 patients, with 550 assigned to nivolumab plus ipilimumab and 546 to sunitinib. The primary endpoints were overall survival, objective response rate, and progression-free survival. Nivolumab plus ipilimumab showed significantly higher overall survival (75% at 18 months vs. 60% with sunitinib) and objective response rate (42% vs. 27%) compared to sunitinib. Median progression-free survival was 11.6 months with nivolumab plus ipilimumab versus 8.4 months with sunitinib. Treatment-related adverse events were common, with 93% of patients in the nivolumab plus ipilimumab group and 97% in the sunitinib group experiencing at least one adverse event. Grade 3 or 4 events occurred in 46% and 63% of patients, respectively. Nivolumab plus ipilimumab was associated with a lower risk of death compared to sunitinib, with a hazard ratio of 0.63. The combination therapy showed significant benefits in overall survival and objective response rate in intermediate- and poor-risk patients. The trial was funded by Bristol-Myers Squibb and Ono Pharmaceutical. The results suggest that nivolumab plus ipilimumab is a more effective treatment option for previously untreated advanced clear-cell renal-cell carcinoma compared to sunitinib.