Multicenter randomized phase 2 trial of 2 belzutifan doses for previously treated advanced clear cell renal cell carcinoma

Belzutifan is a first-in-class HIF-2α inhibitor approved for adult patients with advanced renal cell carcinoma following therapy with a PD-(L)1 inhibitor and a VEGF TKI. The optimal belzutifan dose is nog yet clear. The multicenter randomized phase 2 LITESPARK-013 study compared belzutifan 200 mg once daily and 120 mg once daily in patients with advanced clear cell renal cell carcinoma (accRCC). The median follow-up was 20.1 months (range 14.8-28.4). The objective response rate was 23.7% in the 120 mg group and 23.1% in the 200 mg group (p=0.9312). Median duration of response was not reached in the 120 mg group and was 16.1 months in the 200 mg group. No between-group differenced were observed for progression-free survival or overall survival. Grade 3 or 4 treatment-related adverse events were observed in 46.1% of patients in the 120 mg group and 46.2% of patients in the 200 mg group. The authors conclude that these results support 120 mg once daily as the preferred dose for belzutifan.