The phase 3 LITESPARK-022 trial reported that combining belzutifan, a HIF-2α inhibitor, with pembrolizumab significantly improved disease-free survival in high-risk clear cell renal cell carcinoma patients after nephrectomy. Trial sponsors presented the data showing an extension in cancer-free interval compared with standard care, supporting a potential adjuvant indication for the regimen. The readout positions belzutifan, already notable for HIF-2α inhibition, as a candidate for earlier-stage ccRCC treatment in combination with PD-1 blockade. Sponsors will evaluate regulatory strategies and potential label expansions based on the magnitude and durability of benefit observed in LITESPARK-022.