Merck’s Welireg (belzutifan) combined with Keytruda (pembrolizumab) secured a new FDA approval in adjuvant clear cell renal cell carcinoma (ccRCC). The authorization establishes the PD-1 plus HIF-2α inhibitor regimen for adults at intermediate-high or high risk of recurrence after kidney removal surgery. The decision is tied to Merck’s Litespark-022 pivotal trial, where Welireg plus Keytruda reduced the risk of disease recurrence, metastasis, or death by 28% versus Keytruda and placebo. Estimated disease-free survival was 81% in the combination arm versus 74% in the control group. While overall survival data are not yet mature, the approval places the combination into earlier-stage RCC for the first time following Welireg’s 2023 advanced RCC clearance—reshaping the sequencing conversations in the adjuvant setting.