Background:Belzutifan,a hypoxia-inducible factor 2α inhibitor,showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies. Methods:In a phase 3,multicenter,open-label,active-controlled trial,we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them,in a 1:1 ratio,to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response).