Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease

Background:Patients with von Hippel-Lindau(VHL)disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α(HIF-2α).Methods:In this phase 2,open-label,single-group trial,we investigated the efficacy and safety of the HIF-2αinhibitor belzutifan(MK-6482,previously called PT2977),administered orally at a dose of 120 mg daily,in patients with renal cell carcinoma associated with VHL disease.The primary end point was objective response(complete or partial response)as measured according to the Response Evaluation Criteria in Solid Tumors,version 1.1,by an independent central radiology review committee.We also assessed responses to belzutifan in patients with non-renal cell carcinoma neoplasms and the safety of belzutifan.