EPAS1 and nonpapillary renal cell carcinoma: This approval was based on the results of a phase 2 trial, which showed an overall response rate (ORR) of 49% in RCC patients with VHL disease.17 However, the efficacy of HIF-2α inhibition in non-familial RCC remained relevant, considering that approximately 90% of individuals with ccRCC harbor somatic VHL mutations.