Anti-PD-(L)1 antibodies in combination with a VEGF tyrosine-kinase inhibitor (TKI) or ipilimumab are the standard-of-care first-line therapy for patients with advanced-stage clear cell renal cell carcinoma (ccRCC). Nonetheless, treatment options for patients who fail to respond to, or have disease progression on, such regimens are currently limited. Now, data from a phase II study testing the HIF2α inhibitor belzutifan plus the VEGF TKI cabozantinib demonstrate the efficacy of this new treatment approach in these patients.