Multicenter phase 2 study of belzutifan plus cabozantinib for advanced clear cell renal cell carcinoma after immunotherapy

Few treatment options are available for patients with advanced renal cell carcinoma who have previously received anti-PD-(L)1 based immunotherapy. Cohort 2 of a phase 2 study at ten centers in the USA evaluated the HIF-2α inhibitor belzutifan in combination with the multitargeted TKI cabozantinib for advanced clear cell renal cell carcinoma (accRCC) after immunotherapy. Confirmed objective response was seen in 30.8% of patients (95% CI 18.7-45.1) including complete response in one of 52 patients (2%). Serious treatment-related adverse events occurred in 29% of patients. One death was considered treatment related (respiratory failure). The authors conclude that the combination of belzutifan plus cabozantinib has promising antitumor activity in patients with pretreated accRCC.