Multicenter phase 2 trial of first-line belzutifan plus cabozantinib for advanced clear-cell renal cell carcinoma

The first-in-class HIF-2α inhibitor belzutifan has shown antitumor activity as monotherapy and in combination with cabozantinib in patients with previously treated advanced kidney cancer. Cohort 1 of the multicenter phase 2 LITESPARK-003 study evaluated the combination of belzutifan and cabozantinib for previously untreated advanced clear-cell renal cell carcinoma. The combination induced confirmed objective response in 70% of patients (95% CI 55-82), including complete response in 8%. The most frequent grade 3 or 4 treatment-related adverse events were hypertension (12% of patients), anemia (10%), and fatigue (8%). There were no grade 5 TRAEs. The authors conclude that the combination of belzutifan and cabozantinib has promising antitumor activity in treatment-naïve patients with advanced clear-cell renal cell carcinoma, and further investigation of an HIF-2α inhibitor with a multitargeted tyrosine kinase inhibitor in this population in warranted.