Results from the LITESPARK-011 Phase 3 trial show that the combination of belzutifan (Welireg) and lenvatinib (Lenvima) is more effective than cabozantinib (Cabometyx) for patients with advanced clear cell renal cell carcinoma (ccRCC) previously treated with immunotherapy. The combination improved progression-free survival to 14.8 months compared with 10.7 months for cabozantinib, reducing the risk of disease progression or death by 30%. More patients responded to the combination (52.6% vs. 40.2%), including more complete responses.
The benefit also lasted longer. At 24 months, nearly half of responding patients in the combination group were still benefiting, compared with about one-quarter in the cabozantinib group. Overall survival was longer with the combination (34.9 vs. 27.6 months), but this difference has not yet reached statistical significance.
Side effects were similar between groups and consistent with known drug profiles. Severe adverse events occurred at comparable rates, and quality of life outcomes were similar. These results support the combination as a promising option after initial immunotherapy failure.