Phase 3 trial of belzutifan plus lenvatinib versus cabozantinib for advanced ccRCC after anti-PD-(L)1 therapy: final analysis of LITESPARK-011

The phase 3 LITESPARK-011 trial, at 184 centers in 25 countries, investigated belzutifan plus lenvatinib versus cabozantinib in participants with advanced clear-cell renal-cell carcinoma after anti-PD-(L)1 therapy. At earlier analyses, belzutifan plus lenvatinib significantly improved progression-free survival (PFS) and objective response rate (ORR) versus cabozantinib, while overall survival (OS) did not reach significance. Prespecified final analysis of the trial has now been reported. A total of 747 adult patients were randomized to belzutifan-lenvatinib (n=371) or cabozantinib (n=376). At the final analysis, median time from randomization to data cutoff date was 38.8 months (range 29.1-59.0). Belzutifan-lenvatinib continued to demonstrate benefit versus cabozantinib in PFS (HR 0.74; 95% CI 0.62-0.88), ORR (53.1% versus 40.2%), and median duration of response (DOR; 22.0 versus 11.9 months). Mature OS results did not reach statistical significance at final analysis (median 33.7 versus 28.6 months; HR 0.85; 95% CI 0.70-1.03). Grade ≥ 3 treatment-emergent adverse events occurred in 85.4% of patients with belzutifan-lenvatinib and 83.0% of patients with cabozantinib. The authors conclude that at the final analysis of LITESPARK-011, belzutifan-lenvatinib continued to demonstrate PFS, ORR, and DOR benefit versus cabozantinib, while the safety profile of belzutifan plus lenvatinib remained consistent with each drug as monotherapy. These findings support belzutifan plus lenvatinib as a treatment option for advanced ccRCC after anti-PD-(L)1 therapy.