WELIREG (belzutifan) and LENVIMA (lenvatinib) - (LITESPARK-011)

September 24, 2026: Merck (NYSE: MRK) and Eisai said the FDA approved WELIREG (belzutifan) plus LENVIMA (lenvatinib) for adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) after a PD-1/PD-L1 inhibitor. The companies describe it as the first approved HIF-2α inhibitor plus multi-targeted VEGFR-TKI combination for this setting.

Approval was based on the Phase 3 LITESPARK-011 trial (NCT04586231), which randomized 747 patients to WELIREG + LENVIMA or cabozantinib. At a prespecified interim analysis, the combination significantly improved progression-free survival versus cabozantinib, reducing risk of progression or death by 26% (HR 0.74; 95% CI 0.61-0.89; p=0.001), with median PFS 14.6 months vs 10.6 months. Objective response rate was also significantly better at 53% vs 40% (p=0.0002). At final analysis, overall survival, the other primary endpoint, did not reach statistical significance.

Safety findings included boxed warning language for embryo-fetal harm with WELIREG and notable risks including anemia, hypoxia, and cardiac dysfunction with the combination. Serious adverse reactions occurred in 54% and fatal adverse reactions in 5% of combination-treated patients. LITESPARK-011 results are scheduled for presentation at ESMO Congress 2026 in Madrid.