- FDA reviews sNDAs for WELIREG plus LENVIMA in advanced RCC, target date October 4, 2026.
- Phase 3 LITESPARK-011 trial shows 30% risk reduction in disease progression or death.
- Median PFS: 14.8 months for WELIREG plus LENVIMA vs. 10.7 months for cabozantinib.
- Grade ≥3 TRAEs in 71.6% of WELIREG plus LENVIMA patients vs. 65.8% for cabozantinib.
Trial Overview
The Phase 3 LITESPARK-011 trial evaluated the combination of WELIREG (belzutifan) and LENVIMA (lenvatinib) in patients with advanced renal cell carcinoma (RCC) who had progressed after anti-PD-1/L1 therapy. This trial is the first to show a positive outcome for a HIF-2 alpha inhibitor combined with a tyrosine kinase inhibitor in this patient group.
Key Findings
With a median follow-up of 29 months, the combination therapy demonstrated a 30% reduction in the risk of disease progression or death compared to cabozantinib. The median progression-free survival (PFS) was 14.8 months for the combination versus 10.7 months for cabozantinib. A trend towards improved overall survival (OS) was also noted, with median OS at 34.9 months for the combination compared to 27.6 months for cabozantinib.
Regulatory Status
Based on these results, the U.S. FDA has accepted two supplemental New Drug Applications for WELIREG plus LENVIMA, with a target action date set for October 4, 2026. Discussions with global regulatory authorities are ongoing to support potential submissions outside the U.S.
Adverse Events
Grade ≥3 treatment-related adverse events occurred in 71.6% of patients receiving the combination therapy, compared to 65.8% for those on cabozantinib. Serious adverse events were observed in 51.6% of the combination group versus 43.9% for cabozantinib, with treatment-related deaths reported in 5.4% and 3.2% of patients, respectively.
