FDA approves belzutifan in combination with lenvatinib for advanced renal cell carcinoma with a clear cell component
Regulatory approval: On Sept 24, 2026, the FDA approved belzutifan (Welireg) plus lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component following prior PD-1/PD-L1 inhibitor therapy. Approval was supported by the open-label, randomized LITESPARK-011 trial (n=747), which showed a statistically significant improvement in PFS versus cabozantinib; final OS analysis was not statistically significant. Recommended dosing is lenvatinib 20 mg plus belzutifan 120 mg once daily.
FDA approval (Sept 24, 2026)
The FDA approved belzutifan (Welireg) in combination with lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component (ccRCC) following a PD-1 or PD-L1 inhibitor.
Supporting evidence: LITESPARK-011 (NCT04586231)
- Design/Population: Open-label, randomized, active-controlled trial in 747 patients with locally advanced or metastatic ccRCC progressing on/after PD-1/PD-L1 inhibitor therapy, or within 6 months of completing adjuvant PD-1 therapy.
- Arms: Belzutifan + lenvatinib vs cabozantinib (1:1).
- Primary outcomes: PFS by blinded independent central review (RECIST v1.1) and OS; ORR was additional.
Efficacy
- PFS: Median 14.6 months (95% CI, 11.1–16.6) with belzutifan+lenvatinib vs 10.6 months (95% CI, 9.2–11.1) with cabozantinib; HR 0.74 (95% CI, 0.61–0.89); one-sided p=0.00095.
- OS (final): Not statistically significant; median 33.7 vs 28.6 months; HR 0.85 (95% CI, 0.70–1.03).
- ORR: 53% vs 40%; one-sided p=0.0002.
Safety highlights (label)
Belzutifan includes a boxed warning for embryo-fetal toxicity and warnings/precautions for anemia and hypoxia; for the combination, also cardiac dysfunction. Lenvatinib includes multiple warnings/precautions including hypertension and cardiac dysfunction.
Recommended dosage
Lenvatinib 20 mg + belzutifan 120 mg orally once daily until disease progression or unacceptable toxicity.