The FDA has approved belzutifan (Welireg) in combination with lenvatinib (Lenvima) for the treatment of adult patients with advanced clear cell renal cell carcinoma (ccRCC) following progression on a PD-1 or PD-L1 inhibitor, according to a news release from the agency.
What were the data that supported the belzutifan approval?
Supporting the approval of belzutifan/lenvatinib in this PD-1/PD-L1–refractory group were data from the phase 3 LITESPARK-011 trial (NCT04586231), in which the investigational combination was assessed against cabozantinib (Cabometyx) for the treatment of patients with locally advanced or metastatic ccRCC.
Therein, the median progression-free survival (PFS) per blinded independent central review was 14.6 months (95% CI, 11.1-16.6) with belzutifan/lenvatinib vs 10.6 months (95% CI, 9.2-11.1) with cabozantinib; the HR for PFS was 0.74 (95% CI, 0.61-0.89; P = 0.00095). Moreover, a final analysis for overall survival (OS) revealed respective values of 33.7 months (95% CI: 29.0-46.9) vs 28.6 months (95% CI: 24.1-31.4) in each arm (HR, 0.85; 95% CI: 0.70-1.03). Moreover, the objective response rate (ORR) was 53% (95% CI, 47%-58%) vs 40% (95% CI, 35%-45%) in each arm (P = 0.0002).
What is the recommended dosage of the combination?
The recommended dosage for the combination is 20 mg of lenvatinib and 120 mg of belzutifan taken once daily in the absence of disease progression or unacceptable toxicity.
Prescribing information for belzutifan includes boxed warnings for embryo-fetal toxicity, in addition to warnings and precautions for anemia and hypoxia. The lenvatinib prescribing information includes warnings and precautions for hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation, and gastrointestinal perforation, among other conditions. Collectively, the combination includes warnings and precautions for cardiac dysfunction.
Reference
FDA approves belzutifan in combination with lenvatinib for advanced renal cell carcinoma with a clear cell component. News release. FDA. September 24, 2026. Accessed September 24, 2026. https://tinyurl.com/ynx76c3x
