RAHWAY, N.J. & NUTLEY, N.J. — Merck and Eisai said the U.S. Food and Drug Administration has approved WELIREG (belzutifan) in combination with LENVIMA (lenvatinib) for certain adults with advanced renal cell carcinoma with a clear cell component following treatment with a PD-1 or PD-L1 inhibitor.
The dual oral regimen is the first approved combination of a HIF-2 alpha inhibitor and a multi-targeted VEGFR tyrosine kinase inhibitor for this patient population.
The approval is based on results from the Phase 3 LITESPARK-011 trial, which compared WELIREG plus LENVIMA with cabozantinib.
In a pre-specified interim analysis, the combination reduced the risk of disease progression or death by 26% compared with cabozantinib. Median progression-free survival was 14.6 months with WELIREG plus LENVIMA compared with 10.6 months for cabozantinib.
The combination also produced an objective response rate of 53%, compared with 40% for cabozantinib. Overall survival, however, did not meet statistical significance at the final analysis.
“While there has been much progress in the first-line treatment of advanced kidney cancer, we have limited options to offer patients if the disease progresses after treatment with a PD-1/PD-L1 immunotherapy,” said Dr. Robert Motzer, Principal Investigator and Genitourinary Medical Oncologist at Memorial Sloan Kettering Cancer Center. “With this FDA approval of belzutifan plus lenvatinib, we have a new treatment option for patients who progress following treatment with anti-PD-1/PD-L1 therapy – an important development for patients and the physicians who care for them.”
“By bringing together two therapies that each target different pathways, WELIREG plus LENVIMA is now the first approved regimen of its kind, offering a new treatment option for certain patients with advanced renal cell carcinoma who have progressed after anti-PD-1/PD-L1 therapy,” said Dr. M. Catherine Pietanza, Vice President, Global Clinical Development at Merck Research Laboratories.
The Phase 3 LITESPARK-011 trial enrolled 747 patients with locally advanced or metastatic clear-cell renal cell carcinoma who had progressed on or after a PD-1 or PD-L1 inhibitor, or within six months of completing adjuvant PD-1 therapy.
Serious adverse reactions occurred in 54% of patients treated with WELIREG plus LENVIMA. The most frequently reported serious reactions included hypoxia, pneumonia, hyponatremia, acute kidney injury, hemorrhage, anemia and cardiac failure.
WELIREG carries a boxed warning for embryo-fetal harm and can also cause severe anemia and hypoxia. The combination may also cause serious cardiac dysfunction, including heart failure and cardiomyopathy.
