Merck and Eisai said the US Food and Drug Administration has approved WELIREG (belzutifan) in combination with LENVIMA (lenvatinib) for adults with advanced renal cell carcinoma with a clear cell component (ccRCC) whose disease has progressed after treatment with a PD-1 or PD-L1 inhibitor.

 

The approval marks a new treatment option for patients with advanced kidney cancer following immunotherapy, the companies said.

 

WELIREG is Merck’s first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, while LENVIMA is an oral multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai.

 

The FDA decision is based on results from the Phase 3 LITESPARK-011 trial. At a prespecified interim analysis, the WELIREG-LENVIMA combination significantly improved progression-free survival (PFS), one of the trial’s dual primary endpoints, compared with cabozantinib.

 

The combination reduced the risk of disease progression or death by 26%, with a hazard ratio of 0.74.

 

Median PFS was 14.6 months with WELIREG plus LENVIMA, compared with 10.6 months with cabozantinib.

 

The combination also produced a significantly higher objective response rate (ORR), a key secondary endpoint: 53% versus 40% for cabozantinib.

 

At the final analysis, however, overall survival (OS), the study’s other primary endpoint, did not reach statistical significance for patients treated with WELIREG plus LENVIMA versus cabozantinib.

 

The companies said additional results, including duration-of-response data, will be presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.

 

“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, 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 M. Catherine Pietanza, Vice President, Global Clinical Development, Merck Research Laboratories. 

 

“This approval represents real progress for patients and further reinforces the importance of a HIF-2α inhibitor plus TKI combination as a new treatment approach for these patients.”

 

“Patients facing advanced renal cell carcinoma need treatment options at every stage of their journey, and the complexity of managing this disease over time makes every treatment decision meaningful,” said Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai. 

 

“Combination approaches with LENVIMA have shaped the treatment landscape for advanced RCC from frontline therapy through later lines, and this FDA approval builds on that legacy by introducing WELIREG plus LENVIMA – the first and only approved combination following a PD-1/PD-L1 inhibitor. At Eisai, our science is driven by the humanity of the patients we serve, and, alongside Merck, we are proud to continue advancing combination treatment options with LENVIMA for the kidney cancer community.”