FDA Approves Welireg Plus Lenvima for Advanced Kidney Cancer After Immunotherapy

The Food and Drug Administration (FDA) has approved Welireg (belzutifan) in combination with Lenvima (lenvatinib) for adults with advanced renal cell carcinoma (RCC) with a clear cell component following treatment with a PD-1 or PD-L1 inhibitor.

The approval, announced Sept. 24, 2026, provides a new treatment option for people whose advanced kidney cancer has progressed after immunotherapy or within six months of completing adjuvant treatment with a PD-1 inhibitor.

Welireg is made by Merck & Co., Inc., while Lenvima is manufactured by Eisai Inc.

Welireg and Lenvima Combination Shows Longer Progression-Free Survival

The FDA's decision was based on findings from the phase 3 LITESPARK-011 trial (NCT04586231), which included 747 patients with advanced clear cell RCC.

Patients had locally advanced or metastatic disease that had progressed during or after treatment with a PD-1 or PD-L1 inhibitor, or within six months of completing adjuvant treatment with a PD-1 inhibitor.

Participants were randomly assigned to receive either Welireg plus Lenvima or Cabometyx (cabozantinib).

The combination demonstrated a statistically significant improvement in progression-free survival (PFS), which measures how long patients live without their cancer worsening.

• Median PFS: 14.6 months with Welireg plus Lenvima compared with 10.6 months with Cabometyx
• Risk of disease progression or death: Reduced by 26% with the Welireg-Lenvima combination
• Objective response rate: 53% with Welireg plus Lenvima compared with 40% with Cabometyx

Overall survival (OS), which measures how long patients live regardless of whether their cancer progresses, was not statistically significantly different between the groups at the final analysis. Median OS was 33.7 months with Welireg plus Lenvima compared with 28.6 months with Cabometyx.

What This Means for Patients

For people with advanced clear cell RCC whose cancer has progressed after a PD-1 or PD-L1 inhibitor, treatment options can become more limited. The FDA approval makes the combination of Welireg and Lenvima an additional treatment option in this setting.

The trial results show that patients receiving the combination went longer without their disease progressing compared with those receiving Cabometyx. More than half of patients treated with Welireg and Lenvima experienced a tumor response.

It's important to note that the trial did not demonstrate a statistically significant improvement in overall survival at the final analysis. Patients should discuss their previous treatments, overall health, potential side effects and treatment goals with their cancer care team when considering treatment options.

What Are the Side Effects of Welireg and Lenvima?

Welireg carries a boxed warning for embryo-fetal toxicity, meaning the drug can cause harm to a developing fetus. The drug also includes warnings and precautions for anemia and hypoxia, a condition in which the body does not receive enough oxygen.

When Welireg is used with Lenvima, cardiac dysfunction is also included among the warnings and precautions.

Lenvima has additional warnings and precautions for several potential side effects, including high blood pressure, cardiac dysfunction, blood clots in arteries, liver problems, kidney impairment, proteinuria, diarrhea, fistulas and gastrointestinal perforation, changes in heart rhythm, low calcium levels, reversible posterior leukoencephalopathy syndrome, bleeding, thyroid dysfunction, impaired wound healing and osteonecrosis of the jaw.

Patients should talk with their care team about any new or worsening symptoms during treatment. Their doctors can monitor for potential side effects and determine whether treatment adjustments are needed.

How Is Welireg Plus Lenvima Given?

The FDA-recommended dose is 120 milligrams of Welireg once daily in combination with 20 milligrams of Lenvima once daily.

Treatment is continued until the cancer progresses or side effects become unacceptable.

For people living with advanced clear cell RCC after immunotherapy, this approval adds another treatment approach that can help delay disease progression. As with any cancer treatment, patients should discuss the potential benefits and risks with their oncology team to determine whether the combination is appropriate for them.

References

1. U.S. Food and Drug Administration. “FDA approves belzutifan in combination with lenvatinib for advanced renal cell carcinoma with a clear cell component.” September 24, 2026.