FDA approves Welireg-Keytruda combination for high-risk renal cell carcinoma

FDA has approved Welireg (belzutifan) in combination with Keytruda (pembrolizumab) or Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) for the adjuvant treatment of adults with clear cell renal cell carcinoma (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, or after nephrectomy and resection of metastatic lesions.

The approval introduces the first combination of a PD-1 inhibitor and a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor in renal cell carcinoma and provides a new option for patients at substantial risk of recurrence after surgery. Until now, pembrolizumab monotherapy has been the standard adjuvant systemic treatment in this setting.

The decision was based on the phase 3 LITESPARK-022 trial, which enrolled 1,841 patients with ccRCC at intermediate-high or high risk of recurrence. Adding belzutifan to pembrolizumab reduced the risk of disease recurrence, metastasis, or death by 28% compared with pembrolizumab alone. Disease-free survival improved despite both groups receiving active immunotherapy.

For oncologists, the findings represent the first phase 3 evidence demonstrating improved disease-free survival over adjuvant pembrolizumab alone in this population. The approval provides a new adjuvant treatment option for patients with resected high-risk disease who remain at substantial risk of recurrence following surgery.

Clinicians should be aware of the distinct toxicity profile of belzutifan. The drug carries a boxed warning for embryo-fetal toxicity and requires monitoring for anemia and hypoxia, both of which were common in the trial. Pembrolizumab-related immune-mediated adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, remain important considerations.

“The FDA approval of the novel Keytruda and Welireg combination is exciting news for the kidney cancer community,” said Bryan Lewis, CEO and co-founder, KidneyCan. “This progress reflects an important step in addressing the needs of patients with earlier-stage renal cell carcinoma.”

Sources:

Merck. 2026 June 12. [Press release]. FDA Approves KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), Each With WELIREG (belzutifan), for Adjuvant Treatment of Certain Patients With Clear Cell Renal Cell Carcinoma (ccRCC)

FDA. 2026 June 12. [Press release]. FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma