FDA Approves Welireg Plus Keytruda Combination for Adjuvant Treatment of Renal Cell Carcinoma

The Food and Drug Administration (FDA) on June 12, 2026, approved Welireg (belzutifan) in combination with Keytruda (pembrolizumab) for the adjuvant treatment of adults with renal cell carcinoma with a clear cell component at intermediate-high or high risk of recurrence following surgery to remove the kidney, or following surgery to remove the kidney and resection of metastatic lesions.

The approval also covers the use of Welireg in combination with Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph), a subcutaneous formulation of Keytruda. Both Welireg and Keytruda are manufactured by Merck & Co., Inc.

The LITESPARK-022 Trial

The approval was based on findings from the phase 3 LITESPARK-022 trial, a multicenter, double-blind, randomized study that enrolled 1,841 patients with prior nephrectomy for clear cell renal cell carcinoma who were at intermediate-high or high risk of recurrence, or who had resected metastases with no evidence of remaining disease.

Patients were randomly assigned in a 1-to-1 ratio to receive either Welireg in combination with Keytruda or placebo in combination with Keytruda as adjuvant therapy meaning treatment given after surgery to reduce the risk of the cancer coming back.

Treatment continued until disease recurrence or unacceptable toxicity, for up to 54 weeks of Welireg and up to 12 months of Keytruda.

Disease-Free Survival Results

The major efficacy outcome measured in the trial was disease-free survival defined as the time from randomization until recurrence, metastasis, or death.

At a prespecified interim analysis, the combination of Welireg plus Keytruda demonstrated a statistically significant improvement in disease-free survival compared with placebo plus Keytruda. There were 186 disease-free survival events in the Welireg combination arm compared with 246 events in the placebo arm, with a hazard ratio of 0.72 and a 95% confidence interval of 0.59 to 0.87, and a p-value of 0.0003 reflecting a 28% reduction in the risk of recurrence, metastasis, or death. Median disease-free survival was not reached in either treatment arm at the time of analysis. Overall survival data were not yet mature at the time of the interim analysis.

Recommended Dose and Administration

The recommended dose of Welireg is 120 milligrams taken orally once daily, in combination with Keytruda (pembrolizumab), until disease recurrence or unacceptable toxicity, or for up to 54 weeks.

The recommended dose of Keytruda (pembrolizumab) is 200 milligrams administered intravenously every three weeks, or 400 milligrams every six weeks, in combination with Welireg 120 milligrams orally once daily, until disease recurrence, unacceptable toxicity, or for up to 12 months.

For patients receiving the subcutaneous formulation, the recommended dose of Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) is 395 milligrams per 4,800 units administered subcutaneously every three weeks, or 790 milligrams per 9,600 units every six weeks, in combination with Welireg 120 milligrams orally once daily.

Key Side Effects and Warnings

The prescribing information for Welireg includes a boxed warning for embryo-fetal toxicity, as well as warnings and precautions for anemia and low oxygen levels in the blood. Patients who are pregnant or may become pregnant should be counseled about these risks before starting treatment.

The prescribing information for Keytruda includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

References

1. "FDA Approves Belzutifan (Welireg) With Pembrolizumab (Keytruda) for Adjuvant Treatment of Renal Cell Carcinoma." U.S. Food and Drug Administration. June 12, 2026.

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