FDA Approval

FDA Approves Belzutifan (Welireg) Plus Pembrolizumab (Keytruda) for Adjuvant Treatment of Clear Cell Renal Cell Carcinoma

Anthony Calabro, MA

Key Highlights

  • The FDA approved belzutifan with pembrolizumab, or pembrolizumab and berahyaluronidase alfa-pmph, for adjuvant treatment of adults with renal cell carcinoma with a clear cell component.
  • Approval was based on disease-free survival data from the phase 3 LITESPARK-022 trial.
  • Belzutifan plus pembrolizumab reduced the risk of recurrence, metastasis, or death vs placebo plus pembrolizumab.

On June 12, the FDA approved belzutifan (Welireg, Merck & Co., Inc) in combination with pembrolizumab (Keytruda, Merck & Co., Inc) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex, Merck & Co., Inc) for the adjuvant treatment of adults with renal cell carcinoma with a clear cell component at intermediate-high or high risk of recurrence after nephrectomy, or after nephrectomy and resection of metastatic lesions.

The approval was supported by LITESPARK-022, a multicenter, double-blind, randomized trial enrolling 1841 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 disease.

Patients were randomly assigned 1:1 to receive belzutifan plus pembrolizumab or placebo plus pembrolizumab as adjuvant therapy until recurrence, unacceptable toxicity, or for up to 54 weeks of belzutifan or 12 months of pembrolizumab. The major efficacy outcome was investigator-assessed disease-free survival. At a prespecified interim analysis, belzutifan plus pembrolizumab demonstrated a statistically significant improvement in disease-free survival, with 186 events vs 246 events in the placebo plus pembrolizumab arm (hazard ratio, 0.72; 95% CI, 0.59-0.87; P = .0003). Median disease-free survival was not reached in either arm, and overall survival data were not mature.

Safety information cited in the notice included a boxed warning for embryo-fetal toxicity with belzutifan, as well as warnings and precautions for anemia and hypoxia. Pembrolizumab labeling includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

The recommended belzutifan dose is 120 mg orally once daily in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph until disease recurrence, unacceptable toxicity, or for up to 54 weeks. Pembrolizumab may be given intravenously at 200 mg every 3 weeks or 400 mg every 6 weeks for up to 12 months; pembrolizumab and berahyaluronidase alfa-pmph may be given subcutaneously at 395 mg/4800 units every 3 weeks or 790 mg/9600 units every 6 weeks for up to 12 months.

Reference
Food and Drug Administration. FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma. Published June 12, 2026. Accessed June 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma