FDA Approves Belzutifan Plus Pembrolizumab for Patients With Clear Cell Renal Cell Carcinoma

Clinical Summary: 

• Design/Population: The phase 3 LITESPARK-022 trial evaluated belzutifan plus pembrolizumab vs placebo plus pembrolizumab in patients with clear cell renal cell carcinoma at intermediate-high or high risk of recurrence following nephrectomy.
• Key Outcomes: Belzutifan plus pembrolizumab significantly improved disease-free survival compared with pembrolizumab alone.
• Clinical Relevance: Based on these results the FDA has approved belzutifan plus pembrolizumab, introducing a new adjuvant treatment option in this patient population. 

On June 12, 2026, the US Food and Drug Administration (FDA) approved adjuvant belzutifan (Welireg; Merck) plus pembrolizumab (Keytruda; Merck) for adult patients with clear cell renal cell carcinoma at intermediate- or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. The approval was based on results from the phase 3 LITESPARK-022 trial.

In this multicenter, double-blind study, 1841 patients were randomized 1:1 to receive either belzutifan plus pembrolizumab or placebo plus pembrolizumab until disease recurrence, unacceptable toxicity, or for up to 54 weeks of belzutifan and 12 months of pembrolizumab. The primary end point was investigator-assessed disease-free survival (DFS), defined as time to recurrence, metastasis, or death. A key secondary end point was overall survival (OS). 

At prespecified interim analysis, DFS was significantly improved with belzutifan plus pembrolizumab compared with placebo plus pembrolizumab with 186 DFS reported in the belzutifan arm and 246 events reported in the placebo arm (hazard ratio [HR], 95% confidence interval [CI], 0.59 to 0.87; P = .0003). Median DFS was not reached in either treatment arm. OS data were not mature. 

The recommended dose of belzutifan is 120 mg administered once daily with 200 mg of pembrolizumab  once every 3 weeks or 400 mg once every 6 weeks, until disease recurrence or unacceptable toxicity. 

The FDA has also approved belzutifan plus 395 mg/4,800 units subcutaneously once every weeks or 790 mg/9,600 units every 6 weeks, until disease recurrence, unacceptable toxicity. 

The prescribing information for belzutifan includes a boxed warning for embryo-fetal toxicity and warnings for anemia and hypoxia. Pembrolizumab prescribing information includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

Source: 

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