FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma

FDA approval (June 12, 2026)

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

Supporting trial evidence

Efficacy was evaluated in LITESPARK-022 (NCT05239728), a multicenter, double-blind, randomized trial (n=1,841) in patients with prior nephrectomy for ccRCC at intermediate-high/high risk of recurrence or with resected metastases and no evidence of disease. Patients were randomized 1:1 to belzutifan + pembrolizumab vs placebo + pembrolizumab.

The primary endpoint was investigator-assessed disease-free survival (DFS) (time to recurrence, metastasis, or death). At a prespecified interim analysis, DFS favored belzutifan + pembrolizumab with 186 vs 246 events (HR 0.72, 95% CI 0.59–0.87; p=0.0003). Median DFS was not reached in either arm. Overall survival data were not mature at interim analysis.

Safety and dosing highlights (label)

Belzutifan includes a boxed warning for embryo-fetal toxicity and warnings/precautions for anemia and hypoxia. Pembrolizumab includes warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

Recommended belzutifan dose: 120 mg orally once daily with pembrolizumab (or Keytruda Qlex) until recurrence/unacceptable toxicity, or up to 54 weeks. Pembrolizumab dosing: 200 mg IV q3w or 400 mg IV q6w (or Keytruda Qlex SC q3w/q6w) up to 12 months.

The review was conducted under Project Orbis; reviews at partner agencies were ongoing per the FDA communication.