FDA Approves Welireg plus Keytruda as First Adjuvant HIF-2a Combination for Clear Cell Renal Cell Carcinoma
On June 12, 2026, the U.S. Food and Drug Administration (FDA) approved Merck's Welireg (belzutifan), a first-in-class oral HIF-2α inhibitor, in combination with Keytruda (pembrolizumab) or Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph, the subcutaneous formulation) as an adjuvant treatment for adult patients with clear cell renal cell carcinoma (ccRCC) post-surgery who are at intermediate-high or high risk of recurrence.1
This landmark approval is supported by data from the randomized, double-blind Phase 3 LITESPARK-022 study (NCT05239728) of 1,841 patients. The study met its primary endpoint, demonstrating that the addition of belzutifan to adjuvant pembrolizumab significantly improved disease-free survival (DFS) compared to pembrolizumab monotherapy (Hazard Ratio 0.72; 95% CI, 0.59 to 0.87; P = .0003), representing an approximate 28% reduction in the risk of recurrence, metastasis, or death.
At a median follow-up of 28.4 months, the estimated 24-month DFS rate was 80.7% for the combination arm versus 73.7% for pembrolizumab alone. Overall survival (OS) data were immature at the time of the analysis (HR 0.78; 95% CI, 0.51 to 1.19; P = .1220). In terms of safety, Grade 3 or higher treatment-emergent adverse events occurred in 52.1% of patients receiving the combination compared to 30.2% on pembrolizumab alone, with anemia (12.1%) and hypoxia (4.6%) being the most notable combination-specific adverse events.
"Belzutifan is able to further decrease the chance of recurrence, metastasis, or death by close to 30%, so we're very ecstatic about this." — Dr. Toni K. Choueiri, Dana-Farber Cancer Institute
"The approval was supported by data from the phase 3 LITESPARK-022 study (NCT05239728), which met its primary end point by showing that the addition of belzutifan to adjuvant pembrolizumab significantly improved disease-free survival (DFS) vs pembrolizumab alone (HR, 0.72; 95% CI, 0.59 to 0.87; P = .0003)." — Urology Times
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An instance of Oncology blockbusters must target adjuvant settings to secure massive patient volumes. — Shifting the clinical focus of these blocking agents to early-stage adjuvant settings vastly expands candidate eligibility and treatment durations. ↩︎