CHMP recommends EU approval of belzutifan plus lenvatinib for advanced ccRCC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of belzutifan (Welireg) plus lenvatinib (Lenvima) for the treatment of adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) following a PD-1 or PD-L1 inhibitor.¹

The recommendation will now be reviewed by the European Commission, which is expected to issue a decision in the next 2 months, according to Merck. If granted, marketing authorization would apply to all 27 European Union (EU) member states, as well as Iceland, Liechtenstein and Norway.

Belzutifan plus lenvatinib was approved in the US for advanced ccRCC in September 2026.

Related: Behind the FDA approval of belzutifan plus lenvatinib in advanced ccRCC, with Robert Motzer, MD

“Patients with advanced renal cell carcinoma in the European Union have limited treatment options if their disease progresses following anti-PD-1 or anti-PD-L1 therapy,” said Dr. Christina Derleth, vice president, global oncology clinical development, Merck Research Laboratories, in a news release from the company.¹ “This positive opinion is a meaningful step toward potentially bringing this first-of-its-kind regimen to patients in need in the European Union and underscores the important role of [belzutifan] plus lenvatinib as a new option in the treatment of renal cell carcinoma.”

Efficacy data on belzutifan plus lenvatinib

The recommendation is supported by data from the phase 3 LITESPARK-011 trial (NCT04586231), in which the combination of belzutifan plus lenvatinib demonstrated a statistically significant improvement in progression-free survival (PFS) vs cabozantinib (Cabometyx). The results were initially presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. Final overall survival (OS) results were presented at the 2026 European Society for Medical Oncology Congress in Madrid, Spain and concurrently published in Annals of Oncology.²

In total, the study enrolled 747 patients. Participants were eligible for the trial if they had locally advanced or metastatic ccRCC that had progressed on or after a PD-1 or PD-L1 inhibitor or within 6 months of completing adjuvant therapy with a PD-1 inhibitor. Patients were randomly assigned to 120 mg oral once daily belzutifan in combination with 20 mg oral once daily lenvatinib or to 60 mg oral once daily cabozantinib.

At the updated analysis, belzutifan plus lenvatinib demonstrated a 26% reduction in the risk of disease progression or death compared with cabozantinib (HR, 0.74; 95% CI, 0.61 to 0.89; P = .001). The median PFS was 14.8 months (95% CI, 11.2 to 16.6) with belzutifan plus lenvatinib vs 10.8 months (95% CI, 9.2 to 11.1) with cabozantinib.

The trial’s secondary end point, OS, did not meet statistical significance. The median OS was 33.7 months (95% CI, 29.0 to 46.9) with the combination vs 28.6 months (95% CI, 24.1 to 31.4) with cabozantinib (HR, 0.85; 95% CI, 0.70 to 1.03; 1-sided P = .04689).

The combination continued to demonstrate benefits in key secondary end points at the final analysis. The objective response rate was 53.1% (95% CI, 47.9 to 58.3) with the combination vs 40.2% (95% CI, 35.2 to 45.3) with cabozantinib, representing an estimated difference of 12.9% (95% CI, 5.8 to 19.8). Complete responses occurred in 6.7% vs 1.3% of patients. The median duration of response was 22.0 months with the combination (range, 2.0 to 52.2+) vs 11.9 months with cabozantinib (range, 1.8+ to 44.1+).

Safety data

Grade 3 or higher adverse events (AEs) occurred in 85.4% of patients in the combination arm and 83.0% of patients in the cabozantinib arm. Serious AEs occurred in 55.1% and 46.9% of patients, respectively. Treatment-emergent AEs led to death in 5.4% of particpants in the combination arm and 3.8% of participants in the cabozantinib arm.

Anemia (70.8% vs 27.0%) and hypoxia (15.7% vs 0%) were more frequent with the combination, whereas diarrhea (54.3% vs 71.2%), palmar-plantar erythrodysesthesia (20.5% vs 51.8%), and stomatitis (14.3% vs 28.3%) were more frequent with cabozantinib. Hypertension was common in both arms (59.5% vs 57.1%).

Cardiac dysfunction, an AE of clinical interest, occurred in 13.0% vs 8.1% of patients.

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REFERENCES

1. Merck receives positive EU CHMP opinion for WELIREG® (belzutifan) in combination with lenvatinib for adults with advanced renal cell carcinoma with a clear cell component (ccRCC) following treatment with an anti-PD-1/PD-L1 therapy. News release. Merck. November 13, 2026. Accessed November 13, 2026. https://www.merck.com/news/merck-receives-positive-eu-chmp-opinion-for-welireg-belzutifan-in-combination-with-lenvatinib-for-adults-with-advanced-renal-cell-carcinoma-with-a-clear-cell-component-ccrcc-following-treatm/

2. Heng DYC, Schmidinger M, McDermott R, et al. Final prespecified analysis of the phase 3 LITESPARK-011 study: belzutifan plus lenvatinib versus cabozantinib for advanced renal cell carcinoma after anti–PD-(L)1 therapy. Ann Oncol. 2026 Oct 25:S0923-7534(26)06893-6. doi:10.1016/j.annonc.2026.10.109