Adding belzutifan to adjuvant pembrolizumab shows DFS benefit in ccRCC

The addition of belzutifan (Welireg) to pembrolizumab (Keytruda) in the adjuvant setting achieved a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared with pembrolizumab plus placebo in patients with clear cell renal cell carcinoma (ccRCC) following nephrectomy, thus meeting the primary end point of the phase 3 LITESPARK-022 trial (NCT05239728).¹

The trial’s key secondary end point, overall survival (OS), will continue to be assessed.

"KEYTRUDA monotherapy given in the adjuvant setting remains an important treatment choice for patients with renal cell carcinoma at an increased risk of recurrence following surgery and is the only approved option to have significantly improved disease-free survival and overall survival in this disease setting. Still, many of these patients do remain at risk of recurrence and continue to represent an unmet need," said M. Catherine Pietanza, MD, vice president, global clinical development, Merck Research Laboratories, in a news release from the company.¹ “These encouraging results of KEYTRUDA in combination with WELIREG from LITESPARK-022 demonstrate the potential to provide additional treatment options for those most in need.”

The safety profile for the combination was consistent with the known profiles for each individual agent, and no new safety signals were observed. Merck plans to share findings from the LITESPARK-022 trial at an upcoming medical meeting and with regulatory authorities worldwide.

According to the company, this is the “first combination regimen to demonstrate improvement in DFS compared to KEYTRUDA monotherapy for these patients in the adjuvant setting.”

About LITESPARK-022

Overall, the double-blind, phase 3 LITESPARK-022 trial enrolled 1841 adult patients with ccRCC across 285 clinical trial sites.² To be eligible for enrollment, patients needed to have intermediate-high risk, high risk, or M1 no evidence of disease; an ECOG performance status of 0 or 1; and adequate organ function. Patients were excluded from the study if they had received prior systemic therapy or prior radiotherapy for RCC.

Those included in the study were randomly assigned to received belzutifan 120 mg orally once daily for approximately 1 year plus pembrolizumab 400 mg intravenously every 6 weeks for approximately 1 year or to pembrolizumab plus placebo. The primary end point for the study is DFS, with OS as a key secondary end point. Other secondary end points include safety and quality of life outcomes.

The trial is expected to reach primary completion in October 2026, and final completion is expected in September 2029.

REFERENCES

1. Merck announces KEYTRUDA® (pembrolizumab) plus WELIREG® (belzutifan) met primary endpoint of disease-free survival (DFS) in certain patients with clear cell renal cell carcinoma (RCC) following nephrectomy. News release. Merck. October 28, 2025. Accessed October 28, 2025. https://www.businesswire.com/news/home/20251028020827/en/Merck-Announces-KEYTRUDA-pembrolizumab-Plus-WELIREG-belzutifan-Met-Primary-Endpoint-of-Disease-Free-Survival-DFS-in-Certain-Patients-With-Clear-Cell-Renal-Cell-Carcinoma-RCC-Following-Nephrectomy

2. A study of belzutifan (MK-6482) plus pembrolizumab (MK-3475) versus placebo plus pembrolizumab in participants with clear cell renal cell carcinoma post nephrectomy (MK-6482-022). ClinicalTrials.gov. Last updated August 14, 2025. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT05239728