KEYTRUDA® (pembrolizumab) Plus WELIREG® (belzutifan) Reduced the Risk of Disease Recurrence or Death by 28% in Certain Patients With Earlier-Stage Renal Cell Carcinoma

Combination Therapy Demonstrated Significant Improvement in Disease-Free Survival Compared to KEYTRUDA Monotherapy

Mar. 3, 2026 at 6:47am

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Merck announced the presentation of results from the pivotal Phase 3 LITESPARK-022 trial evaluating KEYTRUDA® (pembrolizumab) in combination with WELIREG® (belzutifan) given in the adjuvant setting for patients with clear cell renal cell carcinoma (RCC) following nephrectomy. The combination therapy significantly improved disease-free survival, reducing the risk of disease recurrence or death by 28% compared to KEYTRUDA monotherapy.

Why it matters

Approximately 40% of patients with renal cell cancer may experience tumor growth after initial treatment. The results from LITESPARK-022 mark an important step forward for certain patients with renal cell cancer, showing a significant reduction in the risk of disease recurrence or death compared to pembrolizumab alone. The combination of pembrolizumab and belzutifan is the first ever regimen in the adjuvant setting for renal cell cancer to demonstrate an improvement in disease-free survival over pembrolizumab monotherapy.

The details

At the first pre-specified interim analysis, KEYTRUDA plus WELIREG given in the adjuvant setting significantly improved disease-free survival (DFS), the study's primary endpoint, reducing the risk of disease recurrence or death by 28% compared to KEYTRUDA plus placebo. Median DFS was not reached in either arm; the estimated 24-month DFS rate was 80.7% for the KEYTRUDA plus WELIREG arm and 73.7% for the KEYTRUDA plus placebo arm.

  • The first pre-specified interim analysis had a median follow-up of 28.4 months (range, 15.0-40.1 months).

The players

KEYTRUDA® (pembrolizumab)

Merck's anti-PD-1 therapy.

WELIREG® (belzutifan)

Merck's first-in-class, oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor.

Dr. Toni K. Choueiri

Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School.

Dr. M. Catherine Pietanza

Vice president, Global Clinical Development, Merck Research Laboratories.

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What they’re saying

“Results from LITESPARK-022 mark an important step forward for certain patients with renal cell cancer, showing a significant reduction in the risk of disease recurrence or death compared to pembrolizumab alone.”

— Dr. Toni K. Choueiri, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Jerome and Nancy Kohlberg professor of medicine, Harvard Medical School

“LITESPARK-022 is a critical part of our comprehensive RCC clinical development program, and the Phase 3 results presented at ASCO GU underscore the importance of KEYTRUDA and WELIREG in helping to treat patients with certain types of renal cell carcinoma.”

— Dr. M. Catherine Pietanza, Vice president, Global Clinical Development, Merck Research Laboratories

What’s next

Based on data from the LITESPARK-022 trial, the U.S. Food and Drug Administration (FDA) has accepted for priority review supplemental applications seeking approval of WELIREG in combination with KEYTRUDA or KEYTRUDA QLEX™ for the adjuvant treatment of adult patients with RCC with a clear cell component with increased risk of recurrence following nephrectomy. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action date, of June 19, 2026 for the WELIREG sNDA and the KEYTRUDA and KEYTRUDA QLEX sBLAs. Merck will also discuss these data with global regulatory authorities.

The takeaway

The combination of pembrolizumab and belzutifan represents a significant advancement in the treatment of certain patients with renal cell carcinoma, demonstrating a 28% reduction in the risk of disease recurrence or death compared to pembrolizumab alone in the adjuvant setting. This regimen has the potential to reshape clinical practice and provide a new treatment option for patients with earlier-stage disease.