Merck announced new Phase III results from the Litespark-022 trial evaluating Keytruda (pembrolizumab) in combination with Welireg (belzutifan) as adjuvant treatment for patients with clear cell renal cell carcinoma (RCC) following nephrectomy.

The late-breaking data were presented at the American Society of Clinical Oncology (ASCO) Genitourinary (Gu) Cancers Symposium and were included in the official ASCO GU press program.¹ Renal cell carcinoma accounts for approximately 90% of kidney cancer diagnoses worldwide, with an estimated 435,000 new cases and 156,000 deaths reported globally in 2022.

What was the Litespark-022 trial?

Litespark-022 enrolled 1,841 patients in a randomized, double-blind trial comparing one year of WELIREG plus Keytruda with Keytruda plus placebo.² The primary endpoint was DFS, with overall survival, safety and quality of life as key secondary measures.²

“Litespark-022 is a critical part of our comprehensive RCC clinical development program, and the Phase III results presented at ASCO GU underscore the importance of Keytruda and Welireg in helping to treat patients with certain types of renal cell carcinoma,” said Dr. M. Catherine Pietanza, vice president, Global Clinical Development, Merck Research Laboratories. “These findings represent the first positive Phase III data for WELIREG in earlier stages of disease, as well as the first positive Phase III results for a HIF‑2α inhibitor and immunotherapy combination, reinforcing our commitment to exploring novel treatment approaches to improve upon established treatment paradigms for patients in need.”

What were the results from the Litespark-022 trial?

At a pre-specified interim analysis with a median follow-up of 28.4 months, the combination significantly improved disease-free survival (DFS), reducing the risk of disease recurrence or death by 28% compared with Keytruda plus placebo (HR=0.72; 95% CI 0.59-0.87; p=0.0003).¹

Median DFS was not reached in either arm. The estimated 24-month DFS rate was 80.7% for the combination versus 73.7% for Keytruda plus placebo. Overall survival, a key secondary endpoint, continues to be evaluated.¹

Investigators noted that the combination marks the first regimen in the adjuvant RCC setting to demonstrate improved DFS over pembrolizumab alone, potentially reshaping treatment approaches for patients at increased risk of recurrence.¹

Merck said the findings also represent the first positive Phase III results for a HIF-2α inhibitor combined with immunotherapy in earlier-stage disease.

What was Keytruda plus Welireg’s safety profile?

The safety profile of Keytruda plus Welireg is consistent with prior studies of both agents, with no new safety signals being observed.² Grade three or higher treatment-emergent adverse events occurred in 52.1% of patients receiving the combination compared with 30.2% in the Keytruda plus placebo arm. The most common Grade three or higher events included anemia, increased alanine aminotransferase and hypoxia. Rates of Grade 5 adverse events were similar between treatment arms.

Based on the Litespark-022 data, the FDA has accepted priority review supplemental applications seeking approval of Welireg in combination with Keytruda or Keytruda Qlex for the adjuvant treatment of adults with RCC with a clear cell component at increased risk of recurrence following nephrectomy.¹

A target action date of June 19, 2026, has been set. Merck said it plans to engage with global regulatory authorities regarding the data.

Resources

1. Keytruda (pembrolizumab) Plus Welireg (belzutifan) Given as Adjuvant Therapy Reduced the Risk of Disease Recurrence or Death by 28% Compared to Keytruda Monotherapy in Certain Patients With Earlier-Stage Renal Cell Carcinoma (RCC) Merck February 28, 2026 https://www.merck.com/news/keytruda-pembrolizumab-plus-welireg-belzutifan-given-as-adjuvant-therapy-reduced-the-risk-of-disease-recurrence-or-death-by-28-compared-to-keytruda-monotherapy-in-certain-patients-with/
2. A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022) National Library of Medicines Accessed March 3, 2026 https://clinicaltrials.gov/study/NCT05239728