Merck, known as MSD outside the United States and Canada, has announced new findings from the pivotal Phase III LITESPARK-022 trial evaluating the combination of Keytruda (pembrolizumab) and Welireg (belzutifan) in patients with clear cell renal cell carcinoma (RCC) following nephrectomy.

The late-breaking results were presented during an oral session at the 2026 ASCO Genitourinary (GU) Cancers Symposium, highlighting the potential of the combination therapy in the adjuvant setting.

At the first pre-specified interim analysis, with a median follow-up of 28.4 months, the combination therapy demonstrated a significant improvement in disease-free survival (DFS), the study’s primary endpoint. The regimen reduced the risk of disease recurrence or death by 28 percent compared with Keytruda combined with placebo.

The estimated 24-month disease-free survival rate was 80.7 percent for patients receiving the combination of Keytruda and Welireg, compared with 73.7 percent for those treated with Keytruda plus placebo. Median DFS had not yet been reached in either group at the time of analysis. The trial will continue evaluating overall survival as a key secondary endpoint.

Dr Toni K. Choueiri, Director of the Lank Centre for Genitourinary Oncology at Dana-Farber Cancer Institute and professor at Harvard Medical School, said that nearly 40 percent of renal cell carcinoma patients may experience tumour recurrence after initial treatment. According to him, the LITESPARK-022 findings represent an important advancement, demonstrating that the combination regimen significantly lowers the risk of recurrence or death compared with pembrolizumab alone and could potentially reshape clinical practice.

Dr M. Catherine Pietanza, Vice President of Global Clinical Development at Merck Research Laboratories, noted that the results mark the first positive Phase III data for Welireg in earlier-stage disease and the first successful Phase III study combining a HIF-2α inhibitor with immunotherapy. She added that the findings highlight the role of novel treatment strategies in improving outcomes for patients with renal cell carcinoma.

The safety profile of the combination therapy was consistent with previous studies of both drugs, and no new safety concerns were identified. Among treated patients, Grade 3 or higher treatment-emergent adverse events occurred in 52.1 percent of patients receiving the combination therapy and 30.2 percent in the control group. The most common severe adverse events included anaemia, elevated liver enzymes and hypoxia.

Based on the trial results, the U.S. Food and Drug Administration has accepted for priority review supplemental regulatory applications seeking approval of Welireg in combination with Keytruda or Keytruda QLEX for the adjuvant treatment of adults with renal cell carcinoma at high risk of recurrence after nephrectomy. The agency has set a target action date of June 19, 2026.

Renal cell carcinoma accounts for about 90 percent of kidney cancer cases worldwide. In 2022, around 435,000 new kidney cancer cases were reported globally, with approximately 156,000 deaths attributed to the disease. The cancer is diagnosed about twice as often in men as in women, and roughly 30 percent of patients are identified at an advanced stage.

Merck continues to advance one of the largest clinical development programmes in genitourinary cancers, including bladder, kidney and prostate cancers. The company is currently conducting more than 50 clinical trials involving over 22,000 patients to explore new treatment strategies and combination therapies aimed at improving outcomes in these cancers.