HMN 2026: How FDA expands use of kidney cancer drug belzutifan

Belzutifan, a first-in-class drug that arose from scientific discoveries at UT Southwestern Medical Center, has been approved by the Food and Drug Administration to treat some patients with earlier-stage kidney cancers in combination with an immunotherapy drug. This move marks the latest expansion of belzutifan’s indications after it was originally approved in 2021.

The latest FDA approval was based on results from LITESPARK-022, a Phase III clinical trial that took place at 285 sites around the world, including UT Southwestern. The results, presented at the 2026 ASCO Genitourinary Cancer Symposium, evaluated belzutifan combined with pembrolizumab—a type of immunotherapy drug known as a checkpoint inhibitor—in patients with clear cell renal cell carcinoma after surgery to remove diseased kidneys.

The findings are also published in the Journal of Clinical Oncology.

At a median follow-up of 28.4 months, results showed that this combination reduced the risk of disease recurrence by 28% compared with pembrolizumab with a placebo.

“LITESPARK-022 demonstrated an improvement in disease-free survival by 28% when belzutifan was combined with pembrolizumab in patients at higher risk of kidney cancer recurrence,” said Hans Hammers, M.D., Ph.D., professor of internal medicine in the Division of Hematology and Oncology, co-leader of the Experimental Therapeutics Research Program in the Harold C. Simmons Comprehensive Cancer Center, and co-leader of clinical research in UTSW’s Kidney Cancer Program, who served as the site leader for the clinical trial at Simmons Cancer Center.

“This trial showed an advance over pembrolizumab monotherapy in this setting, but overall survival was immature at the time of analysis.”

Belzutifan, which is manufactured by Merck, known as MSD outside the United States and Canada, previously received regulatory approvals to treat patients with certain von Hippel-Lindau disease-associated tumors (a type of familial kidney cancer); later-stage renal cell carcinoma; and pheochromocytoma or paraganglioma, two types of rare neuroendocrine tumors.

Belzutifan originated from 1990s research at UT Southwestern by Steven McKnight, Ph.D., professor of biochemistry, and David Russell, Ph.D., professor emeritus of molecular genetics, who discovered HIF-2?, the molecular target of belzutifan.

Originally known for helping cells adapt to low oxygen, HIF-2? was later found to drive kidney cancer growth. UT Southwestern scientists identified a druggable cavity in the HIF-2? protein and pursued inhibitors that bind to that cavity.

To develop an effective HIF-2? inhibitor, McKnight and Russell founded Peloton Therapeutics. Discoveries at Peloton were followed by UT Southwestern-led preclinical studies and first-in-human clinical trials with the drug that later became belzutifan. Merck acquired Peloton in 2019. Merck also manufactures pembrolizumab.

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