Study: Belzutifan Demonstrates Improvement in Progression-Free Survival for Advanced Renal Cell Carcinoma


Belzutifan also demonstrated statistically significant improvements in objective response rate compared to everolimus for advanced renal cell carcinoma.

Topline results from the LITESPARK-005 (NCT04195750) trial of belzutifan (Welireg; Merck) were announced for individuals with advanced renal cell carcinoma (RCC) that progressed following PD-1/L1 checkpoint inhibitor and vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) therapies. Belzutifan, an oral hypoxia-inducible factor-2 alpha inhibitor, demonstrated clinically meaningful improvements in progression-free survival (PFS) when compared to everolimus (Afinitor; Novartis).1

The approval was based on ORR and DOR data from the phase 2 LITESPARK-004 trial (NCT03401788).1

Kidney cancer, illustration and light micrograph

Image Credit: Dr_Microbe -

According to a study published in the World Journal of Oncology, the rate of incidence of RCC has increased, becoming the ninth most common cancer diagnosis in the United States.2 RCC is more prevalent among older men and minorities in the United States, and the study authors noted that there are significant racial disparities in survival of RCC.2 Risk factors can include smoking, obesity, uncontrolled hypertension, poor diet, and occupational exposure.2

“Patients with advanced RCC face low survival rates, and for those whose cancer progresses following PD-1/L1 and VEGF-TKI therapies, there is a need for new treatment options that can reduce their risk of disease progression or death,” Marjorie Green, MD, senior vice president and head of late-stage oncology of global clinical development at Merck Research Laboratories, said in a press release. “This is the first phase 3 trial to show positive results in advanced RCC following these therapies and the first new mechanism to demonstrate potential in advanced RCC in recent years. We look forward to discussing these results with health authorities.”1

LITESPARK-005 is a randomized, open-label phase 3 trial. In the trial, investigators evaluated belzutifan compared to everolimus for the treatment of individuals with advanced RCC that progressed after prior treatment with PD-1/L1 and VEGF-TKI therapies, either in sequence or in combination. There were 746 individuals enrolled to receive either belzutifan 120 mg once daily or everolimus 10 mg once daily.1

The study had the dual primary endpoints of PFS and overall survival (OS) and secondary endpoints of objective response rate (ORR), duration of response (DOR), safety, and tolerability.1

In addition to improvements in PFS, there were statistically significant improvements in ORR, according to investigators. There was also a trend toward improvement in overall survival (OS), but it was not statistically significant.Investigators will test OS in a subsequent analysis.1

The safety profile of belzutifan was consistent with the observed safety profile in other studies. Investigators will share the results at an upcoming medial meeting and they will be shared with regulatory authorities.1

LITESPARK-005 was part of a development program for belzutifan. The program was comprised of 4 phase 3 trials in RCC, including LITESPARK-011 (NCT04586231) and LITESPARK-012 (NCT04736706), which evaluated belzutifan in the second line and treatment naïve advanced disease settings, and LITESPARK-022 (NCT05239728), which evaluated belzutifan in the adjuvant setting.1

Belzutifan was the first HIF-2α inhibitor therapy approved in the United States. It is currently approved in the United States, Great Britain, Canada, and several other countries for adults with von Hippel-Lindau disease, those who require therapy associated with RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors that do not require immediate surgery.1

Additional applications are currently under regulatory agency review worldwide based on the LITESPARK-0004 trial.1


1. Merck announces Welireg (belzutifan) phase 3 LITESPARK-005 trial met primary endpoint of progression-free survival in certain previously treated patients with advanced renal call carcinoma. News release. Merck. August 18, 2023. Accessed August 22, 2023.

2. Padala SA, Barsouk A, Thandra KC, Saginala K, et al. Epidemiology of renal cell carcinoma. World J Oncol. 2020;11(3):79-87. doi:10.14740/wjon1279

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