LITESPARK-005: Belzutifan Improves PFS in Previously Treated Patients With Advanced RCC

By Zachary Bessette - Last Updated: August 22, 2023

Topline results from the LITESPARK-005 trial indicate that WELIREG (belzutifan) provides a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with everolimus in adult patients with advanced renal cell carcinoma (RCC) who have progressed following programmed cell death 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) checkpoint inhibitors and vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) therapies.

A statistically significant improvement was also demonstrated in objective response rate (ORR)—a secondary end point of the trial—but improvement in overall survival (OS) did not reach statistical significance.

Belzutifan is currently approved for the treatment of adult patients with von Hippel-Lindau disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors.

The randomized, open-label, phase 3 LITESPARK-005 study compares belzutifan and everolimus for previously treated advanced RCC. The dual primary end points are PFS and OS, and secondary end points include ORR, duration of response, and safety and tolerability. A total of 746 patients are enrolled in the trial to receive belzutifan (120 mg orally, once daily) or everolimus (10 mg orally, once daily).

“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,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, at Merck, 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.”

LITESPARK-005 is 1 of 4 late-stage trials evaluating belzutifan in RCC. LITESPARK-011 and LITESPARK-012 are investigating belzutifan in the second-line and treatment-naïve advanced disease setting, while LITESPARK-022 is looking at belzutifan in the adjuvant setting.