Treatment with belzutifan demonstrated a statistically significant and clinically meaningful improvement in progression-free survivalcompared with everolimus in patients with advanced renal cell carcinoma that has progressed on prior PD-1/PD-L1 and VEGF inhibitors, in sequence or in combination.
Treatment with belzutifan (Welireg) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with everolimus (Afinitor) in patients with advanced renal cell carcinoma (RCC) that has progressed on prior PD-1/PD-L1 and VEGF inhibitors, in sequence or in combination, according to topline results from the phase 3 LITESPARK-005 trial (NCT04195750).1
In addition to meeting the trial’s co-primary end point in the prespecified interim analysis conducted by an independent data monitoring committee, belzutifan also led to a statistically significant improvement in objective response rate (ORR) vs everolimus, meeting a secondary end point of the study. A trend toward improved overall survival (OS) favored belzutifan; however the co-primary end point fell short of reaching statistical significance. OS will be tested again in subsequent analysis.
No new safety signals were reported with the agent, and complete results will be presented at an upcoming medical meeting and shared with regulatory agencies.
“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, global clinical development, Merck Research Laboratories, said in a news 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.”
In August 2021, the FDA approved belzutifan for patients with von Hippel-Lindau disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery.2
LITESPARK-005 enrolled 746 patients who were randomly assigned to receive 120 mg of oral belzutifan once daily or 10 mg of oral everolimus once daily. To be eligible for enrollment, patients had to have unresectable, locally advanced or metastatic clear cell RCC that has progressed on or after systemic therapy with PD-1/L1 and VEGF inhibitors. No more than 3 prior systemic therapies were allowed.3
The co-primary end points of the study were PFS and OS. Secondary end points included ORR, duration of response, safety, and tolerability.
Belzutifan is also under evaluation in the phase 3 LITESPARK-012 (NCT04736706) and LITESPARK-011 (NCT04586231) trials as frontline and second-line therapy in advanced RCC, respectively, and in the adjuvant setting in the phase 3 LITESPARK-022 trial (NCT05239728).