The LITESPARK-005 phase 3 clinical enrolled 746 patients with metastatic clear cell renal cell carcinoma (ccRCC) who had progressed after treatment with both an immune checkpoint inhibitor (ICI) and an anti-angiogenic therapy.

Patients were randomised to receive treatment with either belzutifan, a HIF-2α inhibitor, or everolimus.

Overabundant HIF-2α is associated with increased cancer-driving activity.

At the second interim analysis of this study, after a median of 25.7 months, patients taking belzutifan were 25% less likely to have progressed compared with those taking everolimus.

Results were presented at the annual European Society for Medical Oncology (ESMO) Congress in 2023 and are now published in the New England Journal of Medicine. 

Based on the evidence from this open-label, randomised, active-controlled trial, belzutifan was approved by the U.S. Food and Drug Administration for adult patients with advanced renal cell carcinoma (RCC) following standard treatment with an ICI or anti-angiogenic therapy.

This approval of a HIF-2α inhibitor meets a need for drugs with novel therapeutic mechanisms in advanced RCC.

Source: Dana-Farber Cancer Institute