Pivotal study supports belzutifan approval for patients with advanced kidney cancer

Belzutifan is a hypoxia-inducible factor 2 Alpha inhibitor that has showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies.

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 randomized 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.

Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals.

At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P=0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%).

Based on the evidence from this randomized, 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 renal cell carcinoma.

Reference:

Toni K. Choueiri, Thomas Powles, Katriina Peltola, Guillermo de Velasco, Mauricio Burotto, Cristina Suarez, Pooja Ghatalia, Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma, New England Journal of Medicine, DOI: 10.1056/NEJMoa2313906.