Study Title: Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study
Publication: The Lancet Oncology - January 2025
Dana-Farber Cancer Institute author: Toni K. Choueiri, MD
Summary: In the open-label phase 2 LITESPARK-003 study, led by Dana-Farber Cancer Institute's Toni Choueiri, MD, researchers investigated for the first time the combination of cabozantinib, an anti-angiogenic agent, plus belzutifan, a first-in-class HIF-2α inhibitor. The researchers previously reported results for cohort 2 of the trial, which includes patients previously treated with immunotherapy. This study reports results for cohort 1, which includes patients who have not yet received treatment for advanced kidney cancer. After a median follow up of 24 months, 70% of patients had a confirmed objective response, with 4 of 50 patients experiencing a complete response and 31 of 50 experiencing a partial response. Seven of the 50 patients had serious treatment-related adverse events, though they were manageable.
Significance: Current first-line treatment for advanced clear-cell renal cell carcinoma includes anti-PD1 or anti-PD-L1 immunotherapy in combination with a CTLA-4 inhibitor or a VEGF tyrosine kinase inhibitor such as cabozantanib. These options have improved outcomes in patients; however, not all patients respond, and some responses do not last. This study's results suggest that further investigation of this novel combination as first-line therapy option is warranted.
Funding: Merck Sharp & Dome, LLC, (a subsidiary of Merck & Co) and the National Cancer Institute.
