Merck & Co., Inc. (MRK.US) has achieved positive results in two Phase III trials of its first-in-class HIF-2 inhibitor.

On February 28th, Merck & Co., Inc. (MRK.US) announced the results of its pioneering HIF-2 inhibitor, belzutifan, in two Phase III clinical trials (LITESPARK-011 and LITESPARK-022) at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), covering advanced kidney cancer (RCC) treatment and adjuvant treatment after surgery. LITESPARK-011 is a randomized, open-label Phase III study (NCT04586231) evaluating belzutifan in combination with lenvatinib compared to the standard treatment of cabozantinib in advanced RCC patients who have previously received anti-PD-1/PD-L1 therapy and experienced disease progression. LITESPARK-022 is a randomized, double-blind Phase III study (NCT05239728) evaluating belzutifan in combination with pembrolizumab compared to pembrolizumab plus placebo for adjuvant treatment of clear cell renal cell carcinoma patients with a high risk of recurrence after kidney removal. Belzutifan is the world's first approved HIF-2 inhibitor, which selectively blocks the formation of the HIF-2-HIF-1 transcription complex, inhibiting downstream VEGF and other pro-angiogenic gene expression in the VHL-HIF signaling pathway, thereby intervening in tumor hypoxia-driven angiogenesis and cell proliferation processes.