Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors

AbstractPurpose of ReviewTo review the biology, drug development, and clinical data regarding the efficacy and safety of belzutifan (MK-6482), a small molecule inhibitor of HIF-2 α.Recent FindingsBelzutifan, a second-generation HIF-2 α inhibitor, was shown to provide clinically meaningful benefit in the treatment of VHL-associated tumors (including ccRCC, pancreatic lesions as well as neuroendocrine tumor, and CNS hemangioblastomas). The recommended dose of belzutifan is 120 mg orally daily and half-life is 14 h. In pretreate d ccRCC, belzutifan achieved disease control rate of 80% in phase I trial. The most common side effects include anemia and hypoxia related symptoms.SummaryInvestigation into the important role HIF-2 α plays in the expression of genes associated with angiogenesis, erythropoiesis, carcinogenesis, and progression of tumors and the discovery of structural vulnerability within HIF-2α have resulted in the development of a new therapy that has demonstrated efficacy and safety in recent clinical tria ls. Further research is ongoing to optimize therapeutic benefits from this new exciting therapeutic modality and to improve the outcome of HIF-2α-driven tumors.
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research