Phase 1 LITESPARK-001 study of belzutifan in participants with advanced solid tumors: results of the glioblastoma expansion cohort

Summary Recurrent isocitrate dehydrogenase (IDH) wild-type glioblastoma has no established standard-of-care treatment. Preclinical models have demonstrated that hypoxia-inducible factor-2 alpha (HIF-2α) contributes to stabilizing the hypoxic environment in glioblastoma. It was thus hypothesized that the first-in-class HIF-2α inhibitor, belzutifan, may improve outcomes in patients with recurrent IDH wild-type glioblastoma. The glioblastoma cohort of the phase 1 LITESPARK-001 trial enrolled participants who had received radiotherapy and temozolomide. Although targeting HIF-2α may have a role in advancing treatment options for patients with glioblastoma, single-agent belzutifan did not have antitumor activity in this cohort.