A phase I dose escalation study of the HIF-2 alpha inhibitor DFF332 in patients with advanced clear cell renal cell carcinoma.

Background: Mutations or silencing of the von Hippel Lindau (VHL) tumor suppressor gene accumulates hypoxia-inducible factors (HIFs). HIF-2α is implicated in the oncogenesis of ~50% of patients with clear cell renal cell carcinoma (ccRCC) but, has been considered "undruggable". DFF332, an orally administered novel allosteric inhibitor of HIF-2α showed dose-dependent antitumor efficacy in preclinical models of ccRCC.