Abstract
HIF-2α is constitutively activated in RCC and is a transcription factor of multiple oncogenic pathways including TGF-α, GLUT1, cyclin D1, CXCR4, and VEGF. VEGF, and its receptor, are key regulators of angiogenesis and are upregulated in RCC. Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumor activity and favorable safety in heavily pretreated advanced RCC. Cabozantinib, a multikinase inhibitor that targets VEGF, is approved for advanced RCC. We present the first data of the use of belzutifan plus cabozantinib for treatment-naive pts with advanced RCC (cohort 1) enrolled in the ongoing, open-label, phase 2 LITESPARK-003 study (NCT03634540).
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