Phase 2 zanzalintinib MET/VEGFR/AXL/MER inhibitor in metastatic pheochromocytoma/paragangliom

This Phase 2, single-arm study at Dana-Farber Cancer Institute evaluates oral once-daily zanzalintinib (XL092) in patients with unresectable, progressive metastatic pheochromocytoma or paraganglioma (PPGL). Zanzalintinib, from Exelixis, is a multi-kinase tyrosine kinase inhibitor that targets c-MET (HGFR), VEGFR2, AXL, and MER—aiming to blunt tumor angiogenesis and growth-factor signaling that can drive these highly vascular neuroendocrine tumors. The primary goal is to estimate antitumor activity (commonly objective response rate) alongside safety and tolerability in this rare population with RECIST-defined progression. For progressive metastatic PPGL, systemic options now include FDA-approved belzutifan, alongside radiopharmaceutical approaches when eligible (such as high-specific-activity I-131 MIBG or SSTR-targeted PRRT), chemotherapy, and selected TKIs—making this a direct test of whether broader VEGFR2/MET/TAM-family inhibition can carve out an effective oral alternative. The commercial/scientific angle is extending Exelixis’ zanzalintinib franchise into rare neuroendocrine tumors, where trial execution is challenging but differentiation can be meaningful if response durability emerges.