Phase 2 zanzalintinib c-MET/HGFR and VEGFR inhibitor for recurrent/progressive meningioma

This Phase 2, single-arm, multicenter, open-label study evaluates zanzalintinib (Exelixis)—an oral small-molecule tyrosine kinase inhibitor of c-MET/HGFR and VEGFR—aiming to suppress tumor growth signaling and angiogenesis in meningioma. Participants have recurrent or progressive WHO grade 1–3 meningioma that is refractory to standard therapies and has previously received radiation, a population where durable systemic options remain limited. The primary goal is to characterize anti-tumor activity alongside safety on once-daily dosing, with a design that prioritizes a clear signal readout over comparative effectiveness. Scientifically, the key angle is whether dual pathway inhibition (tumor-intrinsic MET signaling plus VEGF-driven vascular support) can improve disease control in a tumor type where biology is often pro-angiogenic and where targeted therapy has had uneven results. Today’s care for recurrent/progressive meningioma is repeat surgery when feasible plus re-irradiation or focal techniques in selected patients, with no widely accepted, FDA-approved systemic standard and frequent use of clinical trials or off-label agents.