Phase 2 zanzalintinib (c-MET/VEGFR tyrosine kinase inhibitor) in recurrent/metastatic olfactory neuroblastoma.

This single-arm Phase 2 study at MD Anderson Cancer Center evaluates whether zanzalintinib can control recurrent or metastatic olfactory neuroblastoma (ONB) that is unresectable and not amenable to curative-intent surgery or radiation. Participants (planned N=16) receive oral zanzalintinib 60 mg once daily on continuous 28-day cycles; zanzalintinib (also known as XL092; Exelixis) is a small-molecule inhibitor targeting VEGFR and c-MET (HGFR), aiming to suppress angiogenesis and oncogenic growth signaling. The primary endpoint is overall response rate by RECIST 1.1, with secondary endpoints including DOTATATE-PET metabolic response (PERCIST), duration of response, PFS/OS, and CTCAE v5.0 safety; exploratory work includes tumor molecular profiling/RNAseq and proteomic assays to find response biomarkers. ONB is rare, and for R/M disease today’s care is typically individualized, using systemic chemotherapy regimens (often platinum-based), local salvage when feasible, and occasional off-label targeted/anti-angiogenic strategies—so this trial tests a more defined VEGFR/c-MET TKI approach in VEGFR inhibitor–naïve patients.