Phase 2 zanzalintinib (XL092) multi-kinase VEGFR2/MET/AXL inhibitor + MO-03 microbiome immunomodulator

This single-arm Phase 2 study at City of Hope tests zanzalintinib (XL092) plus MO-03 (CBM588; Clostridium butyricum strain M588) in metastatic clear-cell renal cell carcinoma that has progressed after immunotherapy, in the 2nd–3rd line setting. Participants take zanzalintinib orally once daily and MO-03 orally twice daily in continuous 28-day cycles, with imaging (CT and bone scans) and blood/urine sampling to track response and biology; the primary goal is objective response rate by RECIST 1.1. Zanzalintinib—developed by Exelixis—is a next-generation oral tyrosine kinase inhibitor that blocks VEGFR2 and other kinases including MET and AXL, aiming to suppress angiogenesis and tumor growth. MO-03 is a live biotherapeutic intended to shift gut microbiota and immune tone, building on the commercial/scientific angle that microbiome manipulation may improve outcomes with TKIs and immunotherapy. Today’s care after checkpoint inhibitor progression in clear-cell mRCC typically moves to sequential VEGF/MET-targeted TKIs (often cabozantinib) and/or agents like lenvatinib plus everolimus; this trial explores whether pairing a potent next-gen TKI with a microbiome immunomodulator can improve activity in a post-IO population.