zanzalintinib + AB521

**Zanzalintinib + AB521** is an investigational combination regimen under clinical evaluation primarily for advanced clear cell renal cell carcinoma and other advanced solid tumors. Zanzalintinib (XL092) is a small molecule tyrosine kinase inhibitor targeting multiple receptor tyrosine kinases implicated in tumor angiogenesis and progression, specifically VEGFR2, MET, AXL, and MER. AB521 is a hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor; HIF-2α is a transcription factor that supports cancer cell survival under hypoxic conditions, promoting tumor growth and resistance. The strategic rationale for this combination is to simultaneously inhibit pro-angiogenic and hypoxia survival pathways for enhanced antitumor efficacy. This combination is being evaluated in phase 1b/2 clinical studies, often within the STELLAR-009 trial, sponsored by Exelixis in collaboration with Arcus Biosciences. The regimen may be tested with or without immune checkpoint inhibitors such as nivolumab[1][2][5][7][8].