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Zanzalintinib + atezolizumab is an investigational combination regimen consisting of zanzalintinib (XL092), an oral small-molecule multitargeted tyrosine kinase inhibitor (TKI), and atezolizumab (Tecentriq), an intravenous anti-PD-L1 monoclonal antibody. Zanzalintinib targets VEGFR1/2/3, MET, and the TAM kinases (TYRO3, AXL, MERTK), which are involved in tumor angiogenesis, metastasis, and immunosuppression. By inhibiting these pathways, zanzalintinib promotes an immune-permissive tumor microenvironment, thereby enhancing the antitumor activity of the immune checkpoint inhibitor atezolizumab. The combination has been evaluated in the phase 3 STELLAR-303 trial for previously treated, non-microsatellite instability-high (non-MSI-H) metastatic colorectal cancer (mCRC), demonstrating a statistically significant improvement in overall survival compared to regorafenib. A New Drug Application (NDA) for this combination in previously treated mCRC is currently under FDA review, with an extended PDUFA target action date of March 3, 2027. The regimen is also being investigated in other advanced solid tumors, including renal cell carcinoma, breast cancer, and prostate cancer.
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