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Cabozantinib + ipilimumab is an investigational combination therapy comprised of two agents: cabozantinib, an orally administered small molecule tyrosine kinase inhibitor targeting multiple kinases including VEGFR, MET, and AXL; and ipilimumab, a monoclonal antibody that acts as a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitor. The combination is under study for the treatment of various advanced malignancies, particularly in genitourinary cancers, renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid carcinoma. Mechanistically, cabozantinib exerts antitumor effects by inhibiting angiogenesis, tumor cell proliferation, and promoting immunomodulation that may synergize with the immune checkpoint blockade from ipilimumab, which enhances T-cell–mediated immune responses against tumors. This combination is frequently studied alongside nivolumab, but this entry covers the specific doublet of cabozantinib and ipilimumab in combination.
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