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Lenvatinib plus PD-1 antibody is a combination immunotherapy and targeted therapy regimen investigated for the treatment of unresectable intrahepatic cholangiocarcinoma (iCCA). This specific regimen was the focus of a Phase 2 clinical trial (NCT03779100) led by Dr. Shi Ming at Sun Yat-sen University Cancer Center. The therapy combines lenvatinib, a small-molecule multi-kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), and the RET and KIT proto-oncogenes, with a monoclonal antibody targeting the programmed cell death protein 1 (PD-1) receptor. By inhibiting VEGFR and FGFR, lenvatinib reduces tumor angiogenesis and may modulate the tumor microenvironment to enhance the efficacy of PD-1 blockade. The PD-1 antibody component (which in the trial included agents such as pembrolizumab, sintilimab, or toripalimab) restores anti-tumor T-cell activity by preventing the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
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