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This combination regimen consists of five therapeutics: BL-8040 (motixafortide), pembrolizumab, liposomal irinotecan (Onivyde), 5-fluorouracil, and leucovorin. BL-8040 is a CXCR4 antagonist, which disrupts the CXCL12/CXCR4 axis, enhancing immune cell infiltration and reducing immunosuppressive myeloid-derived suppressor cells in the tumor microenvironment. Pembrolizumab is a monoclonal antibody checkpoint inhibitor targeting programmed cell death protein 1 (PD-1) on T cells, thereby enabling immune-mediated destruction of tumor cells. Liposomal irinotecan inhibits topoisomerase I, interrupting DNA replication in cancer cells. 5-fluorouracil is a pyrimidine antimetabolite inhibiting thymidylate synthase, leading to impaired DNA synthesis; leucovorin enhances the activity of 5-fluorouracil. This regimen is under clinical investigation primarily for second-line treatment of metastatic pancreatic ductal adenocarcinoma, aiming to synergize immune modulation with cytotoxic chemotherapy[1][3][5].
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