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This drug regimen is a **combination therapy** consisting of AK104 (cadonilimab), a **tetrameric bispecific monoclonal antibody targeting PD-1 and CTLA-4**; liposomal irinotecan (nal-IRI; Onivyde), a liposomal formulation of a **topoisomerase I inhibitor**; oxaliplatin, a **platinum-based alkylating agent**; fluorouracil (5-FU), a **pyrimidine analog antimetabolite**; and calcium folinate (leucovorin), a **reduced folate**, which potentiates the action of fluorouracil. - **AK104 (cadonilimab)** induces antitumor immunity by blocking PD-1/PD-L1 and CTLA-4 checkpoint pathways. - **Liposomal irinotecan (nal-IRI)** delivers irinotecan more effectively to tumors via liposomal encapsulation, prolonging drug exposure and enhancing cytotoxicity while reducing systemic toxicity. - **Oxaliplatin** forms DNA crosslinks, disrupting DNA synthesis and function. - **Fluorouracil** inhibits thymidylate synthase, leading to disruption of DNA synthesis. - **Calcium folinate** stabilizes the folate cofactor, enhancing the cytotoxicity of 5-FU. The combination is being studied primarily for **gastrointestinal cancers** (notably metastatic pancreatic and gastric/gastro-oesophageal junction adenocarcinomas) and has shown promising efficacy and tolerable safety as a first-line and neoadjuvant treatment in phase II/III clinical trials[5][7][8][9].
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