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AK112 + irinotecan + oxaliplatin + leucovorin + 5-fluorouracil is an investigational multi-agent combination regimen for cancer therapy. **AK112 (ivonescimab/SMT112)** is a first-in-class, humanized bispecific monoclonal antibody targeting programmed death-1 (PD-1) and vascular endothelial growth factor (VEGF), designed to combine immune checkpoint blockade and anti-angiogenic activity in a single molecule. It is being tested primarily in advanced and metastatic solid tumors, including non-small cell lung cancer (NSCLC)[1][5][7]. **Irinotecan** is a small molecule chemotherapeutic agent that inhibits topoisomerase I, leading to DNA damage and apoptosis in rapidly dividing cells[2][4][6]. **Oxaliplatin** is a platinum-based chemotherapeutic that forms DNA crosslinks, inhibiting DNA replication and transcription, leading to cell death. **Leucovorin** is a reduced folate used to enhance the efficacy of 5-fluorouracil and reduce its toxicity. **5-Fluorouracil** is a pyrimidine analog antimetabolite which inhibits thymidylate synthase, interfering with DNA synthesis and function. This combination is under investigation (no commercial combination product approved) and is being studied for efficacy and safety in various solid tumors, notably NSCLC and potentially gastrointestinal cancers[1][3][5][7]. Developers are Akeso for AK112 (ivonescimab), with Summit Therapeutics as strategic partner in certain territories. Other drugs are established generics.
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