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This investigational combination therapy is a multi-modal regimen being evaluated for the first-line treatment of patients with locally advanced, unresectable, or metastatic cholangiocarcinoma harboring IDH1 mutations. The regimen consists of four distinct components: **ivosidenib**, a small molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that reduces the production of the oncometabolite 2-hydroxyglutarate (2-HG); **durvalumab**, a monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) to enhance anti-tumor immune responses; and the cytotoxic chemotherapy doublet of **gemcitabine** and **cisplatin**. By combining targeted therapy, immune checkpoint blockade, and standard-of-care chemotherapy, the treatment aims to simultaneously inhibit oncogenic metabolic signaling, restore T-cell activity, and induce DNA damage in cancer cells. The therapy is currently being investigated in Phase 1b/2 clinical trials sponsored by Servier and its subsidiary Symphogen.
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