LY3410738 + gemcitabine + cisplatin

LY3410738 + gemcitabine + cisplatin is a **combination regimen** under investigation for the treatment of advanced solid tumors, notably cholangiocarcinoma, characterized by mutations in the isocitrate dehydrogenase 1 gene (IDH1). LY3410738 is a first-in-class, covalent, and brain-penetrant inhibitor of mutant IDH1 (R132), developed to overcome resistance seen with previous IDH1 inhibitors and is being trialed in combination with cisplatin and gemcitabine, both established DNA-damaging cytotoxic chemotherapies. This combination targets tumor metabolic reprogramming, with LY3410738 inhibiting oncogenic IDH1 activity, while gemcitabine (a nucleoside analog interfering with DNA synthesis) and cisplatin (a platinum-based agent causing DNA crosslinking/damage) aim to induce cancer cell death through cytotoxic stress[3][8][9].