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IDE397 + sacituzumab govitecan is an investigational **combination therapy** for the treatment of MTAP-deletion solid tumors, targeting primarily urothelial cancer and non-small cell lung cancer (NSCLC). **IDE397** is a potent and selective small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A), designed to impair tumor growth in cancers with methylthioadenosine phosphorylase (MTAP) deletion[1][4][6]. **Sacituzumab govitecan** (Trodelvy) is an antibody-drug conjugate (ADC) directed against Trophoblast cell surface antigen 2 (Trop-2), conjugated to SN-38, an active metabolite of irinotecan that inhibits topoisomerase I. The combination leverages synthetic lethality and DNA damage in MTAP-deleted cancers, exploring whether dual targeting with a MAT2A inhibitor and a topoisomerase I payload ADC improves response rates over either agent alone[2][4][6]. This approach is currently under clinical investigation in solid tumors with MTAP deletion, particularly in Phase 1/2 urothelial carcinoma cohorts.
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