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**INCB161734 + retifanlimab** is an experimental combination therapy being investigated for the treatment of advanced or metastatic solid tumors harboring *KRAS G12D* mutations. - **INCB161734** is a novel, potent, selective, and orally bioavailable small-molecule inhibitor that targets KRAS G12D, a mutant form of the KRAS protein frequently observed in pancreatic ductal adenocarcinoma and colorectal cancers. INCB161734 binds specifically at the switch II pocket of the KRAS G12D mutant (GDP and GTP forms), inhibits downstream ERK and PI3K signaling, and suppresses tumor growth by disrupting cell proliferation pathways[2][6]. - **Retifanlimab** is a humanized monoclonal antibody that inhibits the programmed death-1 (PD-1) immune checkpoint, resulting in restoration of T-cell activity for anti-tumor immune responses. The clinical combination is currently being studied in a phase 1 trial to determine its safety, tolerability, and potential anti-tumor efficacy in solid tumors with KRAS G12D mutations[1][3][7][9].
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