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ISU104 + cetuximab is an **investigational combination therapy** consisting of ISU104 (also known as barecetamab), a fully human monoclonal antibody targeting ERBB3 (HER3), and cetuximab, an established monoclonal antibody targeting EGFR (Epidermal growth factor receptor). - **ISU104** binds specifically to domain 3 of ERBB3, inhibits heregulin-induced ligand binding, prevents ERBB3 heterodimerization with other ErbBs (such as EGFR and HER2), downregulates ERBB3 expression, and disrupts downstream oncogenic signaling pathways, notably PI3K/AKT, leading to inhibition of tumor cell proliferation and survival[2][3]. - **Cetuximab** blocks EGFR and inhibits cell proliferation signaling. - The combination enhances anti-tumor activity compared to either agent alone in preclinical models, offering a rational approach to overcome resistance mechanisms in cancers with ErbB3 pathway activation, notably in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)[2][5]. - The combination is delivered intravenously at varying doses in clinical trials for advanced solid tumors and HNSCC, with ongoing phase 1/2 development[1][4][5].
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