duligotuzumab + 5-fluorouracil + irinotecan + leucovorin

A combination regimen consisting of **duligotuzumab** (a dual-action humanized monoclonal antibody targeting both epidermal growth factor receptor EGFR and human epidermal growth factor receptor 3 HER3), **5-fluorouracil** (a pyrimidine analog antimetabolite inhibiting thymidylate synthase), **irinotecan** (a topoisomerase I inhibitor), and **leucovorin** (a folinic acid used to enhance the efficacy of 5-fluorouracil). Duligotuzumab blocks ligand binding to both EGFR and HER3, thereby inhibiting downstream signaling critical for tumor cell survival and proliferation, with antibody-dependent cell-mediated cytotoxicity activity. This combination was studied in the context of metastatic colorectal cancer and other solid tumors, aiming to target multiple pathways relevant to tumor growth and drug resistance. Clinical trial data do not support a significant benefit over standard regimens, and development has been discontinued for these indications[3][4][2].