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**SI-B001 + irinotecan** is a combination investigational therapy composed of SI-B001, a first-in-class bispecific monoclonal antibody targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), and irinotecan, a small molecule inhibitor of DNA topoisomerase I. SI-B001 blocks EGFR and HER3 signaling pathways involved in tumor growth and resistance mechanisms. Irinotecan is a cytotoxic agent that induces DNA damage in rapidly dividing tumor cells by stabilizing the DNA-topoisomerase I complex, leading to cell cycle arrest and apoptosis. This combination is being developed primarily for use in patients with locally advanced or metastatic solid tumors such as EGFR/ALK wild-type non-small cell lung cancer (NSCLC), especially in the context of progressing after anti-PD-1/L1-based immunotherapy. SI-B001 is being developed by SystImmune, and irinotecan is an approved chemotherapeutic widely available in generic form and through brands such as Camptosar and Onivyde[1][2][7][8].
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