Abstract 3505: AM105, first-in-class T cell engaging bispecific antibody for metastatic colon cancer, demonstrates strong anti-tumor activity by both neutralizing EGFR activity and engaging T cells

Abstract Globally, colorectal cancer is a significant health concern. In 2020, there were over 1.9 million new cases and more than 930,000 deaths attributed to this disease and 5 year survival rate for distant colorectal cancer is 14.7 percent. Cetuximab, an approved anti-EGFR antibody, is effective in treating metastatic colorectal cancer with wild-type KRAS, improving survival. However, about 80% of patients develop resistance, leading to disease recurrence. To address this high recurrence rate, ongoing research focuses on developing bispecific antibodies that can overcome this resistance, aiming to improve long-term outcomes in metastatic colorectal cancer patients.AM105, a novel T cell-engaging bispecific antibody comprising a newly developed monoclonal antibody (15E3) and an affibody targeting EGFR and 4-1BB respectively. Characterized by its 2+4 architecture, it enhances selective binding to cancer cells by creating a difference in affinity between TAA and 4-1BB. It includes four Affibodies targeting 4-1BB, thereby increasing the likelihood of binding with T cells. Additionally, by enhancing the “clustering of CD137” on T cells, the T cell response is significantly amplified. In addition, AM105 was found to efficiently induce tumor cell death in CRC cell lines, even at very low effector-to-target cell ratio, in a target expression dependent manner. In vivo experiment using humanized 4-1BB mice have demonstrated excellent tumor cell elimination effects, and this therapeutic effect was still observed after newly introduction of tumor cells even in the absence of AM105 in the blood, suggesting the induction of T-cell memory function. Taken together, these results strongly suggested that AM105, a novel 4-1BB based bispecific antibody, exhibits potent anti-tumor T cell activity and could be promising therapeutic agent. Citation Format: Hyun-Jong Lee, Dong-Wook Kim, Seong-Yeol Kim, Min Yoon, Young-ha Lee, In-Sik Hwang, Yoon Lee, Jong-Hoon Kim, Jong-Seo Lee. AM105, first-in-class T cell engaging bispecific antibody for metastatic colon cancer, demonstrates strong anti-tumor activity by both neutralizing EGFR activity and engaging T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3505.