Abstract 2927: CS2011: A novel bispecific antibody targeting EGFR and HER3 that demonstrates promising antitumor activity in preclinical evaluation

Abstract Background: EGFR (also known as HER1) is an epidermal growth factor receptor with tyrosine kinase activity implicated in both tumorigenesis and tumor progression, and its overexpression in approximately 70% of colorectal cancer (CRC), 60% of lung cancers, and over 90% of head and neck squamous cell carcinoma (HNSCC) have been shown associated with advanced diseases. Approved anti-EGFR therapies, including cetuximab, pantitumumab, and necitumumab, are widely used in treating the aforementioned malignancies. Amivantamab, a bispecific antibody targeting EGFR and c-MET, has been approved for treating advanced NSCLC with EGFR mutations. HER3, another member of the HER family, is overexpressed in cancers including CRC and lung cancer. The upregulation of HER3 has been reported in tumors when treated with MAPK/PI3K inhibitors, EGFR TKIs, or hormone therapies. Daiichi’s HER3-ADC, U3-1402, has shown promising clinical results in advanced EGFR-mutant NSCLC, confirming HER3 as a valid therapeutic target. CS2011 is a bispecific antibody composed of a potent anti-EGFR arm and a fully functional anti-HER3 arm. Unlike anti-EGFR, anti-HER2 or anti-HER3 mono-targeting antibodies, CS2011 inhibits almost all functional membrane dimers formed with HER members, and therefore acts as a broad epithelial growth factor signaling blocker to address tumor heterogeneity effectively. Methods Part 1 (Regular Abstracts) ; 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85 (8Suppl₁): Abstract nr 2927.