Innovent’s B7-H3/EGFR bispecific antibody ADC receives clinical trial approval
As a core driver target in solid tumors, EGFR is frequently activated in multiple cancer types, including colorectal cancer, lung cancer, and head and neck squamous cell carcinoma. However, EGFR also exhibits physiological expression in normal epithelial tissues, such as skin and gastrointestinal mucosa. Conventional EGFR inhibitors lack tumor selectivity and often cause severe off-target toxicity, which not only reduces patients’ quality of life but also forces clinicians to lower the dose, thereby limiting therapeutic potential.
TCGA database analysis reveals a significant positive correlation between B7-H3 and EGFR mRNA expression in multiple solid tumors, including lung cancer, head and neck cancer, pancreatic cancer, and esophageal cancer. Immunohistochemistry and multiplex immunofluorescence validation confirm that B7-H3 and EGFR co-localize on the surface of the same tumor cells in lung squamous cell carcinoma and other tumor tissues. In contrast, normal lung tissue and skin show almost no B7-H3 expression, with only physiological EGFR expression present.
Flow cytometry analysis of 44 tumor cell lines further confirms that B7-H3 and EGFR protein co-expression is common in solid tumors, providing a molecular basis for the targeting specificity of bispecific antibodies. Clinical sample analysis shows that the co-expression intensity of B7-H3 and EGFR positively correlates with the malignancy level of lung squamous cell carcinoma. Samples with high co-expression exhibit more pronounced invasive features, suggesting that this patient subgroup may benefit from dual-targeted therapy.
IBI343 is a biomarker-guided, CLDN18.2-targeting antibody-drug conjugate (ADC). As a precision therapeutic agent, it is developed for the treatment of various CLDN18.2-positive tumors. IBI343 utilizes a cleavable linker to selectively deliver a highly active topoisomerase I inhibitor to tumor cells. It also incorporates an Fc-silent design to minimize off-target toxicity outside the tumor. This drug is the first CLDN18.2-targeting ADC globally to submit a regulatory review application.
