SHR-A1403

SHR-A1403 is a novel antibody-drug conjugate (ADC) designed for the targeted treatment of cancers with high c-Met (hepatocyte growth factor receptor; HGFR) expression. It consists of a humanized IgG2 monoclonal antibody directed against c-Met, covalently linked via an uncleavable thioether linker to the proprietary cytotoxic small-molecule drug SHR152852, which acts as a microtubule inhibitor. The mechanism of action involves specific binding to c-Met on tumor cells, internalization and lysosomal trafficking of the ADC, and intracellular release of the cytotoxic payload. This results in microtubule depolymerization, cell cycle arrest, apoptosis induction, inhibition of cell proliferation and migration, and disruption of cholesterol biosynthesis pathways within cancer cells. Preclinical studies have demonstrated significant anti-tumor activity in models of pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) with acquired resistance to EGFR inhibitors such as AZD9291/osimertinib, and other solid tumors overexpressing c-Met[1][2][3][4][5][6].