DHES0815A

DHES0815A is an investigational antibody-drug conjugate (ADC) designed for the treatment of HER2-positive cancers, particularly advanced or metastatic breast cancer. It consists of a humanized monoclonal antibody (MHES0488A) that targets a unique epitope on the human epidermal growth factor receptor 2 (HER2/ERBB2), which does not overlap with binding sites of trastuzumab or pertuzumab. The antibody is conjugated to a pyrrolobenzodiazepine (PBD) dimer payload via an engineered linker; this payload acts as a DNA-damaging agent by alkylating, but not cross-linking, DNA—differentiating it from other HER2-targeted ADCs that use microtubule inhibitors. Preclinical studies demonstrated selective cytotoxicity in HER2-positive cell lines and dose-dependent tumor inhibition in vivo. In phase 1 clinical trials for patients with advanced/metastatic HER2-positive breast cancer, early signs of anti-tumor activity were observed; however, persistent dermal, ocular, and pulmonary toxicities at higher doses led to early termination of the trial[4][5][6].

Other names

anti-HER2/PBD-MA antibody-drug conjugate DHES0815AANTI-HER2/PBD-MONOAMIDE ADC DHES0815A