AstraZeneca's AZD8205 Clinical Trial Application Approved

On June 14, CDE's official website showed that AstraZeneca's clinical trial application for AZD8205 was approved for the treatment of advanced or metastatic solid malignancies. This is the second B7-H4 antibody conjugated drug (ADC) approved for clinical use in China after Hansoh HS-20089.

The cell surface glycoprotein B7-H4 has limited expression in normal tissues, but is overexpressed in a series of solid tumors, including breast, ovarian, endometrial, and cholangiocarcinoma, and is a potential target for tumor immunotherapy.

AZD8205 is a B7-H4 targeting ADC consisting of a novel topoisomerase 1 inhibitor (TOP1i)-linker-targeting antibody against B7-H4. Its mechanism of action is to deliver TOP1i warheads into B7-H4-positive cells, resulting in DNA damage and cell death.

According to the abstract of AstraZeneca's 2022 AACR meeting, in a study of 26 TNBC PDX tumor models, a single intravenous (IV) dose of 3.5 mg/kg AZD8205 resulted in an overall response rate of 69% (tumor regression from baseline ≥ 30%), of which the complete remission rate was 36% (9/26). Further analysis revealed that stronger antitumor activity was observed in models with elevated B7-H4 expression and DNA damage repair (DDR) deficiency.

At present, AstraZeneca has 12 ADC products under development, involving targets including HER2, TROP2, CD25, PCMA, etc.