AstraZeneca's B7-H4 ADC AZD8205 Receives IND Approval in China for Advanced Solid Tumors

On June 14, the CDE website showed that AstraZeneca's AZD8205 clinical trial application was approved for the treatment of advanced or metastatic solid malignant tumors. This is the second B7-H4 antibody-drug conjugate (ADC) to be approved for clinical use in China, following Hansoh Pharma's HS-20089.

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

AZD8205 is a B7-H4-targeted ADC composed of a novel topoisomerase 1 inhibitor (TOP1i) — linker — and an antibody targeting B7-H4. Its mechanism of action involves delivering the TOP1i warhead to B7-H4-positive cells, causing DNA damage and cell death.

According to the AstraZeneca 2022 AACR meeting abstract, in a study involving 26 TNBC PDX tumor models, a single intravenous (IV) dose of 3.5 mg/kg AZD8205 achieved an overall response rate of 69% (tumor regression ≥30% from baseline), with a complete response rate of 36% (9/26). Further analysis showed enhanced anti-tumor activity in models with elevated B7-H4 expression and DNA damage repair (DDR) deficiency.

Currently, AstraZeneca has 12 ADC products under development, targeting HER2, TROP2, CD25, PCMA, and more.

Original Title: AstraZeneca's B7-H4 ADC Approved for Clinical Trials in China