AstraZeneca's AZD5492 Advances to Clinical Trials in China: A New Hope for B-Cell Lymphoma Treatments

On August 17, the Chinese National Medical Products Administration's Centre for Drug Evaluation (CDE) website announced that AstraZeneca's (AZN.US) AZD5492 has applied for clinical trials in China and received acceptance. According to public information, AZD5492 is a CD20×TCR×CD8 tri-specific antibody, a T cell engager guided by CD8. This marks the candidate drug's first clinical trial application in China.

AZD5492 is poised to significantly enhance treatment outcomes in B-cell lymphoma, providing strong biological evidence for further clinical evaluation of this candidate drug.

AstraZeneca has already registered a Phase 1/2 clinical trial to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of AZD5492 in patients with relapsed/refractory B-cell malignancies. The study is planned to be conducted at 19 centers across the United States, Australia, and other regions, with a target enrolment of 174 participants. The study is expected to conclude in February 2028.

The application for clinical trials of AZD5492 in China signifies that this development-stage drug is also progressing into the registration phase in the country.

AZD5492 is an asymmetric tri-specific monoclonal IgG1 antibody containing two anti-CD20 Fab domains, a VHH domain that binds to TCR, and another VHH domain that binds to the CD8 co-receptor. This June, at the 2024 European Hematology Association (EHA) Annual Meeting, preclinical study data for AZD5492 in treating B-type non-Hodgkin lymphoma was presented.

The preclinical study explored AZD5492's mechanism of action both in vitro and in vivo, comparing its bioactivity with traditional CD3xCD20 T cell engagers. The study demonstrated that, in contrast to conventional CD20xCD3 T-cell engagers (which engage and activate both CD4+ and CD8+ T cells), AZD5492 preferentially engages CD8+ T cells, inducing a certain degree of B-cell killing while reducing the activation of CD4+ T cells and the associated cytokine production. This promising outcome suggests AZD5492's potential to greatly improve treatment efficacy for B-cell lymphoma, laying a solid foundation for its further clinical evaluation.

The preclinical and clinical trial developments, along with the CDE's acceptance of the application, underline AstraZeneca's commitment to advancing innovative cancer treatments in China.