AZD5492: A Novel CD20-Targeting, CD8-Selective T-Cell Engaging Bispecific Antibody in Clinical Development for B-Cell Malignancies and Autoimmune Diseases

I. Executive Summary

AZD5492 is an investigational bispecific antibody developed by AstraZeneca, currently undergoing early-stage clinical evaluation. This therapeutic agent is engineered as a CD8-selective, CD20xCD3 T-cell engager, utilizing AstraZeneca's proprietary Target Induced T-cell Activating Nanobody (TITAN) platform.[1] The molecule is designed for subcutaneous administration and is being explored across two distinct therapeutic areas: oncology and autoimmune diseases.

In the oncology domain, AZD5492 is under investigation for the treatment of relapsed or refractory (R/R) B-cell malignancies, including large B-cell lymphoma (LBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).[4] The primary clinical study in this area is the TITANium trial (D9960C00001 / NCT06542250), a Phase I/II open-label, dose escalation and expansion study initiated in late 2024.[6] The objectives of this trial are to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AZD5492.

Concurrently, AZD5492 is being developed for autoimmune indications, specifically Systemic Lupus Erythematosus (SLE) and Idiopathic Inflammatory Myopathies (IIM).[8] The TITAN study (D9961C00001), a Phase I trial, is designed to evaluate the safety, tolerability, PK, and PD of subcutaneously administered AZD5492 in adult participants with these conditions, employing single ascending dose and step-up dosing strategies.[8] This trial was anticipated to begin recruiting in early 2025.