The bispecific antibody AZD0486: an overview of the clinical journey to date with a focus on follicular lymphoma

Follicular Lymphoma (FL) is the most common indolent lymphoma. Patients with advanced stage FL typically respond to therapy, then follow a relapsing/remitting course, with shorter progression-free survival with each subsequent line of therapy. Whilst existing CD-19 directed therapies such as CAR T-cell therapy have shown promising efficacy in the management of relapsed/refractory FL, immune-mediated adverse events, such as cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity (ICANS), are well described. AZD0486 is a fully human bispecific (CD19xCD3) T-cell engager (TCE) that induces T cell-mediated cytotoxicity, but with low affinity binding of CD3, resulting in a reduction in cytokine release. In this review we describe the key pre-clinical data for AZD0486 and evaluate in detail the available clinical data from the ongoing phase 1 first-in-human study, including safety, efficacy, pharmacokinetics, and future development plans. Bispecific TCEs are among the most promising novel therapies in use for the management of relapsed/refractory B-cell lymphomas. AZD0486 results in high complete response rates with low incidence of high grade immune-mediated toxicity compared to alternative TCE therapies. Importantly, it remains active in patients with lymphomas that have lost CD20 expression, an important mechanism of treatment failure following CD20 targeting TCEs.