Odronextamab (REGN1979): A Comprehensive Clinical and Scientific Monograph on a CD20xCD3 Bispecific Antibody for B-Cell Malignancies

I. Executive Summary

Odronextamab is an investigational, fully human, off-the-shelf bispecific antibody developed by Regeneron Pharmaceuticals, engineered to treat CD20-positive B-cell malignancies.[1] Classified as a Bispecific T-Cell Engager (BiTE), this immunoglobulin G4 (IgG4)-based therapy represents a significant advancement in immuno-oncology. Its core mechanism of action involves simultaneously binding to the CD20 antigen on malignant B-cells and the CD3 complex on T-cells. This dual engagement forms a cytolytic synapse, redirecting the patient's own T-cells to recognize and eliminate cancer cells through potent, targeted cytotoxicity, independent of traditional immune recognition pathways.[3]

In pivotal clinical trials, odronextamab has demonstrated compelling and durable efficacy in heavily pretreated patient populations with B-cell non-Hodgkin's lymphomas (B-NHLs). For patients with relapsed or refractory (R/R) Follicular Lymphoma (FL), odronextamab achieved an objective response rate (ORR) of approximately 80%, with a remarkably high complete response (CR) rate of 73% and a median duration of response exceeding two years.[6] In the more aggressive setting of R/R Diffuse Large B-Cell Lymphoma (DLBCL), the therapy produced an ORR of approximately 52% and a CR rate of 31%, with a median duration of CR of 18 months.[8]

Critically, odronextamab has shown significant activity in a population with a profound unmet medical need: DLBCL patients who have progressed after receiving CD19-directed chimeric antigen receptor (CAR) T-cell therapy. In this challenging setting, odronextamab monotherapy yielded an ORR of 48%, effectively doubling the historical median overall survival.[10]