by Dr. C.H. Weaver M.D. 12/2020
Bispecific antibody constructs represent an innovative immunotherapy approach that helps the body’s immune system target cancer cells and appears very promising for the treatment of multiple myeloma. Bispecific antibodies or BiTE which is short for "bispecific T cell engager" are antibodies with two arms. One arm of the drug attaches to a specific protein on the cancer cell. The other arm of the BiTE activates immune cells in the patient to kill the cancer cells.(1)
REGN5458 is a BCMA x CD3 bispecific antibody designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T-cells, bridging them together and activating T-cell killing of the cancerous myeloma cells. REGN5458 was invented using Regeneron's next generation VelocImmune® "human antibody mouse" technology, together with its VelociBi™ platform. These allow for the creation of bispecific antibodies that closely resemble natural human antibodies with no linkers or artificial sequences.(1)
Initial results evaluating REGN5458 were presented at the American Society of Hematology (ASH) Annual Meeting in December 2019 and updated in 2020. Two dose levels of REGN5458 were evaluated in refractory myeloma patients previously treated with a median of seven lines of prior systemic therapy, all of whom had failed CD38 antibody treatment. Responses were observed in 57% of patients, including 75% treated at the highest administered REGN5458 dose.
Results were updated at the 2020 ASH annual meeting. In the trial 49 patients evaluated had a median of five prior lines of therapy (range: 2-17) with 100% being triple-refractory and 57% being penta-refractory to previous treatment and all patients were refractory to anti-CD38 therapy. Among these refractory patients 63% responded to treatment with REGN5458 and among all patients responding to treatment, 95% experienced a very good partial response or better. In responding patients with greater than 6 months of follow-up, 83% have ongoing responses for up to 13 months at the time of analysis. (3)
These results are promising and clinical trials evaluating REGN5458 are currently ongoing.(2)
- Leukemia; 2019; DOI:10.1038/s41375-019-0435-7