New Bispecific Monoclonal Antibody Shows Deep, Durable Responses in Relapsed, Refractory Multiple Myeloma

Multiple myeloma is characterized by expression of the cell surface BCMA, making this a target for therapeutic intervention with REGN5458.

New research to be presented at the American Society of Hematology 62nd Annual Meeting and Exposition has found that REGN5458, a B-cell maturation antigen (BCMA) x CD3 bispecific monoclonal antibody, induced deep and durable responses in patients with relapsed or refractory multiple myeloma.

According to the authors, multiple myeloma is characterized by expression of the cell surface BCMA, making this a target for therapeutic intervention. REGN5458 is a BCMA x CD3 bispecific antibody that binds to both BCMA and CD3, targeting multiple myeloma cells with T-cell effector function. Earlier data have shown an acceptable safety profile with evidence of clinical efficacy in heavily pre-treated patients with relapsed or refractory multiple myeloma.

In the new phase 1 study, the primary objectives are to determine the safety, tolerability, and occurrence of dose-limiting toxicities. As of the June 15, 2020, data cut-off, 45 patients were treated with REGN5458. The median age at enrollment was 64 years and 14 patients were older than 70 years of age. Furthermore, 60% and 22.2% of participants were stage 2 and 3, respectively, and patients had a median of 5 prior lines of therapy.

REGN5458 was escalated in cohorts from 3 mg to 96 mg over 6 dose levels, with a median duration of follow-up of 2.37 months. The most common treatment-related adverse events (AEs) include cytokine release syndrome (CRS), fatigue, nausea, and myalgias. According to the authors, CRS occurred primarily during the initial doses and was grade 1 in 88.2% of patients. Four patients discontinued due to AEs.

Overall response rate (ORR) was 35.6% across all dose levels, with 81.3% of responders achieving at least a very good partial response, according to the study. Furthermore, 31.3% had a complete response or stringent complete response. A total of 43.8% of responders had a duration of response of more than 4 months and 18.8% had a duration of response of more than 8 months. The ORR of patients with extramedullary plasmacytomas was 16.7%.

According to the study authors, this updated analysis of the first in-human study of REGN5458 continued to show an acceptable safety profile and durable efficacy among this patient population. Enrollment in the phase 1 dose escalation portion is ongoing and the phase 2 portion of the study is recruiting.

REFERNECE

REGN5458, a BCMA x CD3 Bispecific Monoclonal Antibody, Induces Deep and Durable Responses in Patients with Relapsed/Refractory Multiple Myeloma (RRMM). Paper presented at: American Society of Hematology 62nd Annual Meeting & Exposition; December 5-8, 2020. Accessed December 3, 2020.