Early Findings Highlight Promising Outcomes With REGN5458 in Relapsed/Refractory Multiple Myeloma

Patients with relapsed/refractory multiple myeloma experienced promising responses with REGN5458.

Findings from a phase 1/2 trial (NCT03761108) highlighted timely and promising responses among patients with heavily pre-treated relapsed/refractory multiple myeloma who were treated with REGN5458.

Data from the study, which were presented at the 2022 European Hematology Association Congress, indicated the overall response rate (ORR) was 51% among patients who were treated with the monotherapy. Moreover, investigators reported a very good partial response (VGPR) of better rate of 86%, of which 43% were complete responses (CR) or better.

When assessing responses by dose level, investigators reported that ORR was 29% in the 3 mg to 12 mg cohort, 48% in the 24 mg to 96 mg cohort, and 75% in the 200 mg to 800 mg cohort. Moreover, in the 3 mg to 12 mg arm, the PR rate was 4%, CR rate was 13%, and stringent CR (sCR) rate was 13%; in the 24 mg to 96 mg arm, the VGPR rate was 24%, CR rate was 4%, and sCR rate was 20%; and in the 200 mg to 800 mg arm, the PR rate was 17%, VGPR rate was 42%, CR rate was 8% and sCR rate was 8%.

This was a first-in-human, open-label trial assessing the use of REGN5458, a BCMA- and CD3-directed bispecific antibody capable of achieving cytotoxicity on BCMA-expressing cancer cells by targeting T-cell effector function. A total of 9 doses of the agent were evaluated using a 4 + 3 design, including 3 mg (n = 4), 6 mg (n = 10), 12 mg (n = 10), 24 mg (n = 10), 48 mg (n = 7), 96 mg (n = 8), 200 mg (n = 12), 400 mg (n = 8), and 800 mg (n = 4). A double step-up dosing strategy was used to administer the intravenous agent, which entailed an initial dose during week 1, a step-up dose in week 2, and a full cohort dose during week 3.

Patients had a median time to response of 1 month, with most responses (70%) taking place within 2 months of treatment. The estimated median duration of response was not reached and the probability of responders maintaining a response at 8 months was 90.2%.

In terms of safety, the most common grade 3 or higher hematologic treatment-emergent adverse effects (TEAEs) occurring in at least 20% of patients or more included pneumonia (11%), back pain (5%), pyrexia (4%), fatigue (3%), diarrhea (3%), headache (3%), and chills (1%).

Although 4% of patients experienced grade 2 immune effector cell–associated neurotoxicity syndrome, there were no grade 3 events. Additionally, 38% of patients developed cytokine release syndrome (CRS), although most events were grade 1 in severity. A total of 3 patients had grade 2 CRS and no grade 3 or higher events were reported. Seven percent of patients experienced grade 5 AEs, including sepsis, COVID-19, and pneumonia.


Zonder JA, Richter J, Bumma N, et al. Early, deep, and durable responses, and low rates of CRS with REGN5458, a BCMAXCD3 bispecific antibody, in a phase 1/2 first-in-human study in patients with relapsed/refractory multiple myeloma. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S189.