REGN5458 is a bispecific BCMA/CD3 T cell engaging antibody.

SparkCures ID 351
Developed By Regeneron Pharmaceuticals
Generic Name REGN5458
Treatment Classifications
Treatment Targets

Clinical Trials

All Clinical Trials

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Early Relapse Multiple Myeloma

The following is a listing of clinical trials for patients with multiple myeloma who have received one to two prior lines of therapy.

Late Relapse Multiple Myeloma

The following is a listing of clinical trials for patients with multiple myeloma who have received three or more prior lines of therapy.

Smoldering Myeloma
Monoclonal Gammopathy of Undetermined Significance (MGUS)

Published Results

Early, Deep, and Durable Responses, and Low Rates of Cytokine Release Syndrome with REGN5458, a BCMAxCD3 Bispecific Monoclonal Antibody, in a Phase 1/2 First-in-Human Study in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

December 11, 2021

As of data cut-off (June 10, 2021), 68 pts were treated with REGN5458 in the dose escalation cohort with full doses ranging from 3–400 mg. The median age at enrollment was 64 years (range, 41‒81) and 20.6% pts were ≥75 years. As per Revised International Staging System, stage was 1, 2 or 3 in 14.7%, 60.3% and 23.5% of pts respectively. Pts had a median of 5 prior lines of systemic therapy (range, 2–17) with the majority of pts (51.5%) being penta-refractory (see Table). The median duration of follow-up was 2.4 months (range, 0.1–20.8).

Treatment-emergent adverse events (TEAE) were reported in 66 pts (97.1%), and Grade (Gr) ≥3 TEAEs in 52 (76.5%) pts. The most frequent TEAEs were fatigue in 29 pts (42.6%), Gr 1/2 in 26 pts (38.2%), Gr 3 in 3 pts (4.4%); cytokine release syndrome (CRS) in 26 pts (38.2%), CRS was Gr 1 in 23 pts (33.8%) and Gr 2 in 3 pts (4.4%). No pt had Gr ≥3 CRS or discontinued treatment due to CRS. There were no Gr ≥3 neurotoxicity events. Nausea was reported in 22 pts (32.4%). The severity of nausea was Gr 1 in 23.5% of pts and Gr 2 in 8.8% of pts.

Treatment-related adverse events (TRAE) were reported in 56 patients (82.4%). The most frequent hematologic TRAE was neutropenia in 11 pts (16.2%), with Gr ≥3 severity in 9 of these pts (13.2%). The most frequent non-hematologic TRAEs were CRS (38.2%) and fatigue (20.6%). The safety profile was consistent across all dose levels, and there was no correlation between CRS and the full dose of REGN5458.

Responses were observed at all dose levels. Amongst pts treated at the 96 and 200 mg dose levels, the response rate was 73.3% (11/15). Across all dose levels, 92.6% (n=25) of all responders achieved at least a very good partial response and 48.1% (n=13) of responders had a complete response (CR) or stringent CR. Pts without extramedullary plasmacytomas (EMP) responded more frequently than those with EMP. The Kaplan–Meier estimated median DOR was not reached and the probability of DOR ≥8 months was 92.1% (95% confidence interval: 72.1, 98.0), with responses ongoing up to 19 months at the latest data cut-off.

Disease response was not impacted by level of BCMA expression in the core biopsy, as assessed by immunohistochemistry.