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High Rate of CR Shown With Monoclonal Antibody REGN5458 for Heavily Pretreated R/R MM
Nearly half of patients with relapsed or refractory (R/R) multiple myeloma (MM) in an ongoing phase 1/2 trial experienced a complete response (CR) with REGN5458, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody monotherapy.
Although a prior report from the phase 1 portion of the trial indicated patients had acceptable safety and tolerability with early, deep, and durable responses in those who were heavily pretreated, with at least triple-refractory R/R MM, the disease remains incurable.
Patients in the trial had received a median of 5 prior lines of systemic therapy, with over half of the patients being penta-refractory. The median duration of follow-up was 2.4 months, but the longest follow-up was 20.8 months.
In the trial patients with progressive R/R MM, who were triple-refractory, or intolerant to prior lines of systemic therapy including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody receive REGN5458 monotherapy following a modified 3+3 dose-escalation design (4+3).
Treatment consists of 16 weekly infusions of REGN5458, followed by dosing every 2 weeks, until disease progression.
As of data cut-off, 68 patients were treated with REGN5458 in the dose escalation cohort. Responses were observed at all dose levels. Amongst patients treated at the 96 and 200 mg dose levels, the response rate was 73.3%. Across all dose levels, 92.6% of all responders achieved at least a very good partial response (PR) and 13 responders had a CR or stringent CR.
Grade or higher treatment-emergent adverse events (TEAEs) occurred in 76.5% of patients, including cytokine release syndrome (CRS) in 38.2%.
“REGN5458 continues to show an acceptable safety and tolerability profile, with grade 2 CRS in only 4.4% of patients, and no grade 3 or higher CRS or neurotoxicity events. No new safety signals were observed during the additional follow-up period. Early, deep, and durable responses were seen in triple- to penta-refractory patients with R/R MM, with a 73.3.% response rate at the combined 96 and 200 mg dose levels,” wrote lead author Jeffrey A. Zonder, MD, Karmanos Cancer Institute, Detroit, and colleagues.
