The investigational treatment REGN5458, a BCMA- and CD3-targeted bispecific monoclonal antibody, demonstrated early, deep, and durable responses in patients with relapsed/refractory multiple myeloma (MM), according to a phase I first-in-human study presented at the ASH Annual Meeting & Exposition.
Enrollment into the phase I portion of the study followed a standard 4+3 dose escalation design. Patients had progressive MM after three or more prior lines of systemic therapy, including a proteasome inhibitor, immunomodulatory agent, and anti‑CD38 antibody. Patients received weekly REGN5458, followed by a maintenance phase administered every two weeks.
As of the June 15, 2020, 45 patients (median age, 64 years; range, 41-81 years) were treated with REGN5458. Patients had received a median of five prior lines of systemic therapy (range, 2-17 therapies), and 32 patients (71.1%) had undergone autologous hematopoietic cell transplantation. Among the cohort, 6.7% were triple-refractory, 33.3% were quadruple-refractory, and 53.3% were penta-refractory. REGN5458 was given at 3 mg to 96 mg over six dose levels. The median duration of follow-up was 2.37 months (range, 0.7-12.3 months).
The most common treatment-related adverse events (AEs) were cytokine release syndrome (CRS; 37.8%), fatigue (17.8%), nausea (17.8%), and myalgias (13.3%). Grade ≥3 treatment-related AEs occurred in 28.9% of patients, the most common of which were anemia (8.9%) and lymphopenia (6.7%). CRS occurred primarily during the initial doses and was grade 1 in most patients (88.2%). Infusion-related reactions occurred in 6.7% of patients, and infection-related AEs occurred in 46.7% of patients, 20% of which were grade ≥3. One patient experienced a grade ≥3 treatment-related neurological event. Four patients discontinued treatment.
One patient had a dose-limiting toxicity due to transient grade 3 liver transaminases associated with CRS. Upon recovery, the patient continued on REGN5458 and has achieved ongoing partial remission.
The objective response rate was 35.6% across all dose levels, reaching 60% in the highest REGN5458 dose cohort. Most responders (81.3%) achieved at least a very-good partial response, and 31.3% had a complete response (CR) or stringent CR. Nearly half of patients (43.8%) had a duration of response (DOR) of four or more months, and 18.8% had a DOR of eight or more months.
Enrollment in the phase I dose escalation portion is ongoing, and the phase II portion of the study is recruiting.