MM-087 Early, Deep, and Durable Responses, and Low Rates of Cytokine Release Syndrome With REGN5458, a BCMAxCD3 Bispecific Antibody, in a Phase 1/2 First-In-Human Study in Patients With Relapsed/Refractory Multiple Myeloma

Abstract

Despite advances in treatment options, multiple myeloma remains incurable. REGN5458 is a BCMAxCD3 bispecific antibody under investigation in relapsed/refractory multiple myeloma (RRMM): ongoing Phase 1/2 trial (NCT03761108). To describe updated safety, overall response, and response durability in patients treated with REGN5458 in the Phase 1 part. The Phase 1 part follows a modified 3+3 dose-escalation design (4+3). Eligible patients with progressive RRMM, who were double- or triple-refractory, or intolerant to prior lines of systemic therapy, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody, were included. Sixteen weekly infusions of REGN5458 monotherapy, then every two weeks until disease progression. Primary objectives were to assess safety, tolerability, and occurrence of dose-limiting toxicities of REGN5458, and to determine a recommended Phase 2 dose regimen. The objective response rate by modified International Myeloma Working Group criteria was a key secondary objective. At data cut-off (September 30, 2021), 73 patients were treated with REGN5458 in the dose-escalation cohort, with full doses ranging from 3-800 mg. The median age at enrollment was 64 years (range, 41-81). As per the Revised International Staging System, stages were 1, 2, or 3 in 15.0%, 57.5%, and 23.3% of patients, respectively. Patients had a median of five prior lines of systemic therapy (range, 2-17), with 89% of patients being triple-refractory. The median duration of follow-up was 3.0 months (range, 0.7-22.1). The most common treatment-emergent adverse events (TEAEs) were fatigue (45.2%), cytokine release syndrome (CRS) (38.4%), pyrexia (35.6%), and nausea (32.9%). There were no Grade ≥3 CRS or Grade ≥3 neurotoxicity events, and no treatment discontinuation due to CRS. Grade 3 and 4 TEAEs were reported in 31 (42.5%) and 24 patients (32.9%), respectively. The most common Grade 3/4 TEAEs were hematologic (39.0%). Responses were observed at all dose levels. Amongst patients treated at the 200-800 mg dose levels, the response rate was 75% (n=18/24). The median duration of response was not reached. REGN5458 shows early, deep, and durable responses with a manageable safety profile in triple or greater-refractory patients with RRMM. This study is funded by Regeneron.