SGNBCMA-001: A phase 1 study of SEA-BCMA, a non-fucosylated monoclonal antibody, in subjects with relapsed or refractory multiple myeloma.

Abstract

TPS8054 Background: Despite recent advances in treatment, multiple myeloma (MM) remains incurable in most patients. The standard of care for MM includes combinations of agents with different mechansims of action, e.g. proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies, alkylating agents, and corticosteroids. Sequential lines of treatment typically yield shorter durations of disease control with each subsequent relapse. Frail patients face a particularly high unmet need, given the toxicity profiles of many agents. SEA-BCMA is a humanized non-fucosylated IgG1 monoclonal antibody targeting BCMA, a plasma cell-specific protein that is expressed on MM cells of most patients. Based on preclinical data, SEA-BCMA displays enhanced antibody dependent cellular cytotoxicity through increased FcγRIII binding, antibody dependent cellular phagocytosis, and blocking of BCMA-mediated pro-survival and proliferative signaling. SEA-BCMA is active at 0.03 mg/kg in xenograft models and does not cause adverse effects in preclinical models, supporting clinical investigation for MM. Methods: This is a phase 1, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, and antitumor activity of SEA-BCMA in adults with relapsed/refractory MM. Enrollment began in November 2018 for adults aged ≥18 years with histologically confirmed MM, Eastern Cooperative Oncology Group performance status of ≤1, and no other therapeutic options available. Prior therapies must include a PI, an IMiD, and an anti-CD38 antibody. Prior receipt of BCMA targeted agents is prohibited. BCMA expression is not required for study entry, but will be tested retrospectively. Dose-escalation is being conducted in ~25 subjects using the modified toxicity probability interval method. During dose-expansion, ~40 subjects will be treated at the maximum tolerated or optimal dose. Responses are assessed per the 2016 International Myeloma Working Group criteria. Biomarker and pharmacokinetic evaluations will be performed on peripheral blood and bone marrow. Clinical trial information: NCT03582033.