Fast track designation and phase II trial initiation with elranatamab, a BCMA/CD3 bispecific antibody

The first patient with relapsed/refractory multiple myeloma (MM) has been given a dose of elranatamab, a B-cell maturation antigen (BCMA) CD3 bispecific antibody in the phase II MagnetisMM-3 trial (NCT04649359). The U.S. Food and Drug Administration (FDA) has also given elranatamab fast track designation to aid the rapid development and review of this novel agent.¹

Elranatamab is a subcutaneously-administered bispecific antibody that functions by bringing cancer cells in closer contact with host cytotoxic T cells. This is achieved by binding CD3 moiety on the host T cell and engaging the BCMA antigen on the MM cell, leading to activation of the immune response.

Elranatamab is designed for patients with MM who are triple refractory (refractory to at least one immunomodulatory drug, one proteasome inhibitor, and an anti-CD38 monoclonal antibody). The MagnetisMM-3 trial has been set up to examine the safety and efficacy of elranatamab monotherapy, and the expected completion date for this study is June 2022. The aim of the study is to enroll both patients with previous experience of an anti-BCMA antibody or chimeric antigen receptor T cell (n = 90) and patients who are naïve to these agents (n = 60). The primary endpoint is the objective response rate, and secondary endpoints are the duration of response, progression-free survival, measurable residual disease negativity, overall survival, and safety.

Phase I data from the MagnetisMM-1 (NCT03269136) trial was presented during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition for elranatamab. A manageable safety profile, with mainly Grade 1–2 cytokine release syndrome events, and a promising efficacy was demonstrated in this small group of patients (N = 18).² The overall response rate was 75% at the top two dose levels. This study is ongoing and enrolling patients to explore the safety and efficacy of elranatamab combined with immunomodulators, such as lenalidomide or pomalidomide, or with an anti-PD-1 antibody.