MM-379: MagnetisMM-1: A Study of Elranatamab (PF-06863135), a B-Cell Maturation Antigen (BCMA)-Targeted, CD3-Engaging Bispecific Antibody, for Patients with Relapsed or Refractory Multiple Myeloma (MM)

Context Elranatamab (PF-06863135), a humanized bispecific monoclonal antibody (IgG2a), targets BCMA expressed in MM and CD3 on T-cells. Objective Characterize efficacy, safety, pharmacokinetics, and pharmacodynamics of elranatamab. Design Phase 1 study (MagnetismMM-1; NCT03269136). Data cut-off: 4 February 2021. Patients Relapsed or refractory MM. Intervention 80, 130, 215, 360, 600, or 1000 µg/kg/week subcutaneously. Main Outcome Measures 1) Treatment-emergent adverse events (TEAEs) graded by CTCAE v4.03 and cytokine release syndrome (CRS) by ASTCT criteria. 2) International Myeloma Working Group criteria-assessed response. 3) Pharmacokinetics, cytokine profiling, and T-cell immunophenotyping. Results Thirty patients received elranatamab at 80 (n=6), 130 (n=4), 215 (n=4), 360 (n=4), 600 (n=6), or 1000 (n=6) µg/kg. Patients had a median of 8 prior treatments; 87% had triple refractory disease, 97% prior anti-CD38 therapy, and 23% prior BCMA-directed antibody drug conjugate or chimeric antigen receptor T-cell therapy. Common all causality TEAEs included lymphopenia (n=25, 83%; 20% G3, 63% G4), CRS (n=22, 73%; none >G2), anemia (n=18, 60%; 50% G3, 0% G4), neutropenia (n=16, 53%; 23% G3, 30% G4), thrombocytopenia (n=16, 53%; 17% G3, 20% G4), and injection site reaction (n=15, 50%; none >G2). CRS and immune effector cell-associated neurotoxicity syndrome (n=6, 20%) were limited to ≤G2; median durations were 3 and 2.5 days, respectively. No dose-limiting toxicity was observed. Exposure increased with dose and Tmax ranged from 3–7 days. Cytokine increases occurred with the first dose, and increased T-cell proliferation was observed in peripheral blood. For doses ≥215 µg/kg, the confirmed overall response rate (ORR) was 70% (n=14/20); partial response (PR; n=1), very good PR (VGPR; n=7), complete response (CR; n=1), and stringent CR (n=5). Median time to response was 22 days. In this dosing group, 3 of 4 pts (75%) with prior BCMA-directed therapy achieved response. Confirmed ORR at the recommended phase 2 dose (RP2D) of 1000 µg/kg was 83% (n=5/6). Conclusions Elranatamab achieved confirmed ORR of 83% at RP2D with a manageable safety profile for patients with relapsed or refractory MM. These results support further development of elranatamab for patients with MM. This study was sponsored by Pfizer.