OAB-026: MagnetisMM-1 study of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA) targeted CD3-engaging bispecific molecule, for patients (pts) with relapsed or refractory multiple myeloma (MM)

Background Elranatamab (PF-06863135), a humanized bispecific molecule, targets both BCMA expressed in MM and CD3 on T cells. MagnetisMM-1 (ClinicalTrials.gov ID: NCT03269136) is a Phase 1 study of elranatamab with the aim of characterizing the efficacy, safety, pharmacokinetics, and pharmacodynamics of elranatamab as single agent and in combination with immunomodulatory agents for pts with relapsed or refractory MM. Methods Pts received single agent elranatamab 80, 130, 215, 360, 600, or 1000µg/kg/week subcutaneously. A modified toxicity probability interval method was used for escalation, with monitoring for dose-limiting toxicity (DLT) to the end of the first cycle. Treatment emergent adverse events (TEAEs) were graded by Common Terminology Criteria for Adverse Events v4.03, and cytokine release syndrome (CRS) by American Society for Transplantation and Cellular Therapy criteria (Biol Blood Marrow Transplant. 2019;25:625). Responses and minimal residual disease (MRD) status (by next-generation sequencing at a sensitivity of 1 × 10-5) were assessed by International Myeloma Working Group criteria. Pharmacokinetics, cytokine profiling, and T cell immunophenotyping were performed. Results 30 pts had received elranatamab as of 4-Feb-2021 at 80 (n=6), 130 (n=4), 215 (n=4), 360 (n=4), 600 (n=6), or 1000 (n=6) µg/kg. Pts 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). Both 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 DLT 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 ≥215µg/kg, confirmed overall response rate (ORR) was 70% (n=14/20) including partial response (PR; n=1), very good PR (VGPR; n=7), complete response (CR; n=1), and stringent CR (sCR; n=5). The majority of patients with sCR achieved MRD negativity. 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 1000µg/kg was 83% (n=5/6). Conclusions Elranatamab achieved confirmed ORR of 83% at RP2D with a manageable safety profile for pts with relapsed or refractory MM. These results confirm the feasibility and potential of BCMA-directed immunotherapy for malignant plasma cell disorders, and support further development of elranatamab for pts with MM. This study was sponsored by Pfizer.