EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA)-CD3 BISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA

Elranatamab (PF-06863135) is a humanized bispecific monoclonal antibody (IgG2a) that targets BCMA, a member of the tumor necrosis factor receptor superfamily expressed in multiple myeloma, and CD3 on T cells. We reported results for intravenous (IV) dosing (Raje et al. Blood. 2019;134(S1):1869) and now update for subcutaneous (SC) dosing from the ongoing Phase 1 study (MagnetisMM-1; NCT03269136). Patients received elranatamab at 80, 130, 215, 360, 600, and 1000 μg/kg SC weekly. A modified toxicity probability interval method was used for escalation, with monitoring for dose-limiting toxicity (DLT) to 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 (Lee et al. Biol Blood Marrow Transplant. 2019;25:625). Response was assessed by International Myeloma Working Group criteria. Pharmacokinetics, cytokine profiling, and T cell immunophenotyping were performed. 30 patients 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 SC weekly. Patients had a median of 8 prior treatments; 87% had triple refractory disease, 97% had prior anti-CD38 therapy, and 23% (7 patients) had prior BCMA-directed antibody drug conjugate (6 of 7 patients) or chimeric antigen receptor T cell therapy (3 of 7 patients). The most common all causality TEAEs included lymphopenia (n = 25, 83%; 20% G3, 63% G4), CRS (n = 22, 73%; 57% G1, 17% G2, none ≥G3), anemia (n = 18, 60%; 50% G3, 0% G4), thrombocytopenia (n = 16, 53%; 17% G3, 20% G4), neutropenia (n = 16, 53%; 23% G3, 30% G4), and injection site reaction (n = 15, 50%; 43% G1, 7% G2, none ≥G3). Both CRS and immune effector cell-associated neurotoxicity syndrome (n = 6, 20%) were limited to ≤G2 with median durations of 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. The overall response rate (ORR) for doses ≥215 μg/kg 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). Median time to response was 22 days, and 3 of 4 patients (75%) with prior BCMA-directed therapy achieved response (VGPR, n = 2 and sCR