Efficacy and safety of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MM).
Authors: Bahlis Nizar J. , Raje Noopur S. , Costello Caitlin , Dholaria Bhagirathbhai R. , Solh Melhem M. , Levy Moshe Y. , Tomasson Michael H , Dube Harman , Liu Feng , Liao Kai Hsin , Basu Cynthia , Skoura Athanasia , Chan Edward Michael , Trudel Suzanne , Jakubowiak Andrzej J. , Chu Michael P , Gasparetto Cristina , Dalovisio Andrew , Sebag Michael , Lesokhin Alexander M. 
Published: June 2021

8006 Background: Elranatamab (PF-06863135) is a humanized bispecific monoclonal antibody (IgG2a) that targets BCMA, a member of the tumor necrosis factor receptor superfamily expressed in MM, 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). Methods: Patients (pts) received elranatamab at 80, 130, 215, 360, 600, and 1000μg/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. Results: 30 pts had received elranatamab as of 4-Aug-2020 at 80 (n = 6), 130 (n = 4), 215 (n = 4), 360 (n = 4), 600 (n = 6), or 1000 (n = 6) μg/kg SC weekly. Pts had a median of 8 prior treatments; 87% had triple refractory disease, 97% had prior anti-CD38 therapy, and 23% had prior BCMA-directed antibody drug conjugate or chimeric antigen receptor T cell therapy. The most common all causality TEAEs included lymphopenia (n = 24, 80%; 20% G3, 60% G4), CRS (n = 22, 73%; none > G2), anemia (n = 17, 57%; 43% G3, 3% G4), injection site reaction (n = 16, 53%; none > G2), thrombocytopenia (n = 16, 53%; 23% G3, 17% G4), and neutropenia (n = 12, 40%; 17% G3, 17% G4). Both CRS and immune effector cell-associated neurotoxicity syndrome (n = 6, 20%) were limited to ≤G2 with median durations of 2 and 1.5 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 ≥215μg/kg was 75% (n = 15/20) including partial response (PR; n = 6), very good PR (VGPR; n = 3), complete response (CR; n = 1), and stringent CR (sCR; n = 5). Median time to response was 22 days, and 3 of 4 pts (75%) with prior BCMA-directed therapy achieved response (VGPR, n = 2 and sCR, n = 1). Updated data, including duration of response, will be presented. Conclusions: Elranatamab demonstrated a manageable safety profile, and SC doses ≥215μg/kg achieved ORR of 75% with CR/sCR rate of 30%. These results demonstrate the safety and efficacy of SC elranatamab in this relapsed/refractory population and support ongoing development of elranatamab for pts with MM, both as monotherapy and in combination with standard or novel therapies. Clinical trial information: NCT03269136.