P897: UPDATED RESULTS FROM THE ONGOING PHASE 1 STUDY OF ELRANATAMAB, A BCMA TARGETED T-CELL REDIRECTING IMMUNOTHERAPY, FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA

Abstract

Background: Elranatamab (PF-06863135), a bispecific molecule that engages B-cell maturation antigen (BCMA) on multiple myeloma (MM) and CD3 on T-cells, induces targeted proliferation and activation of T cells to redirect the immune response against MM. Aims: The Phase 1 study, MagnetisMM-1 (NCT03269136), aims to characterize the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of elranatamab as a single agent or in combination with immunomodulatory agents for patients (pts) with relapsed or refractory MM. Methods: After informed consent, elranatamab was given subcutaneously weekly or every 2 weeks (Q2W) at doses from 80 to 1000µg/kg. A subset of pts received a single priming dose (600µg/kg or 44mg equivalent) followed 1 week later by the recommended Phase 2 dose (RP2D; 1000µg/kg or 76mg equivalent) thereafter. 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. PK, cytokine and soluble BCMA profiling, and lymphocyte subset analyses were performed. Response was evaluated by International Myeloma Working Group (IMWG) criteria. Minimal residual disease (MRD) was assessed by next generation sequencing at a sensitivity of 1×10-5 in accordance with IMWG criteria. Results: A total of 55 pts received elranatamab monotherapy at doses ≥215µg/kg as of 1-Nov-2021. Median age was 64 years (range 42-80), 27% of pts were Black/African American or Asian, and 27% had high risk cytogenetics at baseline. Median number of prior lines of therapy was 6 (range 2-15), 91% were triple-class refractory, 22% received prior BCMA-targeted therapy, and 56% had prior stem cell transplant. The most common TEAEs (all causality) were CRS, neutropenia, anemia, injection site reaction, and lymphopenia. With a single priming dose and premedication, the incidence of CRS at the RP2D was 67% and divided equally between Grade 1 and 2, with no events greater than Grade 2. PK exposure was dose dependent, and elranatamab 1000µg/kg Q2W achieved exposure associated with anti-myeloma activity. Elranatamab therapy induced peripheral T-cell proliferation with a median time to response of 36 days (range 7-73), and the level of soluble BCMA decreased with disease response. With a median follow up of 8.1 months (range 0.3-21) and including only IMWG confirmed responses, overall response rate (ORR) was 64% (95% CI 50-75%), and 31% of pts achieved complete response or better. For responders (n=35), the probability of being event free at 6 months was 91% (95% CI 73-97%). Single-agent elranatamab induced durable clinical and molecular responses, and updated results including serial MRD assessment will be presented. Summary/Conclusion: Elranatamab demonstrates a manageable safety profile and achieves durable clinical and molecular responses for pts with relapsed or refractory MM.