Pfizer Launches Pivotal Phase 2 MagnetisMM-3 Trial of BCMA-CD3 Bispecific Antibody Elranatamab in Relapsed/Refractory Multiple Myeloma

February 18, 2021 /Bio ValleyBIOON/ --Pfizer(Pfizer) recently announced that the first patient has been dosed in the registrational Phase 2 MagnetisMM-3 study evaluating the bispecific antibody elranatamab (PF-06863135) for the treatment of relapsed or refractory multiple myeloma (R/R MM). Elranatamab is an investigational bispecific antibody targeting BCMA and CD3. In this study, enrolled patients had disease refractory to at least one agent from each of the three approved drug classes in the field of multiple myeloma treatment. The study assessed the efficacy and safety of subcutaneous administration of elranatamab. The primary completion date of the study is expected to be June 2022.

Elranatamab is a BCMAxCD3 bispecific antibody that has been granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA). FTD aims to accelerate drug development and expedited review for serious conditions, addressing critical areas of unmet medical needs. Obtaining FTD for an investigational drug means that pharmaceutical companies can engage withFDAEngage in more frequent interactions; if the relevant criteria are met after submission of the marketing application, it will be eligible for accelerated approval and priority review, as well as rolling review.

Bispecific Antibody Is a Novel Type ofTumorImmunotherapy methods can simultaneously target two different sites, with one arm directly binding to specific antigens on cancer cells and the other arm activating the patient.AutoimmunityT cells in the system and bring them closer to cancer cells to kill them.

Elranatamab is designed to bind to B-cell maturation antigen (BCMA), which is highly expressed on the surface of multiple myeloma cells, and to the CD3 receptor on the surface of anti-tumor T cells, thereby linking them together to activate an immune response. The binding affinity of elranatamab for BCMA and CD3 has been optimized to enhance T cell-mediated anti-myeloma activity. Subcutaneous administration of elranatamab aims to allow higher doses than intravenous injection without increasing adverse events. In addition to the MagnetisMM-3 trial, other clinical trials evaluating elranatamab for the treatment of multiple myeloma include its use as monotherapy or in combination with standard-of-care therapies and novel agents.

Pfizer Global Product DevelopmentTumorChris Boshoff, M.D., Chief Development Officer, stated, “The initiation of the pivotal MagnetisMM-3 trial marks a significant step forward in the development program for elranatamab. Bispecific antibodies hold promise as the next potential breakthrough in the treatment of multiple myeloma. We are highly encouraged by the early data on subcutaneous administration of elranatamab, an antibody discovered and developed at Pfizer to enhance safety and convenience.”

Effective Biologic Therapeutic Targets on the Surface of Multiple Myeloma Cells (Image source: PMID:30545798)

At the 62nd American Society of Hematology (ASH) Annual Meeting held in December 2020, Pfizer presented safety and clinical response results from the Phase I study (NCT03269136) of elranatamab for the treatment of relapsed or refractory multiple myeloma (R/R MM). Data from 30 patients with R/R MM (including three patients whose disease had progressed after prior BCMA-targeted therapy) demonstrated that elranatamab had a manageable safety profile across all subcutaneous dose levels, with no dose-limiting toxicities observed. At the highest dose level, 83% of patients achieved a clinical response.

This Phase I study (NCT03269136) was an open-label, multiple-dose, multicenter, dose-escalation study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics of elranatamab in adult patients with multiple myeloma (MM) who had relapsed after or were refractory to standard therapy. The study consisted of two parts; Part 1 assessed the safety and tolerability of escalating dose levels of elranatamab. A total of 80 patients were enrolled and evaluated intravenous or subcutaneous administration of elranatamab. Preliminary results for the intravenous route were presented at the 2019 American Society of Hematology (ASH) Annual Meeting.

The primary objectives of this study, presented at the 2020 ASH Annual Meeting, were to evaluate the safety and tolerability of subcutaneous elranatamab, determine the maximum tolerated dose, and select the recommended Phase 2 dose. During the dose-escalation phase, no dose-limiting toxicities were observed at any subcutaneous dose level (80–1000 μg/kg weekly). Cytokine release syndrome (CRS) occurred in 73.3% of patients, limited to Grade 1 (56.7%) or Grade 2 (16.7%). Grade ≥3 adverse events occurring in >10% of patients included lymphopenia (53.3%), neutropenia (26.7%), thrombocytopenia (16.7%), andAnemia（16.7%）。

Among the 20 patients treated within the effective dose range of 215–1000 μg/kg once weekly, the overall response rate (ORR) was 80%. Of these 20 patients, 6 achieved a stringent complete response (sCR) or complete response (CR), 3 achieved a very good partial response (VGPR), and 6 achieved a partial response (PR). Three responding patients had previously received at least one BCMA-targeted therapy. At the highest dose of 1000 μg/kg, the ORR was 83% (n=5/6). Based on these data, the recommended Phase 2 dose is 1000 μg/kg once weekly.

Despite advances in the treatment of multiple myeloma (MM), the disease remains incurable. There is an urgent need for significant therapeutic breakthroughs for patients. The very high response rates observed with elranatamab, combined with its manageable safety profile and the convenience of subcutaneous administration, underscore the potential impact of this drug on the patient population suffering from this devastating disease. These findings support the continued development of elranatamab in the treatment of multiple myeloma, both as a monotherapy and in combination with standard or novel therapies. (Bioon.com)

Original Source: Pfizer Initiates Pivotal Phase 2 MagnetisMM-3 Trial of BCMA-CD3 Bispecific Antibody Elranatamab (PF-06863135) in Multiple Myeloma