Pfizer Inc. (NYSE:PFE) today announced 10.4 month follow-up data from the pivotal Phase 2 MagnetisMM-3 clinical trial suggesting elranatamab, a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody (BsAb), is efficacious and has a manageable safety profile in patients with relapsed or refractory multiple myeloma (RRMM) in a heavily pretreated population, who have received at least three classes of prior therapies including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody (i.e. triple-class refractory or exposed). These data are being presented today in an oral session at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition 2022 (abstract 159).
“Although there are approved treatments for multiple myeloma, none are currently curative, and patients often find themselves with dwindling therapeutic options as their disease relapses or becomes refractory to successive medicines,” said Nizar Bahlis, M.D., Associate Professor, Arnie Charbonneau Cancer Institute, University of Calgary, Canada, and lead investigator. “These longer-term results show early and deep responses with elranatamab in a heavily pretreated patient population, adding to the growing body of evidence showing elranatamab has the potential to be a transformative option in an area of high need.”
Elranatamab is an investigational humanized BsAb that targets both BCMA-expressing multiple myeloma cells and CD3-expressing T-cells, bridging them together and activating the T-cells to kill the myeloma cells. The binding affinities of elranatamab for BCMA and CD3 have been engineered to elicit potent T-cell-mediated anti-myeloma activity. Given factors currently limiting the availability of novel therapies in the triple-class exposed setting, elranatamab has the potential to reach a broader and greater number of patients as an off-the-shelf option that is administered subcutaneously (SC), which offers more convenience over intravenous administration.
In this analysis, safety and efficacy were analyzed in 123 patients who had received at least one dose of elranatamab (cohort A – BCMA-naïve) as of the data cut-off on October 14, 2022. Patients received SC elranatamab 76 mg weekly (QW) on a 28-day cycle with a step-up priming dose regimen, 12 mg and 32 mg administered on Day 1 and Day 4, respectively, during Cycle 1. With a median follow up of 10.4 months, patients who received elranatamab achieved a high objective response rate of 61%, with 84% probability of maintaining response at nine months. Probability of progression-free survival and overall survival were 63% and 70%, respectively, at nine months. The results also suggest elranatamab has a manageable safety profile and that the two-step-up priming dose regimen (12/32 mg) mitigated the rate and severity of cytokine release syndrome (CRS) (58%, all Grade 1/2) and immune effector cell-associated neurotoxicity syndrome (ICANS, 3%, all Grade 1/2) in cohort A of MagnetisMM-3 (n=119). The most common hematologic treatment emergent adverse events (TEAEs) of any grade were – anemia (48%), neutropenia (48%), thrombocytopenia (30%) and lymphopenia (26%).
“Discovered and developed at Pfizer, elranatamab is just one example of our focus on investing in breakthrough science. We’re applying our expertise in hematology developed over a decade to advance elranatamab as an innovative treatment for multiple myeloma,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. “We are excited to be sharing our latest research at ASH, which further supports the efficacy and safety of elranatamab, and will continue to evaluate its potential benefits through the MagnetisMM clinical trial program across earlier and broader populations, including newly diagnosed patients. We are excited by the potential for elranatamab, if approved, to reach a greater number of patients globally across the treatment paradigm.”
Additional Pfizer elranatamab presentations at ASH include:
- Elranatamab, a BCMA Targeted T-Cell Engaging Bispecific Antibody, Induces Durable Clinical and Molecular Responses for Patients with RRMM (abstract 158, oral)
MagnetisMM-1 Phase 1/2 first in human MagnetisMM-1 study (NCT03269136)
- Safety and preliminary efficacy results from Part 1 (safety lead-in cohort) of MagnetisMM-5, a Phase 3 study of elranatamab + daratumumab in patients with RRMM (NCT05020236) (poster 1921)
- MagnetisMM-4: An Open Label, Phase 1b/2 Umbrella Study of Elranatamab in Combination with Other Anti-cancer Treatments for Patients with Multiple Myeloma (poster 4567)
Phase 1b/2 MagnetisMM-4 (NCT05090566) ongoing clinical trial
- Dose Optimization to Mitigate the Risk of CRS with Elranatamab in Multiple Myeloma (poster 3192)
Dose-optimization analysis from across MagnetisMM-1 (NCT03269136), MagnetisMM-2 (NCT04798586), MagnetisMM-3 (NCT04649359) and MagnetisMM-9 (NCT05014412)
- A Systematic Meta-analysis of Cytokine Release Syndrome Incidence in B-Cell Maturation Antigen-Targeting Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies for Patients with Relapsed and/or Refractory Multiple Myeloma (poster 4509)
Meta-analysis of CRS among patients treated with BCMA-targeting CAR-Ts and BsAbs across 53 studies
MagnetisMM-3 (NCT04649359) is an ongoing open-label, multicenter, non-randomized study designed to evaluate the safety and efficacy of elranatamab as monotherapy in patients with RRMM. Additional data continue to be collected and will be shared as they mature. Prior to enrollment, participants had received a median of five lines of treatment. The participants included in this study represent a difficult-to-treat multiple myeloma patient population; almost all (97%) of the 123 patients included in this analysis were triple-class refractory and nearly half (42%) were penta-drug refractory*. The trial is part of the robust MagnetisMM multiple indication clinical research program that expands to additional patient populations over time, with ongoing registration-intent trials that explore elranatamab both as monotherapy and in combination with standard or novel therapies, spanning multiple patient populations from newly diagnosed multiple myeloma, double-class exposed disease and RRMM.
In November 2022, Pfizer announced elranatamab received Breakthrough Therapy Designation from the Food and Drug Administration (FDA) for the treatment of RRMM. Elranatamab has also been granted Orphan Drug Designation by the FDA and the European Medicines Agency (EMA) for the treatment of MM. The FDA and EMA have granted elranatamab Fast Track Designation and the PRIME scheme, respectively, for the treatment of patients with RRMM. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has also granted elranatamab Innovative Medicine Designation and the Innovation Passport for the treatment of MM.
* Penta-drug refers to at least 2 proteosome inhibitors, 2 immunomodulatory drugs, and 1 anti-CD38 antibody.News Source: Businesswire