18 February 2021 - - The first participant has been dosed in the registration-enabling Phase 2 MagnetisMM-3 study (NCT04649359) of elranatamab (PF-06863135), an investigational B-cell maturation antigen CD3-targeted bispecific antibody, in patients with relapsed/refractory multiple myeloma, US-based pharmaceutical company Pfizer Inc. (NYSE: PFE) said.

The study evaluates the efficacy and safety of elranatamab, administered subcutaneously, in patients with disease that is refractory to at least one agent in each of three major classes of medications approved for multiple myeloma.

The study's estimated primary completion date is June 2022.

Elranatamab has also been granted Fast Track Designation by the US Food and Drug Administration. Fast Track is a process designed to facilitate the development, and expedite the review, of new drugs and vaccines that are intended to treat or prevent serious conditions that have the potential to address an unmet medical need.

At the Virtual American Society of Hematology annual meeting and Exposition in December 2020, Pfizer presented encouraging data from an ongoing Phase 1 trial of elranatamab (MagnetisMM-1) demonstrating manageable safety and high response rates in patients with relapsed/refractory multiple myeloma including three patients whose disease relapsed on or progressed after prior BCMA-targeted therapies.

At the highest dose level, which informed the dose selected for the Phase 2 study, 83% of patients achieved a clinical response.

Safety was manageable across all subcutaneous dose levels with no dose-limiting toxicities observed.

Bispecific antibodies are a novel type of cancer immunotherapy that bind to and engage two different targets at once.

One arm binds directly to specific antigens on cancer cells and the other activates and brings a person's own T-cells from the immune system closer to kill the cancer cells.

Elranatamab is a bispecific antibody designed to bind to BCMA which is highly expressed on the surface of multiple myeloma cells, and the CD3 receptor found on the surface of cancer-fighting T-cells, bridging them together to activate an immune response.

Binding affinity to BCMA and CD3 has been optimized, to potentially elicit more potent T-cell-mediated anti-myeloma activity. Subcutaneous administration of elranatamab is intended to allow higher doses than intravenous administration without increasing adverse events.

In addition to MagnetisMM-3, other trials of elranatamab in multiple myeloma are planned both as monotherapy and in combination with standard or novel therapies.

MagnetisMM-3 is an open-label, multicenter, nonrandomized Phase 2 study of elranatamab monotherapy enrolling approximately 150 people with multiple myeloma who are refractory to at least one proteasome inhibitor, one immunomodulatory drug and one anti-CD38 monoclonal antibody.

This study will enroll two cohorts of participants: one with and one without prior treatment with a BCMA-directed ADC or CAR-T therapy.

Participants will receive a weekly 76 mg subcutaneous injection of elranatamab following a priming dose of 44 mg. The primary endpoint is objective response rate as assessed by blinded independent central review.

Key secondary endpoints include: duration of response, progression-free survival, minimal residual disease negativity rate, overall survival and safety.

Multiple myeloma is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.

According to the latest figures available, there are approximately 32,270 new cases of multiple myeloma diagnosed annually in the U.S and 176,000 globally.

Despite treatment advances, multiple myeloma remains incurable. The median survival is just over 5 years, and most patients receive four or more lines of therapy.