Pfizer Presents Initial Phase 2 MagnetisMM-3 Trial Data of BCMA-CD3 Bispecific Antibody Elranatamab in Relapsed/Refractory Multiple Myeloma at ASCO 2022

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Recently, Pfizer announced the interim analysis data of the Phase 2 MagnetisMM-3 study on elranatamab, a BCMA-CD3 bispecific antibody for the treatment of relapsed/refractory multiple myeloma (RRMM), at the ASCO Annual Meeting.

Elranatamab is an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody being developed for the treatment of multiple myeloma (MM). MagnetisMM-3 is an open-label, multicenter, single-arm, Phase 2 study evaluating the safety and efficacy of elranatamab monotherapy in patients with relapsed or refractory multiple myeloma (RRMM). The study enrolled patients whose disease was refractory to at least one drug in each of the three classes of approved major drugs, representing a particularly difficult-to-treat population of MM patients.

This interim analysis conducted safety and efficacy analyses on 94 patients from Cohort A. This cohort was a BCMA-targeted therapy-naïve group, with patients receiving weekly subcutaneous injections (SC) of elranatamab 76mg (QW), utilizing a two-step priming dose regimen in the first week. As of the data cutoff date of March 23, 2022, all 94 patients had received at least one dose of elranatamab.

With a median follow-up of 3.71 months, preliminary efficacy results showed that the objective response rate (ORR) for elranatamab treatment was 60.6%. As of the data cutoff, 89.5% of those who achieved an objective response remained in remission, with no confirmed disease progression or death.

Moreover, the analysis results also showed that the elranatamab 76mg QW regimen had a manageable safety profile for three types of refractory MM patients. The most common treatment-emergent adverse events (TEAEs) were hematological adverse events— anemia (43.6%), neutropenia (38.3%), thrombocytopenia (28.7%), and lymphopenia (25.5%) — as well as cytokine release syndrome (CRS) (60.6%).

The two-step initiation regimen aims to help mitigate the incidence and severity of CRS, which appears to be predictable, with most events limited to the first two doses (88.4%) or the first three doses (98.6%). Among the 90 patients receiving the two-step initiation regimen, all CRs were grade 1 (40.0%) or grade 2 (18.9%). Additionally, 2.2% of patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), all of which were grade 2 or lower.

The results disclosed at the ASCO meeting are the first batch of data from the MagnetisMM-3 study. The study is still ongoing, with primary endpoint analysis results expected to be announced later this year. If the results are positive, they will serve as the basis for elranatamab's marketing application. These data also support the continued development of elranatamab within the robust MagnetisMM program, including as a monotherapy and in combination with standard care or other novel therapies.

It is worth mentioning that previously, the BCMAxCD3 bispecific antibody encountered safety issues, and Pfizer suspended patient enrollment in the phase II clinical trial of elranatamab.

In February 2021, based on the 80% overall response rate observed in 20 patients treated in the Phase 1 clinical trial MagnetisMM-1, Pfizer advanced elranatamab into a pivotal Phase 2 clinical trial. However, after dosing the first group of relapsed and refractory multiple myeloma (MM) patients, Pfizer paused this Phase 2 study to allow time to gather information on safety signals.

The suspension was due to the discovery of three cases of peripheral neuropathy in the MagnetisMM-1 trial. Facing its own BCMA safety issues, Pfizer paused patient dosing in the pivotal Phase 2 clinical trial while providing the FDA with more information regarding the cases of peripheral neuropathy.

Reference Source: Pfizer Presents First Data from Planned Interim Analysis of Pivotal Phase 2 MagnetisMM-3 Trial of BCMA-CD3 Bispecific Antibody Elranatamab Under Investigation for Relapsed/Refractory Multiple Myeloma