Pfizer has launched MagnetisMM-6 (NCT05623020), a pivotal phase 3 clinical trial evaluating a novel triple combination therapy for patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation. The study compares elranatamab plus daratumumab and lenalidomide (EDR) against the current standard of care combination of daratumumab, lenalidomide, and dexamethasone (DRd).
Study Design and Patient Population
The ongoing, open-label, two-arm, multicenter trial is estimated to enroll approximately 646 patients across multiple international sites. As of February 2023, the study was actively recruiting at 9 sites in 5 countries, with the UK participating in Part 2 of the trial.
The study employs a two-part design. Part 1 evaluates the safety and establishes the recommended phase 3 dose of the EDR combination in both transplant-ineligible patients with newly diagnosed multiple myeloma and patients with relapsed/refractory multiple myeloma who have received 1-2 prior lines of therapy. Part 2 focuses exclusively on transplant-ineligible patients with newly diagnosed multiple myeloma, comparing the efficacy and safety of EDR at the recommended dose versus DRd.
Transplant ineligibility is defined as patients aged 65 years or older, or those under 65 with comorbidities that impact transplant feasibility. Key inclusion criteria include patients aged 18 years or older with a diagnosis of multiple myeloma according to International Myeloma Working Group criteria, an ECOG performance status of 2 or better, and measurable disease based on specific parameters including serum M-protein ≥0.5 g/dL, urinary M-protein excretion ≥200 mg/24 hours, or involved serum free light chain ≥100 mg/L with abnormal serum immunoglobulin κ:λ free light chain ratio.
Primary and Secondary Endpoints
The study's dual primary endpoints are minimal residual disease at 12 months and progression-free survival. Secondary endpoints encompass a comprehensive assessment including overall and sustained MRD negativity rates, duration of MRD negativity, objective response rate, complete response rate, time to response, duration of response, duration of complete response, overall survival, safety, quality of life, immunogenicity, and pharmacokinetics.
Elranatamab's Mechanism and Previous Results
Elranatamab represents a humanized bispecific antibody that simultaneously targets B cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells. This dual targeting mechanism enables T cell-mediated destruction of myeloma cells. The agent has demonstrated promising efficacy and acceptable safety profiles in previous clinical studies, both as monotherapy in the MagnetisMM-3 study (NCT04649359) and in combination with daratumumab in the MagnetisMM-5 trial (NCT05020236), specifically in patients with relapsed/refractory multiple myeloma.
Clinical Rationale and Unmet Need
Despite recent therapeutic advances in newly diagnosed multiple myeloma treatment, the disease remains incurable, creating a compelling need for more effective treatment options. The MagnetisMM-6 study addresses this critical gap by investigating whether the addition of elranatamab to the established daratumumab-lenalidomide backbone can improve outcomes for transplant-ineligible patients.
The study will monitor participants for approximately 5 years through regular clinic visits, assessing treatment response, safety parameters, and quality of life measures. Pfizer, Inc. is funding this global clinical trial, reflecting the company's commitment to advancing multiple myeloma treatment options for patients who cannot undergo stem cell transplantation.
