A Study to Learn About the Effects of the Combination of Elranatamab (PF-06863135), Daratumumab, Lenalidomide or Elranatamab and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant (MagnetisMM-6)

Pfizer

Status and phase: Enrolling; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Daratumumab; Drug: Dexamethasone; Drug: Elranatamab; Drug: Lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05623020

2024-514139-50-00 (Registry Identifier)

2021-000803-20 (EudraCT Number)

MAGNETISMM-6 (Other Identifier)

C1071006

Details and patient eligibility

About

Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity. The main purpose of the study is to evaluate if the combination of Elranatamab, Daratumumab and Lenalidomide or Elranatamab and Lenalidomide offers superior clinical benefit compared with the combination of Daratumumab, Lenalidomide and Dexamethasone in people with multiple myeloma.

There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the minimal residual disease (MRD) negativity rate and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide or elranatamab and lenalidomide compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed transplant-ineligible multiple myeloma.

Enrollment: 1,116 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of multiple myeloma (MM) as defined by IMWG criteria (Rajkumar et al., 2014)

• Measurable disease based on IMWG criteria as defined by at least 1 of the following:

  • Serum M-protein ≥0.5 g/dL;
  • Urinary M-protein excretion ≥200 mg/24 hours;
  • Involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).

• Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.

• Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant

• ECOG performance status ≤2.

• Not pregnant and willing to use contraception

• For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.

Exclusion criteria

• Smoldering Multiple Myeloma.
• Monoclonal gammopathy of undetermined significance.
• Waldenströms Macroglobulinemia
• Plasma cell leukemia.
• Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness.
• Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
• For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant ≤3 months prior to first dose of study intervention or active GVHD.
• For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, up to 4 days of 40 mg dexamethasone or equivalent before the first dose of study intervention).
• Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
• Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,116 participants in 6 patient groups

Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide

Experimental group

Treatment:

Drug: Lenalidomide

Drug: Elranatamab

Drug: Daratumumab

Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide

Experimental group

Treatment:

Drug: Lenalidomide

Drug: Elranatamab

Drug: Daratumumab

Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide

Experimental group

Treatment:

Drug: Lenalidomide

Drug: Elranatamab

Drug: Daratumumab

Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone

Active Comparator group

Treatment:

Drug: Lenalidomide

Drug: Dexamethasone

Drug: Daratumumab

Part 1: Elranatamab + Lenalidomide

Experimental group

Treatment:

Drug: Lenalidomide

Drug: Elranatamab

Part 2: Randomized Arm A: Elranatamab + Lenalidomide

Experimental group

Treatment:

Drug: Lenalidomide

Drug: Elranatamab