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

• ClinicalTrials.gov Identifier: NCT05623020
• Recruitment Status: Recruiting
• First Posted: November 21, 2022
• Last Update Posted: April 16, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 26, 2022
• First Posted Date: November 21, 2022
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: November 10, 2022
• Estimated Primary Completion Date: March 31, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2023)

• Part 1 Dose Limiting Toxicity [ Time Frame: From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab 76 with daratumumab and lenalidomide ]
• Part 2: Progression free survival by blinded independent central review [ Time Frame: From randomization up to 73 months. ]
• Part 2: Sustained minimal residual disease negativity rate [ Time Frame: For at least 12 months after date of initial MRD-negative status ]

Original Primary Outcome Measures (submitted: November 11, 2022)

• Part 1 Dose Limiting Toxicity [ Time Frame: From the first dose of elranatamab up until the end of Cycle 1 (each Cycle is 28 days). ]
• Part 2: Progression free survival [ Time Frame: From randomization up to 61 months. ]
• Part 2: Minimal residual disease negativity rate [ Time Frame: At 12 months after randomization ]

Current Secondary Outcome Measures (submitted: May 17, 2023)

• Overall Survival [ Time Frame: From date of randomization up to 73 months ]
• Overall minimal residual disease negativity rate [ Time Frame: From date of randomization up to 73 months ]
• Duration of minimal residual disease negativity (Part 2) [ Time Frame: From date of minimal residual disease negative status up to 73 months ]
• PFS by investigator [ Time Frame: From date of randomization up to 73 months ]
• PFS2 by investigator (Part 2) [ Time Frame: From the date of randomization up to 73 months ]
• Objective Response Rate [ Time Frame: From the date of randomization up to 73 months ]
• Complete Response Rate [ Time Frame: From the date of randomization up to 73 months ]
• Time to Response [ Time Frame: From the date of randomization to date of confirmed objective response up to 73 months ]
• Duration of Response [ Time Frame: From the date of confirmed objective response up to 73 months ]
• Duration of Complete Response [ Time Frame: From the date of confirmed complete response up to 73 months ]
• Frequency of treatment-emergent adverse events [ Time Frame: From the date of first dose of study intervention up to 73 months ]
• Frequency of abnormal laboratory results [ Time Frame: From the date of first dose of study intervention up to 73 months ]
• Elranatamab pharmacokinetics by pre-dose concentrations when used with lenalidomide and daratumumab [ Time Frame: From date of first dose of study intervention up to 73 months ]
  Pharmacokinetics of elranatamab (trough concentrations of elranatamab)
• Elranatamab pharmacokinetics by post-dose concentrations when used with lenalidomide and daratumumab [ Time Frame: From date of first dose of study intervention up to 73 months ]
  Pharmacokinetics of elranatamab (post-dose serum concentrations of elranatamab)
• Incidence of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [ Time Frame: From date of first dose of study intervention up to 73 months ]
  Immunogenicity of elranatamab
• Titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [ Time Frame: From date of first dose of study intervention up to 73 months ]
  Immunogenicity of elranatamab
• Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20 [ Time Frame: From date the informed consent is signed up to 73 months ]
  Higher scores on the functioning subscales (body image, future perspective) represent higher levels of functioning, whereas higher scores on the symptom subscales (disease symptoms, side effects) represent a greater presence of symptoms
• Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 [ Time Frame: From date the informed consent is signed up to 73 months ]
  Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the symptom scales/items represent a greater presence of symptoms.
• Part 1: Daratumumab and lenalidomide pharmacokinetics by pre-dose concentrations in combination with elranatamab [ Time Frame: From date of first dose of study intervention up to 73 months ]
  Pharmacokinetics of daratumumab and lenalidomide (trough concentrations of daratumumab and lenalidomide)

Original Secondary Outcome Measures (submitted: November 11, 2022)

• Overall minimal residual disease negativity rate [ Time Frame: From date of randomization up to 61 months ]
• Duration of minimal residual disease negativity (Part 2) [ Time Frame: From date of minimal residual disease negative status up to 61 months ]
• Sustained minimal residual disease negativity rate (Part 2) [ Time Frame: From date of randomization up to 61 months ]
• Objective Response Rate [ Time Frame: From the date of randomization up to 61 months ]
• Complete Response Rate [ Time Frame: From the date of randomization up to 61 months ]
• Time to Response [ Time Frame: From the date of randomization to date of confirmed objective response up to 61 months ]
• Duration of Response [ Time Frame: From the date of confirmed objective response up to 61 months ]
• Duration of Complete Response [ Time Frame: From the date of confirmed complete response up to 61 months ]
• Overall Survival [ Time Frame: From date of randomization up to 61 months ]
• Frequency of treatment-emergent adverse events [ Time Frame: From the date of first dose of study intervention up to 61 months ]
• Frequency of abnormal laboratory results [ Time Frame: From the date of first dose of study intervention up to 61 months ]
• Elranatamab pharmacokinetics by pre-dose concentrations when used with lenalidomide and daratumumab [ Time Frame: From date of first dose of study intervention up to 61 months ]
  Pharmacokinetics of elranatamab (trough concentrations of elranatamab)
• Elranatamab pharmacokinetics by post-dose concentrations when used with lenalidomide and daratumumab [ Time Frame: From date of first dose of study intervention up to 61 months ]
  Pharmacokinetics of elranatamab (post-dose serum concentrations of elranatamab)
• Incidence of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [ Time Frame: From date of first dose of study intervention up to 61 months ]
  Immunogenicity of elranatamab
• Titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [ Time Frame: From date of first dose of study intervention up to 61 months ]
  Immunogenicity of elranatamab
• Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20 [ Time Frame: From date the informed consent is signed up to 61 months ]
  Higher scores on the functioning subscales (body image, future perspective) represent higher levels of functioning, whereas higher scores on the symptom subscales (disease symptoms, side effects) represent a greater presence of symptoms
• Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 [ Time Frame: From date the informed consent is signed up to 61 months ]
  Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the symptom scales/items represent a greater presence of symptoms.
• Part 1: Daratumumab and lenalidomide pharmacokinetics by pre-dose concentrations in combination with elranatamab [ Time Frame: From date of first dose of study intervention up to 61 months ]
  Pharmacokinetics of daratumumab and lenalidomide (trough concentrations of daratumumab and lenalidomide)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Learn About the Effects of the Combination of Elranatamab (PF-06863135), Daratumumab, and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant
• Official Title: MAGNETISMM-6: AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS WITH NEWLY-DIAGNOSED MULTIPLE MYELOMA

Brief Summary

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 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 when administered in combination with daratumumab and 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 compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed transplant-ineligible multiple myeloma.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Elranatamab
  Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Drug: Daratumumab
  Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Drug: Lenalidomide
  Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
• Drug: Dexamethasone
  Randomized

Study Arms

• Experimental: Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide
  Interventions:

  • Drug: Elranatamab
  • Drug: Daratumumab
  • Drug: Lenalidomide
• Experimental: Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide
  Interventions:

  • Drug: Elranatamab
  • Drug: Daratumumab
  • Drug: Lenalidomide
• Experimental: Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide
  Interventions:

  • Drug: Elranatamab
  • Drug: Daratumumab
  • Drug: Lenalidomide
• Active Comparator: Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone
  Interventions:

  • Drug: Daratumumab
  • Drug: Lenalidomide
  • Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 1, 2023): 966
• Original Estimated Enrollment (submitted: November 11, 2022): 646
• Estimated Study Completion Date: November 29, 2031
• Estimated Primary Completion Date: March 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

• Listed Location Countries: Australia, Canada, Czechia, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Poland, Spain, Taiwan

Administrative Information

• NCT Number: NCT05623020
• Other Study ID Numbers: C1071006; 2021-000803-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024