MagnetisMM-6: 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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05623020

Collaborator

(none)

646

Enrollment

Locations

Arms

66.4

Anticipated Duration (Months)

80.8

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Elranatamab Drug: Daratumumab Drug: Lenalidomide Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

646 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 10, 2022

Anticipated Primary Completion Date :

May 24, 2028

Anticipated Study Completion Date :

May 24, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide	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.
Experimental: Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide	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.
Experimental: Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide	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.
Active Comparator: Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone	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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Overall minimal residual disease negativity rate [From date of randomization up to 61 months]
Duration of minimal residual disease negativity (Part 2) [From date of minimal residual disease negative status up to 61 months]
Sustained minimal residual disease negativity rate (Part 2) [From date of randomization up to 61 months]
Objective Response Rate [From the date of randomization up to 61 months]
Complete Response Rate [From the date of randomization up to 61 months]
Time to Response [From the date of randomization to date of confirmed objective response up to 61 months]
Duration of Response [From the date of confirmed objective response up to 61 months]
Duration of Complete Response [From the date of confirmed complete response up to 61 months]
Overall Survival [From date of randomization up to 61 months]
Frequency of treatment-emergent adverse events [From the date of first dose of study intervention up to 61 months]
Frequency of abnormal laboratory results [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 [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 [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 [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 [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 [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 [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 [From date of first dose of study intervention up to 61 months]
Pharmacokinetics of daratumumab and lenalidomide (trough concentrations of daratumumab and lenalidomide)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shizuoka Cancer Center	Nagaizumi-cho,Sunto-gun	Shizuoka	Japan	411-8777
2	Yamagata University Hospital	Yamagata		Japan	990-9585
3	Seoul National University Bundang Hospital	Seongnam	Kyǒnggi-do	Korea, Republic of	13620
4	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [seoul]	Korea, Republic of	03080
5	Centrum Medyczne Pratia Poznań	Skorzewo	Wielkopolskie	Poland	60-185
6	Pratia Onkologia Katowice	Katowice	Śląskie	Poland	40-519
7	China Medical University Hospital	Taichung		Taiwan	404332
8	National Taiwan University Hospital	Taipei		Taiwan	10002