MagnetisMM-5: Study of Elranatamab (PF-06863135) Monotherapy and Elranatamab + Daratumumab Versus Daratumumab + Pomalidomide + Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether the BCMA-CD3 bispecific antibody elranatamab, alone and/or in combination with the anti-CD38 monoclonal antibody, daratumumab, can provide more benefit to people with multiple myeloma compared to a combination therapy including daratumumab, pomalidomide, and dexamethasone. People with multiple myeloma who have received previous treatment including lenalidomide and a proteasome inhibitor will be enrolled in the study. Part 1 of the study will assess the safety and activity of different doses of elranatamab in combination with daratumumab. People participating in Part 2 of the study will be randomly assigned to receive either elranatamab alone, elranatamab plus daratumumab, or daratumumab, pomalidomide, and dexamethasone. Part 2 will compare the safety and activity of (1) elranatamab alone compared to daratumumab, pomalidomide, and dexamethasone, and (2) elranatamab plus daratumumab compared to daratumumab, pomalidomide, and dexamethasone. Participants in all parts of the study will receive study treatment until their disease progresses, they experience unacceptable side effects, or they choose to no longer participate in the study.

Official Title
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AN OPEN-LABEL, 3-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) MONOTHERAPY AND ELRANATAMAB + DARATUMUMAB VERSUS DARATUMUMAB + POMALIDOMIDE + DEXAMETHASONE IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 1 PRIOR LINE OF THERAPY INCLUDING LENALIDOMIDE AND A PROTEASOME INHIBITOR

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Elranatamab
* Drug: Daratumumab
* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior diagnosis of multiple myeloma 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. Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65). Prior anti-multiple myeloma therapy including treatment with lenalidomide and a proteasome inhibitor. ECOG performance status ≤2. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1. Not pregnant and willing to use contraception. Exclusion Criteria: Smoldering multiple myeloma. Plasma cell leukemia. Amyloidosis. POEMS Syndrome. Stem cell transplant within 12 weeks prior to enrolment, or active graft versus host disease. Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Any other active malignancy within 3 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. Previous treatment with a BCMA-directed therapy. Anti-CD38-directed therapy within 6 months preceding the first dose of treatment in this study. Live attenuated vaccine within 4 weeks of the first dose of study intervention. Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days preceding the first dose of study intervention used in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Safety Lead-In Dose Escalation: Elranatamab + Daratumumab<br> | Drug: Elranatamab<br>* subcutaneous<br>* Other names: PF-06863135;Drug: Daratumumab<br>* Daratumumab / hyaluronidase, subcutaneous<br>* Other names: Darzalex Faspro; Darzalex solution for injection;|
| Experimental: Part 2 Randomized Arm A: Elranatamab<br> | Drug: Elranatamab<br>* subcutaneous<br>* Other names: PF-06863135;|
| Experimental: Part 2 Randomized Arm B: Elranatamab + Daratumumab<br> | Drug: Elranatamab<br>* subcutaneous<br>* Other names: PF-06863135;Drug: Daratumumab<br>* Daratumumab / hyaluronidase, subcutaneous<br>* Other names: Darzalex Faspro; Darzalex solution for injection;|
| Active Comparator: Part 2 Randomized Arm C: Daratumumab + Pomalidomide + Dexamethasone<br> | Drug: Daratumumab<br>* Daratumumab / hyaluronidase, subcutaneous<br>* Other names: Darzalex Faspro; Darzalex solution for injection;Drug: Pomalidomide<br>* oral<br>* Other names: Pomalyst, Imnovid;Drug: Dexamethasone<br>* oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 Safety Lead-In: Incidence of dose limiting toxicities |  | First 42 days after first elranatamab dose | 
| Part 2 Randomized: Progression free survival per International Myeloma Working Group criteria |  | From date of randomization to date of progressive disease, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 51 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 Safety Lead-In: Progression free survival per International Myeloma Working Group criteria |  | From date of randomization to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months | 
| Overall survival |  | From date of randomization to date of discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months | 
| Objective response rate per International Myeloma Working Group criteria |  | From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months | 
| Duration of response per International Myeloma Working Group criteria |  | From date of confirmed objective response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months | 
| Time to response per International Myeloma Working Group criteria |  | From date of randomization to date of confirmed objective response, assessed up to 51 months | 
| Complete response rate per International Myeloma Working Group criteria |  | From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months | 
| Duration of complete response per International Myeloma Working Group criteria |  | From date of confirmed complete response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months | 
| Minimal residual disease negativity rate per International Myeloma Working Group criteria |  | From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months | 
| Sustained minimal residual disease negativity rate per International Myeloma Working Group criteria |  | From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months | 
| Progression free survival on next-line treatment per International Myeloma Working Group criteria |  | From date of randomization to date of second objective disease progression, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 51 months | 
| Frequency of treatment-emergent adverse events |  | From date of first dose of study intervention through minimum of 90 days after last study intervention administration. Reporting of non-serious AEs ends at start of new anti-cancer therapy. | 
| Frequency of abnormal laboratory results |  | From date of first dose of study intervention through minimum of 90 days after last study intervention administration. Reporting of non-serious AEs ends at start of new anti-cancer therapy. | 
| Rate of Grade ≥2 cytokine release syndrome |  | First 28 days after first elranatamab dose | 
| Elranatamab pharmacokinetics by pre- and post-dose concentrations |  | From date of first dose through up to 14 days after date of last dose of elranatamab | 
| Elranatamab immunogenicity by anti-drug antibodies against elranatamab |  | From date of first dose through up to 14 days after date of last dose of elranatamab | 
| Daratumumab pharmacokinetics by pre-dose concentrations |  | From date of first dose through up to 14 days after date of last dose of daratumumab | 
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 |  | From date of informed consent through up to 35 days after date of last dose of study intervention | 
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20 |  | From date of informed consent through up to 35 days after date of last dose of study intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elranatamab, PF-06863135, B-Cell Maturation Antigen, BCMA, Bispecific antibody, BCMA-CD3 bispecific antibody, Daratumumab, Pomalidomide, Multiple myeloma, Relapsed multiple myeloma, Refractory multiple myeloma, MagnetisMM-5