Study With Elranatamab Versus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma After Transplant

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether elranatamab monotherapy can provide clinical benefit compared to lenalidomide monotherapy (control) in participants with newly diagnosed multiple myeloma after undergoing autologous stem cell transplant. In Part 1 and Part 2 of the study, participants in the study will either receive elranatamab (arm A and C) as an injection under the skin at the study clinic or lenalidomide orally once daily at home (arm B). Participation in the study will be approximately five years

Detailed Description
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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.

Official Title
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A RANDOMIZED, 2-ARM, PHASE 3 STUDY OF ELRANATAMAB (PF-06863135) VERSUS LENALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA AFTER UNDERGOING AUTOLOGOUS STEM-CELL TRANSPLANTATION

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Elranatamab
* Drug: Lenalidomide
* Drug: Lenalidomide
* Drug: Elranatamab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MM as defined according to IMWG criteria (Rajkumar, 2014) with measurable disease at diagnosis Part 1 patients must be MRD positive, Part 2 patients can be MRD negative or MRD positive History of induction therapy for newly diagnosed MM, followed by high dose therapy and autologous stem cell transplant. Randomization must occur within 120 days from the stem cell transplant. For participants who receive consolidation therapy after ASCT, randomization must occur within 60 days of consolidation and within 7 months from ASCT. Partial Response or better according to IMWG criteria at the time of randomization Must have an archival bone marrow aspirate sample(s) to identify the dominant malignant (index) clone by central laboratory NGS test (ClonoSEQ assay) that is used to track MRD status. This sample should preferably be collected before induction treatment (eg, at diagnosis) or before transplant. ECOG performance status ≤1 Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤ 1 Not pregnant and willing to use contraception Exclusion Criteria: Plasma cell leukemia Amyloidosis, Waldenström's macroglobulinemia POEMS syndrome Known active CNS involvement or clinical signs of myelomatous meningeal involvement Previous MM maintenance treatment Prior treatment with BCMA targeted therapy Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, and known HIV or AIDS-related illness Previous administration with an investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A - Part 1<br>Elranatamab | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>|
| Active Comparator: Arm B - Part 1<br>Lenalidomide | Drug: Lenalidomide<br>* Immunomodulatory drug<br>|
| Active Comparator: Arm B - Part 2<br>Lenalidomide | Drug: Lenalidomide<br>* Immunomodulatory drug<br>|
| Experimental: Arm C - Part 2<br>Elranatamab | Drug: Elranatamab<br>* BCMA-CD3 bispecific antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression Free Survival assessed by Blinded Independent Central review per IMWG response criteria | Assessed for up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time from randomization until death due to any cause | Assessed for up to approximately 5 years | 
| Minimal Residual Disease negativity rate | Minimal Residual Disease negativity rate per IMWG criteria as assessed via Next Generation Sequencing | 12 months after randomization | 
| Sustained MRD negativity rate | Sustained Minimal Residual Disease negativity rate per IMWG criteria as assessed via Next Generation Sequencing | 24 months after randomization | 
| Progression Free Survival | Progression Free Survival by investigator per IMWG response criteria | Assessed for up to approximately 5 years | 
| Overall minimal residual disease negativity rate | Minimal residual disease negativity rate per IMWG criteria | Assessed for up to approximately 5 years | 
| Duration of minimal residual disease negativity | Minimal residual disease negativity per IMWG criteria | Assessed for up to approximately 5 years | 
| Sustained minimal residual disease negativity rate | Minimal residual disease negativity per IMWG criteria that has lasted a minimum of 12 months | Assessed for up to approximately 5 years | 
| Complete response rate | Complete response rate by blinded independent central review and by investigator per IMWG criteria | Assessed for up to approximately 5 years | 
| Duration of complete response | Duration of complete response by blinded independent central review and by investigator per IMWG criteria | Assessed for up to approximately 5 years | 
| Frequency of adverse events | Adverse event as characterized by type, frequency, severity per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5, seriousness and relationship to the study intervention | Up to 90 days after last dose | 
| Frequency of laboratory abnormalities |  | Assessed for up to approximately 5 years | 
| Pre-dose concentrations of elranatamab | Pharmacokinetics of elranatamab (trough concentrations of elranatamab) | Assessed for up to approximately 5 years | 
| Post-dose concentrations of elranatamab | Pharmacokinetics of elranatamab (Post-dose serum concentrations of elranatamab) | Assessed for up to approximately 5 years | 
| Incidence and titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab | Immunogenicity of elranatamab | Assessed for up to approximately 5 years | 
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 | 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 symptom scales/items represent a greater presence of symptoms | Assessed for up to approximately 5 years | 
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20 | 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 | Assessed for up to approximately 5 years | 
| Progression Free Survival 2 | Progression Free Survival to the date of second objective disease progression by investigator per IMWG response criteria | Assessed for up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCMA, Multiple Myeloma, Newly diagnosed, Elranatamab, Targeted T-cell, MagnetisMM, MM7, Phase 3, B-cell Maturation Antigen, monoclonal antibody, Stem cell transplant, Autologous stem cell transplant (ASCT), Hematologic disease, Minimum residual disease, Lenalidomide