Multiple Myeloma
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGElranatamab
BCMA-CD3 bispecific antibody
DRUGLenalidomide
Immunomodulatory drug
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Assessed for up to approximately 5 years | Progression Free Survival assessed by Blinded Independent Central review per IMWG response criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimal residual disease Negative rate | 12 months after randomization | per IMWG as assessed via next generation sequencing (NGS) |
| Progression Free Survival by BICR per IMWG in IMWG 2025 high-risk participants | Assessed up to approximately 5 years | Progression Free Survival by BICR per IMWG in IMWG 2025 high-risk participants |
| PFS by BICR per IMWG in IMWG 2025 standard-risk participant | Assessed up to approximately 5 years | PFS by BICR per IMWG in IMWG 2025 standard-risk participant |
| Overall Survival | Assessed for up to approximately 5 years | Defined as the time from randomization until death due to any cause |
| MRD-negative rate per IMWG 2025 | 12 months after randomization | Assessed via NGS in IMWG 2025 subgroups |
| Sustained MRD negative rate | 24 months after randomization | Sustained Minimal Residual Disease negative rate per IMWG criteria as assessed via Next Generation Sequencing |
| Progression Free Survival | Assessed for up to approximately 5 years | Progression Free Survival by investigator per IMWG response criteria |
| Overall minimal residual disease negative rate | Assessed for up to approximately 5 years | Minimal residual disease negative rate per IMWG criteria |
| Duration of minimal residual disease negativity | Assessed for up to approximately 5 years | Minimal residual disease negativity per IMWG criteria |
| Sustained minimal residual disease negativity rate | Assessed for up to approximately 5 years | Minimal residual disease negativity per IMWG criteria that has lasted a minimum of 12 months |
| Complete response rate | Assessed for up to approximately 5 years | Complete response rate by blinded independent central review and by investigator per IMWG criteria |
| Duration of complete response | Assessed for up to approximately 5 years | Duration of complete response by blinded independent central review and by investigator per IMWG criteria |
| Progression Free Survival 2 | Assessed for up to approximately 5 years | Progression Free Survival to the date of second objective disease progression by investigator per IMWG response criteria |
| Frequency of adverse events | Up to 90 days after last dose | 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 |
| Severity of Cytokine Release Syndrome and Immune effector Cell Associated Neurotoxicity syndrome | Assessed for up to approximately 5 years | Cytokine Release Syndrome and Immune effector Cell Associated Neurotoxicity syndrome severity assessed per ASH-ASTCT criteria |
| Pre-dose concentrations of elranatamab | Assessed for up to approximately 5 years | Pharmacokinetics of elranatamab (trough concentrations of elranatamab) |
| Post-dose concentrations of elranatamab | Assessed for up to approximately 5 years | Pharmacokinetics of elranatamab (Post-dose serum concentrations of elranatamab)" |
| Incidence and titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab | Assessed for up to approximately 5 years | Immunogenicity of elranatamab |
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 | Assessed for up to approximately 5 years | 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 |
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20 | Assessed for up to approximately 5 years | 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 |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Netherlands, Norway, Poland, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed