Multiple Myeloma
Conditions
Keywords
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
Brief summary
The purpose of this clinical trial is to (1) learn whether the BCMA-CD3 bispecific antibody elranatamab can provide more benefit to people with multiple myeloma compared to a combination therapy including daratumumab, pomalidomide, and dexamethasone, and (2) learn about the safety and activity of elranatamab in combination with the anti-CD38 monoclonal antibody daratumumab. People with multiple myeloma who have received previous treatment including lenalidomide 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 evaluate the safety and activity of (1) elranatamab alone compared to daratumumab, pomalidomide, and dexamethasone, and (2) elranatamab plus daratumumab. Part 3 will assess the effect of increased measures to protect against infection in people treated with either elranatamab alone or together with daratumumab. All people participating in 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.
Interventions
DRUGElranatamab
subcutaneous
DRUGDaratumumab
Daratumumab / hyaluronidase, subcutaneous
DRUGPomalidomide
oral
DRUGDexamethasone
oral
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * 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. * 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.
Design outcomes
Primary
| Measure | 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 |
| Part 3: Frequency of treatment-emergent adverse events | First 84 days after first elranatamab dose |
Secondary
| Measure | 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 |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Finland, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Poland, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed