Multiple Myeloma
Conditions
Keywords
Elranatamab, PF-06863135, B-Cell Maturation Antigen, Daratumumab, Lenalidomide, Multiple myeloma, MagnetisMM-6, Bortezomib
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, Bortezomib, Lenalidomide and Dexamethasone in people with newly diagnosed multiple myeloma. There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the rate of minimal residual disease (MRD) negative CR and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide compared with the combination of daratumumab, bortezomib, lenalidomide, and dexamethasone in participants with newly diagnosed multiple myeloma.
Interventions
DRUGElranatamab
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
DRUGDaratumumab
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
DRUGLenalidomide
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
DRUGDexamethasone
Randomized
DRUGBortezomib
Randomized
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 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 (Part 1) and ≥1 g/dL (Part 2); * 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 defined as: * Participants not considered candidates for high-dose chemotherapy and ASCT due to age or * Participants with important comorbidities likely to have a negative impact on tolerability of high dose chemotherapy and ASCT. * 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, total of 160 mg dexamethasone or equivalent before the first dose of study intervention). A cumulative dose of systemic corticosteroids equivalent to ≥20 mg of dexamethasone during screening. * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 Dose Limiting Toxicity | From the first dose of elranatamab/first full dose in combination with EDR until 28 days (+/- visit window) from the first administration of elranatamab with daratumumab and lenalidomide |
| Part 2: Progression free survival per IMWG | From randomization up to 97 months. |
| Part 2: Minimal Residual Disease negative CR rate | At 12 months after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From date of randomization up to 97 months | — |
| Overall minimal residual disease negative CR rate | From date of randomization up to 97 months | — |
| Sustained MRD negative CR rate (Part 2) | From date of randomization up to 97 months | — |
| Duration of minimal residual disease negative CR (Part 2) | From date of minimal residual disease negative CR status up to 97 months | — |
| PFS by investigator | From date of randomization up to 97 months | — |
| PFS2 by investigator (Part 2) | From the date of randomization up to 97 months | — |
| Objective Response Rate | From the date of randomization up to 97 months | — |
| Complete Response Rate | From the date of randomization up to 97 months | — |
| Time to Response | From the date of randomization to date of confirmed objective response up to 97 months | — |
| Duration of Response | From the date of confirmed objective response up to 97 months | — |
| Duration of Complete Response | From the date of confirmed complete response up to 97 months | — |
| Frequency of treatment-emergent adverse events | From the date of first dose of study intervention up to 97 months | — |
| Frequency of abnormal laboratory results | From the date of first dose of study intervention up to 97 months | — |
| Pharmacokinetics of elranatamab when used in the elranatamab + daratumumab + lenalidomide or elranatamab + lenalidomide combinations | From date of first dose of study intervention up to 97 months | Predose and post dose concentrations of elranatamab |
| Incidence of Anti-Drug Antibody against elranatamab | From date of first dose of study intervention up to 97 months | Immunogenicity of elranatamab |
| Pharmacokinetics of daratumumab and lenalidomide when used in the elranatamab+daratumumab+lenalidomide or elranatamab+lenalidomide combinations (Part 1) | From date of first dose of study intervention up to 97 months | Predose concentrations of daratumumab and lenalidomide |
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (Part 2) | From date the informed consent is signed up to 97 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. |
| Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Myeloma 20 (Part 2) | From date the informed consent is signed up to 97 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 |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Finland, France, Germany, Greece, Israel, Italy, Japan, Netherlands, New Zealand, Poland, Puerto Rico, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed