A Study to Learn About Effects of the Combination of Elranatamab, Daratumumab and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant or Who Will Not Receive a Transplant as Initial Therapy
AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE OR TRANSPLANT-DEFERRED PARTICIPANTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
Pfizer
1,116 participants
Nov 10, 2022
INTERVENTIONAL
Conditions
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, 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 minimal residual disease (MRD) negativity rate and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed multiple myeloma.
Eligibility
Inclusion Criteria12
- 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;
- 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 by age or comorbidities impacting the possibility of transplant) or
- transplant deferred (defined as clinically transplant-eligible but who does not intend to receive transplant as a first line of therapy).
- 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 Criteria10
- 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.
Interventions
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
Part 1 Dose Level 1 is not randomized. All other cohorts are randomized.
Randomized
Locations(88)
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NCT05623020