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RecruitingInterventionalPhase 3

AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + BORTEZOMIB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA

NCT ID: NCT05623020Sponsor: PfizerLast updated: 2026-06-09

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.

Arms & 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

Outcome measures

Primary

  • Part 1 Dose Limiting Toxicity

    Time frame: 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

    Time frame: From randomization up to 97 months.

  • Part 2: Minimal Residual Disease negative CR rate

    Time frame: At 12 months after randomization

Secondary

  • Overall Survival

    Time frame: From date of randomization up to 97 months

  • Overall minimal residual disease negative CR rate

    Time frame: From date of randomization up to 97 months

  • Sustained MRD negative CR rate (Part 2)

    Time frame: From date of randomization up to 97 months

  • Duration of minimal residual disease negative CR (Part 2)

    Time frame: From date of minimal residual disease negative CR status up to 97 months

  • PFS by investigator

    Time frame: From date of randomization up to 97 months

  • PFS2 by investigator (Part 2)

    Time frame: From the date of randomization up to 97 months

  • Objective Response Rate

    Time frame: From the date of randomization up to 97 months

  • Complete Response Rate

    Time frame: From the date of randomization up to 97 months

  • Time to Response

    Time frame: From the date of randomization to date of confirmed objective response up to 97 months

  • Duration of Response

    Time frame: From the date of confirmed objective response up to 97 months

  • Duration of Complete Response

    Time frame: From the date of confirmed complete response up to 97 months

  • Frequency of treatment-emergent adverse events

    Time frame: From the date of first dose of study intervention up to 97 months

  • Frequency of abnormal laboratory results

    Time frame: 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

    Time frame: From date of first dose of study intervention up to 97 months

  • Incidence of Anti-Drug Antibody against elranatamab

    Time frame: From date of first dose of study intervention up to 97 months

  • Pharmacokinetics of daratumumab and lenalidomide when used in the elranatamab+daratumumab+lenalidomide or elranatamab+lenalidomide combinations (Part 1)

    Time frame: From date of first dose of study intervention up to 97 months

  • Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (Part 2)

    Time frame: From date the informed consent is signed up to 97 months

  • Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Myeloma 20 (Part 2)

    Time frame: From date the informed consent is signed up to 97 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (10)

MSK Basking Ridge

Basking Ridge, New Jersey, 07920

Recruiting

MSK Monmouth

Middletown, New Jersey, 07748

Recruiting

MSK Bergen

Montvale, New Jersey, 07645

Recruiting

MSK Commack

Commack, New York, 11725

Recruiting

MSK Westchester

Harrison, New York, 10604

Recruiting

Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).

New York, New York, 10021

Recruiting

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, 10065

Recruiting

Memorial Sloan Kettering Cancer Center-Main Campus

New York, New York, 10065

Recruiting

MSK Nassau

Uniondale, New York, 11553

Recruiting

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Not Yet Recruiting