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

Phase 3RecruitingNCT05623020

Pfizer1,116 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,116

Conditions

Multiple Myeloma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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; * 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 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.

Locations (85)

Pindara Private Hospital

Benowa, Queensland, Australia

RECRUITING

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

RECRUITING

Epworth Freemasons

Melbourne, Victoria, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

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 negativity rate

Time frame: At 12 months after randomization

Secondary Outcomes

Overall Survival

Time frame: From date of randomization up to 97 months

Overall minimal residual disease negativity rate

Time frame: From date of randomization up to 97 months

Sustained MRD negativity rate (Part 2)

Time frame: From date of randomization up to 97 months

Duration of minimal residual disease negativity (Part 2)

Time frame: From date of minimal residual disease negative 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

Predose and post dose concentrations of elranatamab

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

Incidence of Anti-Drug Antibody against elranatamab

Immunogenicity of 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)

Predose concentrations of daratumumab and lenalidomide

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)

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.

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)

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

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

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

Overview

Conditions

Interventions

Eligibility

Locations (85)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts