A Study to Learn About the Study Medicine Elranatamab Alone and With Daratumumab in People With Multiple Myeloma Who Have Received Other Treatments

Phase 3RecruitingNCT05020236

Pfizer944 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

944

Conditions

Multiple Myeloma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Part 1 Safety Lead-In: Incidence of dose limiting toxicities

Time frame: First 42 days after first elranatamab dose

Part 2 Randomized: Progression free survival per International Myeloma Working Group criteria

Time frame: 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

Time frame: First 84 days after first elranatamab dose

Secondary Outcomes

Part 1 Safety Lead-In: Progression free survival per International Myeloma Working Group criteria

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: From date of randomization to date of confirmed objective response, assessed up to 51 months

Complete response rate per International Myeloma Working Group criteria

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Rate of Grade ≥2 cytokine release syndrome

Time frame: First 28 days after first elranatamab dose

Elranatamab pharmacokinetics by pre- and post-dose concentrations

Time frame: 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

Time frame: From date of first dose through up to 14 days after date of last dose of elranatamab

Daratumumab pharmacokinetics by pre-dose concentrations

Time frame: 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

Time frame: 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

Time frame: From date of informed consent through up to 35 days after date of last dose of study intervention

A Study to Learn About the Study Medicine Elranatamab Alone and With Daratumumab in People With Multiple Myeloma Who Have Received Other Treatments

Overview

Conditions

Interventions

Eligibility

Locations (239)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts