A Study to Learn About the Study Medicine Called Elranatamab in People With Multiple Myeloma (MM) That Has Come Back After Taking Other Treatments (Including Prior Treatment With an Anti-CD38 Antibody and Lenalidomide)

Sponsor

Pfizer (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06152575

Collaborator

(none)

492

Enrollment

Arms

50.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to learn about the study medicine called elranatamab.This study aims to compare elranatamab to other medicines for the treatment of MM (a type of cancer).

This study is seeking participants who:

Are 18 years of age or older and have MM.
Have received treatments before for MM.
Have MM that has returned or not responded to their most recent treatment.

Half of the participants will receive elranatamab. The other half of participants will receive a combination therapy selected by the study doctor. The selected combination therapy will include 2 to 3 different medicines commonly used to treat MM.

Elranatamab will be given as a shot under the skin at the study clinic about once a week. This may change to a smaller number of shots later in the study.

The medicines in the combination therapy will be taken by mouth (at home or at the study clinic) AND will be given either as:

a shot under the skin at the study clinic
through a needle in the vein at the study clinic The number of times these medicines will be taken depends on what combination therapy the study doctor selects.

Participants may continue to receive elranatamab or a combination therapy until their MM is no longer responding. The study team will see how each participant is doing with the study treatment during regular visits at the study clinic. The study team will continue to follow-up with participants after study treatment with telephone contacts (or visits).

The study will compare the experiences of people receiving elranatamab to those people receiving a combination therapy. This will help learn about the safety and how effective elranatamab is.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Elranatamab Drug: Elotuzumab Drug: Pomalidomide Drug: Dexamethasone Drug: Bortezomib Drug: Carfilzomib	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

492 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Open-Label Study of Elranatamab Monotherapy Versus Elotuzumab, Pomalidomide, Dexamethasone (EPd) Or Pomalidomide, Bortezomib, Dexamethasone (PVd) Or Carfilzomib, Dexamethasone (Kd) In Participants With Relapsed/Refractory Multiple Myeloma Who Received Prior Anti-CD38 Directed Therapy (MagnetisMM-32)

Anticipated Study Start Date :

Dec 18, 2023

Anticipated Primary Completion Date :

Dec 3, 2025

Anticipated Study Completion Date :

Mar 7, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elranatamab Participants will receive elranatamab monotherapy	Drug: Elranatamab Elranatamab will be administered subcutaneously
Active Comparator: Investigator's Choice Participants will receive either Elotuzumab, Pomalidomide and Dexamethasone (EPd), or Pomalidomide, Bortezomib and Dexamethasone (PVd), or Carfilzomib and Dexamethasone (Kd)	Drug: Elotuzumab Elotuzumab will be administered intravenously Drug: Pomalidomide Pomalidomide will be administered orally Drug: Dexamethasone Dexamethasone will be administered orally Drug: Bortezomib Bortezomib will be administered subcutaneously or intravenously Drug: Carfilzomib Carfilzomib will be administered intravenously

Arm

Intervention/Treatment

Experimental: Elranatamab

Participants will receive elranatamab monotherapy

Drug: Elranatamab

Elranatamab will be administered subcutaneously

Active Comparator: Investigator's Choice

Participants will receive either Elotuzumab, Pomalidomide and Dexamethasone (EPd), or Pomalidomide, Bortezomib and Dexamethasone (PVd), or Carfilzomib and Dexamethasone (Kd)

Drug: Elotuzumab

Elotuzumab will be administered intravenously

Drug: Pomalidomide

Pomalidomide will be administered orally

Drug: Dexamethasone

Dexamethasone will be administered orally

Drug: Bortezomib

Bortezomib will be administered subcutaneously or intravenously

Drug: Carfilzomib

Carfilzomib will be administered intravenously

Outcome Measures

Primary Outcome Measures

Progression free survival per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first

Secondary Outcome Measures

Overall survival [Up to approximately 5 years]
From date of randomization to date of discontinuation from study, death, or censoring, whichever occurs first
Progression free survival on next-line treatment per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of second objective disease progression, discontinuation from the study, death, or censoring, whichever occurs first
Objective response rate per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy
Duration of response per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of confirmed objective response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first
Very good partial response or better response rate per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first
Complete response rate per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first
Duration of complete response per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of confirmed complete response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first
Time to response per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of confirmed objective response
Minimal residual disease negativity rate per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first
Sustained minimal residual disease negativity rate per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first
Duration of minimal residual disease negativity rate per International Myeloma Working Group criteria [Up to approximately 5 years]
From date of minimal residual disease negativity to date of relapse, death, or censoring, whichever occurs first
Frequency of treatment-emergent adverse events [From date of first dose of study intervention up to 90 days after last study intervention administration]
Frequency of abnormal laboratory results [From date of first dose of study intervention up to 90 days after last study intervention administration]
Free elranatamab serum trough concentration [Ctrough] [From date of first dose of elranatamab up to approximately 14 days after last dose of elranatamab]
Elranatamab immunogenicity by anti-drug antibodies against elranatamab [From date of first dose of elranatamab up to approximately 14 days after last dose of elranatamab]
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 [From date of informed consent up to approximately 35 days after last administration of study intervention]
Change from baseline scores
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20 [From date of informed consent up to approximately 35 days after last administration of study intervention]
Change from baseline scores

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Prior diagnosis of multiple myeloma as defined by International Myeloma Working Group (IMWG) criteria and previously received 1 to 4 prior lines of therapy including prior anti-cluster of differentiation 38 (CD38) antibody and prior lenalidomide.
Documented evidence of progressive disease or failure to achieve a response to last line of therapy per IMWG criteria.
Measurable disease defined as at least 1 of the following: (a) Serum M-protein ≥0.5 g/dL; (b) Urinary M-protein excretion ≥200 mg/24 hours; (c) Serum involved immunoglobulin FLC ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
Have clinical laboratory values within the specified range.
ECOG (Eastern Cooperative Oncology Group) performance status ≤2.
Not pregnant or breastfeeding and willing to use contraception.

Exclusion Criteria:

Smoldering multiple myeloma.
Plasma cell leukemia.
Amyloidosis.
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities (POEMS) syndrome.
Known central nervous system (CNS) involvement or clinical signs of myelomatous meningeal involvement.
Stem cell transplant within 12 weeks prior to enrolment, or active graft versus host disease.
Any active, uncontrolled bacterial, fungal, or viral infection.
Any other active malignancy within 3 years prior to enrolment (exceptions include, adequately treated basal cell or squamous cell skin cancer, carcinoma in situ)
Previous treatment with a B cell maturation antigen (BCMA)-directed therapy or CD3-redirecting therapy.
Unable to receive investigator's choice therapy.
Live attenuated vaccine within 4 weeks of the first dose of study intervention.
Administration with an investigational product (e.g. drug or vaccine) within 30 days preceding the first dose of study intervention used in this study.