A Study to Compare Linvoseltamab Monotherapy and Linvoseltamab + Carfilzomib Combination Therapy With Standard-of-Care Combination Regimens in Adult Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (LINKER-MM5)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Relapsed and/or Refractory Multiple Myeloma (RRMM)

Treatments: Drug: Dexamethasone; Drug: Carfilzomib; Drug: Bortezomib; Drug: Pomalidomide; Drug: Linvoseltamab; Drug: Daratumumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07222761

R5458-ONC-2246

2024-519504-27-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

This study is researching a drug called linvoseltamab (also called "study drug") either given alone or in combination with another anti-myeloma drug called carfilzomib, compared to several standard treatments for progressive Multiple Myeloma (MM) after at least 1 but no more than 3 prior therapies.

The aim of this study is to see if the safety and efficacy of linvoseltamab alone or in combination with carfilzomib can deliver better outcomes (deeper and longer responses that help extend life) than standard treatment options.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Enrollment: 915 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Participant with RRMM who received at least 1 but not more than 3 prior lines of therapy, which must have included treatment with lenalidomide and either a Protease Inhibitor (PI) or anti-CD38 monoclonal antibody
2. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
3. Confirmed progressive disease according to IMWG criteria during or after the most recent line of therapy

Key Exclusion Criteria:

1. Prior treatment with a T cell-based immunotherapy targeting BCMA, including BCMA-directed bispecific antibodies, Bispecific T-cell Engagers (BiTEs), and Chimeric Antigen Receptor (CAR) T cells. Antibody-drug conjugates targeting BCMA (eg, belantamab mafodotin) are not excluded
2. Diagnosis of plasma cell leukemia, symptomatic amyloidosis (including myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
3. Known Central Nervous System (CNS) involvement of myeloma including meningeal involvement
4. History of neurodegenerative condition, Progressive Multifocal Leukoencephalopathy (PML), or CNS movement disorder

NOTE: Other protocol defined inclusion/exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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915 participants in 5 patient groups

Part 1: Arm A

Experimental group

Treatment:

Drug: Linvoseltamab

Part 1: Arm B

Experimental group

Treatment:

Drug: Linvoseltamab

Drug: Carfilzomib

Part 2: Arm A

Experimental group

Treatment:

Drug: Linvoseltamab

Part 2: Arm B

Experimental group

Treatment:

Drug: Linvoseltamab

Drug: Carfilzomib

Part 2: Arm C

Experimental group

Treatment:

Drug: Daratumumab

Drug: Pomalidomide

Drug: Bortezomib

Drug: Carfilzomib

Drug: Dexamethasone