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)

NCT07222761 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: R5458-ONC-22462024-519504-27-00
• Study Type: interventional
• Target: 915
• Locations: 4 countries
• Sites: 16

Brief Summary

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)

Conditions

Relapsed and/or Refractory Multiple Myeloma (RRMM)

Keywords

BCMA X CD3 Bispecific Monoclonal Antibody; Bispecific combination therapy; Linvoseltamab; Carfilzomib; Proteasome inhibitor

Outcome Measures

Primary Outcomes (8)

• Occurrence of Treatment Emergent Adverse Events (TEAEs)

  Part 1

  Up to 5 years

• Severity of TEAEs

  Part 1

  Up to 5 years

• Occurrence of Adverse Events of Special Interest (AESI)

  Part 1

  Up to 5 years

• Severity of AESIs

  Part 1

  Up to 5 years

• Occurrence of Serious Adverse Events (SAEs)

  Part 1

  Up to 5 years

• Severity of SAEs

  Part 1

  Up to 5 years

• Minimal Residual Disease (MRD)-negative Complete Response (CR)

  Part 2

  At 12 months

• Progression-Free Survival (PFS) per IMWG response criteria as determined by BIRC

  Part 2

  Up to 5 years

Secondary Outcomes (36)

• Occurrence of grade ≥2 Cytokine Release Syndrome (CRS)

  Up to 28 days

• Timing of grade ≥2 CRS

  Up to 28 days

• Overall Survival (OS)

  Up to 7 years

• Achievement of Partial Response (PR) or better per IMWG response criteria as determined by BIRC

  Up to 5 years

• Achievement of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by BIRC

  Up to 5 years

Study Arms (5)

Part 1: Arm A

EXPERIMENTAL

Drug: Linvoseltamab

Part 1: Arm B

EXPERIMENTAL

Drug: Linvoseltamab; Drug: Carfilzomib

Part 2: Arm A

EXPERIMENTAL

Drug: Linvoseltamab

Part 2: Arm B

EXPERIMENTAL

Drug: Linvoseltamab; Drug: Carfilzomib

Part 2: Arm C

EXPERIMENTAL

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

Interventions

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458, Lynozyfic™

Part 1: Arm A; Part 1: Arm B; Part 2: Arm A; Part 2: Arm B

Carfilzomib DRUG

Administered per the protocol

Also known as: Kyprolis®

Part 1: Arm B; Part 2: Arm B; Part 2: Arm C

Pomalidomide DRUG

Administered per the protocol

Also known as: Imnovid®, Pomalyst®

Part 2: Arm C

Bortezomib DRUG

Administered per the protocol

Also known as: Velcade®

Part 2: Arm C

Daratumumab DRUG

Administered per the protocol

Also known as: Darzalex Faspro®, Darzalex®

Part 2: Arm C

Dexamethasone DRUG

Administered per the protocol

Also known as: Dexahexal®

Part 2: Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
• Confirmed progressive disease according to IMWG criteria during or after the most recent line of therapy

You may not qualify if:

• 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
• 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)
• Known Central Nervous System (CNS) involvement of myeloma including meningeal involvement
• History of neurodegenerative condition, Progressive Multifocal Leukoencephalopathy (PML), or CNS movement disorder

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (16)

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

OhioHealth

Columbus, Ohio, 43214, United States

RECRUITING

Mater Misericordiae Ltd

Brisbane, Queensland, 4101, Australia

RECRUITING

Gold Coast Hospital and Health Service

Southport, Queensland, 4215, Australia

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, 58128, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital; Division of Hematology

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, 06591, South Korea

RECRUITING

Ulsan University Hospital

Ulsan, 44033, South Korea

RECRUITING

Aberdeen Royal Infirmary

Aberdeen, Aberdeenshire, AB25 2ZN, United Kingdom

RECRUITING

Royal Cornwall Hospital National Health Service (NHS) Foundation Trust

Truro, Cornwall, TR1 3LJ, United Kingdom

RECRUITING

University Hospitals Plymouth National Health Service (NHS) Foundation Trust - Hematology

Plymouth, Devon, PL6 8DH, United Kingdom

RECRUITING

Norfolk and Norwich University Hospital National Health Service (NHS) Foundation Trust

Norwich, Norfolk, NR4 7UY, United Kingdom

RECRUITING

University Hospitals Birmingham NHS Trust, Center for Clinical

Birmingham, West Midlands, B15 2GW, United Kingdom

RECRUITING

Ninewells Hospital and Medical School

Dundee, DD1 9SY, United Kingdom

RECRUITING

MeSH Terms

Interventions

carfilzomib; daratumumab; Dexamethasone; pomalidomide; Bortezomib

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2025
• First Posted: October 30, 2025
• Study Start: January 2, 2026
• Primary Completion (Estimated): May 21, 2029
• Study Completion (Estimated): August 23, 2034
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

KR (6); AU (2); GB (6); US (2)