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)

An Open-Label, Randomized Phase 3 Study of Linvoseltamab Monotherapy and Linvoseltamab Plus Carfilzomib Versus Standard of Care Combination Regimens in Patients With Relapsed/Refractory Multiple Myeloma

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)

Study Overview

• Status: Recruiting
• Conditions: Relapsed and/or Refractory Multiple Myeloma (RRMM)
• Intervention / Treatment: Drug: Daratumumab; Drug: Dexamethasone; Drug: Linvoseltamab; Drug: Carfilzomib; Drug: Pomalidomide; Drug: Bortezomib

• Study Type: Interventional
• Enrollment (Estimated): 915
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Mater Misericordiae Ltd
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast Hospital and Health Service
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital; Division of Hematology
  • Seoul, South Korea, 06591
    • Recruiting
    • Seoul St. Mary's Hospital, The Catholic University of Korea
  • Ulsan, South Korea, 44033
    • Recruiting
    • Ulsan University Hospital
  • Jeollanam-do
    • Hwasun, Jeollanam-do, South Korea, 58128
      • Recruiting
      • Chonnam National University Hwasun Hospital
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Recruiting
    • Ninewells Hospital and Medical School
  • Aberdeenshire
    • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZN
      • Recruiting
      • Aberdeen Royal Infirmary
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Recruiting
      • Royal Cornwall Hospital National Health Service (NHS) Foundation Trust
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Recruiting
      • University Hospitals Plymouth National Health Service (NHS) Foundation Trust - Hematology
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Recruiting
      • Norfolk and Norwich University Hospital National Health Service (NHS) Foundation Trust
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2GW
      • Recruiting
      • University Hospitals Birmingham NHS Trust, Center for Clinical
• United States
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Recruiting
      • OhioHealth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Arm A	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™
Experimental: Part 1: Arm B	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™; Drug: Carfilzomib; Administered per the protocol; Other Names: Kyprolis®
Experimental: Part 2: Arm A	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™
Experimental: Part 2: Arm B	Drug: Linvoseltamab; Administered per the protocol; Other Names: REGN5458; Lynozyfic™; Drug: Carfilzomib; Administered per the protocol; Other Names: Kyprolis®
Experimental: Part 2: Arm C	Drug: Daratumumab; Administered per the protocol; Other Names: Darzalex®; Darzalex Faspro®; Drug: Dexamethasone; Administered per the protocol; Other Names: Dexahexal®; Drug: Carfilzomib; Administered per the protocol; Other Names: Kyprolis®; Drug: Pomalidomide; Administered per the protocol; Other Names: Pomalyst®; Imnovid®; Drug: Bortezomib; Administered per the protocol; Other Names: Velcade®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of grade ≥2 Cytokine Release Syndrome (CRS)	Part 1	Up to 28 days
Timing of grade ≥2 CRS	Part 1	Up to 28 days
Overall Survival (OS)	Part 2	Up to 7 years
Achievement of Partial Response (PR) or better per IMWG response criteria as determined by BIRC	Part 2	Up to 5 years
Achievement of Very Good Partial Response (VGPR) or better per IMWG response criteria as determined by BIRC	Part 2	Up to 5 years
Achievement of CR or better per IMWG response criteria as determined by BIRC	Part 2	Up to 5 years
Duration Of Response (DOR) as per IMWG response criteria	Part 2	Up to 5 years
Time To Progression (TTP) as per IMWG response criteria	Part 2	Up to 5 years
Time To Next Treatment (TTNT)	Part 2	Up to 5 years
Second PFS	Part 2	Up to 5 years
MRD-negative CR criteria at any time	Part 2	Up to 5 years
Time to PR IMWG response category	Part 2	Up to 5 years
Time to VGPR IMWG response category	Part 2	Up to 5 years
Time to CR IMWG response category	Part 2	Up to 5 years
Time to stringent Complete Response (sCR) IMWG response category	Part 2	Up to 5 years
Sustained MRD-negative CR	Part 2	Up to 5 years
Duration of MRD-negative CR	Part 2	Up to 5 years
Occurrence of TEAEs	Part 2	Up to 5 years
Severity of TEAEs	Part 2	Up to 5 years
Occurrence of AESIs	Part 2	Up to 5 years
Severity of AESIs	Part 2	Up to 5 years
Occurrence of SAEs	Part 2	Up to 5 years
Severity of SAEs	Part 2	Up to 5 years
Concentrations of linvoseltamab in serum over time	Part 2	Up to 5 years
Incidence of Antidrug Antibodies (ADAs) to linvoseltamab	Part 2	Up to 5 years
Magnitude of ADAs to linvoseltamab	Part 2	Up to 5 years
Concentrations total soluble B-cell Maturation Antigen (sBCMA) in serum over time	Part 2	Up to 5 years
Change from baseline in Global Health Status (GHS)/Quality of Life (QoL), per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	Part 2 The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."	Up to 5 years
Change from baseline in Physical Functioning (PF), per EORTC QLQ-C30	Part 2	Up to 5 years
Change from baseline in Role Functioning (RF), per EORTC QLQ-C30	Part 2	Up to 5 years
Change from baseline in pain, per EORTC QLQ-C30	Part 2	Up to 5 years
Change from baseline in fatigue, per EORTC QLQ-C30	Part 2	Up to 5 years
Change in patient reported Disease Symptoms (DS) per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20])	Part 2 EORTC QLQ-MY20 is an accompanying 20-item validated questionnaire that measure quality of life among patients living with MM across 4 scales (disease symptoms, side effect of treatment, body image and future perspective). A high score represents a high level of symptoms or problems.	Up to 5 years
Change in patient reported Treatment Side Effects (TSE) per EORTC QLQ-MY20	Part 2	Up to 5 years
Change in patient-reported health state per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) Visual Analogue Scale (VAS)	Part 2 The EQ-5D-5L is a generic questionnaire that measures HRQoL across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (no problems, slight problems, some problems, severe problems and extreme problems) and a VAS of pain (where 0: no pain and 10: worst pain), higher scores indicate higher pain.	Up to 5 years
Change in patient-reported overall impact of treatment per Functional Assessment of Chronic Illness Therapy (FACIT) item GP5	Part 2 FACIT Item GP5 is a recommended item by the Federal Drug Administration (FDA) in its recent draft guidance for cancer trials to assess patient-reported overall impact of treatment toxicity. It uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much)	Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2026
• Primary Completion (Estimated): May 21, 2029
• Study Completion (Estimated): August 23, 2034

Study Registration Dates

• First Submitted: October 28, 2025
• First Submitted That Met QC Criteria: October 28, 2025
• First Posted (Actual): October 30, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Carfilzomib; Proteasome inhibitor; BCMA X CD3 Bispecific Monoclonal Antibody; Linvoseltamab; Bispecific combination therapy
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Bortezomib; Dexamethasone; carfilzomib; pomalidomide; daratumumab
• Other Study ID Numbers: R5458-ONC-2246; 2024-519504-27-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing 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

• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No