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NCT Number: NCT07222761

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)

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)

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Key information

Conditions

Relapsed and/or Refractory Multiple Myeloma (RRMM)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Mater Misericordiae Ltd, Brisbane, Queensland, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

NOTE: Other protocol defined inclusion/exclusion criteria apply

Treatment and study plan

Linvoseltamab

Drug

Administered per the protocol

Other names: REGN5458, Lynozyfic™

Carfilzomib

Drug

Administered per the protocol

Other names: Kyprolis®

Daratumumab

Drug

Administered per the protocol

Other names: Darzalex Faspro®, Darzalex®

Dexamethasone

Drug

Administered per the protocol

Other names: Dexahexal®

Pomalidomide

Drug

Administered per the protocol

Other names: Imnovid®, Pomalyst®

bortezomib

Drug

Administered per the protocol

Other names: Velcade®

Primary outcomes

  1. Occurrence of Treatment Emergent Adverse Events (TEAEs)

    Time frame: Up to 5 years

    Part 1

  2. Severity of TEAEs

    Time frame: Up to 5 years

    Part 1

  3. Occurrence of Adverse Events of Special Interest (AESI)

    Time frame: Up to 5 years

    Part 1

  4. Severity of AESIs

    Time frame: Up to 5 years

    Part 1

  5. Occurrence of Serious Adverse Events (SAEs)

    Time frame: Up to 5 years

    Part 1

  6. Severity of SAEs

    Time frame: Up to 5 years

    Part 1

  7. Minimal Residual Disease (MRD)-negative Complete Response (CR)

    Time frame: At 12 months

    Part 2

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

    Time frame: Up to 5 years

    Part 2

Secondary outcomes

  1. Occurrence of grade ≥2 Cytokine Release Syndrome (CRS)

    Time frame: Up to 28 days

    Part 1

  2. Timing of grade ≥2 CRS

    Time frame: Up to 28 days

    Part 1

  3. Overall Survival (OS)

    Time frame: Up to 7 years

    Part 2

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

    Time frame: Up to 5 years

    Part 2

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

    Time frame: Up to 5 years

    Part 2

  6. Achievement of CR or better per IMWG response criteria as determined by BIRC

    Time frame: Up to 5 years

    Part 2

  7. Duration Of Response (DOR) as per IMWG response criteria

    Time frame: Up to 5 years

    Part 2

  8. Time To Progression (TTP) as per IMWG response criteria

    Time frame: Up to 5 years

    Part 2

  9. Time To Next Treatment (TTNT)

    Time frame: Up to 5 years

    Part 2

  10. Second PFS

    Time frame: Up to 5 years

    Part 2

  11. MRD-negative CR criteria at any time

    Time frame: Up to 5 years

    Part 2

  12. Time to PR IMWG response category

    Time frame: Up to 5 years

    Part 2

  13. Time to VGPR IMWG response category

    Time frame: Up to 5 years

    Part 2

  14. Time to CR IMWG response category

    Time frame: Up to 5 years

    Part 2

  15. Time to stringent Complete Response (sCR) IMWG response category

    Time frame: Up to 5 years

    Part 2

  16. Sustained MRD-negative CR

    Time frame: Up to 5 years

    Part 2

  17. Duration of MRD-negative CR

    Time frame: Up to 5 years

    Part 2

  18. Occurrence of TEAEs

    Time frame: Up to 5 years

    Part 2

  19. Severity of TEAEs

    Time frame: Up to 5 years

    Part 2

  20. Occurrence of AESIs

    Time frame: Up to 5 years

    Part 2

  21. Severity of AESIs

    Time frame: Up to 5 years

    Part 2

  22. Occurrence of SAEs

    Time frame: Up to 5 years

    Part 2

  23. Severity of SAEs

    Time frame: Up to 5 years

    Part 2

  24. Concentrations of linvoseltamab in serum over time

    Time frame: Up to 5 years

    Part 2

  25. Incidence of Antidrug Antibodies (ADAs) to linvoseltamab

    Time frame: Up to 5 years

    Part 2

  26. Magnitude of ADAs to linvoseltamab

    Time frame: Up to 5 years

    Part 2

  27. Concentrations total soluble B-cell Maturation Antigen (sBCMA) in serum over time

    Time frame: Up to 5 years

    Part 2

  28. 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)

    Time frame: Up to 5 years

    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."

  29. Change from baseline in Physical Functioning (PF), per EORTC QLQ-C30

    Time frame: Up to 5 years

    Part 2

  30. Change from baseline in Role Functioning (RF), per EORTC QLQ-C30

    Time frame: Up to 5 years

    Part 2

  31. Change from baseline in pain, per EORTC QLQ-C30

    Time frame: Up to 5 years

    Part 2

  32. Change from baseline in fatigue, per EORTC QLQ-C30

    Time frame: Up to 5 years

    Part 2

  33. Change in patient reported Disease Symptoms (DS) per EORTC Quality of Life Questionnaire-Multiple Myeloma (MM) module 20 [QLQ-MY20])

    Time frame: Up to 5 years

    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.

  34. Change in patient reported Treatment Side Effects (TSE) per EORTC QLQ-MY20

    Time frame: Up to 5 years

    Part 2

  35. Change in patient-reported health state per EuroQoL-5 Dimension-5 Level Scale [EQ-5D-5L]) Visual Analogue Scale (VAS)

    Time frame: Up to 5 years

    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.

  36. Change in patient-reported overall impact of treatment per Functional Assessment of Chronic Illness Therapy (FACIT) item GP5

    Time frame: Up to 5 years

    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)

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

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

Acronym: LINKER-MM5

Important dates

Study start
2026
Primary completion
2029
Study completion
2034
First posted
Oct 30, 2025
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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