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NCT Number: NCT05828511

A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment

This study is researching an experimental drug called linvoseltamab (called "study drug"). The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy with autologous stem cell transplantation (transplant-eligible) or ineligible for autologous stem cell transplantation (transplant-ineligible).

The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM.

This study consists of 2 phases:

* In Phase 1 Parts A and B, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2. * In Phase 1 Part C, the study drug will be given to participants to study the side effects when using different initial doses of the study drug. * In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the activity of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM.

The study is looking at several research questions, including:

* What side effects may happen from taking linvoseltamab? * What the right dosing regimen is for linvoseltamab? * How many participants treated with linvoseltamab have improvement of their disease and for how long? * The effects of linvoseltamab study treatment before and after transplant * How much linvoseltamab is in the blood at different times? * Whether the body makes antibodies against linvoseltamab (which could make the drug less effective or could lead to side effects).

Recruiting

Interested in participating?

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Centre Hospitalier Universitaire (CHU) de Poitiers, Poitiers, Vienne, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Confirmed diagnosis of symptomatic Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol
  • Response-evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol
  • No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
  • Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
  • Participants must be age <70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.

Key Exclusion Criteria:

  • Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
  • Known Central Nervous System (CNS) involvement with MM, known or suspected Progressive Multifocal Leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment
  • Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
  • Diagnosis of non-secretory MM, active plasma cell leukemia primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (Plasma cell dyscrasia with polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Treatment and study plan

Linvoseltamab

Drug

Linvoseltamab will be administered by intravenous (IV) infusion

Other names: REGN5458, Lynozyfic™

Primary outcomes

  1. Incidence of Dose-Limiting Toxicities (DLTs)

    Time frame: End of the Observation period; up to day 28

    Phase 1

  2. Incidence of Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  3. Severity of TEAEs

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  4. Incidence of Adverse Events of Special Interest (AESIs)

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  5. Severity of AESIs

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  6. Proportion of participants with a Very Good Partial Response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria

    Time frame: Up to 5 years

    Phase 2

  7. Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy

    Time frame: Up to 5 years

    Phase 2 Transplant-eligible cohort

  8. Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy

    Time frame: Up to 5 years

    Phase 2 Transplant-eligible cohort

  9. Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II

    Time frame: Up to 5 years

    Phase 2 Transplant-ineligible cohort

  10. Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II

    Time frame: Up to 5 years

    Phase 2 Transplant ineligible cohort

Secondary outcomes

  1. Concentrations of Linvoseltamab in serum

    Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks

    Phases 1 and 2

  2. Concentrations of total soluble B-Cell Maturation Antigen (BCMA)

    Time frame: Post-Last Linvoseltamab Dose, up to 12 weeks

    Phases 1 and 2

  3. Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab

    Time frame: Post-Last Linvoseltamab Dose, up to 30 days

    Phases 1 and 2

  4. Magnitude of ADAs to Linvoseltamab

    Time frame: Post-Last Linvoseltamab Dose, up to 30 days

    Phases 1 and 2

  5. Objective Response Rate (ORR) measured using the IMWG criteria

    Time frame: Up to 5 years

    Phase 1

  6. Duration Of Response (DOR) measured using the IMWG criteria

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  7. Progression-Free Survival (PFS) measured using the IMWG criteria

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  8. Proportion of participants achieving MRD-negative status (at 10^-5) in participants with NDMM measured using the IMWG criteria

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 1

  9. Incidence of TEAEs

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  10. Severity of TEAEs

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  11. Incidence of AESIs

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  12. Severity of AESIs

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  13. ORR of participants deemed transplant-eligible and transplant-ineligible by the treating physician

    Time frame: Up to 5 years

    Phase 2

  14. MRD-negative status of participants deemed transplant-eligible and transplant-ineligible by the treating physician

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  15. DOR of participants deemed transplant-eligible and transplant-ineligible by the treating physician

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  16. PFS of participants deemed transplant-eligible and transplant-ineligible by the treating physician

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  17. Overall Survival (OS) of participants deemed transplant-eligible and transplant-ineligible by the treating physician

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  18. Time To Response (TTR) as measured using the IMWG criteria

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  19. ORR by risk levels

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  20. MRD-negative status by risk levels

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  21. DOR by risk levels

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  22. TTR by risk levels

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  23. PFS by risk levels

    Time frame: Post-Last Linvoseltamab Dose, up to 90 days

    Phase 2

  24. Incidence of MRD-negative status

    Time frame: Up to 5 years

    Phase 2

  25. Cluster of Differentiation 34+ (CD34+) stem cell yield

    Time frame: At cycle 4 of induction (each cycle is 28 days long)

    Phase 2 Transplant-eligible cohort

  26. Time to neutrophil engraftment

    Time frame: Up to 100 days post-transplant

    Phase 2 Transplant-eligible cohort

  27. Time to platelet engraftment

    Time frame: Up to 100 days post-transplant

    Phase 2 Transplant-eligible cohort

  28. PFS after ASCT followed by 3 cycles of linvoseltamab

    Time frame: Up to 5 years

    Phase 2 Transplant-eligible cohort

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

Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma

Acronym: LINKER-MM4

Important dates

Study start
2023
Primary completion
2035
Study completion
2035
First posted
Apr 25, 2023
Registry last updated
May 13, 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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