Phase 1/2 Study of Linvoseltamab in Adult Patients With Relapsed or Refractory Multiple Myeloma (LINKER-MM1)

April 15, 2026 updated by: Regeneron Pharmaceuticals

Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma

The main purpose of this study is to learn about the safety of linvoseltamab and to find out what is the best dose of linvoseltamab to give to patients with multiple myeloma and to look for any signs that linvoseltamab can effectively treat cancer.

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

  • Side effects that may be experienced by people receiving linvoseltamab
  • How linvoseltamab works in the body
  • How much linvoseltamab is present in the blood
  • How linvoseltamab may work to treat cancer

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

387

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Antwerp, Belgium, 2060
        • Recruiting
        • ZNA Psychiatrisch Ziekenhuis Stuivenberg
      • Brussels, Belgium, 1200
  • Germany
      • Würzburg, Germany, 6 97080
        • Completed
        • Universitätsklinikum Würzburg
    • North Rhine-Westphalia
      • Essen, North Rhine-Westphalia, Germany, 45147
        • Completed
        • Universitätsklinikum Essen
    • Rhineland-Palatinate
      • Mainz, Rhineland-Palatinate, Germany, 55131
        • Completed
        • Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
  • Japan
      • Tokyo, Japan, 160-8582
        • Recruiting
        • Keio University Hospital
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 467-8602
        • Recruiting
        • Nagoya City University Hospital
      • Nagoya, Aichi-ken, Japan, 466-8650
        • Completed
        • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
    • Chiba
      • Kashiwa-shi, Chiba, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
    • Gunma
      • Maebashi, Gunma, Japan, 371-8511
        • Recruiting
        • Gunma University Hospital
    • Ibaraki
      • Kasama-shi, Ibaraki, Japan, 309-1793
        • Recruiting
        • Ibaraki Prefectural Central Hospital
    • Kyoto
      • Kyoto, Kyoto, Japan, 602-8566
        • Recruiting
        • University Hospital Kyoto Prefectural Univ of Medicine
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Completed
        • Saitama Medical University International Medical Center
    • Tokushima
      • Tokushima, Tokushima, Japan, 770-8539
        • Recruiting
        • Tokushima Prefectural Central Hospital
    • Tokyo
      • Shibuya-ku, Tokyo, Japan, 150-8935
        • Completed
        • Japanese Red Cross Medical Center
  • South Korea
      • Goyang, South Korea, 10408
        • Recruiting
        • National Cancer Center Korea
      • Seoul, South Korea, 06591
        • Recruiting
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Cancer Hospital
      • Seoul, South Korea, 3722
        • Recruiting
        • Yonsei University College of Medicine, Severance Hospital
  • Spain
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Salamanca, Spain, 37007
        • Recruiting
        • Hospital Clinico Universitario de Salamanca
    • Catalonia
      • Barcelona, Catalonia, Spain, 08041
        • Recruiting
        • Hospital de La Santa Creu i Sant Pau
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
    • Salamanca
      • Madrid, Salamanca, Spain, 28006
        • Recruiting
        • Universitary Hospital La Princesa
  • United Kingdom
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Withdrawn
        • Royal Marsden Hospital
  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Active, not recruiting
        • Sylvester Comprehensive Cancer Center
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center - McKinley Drive
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Active, not recruiting
        • Indiana University_Michigan Street
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Recruiting
        • Norton Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Active, not recruiting
        • C. S. Mott_University of Michigan
      • Detroit, Michigan, United States, 48201
        • Active, not recruiting
        • Barbara Ann Karmanos Cancer Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Active, not recruiting
        • Rutgers Cancer Institute of New Jersey
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
      • New York, New York, United States, 10032
        • Active, not recruiting
        • Columbia University Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University James Cancer Hospital
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University (OHSU) Marquam Hill Campus
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • University of Texas MD Anderson Clinic
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  2. Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria

  3. Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.

    • Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either:

      a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.

    • Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria:

      a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an IMiD.

    • Phase 2 (Cohorts 1 and 2):

    Patients with MM whose disease meets the following criteria:

    a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.

    • Phase 2 (Cohort 3):

    Patients with MM whose disease meets the following criteria:

    1. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR

    2. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody.

      • Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.

    AND, for ALL patients, if they have relapsed after a BCMA-directed CAR-T cellular therapy then:

    • Treatment with a CAR-T must have been associated with a response of PR or better, and

    • If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with linvoseltamab.

    Key Exclusion Criteria:

1. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 2. Patients with known MM brain lesions or meningeal involvement 3. Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA) 4. Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excluded and BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.

5. History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment

Note: Other protocol defined inclusion / exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Linvoseltamab - Phase 2 - Cohort 1
Low Dose of linvoseltamab IV monotherapy.
Drug: Linvoseltamab
Administered per the protocol
Other Names:
  • REGN5458
  • Lynozyfic™
Experimental: Linvoseltamab - Phase 2 - Cohort 2
High Dose of linvoseltamab IV monotherapy.
Drug: Linvoseltamab
Administered per the protocol
Other Names:
  • REGN5458
  • Lynozyfic™
Experimental: Linvoseltamab - Phase 1
Phase 1 has two parts. Part 1, consists of linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration.
Drug: Linvoseltamab
Administered per the protocol
Other Names:
  • REGN5458
  • Lynozyfic™
Experimental: Linvoseltamab - Phase 2 - Cohort 3
Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV linvoseltamab monotherapy.
Drug: Linvoseltamab
Administered per the protocol
Other Names:
  • REGN5458
  • Lynozyfic™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
Time Frame: Up to 28 days
Phase 1 and Phase 2 for Japanese cohort only
Up to 28 days
Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
Time Frame: Up to 5 years
Phase 2, cohorts 1 and 2
Up to 5 years
Concentrations of linvoseltamab in serum over time
Time Frame: Up to 5 years
Phase 2, for Japanese cohort only
Up to 5 years
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: Up to 5 years
Phase 1
Up to 5 years
Incidence and severity of adverse events of special interest (AESI)
Time Frame: Up to 5 years
Phase 1
Up to 5 years
Assessment of the pharmacokinetics (PK) of linvoseltamab
Time Frame: Up to 5 years
Phase 1 part 2
Up to 5 years
Incidence and severity of cytokine release syndrome (CRS) with linvoseltamab
Time Frame: Up to 5 years
Phase 2, cohort 3
Up to 5 years
ORR of IV linvoseltamab as assessed by investigator
Time Frame: Up to 5 years
Phase 2, cohort 3
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria
Time Frame: Up to 5 years
Phase 2, cohorts 1 and 2
Up to 5 years
ORR as measured as determined by blinded IRC, as measured using the IMWG criteria
Time Frame: Up to 5 years
Phase 1, part 1 dose level 7 (DL7)
Up to 5 years
Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Concentrations of linvoseltamab in the serum over time
Time Frame: Up to 5 years
Phase 1 part 1 and Phase 2
Up to 5 years
Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
Titer of anti-drug antibodies (ADAs) to linvoseltamab over time
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
Incidence of neutralizing antibodies (NAb) to linvoseltamab over time
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
PFS as determined by an investigator, measured using the IMWG criteria
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
Rate of minimal residual disease (MRD) negative status, using the IMWG criteria
Time Frame: Up to 5 years
Phase 1
Up to 5 years
Rate of MRD negative status
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Overall survival (OS)
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
ORR as determined by the investigator, measured using the IMWG criteria
Time Frame: Up to 5 years
Phase 1 and Phase 2
Up to 5 years
Effects of linvoseltamab on health-related quality of life (HRQoL) and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Time Frame: Up to 5 years

Phase 2

The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Up to 5 years
Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])
Time Frame: Up to 5 years

Phase 2

The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.
Up to 5 years
Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])
Time Frame: Up to 5 years

Phase 2

The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.
Up to 5 years
Change in patient-reported global health status/QoL per EORTC QLQ-C30
Time Frame: Baseline up to Up to 5 years
Phase 2
Baseline up to Up to 5 years
Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Effects of linvoseltamab on general health status per EQ-5D-3L
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Effects of linvoseltamab on patient-reported functions and symptoms per EORTC QLQ-C30
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Effects of linvoseltamab on patient-reported functions and symptoms per QLQ-MY20
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Incidence and severity of TEAEs with linvoseltamab
Time Frame: Up to 5 years
Phase 2
Up to 5 years
Incidence and severity of AESIs with linvoseltamab
Time Frame: Up to 5 years
Phase 2
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 23, 2019

Primary Completion (Estimated)

March 30, 2033

Study Completion (Estimated)

June 16, 2033

Study Registration Dates

First Submitted

November 29, 2018

First Submitted That Met QC Criteria

November 29, 2018

First Posted (Actual)

December 3, 2018

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R5458-ONC-1826
  • 2024-511454-45-00 (Ctis: EUCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in a publication.

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 may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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