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Multiple MyelomaPhase 1/2LINKER-MM1NCT03761108

Phase 1/2 Study of Linvoseltamab in Adult Patients With Relapsed or Refractory Multiple Myeloma

A Phase 1/2 study testing Linvoseltamab in people with Multiple Myeloma, run by Regeneron Pharmaceuticals at 40 sites in 7 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Linvoseltamab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
387 participants
Where
40 sitesin 7 countries
Study dates
23 Jan 2019to 16 Jun 2033
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
  • 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:
  • 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:
Show all 18Show fewer
  • 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:
  • 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:
  • Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR
  • 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.

Who cannot join

  • 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

Trial locations and contacts

40 sites in 7 countries. Contact the study team or a site near you to ask about taking part.

Clinical Trial Administrator contact

844-734-6643

clinicaltrials@regeneron.com

40 sites in 7 countries

United States14 sites, 7 recruiting

  • C. S. Mott_University of Michigan

    Ann Arbor, Michigan, 48109

    Active, not recruiting

  • Emory University Hospital

    Atlanta, Georgia, 30322

    Recruiting

  • Ohio State University James Cancer Hospital

    Columbus, Ohio, 43210

    Recruiting

  • Barbara Ann Karmanos Cancer Center

    Detroit, Michigan, 48201

    Active, not recruiting

  • University of Texas MD Anderson Clinic

    Houston, Texas, 77030

    Active, not recruiting

  • Indiana University_Michigan Street

    Indianapolis, Indiana, 46202

    Active, not recruiting

  • Norton Cancer Institute

    Louisville, Kentucky, 40207

    Recruiting

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

    Active, not recruiting

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

    Active, not recruiting

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

    Recruiting

  • Columbia University Medical Center

    New York, New York, 10032

    Active, not recruiting

  • Oregon Health and Science University (OHSU) Marquam Hill Campus

    Portland, Oregon, 97239

    Recruiting

  • Swedish Cancer Institute

    Seattle, Washington, 98104

    Recruiting

  • Moffitt Cancer Center - McKinley Drive

    Tampa, Florida, 33612

    Recruiting

Other trials in United States

Japan10 sites, 7 recruiting

  • Saitama Medical University International Medical Center

    Hidaka, Saitama, 350-1298

    Completed

  • Ibaraki Prefectural Central Hospital

    Kasama-shi, Ibaraki, 309-1793

    Recruiting

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

    Recruiting

  • University Hospital Kyoto Prefectural Univ of Medicine

    Kyoto, Kyoto, 602-8566

    Recruiting

  • Gunma University Hospital

    Maebashi, Gunma, 371-8511

    Recruiting

  • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

    Nagoya, Aichi-ken, 466-8650

    Completed

  • Nagoya City University Hospital

    Nagoya, Aichi-ken, 467-8602

    Recruiting

  • Japanese Red Cross Medical Center

    Shibuya-ku, Tokyo, 150-8935

    Completed

  • Tokushima Prefectural Central Hospital

    Tokushima, Tokushima, 770-8539

    Recruiting

  • Keio University Hospital

    Tokyo, 160-8582

    Recruiting

Other trials in Japan

Spain6 sites, 6 recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, Catalonia, 08041

    Recruiting

  • Universitary Hospital La Princesa

    Madrid, Salamanca, 28006

    Recruiting

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Recruiting

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

    Recruiting

  • Hospital Clinico Universitario de Salamanca

    Salamanca, 37007

    Recruiting

Other trials in Spain

South Korea4 sites, 4 recruiting

  • National Cancer Center Korea

    Goyang, 10408

    Recruiting

  • Seoul National University Cancer Hospital

    Seoul, 03080

    Recruiting

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

    Seoul, 06591

    Recruiting

  • Yonsei University College of Medicine, Severance Hospital

    Seoul, 3722

    Recruiting

Other trials in South Korea

Germany3 sites

  • Universitatsklinikum Essen

    Essen, North Rhine-Westphalia, 45147

    Completed

  • Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

    Mainz, Rhineland-Palatinate, 55131

    Completed

  • Universitatsklinikum Wurzburg

    Würzburg, 6 97080

    Completed

Other trials in Germany

Belgium2 sites, 1 recruiting

  • ZNA Psychiatrisch Ziekenhuis Stuivenberg

    Antwerp, 2060

    Recruiting

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

    Completed

Other trials in Belgium

United Kingdom1 site

  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

    Withdrawn

Other trials in United Kingdom

About this study

Official title: 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
Being tested
Linvoseltamab
Keywords
Relapsed, Refractory
Medical subject headings
Multiple Myeloma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LinvoseltamabDrug

    Also called REGN5458, Lynozyfic™

    Administered per the protocol

Study groups in NCT03761108
Study groupRoleWhat they receive
Linvoseltamab - Phase 1ExperimentalPhase 1 has two parts. Part 1, consists of linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration.
Receives: Drug: Linvoseltamab
Linvoseltamab - Phase 2 - Cohort 1ExperimentalLow Dose of linvoseltamab IV monotherapy.
Receives: Drug: Linvoseltamab
Linvoseltamab - Phase 2 - Cohort 2ExperimentalHigh Dose of linvoseltamab IV monotherapy.
Receives: Drug: Linvoseltamab
Linvoseltamab - Phase 2 - Cohort 3ExperimentalAnti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV linvoseltamab monotherapy.
Receives: Drug: Linvoseltamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period

    Phase 1 and Phase 2 for Japanese cohort only

    Measured: Up to 28 days

  2. Incidence and severity of treatment-emergent adverse events (TEAEs)

    Phase 1

    Measured: Up to 5 years

  3. Incidence and severity of adverse events of special interest (AESI)

    Phase 1

    Measured: Up to 5 years

  4. Assessment of the pharmacokinetics (PK) of linvoseltamab

    Phase 1 part 2

    Measured: Up to 5 years

  5. Concentrations of linvoseltamab in serum over time

    Phase 2, for Japanese cohort only

    Measured: Up to 5 years

  6. Objective response rate (ORR) as determined by an Independent Review Committee (IRC)

    Phase 2, cohorts 1 and 2

    Measured: Up to 5 years

  7. Incidence and severity of cytokine release syndrome (CRS) with linvoseltamab

    Phase 2, cohort 3

    Measured: Up to 5 years

  8. ORR of IV linvoseltamab as assessed by investigator

    Phase 2, cohort 3

    Measured: Up to 5 years

Secondary outcomes (23)

  1. Concentrations of linvoseltamab in the serum over time

    Phase 1 part 1 and Phase 2

    Measured: Up to 5 years

  2. Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab

    Phase 1 and Phase 2

    Measured: Up to 5 years

  3. Titer of anti-drug antibodies (ADAs) to linvoseltamab over time

    Phase 1 and Phase 2

    Measured: Up to 5 years

  4. Incidence of neutralizing antibodies (NAb) to linvoseltamab over time

    Phase 1 and Phase 2

    Measured: Up to 5 years

  5. Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria

    Phase 2, cohorts 1 and 2

    Measured: Up to 5 years

  6. DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria

    Phase 1 and Phase 2

    Measured: Up to 5 years

  7. Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria

    Phase 2

    Measured: Up to 5 years

  8. PFS as determined by an investigator, measured using the IMWG criteria

    Phase 1 and Phase 2

    Measured: Up to 5 years

  9. Rate of minimal residual disease (MRD) negative status, using the IMWG criteria

    Phase 1

    Measured: Up to 5 years

  10. Rate of MRD negative status

    Phase 2

    Measured: Up to 5 years

  11. Overall survival (OS)

    Phase 1 and Phase 2

    Measured: Up to 5 years

  12. ORR as measured as determined by blinded IRC, as measured using the IMWG criteria

    Phase 1, part 1 dose level 7 (DL7)

    Measured: Up to 5 years

  13. ORR as determined by the investigator, measured using the IMWG criteria

    Phase 1 and Phase 2

    Measured: Up to 5 years

  14. 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)

    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."

    Measured: Up to 5 years

  15. Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])

    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.

    Measured: Up to 5 years

  16. Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])

    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.

    Measured: Up to 5 years

  17. Change in patient-reported global health status/QoL per EORTC QLQ-C30

    Phase 2

    Measured: Baseline up to Up to 5 years

  18. Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30

    Phase 2

    Measured: Up to 5 years

  19. Effects of linvoseltamab on general health status per EQ-5D-3L

    Phase 2

    Measured: Up to 5 years

  20. Effects of linvoseltamab on patient-reported functions and symptoms per EORTC QLQ-C30

    Phase 2

    Measured: Up to 5 years

  21. Effects of linvoseltamab on patient-reported functions and symptoms per QLQ-MY20

    Phase 2

    Measured: Up to 5 years

  22. Incidence and severity of TEAEs with linvoseltamab

    Phase 2

    Measured: Up to 5 years

  23. Incidence and severity of AESIs with linvoseltamab

    Phase 2

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2018
  2. Study start23 Jan 2019
  3. Primary completion30 Mar 2033 (estimated)
  4. Study completion16 Jun 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
387 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03761108
Sponsor's protocol ID
R5458-ONC-1826
Other IDs
2024-511454-45-00
Acronym
LINKER-MM1
Status last verified
Oct 2026
First submitted
29 Nov 2018
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in a publication.

Publications

  • Hoffman JE, Bumma N, Richter J, Dhodapkar MV, Lee HC, Suvannasankha A, Zonder JA, Maly JJ, Shah MR, Baz R, Inocencio TJ, DeVeaux M, Ivanescu C, Rodriguez Lorenc K, Kroog GS, Knorr K, Chi L, Harnett J, Ma Q, Jagannath S. Health-related quality of life with linvoseltamab treatment for relapsed/refractory multiple myeloma in LINKER-MM1. Blood Neoplasia. 2026 Mar 27;3(3):100225. doi: 10.1016/j.bneo.2026.100225. eCollection 2026 Aug.

    PubMed 42564571

  • Lowy JA, Rogers MF, Avigan ZM, Flores MS, Samuel M, Rattu MA, Richter J. Linvoseltamab, a BCMA-directed CD3 T-cell engager for multiple myeloma: a patient-centric option via a response-adapted dosing regimen. Expert Rev Hematol. 2026 Apr;19(4):361-372. doi: 10.1080/17474086.2026.2634283. Epub 2026 Mar 4.

    PubMed 41708325

  • Lee HC, Zonder JA, Dhodapkar MV, Jagannath S, Hoffman JE, Suvannasankha A, Shah MR, Lentzsch S, Baz R, Maly JJ, Namburi S, Pianko MJ, Ye JC, Wu KL, Silbermann R, Min CK, Vekemans MC, Munder M, Byun JM, Martinez-Lopez J, DeVeaux M, Roccia T, Chokshi D, Seraphin M, Knorr K, Boyapati A, Hazra A, Rodriguez Lorenc K, Kroog GS, Bumma N, Richter J. Linvoseltamab in Patients With Relapsed/Refractory Multiple Myeloma in the LINKER-MM1 Study: Longer Follow-Up and Subgroup Analyses. Clin Lymphoma Myeloma Leuk. 2026 Feb;26(2):e201-e212.e8. doi: 10.1016/j.clml.2025.11.004. Epub 2025 Nov 12.

    PubMed 41387038

  • Bumma N, Richter J, Jagannath S, Lee HC, Hoffman JE, Suvannasankha A, Zonder JA, Shah MR, Lentzsch S, Baz R, Maly JJ, Namburi S, Pianko MJ, Ye JC, Wu KL, Silbermann R, Min CK, Vekemans MC, Munder M, Byun JM, Martinez-Lopez J, Cassady K, DeVeaux M, Chokshi D, Boyapati A, Hazra A, Yancopoulos GD, Sirulnik LA, Rodriguez Lorenc K, Kroog GS, Houvras Y, Dhodapkar MV. Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma. J Clin Oncol. 2024 Aug 1;42(22):2702-2712. doi: 10.1200/JCO.24.01008. Epub 2024 Jun 16.

    PubMed 38879802

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Linvoseltamab in people with Multiple Myeloma, run by Regeneron Pharmaceuticals at 40 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States, Japan, Spain, South Korea, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trial Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period (time frame: Up to 28 days). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03761108, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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