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NCT03761108 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1, PHASE2
Status at capture
RECRUITING
Registry last update
2026-04-20

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Phase 1 has two parts. Part 1, consists of linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration.
    intervention Names
    1. Drug: Linvoseltamab
    label
    Linvoseltamab - Phase 1
    type
    EXPERIMENTAL
  2. description
    Low Dose of linvoseltamab IV monotherapy.
    intervention Names
    1. Drug: Linvoseltamab
    label
    Linvoseltamab - Phase 2 - Cohort 1
    type
    EXPERIMENTAL
  3. description
    High Dose of linvoseltamab IV monotherapy.
    intervention Names
    1. Drug: Linvoseltamab
    label
    Linvoseltamab - Phase 2 - Cohort 2
    type
    EXPERIMENTAL
  4. description
    Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV linvoseltamab monotherapy.
    intervention Names
    1. Drug: Linvoseltamab
    label
    Linvoseltamab - Phase 2 - Cohort 3
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Linvoseltamab - Phase 1
    2. Linvoseltamab - Phase 2 - Cohort 1
    3. Linvoseltamab - Phase 2 - Cohort 2
    4. Linvoseltamab - Phase 2 - Cohort 3
    description
    Administered per the protocol
    name
    Linvoseltamab
    other Names
    1. REGN5458
    2. Lynozyfic™
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
387
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Phase 1 and Phase 2 for Japanese cohort only
    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
  2. description
    Phase 1
    measure
    Incidence and severity of treatment-emergent adverse events (TEAEs)
    time Frame
    Up to 5 years
  3. description
    Phase 1
    measure
    Incidence and severity of adverse events of special interest (AESI)
    time Frame
    Up to 5 years
  4. description
    Phase 1 part 2
    measure
    Assessment of the pharmacokinetics (PK) of linvoseltamab
    time Frame
    Up to 5 years
  5. description
    Phase 2, for Japanese cohort only
    measure
    Concentrations of linvoseltamab in serum over time
    time Frame
    Up to 5 years
  6. description
    Phase 2, cohorts 1 and 2
    measure
    Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
    time Frame
    Up to 5 years
  7. description
    Phase 2, cohort 3
    measure
    Incidence and severity of cytokine release syndrome (CRS) with linvoseltamab
    time Frame
    Up to 5 years
  8. description
    Phase 2, cohort 3
    measure
    ORR of IV linvoseltamab as assessed by investigator
    time Frame
    Up to 5 years
secondary Outcomes
  1. description
    Phase 1 part 1 and Phase 2
    measure
    Concentrations of linvoseltamab in the serum over time
    time Frame
    Up to 5 years
  2. description
    Phase 1 and Phase 2
    measure
    Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab
    time Frame
    Up to 5 years
  3. description
    Phase 1 and Phase 2
    measure
    Titer of anti-drug antibodies (ADAs) to linvoseltamab over time
    time Frame
    Up to 5 years
  4. description
    Phase 1 and Phase 2
    measure
    Incidence of neutralizing antibodies (NAb) to linvoseltamab over time
    time Frame
    Up to 5 years
  5. description
    Phase 2, cohorts 1 and 2
    measure
    Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria
    time Frame
    Up to 5 years
  6. description
    Phase 1 and Phase 2
    measure
    DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria
    time Frame
    Up to 5 years
  7. description
    Phase 2
    measure
    Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria
    time Frame
    Up to 5 years
  8. description
    Phase 1 and Phase 2
    measure
    PFS as determined by an investigator, measured using the IMWG criteria
    time Frame
    Up to 5 years
  9. description
    Phase 1
    measure
    Rate of minimal residual disease (MRD) negative status, using the IMWG criteria
    time Frame
    Up to 5 years
  10. description
    Phase 2
    measure
    Rate of MRD negative status
    time Frame
    Up to 5 years
  11. description
    Phase 1 and Phase 2
    measure
    Overall survival (OS)
    time Frame
    Up to 5 years
  12. description
    Phase 1, part 1 dose level 7 (DL7)
    measure
    ORR as measured as determined by blinded IRC, as measured using the IMWG criteria
    time Frame
    Up to 5 years
Full study description
brief 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. 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
Source references
references
  1. citation
    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.
    pmid
    42564571
    type
    DERIVED
  2. citation
    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.
    pmid
    41708325
    type
    DERIVED
  3. citation
    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.
    pmid
    41387038
    type
    DERIVED
  4. citation
    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.
    pmid
    38879802
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
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        d on <a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">Drugs@FDA</a>.</p><h2>Efficacy and Safety</h2><p>Efficacy was evaluated in LINKER-MM1 (NCT03761108), an open-label, multi-center multi-cohort trial. The trial included patients who had previously received at least 3 prior therapies, including a PI, an IMiD,
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      source event date
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      source file
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      FDA grants accelerated approval to linvoseltamab-gcpt for relapsed or refractory multiple myeloma

    Preserved source evidence · Not medical advice