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

NCT ID: NCT03761108

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

387 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-23

Study Completion Date

2033-06-16

Brief Summary

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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

Detailed Description

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Conditions

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Multiple Myeloma

Keywords

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Relapsed, Refractory

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Note: subcutaneous (SC) administration is not applicable for US.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type DRUG

Administered per the protocol

Linvoseltamab - Phase 2 - Cohort 1

Low Dose of linvoseltamab IV monotherapy.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type DRUG

Administered per the protocol

Linvoseltamab - Phase 2 - Cohort 2

High Dose of linvoseltamab IV monotherapy.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type DRUG

Administered per the protocol

Linvoseltamab - Phase 2 - Cohort 3

Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV linvoseltamab monotherapy

Note: Cohort 3 is not applicable for US.

Group Type EXPERIMENTAL

Linvoseltamab

Intervention Type DRUG

Administered per the protocol

Interventions

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Linvoseltamab

Administered per the protocol

Intervention Type DRUG

Other Intervention Names

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REGN5458 Lynozyfic™

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Moffitt Cancer Center - McKinley Drive

Tampa, Florida, United States

Site Status RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Indiana University_Michigan Street

Indianapolis, Indiana, United States

Site Status ACTIVE_NOT_RECRUITING

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status RECRUITING

C. S. Mott_University of Michigan

Ann Arbor, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status ACTIVE_NOT_RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Ohio State University James Cancer Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Oregon Health and Science University (OHSU) Marquam Hill Campus

Portland, Oregon, United States

Site Status RECRUITING

University of Texas MD Anderson Clinic

Houston, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

Swedish Cancer Institute

Seattle, Washington, United States

Site Status RECRUITING

ZNA Psychiatrisch Ziekenhuis Stuivenberg

Antwerp, , Belgium

Site Status RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status RECRUITING

Universitatsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Site Status COMPLETED

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, Rhineland-Palatinate, Germany

Site Status COMPLETED

Universitatsklinikum Wurzburg

Würzburg, , Germany

Site Status COMPLETED

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

Nagoya City University Hospital

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Site Status RECRUITING

Gunma University Hospital

Maebashi, Gunma, Japan

Site Status RECRUITING

Ibaraki Prefectural Central Hospital

Kasama-shi, Ibaraki, Japan

Site Status RECRUITING

University Hospital Kyoto Prefectural Univ of Medicine

Kyoto, Kyoto, Japan

Site Status RECRUITING

Saitama Medical University International Medical Center

Hidaka, Saitama, Japan

Site Status COMPLETED

Tokushima Prefectural Central Hospital

Tokushima, Tokushima, Japan

Site Status RECRUITING

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, Japan

Site Status RECRUITING

Keio University Hospital

Tokyo, , Japan

Site Status RECRUITING

Center for Hematologic Malignancy

Goyang-si, Gyeonggi-do, South Korea

Site Status RECRUITING

Seoul National University Cancer Hospital

Seoul, , South Korea

Site Status RECRUITING

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

Seoul, , South Korea

Site Status RECRUITING

Yonsei University College of Medicine, Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, Spain

Site Status RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Universitary Hospital La Princesa

Madrid, Salamanca, Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status RECRUITING

Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status WITHDRAWN

Countries

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United States Belgium Germany Japan South Korea Spain United Kingdom

Central Contacts

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Clinical Trial Administrator

Role: CONTACT

Phone: 844-734-6643

Email: [email protected]

References

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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. 2025 Nov 12:S2152-2650(25)04283-1. doi: 10.1016/j.clml.2025.11.004. Online ahead of print.

Reference Type DERIVED
PMID: 41387038 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38879802 (View on PubMed)

Other Identifiers

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2024-511454-45-00

Identifier Type: CTIS

Identifier Source: secondary_id

R5458-ONC-1826

Identifier Type: -

Identifier Source: org_study_id