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

NCT03761108 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: R5458-ONC-18262024-511454-45-00
• Study Type: interventional
• Target: 387
• Locations: 7 countries
• Sites: 40

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

Conditions

Multiple Myeloma

Keywords

Relapsed, Refractory

Outcome Measures

Primary Outcomes (8)

• 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

  Up to 28 days

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

  Phase 1

  Up to 5 years

• Incidence and severity of adverse events of special interest (AESI)

  Phase 1

  Up to 5 years

• Assessment of the pharmacokinetics (PK) of linvoseltamab

  Phase 1 part 2

  Up to 5 years

• Concentrations of linvoseltamab in serum over time

  Phase 2, for Japanese cohort only

  Up to 5 years

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

  Phase 2, cohorts 1 and 2

  Up to 5 years

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

  Phase 2, cohort 3

  Up to 5 years

• ORR of IV linvoseltamab as assessed by investigator

  Phase 2, cohort 3

  Up to 5 years

Secondary Outcomes (23)

• Concentrations of linvoseltamab in the serum over time

  Up to 5 years

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

  Up to 5 years

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

  Up to 5 years

• Incidence of neutralizing antibodies (NAb) to linvoseltamab over time

  Up to 5 years

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

  Up to 5 years

Study Arms (4)

Linvoseltamab - Phase 1

EXPERIMENTAL

Phase 1 has two parts. Part 1, consists of linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration.

Drug: Linvoseltamab

Linvoseltamab - Phase 2 - Cohort 1

EXPERIMENTAL

Low Dose of linvoseltamab IV monotherapy.

Drug: Linvoseltamab

Linvoseltamab - Phase 2 - Cohort 2

EXPERIMENTAL

High Dose of linvoseltamab IV monotherapy.

Drug: Linvoseltamab

Linvoseltamab - Phase 2 - Cohort 3

EXPERIMENTAL

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

Drug: Linvoseltamab

Interventions

Linvoseltamab DRUG

Administered per the protocol

Also known as: REGN5458, Lynozyfic™

Linvoseltamab - Phase 1; Linvoseltamab - Phase 2 - Cohort 1; Linvoseltamab - Phase 2 - Cohort 2; Linvoseltamab - Phase 2 - Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (40)

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

ACTIVE NOT RECRUITING

Moffitt Cancer Center - McKinley Drive

Tampa, Florida, 33612, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Indiana University_Michigan Street

Indianapolis, Indiana, 46202, United States

ACTIVE NOT RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

RECRUITING

C. S. Mott_University of Michigan

Ann Arbor, Michigan, 48109, United States

ACTIVE NOT RECRUITING

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, 48201, United States

ACTIVE NOT RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

ACTIVE NOT RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Ohio State University James Cancer Hospital

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health and Science University (OHSU) Marquam Hill Campus

Portland, Oregon, 97239, United States

RECRUITING

University of Texas MD Anderson Clinic

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

ZNA Psychiatrisch Ziekenhuis Stuivenberg

Antwerp, 2060, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Universitatsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

COMPLETED

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, Rhineland-Palatinate, 55131, Germany

COMPLETED

Universitatsklinikum Wurzburg

Würzburg, 6 97080, Germany

COMPLETED

Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital

Nagoya, Aichi-ken, 466-8650, Japan

COMPLETED

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

Gunma University Hospital

Maebashi, Gunma, 371-8511, Japan

RECRUITING

Ibaraki Prefectural Central Hospital

Kasama-shi, Ibaraki, 309-1793, Japan

RECRUITING

University Hospital Kyoto Prefectural Univ of Medicine

Kyoto, Kyoto, 602-8566, Japan

RECRUITING

Saitama Medical University International Medical Center

Hidaka, Saitama, 350-1298, Japan

COMPLETED

Tokushima Prefectural Central Hospital

Tokushima, Tokushima, 770-8539, Japan

RECRUITING

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, 150-8935, Japan

COMPLETED

Keio University Hospital

Tokyo, 160-8582, Japan

RECRUITING

National Cancer Center Korea

Goyang, 10408, South Korea

RECRUITING

Seoul National University Cancer Hospital

Seoul, 03080, South Korea

RECRUITING

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

Seoul, 06591, South Korea

RECRUITING

Yonsei University College of Medicine, Severance Hospital

Seoul, 3722, South Korea

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Universitary Hospital La Princesa

Madrid, Salamanca, 28006, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

WITHDRAWN

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trial Administrator

CONTACT

844-734-6643; clinicaltrials@regeneron.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 3, 2018
• Study Start: January 23, 2019
• Primary Completion (Estimated): March 30, 2033
• Study Completion (Estimated): June 16, 2033
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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
• 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.

Locations

BE (2); US (14); JP (10); ES (6); GB (1); DE (3); KR (4)