A Trial to Learn if Linvoseltamab is Safe and Works in Adults With Relapsed or Refractory Systemic Light Chain Amyloidosis (AL Amyloidosis)

NCT06292780 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: R5458-ONC-22742023-507809-34-00
• Study Type: interventional
• Target: 220
• Locations: 5 countries
• Sites: 19

Brief Summary

This study is researching an experimental drug called linvoseltamab ("study drug"). This study is focused on patients who have AL amyloidosis that has returned or have failed other therapies and need to be treated again. The study consists of 2 phases (Phase 1 and Phase 2):

• In Phase 1, linvoseltamab will be given to a small number of participants to study the side effects of the study drug and to determine the recommended doses of the study drug to be given to participants in Phase 2.
• In Phase 2, linvoseltamab will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of linvoseltamab to treat AL amyloidosis. The study is looking at several other research questions, including:
• How many participants treated with linvoseltamab have improvement in the abnormal proteins that cause organ problems and for how long
• How many participants treated with linvoseltamab have improvement in the heart or kidney and for how long
• What the right dosing regimen is for linvoseltamab
• What side effects may happen from taking linvoseltamab
• How much linvoseltamab is in the blood at different times
• Whether the body makes antibodies against linvoseltamab (which could make the drug less effective or could lead to side effects)

Conditions

Relapsed/Refractory Systemic Light Chain Amyloidosis

Keywords

Amyloid light-chain (AL); Multiple Myeloma (MM); Pathogenic light chains

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity (DLTs)

  Phase 1

  Up to 28 Days

• Achievement of hematologic complete response (CR) as determined by the Independent Review Committee (IRC)

  Phase 2

  Up to 3 years

Secondary Outcomes (33)

• Achievement of hematologic CR, as determined by the IRC

  Up to 3 years

• Achievement of hematologic very good partial response (VGPR) or better response (CR + VGPR), as determined by the IRC

  Up to 3 years

• Achievement of overall hematologic response (PR or better), as determined by the IRC

  Up to 3 years

• Time to initial hematologic response

  Up to 3 years

• Time to best hematologic response

  Up to 3 years

Study Arms (4)

Phase 1: Cohort 1: Low Dose

EXPERIMENTAL

Dose Escalation: Non-Randomized

Drug: Linvoseltamab

Phase 1: Cohort 2: High Dose

EXPERIMENTAL

Dose Escalation: Non-Randomized

Drug: Linvoseltamab

Phase 2: Low Dose

EXPERIMENTAL

Dose Expansion: Participants will be randomized in a 1:1 ratio

Drug: Linvoseltamab

Phase 2: High Dose

EXPERIMENTAL

Dose Expansion: Participants will be randomized in a 1:1 ratio

Drug: Linvoseltamab

Interventions

Linvoseltamab DRUG

anti-B-cell maturation antigen x anti-Cluster of differentiation 3 bispecific antibody

Also known as: REGN5458, Lynozyfic™

Phase 1: Cohort 1: Low Dose; Phase 1: Cohort 2: High Dose; Phase 2: High Dose; Phase 2: Low Dose

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of AL amyloidosis, as described in the protocol
• Measurable disease as defined by serum difference between involved and uninvolved free light chains (dFLC) concentration, as described in the protocol
• Previously treated after at least 1 prior therapy and requiring further treatment as assessed by the Investigator
• N-terminal pro b-type natriuretic peptide (NT-proBNP) ≤8500 ng/L during screening
• Adequate hepatic, hematologic, renal, and cardiac function, as described in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance score ≤2 at screening

You may not qualify if:

• History of other non-AL amyloidosis
• Greater than 60% plasmacytosis on a bone marrow biopsy and/or aspirate during screening
• Presence of lytic bone lesion(s) or extramedullary plasmacytoma on imaging during screening
• Myocardial infarction within the past 6 months prior to the first screening visit
• Known active infection requiring hospitalization or treatment with IV anti-infectives within 28 days of first administration of study drug

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (19)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Colorado Blood Cancer Institute/SCRI

Denver, Colorado, 80218, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

National and Kapodistrian University of Athens

Athens, 11528, Greece

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

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

Seoul, 065791, South Korea

RECRUITING

Hospital Universitari Son Espases

Palma, Balearic Islands, 07120, Spain

RECRUITING

Clinica Universidad de Navarra - Pamplona

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital de Cabuenes

Gijón, Principality of Asturias, 33203, Spain

RECRUITING

Universität de Barcelona- Institut d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS)

Barcelona, 08036, Spain

RECRUITING

University Hospital La Fe

Valencia, 46026, Spain

RECRUITING

University College London Hospitals

London, NW1 2PG, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials 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

Model Details: Note: Participants enrolled in Phase 2 will be randomized 1:1

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 5, 2024
• Study Start: August 7, 2024
• Primary Completion (Estimated): August 20, 2028
• Study Completion (Estimated): February 20, 2035
• Last Updated: April 29, 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 can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

GR (1); KR (4); ES (5); US (7); GB (2)