A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment

NCT05828511 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: R5458-ONC-21582022-500800-24-00
• Study Type: interventional
• Target: 149
• Locations: 3 countries
• Sites: 32

Brief Summary

This study is researching an experimental drug called linvoseltamab (called "study drug"). The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy with autologous stem cell transplantation (transplant-eligible) or ineligible for autologous stem cell transplantation (transplant-ineligible). The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM. This study consists of 2 phases:

• In Phase 1 Parts A and B, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2.
• In Phase 1 Part C, the study drug will be given to participants to study the side effects when using different initial doses of the study drug.
• In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the activity of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM. The study is looking at several research questions, including:
• What side effects may happen from taking linvoseltamab?
• What the right dosing regimen is for linvoseltamab?
• How many participants treated with linvoseltamab have improvement of their disease and for how long?
• The effects of linvoseltamab study treatment before and after transplant
• 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

Multiple Myeloma

Keywords

Newly Diagnosed Multiple Myeloma (NDMM); Autologous Stem Cell Transplantation (ASCT); Cluster of Differentiation 3 (CD3); BCMA; High Dose chemoTherapy (HDT); International Myeloma Working Group (IMWG)

Outcome Measures

Primary Outcomes (10)

• Incidence of Dose-Limiting Toxicities (DLTs)

  Phase 1

  End of the Observation period; up to day 28

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  Phase 1

  Post-Last Linvoseltamab Dose, up to 90 days

• Severity of TEAEs

  Phase 1

  Post-Last Linvoseltamab Dose, up to 90 days

• Incidence of Adverse Events of Special Interest (AESIs)

  Phase 1

  Post-Last Linvoseltamab Dose, up to 90 days

• Severity of AESIs

  Phase 1

  Post-Last Linvoseltamab Dose, up to 90 days

• Proportion of participants with a Very Good Partial Response (VGPR) or better using the International Myeloma Working Group (IMWG) response criteria

  Phase 2

  Up to 5 years

• Proportion of participants achieving Minimal Residual Disease (MRD) negative status (at 10^-5) after induction with consolidation therapy

  Phase 2 Transplant-eligible cohort

  Up to 5 years

• Proportion of participants achieving MRD-negative status (at 10^-5) after induction without consolidation therapy

  Phase 2 Transplant-eligible cohort

  Up to 5 years

• Proportion of participants achieving MRD-negative status as their best response after treatment period I with continuing to treatment period II

  Phase 2 Transplant-ineligible cohort

  Up to 5 years

• Proportion of participants achieving MRD-negative status as their best response after treatment period I without continuing to treatment period II

  Phase 2 Transplant ineligible cohort

  Up to 5 years

Secondary Outcomes (28)

• Concentrations of Linvoseltamab in serum

  Post-Last Linvoseltamab Dose, up to 12 weeks

• Concentrations of total soluble B-Cell Maturation Antigen (BCMA)

  Post-Last Linvoseltamab Dose, up to 12 weeks

• Incidence of Anti-Drug Antibodies (ADAs) to Linvoseltamab

  Post-Last Linvoseltamab Dose, up to 30 days

• Magnitude of ADAs to Linvoseltamab

  Post-Last Linvoseltamab Dose, up to 30 days

• Objective Response Rate (ORR) measured using the IMWG criteria

  Up to 5 years

Study Arms (3)

Phase 1 cohorts

EXPERIMENTAL

Linvoseltamab dose escalation (part A), dose expansion (part B), and evaluation of alternative step-up regimen (part C) for participants with NDMM who are treatment-naïve.

Drug: Linvoseltamab

Phase 2 - transplant ineligible cohort

EXPERIMENTAL

Transplant-ineligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen until disease progression as per protocol.

Drug: Linvoseltamab

Phase 2 - transplant eligible cohort

EXPERIMENTAL

Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol

Drug: Linvoseltamab

Interventions

Linvoseltamab DRUG

Linvoseltamab will be administered by intravenous (IV) infusion

Also known as: REGN5458, Lynozyfic™

Phase 1 cohorts; Phase 2 - transplant eligible cohort; Phase 2 - transplant ineligible cohort

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 of 0, 1, or 2
• Confirmed diagnosis of symptomatic Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnosis criteria, as described in the protocol
• Response-evaluable myeloma, according to the 2016 IMWG response criteria, as defined in the protocol
• No prior therapy for MM, with the exception of prior emergent or palliative radiation and up to 1 month of single-agent corticosteroids, with washout periods as per the protocol
• Participants must have evidence of adequate bone marrow reserves and hepatic, renal and cardiac function as defined in the protocol
• Participants must be age \<70 and have adequate hepatic, renal, pulmonary and cardiac function to be considered transplant-eligible. The specific thresholds for adequate organ function are as per institutional guidance.

You may not qualify if:

• Receiving any concurrent investigational agent with known or suspected activity against MM, or agents targeting the A proliferation-inducing ligand (APRIL)/ Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)/BCMA axis
• Known Central Nervous System (CNS) involvement with MM, known or suspected Progressive Multifocal Leukoencephalopathy (PML), a history of neurocognitive conditions, or CNS movement disorder, or history of seizure within 12 months prior to study enrollment
• Rapidly progressive symptomatic disease, (e.g. progressing renal failure or hypercalcemia not responsive to standard medical interventions), in urgent need of treatment with chemotherapy
• Diagnosis of non-secretory MM, active plasma cell leukemia primary light-chain (AL) amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (Plasma cell dyscrasia with polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (32)

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

RECRUITING

UC Irvine Health

Orange, California, 92868, United States

RECRUITING

Colorado Blood Cancer Institute/SCRI

Denver, Colorado, 80218, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

Perlmutter Cancer Center

New York, New York, 10016, United States

RECRUITING

Columbia University _ New York Presbyterian

New York, New York, 10032, United States

RECRUITING

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke University Health System (DUHS)

Durham, North Carolina, 27705, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, Nouvelle-Aquitaine, 86021, France

RECRUITING

CHU De Lille

Lille, 59000, France

NOT YET RECRUITING

Centre Hospitalier Universitaire (CHU) Montpellier

Montpellier, 342950, France

RECRUITING

Hopital Saint Louis

Paris, 75010, France

RECRUITING

University Hospitals Pitie Salpetriere - Charles Foix

Paris, 75651, France

RECRUITING

Hopital Prive d'Antony

Antony, Île-de-France Region, 92160, France

RECRUITING

Hopital Necker

Paris, Île-de-France Region, 75015, France

RECRUITING

Gustave Roussy

Villejuif, Île-de-France Region, 94800, France

RECRUITING

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital Universitario Quiron Salud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital General Universitario Doctor Balmis Alicante

Alicante, Valencia, 03010, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Institut Catala dOncologia (ICO Hospitalet)

Barcelona, 08908, Spain

RECRUITING

Universitary Hospital La Princesa

Madrid, 28006, Spain

RECRUITING

Clinica Universidad de Navarra - Madrid

Madrid, 28027, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

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

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: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: April 25, 2023
• Study Start: December 19, 2023
• Primary Completion (Estimated): November 2, 2035
• Study Completion (Estimated): November 2, 2035
• Last Updated: March 19, 2026

Record last verified: 2026-03

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

ES (11); US (13); FR (8)