A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Patients With Multiple Myeloma That is Resistant to Current Standard of Care Treatments

NCT05137054 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: R5458-ONC-20122020-004638-392023-506247-42-00
• Study Type: interventional
• Target: 317
• Locations: 5 countries
• Sites: 42

Brief Summary

This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again. In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies). This study is the first time linvoseltamab will be combined with other cancer therapies. The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination. The study is looking at several other research questions, including:

• How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma
• What side effects may happen from taking linvoseltamab together with another cancer treatment
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)

Conditions

Multiple Myeloma

Keywords

Relapsed/Refractory Multiple Myeloma (RRMM); B-cell maturation antigen (BCMA); Anti-CD3 monoclonal antibodies (mAbs)

Outcome Measures

Primary Outcomes (8)

• Incidence of pre-defined safety criteria or dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period

  Dose finding portion only

  Up to 28 Days

• Incidence of treatment-emergent adverse events (TEAEs)

  Up to 5 Years

• Severity of TEAEs

  Up to 5 Years

• Incidence of serious adverse events (SAEs)

  Up to 5 Years

• Severity of SAEs

  Up to 5 Years

• Incidence of adverse events of special interest (AESIs)

  Up to 5 Years

• Severity of AESIs

  Up to 5 Years

• Incidence of laboratory abnormalities

  ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\]

  Up to 5 Years

Secondary Outcomes (7)

• Objective response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria

  Up to 5 Years

• Duration of response (DOR) by IMWG criteria

  Up to 5 Years

• Progression-free survival (PFS) as measured by IMWG criteria

  Up to 5 Years

• Rate of minimal residual disease (MRD) negative status by IMWG criteria

  Up to 5 Years

• Concentrations of total linvoseltamab in serum over time

  Up to 5 Years

Study Arms (10)

Cohort 1: Linvoseltamab + Daratumumab

EXPERIMENTAL

Linvoseltamab + Daratumumab

Drug: Linvoseltamab; Drug: Daratumumab

Cohort 2: Linvolseltamab + Carfilzomib

EXPERIMENTAL

Linvoseltamab + Carfilzomib

Drug: Linvoseltamab; Drug: Carfilzomib

Cohort 3: Linvoseltamab + Lenalidomide

EXPERIMENTAL

Linvoseltamab + Lenalidomide

Drug: Linvoseltamab; Drug: Lenalidomide

Cohort 4: Linvoseltamab + Bortezomib

EXPERIMENTAL

Linvoseltamab + Bortezomib

Drug: Linvoseltamab; Drug: Bortezomib

Cohort 5: Linvoseltamab + Pomalidomide

EXPERIMENTAL

Linvoseltamab + Pomalidomide

Drug: Linvoseltamab; Drug: Pomalidomide

Cohort 6: Linvoseltamab + Isatuximab

EXPERIMENTAL

Linvoseltamab + Isatuximab

Drug: Linvoseltamab; Drug: Isatuximab

Cohort 7: Linvoseltamab + Fianlimab

EXPERIMENTAL

Linvoseltamab + Fianlimab

Drug: Linvoseltamab; Drug: Fianlimab

Cohort 8: Linvoseltamab + Cemiplimab

EXPERIMENTAL

Linvoseltamab + Cemiplimab

Drug: Linvoseltamab; Drug: Cemiplimab

Cohort 9: Linvoseltamab + Nirogacestat

EXPERIMENTAL

Linvoseltamab + Nirogacestat

Drug: Linvoseltamab; Drug: Nirogacestat

Cohort 10: Linvoseltamab + Cevostamab

EXPERIMENTAL

Linvoseltamab + Cevostamab

Drug: Linvoseltamab; Drug: Cevostamab

Interventions

Linvoseltamab DRUG

Linvoseltamab is administered by intravenous (IV) infusion

Also known as: REGN5458, Lynozyfic™

Cohort 10: Linvoseltamab + Cevostamab; Cohort 1: Linvoseltamab + Daratumumab; Cohort 2: Linvolseltamab + Carfilzomib; Cohort 3: Linvoseltamab + Lenalidomide; Cohort 4: Linvoseltamab + Bortezomib; Cohort 5: Linvoseltamab + Pomalidomide; Cohort 6: Linvoseltamab + Isatuximab; Cohort 7: Linvoseltamab + Fianlimab; Cohort 8: Linvoseltamab + Cemiplimab; Cohort 9: Linvoseltamab + Nirogacestat

Daratumumab DRUG

Daratumumab is administered by IV infusion and/or subcutaneous (SC) injection; SC injection may be used after a minimum of 2 cycles of IV administration at the investigator's discretion.

Also known as: Darzalex®; Darzalex Faspro™

Cohort 1: Linvoseltamab + Daratumumab

Carfilzomib DRUG

Carfilzomib is administered by IV infusion

Also known as: Kyprolis®

Cohort 2: Linvolseltamab + Carfilzomib

Lenalidomide DRUG

Lenalidomide is administered by mouth (PO) as a capsule

Also known as: Revlimid®

Cohort 3: Linvoseltamab + Lenalidomide

Bortezomib DRUG

Bortezomib is administered by IV infusion or SC injection

Also known as: Velcade®

Cohort 4: Linvoseltamab + Bortezomib

Pomalidomide DRUG

Pomalidomide is administered by mouth (PO) as a capsule

Also known as: Imnovid, Pomalyst®

Cohort 5: Linvoseltamab + Pomalidomide

Isatuximab DRUG

Isatuximab is administered by IV infusion

Also known as: Sarclisa®

Cohort 6: Linvoseltamab + Isatuximab

Fianlimab DRUG

Fianlimab is administered by IV infusion

Also known as: REGN3767

Cohort 7: Linvoseltamab + Fianlimab

Cemiplimab DRUG

Cemiplimab is administered by IV infusion

Also known as: LIBTAYO, REGN2810

Cohort 8: Linvoseltamab + Cemiplimab

Nirogacestat DRUG

Nirogacestat is administered by mouth (PO) as a tablet

Also known as: PF-03084014

Cohort 9: Linvoseltamab + Nirogacestat

Cevostamab DRUG

Cevostamab is administered by IV infusion

Also known as: BFCR4350A, RO7187797

Cohort 10: Linvoseltamab + Cevostamab

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
• Participants must have measurable disease as defined in the protocol according to International Myeloma Working Group (IMWG) consensus criteria
• Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
• Life expectancy of at least 6 months.
• For cohorts 1-6, each participant must have RRMM with progression following at least 3 lines of therapy, or at least 2 lines of therapy and either prior exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD) and 1 proteasome inhibitor (PI), or double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD.
• Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated. However, participants enrolled in the expansion portion cannot be refractory to an anti-CD38 antibody containing regimen. In addition, all participants must have at least a 6-month washout from prior anti-CD38 antibody therapy.
• Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose. Carfilzomib-refractory participants may enroll in the dose finding portion provided they are triple-class refractory (PI, IMiD, anti-CD38 antibody). However, participants enrolled in the dose expansion portion cannot be refractory to carfilzomib. In addition, all participants must have at least a 6-month washout from prior carfilzomib therapy.
• Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose. However, a participant cannot be refractory to any combination regimen that included 25 mg of lenalidomide. In addition, participants must have at least a 6-month washout from any prior lenalidomide therapy (including maintenance therapy).
• Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose. Bortezomib-refractory participants may enroll in the dose finding portion provided they are triple-class refractory (PI, IMiD, anti-CD38 antibody). However, participants enrolled in the dose expansion portion cannot be refractory to bortezomib. In addition, all participants must have at least a 6-month washout from prior bortezomib therapy.
• Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose. Additionally, participants must undergo at least a 6-month washout following prior pomalidomide therapy before enrollment.
• Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated. Additionally, participants must undergo at least a 3-month washout following prior anti-CD38 antibody therapy before enrollment.
• Cohort 7 and 8: RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1IMiD, and 1 PI or triple-class refractory disease (anti-CD38 antibody, IMiD, PI).
• Cohort 9: Progressive RRMM in participants with triple-class refractory disease (anti-CD38 antibody, IMiD, PI) after at least 3 lines of therapy Cohort 10: Progressive RRMM after at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI.

You may not qualify if:

• Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Participants with known MM brain lesions or meningeal involvement
• Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter
• History of allogeneic and autologous stem cell transplantation, as described in the protocol
• Unless stated otherwise in a specific sub-protocol, prior treatment with a T cell-based immunotherapy directed against BCMA bispecific antibodies and bispecific T-cell engagers (BiTEs), and BCMA chimeric antigen receptor (CAR) T cells (Note: BCMA antibody-drug conjugates are not excluded)
• History of progressive multifocal leukoencephalopathy, neurodegenerative condition or central nervous system (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded
• Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
• Cardiac ejection fraction \<40% by echocardiogram (Echo) or multigated acquisition (MUGA) scan.
• Cohort 2:
• Cohort 3:
• \. Known malabsorption syndrome or pre-existing gastrointestinal (GI) condition that may impair absorption of lenalidomide; delivery of lenalidomide via nasogastric tube or gastrostomy tube is not allowed.
• Cohort 4:
• \. Peripheral neuropathy grade ≥2
• Cohort 5:
• \. Known malabsorption syndrome or pre-existing GI conditions that may impair absorption of pomalidomide; delivery of pomalidomide via nasogastric tube or gastrostomy tube is not allowed.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (42)

Scripps Clinic Torrey Pines

La Jolla, California, 92037, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30004, United States

RECRUITING

Indiana University Health Simon Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Dana Farber/Harvard Cancer Center

Boston, Massachusetts, 02215, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Weill Cornell Medicine/New York Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

New York Presbyterian Hospital Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

The Ohio State University James Cancer Hospital

Columbus, Ohio, 43210, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

RECRUITING

CHU de Lille - Rue Michel Polonovski

Lille, Nord, 59037, France

SUSPENDED

Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, Nouvelle-Aquitaine, 86021, France

RECRUITING

Nantes University Hospital

Nantes, Pays de la Loire Region, 44093, France

RECRUITING

Centre Hospitalier Universitaire Angers

Angers, 49933, France

RECRUITING

CHU Montpellier - Departement D'Hematologie

Montpellier, 34295, France

RECRUITING

Saint Antoine Hospital

Paris, 75571, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Hospital Henri Mondor

Créteil, Île-de-France Region, 94000, France

RECRUITING

Saint Louis Hospital

Paris, Île-de-France Region, 75010, France

RECRUITING

Hopital Necker

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

RECRUITING

Evangelismos General Hospital

Athens, Attica, 10676, Greece

RECRUITING

General Hospital of Athens Alexandra

Athens, 11528, Greece

RECRUITING

Sheba Medical Center

Ramat Gan, Central District, 5265601, Israel

RECRUITING

Rambam Health Care Campus

Haifa, 3109601, Israel

RECRUITING

Hadassah Medical Center

Jerusalem, 91120, Israel

RECRUITING

Hospital Clinico Universitario de Santiago

Santiago de Compostela, A Coruna, 15706, Spain

RECRUITING

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, 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 Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,

Barcelona, 08908, Spain

RECRUITING

Universitaru Hospital La Princesa

Madrid, 28006, Spain

RECRUITING

Clinica Universidad de Navarra - Madrid

Madrid, 28027, Spain

RECRUITING

Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria

Madrid, 28034, Spain

RECRUITING

University Hospital and Research Institute

Madrid, 28041, Spain

RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

University Hospital of Salamanca

Salamanca, 37007, Spain

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; carfilzomib; Lenalidomide; Bortezomib; pomalidomide; isatuximab; cemiplimab; nirogacestat

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

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

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: November 30, 2021
• Study Start: August 17, 2022
• Primary Completion (Estimated): April 11, 2028
• Study Completion (Estimated): September 26, 2034
• Last Updated: January 22, 2026

Record last verified: 2025-05

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

US (13); FR (10); IL (3); GR (2); ES (14)