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
NCT ID: NCT05137054
Last Updated: 2026-01-22
Study Results
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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RECRUITING
PHASE1
317 participants
INTERVENTIONAL
2022-08-17
2034-09-26
Brief Summary
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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)
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Cohort 1: Linvoseltamab + Daratumumab
Linvoseltamab + Daratumumab
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Daratumumab
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.
Cohort 2: Linvolseltamab + Carfilzomib
Linvoseltamab + Carfilzomib
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Carfilzomib
Carfilzomib is administered by IV infusion
Cohort 3: Linvoseltamab + Lenalidomide
Linvoseltamab + Lenalidomide
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Lenalidomide
Lenalidomide is administered by mouth (PO) as a capsule
Cohort 4: Linvoseltamab + Bortezomib
Linvoseltamab + Bortezomib
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Bortezomib
Bortezomib is administered by IV infusion or SC injection
Cohort 5: Linvoseltamab + Pomalidomide
Linvoseltamab + Pomalidomide
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Pomalidomide
Pomalidomide is administered by mouth (PO) as a capsule
Cohort 6: Linvoseltamab + Isatuximab
Linvoseltamab + Isatuximab
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Isatuximab
Isatuximab is administered by IV infusion
Cohort 7: Linvoseltamab + Fianlimab
Linvoseltamab + Fianlimab
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Fianlimab
Fianlimab is administered by IV infusion
Cohort 8: Linvoseltamab + Cemiplimab
Linvoseltamab + Cemiplimab
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Cemiplimab
Cemiplimab is administered by IV infusion
Cohort 9: Linvoseltamab + Nirogacestat
Linvoseltamab + Nirogacestat
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Nirogacestat
Nirogacestat is administered by mouth (PO) as a tablet
Cohort 10: Linvoseltamab + Cevostamab
Linvoseltamab + Cevostamab
Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Cevostamab
Cevostamab is administered by IV infusion
Interventions
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Linvoseltamab
Linvoseltamab is administered by intravenous (IV) infusion
Daratumumab
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.
Carfilzomib
Carfilzomib is administered by IV infusion
Lenalidomide
Lenalidomide is administered by mouth (PO) as a capsule
Bortezomib
Bortezomib is administered by IV infusion or SC injection
Pomalidomide
Pomalidomide is administered by mouth (PO) as a capsule
Isatuximab
Isatuximab is administered by IV infusion
Fianlimab
Fianlimab is administered by IV infusion
Cemiplimab
Cemiplimab is administered by IV infusion
Nirogacestat
Nirogacestat is administered by mouth (PO) as a tablet
Cevostamab
Cevostamab is administered by IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Participants must have measurable disease as defined in the protocol according to International Myeloma Working Group (IMWG) consensus criteria
3. Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
4. 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.
Exclusion Criteria
2. Participants with known MM brain lesions or meningeal involvement
3. 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
4. History of allogeneic and autologous stem cell transplantation, as described in the protocol
5. 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)
6. 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
7. Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
8. Cardiac ejection fraction \<40% by echocardiogram (Echo) or multigated acquisition (MUGA) scan.
Cohort 2:
1\. Dose expansion: Prior treatment with a B-cell maturation antigen (BCMA) -directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment
Cohort 3:
1\. 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:
1\. Peripheral neuropathy grade ≥2
Cohort 5:
1\. 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.
Cohort 7:
1. Prior treatment with anti-lymphocyte activation gene 3 (LAG-3) agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-programmed cell death protein 1 (PD-1) antibodies is permitted, as described in the protocol.
2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
3. Prior solid organ transplant.
4. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies.
Cohort 8:
1. Prior treatment with anti-PD-1 or anti-PD-L1 agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies is permitted, as described in the protocol.
2. Encephalitis or meningitis in the year prior to enrollment.
3. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment.
4. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
5. Prior solid organ transplant.
6. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies.
Cohort 9:
1. Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol
2. Use of concomitant medications that are known to prolong the QT/QTcF interval including Class Ia and Class III antiarrhythmics at the time of informed consent
3. Ongoing use or anticipated use of food or drugs that are known strong/moderate cytochrome P450 (CYP)3A4 inhibitors, or strong CYP3A inducers within 14 days prior to first dose of nirogacestat
4. Known malabsorption syndrome or existing gastrointestinal GI condition that may impair absorption of nirogacestat; delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed.
Cohort 10:
1. Known or suspected active Epstein-Barr virus (EBV) infection.
2. Known history of Hemophagocytic lymphohistiocytosis/Macrophage activation syndrome (HLH/MAS).
3. Prior treatment with cevostamab or another agent with the same target \[Fragment crystallizable receptor-like 5 (FcRH5)\].
18 Years
ALL
No
Sponsors
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Regeneron Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trial Management
Role: STUDY_DIRECTOR
Regeneron Pharmaceuticals
Locations
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Scripps Clinic Torrey Pines
La Jolla, California, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Indiana University Health Simon Cancer Center
Indianapolis, Indiana, United States
Dana Farber/Harvard Cancer Center
Boston, Massachusetts, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Weill Cornell Medicine/New York Presbyterian Hospital
New York, New York, United States
New York Presbyterian Hospital Columbia University Medical Center
New York, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
The Ohio State University James Cancer Hospital
Columbus, Ohio, United States
University of Texas Southwestern
Dallas, Texas, United States
VA Puget Sound Health Care System
Seattle, Washington, United States
CHU de Lille - Rue Michel Polonovski
Lille, Nord, France
Centre Hospitalier Universitaire (CHU) de Poitiers
Poitiers, Nouvelle-Aquitaine, France
Nantes University Hospital
Nantes, Pays de la Loire Region, France
Centre Hospitalier Universitaire Angers
Angers, , France
CHU Montpellier - Departement D'Hematologie
Montpellier, , France
Saint Antoine Hospital
Paris, , France
Institut Gustave Roussy
Villejuif, , France
Hospital Henri Mondor
Créteil, Île-de-France Region, France
Saint Louis Hospital
Paris, Île-de-France Region, France
Hopital Necker
Paris, Île-de-France Region, France
Evangelismos General Hospital
Athens, Attica, Greece
General Hospital of Athens Alexandra
Athens, , Greece
Sheba Medical Center
Ramat Gan, Central District, Israel
Rambam Health Care Campus
Haifa, , Israel
Hadassah Medical Center
Jerusalem, , Israel
Hospital Clinico Universitario de Santiago
Santiago de Compostela, A Coruna, Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
Hospital Universitario Quiron Salud Madrid
Pozuelo de Alarcón, Madrid, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, Spain
Hospital Universitario Vall d'Hebron
Barcelona, , Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,
Barcelona, , Spain
Universitaru Hospital La Princesa
Madrid, , Spain
Clinica Universidad de Navarra - Madrid
Madrid, , Spain
Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria
Madrid, , Spain
University Hospital and Research Institute
Madrid, , Spain
Hospital Universitario HM Sanchinarro
Madrid, , Spain
University Hospital of Salamanca
Salamanca, , Spain
Countries
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Central Contacts
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Other Identifiers
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2020-004638-39
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-506247-42-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
R5458-ONC-2012
Identifier Type: -
Identifier Source: org_study_id
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