Linvolseltamab (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Andre kræftbehandlinger til deltagere med recidiverende/refraktær myelomatose (LINKER-MM2)
Fase 1b undersøgelse af REGN5458 (Anti-BCMA x Anti-CD3 bispecifikt antistof) plus andre kræftbehandlinger til patienter med recidiverende/refraktær myelomatose
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)
Studieoversigt
Status
Betingelser
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Clinical Trials Administrator
- Telefonnummer: 844-734-6643
- E-mail: clinicaltrials@regeneron.com
Studiesteder
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California
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La Jolla, California, Forenede Stater, 92037
- Rekruttering
- Scripps Clinic Torrey Pines
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Georgia
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Atlanta, Georgia, Forenede Stater, 30004
- Rekruttering
- Winship Cancer Institute of Emory University
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Rekruttering
- Indiana University Health Simon Cancer Center
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Rekruttering
- Dana Farber/Harvard Cancer Center
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Michigan
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Detroit, Michigan, Forenede Stater, 48201
- Rekruttering
- Karmanos Cancer Institute
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Rekruttering
- Mayo Clinic
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New York
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New York, New York, Forenede Stater, 10021
- Rekruttering
- Weill Cornell Medicine/New York Presbyterian Hospital
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New York, New York, Forenede Stater, 10032
- Rekruttering
- New York Presbyterian Hospital Columbia University Medical Center
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599
- Rekruttering
- University of North Carolina at Chapel Hill
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Winston-Salem, North Carolina, Forenede Stater, 27157
- Rekruttering
- Wake Forest University Health Sciences
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Ohio
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Columbus, Ohio, Forenede Stater, 43210
- Rekruttering
- The Ohio State University James Cancer Hospital
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Texas
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Dallas, Texas, Forenede Stater, 75390
- Rekruttering
- University of Texas Southwestern
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Washington
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Seattle, Washington, Forenede Stater, 98108
- Rekruttering
- VA Puget Sound Health Care System
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Angers, Frankrig, 49933
- Rekruttering
- Centre Hospitalier Universitaire Angers
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Montpellier, Frankrig, 34295
- Rekruttering
- CHU Montpellier - Departement D'Hematologie
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Paris, Frankrig, 75571
- Rekruttering
- Saint Antoine Hospital
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Villejuif, Frankrig, 94805
- Rekruttering
- Institut Gustave Roussy
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New Aquitaine
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Poitiers, New Aquitaine, Frankrig, 86021
- Rekruttering
- Centre Hospitalier Universitaire (CHU) de Poitiers
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Nord
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Lille, Nord, Frankrig, 59037
- Rekruttering
- CHU de Lille - Rue Michel Polonovski
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Pays de la Loire Region
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Nantes, Pays de la Loire Region, Frankrig, 44093
- Rekruttering
- Nantes University Hospital
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Île-de-France Region
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Créteil, Île-de-France Region, Frankrig, 94000
- Rekruttering
- Hospital Henri Mondor
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Paris, Île-de-France Region, Frankrig, 75015
- Rekruttering
- Hopital Necker
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Paris, Île-de-France Region, Frankrig, 75010
- Rekruttering
- Saint Louis Hospital
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Athens, Grækenland, 11528
- Rekruttering
- General Hospital of Athens Alexandra
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Attica
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Athens, Attica, Grækenland, 10676
- Rekruttering
- Evangelismos General Hospital
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Haifa, Israel, 3109601
- Rekruttering
- Rambam Health Care Campus
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Jerusalem, Israel, 91120
- Rekruttering
- Hadassah Medical Center
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Central District
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Ramat Gan, Central District, Israel, 5265601
- Rekruttering
- Sheba Medical Center
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Barcelona, Spanien, 08035
- Rekruttering
- Hospital Universitario Vall d'Hebron
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Barcelona, Spanien, 08036
- Rekruttering
- Hospital Clinic de Barcelona
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Barcelona, Spanien, 08908
- Rekruttering
- Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,
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Madrid, Spanien, 28050
- Rekruttering
- Hospital Universitario HM Sanchinarro
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Madrid, Spanien, 28027
- Rekruttering
- Clinica Universidad de Navarra - Madrid
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Madrid, Spanien, 28006
- Rekruttering
- Universitaru Hospital La Princesa
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Madrid, Spanien, 28041
- Rekruttering
- University Hospital and Research Institute
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Madrid, Spanien, 28034
- Rekruttering
- Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria
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Salamanca, Spanien, 37007
- Rekruttering
- University Hospital of Salamanca
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A Coruna
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Santiago de Compostela, A Coruna, Spanien, 15706
- Rekruttering
- Hospital Clinico Universitario de Santiago
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Barcelona
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Badalona, Barcelona, Spanien, 08916
- Rekruttering
- Hospital Germans Trias i Pujol
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Cantabria
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Santander, Cantabria, Spanien, 39008
- Rekruttering
- Hospital Universitario Marques de Valdecilla
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Madrid
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Pozuelo de Alarcón, Madrid, Spanien, 28223
- Rekruttering
- Hospital Universitario Quiron Salud Madrid
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Navarre
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Pamplona, Navarre, Spanien, 31008
- Rekruttering
- Clinica Universidad de Navarra
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
General Key Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Participants must have measurable disease as defined in the protocol according to IMWG consensus criteria
- Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
- Life expectancy of at least 6 months
Cohort Specific Inclusion Criteria:
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, as described in the protocol Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated, as described in the protocol
Cohort 7 and 8:
- For participants without measurable disease by biochemical parameters [serum or urine M-protein, or serum involved Free Light Chain (FLC)], presence of at least 1 soft tissue plasmacytoma with a single diameter of ≥2 cm
- RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, 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
General Key Exclusion Criteria:
- 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 B-Cell Maturation Antigen (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 Specific Exclusion Criteria:
Cohort 2: Dose expansion: Prior treatment with a BCMA-directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment 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
Cohort 7:
- 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
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol
- Prior solid organ transplant
- 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:
- 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
- Encephalitis or meningitis in the year prior to enrollment
- 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
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
- Prior solid organ transplant
- 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:
- Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol
- 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
- 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
- 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:
- Known or suspected active Epstein-Barr Virus (EBV) infection
- Known history of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)
- Prior treatment with cevostamab or another agent with the same target [Fragment crystallizable Receptor-like 5 (FcRH5)]
Dose finding portion: Prior treatment with any BCMA-directed immunotherapy will not be exclusionary, as described in the protocol Dose expansion portion: Prior treatment with any T cell-engaging bispecific antibody directed against BCMA will be exclusionary, as described in the protocol
NOTE: Other protocol defined inclusion/exclusion criteria apply
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Cohort 1: Linvoseltamab + Daratumumab
Linvoseltamab + Daratumumab |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 2: Linvoseltamab + Carfilzomib
Linvoseltamab + Carfilzomib |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 3: Linvoseltamab + Lenalidomide
Linvoseltamab + Lenalidomide |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 4: Linvoseltamab + Bortezomib
Linvoseltamab + Bortezomib |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 5: Linvoseltamab + Pomalidomide
Linvoseltamab + Pomalidomide |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 6: Linvoseltamab + Isatuximab
Linvoseltamab + Isatuximab |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 7: Linvoseltamab + Fianlimab
Linvoseltamab + Fianlimab |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 8: Linvoseltamab + Cemiplimab
Linvoseltamab + Cemiplimab |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 9: Linvoseltamab + Nirogacestat
Linvoseltamab + Nirogacestat |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Eksperimentel: Cohort 10: Linvoseltamab + Cevostamab
Linvoseltamab + Cevostamab |
Administered per the protocol
Andre navne:
Administered per the protocol
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Forekomst af alvorlige bivirkninger (SAE)
Tidsramme: Op til 5 år
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Op til 5 år
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Sværhedsgraden af TEAE'er
Tidsramme: Op til 5 år
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Op til 5 år
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Sværhedsgraden af SAE'er
Tidsramme: Op til 5 år
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Op til 5 år
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Sværhedsgraden af AESI'er
Tidsramme: Op til 5 år
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Op til 5 år
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Incidence of Treatment-Emergent Adverse Events (TEAEs)
Tidsramme: Up to 5 Years
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Up to 5 Years
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Incidence of Adverse Events of Special Interest (AESIs)
Tidsramme: Up to 5 Years
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Up to 5 Years
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Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period
Tidsramme: Up to 28 Days
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Dose finding portion only |
Up to 28 Days
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Incidence of laboratory abnormalities
Tidsramme: Up to 5 Years
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≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0] |
Up to 5 Years
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Samlet overlevelse (OS)
Tidsramme: Op til 5 år
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Op til 5 år
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Koncentrationer af total linvoseltamab i serum over tid
Tidsramme: Op til 5 år
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Op til 5 år
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Overall Response Rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria
Tidsramme: Up to 5 Years
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Up to 5 Years
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Duration of Response (DOR) by IMWG criteria
Tidsramme: Up to 5 Years
|
Up to 5 Years
|
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Progression-Free Survival (PFS) as measured by IMWG criteria
Tidsramme: Up to 5 Years
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Up to 5 Years
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Rate of Minimal Residual Disease (MRD) negative status by IMWG criteria
Tidsramme: Up to 5 Years
|
Up to 5 Years
|
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Incidence over time of Anti-Drug Antibodies (ADAs) to linvoseltamab
Tidsramme: Up to 5 Years
|
Up to 5 Years
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Clinical Trial Management, Regeneron Pharmaceuticals
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Karsygdomme
- Hjerte-kar-sygdomme
- Neoplasmer
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Hæmatologiske sygdomme
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Neoplasmer, Plasmacelle
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Hæmoragiske lidelser
- Hemiske og lymfatiske sygdomme
- Myelomatose
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Carboxylsyrer
- Piperidiner
- Uorganiske kemikalier
- Boronsyrer
- Syrer, ikke -carboxylisk
- Syrer
- Borforbindelser
- Pyraziner
- Phthalimider
- Phthalinsyrer
- Syrer, carbocykliske
- Piperidones
- Isoindoler
- Lenalidomid
- Bortezomib
- carfilzomib
- Pomalidomid
- Daratumumab
- cemiplimab
- isatuximab
- Nirogacestat
Andre undersøgelses-id-numre
- R5458-ONC-2012
- 2020-004638-39 (EudraCT nummer)
- 2023 (U.S. NIH-bevilling/kontrakt)
- 2023-506247-42-00 (Ctis)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD-delingstidsramme
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
IPD-delingsadgangskriterier
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
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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