Linvolseltamab (bispezifischer Anti-BCMA x Anti-CD3-Antikörper) plus andere Krebsbehandlungen für Teilnehmer mit rezidiviertem/refraktärem multiplem Myelom (LINKER-MM2)
Phase-1b-Studie zu REGN5458 (bispezifischer Anti-BCMA x Anti-CD3-Antikörper) und anderen Krebsbehandlungen für Patienten mit rezidiviertem/refraktärem multiplem Myelom
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)
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 1
Kontakte und Standorte
Studienkontakt
- Name: Clinical Trials Administrator
- Telefonnummer: 844-734-6643
- E-Mail: clinicaltrials@regeneron.com
Studienorte
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Angers, Frankreich, 49933
- Rekrutierung
- Centre Hospitalier Universitaire Angers
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Montpellier, Frankreich, 34295
- Rekrutierung
- CHU Montpellier - Departement D'Hematologie
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Paris, Frankreich, 75571
- Rekrutierung
- Saint Antoine Hospital
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Villejuif, Frankreich, 94805
- Rekrutierung
- Institut Gustave Roussy
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New Aquitaine
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Poitiers, New Aquitaine, Frankreich, 86021
- Rekrutierung
- Centre Hospitalier Universitaire (CHU) de Poitiers
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Nord
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Lille, Nord, Frankreich, 59037
- Rekrutierung
- 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, Frankreich, 44093
- Rekrutierung
- Nantes University Hospital
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Île-de-France Region
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Créteil, Île-de-France Region, Frankreich, 94000
- Rekrutierung
- Hospital Henri Mondor
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Paris, Île-de-France Region, Frankreich, 75015
- Rekrutierung
- Hopital Necker
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Paris, Île-de-France Region, Frankreich, 75010
- Rekrutierung
- Saint Louis Hospital
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Athens, Griechenland, 11528
- Rekrutierung
- General Hospital of Athens Alexandra
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Attica
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Athens, Attica, Griechenland, 10676
- Rekrutierung
- Evangelismos General Hospital
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-
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Haifa, Israel, 3109601
- Rekrutierung
- Rambam Health Care Campus
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Jerusalem, Israel, 91120
- Rekrutierung
- Hadassah Medical Center
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Central District
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Ramat Gan, Central District, Israel, 5265601
- Rekrutierung
- Sheba Medical Center
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Barcelona, Spanien, 08035
- Rekrutierung
- Hospital Universitario Vall d'Hebron
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Barcelona, Spanien, 08036
- Rekrutierung
- Hospital Clinic de Barcelona
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Barcelona, Spanien, 08908
- Rekrutierung
- Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,
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Madrid, Spanien, 28050
- Rekrutierung
- Hospital Universitario HM Sanchinarro
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Madrid, Spanien, 28027
- Rekrutierung
- Clinica Universidad de Navarra - Madrid
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Madrid, Spanien, 28006
- Rekrutierung
- Universitaru Hospital La Princesa
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Madrid, Spanien, 28041
- Rekrutierung
- University Hospital and Research Institute
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Madrid, Spanien, 28034
- Rekrutierung
- Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria
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Salamanca, Spanien, 37007
- Rekrutierung
- University Hospital of Salamanca
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A Coruna
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Santiago de Compostela, A Coruna, Spanien, 15706
- Rekrutierung
- Hospital Clinico Universitario de Santiago
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Barcelona
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Badalona, Barcelona, Spanien, 08916
- Rekrutierung
- Hospital Germans Trias i Pujol
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Cantabria
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Santander, Cantabria, Spanien, 39008
- Rekrutierung
- Hospital Universitario Marques de Valdecilla
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Madrid
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Pozuelo de Alarcón, Madrid, Spanien, 28223
- Rekrutierung
- Hospital Universitario Quiron Salud Madrid
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Navarre
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Pamplona, Navarre, Spanien, 31008
- Rekrutierung
- Clinica Universidad de Navarra
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California
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La Jolla, California, Vereinigte Staaten, 92037
- Rekrutierung
- Scripps Clinic Torrey Pines
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Georgia
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Atlanta, Georgia, Vereinigte Staaten, 30004
- Rekrutierung
- Winship Cancer Institute of Emory University
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Indiana
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Indianapolis, Indiana, Vereinigte Staaten, 46202
- Rekrutierung
- Indiana University Health Simon Cancer Center
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Massachusetts
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Boston, Massachusetts, Vereinigte Staaten, 02215
- Rekrutierung
- Dana Farber/Harvard Cancer Center
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Michigan
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Detroit, Michigan, Vereinigte Staaten, 48201
- Rekrutierung
- Karmanos Cancer Institute
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Minnesota
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Rochester, Minnesota, Vereinigte Staaten, 55905
- Rekrutierung
- Mayo Clinic
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New York
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New York, New York, Vereinigte Staaten, 10021
- Rekrutierung
- Weill Cornell Medicine/New York Presbyterian Hospital
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New York, New York, Vereinigte Staaten, 10032
- Rekrutierung
- New York Presbyterian Hospital Columbia University Medical Center
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North Carolina
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Chapel Hill, North Carolina, Vereinigte Staaten, 27599
- Rekrutierung
- University of North Carolina at Chapel Hill
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Winston-Salem, North Carolina, Vereinigte Staaten, 27157
- Rekrutierung
- Wake Forest University Health Sciences
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Ohio
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Columbus, Ohio, Vereinigte Staaten, 43210
- Rekrutierung
- The Ohio State University James Cancer Hospital
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Texas
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Dallas, Texas, Vereinigte Staaten, 75390
- Rekrutierung
- University of Texas Southwestern
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Washington
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Seattle, Washington, Vereinigte Staaten, 98108
- Rekrutierung
- VA Puget Sound Health Care System
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Cohort 1: Linvoseltamab + Daratumumab
Linvoseltamab + Daratumumab |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 2: Linvoseltamab + Carfilzomib
Linvoseltamab + Carfilzomib |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 3: Linvoseltamab + Lenalidomide
Linvoseltamab + Lenalidomide |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 4: Linvoseltamab + Bortezomib
Linvoseltamab + Bortezomib |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 5: Linvoseltamab + Pomalidomide
Linvoseltamab + Pomalidomide |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 6: Linvoseltamab + Isatuximab
Linvoseltamab + Isatuximab |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 7: Linvoseltamab + Fianlimab
Linvoseltamab + Fianlimab |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 8: Linvoseltamab + Cemiplimab
Linvoseltamab + Cemiplimab |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 9: Linvoseltamab + Nirogacestat
Linvoseltamab + Nirogacestat |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
|
Experimental: Cohort 10: Linvoseltamab + Cevostamab
Linvoseltamab + Cevostamab |
Administered per the protocol
Andere Namen:
Administered per the protocol
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Häufigkeit schwerwiegender unerwünschter Ereignisse (SUE)
Zeitfenster: Bis zu 5 Jahre
|
Bis zu 5 Jahre
|
|
|
Schweregrad der TEAEs
Zeitfenster: Bis zu 5 Jahre
|
Bis zu 5 Jahre
|
|
|
Schweregrad der SAEs
Zeitfenster: Bis zu 5 Jahre
|
Bis zu 5 Jahre
|
|
|
Schweregrad der AESIs
Zeitfenster: Bis zu 5 Jahre
|
Bis zu 5 Jahre
|
|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
|
|
Incidence of Adverse Events of Special Interest (AESIs)
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
|
|
Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period
Zeitfenster: Up to 28 Days
|
Dose finding portion only |
Up to 28 Days
|
|
Incidence of laboratory abnormalities
Zeitfenster: Up to 5 Years
|
≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0] |
Up to 5 Years
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Gesamtüberleben (OS)
Zeitfenster: Bis zu 5 Jahre
|
Bis zu 5 Jahre
|
|
Konzentrationen des gesamten Linvoseltamab im Serum im Zeitverlauf
Zeitfenster: Bis zu 5 Jahre
|
Bis zu 5 Jahre
|
|
Overall Response Rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
|
Duration of Response (DOR) by IMWG criteria
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
|
Progression-Free Survival (PFS) as measured by IMWG criteria
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
|
Rate of Minimal Residual Disease (MRD) negative status by IMWG criteria
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
|
Incidence over time of Anti-Drug Antibodies (ADAs) to linvoseltamab
Zeitfenster: Up to 5 Years
|
Up to 5 Years
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: Clinical Trial Management, Regeneron Pharmaceuticals
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Gefäßerkrankungen
- Herz-Kreislauf-Erkrankungen
- Neubildungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Hämatologische Erkrankungen
- Lymphoproliferative Erkrankungen
- Immunproliferative Erkrankungen
- Neubildungen, Plasmazelle
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- Hämorrhagische Störungen
- Hämische und lymphatische Krankheiten
- Multiples Myelom
- Organische Chemikalien
- Heterocyclische Verbindungen, 1-Ring
- Heterocyclische Verbindungen
- Heterocyclische Verbindungen, 2-Ring
- Heterocyclische Verbindungen, Fusionsring
- Carboxylsäuren
- Piperidine
- Anorganische Chemikalien
- Boronsäuren
- Säuren, nicht carboxylisch
- Säuren
- Borverbindungen
- Pyraziner
- Phthalimides
- Phthalsäuren
- Säuren, carbocyclisch
- Piperidones
- Isoindolen
- Lenalidomid
- Bortezomib
- CARFILZOMIB
- Pomalidomid
- Daratumumab
- Cemiplimab
- Isatuximab
- Nirogacestat
Andere Studien-ID-Nummern
- R5458-ONC-2012
- 2020-004638-39 (EudraCT-Nummer)
- 2023 (US NIH Stipendium/Vertrag)
- 2023-506247-42-00 (Ctis)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD-Sharing-Zeitrahmen
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-Sharing-Zugriffskriterien
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
Art der unterstützenden IPD-Freigabeinformationen
- STUDIENPROTOKOLL
- SAFT
- ICF
- ANALYTIC_CODE
- CSR
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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