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- Klinische proef NCT03489369
Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
1 februari 2021 bijgewerkt door: Symphogen A/S
A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
This is the first study to test Sym022 in humans.
The primary purpose of this study is to see if Sym022 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-3) monoclonal antibody (mAb).
The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym022 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/ unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.
If an MTD is not identified, a maximum administered dose (MAD) will be determined.
Sym022 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
15
Fase
- Fase 1
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Cancer Centre
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Michigan
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Grand Rapids, Michigan, Verenigde Staten, 49503
- South Texas Accelerated Research Therapeutics (START) Midwest
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Texas
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Houston, Texas, Verenigde Staten, 77030
- The University of Texas MD Anderson Cancer Center
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.
- Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
- Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
- Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
- Measurable or non-measurable disease according to RECIST v1.1 or RECIL 2017.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.
Exclusion Criteria:
- Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
- Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- Hematologic malignancies other than lymphomas.
- Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable
- Active uncontrolled bleeding or a known bleeding diathesis
- Clinically significant cardiovascular disease or condition
- Significant pulmonary disease or condition
- Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
- An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
- History of organ transplantation (e.g. stem cell or solid organ transplant)
- History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
- Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
- Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D1.
- Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Other Inhibitors of LAG-3
- Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to first administration of study drug and during study
- Any other investigational treatments within 4 weeks prior to and during study
- Radiotherapy for target lesions within 4 weeks prior to first administration of study drug unless PD has been documented in the lesion following treatment, and during study.
- Radiotherapy for non-target lesions within 1 week prior to first administration of study drug
- Immunosuppressive or systemic hormonal therapy
- Prophylactic use of hematopoietic growth factors within 1 week prior to first administration of study drug and during Cycle 1 of study
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Sym022
Sym022 will be administered at up to 4 planned dose levels.
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Sym022 is een recombinant, volledig humaan antilichaam dat LAG-3 bindt en de LAG-3/major histocompatibiliteitscomplex klasse II (MHC-II)-interactie blokkeert, waardoor een verhoogde T-celproliferatie en cytokineproductie mogelijk wordt.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Assessment of Treatment Related Adverse Events (AEs).
Tijdsspanne: 19 months
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Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
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19 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Evaluation of the Immunogenicity of Sym022.
Tijdsspanne: 19 months
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Serum sampling and incidence (%) per dose level to assess the potential for anti-drug antibody (ADA) formation.
Count of participants show the number of participants who were tested positive for anti-Sym022 ADA.
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19 months
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Evaluation of Objective Response (OR) or Stable Disease (SD).
Tijdsspanne: 13 months
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Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), Response Evaluation Criteria in Lymphomas 2017 (RECIL 2017), or Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST), depending on tumor type.
The numbers shown below correspond to the values related to RECIST v1.1.
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13 months
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Time to Progression (TTP) of Disease.
Tijdsspanne: 13 months
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Based on time of enrollment to first evidence of progression on imaging studies, as assessed by RECIST v1.1, RECIL 2017, or iRECIST, depending on tumor type.
The numbers shown below correspond to the values related to RECIST v1.1.
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13 months
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Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Tijdsspanne: 19 months
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Will be estimated using non-compartmental methods and actual timepoints.
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19 months
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Maximum Concentration (Cmax)
Tijdsspanne: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be derived from observed data.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Time to Reach Maximum Concentration (Tmax)
Tijdsspanne: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be derived from observed data.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Trough Concentration (Ctrough)
Tijdsspanne: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be derived from observed data.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Terminal Elimination Half-life (T½)
Tijdsspanne: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be estimated using non-compartmental methods and actual timepoints.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Clearance (CL)
Tijdsspanne: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Will be estimated using non-compartmental methods and actual timepoints.
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0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
8 mei 2018
Primaire voltooiing (Werkelijk)
6 januari 2020
Studie voltooiing (Werkelijk)
6 januari 2020
Studieregistratiedata
Eerst ingediend
26 maart 2018
Eerst ingediend dat voldeed aan de QC-criteria
3 april 2018
Eerst geplaatst (Werkelijk)
5 april 2018
Updates van studierecords
Laatste update geplaatst (Werkelijk)
18 februari 2021
Laatste update ingediend die voldeed aan QC-criteria
1 februari 2021
Laatst geverifieerd
1 februari 2021
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- Sym022-01
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
NEE
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Sym022
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Symphogen A/SVoltooidLymfoom | Vaste tumor | Uitgezaaide kankerCanada, Verenigde Staten
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Symphogen A/SVoltooidVaste tumor | Uitgezaaide kankerVerenigde Staten, Canada, Frankrijk, Spanje