- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT03489369
Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
1. februar 2021 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
15
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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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, Forenede Stater, 49503
- South Texas Accelerated Research Therapeutics (START) Midwest
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Texas
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Houston, Texas, Forenede Stater, 77030
- The University of Texas MD Anderson Cancer Center
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Sym022
Sym022 will be administered at up to 4 planned dose levels.
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Sym022 er et rekombinant, fuldt humant antistof, der binder LAG-3 og blokerer LAG-3/større histokompatibilitetskompleks klasse II (MHC-II) interaktion, hvilket giver mulighed for øget T-celleproliferation og cytokinproduktion.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Assessment of Treatment Related Adverse Events (AEs).
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Evaluation of the Immunogenicity of Sym022.
Tidsramme: 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).
Tidsramme: 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.
Tidsramme: 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).
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
8. maj 2018
Primær færdiggørelse (Faktiske)
6. januar 2020
Studieafslutning (Faktiske)
6. januar 2020
Datoer for studieregistrering
Først indsendt
26. marts 2018
Først indsendt, der opfyldte QC-kriterier
3. april 2018
Først opslået (Faktiske)
5. april 2018
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
18. februar 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
1. februar 2021
Sidst verificeret
1. februar 2021
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- Sym022-01
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
INGEN
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
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Kliniske forsøg med Sym022
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Symphogen A/SAfsluttetLymfom | Solid tumor | Metastatisk kræftCanada, Forenede Stater
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Symphogen A/SAfsluttetSolid tumor | Metastatisk kræftForenede Stater, Canada, Frankrig, Spanien