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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

    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
    • Michigan
      • Grand Rapids, Michigan, Forenede Stater, 49503
        • South Texas Accelerated Research Therapeutics (START) Midwest
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • The University of Texas MD Anderson Cancer Center

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
Eksperimentel: Sym022
Sym022 will be administered at up to 4 planned dose levels.
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:
  • Anti-LAG-3

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Assessment of Treatment Related Adverse Events (AEs).
Tidsramme: 19 months
Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
19 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Evaluation of the Immunogenicity of Sym022.
Tidsramme: 19 months
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.
19 months
Evaluation of Objective Response (OR) or Stable Disease (SD).
Tidsramme: 13 months
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.
13 months
Time to Progression (TTP) of Disease.
Tidsramme: 13 months
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.
13 months
Area Under the Concentration-time Curve in a Dosing Interval (AUC).
Tidsramme: 19 months
Will be estimated using non-compartmental methods and actual timepoints.
19 months
Maximum Concentration (Cmax)
Tidsramme: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be derived from observed data.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Time to Reach Maximum Concentration (Tmax)
Tidsramme: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be derived from observed data.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Trough Concentration (Ctrough)
Tidsramme: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be derived from observed data.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Terminal Elimination Half-life (T½)
Tidsramme: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be estimated using non-compartmental methods and actual timepoints.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Clearance (CL)
Tidsramme: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)
Will be estimated using non-compartmental methods and actual timepoints.
0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week)

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

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

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Sym022

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