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Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

1 februari 2021 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

15

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Sym022
Sym022 will be administered at up to 4 planned dose levels.
Sym022 är en rekombinant, helt human antikropp som binder LAG-3 och blockerar LAG-3/major histocompatibility complex class II (MHC-II) interaktionen, vilket möjliggör ökad T-cellsproliferation och cytokinproduktion.
Andra namn:
  • Anti-LAG-3

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Assessment of Treatment Related Adverse Events (AEs).
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Evaluation of the Immunogenicity of Sym022.
Tidsram: 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).
Tidsram: 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.
Tidsram: 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).
Tidsram: 19 months
Will be estimated using non-compartmental methods and actual timepoints.
19 months
Maximum Concentration (Cmax)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Utredare

  • Huvudutredare: Lillian Siu, MD, FRCPC, Princess Margaret Cancer Centre

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

8 maj 2018

Primärt slutförande (Faktisk)

6 januari 2020

Avslutad studie (Faktisk)

6 januari 2020

Studieregistreringsdatum

Först inskickad

26 mars 2018

Först inskickad som uppfyllde QC-kriterierna

3 april 2018

Första postat (Faktisk)

5 april 2018

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

18 februari 2021

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

1 februari 2021

Senast verifierad

1 februari 2021

Mer information

Termer relaterade till denna studie

Plan för individuella deltagardata (IPD)

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Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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Kliniska prövningar på Sym022

3
Prenumerera