Clinical Trials /

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

NCT03489369

Description:

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.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Sym022-01
  • NCT ID: NCT03489369

Conditions

  • Metastatic Cancer
  • Solid Tumor
  • Lymphoma

Interventions

DrugSynonymsArms
Sym022Anti-LAG-3Sym022

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Sym022ExperimentalSym022 will be administered at up to 4 planned dose levels.
  • Sym022

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of Treatment Related Adverse Events (AEs).
Time Frame:19 months
Safety Issue:
Description:Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Symphogen A/S

Trial Keywords

  • Locally advanced/unresectable
  • Metastatic solid tumor
  • Lymphoma
  • Anti-LAG-3
  • LAG-3
  • LAG3

Last Updated

February 18, 2021