Clinical Trials /

Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

NCT03489343

Description:

This is the first study to test Sym023 in humans. The primary purpose of this study is to see if Sym023 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:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Sym023 (Anti-TIM-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 Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: Sym023-01
  • NCT ID: NCT03489343

Conditions

  • Metastatic Cancer
  • Solid Tumor
  • Lymphoma

Interventions

DrugSynonymsArms
Sym023Anti-TIM-3Sym023

Purpose

This is the first study to test Sym023 in humans. The primary purpose of this study is to see if Sym023 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 Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain
      containing-3 (anti-TIM-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
      Sym023 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.
      Sym023 will be given to patients in escalating dose cohorts; each patient will be given one
      fixed dose level.
    

Trial Arms

NameTypeDescriptionInterventions
Sym023ExperimentalSym023 will be administered at up to 7 planned dose levels.
  • Sym023

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 ocular disease or condition, including history of autoimmune or
             inflammatory disorder.

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

Primary Outcome Measures

Measure:Assessment of treatment emergent adverse events (AEs) meeting DLT criteria.
Time Frame:24 months
Safety Issue:
Description:Assess the safety and tolerability of Sym023 on a Q2W schedule to establish the MTD and/or RP2D. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1.

Secondary Outcome Measures

Measure:Evaluation of the immunogenicity of Sym023.
Time Frame:24 months
Safety Issue:
Description:Serum sampling to assess the potential for anti-drug antibody (ADA) formation.
Measure:Evaluation of objective response (OR) or stable disease (SD).
Time Frame:24 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.
Measure:Time to progression (TTP) of disease.
Time Frame:24 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.
Measure:Area under the concentration-time curve in a dosing interval (AUC).
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints.
Measure:Maximum concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data.
Measure:Time to reach maximum concentration (Tmax)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data.
Measure:Trough concentration (Ctrough)
Time Frame:24 months
Safety Issue:
Description:Will be derived from observed data.
Measure:Terminal elimination half-life (T½)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints.
Measure:Clearance (CL)
Time Frame:24 months
Safety Issue:
Description:Will be estimated using non-compartmental methods and actual timepoints.

Details

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

Trial Keywords

  • Locally advanced/unresectable
  • Metastatic solid tumor
  • Lymphoma
  • Anti-TIM-3
  • TIM-3
  • TIM3

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