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Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors

NCT03967223

Description:

This trial will evaluate safety and efficacy of GSK3377794 in patients with solid tumors, initially in patients with synovial sarcoma.

Related Conditions:
  • Synovial Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors
  • Official Title: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, Alone or in Combination With Other Agents, in HLA-A2+ Participants With NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO)

Clinical Trial IDs

  • ORG STUDY ID: 208467
  • NCT ID: NCT03967223

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
GSK3377794Substudy 1: GSK3377794
FludarabineSubstudy 1: GSK3377794
CyclophosphamideSubstudy 1: GSK3377794

Purpose

This trial will evaluate safety and efficacy of GSK3377794 in patients with solid tumors, initially in patients with synovial sarcoma.

Detailed Description

      Adoptive T-cell therapy (ACT) is a therapeutic approach that uses T lymphocytes of patients
      with cancer, obtained by leukapheresis, with the aim of generating an anti-tumor T-cell
      immune response. New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are
      tumor-associated proteins that have been found in several tumor types. Clinical trials using
      adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective
      responses. GSK3377794 is the first generation of NY-ESO-1 specific T-cell receptor engineered
      T-cells. This is a master protocol that will initially consist of two substudies,
      investigating GSK3377794 in previously untreated patients with advanced metastatic synovial
      sarcoma (Substudy 1) and in patients with advanced metastatic synovial sarcoma who have
      progressed following treatment with anthracycline-based chemotherapy (Substudy 2).
    

Trial Arms

NameTypeDescriptionInterventions
Substudy 1: GSK3377794ExperimentalAfter screening, eligible patients will enter a leukapheresis phase. Patients with previously untreated advanced metastatic synovial sarcoma will receive GSK3377794, administered as a single intravenous (IV) infusion.
  • GSK3377794
  • Fludarabine
  • Cyclophosphamide
Substudy 2: GSK3377794ExperimentalAfter screening, eligible patients will enter a leukapheresis phase. Patients with advanced metastatic synovial sarcoma who have progressed following treatment with anthracycline-based chemotherapy will receive GSK3377794, administered as a single IV infusion.
  • GSK3377794
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must be >=10 years of age at the time of signing the informed consent.

          -  Patient has a diagnosis of synovial sarcoma confirmed by histology.

          -  Patient has advanced (metastatic or unresectable) synovial sarcoma.

          -  In substudy 1, patient with metastatic synovial sarcoma who is newly diagnosed or
             previously untreated.

          -  In substudy 2, at the time of treatment, patient has received/completed treatment with
             anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable)
             disease and progressed.

          -  Male or female. Contraception requirements will apply at the time of leukapheresis and
             treatment.

          -  Patient must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05,
             and/or HLA-A*02:06 alleles by a validated test in a designated central laboratory.

          -  Patients tumor has been pathologically reviewed by a designated central laboratory
             with confirmed positive NY-ESO-1 expression.

          -  Performance status: Eastern Cooperative Oncology Group of 0-1.

          -  Patient must have adequate organ function and blood cell counts 7 days prior to
             leukapheresis.

          -  Female patients of childbearing potential must have a negative urine or serum
             pregnancy test.

          -  Patient has measurable disease according to RECIST v1.1.

          -  Supportive radiotherapy has not affected >25 percent of bone marrow.

        Exclusion Criteria:

          -  In substudy 1, patient has been previously treated for metastatic synovial sarcoma.

          -  Central nervous system metastases.

          -  Any other prior malignancy that is not in complete remission.

          -  Previous treatment with genetically engineered NY-ESO-1-specific T cells.

          -  Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.

          -  Prior gene therapy using an integrating vector.

          -  Previous allogeneic hematopoietic stem cell transplant.

          -  Clinically significant systemic illness: serious active infections or significant
             cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the
             Investigator would compromise the Patient 's ability to tolerate protocol therapy or
             significantly increase the risk of complications, or, prior or active demyelinating
             disease.

          -  Patient has history of chronic or recurrent (within the last year prior to
             leukapheresis) severe autoimmune or immune mediated disease requiring steroids or
             other immunosuppressive treatments.

          -  Uncontrolled intercurrent illness.

          -  Current active liver or biliary disease.

          -  Pregnant or breastfeeding females (due to risk to fetus or newborn).

          -  Prior/concomitant therapy: any prior treatment-related toxicities must be Common
             terminology criteria for adverse events <=Grade 1 at the time of initiating study
             intervention (except for non-clinically significant toxicities).

          -  Other standard of care lines of therapy are allowed only if guidelines and washout
             periods are followed.

          -  Patient has active infection as defined in the protocol.

          -  Patient has known psychiatric or substance abuse disorders that would interfere with
             cooperating with the requirements of the study.

          -  Patient had major surgery <=28 days of first dose of study intervention.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:10 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Substudy 1: Overall response rate
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Overall response rate is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of patients within the analysis population at any time as assessed by Investigators per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

Secondary Outcome Measures

Measure:Substudy 1: Time to response
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Time to response is the time from the date of T-cell infusion to initial date of confirmed response (PR or CR) as assessed by Investigators per RECIST v1.1 in the subset of patients who achieved a confirmed PR or CR.
Measure:Substudy 1: Duration of response
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Duration of response is defined as, in the subset of patients who show a confirmed CR or PR as assessed by Investigators per RECIST v1.1, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
Measure:Substudy 1: Disease control rate
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Disease control rate is defined as the percentage of patients with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration relative to the total number of patients within the analysis population at the time of primary analysis as determined by Investigators per RECIST v1.1.
Measure:Substudy 1: Progression free survival
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Progression free survival is defined as the time from the date of T-cell infusion until the earliest date of radiological progression of disease (PD) as assessed by the Investigator per RECIST v1.1, or death due to any cause.
Measure:Substudy 1: Number of patients with adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study patient, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment.
Measure:Substudy 1: Severity and duration of adverse events of special interest (AESIs)
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:To assess the AESIs as a criteria of safety.
Measure:Substudy 1: Number of patients with replication competent lentivirus (RCL)
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
Measure:Substudy 1: Number of patients with insertional oncogenesis
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
Measure:Substudy 1: Change from Baseline in hematology parameters: platelets
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 1: Change from Baseline in hematology parameters: hematocrit
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 1: Change from Baseline in hematology parameters: hemoglobin
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 1: Change from Baseline in hematology parameters: Red blood cell (RBC) count
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 1: Change from Baseline in hematology parameters: White blood cell (WBC) count
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 1: Change from Baseline in clinical chemistry parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of clinical chemistry parameters.
Measure:Substudy 1: Change from Baseline in clinical chemistry parameters: Blood Urea Nitrogen (BUN)
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of clinical chemistry parameters.
Measure:Substudy 1: Change from Baseline in clinical chemistry parameters: Total and Direct bilirubin, Creatinine
Time Frame:Baseline and until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for analysis of clinical chemistry parameters.
Measure:Substudy 1: Change from Baseline in urine parameters: potential of hydrogen (pH)
Time Frame:Baseline and up to day -4
Safety Issue:
Description:Urine samples will be collected for analysis of urine parameters.
Measure:Substudy 1: Change from Baseline in urine parameters: glucose, protein, blood, bilirubin
Time Frame:Baseline and up to day -4
Safety Issue:
Description:Urine samples will be collected for analysis of urine parameters.
Measure:Substudy 1: T Cell Persistence of GSK3377794
Time Frame:Until disease progression (up to 5 years)
Safety Issue:
Description:Blood samples will be collected for T Cell Persistence analysis of GSK3377794 transduced cell quantities.
Measure:Substudy 2: Time to response
Time Frame:Up to 5 years
Safety Issue:
Description:Time to response is the time from the date of T-cell infusion to initial date of confirmed response (PR or CR) as assessed by independent central review per RECIST v1.1 in the subset of patients who achieved a confirmed PR or CR.
Measure:Substudy 2: Duration of response
Time Frame:Up to 5 years
Safety Issue:
Description:Duration of response is defined as, in the subset of patients who show a confirmed CR or PR as assessed by independent central review per RECIST v1.1, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
Measure:Substudy 2: Disease control rate
Time Frame:Up to 5 years
Safety Issue:
Description:Disease control rate is defined as the percentage of patients with a confirmed CR, PR, or SD with minimal 12 weeks duration relative to the total number of patients within the analysis population at the time of primary analysis as determined by independent central review per RECIST v1.1.
Measure:Substudy 2: Progression free survival
Time Frame:Up to 5 years
Safety Issue:
Description:Progression free survival is defined as the time from the date of T-cell infusion until the earliest date of radiological PD as assessed by the independent central review per RECIST v1.1, or death due to any cause.
Measure:Substudy 2: Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:Overall survival is defined as the interval of time between the date of T-cell infusion and the date of death due to any cause.
Measure:Substudy 2: Number of patients with AEs and SAEs
Time Frame:Up to 5 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study patient, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity is a congenital anomaly/birth defect or any other situation as per Medical or scientific judgment.
Measure:Substudy 2: Severity and duration of adverse events of special interest (AESIs)
Time Frame:Up to 5 years
Safety Issue:
Description:To assess the AESIs as a criteria of safety.
Measure:Substudy 2: Number of patients with RCL
Time Frame:Up to 5 years
Safety Issue:
Description:RCL exposure will be assessed by PCR based assay.
Measure:Substudy 2: Number of patients with insertional oncogenesis
Time Frame:Up to 5 years
Safety Issue:
Description:PBMC samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
Measure:Substudy 2: Number of patients with positive anti-drug antibodies (ADA) against GSK3377794
Time Frame:Up to 36 months
Safety Issue:
Description:Serum samples will be collected up to 36 months for ADA test.
Measure:Substudy 2: Titers of ADA against GSK3377794
Time Frame:Up to 36 months
Safety Issue:
Description:Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
Measure:Substudy 2: Change from Baseline in hematology parameters: platelets
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 2: Change from Baseline in hematology parameters: hematocrit
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 2: Change from Baseline in hematology parameters: hemoglobin
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 2: Change from Baseline in hematology parameters: Red blood cell (RBC) count
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 2: Change from Baseline in hematology parameters: White blood cell (WBC) count
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of hematology parameters.
Measure:Substudy 2: Change from Baseline in clinical chemistry parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of clinical chemistry parameters.
Measure:Substudy 2: Change from Baseline in clinical chemistry parameters: Blood Urea Nitrogen (BUN)
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of clinical chemistry parameters.
Measure:Substudy 2: Change from Baseline in clinical chemistry parameters: Total and Direct bilirubin, Creatinine
Time Frame:Baseline and up to 5 years
Safety Issue:
Description:Blood samples will be collected for analysis of clinical chemistry parameters.
Measure:Substudy 2: Change from Baseline in urine parameters: potential of hydrogen (pH)
Time Frame:Baseline and up to day -4
Safety Issue:
Description:Urine samples will be collected for analysis of urine parameters.
Measure:Substudy 2: Change from Baseline in urine parameters: glucose, protein, blood, bilirubin
Time Frame:Baseline and up to day -4
Safety Issue:
Description:Urine samples will be collected for analysis of urine parameters.
Measure:Substudy 2: T Cell Persistence of GSK3377794
Time Frame:Up to 5 years
Safety Issue:
Description:Blood samples will be collected for T Cell Persistence analysis of GSK3377794 transduced cell quantities.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Adoptive T-cell therapy
  • Advanced metastatic synovial sarcoma
  • GSK3377794
  • Positive solid tumors
  • T-cell receptors

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