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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03967223
Recruitment Status : Recruiting
First Posted : May 30, 2019
Last Update Posted : September 4, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE May 10, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date September 4, 2020
Actual Study Start Date  ICMJE December 31, 2019
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • Substudy 1: Overall response rate [ Time Frame: Until disease progression (up to 5 years) ]
    Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants within the analysis population at any time as assessed by Investigators per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
  • Substudy 2: Overall response rate [ Time Frame: Up to 5 years ]
    Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time as assessed by central independent review per RECIST v1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
  • Substudy 1: Overall response rate [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 2: Overall response rate [ Time Frame: Up to 5 years ]
    Overall response rate is defined as the percentage of patients with a confirmed CR or PR relative to the total number of patients within the analysis population at any time as assessed by central independent review per RECIST v1.1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • Substudy 1 and 2: Time to response [ Time Frame: Until disease progression (up to 5 years) ]
    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 participants who achieved a confirmed PR or CR.
  • Substudy 1 and 2: Duration of response [ Time Frame: Until disease progression (up to 5 years) ]
    Duration of response is defined as, in the subset of participants 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.
  • Substudy 1 and 2: Disease control rate [ Time Frame: Until disease progression (up to 5 years) ]
    Disease control rate is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration relative to the total number of participants within the analysis population at the time of primary analysis as determined by Investigators per RECIST v1.1.
  • Substudy 1 and 2: Progression free survival [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 1 and 2: Number of partiipants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Until disease progression (up to 5 years) ]
    AEs and SAEs will be collected.
  • Substudy 1 and 2: Severity and duration of adverse events of special interest (AESIs) [ Time Frame: Until disease progression (up to 5 years) ]
    To assess the AESIs as a criteria of safety.
  • Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL) [ Time Frame: Until disease progression (up to 5 years) ]
    RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
  • Substudy 1 and 2: Number of participants with insertional oncogenesis [ Time Frame: Until disease progression (up to 5 years) ]
    Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
  • Substudy 1 and 2: Number of participants with clinically significant changes in hematology and clinical chemistry parameters [ Time Frame: Until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of hematology and clinical chemistry parameters.
  • Substudy 1 and 2: Number of participants with clinically significant changes in urinalysis parameters [ Time Frame: Up to day -4 ]
    Urine samples will be collected for analysis of urine parameters.
  • Substudy 1 and 2: T Cell Persistence of GSK3377794 [ Time Frame: Until disease progression (up to 5 years) ]
    Blood samples will be collected for T Cell Persistence analysis of GSK3377794 transduced cell quantities.
  • Substudy 2: Number of participants with positive anti-drug antibodies (ADA) against GSK3377794 [ Time Frame: Up to 36 months ]
    Serum samples will be collected up to 36 months for ADA test.
  • Substudy 2: Titers of ADA against GSK3377794 [ Time Frame: Up to 36 months ]
    Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
  • Substudy 1: Time to response [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 1: Duration of response [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 1: Disease control rate [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 1: Progression free survival [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 1: Number of patients with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Until disease progression (up to 5 years) ]
    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.
  • Substudy 1: Severity and duration of adverse events of special interest (AESIs) [ Time Frame: Until disease progression (up to 5 years) ]
    To assess the AESIs as a criteria of safety.
  • Substudy 1: Number of patients with replication competent lentivirus (RCL) [ Time Frame: Until disease progression (up to 5 years) ]
    RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
  • Substudy 1: Number of patients with insertional oncogenesis [ Time Frame: Until disease progression (up to 5 years) ]
    Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
  • Substudy 1: Change from Baseline in hematology parameters: platelets [ Time Frame: Baseline and until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 1: Change from Baseline in hematology parameters: hematocrit [ Time Frame: Baseline and until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 1: Change from Baseline in hematology parameters: hemoglobin [ Time Frame: Baseline and until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 1: Change from Baseline in hematology parameters: Red blood cell (RBC) count [ Time Frame: Baseline and until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 1: Change from Baseline in hematology parameters: White blood cell (WBC) count [ Time Frame: Baseline and until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of hematology parameters.
  • 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) ]
    Blood samples will be collected for analysis of clinical chemistry parameters.
  • Substudy 1: Change from Baseline in clinical chemistry parameters: Blood Urea Nitrogen (BUN) [ Time Frame: Baseline and until disease progression (up to 5 years) ]
    Blood samples will be collected for analysis of clinical chemistry parameters.
  • 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) ]
    Blood samples will be collected for analysis of clinical chemistry parameters.
  • Substudy 1: Change from Baseline in urine parameters: potential of hydrogen (pH) [ Time Frame: Baseline and up to day -4 ]
    Urine samples will be collected for analysis of urine parameters.
  • Substudy 1: Change from Baseline in urine parameters: glucose, protein, blood, bilirubin [ Time Frame: Baseline and up to day -4 ]
    Urine samples will be collected for analysis of urine parameters.
  • Substudy 1: T Cell Persistence of GSK3377794 [ Time Frame: Until disease progression (up to 5 years) ]
    Blood samples will be collected for T Cell Persistence analysis of GSK3377794 transduced cell quantities.
  • Substudy 2: Time to response [ Time Frame: Up to 5 years ]
    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.
  • Substudy 2: Duration of response [ Time Frame: Up to 5 years ]
    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.
  • Substudy 2: Disease control rate [ Time Frame: Up to 5 years ]
    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.
  • Substudy 2: Progression free survival [ Time Frame: Up to 5 years ]
    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.
  • Substudy 2: Overall survival [ Time Frame: Up to 5 years ]
    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.
  • Substudy 2: Number of patients with AEs and SAEs [ Time Frame: Up to 5 years ]
    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.
  • Substudy 2: Severity and duration of adverse events of special interest (AESIs) [ Time Frame: Up to 5 years ]
    To assess the AESIs as a criteria of safety.
  • Substudy 2: Number of patients with RCL [ Time Frame: Up to 5 years ]
    RCL exposure will be assessed by PCR based assay.
  • Substudy 2: Number of patients with insertional oncogenesis [ Time Frame: Up to 5 years ]
    PBMC samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
  • Substudy 2: Number of patients with positive anti-drug antibodies (ADA) against GSK3377794 [ Time Frame: Up to 36 months ]
    Serum samples will be collected up to 36 months for ADA test.
  • Substudy 2: Titers of ADA against GSK3377794 [ Time Frame: Up to 36 months ]
    Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
  • Substudy 2: Change from Baseline in hematology parameters: platelets [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 2: Change from Baseline in hematology parameters: hematocrit [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 2: Change from Baseline in hematology parameters: hemoglobin [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 2: Change from Baseline in hematology parameters: Red blood cell (RBC) count [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of hematology parameters.
  • Substudy 2: Change from Baseline in hematology parameters: White blood cell (WBC) count [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of hematology parameters.
  • 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 ]
    Blood samples will be collected for analysis of clinical chemistry parameters.
  • Substudy 2: Change from Baseline in clinical chemistry parameters: Blood Urea Nitrogen (BUN) [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of clinical chemistry parameters.
  • Substudy 2: Change from Baseline in clinical chemistry parameters: Total and Direct bilirubin, Creatinine [ Time Frame: Baseline and up to 5 years ]
    Blood samples will be collected for analysis of clinical chemistry parameters.
  • Substudy 2: Change from Baseline in urine parameters: potential of hydrogen (pH) [ Time Frame: Baseline and up to day -4 ]
    Urine samples will be collected for analysis of urine parameters.
  • Substudy 2: Change from Baseline in urine parameters: glucose, protein, blood, bilirubin [ Time Frame: Baseline and up to day -4 ]
    Urine samples will be collected for analysis of urine parameters.
  • Substudy 2: T Cell Persistence of GSK3377794 [ Time Frame: Up to 5 years ]
    Blood samples will be collected for T Cell Persistence analysis of GSK3377794 transduced cell quantities.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
Brief Summary This trial will evaluate safety and efficacy of GSK3377794 in participants with solid tumors, initially in participants with synovial sarcoma. Adoptive T-cell therapy (ACT) is a therapeutic approach that uses T lymphocytes of participants with cancer, obtained by leukapheresis, with the aim of generating an anti-tumor T-cell immune response.
Detailed Description 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 consisting of a core protocol with multiple independent substudies, investigating GSK3377794 treatment in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO1+ advanced metastatic or unresectable synovial sarcoma (Substudy 1) and GSK3377794 as second line or higher (2L+) treatment HLA-A*02+ participants with NY-ESO-1+ advanced metastatic or unresectable synovial sarcoma who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
This will be an open-label study. Hence, there will be no masking.
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: letetresgene autoleucel
    letetresgene autoleucel as a single IV infusion.
  • Drug: Fludarabine
    Fludarabine will be used as the lymphodepleting chemotherapy via IV administration.
  • Drug: Cyclophosphamide
    Cyclophosphamide will be used as the lymphodepleting chemotherapy via IV administration.
Study Arms  ICMJE
  • Experimental: Substudy 1: letetresgene autoleucel
    Participants with previously untreated advanced metastatic synovial sarcoma will receive letetresgene autoleucel, administered as a single intravenous (IV) infusion.
    Interventions:
    • Drug: letetresgene autoleucel
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Substudy 2: letetresgene autoleucel
    Participants with advanced metastatic synovial sarcoma who have progressed following treatment with anthracycline-based chemotherapy will receive letetresgene autoleucel, administered as a single IV infusion.
    Interventions:
    • Drug: letetresgene autoleucel
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 28, 2019)
65
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2026
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must be greater than or equal to 10 years of age at the time of signing the informed consent. Participant enrolled under clinical drug product supply must also weigh greater than or equal to 40 kg.
  • Participant has a diagnosis of synovial sarcoma confirmed by histology.
  • Participant has advanced (metastatic or unresectable) synovial sarcoma.
  • In substudy 1, participant with metastatic synovial sarcoma who is newly diagnosed or previously untreated.
  • In substudy 2, at the time of treatment, participant 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.
  • Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a designated central laboratory.
  • Participant tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression.
  • Performance status: for participants less than 16 years of age, Lansky greater than 60, or for participants greater than or equal to 16 and less than 18 years of age, Karnofsky greater than 60, or for participants greater than or equal to 18 years of age, Eastern Cooperative Oncology Group of 0-1.
  • Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis.
  • Female participant of childbearing potential must have a negative urine or serum pregnancy test.
  • Participant has measurable disease according to RECIST v1.1.
  • Supportive radiotherapy has not affected greater than 25 percent of bone marrow.
  • A biopsy of non-target tumor tissue obtained within 28 days prior to lymphodepletion.

Exclusion Criteria:

  • In substudy 1, participant 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 participant's ability to tolerate protocol therapy or significantly increase the risk of complications, or, prior or active demyelinating disease.
  • Participant 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 less than or equal to 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.
  • Participant has active infection as defined in the protocol.
  • Participant has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
  • Participant had major surgery in less than or equal to 28 days of first dose of study intervention.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Canada,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03967223
Other Study ID Numbers  ICMJE 208467
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP