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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

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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: letetresgene autoleucel Drug: Fludarabine Drug: Cyclophosphamide Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
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
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)
Actual Study Start Date : December 31, 2019
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : July 31, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Substudy 1: letetresgene autoleucel
Participants with previously untreated advanced metastatic synovial sarcoma will receive letetresgene autoleucel, administered as a single intravenous (IV) infusion.
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.

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.
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.




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03967223


Contacts
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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

Locations
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United States, California
GSK Investigational Site Recruiting
Duarte, California, United States, 91010
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Warren Chow         
GSK Investigational Site Recruiting
Stanford, California, United States, 94305
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kristen Ganjoo         
United States, Colorado
GSK Investigational Site Recruiting
Denver, Colorado, United States, 80218
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Shiraj Sen         
United States, Florida
GSK Investigational Site Recruiting
Jacksonville, Florida, United States, 32224
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Steven Attia         
United States, Illinois
GSK Investigational Site Recruiting
Chicago, Illinois, United States, 60637
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ami V Desai         
United States, Iowa
GSK Investigational Site Recruiting
Iowa City, Iowa, United States, 52242-1009
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Varun V Monga         
United States, Michigan
GSK Investigational Site Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Rashmi Chugh         
United States, Minnesota
GSK Investigational Site Recruiting
Rochester, Minnesota, United States, 55905
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Steven I Robinson         
United States, Missouri
GSK Investigational Site Recruiting
Saint Louis, Missouri, United States, 63110
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Brian Van Tine         
United States, New York
GSK Investigational Site Recruiting
New York, New York, United States, 10065
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sandra P D'Angelo         
United States, North Carolina
GSK Investigational Site Recruiting
Durham, North Carolina, United States, 27710
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Richard Riedel         
United States, Oregon
GSK Investigational Site Recruiting
Portland, Oregon, United States, 97239
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Lara Davis         
United States, Pennsylvania
GSK Investigational Site Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Melissa Burgess         
United States, Tennessee
GSK Investigational Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Melissa L Johnson         
United States, Texas
GSK Investigational Site Recruiting
Dallas, Texas, United States, 75390-9063
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Samuel John         
United States, Utah
GSK Investigational Site Recruiting
Salt Lake City, Utah, United States, 84112
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Anna Chalmers         
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Albiruni Ryan Abdul Razak         
Canada, Quebec
GSK Investigational Site Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Jonathan Noujaim         
Italy
GSK Investigational Site Recruiting
Milano, Lombardia, Italy, 20133
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Silvia Stacchiotti         
Netherlands
GSK Investigational Site Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: John B.A.G. Haanen         
Spain
GSK Investigational Site Recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Juan Jesús Martín Liberal         
GSK Investigational Site Recruiting
Sevilla, Spain, 41013
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Javier Martín Broto         
United Kingdom
GSK Investigational Site Recruiting
London, United Kingdom, WC1E 6AG
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Sandra Strauss         
GSK Investigational Site Recruiting
Manchester, United Kingdom, M20 4BX
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Fiona Thistlethwaite         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03967223    
Other Study ID Numbers: 208467
First Posted: May 30, 2019    Key Record Dates
Last Update Posted: September 4, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Adoptive T-cell therapy
Advanced metastatic synovial sarcoma
GSK3377794
Positive solid tumors
T-cell receptors
Leukapheresis
Personalized T-cell Therapy
letetresgene autoleucel
Additional relevant MeSH terms:
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Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists