ClinicalTrials.gov

History of Changes for Study: NCT03967223
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
Latest version (submitted February 1, 2022) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 May 28, 2019 None (earliest Version on record)
2 September 19, 2019 Study Status and Study Identification
3 September 25, 2019 Study Status
4 October 15, 2019 Study Status and Contacts/Locations
5 October 20, 2019 Study Status and Contacts/Locations
6 October 28, 2019 Study Status
7 November 11, 2019 Study Status and Contacts/Locations
8 December 12, 2019 Study Status
9 January 9, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
10 January 22, 2020 Contacts/Locations and Study Status
11 February 4, 2020 Study Status and Contacts/Locations
12 February 25, 2020 Contacts/Locations and Study Status
13 March 9, 2020 Study Status and Contacts/Locations
14 March 22, 2020 Contacts/Locations and Study Status
15 March 26, 2020 Contacts/Locations and Study Status
16 April 17, 2020 Study Status and Contacts/Locations
17 April 27, 2020 Contacts/Locations and Study Status
18 May 5, 2020 Study Status and Contacts/Locations
19 August 11, 2020 Arms and Interventions, Contacts/Locations, Outcome Measures, Study Status, IPDSharing, Study Description, Eligibility and Conditions
20 September 2, 2020 Contacts/Locations and Study Status
21 October 6, 2020 Study Status and Contacts/Locations
22 October 23, 2020 Contacts/Locations and Study Status
23 November 25, 2020 Contacts/Locations and Study Status
24 February 22, 2021 Outcome Measures, Arms and Interventions, Contacts/Locations, Study Description, Study Status, IPDSharing, Eligibility, Study Design, Conditions and Study Identification
25 April 16, 2021 Study Status and Contacts/Locations
26 June 3, 2021 Study Status and Contacts/Locations
27 September 20, 2021 Outcome Measures, Arms and Interventions, Study Status, Contacts/Locations, Eligibility and Study Description
28 November 16, 2021 Contacts/Locations and Study Status
29 February 1, 2022 Study Status, Outcome Measures, Study Design, Conditions and Study Description
Comparison Format:

Scroll up to access the controls

Study NCT03967223
Submitted Date:  May 28, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 208467
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
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2019
Overall Status: Not yet recruiting
Study Start: September 30, 2019
Primary Completion: January 14, 2022 [Anticipated]
Study Completion: December 15, 2025 [Anticipated]
First Submitted: May 10, 2019
First Submitted that
Met QC Criteria:
May 28, 2019
First Posted: May 30, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
May 28, 2019
Last Update Posted: May 30, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: GlaxoSmithKline
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: 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).
Open or close this module Conditions
Conditions: Neoplasms
Keywords: Adoptive T-cell therapy
Advanced metastatic synovial sarcoma
GSK3377794
Positive solid tumors
T-cell receptors
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 65 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Substudy 1: GSK3377794
After 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.
Drug: GSK3377794
GSK3377794 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: GSK3377794
After 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.
Drug: GSK3377794
GSK3377794 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.
Open or close this module Outcome Measures
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 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.
2. 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.
Secondary Outcome Measures:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. Substudy 2: Number of patients with RCL
[ Time Frame: Up to 5 years ]

RCL exposure will be assessed by PCR based assay.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.
Open or close this module Eligibility
Minimum Age: 10 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Central Contact Person: US GSK Clinical Trials Call Center
Telephone: 877-379-3718
Email: GSKClinicalSupportHD@gsk.com
Central Contact Backup: EU GSK Clinical Trials Call Center
Telephone: +44 (0) 20 89904466
Email: GSKClinicalSupportHD@gsk.com
Study Officials: GSK Clinical Trials
Study Director
GlaxoSmithKline
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Information:
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 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
Open or close this module References
Citations:
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services