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History of Changes for Study: NCT04526509
Investigation of Autologous Enhanced T Cells in Advanced Tumors
Latest version (submitted August 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 21, 2020 None (earliest Version on record)
2 September 2, 2020 Study Status and Contacts/Locations
3 September 13, 2020 Contacts/Locations and Study Status
4 September 24, 2020 Study Status
5 October 6, 2020 Study Status
6 January 11, 2021 Recruitment Status, Outcome Measures, Study Status, Contacts/Locations, Study Description, Eligibility, Conditions and Study Identification
7 January 25, 2021 Contacts/Locations and Study Status
8 April 1, 2021 Study Status and Contacts/Locations
9 May 5, 2021 Study Status and Contacts/Locations
10 September 20, 2021 Contacts/Locations, Outcome Measures, Study Status, Eligibility and Study Description
11 February 2, 2022 Arms and Interventions, Study Status, Contacts/Locations, Eligibility, Outcome Measures, Conditions, Study Description and Study Identification
12 April 14, 2022 Arms and Interventions, Study Status, Outcome Measures, Contacts/Locations, Eligibility, Study Design, Conditions, Study Description and Study Identification
13 August 28, 2022 Study Status, Contacts/Locations, Eligibility, Outcome Measures and Study Design
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Study NCT04526509
Submitted Date:  August 21, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: 209012
Brief Title: Investigation of Autologous Enhanced T Cells in Advanced Tumors
Official Title: Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2020
Overall Status: Not yet recruiting
Study Start: September 21, 2020
Primary Completion: February 12, 2024 [Anticipated]
Study Completion: February 12, 2024 [Anticipated]
First Submitted: August 21, 2020
First Submitted that
Met QC Criteria:
August 21, 2020
First Posted: August 25, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
August 21, 2020
Last Update Posted: August 25, 2020 [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: No
Open or close this module Study Description
Brief Summary: This is a study evaluating treatment with adoptive transfer of autologous T-cells engineered to express a T-cell receptor (TCR) that targets the tumor associated protein New York esophageal antigen-1 (NY-ESO-1).
Detailed Description: Clinical trials using adoptively transferred T-cells directed against NY-ESO-1 have shown objective responses. GSK3901961 and GSK3845097 included in this trial, are NY-ESO-1 specific TCR engineered T-cells that incorporate additional modifications within the gene construct for the same NYESO-1 targeting TCR evaluated in previous clinical trials, that allow for co-expression with the TCR, of molecules that potentially enhance the function and survival of transduced T-cells. This is a master protocol that will initially consist of two substudies: the first investigating GSK3901961 in previously treated advanced (metastatic or unresectable) synovial sarcoma (SS) and previously treated metastatic non-small cell lung cancer (NSCLC) (Substudy 1); the second investigating GSK3845097 in previously treated advanced synovial sarcoma (Substudy 2).
Open or close this module Conditions
Conditions: Neoplasms
Keywords: Adoptive T-cell therapy
Advanced synovial sarcoma
Advanced non-small cell lung cancer
Advanced tumors
GSK3845097
GSK3901961
T cell receptors
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 38 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Substudy 1: GSK3901961 in previously treated advanced SS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Drug: GSK3901961
GSK3901961 as an IV infusion.
Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 1: GSK3901961 in previously treated metastatic NSCLC
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3901961, as a single IV infusion after completing lymphodepleting chemotherapy.
Drug: GSK3901961
GSK3901961 as an IV infusion.
Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
Experimental: Substudy 2: GSK3845097 in previously treated advanced SS
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive GSK3845097, as a single IV infusion after completing lymphodepleting chemotherapy.
Drug: GSK3845097
GSK3845097 as an IV infusion.
Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Substudy 1 and 2: Number of participants with dose limiting toxicities (DLTs)
[ Time Frame: Until disease progression (up to 4 years) ]

Toxicities will be considered DLTs if they are considered at least possibly related to transduced T-cells; and they occur within the DLT-assessment period.
2. Substudy 1 and 2: Severity of DLTs
[ Time Frame: Until disease progression (up to 4 years) ]

Severity of DLTs will be summarized using National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0.
3. Substudy 1 and 2: Number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI)
[ Time Frame: Until disease progression (up to 4 years) ]

AEs, SAEs and AESIs will be collected.
4. Substudy 1 and 2: Severity of AEs, SAEs and AESIs
[ Time Frame: Until disease progression (up to 4 years) ]

Severity of AEs, SAEs and AESIs will be summarized using NCI-CTCAE, version 5.0.
Secondary Outcome Measures:
1. Substudy 1 and 2: Overall response rate
[ Time Frame: Until disease progression (up to 4 years) ]

Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or a confirmed partial response (PR) relative to the total number of participants within the analysis population at any time per Response evaluation criteria in solid tumors (RECIST) version 1.1 as determined by the local investigators.
2. Substudy 1 and 2: Duration of response
[ Time Frame: Until disease progression (up to 4 years) ]

Duration of response is defined as, in the subset of participants who show a confirmed CR or PR as assessed by local investigators, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
3. Substudy 2: Progression free survival
[ Time Frame: Until disease progression (up to 4 years) ]

Progression free survival is defined as the time from the date of T-cell infusion until the first documented sign of disease progression per RECIST version 1.1 as determined by the local investigators or death due to any cause.
4. Substudy 2: Disease control rate
[ Time Frame: Until disease progression (up to 4 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 participants within the analysis population at any time per RECIST version 1.1 as determined by the local investigators.
5. Substudy 2: Time to response
[ Time Frame: Until disease progression (up to 4 years) ]

Time to response is defined as, in the subset of patients who achieved a confirmed PR or CR as assessed by local investigators per Response evaluation criteria in solid tumors (RECIST) version 1.1, the time from the date of T-cell infusion to first documented evidence of confirmed CR or PR.
6. Substudy 1 and 2: Maximum expansion/persistence (Cmax)
[ Time Frame: Until disease progression (up to 4 years) ]

Whole blood samples will be collected at indicated time points for evaluation of Cmax.
7. Substudy 1 and 2: Time to Cmax (Tmax)
[ Time Frame: Until disease progression (up to 4 years) ]

Whole blood samples will be collected at indicated time points for evaluation of Tmax.
8. Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t])
[ Time Frame: Until disease progression (up to 4 years) ]

Whole blood samples will be collected at indicated time points for evaluation of AUC (0 to t).
9. Substudy 1 and 2: Phenotype of transduced T cells
[ Time Frame: Until disease progression (up to 4 years) ]

Tumor samples will be collected to assess phenotype of transduced T cells.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Eligibility Criteria: Inclusion criteria:

  • Participant must be >=18 years of age on the day of signing informed consent.
  • Participant must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles
  • Participant's tumor is positive NY-ESO-1 expression by a designated central laboratory.
  • Performance status: Eastern Cooperative Oncology Group of 0-1.
  • Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis.
  • Participant must have measurable disease according to RECIST v1.1 Additional criteria for participants with synovial sarcoma
  • Participant has advanced (metastatic or unresectable) synovial sarcoma confirmed by histology.
  • Participant has received/completed treatment with anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable) disease and progressed.

Additional criteria for participants with non-small cell lung cancer (NSCLC):

  • Participant has Stage IV NSCLC as confirmed by histology or cytology.
  • Participant has been previously treated with or is intolerant to programmed death receptor-1 (PD)-1/Programmed cell death ligand 1 (PD-L1) checkpoint blockade therapy and doublet taxane & platinum chemotherapy.

Exclusion criteria:

  • Central nervous system metastases, except in rare cases of NSCLC as specified in the protocol.
  • Any other prior malignancy that is not in complete remission.
  • Clinically significant systemic illness.
  • Prior or active demyelinating disease.
  • History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
  • 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.
  • Washout periods for prior radiotherapy and systemic chemoterapy must be followed
  • Major surgery <=28 days of first dose of study intervention.
  • For participants with NSCLC that harbors an actionable genetic aberration, e.g. BRAF, anaplastic lymphoma kinase (ALK)/ c-ros oncogene 1 (ROS1) or others, has received and failed >=3 lines of systemic therapy.
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, 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
Open or close this module References
Citations:
Links:
Available IPD/Information:

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