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Trial record 1 of 1 for:    NCT03967223
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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 (IGNYTE-ESO)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03967223
Recruitment Status : Active, not recruiting
First Posted : May 30, 2019
Last Update Posted : October 31, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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Brief Summary:
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Letetresgene autoleucel (lete-cel, GSK3377794) 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. Letetresgene autoleucel (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor engineered T cells. This is a master protocol investigating T-cell therapies. It will initially consist of a core protocol with two independent substudies investigating Letetresgene autoleucel in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS) (Substudy 1) and Letetresgene autoleucel as second line or higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) SS or MRCLS who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 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


Arms and Interventions
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Arm Intervention/treatment
Experimental: Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
 Drug: Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered.

Drug: Fludarabine
Fludarabine will be used as the lymphodepleting chemotherapy

Drug: Cyclophosphamide
Cyclophosphamide will be used as the lymphodepleting chemotherapy.
Experimental: Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
 Drug: Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered.

Drug: Fludarabine
Fludarabine will be used as the lymphodepleting chemotherapy

Drug: Cyclophosphamide
Cyclophosphamide will be used as the lymphodepleting chemotherapy.


Outcome Measures
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Primary Outcome Measures :
  1. Substudy 1: Overall response rate (ORR) [ 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 per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. as determined by the local investigators.

  2. Substudy 2: Overall response rate (ORR) as assessed by central independent review [ 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 per RECIST v1.1. as assessed by central independent review.


Secondary Outcome Measures :
  1. Substudy 1 and 2: Time to response (TTR) [ Time Frame: Until disease progression (up to 5 years) ]
    Time to response is defined as time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by local investigators per RECIST v1.1.

  2. Substudy 1 and 2: Duration of response (DOR) [ 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 local investigators, 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 (DCR) [ 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 (PFS) [ Time Frame: Until disease progression (up to 5 years) ]
    Progression free survival is defined as the time from the date of T-cell administration until first documented sign of disease progression per RECIST v1.1, or death.

  5. Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity [ Time Frame: Until disease progression (up to 5 years) ]
    AEs, SAEs and AESIs will be collected. Severity of AEs and SAEs will be summarized using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

  6. 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.

  7. Substudy 1 and 2: Number of participants with insertional oncogenesis (IO) [ 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.

  8. Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters [ Time Frame: Until disease progression (up to 5 years) ]
    Blood and urine samples will be collected for assessment of hematology, clinical chemistry and urinalysis parameters.

  9. Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel [ Time Frame: Until disease progression (up to 5 years) ]
    Whole blood samples will be collected at indicated time points for evaluation of Cmax.

  10. Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel [ Time Frame: Until disease progression (up to 5 years) ]
    Whole blood samples will be collected at indicated time points for evaluation of Tmax.

  11. Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel [ Time Frame: Until disease progression (up to 5 years) ]
    Whole blood samples will be collected at indicated time points for evaluation of AUC(0-t).

  12. Substudy 2: Overall response rate (ORR) as determined by the local investigators [ 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 per RECIST v1.1. as determined by the local investigators.

  13. Substudy 2: Overall Survival (OS) [ 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.

  14. Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel [ Time Frame: Up to 36 months ]
    Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.


Eligibility Criteria
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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 on the day of signing informed consent.
  • Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a designated central laboratory
  • Participant's tumor is positive for NY-ESO-1 expression by a designated central laboratory.
  • Participant has a diagnosis of synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS)
  • Performance status: dependent on age - Lansky > 60, Karnofsky > 60, Eastern Cooperative Oncology Group 0-1.
  • Participant must have adequate organ function and blood cell counts, within 7 days prior to leukapheresis.
  • At time of treatment, participant has measurable disease according to RECIST v1.1.
  • Consultation for prior history per protocol specifications.

Exclusion Criteria:

  • Central nervous system metastases.
  • 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 (e.g. Crohn's disease, systemic lupus) 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 chemotherapy must be followed.
  • Participant had major surgery in less than or equal to 28 days of first dose of study intervention.
  • Prior radiation exceeds protocol specified limits.
Contacts and Locations
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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


Locations
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United States, California
GSK Investigational Site
Duarte, California, United States, 91010
GSK Investigational Site
Stanford, California, United States, 94305
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80218
United States, Florida
GSK Investigational Site
Jacksonville, Florida, United States, 32224
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60637
United States, Iowa
GSK Investigational Site
Iowa City, Iowa, United States, 52242-1009
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02114
United States, Michigan
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55455
GSK Investigational Site
Rochester, Minnesota, United States, 55905
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63110
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27710
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97239
United States, Pennsylvania
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75390-8565
GSK Investigational Site
Dallas, Texas, United States, 75390-9063
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84112
United States, Virginia
GSK Investigational Site
Richmond, Virginia, United States, 23298
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98109-1024
United States, Wisconsin
GSK Investigational Site
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H1T 2M4
France
GSK Investigational Site
Lyon cedex 08, France, 69373
GSK Investigational Site
Pessac cedex, France, 33604
Italy
GSK Investigational Site
Milano, Lombardia, Italy, 20133
GSK Investigational Site
Rozzano (MI), Lombardia, Italy, 20089
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
Spain
GSK Investigational Site
Barcelona, Spain, 08025
GSK Investigational Site
Hospitalet de Llobregat, Barcelona, Spain, 08907
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Sevilla, Spain, 41013
United Kingdom
GSK Investigational Site
London, United Kingdom, SW3 6JJ
GSK Investigational Site
London, United Kingdom, WC1E 6AG
GSK Investigational Site
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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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: October 31, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
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 disease
Advanced unresectable disease
Synovial sarcoma
Myxoid/round cell liposarcoma
GSK3377794
 Positive solid tumors
T-cell receptors
Leukapheresis
Letetresgene autoleucel
Lete-cel
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