Back to resultsStudy to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Primary Purpose
Neoplasms
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Letetresgene autoleucel
Cyclophosphamide
Fludarabine
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring Adoptive T-cell therapy, Letetresgene autoleucel, Lete-cel, GSK3377794
Eligibility 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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Letetresgene autoleucel
Arm Description
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). 95% CI is based on Clopper-Pearson exact confidence interval.
Secondary Outcome Measures
Time to Response (TTR)
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
Duration of Response (DOR)
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease as assessed by local investigators, or death among participants with a confirmed response per RECIST 1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with a minimal 12 weeks (84 days ± 7 day window) duration relative to the total number of participants within the analysis population at the time of primary analysis as determined by local investigators per RECIST v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. The disease progression (PD) is defined as the date of radiological disease progression based on imaging data per RECIST v1.1. 95% CI is based on Clopper-Pearson exact confidence interval.
Progression Free Survival (PFS)
PFS is defined as the interval of time between from the date of T-cell infusion to the earliest date of radiological progression of disease (PD) as assessed by local investigator per RECIST v1.1, or death due to any cause. The PD is defined as the date of radiological disease progression based on imaging data per RECIST v1.1.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
Number of Participants With AEs of Special Interest (AESIs)
An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome (CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.
Number of Participants With TEAEs and TESAEs by Severity
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs and SAEs were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences; Grade 5- Death related to AE.
Number of Participants With AESIs by Severity
An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome (CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.
Percentage of Participants With Replication Competent Lentivirus (RCL) Positive
RCL was monitored using a polymerase chain reaction (PCR)-based assay that detects and measures copies of the gene coding for the vector's envelope protein, namely vesicular stomatitis virus G protein (VSV-G).
Instances of Insertional Oncogenesis (IO)
Instances of Insertional Oncogenesis (IO) was summarized descriptively.
Maximum Transgene Expansion (Cmax)
Cmax was defined as maximum observed persistence, determined directly from the persistence-time data. Blood samples were collected for PK analysis.
Time to Cmax (Tmax)
Tmax was defined as time to reach Cmax, determined directly from the persistence-time data. Blood samples were collected for PK analysis.
Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])
Area under the persistence-time curve from time zero to Day 28. Blood samples were collected for PK analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05993299
Brief Title
Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Official Title
Evaluation of Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 31, 2019 (Actual)
Primary Completion Date
October 12, 2022 (Actual)
Study Completion Date
July 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors. This trial is a sub study of the Master study NCT03967223.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
Adoptive T-cell therapy, Letetresgene autoleucel, Lete-cel, GSK3377794
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Letetresgene autoleucel
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Letetresgene autoleucel
Intervention Description
Letetresgene autoleucel will be administered.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide will be used as a lymphodepleting chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine will be used as a lymphodepleting chemotherapy.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). 95% CI is based on Clopper-Pearson exact confidence interval.
Time Frame
Up to approximately 36 months
Secondary Outcome Measure Information:
Title
Time to Response (TTR)
Description
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
Time Frame
Up to approximately 54 months
Title
Duration of Response (DOR)
Description
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease as assessed by local investigators, or death among participants with a confirmed response per RECIST 1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
Time Frame
Up to approximately 54 months
Title
Disease Control Rate (DCR)
Description
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with a minimal 12 weeks (84 days ± 7 day window) duration relative to the total number of participants within the analysis population at the time of primary analysis as determined by local investigators per RECIST v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. The disease progression (PD) is defined as the date of radiological disease progression based on imaging data per RECIST v1.1. 95% CI is based on Clopper-Pearson exact confidence interval.
Time Frame
Up to approximately 36 months
Title
Progression Free Survival (PFS)
Description
PFS is defined as the interval of time between from the date of T-cell infusion to the earliest date of radiological progression of disease (PD) as assessed by local investigator per RECIST v1.1, or death due to any cause. The PD is defined as the date of radiological disease progression based on imaging data per RECIST v1.1.
Time Frame
Up to approximately 54 months
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
Time Frame
Up to approximately 54 months
Title
Number of Participants With AEs of Special Interest (AESIs)
Description
An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome (CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.
Time Frame
Up to approximately 54 months
Title
Number of Participants With TEAEs and TESAEs by Severity
Description
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. AEs and SAEs were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences; Grade 5- Death related to AE.
Time Frame
Up to approximately 54 months
Title
Number of Participants With AESIs by Severity
Description
An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome (CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.
Time Frame
Up to approximately 54 months
Title
Percentage of Participants With Replication Competent Lentivirus (RCL) Positive
Description
RCL was monitored using a polymerase chain reaction (PCR)-based assay that detects and measures copies of the gene coding for the vector's envelope protein, namely vesicular stomatitis virus G protein (VSV-G).
Time Frame
Up to approximately 54 months
Title
Instances of Insertional Oncogenesis (IO)
Description
Instances of Insertional Oncogenesis (IO) was summarized descriptively.
Time Frame
Up to approximately 54 months
Title
Maximum Transgene Expansion (Cmax)
Description
Cmax was defined as maximum observed persistence, determined directly from the persistence-time data. Blood samples were collected for PK analysis.
Time Frame
Day 1 to Day 14
Title
Time to Cmax (Tmax)
Description
Tmax was defined as time to reach Cmax, determined directly from the persistence-time data. Blood samples were collected for PK analysis.
Time Frame
Day 1 to Day 14
Title
Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])
Description
Area under the persistence-time curve from time zero to Day 28. Blood samples were collected for PK analysis.
Time Frame
Up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
GSK Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9063
Country
United States
Facility Name
GSK Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
IPD Sharing Time Frame
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
IPD Sharing Access Criteria
Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
IPD Sharing URL
http://www.gsk.com/en-gb/innovation/trials/data-transparency/
Learn more about this trial
Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
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