- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05993299
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
September 18, 2023 updated by: GlaxoSmithKline
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
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
7
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Quebec
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Montreal, Quebec, Canada, H1T 2M4
- GSK Investigational Site
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Amsterdam, Netherlands, 1066 CX
- GSK Investigational Site
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London, United Kingdom, SW3 6JJ
- GSK Investigational Site
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- GSK Investigational Site
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Texas
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Dallas, Texas, United States, 75390-9063
- GSK Investigational Site
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Letetresgene autoleucel
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Fludarabine will be used as a lymphodepleting chemotherapy.
Cyclophosphamide will be used as a lymphodepleting chemotherapy.
Letetresgene autoleucel will be administered.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Up to approximately 36 months
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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.
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Up to approximately 36 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Response (TTR)
Time Frame: Up to approximately 54 months
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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).
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Up to approximately 54 months
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Duration of Response (DOR)
Time Frame: Up to approximately 54 months
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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).
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Up to approximately 54 months
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Disease Control Rate (DCR)
Time Frame: Up to approximately 36 months
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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.
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Up to approximately 36 months
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Progression Free Survival (PFS)
Time Frame: Up to approximately 54 months
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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.
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Up to approximately 54 months
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time Frame: Up to approximately 54 months
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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.
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Up to approximately 54 months
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Number of Participants With AEs of Special Interest (AESIs)
Time Frame: Up to approximately 54 months
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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.
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Up to approximately 54 months
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Number of Participants With TEAEs and TESAEs by Severity
Time Frame: Up to approximately 54 months
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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.
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Up to approximately 54 months
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Number of Participants With AESIs by Severity
Time Frame: Up to approximately 54 months
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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.
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Up to approximately 54 months
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Percentage of Participants With Replication Competent Lentivirus (RCL) Positive
Time Frame: Up to approximately 54 months
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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).
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Up to approximately 54 months
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Instances of Insertional Oncogenesis (IO)
Time Frame: Up to approximately 54 months
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Instances of Insertional Oncogenesis (IO) was summarized descriptively.
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Up to approximately 54 months
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Maximum Transgene Expansion (Cmax)
Time Frame: Day 1 to Day 14
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Cmax was defined as maximum observed persistence, determined directly from the persistence-time data.
Blood samples were collected for PK analysis.
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Day 1 to Day 14
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Time to Cmax (Tmax)
Time Frame: Day 1 to Day 14
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Tmax was defined as time to reach Cmax, determined directly from the persistence-time data.
Blood samples were collected for PK analysis.
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Day 1 to Day 14
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Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])
Time Frame: Up to 28 days
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Area under the persistence-time curve from time zero to Day 28.
Blood samples were collected for PK analysis.
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Up to 28 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 31, 2019
Primary Completion (Actual)
October 12, 2022
Study Completion (Estimated)
July 1, 2024
Study Registration Dates
First Submitted
August 7, 2023
First Submitted That Met QC Criteria
August 7, 2023
First Posted (Actual)
August 15, 2023
Study Record Updates
Last Update Posted (Actual)
October 16, 2023
Last Update Submitted That Met QC Criteria
September 18, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Connective Tissue
- Sarcoma
- Neoplasms, Adipose Tissue
- Liposarcoma
- Liposarcoma, Myxoid
- Sarcoma, Synovial
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
Other Study ID Numbers
- 208467 Substudy 1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD 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 Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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