- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03709706
Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells in New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1)/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab
February 20, 2024 updated by: GlaxoSmithKline
A Phase 1b/2a Pilot Study to Evaluate the Safety and Tolerability of Autologous T-Cells Expressing Enhanced TCRs (T Cell Receptors) Specific for NY-ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination With Pembrolizumab in HLA-A2+ Participants With NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent Non-Small Cell Lung Cancer
This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.
Study Overview
Detailed Description
New York esophageal squamous cell carcinoma-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 (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells.
This is a multi-arm, open-label study of letetresgene autoleucel (lete-cel, GSK3377794) in Human Leukocyte Antigen (HLA)-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive adults whose tumors express NY-ESO-1 and/or LAGE-1a.
This study will enroll participants who have unresectable Stage IIIb or Stage IV NSCLC.
Study Type
Interventional
Enrollment (Actual)
34
Phase
- Phase 2
- Phase 1
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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Ontario
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Toronto, Ontario, Canada, M5G 1X6
- GSK Investigational Site
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Quebec
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Montréal, Quebec, Canada, H2X 0A9
- GSK Investigational Site
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Amsterdam, Netherlands, 1066 CX
- GSK Investigational Site
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Groningen, Netherlands, 9713 GZ
- GSK Investigational Site
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Rotterdam, Netherlands, 3015 GD
- GSK Investigational Site
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Utrecht, Netherlands, 3584 CX
- GSK Investigational Site
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Barcelona, Spain, 08035
- GSK Investigational Site
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Madrid, Spain, 28040
- GSK Investigational Site
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Madrid, Spain, 28050
- GSK Investigational Site
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London, United Kingdom, WC1E 6AG
- GSK Investigational Site
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Manchester, United Kingdom, M20 4BX
- GSK Investigational Site
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California
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Duarte, California, United States, 91010
- GSK Investigational Site
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La Jolla, California, United States, 92093-0987
- GSK Investigational Site
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Sacramento, California, United States, 95817
- GSK Investigational Site
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Stanford, California, United States, 94305
- GSK Investigational Site
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Colorado
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Denver, Colorado, United States, 80218
- GSK Investigational Site
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Florida
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Hollywood, Florida, United States, 33021
- GSK Investigational Site
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Georgia
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Atlanta, Georgia, United States, 30322
- GSK Investigational Site
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Illinois
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Chicago, Illinois, United States, 60637
- GSK Investigational Site
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Iowa
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Iowa City, Iowa, United States, 52242
- GSK Investigational Site
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Kentucky
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Lexington, Kentucky, United States, 40536
- GSK Investigational Site
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Maryland
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Baltimore, Maryland, United States, 21201
- GSK Investigational Site
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Missouri
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Saint Louis, Missouri, United States, 63110
- GSK Investigational Site
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New York
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New York, New York, United States, 10065
- GSK Investigational Site
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North Carolina
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Durham, North Carolina, United States, 27710
- GSK Investigational Site
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Ohio
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Columbus, Ohio, United States, 43210
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- GSK Investigational Site
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Pittsburgh, Pennsylvania, United States, 15232
- GSK Investigational Site
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Tennessee
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Nashville, Tennessee, United States, 37203
- GSK Investigational Site
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Texas
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Houston, Texas, United States, 77030
- GSK Investigational Site
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Utah
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Salt Lake City, Utah, United States, 84112-5550
- 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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age >=18 years on the day of signing informed consent.
- Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Participant is positive for any of the following alleles: human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and a) or HLA-A*02:06 by a validated test.
- Participant's tumor meets the pre-defined threshold for expression of NY-ESO-1 and/or LAGE-1a.
- Adequate organ function and blood cell counts, as defined in the protocol.
- Predicted life expectancy that is >=24 weeks from leukapheresis.
- Left ventricular ejection fraction >=45%.
- Prior therapies prior to lymphodepletion: a) All participants with NSCLC lacking actionable genetic aberrations, per National Comprehensive Cancer Network (NCCN) guidelines (Arms A and B), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy. For participants in the metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. OR b) All participants with NSCLC with actionable genetic aberrations, per NCCN guidelines (Arm C only), should have received appropriate targeted therapy following NCCN or equivalent country-level guidelines.
- Disease progression at time of treatment, as defined in the protocol.
- Measurable disease at time of treatment per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by local site investigator/radiology.
Exclusion Criteria:
- Prior treatment: 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.
- Prior allogeneic/autologous bone marrow or solid organ transplantation.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (DMSO) or other agents used in the study.
- Severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its excipients.
- Active autoimmune disease that has required systemic treatment in past 2 years.
- History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
- Uncontrolled intercurrent illness.
- Participant has active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), syphilis, or human T lymphotropic virus (HTLV), as defined in protocol.
- Known psychiatric or substance abuse disorders.
- Symptomatic or untreated central nervous system (CNS) metastases.
- Radiotherapy that involves the lung (Percentage of normal lung receiving at least 20 Gray [Gy] during radiotherapy [V20] exceeding 30% lung volume or mean heart dose >20 Gy) within 3 months or radiotherapy (including but not limited to palliative radiotherapy) to lung/mediastinum with V20 less than 30% lung volume and with mean heart dose <=20 Gy within 4 weeks (+/- 3 days).
- Radiotherapy of >=50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the investigator's opinion would predispose participants to prolonged cytopenia after lymphodepletion.
- All of the participant's measurable lesions have been irradiated within 3 months before lymphodepletion.
- Other protocol-defined inclusion/exclusion criteria may apply.
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: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Arm A: lete-cel monotherapy
In Arm A, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel monotherapy.
Participants who subsequently progress by Week 25 will be offered pembrolizumab.
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lete-cel will be administered to eligible participants.
Pembrolizumab will be administered to eligible participants.
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Experimental: Arm B: lete-cel plus pembrolizumab
In Arm B, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
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lete-cel will be administered to eligible participants.
Pembrolizumab will be administered to eligible participants.
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Experimental: Arm C: lete-cel plus pembrolizumab
In Arm C, participants with NSCLC (with actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
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lete-cel will be administered to eligible participants.
Pembrolizumab will be administered to eligible participants.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to approximately 10 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 which start or worsen on or after T-cell infusion are defined as treatment-emergent.
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Up to approximately 10 months
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Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
Time Frame: Up to approximately 10 months
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AESI included cytokine release syndrome (CRS), pneumonitis/pneumonia, graft vs host disease (GvHD), guillain barre syndrome (GBS) or acute inflammatory demyelinating polyneuropathy (AIDP), pancytopenia/aplastic anemia (including analysis of all hematopoietic cytopenias), immune effector cell-associated neurotoxicity syndrome (ICANS) and treatment-related inflammatory response at tumor site.
AEs which start or worsen on or after T-cell infusion are defined as treatment-emergent.
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Up to approximately 10 months
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Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades
Time Frame: Up to approximately 10 months
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An AE is any untoward medical occurrence in a clinical investigation, 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 which start or worsen on or after T-cell infusion are defined as TE.
Severity was reported during study and was assigned a grade according to the National Institutes of Health National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
SAEs are subset of AEs.
AEs and SAEs severity graded on a 5-point scale as: 1 = mild, 2 = moderate discomfort, 3 = severe, 4 = life-threatening and 5 = death due to AE.
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Up to approximately 10 months
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Number of Participants With AEs Leading to Dose Delays
Time Frame: Up to approximately 10 months
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An AE is any untoward medical occurrence in a clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Number of participants with AEs leading to dose delays were summarized.
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Up to approximately 10 months
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Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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Overall response rate (ORR) defined as the percentage of participants with a complete response (CR) or partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria in Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population.
Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Complete response is defined as the 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).
Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
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Up to approximately 10 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause.
Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
PFS based on responses assessed by investigator per RECIST v1.1 is presented.
Kaplan-Meier Median and 95% confidence intervals are presented.
Confidence intervals were calculated using the Brookmeyer-Crowley method.
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Up to approximately 10 months
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Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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DCR was defined as the percentage of participants with a confirmed complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months as per RECIST v1.1.
Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Complete response is defined as the 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).
SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
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Up to approximately 10 months
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Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 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 or death among participants with a confirmed response per RECIST 1.1.
Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Complete response is defined as the 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.
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Up to approximately 10 months
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Time to Response (TTR) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 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.
Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Complete response is defined as the disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.
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Up to approximately 10 months
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Maximum Transgene Expansion (Cmax) of Lete-cel
Time Frame: Day 1 to Day 15
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Cmax was defined as peak cell expansion during the study.
Blood samples were collected for analysis of Cmax of lete-cel.
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Day 1 to Day 15
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Time to Cmax (Tmax) of Lete-cel
Time Frame: Day 1 to Day 15
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Tmax was defined as time to reach peak cell expansion during the study.
Blood samples were collected for analysis of Tmax of lete-cel.
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Day 1 to Day 15
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Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel
Time Frame: Up to 28 days
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Area under the cell expansion-time curve from first T-cell infusion to Day 28.
Blood samples were collected to measure AUC (0-28 days).
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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
Collaborators
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, 2018
Primary Completion (Actual)
June 27, 2022
Study Completion (Actual)
November 4, 2022
Study Registration Dates
First Submitted
October 15, 2018
First Submitted That Met QC Criteria
October 15, 2018
First Posted (Actual)
October 17, 2018
Study Record Updates
Last Update Posted (Estimated)
February 23, 2024
Last Update Submitted That Met QC Criteria
February 20, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- 208471
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing 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
IPD Sharing 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
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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