This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
lete-cel will be administered to eligible participants.
Pembrolizumab will be administered to eligible participants.
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Up to approximately 10 months
Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
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.
Time frame: Up to approximately 10 months
Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades
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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GSK Investigational Site
Duarte, California, United States
GSK Investigational Site
La Jolla, California, United States
GSK Investigational Site
Sacramento, California, United States
GSK Investigational Site
Stanford, California, United States
GSK Investigational Site
Denver, Colorado, United States
GSK Investigational Site
Hollywood, Florida, United States
GSK Investigational Site
Atlanta, Georgia, United States
GSK Investigational Site
Chicago, Illinois, United States
GSK Investigational Site
Iowa City, Iowa, United States
GSK Investigational Site
Lexington, Kentucky, United States
...and 21 more locations
Time frame: Up to approximately 10 months
Number of Participants With AEs Leading to Dose Delays
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.
Time frame: Up to approximately 10 months
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
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.
Time frame: Up to approximately 10 months
Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
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.
Time frame: Up to approximately 10 months
Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
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.
Time frame: Up to approximately 10 months
Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
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.
Time frame: Up to approximately 10 months
Time to Response (TTR) Per RECIST Version 1.1 by Investigator Assessment
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.
Time frame: Up to approximately 10 months
Maximum Transgene Expansion (Cmax) of Lete-cel
Cmax was defined as peak cell expansion during the study. Blood samples were collected for analysis of Cmax of lete-cel.
Time frame: Day 1 to Day 15
Time to Cmax (Tmax) of Lete-cel
Tmax was defined as time to reach peak cell expansion during the study. Blood samples were collected for analysis of Tmax of lete-cel.
Time frame: Day 1 to Day 15
Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel
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).
Time frame: Up to 28 days