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NCT02588612

Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

Completed Phase 1 Results posted Last updated 5 September 2021
What this trial tests

Phase 1 trial testing letetresgene autoleucel (GSK3377794) in Neoplasms in 10 participants. Completed in 10 August 2020.

Timeline
1 February 2016
Primary endpoint
10 August 2020
10 August 2020

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment10
Start date1 February 2016
Primary completion10 August 2020
Estimated completion10 August 2020
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Primary · Up to 24 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is clinically significant or requires intervention to prevent one of the outcomes listed before. Number of participants with common (greater

Non SAEs
GroupValue95% CI
Lete-cel6
SAEs
GroupValue95% CI
Lete-cel4
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Primary · Up to 24 months

Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grad

Hemoglobin increased
GroupValue95% CI
Lete-cel0
Hemoglobin (Anemia)
GroupValue95% CI
Lete-cel3
Lymphocytes increased
GroupValue95% CI
Lete-cel1
Lymphocytes decreased
GroupValue95% CI
Lete-cel5
Neutrophils
GroupValue95% CI
Lete-cel5
Platelets
GroupValue95% CI
Lete-cel5
Leukocytes (Leukocytosis)
GroupValue95% CI
Lete-cel0
Leukocytes (Leukopenia)
GroupValue95% CI
Lete-cel5
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Primary · Up to 24 months

Blood samples were collected for analysis of clinical chemistry parameters: glucose (Gl), albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (Bil), creatinine (Creat), potassium (Pot), magnesium (Mg), phosphate (Ph), sodium (Sod) and calcium. Laboratory parameters were graded according to NCI-CTCAE version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any

Gl, Hyperglycemia
GroupValue95% CI
Lete-cel2
Gl, Hypoglycemia
GroupValue95% CI
Lete-cel0
Albumin
GroupValue95% CI
Lete-cel2
ALP
GroupValue95% CI
Lete-cel2
ALT
GroupValue95% CI
Lete-cel3
AST
GroupValue95% CI
Lete-cel4
Bil
GroupValue95% CI
Lete-cel1
Creat
GroupValue95% CI
Lete-cel1
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Primary · Up to 24 months

12-lead ECGs were recorded in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate and measured PR, RR, QRS and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings for worst case post-Baseline have been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expecte

Abnormal, NCS
GroupValue95% CI
Lete-cel2
Abnormal, CS
GroupValue95% CI
Lete-cel1
Change From Baseline in Oxygen Saturation Primary · Baseline, Day 1 (pre-dose, 5, 15, and 30 minutes, 1, 1.5, 2, and 4 hours post dose), Days 2, 3, 4, 5, 8 and Week 2

Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen saturation was measured using a pulse oximeter. Baseline is the most recent, non-missing value within 7 days prior to initiating the lymphodepleting chemotherapy. Change from Baseline is the post-Baseline visit value minus Baseline value.

Day 1, pre dose, n=5
GroupValue95% CI
Lete-cel2.0-2 – 6
Day 1, 5 minutes post dose, n=4
GroupValue95% CI
Lete-cel2.51 – 3
Day 1, 15 minutes post dose, n=4
GroupValue95% CI
Lete-cel2.0-3 – 5
Day 1, 30 minutes post dose, n=4
GroupValue95% CI
Lete-cel3.0-2 – 3
Day 1, 1 hour post dose, n=5
GroupValue95% CI
Lete-cel2.0-2 – 5
Day 1, 1.5 hours post dose, n=2
GroupValue95% CI
Lete-cel1.51 – 2
Day 1, 2 hours post dose, n=3
GroupValue95% CI
Lete-cel3.02 – 5
Day 1, 4 hours post dose, n=4
GroupValue95% CI
Lete-cel-1.0-3 – 3
Overall Response Rate (ORR) Secondary · Up to 24 Months

ORR is defined as the percentage of participants with a confirmed Partial response (PR) or Complete response (CR) as the Best overall response (BOR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Confidence Interval (CI) was calculated using the exact method. 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-targe

GroupValue95% CI
Lete-cel200.5 – 71.6
Time to Response Secondary · Up to 24 months

Time to response is defined as the interval of time (in months) between the date of T-cell infusion and the first documented evidence of response (PR or CR) in the subset of participants with a confirmed PR or CR as the BOR as assessed by the investigator per RECIST v1.1.

GroupValue95% CI
Lete-cel12.09
Duration of Response Secondary · Up to 24 months

Duration of response (DoR), defined as the interval of time in months from first documented evidence of PR or better to the time when disease progression is documented as assessed by RECIST v1.1 or death due to any cause among participants with a confirmed PR or CR as the BOR.

GroupValue95% CI
Lete-cel6.18
Disease Control Rate (DCR) Secondary · Up to 24 months

DCR is defined as the percentage of participants with a stable disease (SD) or better as the BOR (Confirmed PR, confirmed CR, or SD \>=12 weeks), as assessed by the investigator per RECIST v1.1. CI was calculated using the exact method.

GroupValue95% CI
Lete-cel200.5 – 71.6
Progression-Free Survival (PFS) by Investigator Assessment Secondary · Up to 24 months

Progression-free survival (PFS) is defined as the interval of time (in months) between the date of T-cell infusion and the earlier of the date of disease progression as assessed by the investigator and the date of 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. Median and inter-quartile range (first quartile and third quartile) are presented.

GroupValue95% CI
Lete-cel1.810.99 – 5.29

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lete-cel
Serious: 4/10 (40%)
Deaths: 4/10

Serious adverse events (10 terms)

ReactionSystemLete-cel
Cytokine release syndromeImmune system disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
EncephalopathyNervous system disorders
Haemorrhage intracranialNervous system disorders
Respiratory distressRespiratory, thoracic and mediastinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HypotensionVascular disorders
Other adverse events (58 terms — click to expand)

ReactionSystemLete-cel
Lymphocyte count decreasedInvestigations
White blood cell count decreasedInvestigations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
HeadacheNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Oedema peripheralGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Sinus tachycardiaCardiac disorders
Confusional statePsychiatric disorders
InsomniaPsychiatric disorders
HypotensionVascular disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
LeukocytosisBlood and lymphatic system disorders
Lymph node painBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
ChillsGeneral disorders
PyrexiaGeneral disorders
Bone painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
LethargyNervous system disorders
Memory impairmentNervous system disorders
ParalysisNervous system disorders
Peripheral sensory neuropathyNervous system disorders
Spinal cord compressionNervous system disorders
Supraventricular tachycardiaCardiac disorders
Ventricular tachycardiaCardiac disorders
BronchitisInfections and infestations
PneumoniaInfections and infestations

Most-reported serious reactions: Cytokine release syndrome, Pneumonia, Anaemia, Constipation, Nausea, Encephalopathy, Haemorrhage intracranial, Respiratory distress.

Data from ClinicalTrials.gov NCT02588612 adverse events section.

Sponsor's own description

This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in participants with metastatic NSCLC.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Lung cancer immunotherapy: progress, pitfalls, and promises.
    Lahiri A, Maji A, Potdar PD, Singh N, et al · · 2023 · cited 737× · PMID 36810079 · DOI 10.1186/s12943-023-01740-y
  2. NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives.
    Thomas R, Al-Khadairi G, Roelands J, Hendrickx W, et al · · 2018 · cited 298× · PMID 29770138 · DOI 10.3389/fimmu.2018.00947
  3. Driving gene-engineered T cell immunotherapy of cancer.
    Johnson LA, June CH. · · 2017 · cited 211× · PMID 28025979 · DOI 10.1038/cr.2016.154
  4. Heterogeneity of the tumor immune microenvironment and its clinical relevance.
    Jia Q, Wang A, Yuan Y, Zhu B, et al · · 2022 · cited 176× · PMID 35461288 · DOI 10.1186/s40164-022-00277-y
  5. T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors.
    Tsimberidou AM, Van Morris K, Vo HH, Eck S, et al · · 2021 · cited 119× · PMID 34193217 · DOI 10.1186/s13045-021-01115-0
  6. The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.
    Zhang J, Wang L. · · 2019 · cited 115× · PMID 30798772 · DOI 10.1177/1533033819831068
  7. Emerging therapeutic agents for lung cancer.
    Dholaria B, Hammond W, Shreders A, Lou Y. · · 2016 · cited 66× · PMID 27938382 · DOI 10.1186/s13045-016-0365-z
  8. Immunotherapy in surgically resectable non-small cell lung cancer.
    Owen D, Chaft JE. · · 2018 · cited 48× · PMID 29593886 · DOI 10.21037/jtd.2017.12.93

Verify or expand the search:

Other trials of letetresgene autoleucel (GSK3377794)

Trials testing the same drug.

Other recruiting trials for Neoplasms

Currently open trials in the same condition.

Other GlaxoSmithKline trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02588612.

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