- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02588612
Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
August 10, 2021 updated by: GlaxoSmithKline
A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in participants with metastatic NSCLC.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
New York esophageal antigen-1 (NY-ESO-1) and L antigen family member (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 engineered TCR T-cells.
This protocol investigates letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)*-A*02+ participants with NY-ESO1+ advanced metastatic non-small cell lung cancer as second line treatment.
Study Type
Interventional
Enrollment (Actual)
10
Phase
- 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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Florida
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Miami, Florida, United States, 33136
- GSK Investigational Site
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Tampa, Florida, United States, 33612
- GSK Investigational Site
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Texas
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Houston, Texas, United States, 77030
- 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
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Participant is >=18 years of age on the day of signing informed consent.
- Participant has a diagnosis of histologically or cytologically confirmed advanced non-small cell lung cancer (Stage IIIB or IV) or recurrent disease.
- Participants with known epidermal growth factor receptor (EGFR) mutations or Anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (disease progression [PD] or unacceptable toxicity) prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively (PD or unacceptable toxicity). There is no limit to lines of prior anti-cancer therapy.
- Participant has measurable disease according RECIST v1.1 criteria.
- Participant is HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.
- Participant's tumor is positive for NYESO and/or LAGE-1a expression by a designated central laboratory.
- Participant has Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Participant has an anticipated life expectancy >3 months.
- Participant has left ventricular ejection fraction >=50 percent(%).
- Participant is fit for leukapheresis and has adequate venous access for the cell collection.
- Male or Female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Participant must have adequate organ function.
Exclusion Criteria:
- Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment).
- Washout periods for prior radiotherapy and chemotherapy and other systemic therapy must be followed.
- Experimental anti-cancer vaccine within 2 months prior to leukapheresis in the absence of response or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months prior to leukapheresis.
- Any prior gene therapy using an integrating vector.
- Toxicity from previous anti-cancer therapy that has not recovered to less than or equal to (<=)Grade 1 prior to enrollment (with exceptions).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, or other agents used in the study.
- Central nervous system (CNS) metastases.
- Active brain metastases or leptomeningeal metastases.
- 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.
- Other active malignancies besides NSCLC within 3 years prior to Screening not in complete remission.
- Unintended weight loss >10% in 6 months preceding study entry.
- Corrected QT interval (QTc) >450 milliseconds (msec) or QTc >480 msec for participants with Bundle Branch Block (BBB).
- Uncontrolled intercurrent illness.
- Participants who in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
- Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human T-cell lymphotropic virus (HTLV).
- Participant is pregnant or breastfeeding.
- Major surgery within 4 weeks prior to lymphodepleting chemotherapy.
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: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: letetresgene autoleucel (GSK3377794)
Eligible participants will be leukapheresed to manufacture engineered T-cells.
Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
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Fludarabine will be used as a lymphodepleting chemotherapy.
Cyclophosphamide will be used as a lymphodepleting chemotherapy.
letetresgene autoleucel (GSK3377794) as an IV infusion.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 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 than or equal to [>=]5 percent[%]) non-serious AEs and SAEs are presented.
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Up to 24 months
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Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline
Time Frame: Up to 24 months
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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 grade relative to Baseline grade.
Data for any grade increase at worst-case post-Baseline is presented
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Up to 24 months
|
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters
Time Frame: 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 grade increase at worst-case post-Baseline is presented.
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Up to 24 months
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Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Time Frame: 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 expected for the participant's condition.
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Up to 24 months
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Change From Baseline in Oxygen Saturation
Time Frame: 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
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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.
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Up to 24 Months
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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-target) must have reduction in short axis to less than (<)10 millimeters.
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Up to 24 Months
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Time to Response
Time Frame: Up to 24 months
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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.
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Up to 24 months
|
Duration of Response
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Disease Control Rate (DCR)
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Progression-Free Survival (PFS) by Investigator Assessment
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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)
February 1, 2016
Primary Completion (Actual)
August 10, 2020
Study Completion (Actual)
August 10, 2020
Study Registration Dates
First Submitted
October 26, 2015
First Submitted That Met QC Criteria
October 26, 2015
First Posted (Estimate)
October 28, 2015
Study Record Updates
Last Update Posted (Actual)
September 5, 2021
Last Update Submitted That Met QC Criteria
August 10, 2021
Last Verified
August 1, 2021
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
- 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
- 208749
- ADP-0011-004 (Other Identifier: Adaptimmune Therapeutics)
- 2016-002517-21 (EudraCT Number)
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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