Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02588612
Recruitment Status : Completed
First Posted : October 28, 2015
Results First Posted : September 5, 2021
Last Update Posted : September 5, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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

Condition or disease Intervention/treatment Phase
Neoplasms Drug: letetresgene autoleucel (GSK3377794) Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : February 1, 2016
Actual Primary Completion Date : August 10, 2020
Actual Study Completion Date : August 10, 2020

Resource links provided by the National Library of Medicine


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.
Drug: letetresgene autoleucel (GSK3377794)
letetresgene autoleucel (GSK3377794) as an IV infusion.

Drug: Cyclophosphamide
Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Drug: Fludarabine
Fludarabine will be used as a lymphodepleting chemotherapy.




Primary Outcome Measures :
  1. 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.

  2. Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline [ Time Frame: 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 grade relative to Baseline grade. Data for any grade increase at worst-case post-Baseline is presented

  3. 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.

  4. 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.

  5. 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 ]
    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.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 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-target) must have reduction in short axis to less than (<)10 millimeters.

  2. Time to Response [ Time Frame: 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.

  3. Duration of Response [ Time Frame: 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.

  4. Disease Control Rate (DCR) [ Time Frame: 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.

  5. Progression-Free Survival (PFS) by Investigator Assessment [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02588612


Locations
Layout table for location information
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33136
GSK Investigational Site
Tampa, Florida, United States, 33612
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] September 25, 2019
Statistical Analysis Plan  [PDF] October 2, 2020

Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02588612    
Other Study ID Numbers: 208749
ADP-0011-004 ( Other Identifier: Adaptimmune Therapeutics )
2016-002517-21 ( EudraCT Number )
First Posted: October 28, 2015    Key Record Dates
Results First Posted: September 5, 2021
Last Update Posted: September 5, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
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.
URL: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Letetresgene autoleucel
Adoptive TCR T-cell therapy
NY-ESO-1
T Cell Receptor
Non-Small Cell Lung Cancer
Leukapheresis
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists