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

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
34

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X6
        • GSK Investigational Site
    • Quebec
      • Montréal, Quebec, Canada, H2X 0A9
        • GSK Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • GSK Investigational Site
      • Groningen, Netherlands, 9713 GZ
        • GSK Investigational Site
      • Rotterdam, Netherlands, 3015 GD
        • GSK Investigational Site
      • Utrecht, Netherlands, 3584 CX
        • GSK Investigational Site
  • Spain
      • Barcelona, Spain, 08035
        • GSK Investigational Site
      • Madrid, Spain, 28040
        • GSK Investigational Site
      • Madrid, Spain, 28050
        • GSK Investigational Site
  • United Kingdom
      • London, United Kingdom, WC1E 6AG
        • GSK Investigational Site
      • Manchester, United Kingdom, M20 4BX
        • GSK Investigational Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • GSK Investigational Site
      • La Jolla, California, United States, 92093-0987
        • GSK Investigational Site
      • Sacramento, California, United States, 95817
        • GSK Investigational Site
      • Stanford, California, United States, 94305
        • GSK Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80218
        • GSK Investigational Site
    • Florida
      • Hollywood, Florida, United States, 33021
        • GSK Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • GSK Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • GSK Investigational Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • GSK Investigational Site
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • GSK Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • GSK Investigational Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10065
        • GSK Investigational Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • GSK Investigational Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • GSK Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • GSK Investigational Site
      • Pittsburgh, Pennsylvania, United States, 15232
        • GSK Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • GSK Investigational Site
    • Texas
      • Houston, Texas, United States, 77030
        • GSK Investigational Site
    • Utah
      • Salt Lake City, Utah, United States, 84112-5550
        • GSK Investigational Site

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Lete-cel
lete-cel will be administered to eligible participants.
Drug: Pembrolizumab
Pembrolizumab will be administered to eligible participants.
Experimental: Arm B: lete-cel plus pembrolizumab
In Arm B, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
Drug: Lete-cel
lete-cel will be administered to eligible participants.
Drug: Pembrolizumab
Pembrolizumab will be administered to eligible participants.
Experimental: Arm C: lete-cel plus pembrolizumab
In Arm C, participants with NSCLC (with actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
Drug: Lete-cel
lete-cel will be administered to eligible participants.
Drug: Pembrolizumab
Pembrolizumab will be administered to eligible participants.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events Based on Maximum Severity Grades
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Number of Participants With AEs Leading to Dose Delays
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
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
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.
Up to approximately 10 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Disease Control Rate (DCR) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Duration of Response (DOR) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Time to Response (TTR) Per RECIST Version 1.1 by Investigator Assessment
Time Frame: Up to approximately 10 months
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.
Up to approximately 10 months
Maximum Transgene Expansion (Cmax) of Lete-cel
Time Frame: Day 1 to Day 15
Cmax was defined as peak cell expansion during the study. Blood samples were collected for analysis of Cmax of lete-cel.
Day 1 to Day 15
Time to Cmax (Tmax) of Lete-cel
Time Frame: Day 1 to Day 15
Tmax was defined as time to reach peak cell expansion during the study. Blood samples were collected for analysis of Tmax of lete-cel.
Day 1 to Day 15
Area Under the Plasma Concentration-time Curve to Day 28 (AUC0-28d) of Lete-cel
Time Frame: Up to 28 days
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).
Up to 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 31, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 27, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 4, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 17, 2018

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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