AzTrials
AzTrials

NeoplasmsPhase 1/2NCT03709706

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

A Phase 1/2 study testing Lete-cel and Pembrolizumab in people with Neoplasms, run by GlaxoSmithKline at 31 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
Lete-cel and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
31 sitesin 5 countries
Study dates
31 Dec 2018to 4 Nov 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

31 sites in 5 countries.

31 sites in 5 countries

United States20 sites

  • GSK Investigational Site

    Atlanta, Georgia, 30322

  • GSK Investigational Site

    Baltimore, Maryland, 21201

  • GSK Investigational Site

    Chicago, Illinois, 60637

  • GSK Investigational Site

    Columbus, Ohio, 43210

  • GSK Investigational Site

    Denver, Colorado, 80218

  • GSK Investigational Site

    Duarte, California, 91010

  • GSK Investigational Site

    Durham, North Carolina, 27710

  • GSK Investigational Site

    Hollywood, Florida, 33021

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Iowa City, Iowa, 52242

  • GSK Investigational Site

    La Jolla, California, 92093-0987

  • GSK Investigational Site

    Lexington, Kentucky, 40536

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    New York, New York, 10065

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19111

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15232

  • GSK Investigational Site

    Sacramento, California, 95817

  • GSK Investigational Site

    Salt Lake City, Utah, 84112-5550

  • GSK Investigational Site

    St Louis, Missouri, 63110

  • GSK Investigational Site

    Stanford, California, 94305

Other trials in United States

Netherlands4 sites

  • GSK Investigational Site

    Amsterdam, 1066 CX

  • GSK Investigational Site

    Groningen, 9713 GZ

  • GSK Investigational Site

    Rotterdam, 3015 GD

  • GSK Investigational Site

    Utrecht, 3584 CX

Other trials in Netherlands

Spain3 sites

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Madrid, 28040

  • GSK Investigational Site

    Madrid, 28050

Other trials in Spain

Canada2 sites

  • GSK Investigational Site

    Montreal, Quebec, H2X 0A9

  • GSK Investigational Site

    Toronto, Ontario, M5G 1X6

Other trials in Canada

United Kingdom2 sites

  • GSK Investigational Site

    London, WC1E 6AG

  • GSK Investigational Site

    Manchester, M20 4BX

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Conditions
Neoplasms
Being tested
Lete-cel, Pembrolizumab
Keywords
GSK3377794, Pembrolizumab, T Cell Receptors, Adoptive T-cell therapy, Non-Small Cell Lung Cancer, Immuno-oncology, NY-ESO-1, LAGE-1a, Leukapheresis, Letetresgene autoleucel
Medical subject headings
Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lete-celDrug

    lete-cel will be administered to eligible participants.

  • PembrolizumabDrug

    Pembrolizumab will be administered to eligible participants.

Study groups in NCT03709706
Study groupRoleWhat they receive
Arm A: lete-cel monotherapyExperimentalIn 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.
Receives: Drug: Lete-cel; Drug: Pembrolizumab
Arm B: lete-cel plus pembrolizumabExperimentalIn Arm B, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
Receives: Drug: Lete-cel; Drug: Pembrolizumab
Arm C: lete-cel plus pembrolizumabExperimentalIn Arm C, participants with NSCLC (with actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
Receives: Drug: Lete-cel; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to approximately 10 months

  2. 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.

    Measured: Up to approximately 10 months

  3. 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.

    Measured: Up to approximately 10 months

  4. 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.

    Measured: Up to approximately 10 months

  5. 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.

    Measured: Up to approximately 10 months

Secondary outcomes (7)

  1. 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.

    Measured: Up to approximately 10 months

  2. 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.

    Measured: Up to approximately 10 months

  3. 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.

    Measured: Up to approximately 10 months

  4. 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.

    Measured: Up to approximately 10 months

  5. 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.

    Measured: Day 1 to Day 15

  6. 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.

    Measured: Day 1 to Day 15

  7. 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).

    Measured: Up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2018
  2. Study start31 Dec 2018
  3. Primary completion27 Jun 2022
  4. Study completion4 Nov 2022

Why it stopped: The study was terminated for reasons pertaining to feasibility

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Participants will receive GSK3377794, either as monotherapy or in combination with pembrolizumab.
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03709706
Sponsor's protocol ID
208471
Status last verified
Feb 2024
First submitted
15 Oct 2018
Last updated
23 Feb 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lete-cel and Pembrolizumab in people with Neoplasms, run by GlaxoSmithKline at 31 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Netherlands, Spain, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to approximately 10 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03709706.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.

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