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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

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ClinicalTrials.gov Identifier: NCT03709706
Recruitment Status : Terminated (The study was terminated for reasons pertaining to feasibility)
First Posted : October 17, 2018
Last Update Posted : December 5, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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Brief Summary:
This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Lete-cel Drug: Pembrolizumab Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will receive GSK3377794, either as monotherapy or in combination with pembrolizumab.
Masking: None (Open Label)
Masking Description: This will be an open-label study. Hence, there will be no masking.
Primary Purpose: Treatment
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
Actual Study Start Date : December 31, 2018
Actual Primary Completion Date : June 27, 2022
Actual Study Completion Date : November 4, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs) based on severity [ Time Frame: Up to 106 weeks post-dose ]
  2. AEs and SAEs leading to dose delays and/or withdrawals [ Time Frame: Up to 106 weeks post-dose ]
  3. Overall response rate (ORR) [ Time Frame: Up to 106 weeks post-dose ]

Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Up to 106 weeks post-dose ]
  2. Disease Control Rate (DCR) [ Time Frame: Up to 106 weeks post-dose ]
  3. Duration of Response (DoR) [ Time Frame: Up to 106 weeks post-dose ]
  4. Time to Response (TTR) [ Time Frame: Up to 106 weeks post-dose ]
  5. Maximum transgene expansion (Cmax) for lete-cel [ Time Frame: Up to 106 weeks post-dose ]
  6. Time to Cmax (Tmax) for lete-cel [ Time Frame: Up to 106 weeks post-dose ]
  7. Area under the time curve from zero to time t (AUC[0 to t]) of lete-cel [ Time Frame: Up to 106 weeks post-dose ]

Eligibility Criteria
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Information from the National Library of Medicine

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

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.
Contacts and Locations
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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): NCT03709706


Locations
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United States, California
GSK Investigational Site
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
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80218
United States, Florida
GSK Investigational Site
Hollywood, Florida, United States, 33021
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30322
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60637
United States, Iowa
GSK Investigational Site
Iowa City, Iowa, United States, 52242
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40536
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21201
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63110
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27710
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19111
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84112-5550
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 1X6
Canada, Quebec
GSK Investigational Site
Montréal, Quebec, Canada, H2X 0A9
Netherlands
GSK Investigational Site
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
Spain
GSK Investigational Site
Barcelona, Spain, 08035
GSK Investigational Site
Madrid, Spain, 28040
GSK Investigational Site
Madrid, Spain, 28050
United Kingdom
GSK Investigational Site
London, United Kingdom, WC1E 6AG
GSK Investigational Site
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme LLC
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03709706    
Other Study ID Numbers: 208471
First Posted: October 17, 2018    Key Record Dates
Last Update Posted: December 5, 2022
Last Verified: November 2022
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK3377794
Pembrolizumab
T Cell Receptors
Adoptive T-cell therapy
Non-Small Cell Lung Cancer
 Immuno-oncology
NY-ESO-1
LAGE-1a
Leukapheresis
Letetresgene autoleucel
Additional relevant MeSH terms:
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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
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents