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

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.
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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. |
- 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 ]
- AEs and SAEs leading to dose delays and/or withdrawals [ Time Frame: Up to 106 weeks post-dose ]
- Overall response rate (ORR) [ Time Frame: Up to 106 weeks post-dose ]
- Progression-Free Survival (PFS) [ Time Frame: Up to 106 weeks post-dose ]
- Disease Control Rate (DCR) [ Time Frame: Up to 106 weeks post-dose ]
- Duration of Response (DoR) [ Time Frame: Up to 106 weeks post-dose ]
- Time to Response (TTR) [ Time Frame: Up to 106 weeks post-dose ]
- Maximum transgene expansion (Cmax) for lete-cel [ Time Frame: Up to 106 weeks post-dose ]
- Time to Cmax (Tmax) for lete-cel [ Time Frame: Up to 106 weeks post-dose ]
- 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 ]

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

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
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 |
Study Director: | GSK Clinical Trials | GlaxoSmithKline |
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
GSK3377794 Pembrolizumab T Cell Receptors Adoptive T-cell therapy Non-Small Cell Lung Cancer |
Immuno-oncology NY-ESO-1 LAGE-1a Leukapheresis Letetresgene autoleucel |
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 |