Last updated: 07/17/2024 17:37:03
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
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
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
Trial description: This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs) based on severity
Timeframe: Up to 106 weeks post-dose
AEs and SAEs leading to dose delays and/or withdrawals
Timeframe: Up to 106 weeks post-dose
Overall response rate (ORR)
Timeframe: Up to 106 weeks post-dose
Secondary outcomes:
Progression-Free Survival (PFS)
Timeframe: Up to 106 weeks post-dose
Disease Control Rate (DCR)
Timeframe: Up to 106 weeks post-dose
Duration of Response (DoR)
Timeframe: Up to 106 weeks post-dose
Time to Response (TTR)
Timeframe: Up to 106 weeks post-dose
Maximum transgene expansion (Cmax) for lete-cel
Timeframe: Up to 106 weeks post-dose
Time to Cmax (Tmax) for lete-cel
Timeframe: Up to 106 weeks post-dose
Area under the time curve from zero to time t (AUC[0 to t]) of lete-cel
Timeframe: Up to 106 weeks post-dose
Interventions:
Enrollment:
34
Primary completion date:
2022-27-06
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
fludarabine
Collaborators
Merck
Study date(s)
December 2018 to November 2022
Type
Interventional
Phase
1/2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Age >=18 years on the day of signing informed consent.
- Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Duarte, California, United States, 91010
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15232
Status
Study Complete
Location
GSK Investigational Site
Hollywood, Florida, United States, 33021
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95817
Status
Study Complete
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30322
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10065
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19111
Status
Study Complete
Location
GSK Investigational Site
Saint Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Stanford, California, United States, 94305
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80218
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84112-5550
Status
Study Complete
Location
GSK Investigational Site
Lexington, Kentucky, United States, 40536
Status
Study Complete
Location
GSK Investigational Site
Chicago, Illinois, United States, 60637
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27710
Status
Study Complete
Location
GSK Investigational Site
La Jolla, California, United States, 92093-0987
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21201
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2022-27-06
Actual study completion date
2022-04-11
Plain language summaries
Summary of results in plain language
Available language(s): English, Dutch
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website