Last updated: 08/10/2021 18:30:06
Letetresgene autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects with Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
Trial description: This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in participants with metastatic NSCLC.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Number of participants with adverse events (AE), including serious adverse events (SAE)
Timeframe: Up to 2 years
Number of participants with abnormal laboratory parameters
Timeframe: Up to 2 years
Number of participants with abnormal electrocardiogram (ECG) findings
Timeframe: Up to 2 years
Number of participants with abnormal pulse oximetry findings
Timeframe: Up to 2 years
Secondary outcomes:
Overall Response rate (ORR)
Timeframe: Up to 2 years
Time to response (TTR)
Timeframe: Up to 2 years
Duration of response (DOR)
Timeframe: Up to 2 years
Disease control rate (DCR)
Timeframe: Up to 2 years
Progression free survival (PFS)
Timeframe: Up to 2 years
Interventions:
Drug: letetresgene autoleucel (GSK3377794)
Drug: Cyclophosphamide
Drug: Fludarabine
Enrollment:
10
Observational study model:
Not applicable
Primary completion date:
2020-10-08
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
GR49187, GSK3377794, cyclophosphamide, fludarabine, sargramostim
Collaborators
Not applicable
Study date(s)
February 2016 to August 2020
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Participant is >=18 years of age on the day of signing informed consent.
- Participant has a diagnosis of histologically or cytologically confirmed advanced non-small cell lung cancer (Stage IIIB or IV) or recurrent disease.
- Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment).
- Washout periods for prior radiotherapy and chemotherapy and other systemic therapy must be followed.
Inclusion and exclusion criteria
Inclusion criteria:
- Participant is >=18 years of age on the day of signing informed consent.
- Participant has a diagnosis of histologically or cytologically confirmed advanced non-small cell lung cancer (Stage IIIB or IV) or recurrent disease.
- Participants with known epidermal growth factor receptor (EGFR) mutations or Anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (disease progression [PD] or unacceptable toxicity) prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively (PD or unacceptable toxicity). There is no limit to lines of prior anti-cancer therapy.
- Participant has measurable disease according RECIST v1.1 criteria.
- Participant is HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.
- Participant's tumor is positive for NYESO and/or LAGE-1a expression by a designated central laboratory.
- Participant has Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Participant has an anticipated life expectancy >3 months.
- Participant has left ventricular ejection fraction >=50 percent(%).
- Participant is fit for leukapheresis and has adequate venous access for the cell collection.
- Male or Female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Participant must have adequate organ function.
Exclusion criteria:
- Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment).
- Washout periods for prior radiotherapy and chemotherapy and other systemic therapy must be followed.
- Experimental anti-cancer vaccine within 2 months prior to leukapheresis in the absence of response or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months prior to leukapheresis.
- Any prior gene therapy using an integrating vector.
- Toxicity from previous anti-cancer therapy that has not recovered to less than or equal to (<=)Grade 1 prior to enrollment (with exceptions).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, or other agents used in the study.
- Central nervous system (CNS) metastases.
- Active brain metastases or leptomeningeal metastases.
- 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.
- Other active malignancies besides NSCLC within 3 years prior to Screening not in complete remission.
- Unintended weight loss >10% in 6 months preceding study entry.
- Corrected QT interval (QTc) >450 milliseconds (msec) or QTc >480 msec for participants with Bundle Branch Block (BBB).
- Uncontrolled intercurrent illness.
- Participants who in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
- Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human T-cell lymphotropic virus (HTLV).
- Participant is pregnant or breastfeeding.
- Major surgery within 4 weeks prior to lymphodepleting chemotherapy.
Trial location(s)
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
Completed
Actual primary completion date
2020-10-08
Actual study completion date
2020-10-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website