Description:
This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in
participants with metastatic NSCLC.
Title
- Brief Title: Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
- 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)
Clinical Trial IDs
- ORG STUDY ID:
208749
- SECONDARY ID:
ADP-0011-004
- SECONDARY ID:
2016-002517-21
- NCT ID:
NCT02588612
Conditions
Interventions
Drug | Synonyms | Arms |
---|
letetresgene autoleucel (GSK3377794) | | letetresgene autoleucel (GSK3377794) |
Cyclophosphamide | | letetresgene autoleucel (GSK3377794) |
Fludarabine | | letetresgene autoleucel (GSK3377794) |
Purpose
This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in
participants with metastatic NSCLC.
Detailed Description
New York esophageal antigen-1 (NY-ESO-1) and L antigen family member (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 engineered TCR T-cells. This protocol investigates letetresgene autoleucel
treatment in Human Leukocyte Antigen (HLA)*-A*02+ participants with NY-ESO1+ advanced
metastatic non-small cell lung cancer as second line treatment.
Trial Arms
Name | Type | Description | Interventions |
---|
letetresgene autoleucel (GSK3377794) | Experimental | Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy. | - letetresgene autoleucel (GSK3377794)
- Cyclophosphamide
- Fludarabine
|
Eligibility 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with adverse events (AE), including serious adverse events (SAE) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | All AEs and SAEs will be collected. |
Secondary Outcome Measures
Measure: | Overall Response rate (ORR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Overall response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 |
Measure: | Time to response (TTR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Time to Response is defined as the time from date of T-cell infusion dose and the first documented evidence of response (CR or PR) in the subset of participants with a confirmed PR or CR as the best overall response (BOR) as assessed by the RECIST 1.1. |
Measure: | Duration of response (DOR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Duration of response is defined as the time from first documented evidence of CR or PR until first documented disease progression or death due to any cause. |
Measure: | Disease control rate (DCR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Disease control rate is defined as the percentage of participants with a confirmed stable disease (SD) or better as the BOR (PR, CR, or SD more than or equal to [>=]12 weeks). |
Measure: | Progression free survival (PFS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Progression free survival is defined as the time from the date of T-cell infusion until the earliest date of disease progression or death due to any cause. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | GlaxoSmithKline |
Trial Keywords
- Letetresgene autoleucel
- Adoptive TCR T-cell therapy
- NY-ESO-1
- T Cell Receptor
- Non-Small Cell Lung Cancer
- Leukapheresis
Last Updated
January 27, 2021