Clinical Trials /

Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)



This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in participants with metastatic NSCLC.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:



Phase 1

Trial Eligibility



  • 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


  • Neoplasms


letetresgene autoleucel (GSK3377794)letetresgene autoleucel (GSK3377794)
Cyclophosphamideletetresgene autoleucel (GSK3377794)
Fludarabineletetresgene autoleucel (GSK3377794)


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

letetresgene autoleucel (GSK3377794)ExperimentalEligible 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

          -  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

          -  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.


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