Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
Condition: Neoplasms
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: letetresgene autoleucel (GSK3377794); Cyclophosphamide; Fludarabine
Intervention description: letetresgene autoleucel (GSK3377794) as an IV infusion.; Cyclophosphamide will be used as a lymphodepleting chemotherapy.; Fludarabine will be used as a lymphodepleting chemotherapy.
Intervention MeSH terms: Cyclophosphamide; Fludarabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Letetresgene autoleucel; Adoptive TCR T-cell therapy; NY-ESO-1; T Cell Receptor; Non-Small Cell Lung Cancer; Leukapheresis

Summary:

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

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.