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.

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.

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.