Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells in New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1)/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab

Inclusion Criteria

• Age >=18 years on the day of signing informed consent.
• Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Participant is positive for any of the following alleles: human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and a) or HLA-A*02:06 by a validated test.
• Participant's tumor meets the pre-defined threshold for expression of NY-ESO-1 and/or LAGE-1a.
• Adequate organ function and blood cell counts, as defined in the protocol.
• Predicted life expectancy that is >=24 weeks from leukapheresis.
• Left ventricular ejection fraction >=45%.
• Prior therapies prior to lymphodepletion: a) All participants with NSCLC lacking actionable genetic aberrations, per National Comprehensive Cancer Network (NCCN) guidelines (Arms A and B), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy. For participants in the metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. OR b) All participants with NSCLC with actionable genetic aberrations, per NCCN guidelines (Arm C only), should have received appropriate targeted therapy following NCCN or equivalent country-level guidelines.
• Disease progression at time of treatment, as defined in the protocol.
• Measurable disease at time of treatment per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by local site investigator/radiology.

Exclusion Criteria

• Prior treatment: Previous treatment with genetically engineered NY-ESO-1-specific T-cells. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. Prior gene therapy using an integrating vector.
• Prior allogeneic/autologous bone marrow or solid organ transplantation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (DMSO) or other agents used in the study.
• Severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its excipients.
• Active autoimmune disease that has required systemic treatment in past 2 years.
• 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.
• Uncontrolled intercurrent illness.
• Participant has active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), syphilis, or human T lymphotropic virus (HTLV), as defined in protocol.
• Known psychiatric or substance abuse disorders.
• Symptomatic or untreated central nervous system (CNS) metastases.
• Radiotherapy that involves the lung (Percentage of normal lung receiving at least 20 Gray [Gy] during radiotherapy [V20] exceeding 30% lung volume or mean heart dose >20 Gy) within 3 months or radiotherapy (including but not limited to palliative radiotherapy) to lung/mediastinum with V20 less than 30% lung volume and with mean heart dose <=20 Gy within 4 weeks (+/- 3 days).
• Radiotherapy of >=50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the investigator's opinion would predispose participants to prolonged cytopenia after lymphodepletion.
• All of the participant's measurable lesions have been irradiated within 3 months before lymphodepletion.
• Other protocol-defined inclusion/exclusion criteria may apply.