Pilot Immunotherapy With Autologous T-cells Specific for New York Esophageal Antigen-1 (NY-ESO-1)/ Cancer-testis Antigen-2 (LAGE-1a)-Positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab

Inclusion Criteria:

Screening:

- The subject (or legally acceptable representative if applicable) provides written
informed consent for the trial.

- Age >=18 years on the day of signing informed consent.

- Pending approval of Medical Monitor (or designee), subjects can be enrolled in other
experimental interventional clinical studies during the screening and leukapheresis
stages of this study (GSK208471).

- Have measurable disease per RECIST 1.1 as assessed by investigator.

- ECOG Performance Status of 0 or 1.

- Predicted life expectancy that is >=3 months.

- Subject has left ventricular ejection fraction >=50% or as per institution's
guidelines.

- Adequate venous access for leukapheresis.

- In the Investigator's opinion, the subject is fit for lymphodepleting chemotherapy and
infusion of GSK3377794.

- An archived biopsy of the tumor tissue obtained at any time from the initial diagnosis
of NSCLC to time of study entry is mandatory for expression of NY-ESO-1 and, when
available, LAGE1a.

Leukapheresis:

- Subjects who have successfully completed screening. Subject is HLA-A*02:01,
HLA-A*02:05 and/or HLA-A*02:06 positive.

- In the Investigator's opinion, the subject is suitable for leukapheresis, for:
Absolute neutrophil count (ANC) >=1.5 x 10^9 cells/Liter (L), cluster of
differentiation 3 (CD3) count >=200/microliter (μL) and Lymphocyte count >=0.5 x 10^9
cells/L.

- Leukapheresis can be collected as follows: Between 1st and 2nd line therapies; after
the first 3 cycles of prior chemotherapy; During prior programmed death receptor-1
(PD-1)/PD-1 ligand (PD-L1) regimen (alone or in combination with chemotherapy) or
after the first 3 cycles of checkpoint blockade therapy. Wash-out for anti-PD-1/ PD-L1
monotherapy is not required; At any time during first or second line tyrosine kinase
inhibitor (TKI) therapy; after radiotherapy; pending approval of Medical Monitor (or
designee), if prior standard of care (SoC) therapy is refused by the subject.

- A SoC line of therapy between leukapheresis and treatment is allowed if: it is based
on risk/benefit assessment and/or local regulatory requirements and following
agreement with Sponsor's Medical Monitor (or designee); it is performed at the same
site and staff where the subject has enrolled to this study;and treatments, AEs, and
other clinical observations are reported in this study..

Lymphodepletion/Treatment:

- Prior to lymphodepleting chemotherapy, subjects must meet all the criteria for
screening and Leukapheresis.

- Must have received or are receiving at least 1 line of prior systemic therapy:
Subjects with epidermal growth factor receptor (EGFR) mutations , anaplastic lymphoma
kinase (ALK) rearrangement, receptor tyrosine kinase which is encoded by the gene ROS1
(ROS1) rearrangement, or BRAF V600E mutation must have received or are receiving a
targeted therapy regimen with or without cytotoxic therapy; Subjects who received or
are receiving a PD-1/PD-L1 checkpoint blocker alone or in combination with other
therapies; subjects who received or are receiving any other systemic regimen; pending
approval of Medical Monitor (or designee), prior SoC therapy is refused by the subject
, subjects not eligible for radical chemo-radiotherapy, or have terminated prior
treatment due to intolerable side effects.

- Following treatment with therapies other than PD-1/PD-L1 checkpoint blockade,
progression is defined by RECIST 1.1. Alternatively, lymphodepleting regimen may start
after clinical AND/OR radiographic disease progression without second confirmatory
imaging, based upon risk/benefit evaluation in agreement with the Medical Monitor (or
designee);

- Have at least 2 lesions, 1 measurable as a target lesion and the other required for
biopsy.

- Prior radiotherapy is allowed if prior palliative or stereotactic radiosurgery to
solitary lesions outside of the chest (no wash-out required).

- Central nervous system (CNS) metastases with low CNS disease burden are allowed on a
case by case basis after risk-benefit evaluation in consultation with the Sponsor
Medical Monitor (or designee)

- Lymphodepleting regimen initiation is allowed if: There is clinical and/or
radiographic evidence of disease progression; the wash-out period for supportive
therapy (chemotherapy or radiotherapy) has been fulfilled;

- A SoC line of therapy between leukapheresis and treatment is allowed based on
risk/benefit assessment and/or local regulatory requirements and following agreement
with Sponsor's Medical Monitor (or designee), performed at the same site and staff
where the subject has enrolled to this study and treatments, AEs, and other clinical
observations are reported in this study.

- A biopsy of tumor tissue obtained following cessation of the last line of treatment
for NSCLC but prior to initiating lymphodepleting chemotherapy is mandatory if
feasible.

- Male subjects are eligible to participate if they agree to the following: refrain from
donating sperm plus either be abstinent from heterosexual or homosexual intercourse as
their preferred and usual lifestyle (abstinent on a long term and persistent basis)
and agree to remain abstinent or must agree to use contraception/barrier as detailed:)
agree to use a male condom and should also be advised of the benefit for a female
partner to use a highly effective method of contraception as a condom may break or
leak when having sexual intercourse with a woman of childbearing potential who is not
currently pregnant.

- A female subject is eligible to participate if they are not pregnant or breastfeeding
and if she is not of childbearing potential.

- Adequate Organ Function is defined as f >=1.5 x 10^9 cells/L for absolute neutrophil
count, >=9 g/L or >=5.6 millimoles (mmol)/L for Hemoglobin, >=100 x 10^9/L for
Platelets, >=2.5 grams/deciliter (g/dL) for albumin, <=1.5 x upper limit of normal
(ULN) (isolated bilirubin <=1.5 x ULN is acceptable if bilirubin is fractionated and
direct bilirubin <35%) for total bilirubin, <=2.5 x ULN (or <=5 x ULN if documented
history of liver metastases for ALT, >=50 milliliters/minute/1.73 square meters for
calculated creatinine clearance (CrCl) and <=1.5 × ULN unless subject is receiving
anticoagulant therapy as long as International normalized ratio (INR)/ prothrombin
time (PT) or activated partial thromboplastin time (aPTT) is within therapeutic range.

Anti-PD1 Rescue with Pembrolizumab (Arm A only):

- Subjects who have received GSK3377794 on Arm A are eligible for anti-PD-1 rescue
therapy with pembrolizumab 200 milligrams flat dose once every 3 weeks (Q3W) if they
fulfil all the following criteria:

- The subject (or legally acceptable representative if applicable) provides written
informed consent for the trial.

- Radiographically confirmed progressive disease following treatment with GSK3377794.

- Any toxicity must be <= Grade 1 Common Terminology Criteria for Adverse Events (CTCAE)
v4.03 at the time of first/dose (except for non-clinically significant toxicities
e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or
irreversible (e.g., peripheral neuropathy) can be enrolled on a case-by-case basis
with prior consultation and agreement with the Sponsor's Medical Monitor (or
designee).

- Treatment with anti-PD-1 rescue therapy with pembrolizumab is deemed appropriate by
the Investigator and in agreement with the Sponsor Medical Monitor (or designee).

Exclusion Criteria:

For screening:

- Has received >=3 lines of prior systemic therapy.

- Prior treatment: Any prior treatment with oncology cell therapy TCR-T-cell therapy or
chimeric antigen receptor (CAR)-T therapy; Prior gene therapy using an integrating
vector

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression.

- Prior malignancy other than NSCLC, with exceptions agreed upon consultation between
the Investigator and Sponsor Medical Monitor (or designee).

- Subject has a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to agents used in the study.

- Has severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its
excipients.

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Subject has a 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.

- Prior allogeneic/autologous bone marrow or solid organ transplantation with some
exceptions if occurred more than 5 years ago.

- Uncontrolled intercurrent illness including, but not limited to: Ongoing or active
infection; Clinically significant cardiac disease defined by congestive heart failure
New York Heart Association (NYHA) Class >1; Uncontrolled clinically significant
arrhythmia in last 6 months; Acute coronary syndrome (angina or myocardial infarction)
in last 6 months; Severe aortic stenosis, symptomatic mitral stenosis; Inadequate
pulmonary function with mechanical parameters <40% predicted (forced expiratory volume
in 1 second [FEV1], forced vital capacity [FVC], total lung capacity [TLC], Pulmonary
diffusing capacity for carbon monoxide [DLCO]); Interstitial lung disease (subjects
with existing pneumonitis as a result of radiation are not excluded; however, subjects
cannot be oxygen dependent)

- Current unstable liver or biliary disease per Investigator assessment

- Subject has positive viral serology as defined in protocol.

- Subject is pregnant or breastfeeding.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study in the opinion of the Investigator and
Sponsor's Medical Monitor (or designee).

- Has known psychiatric or substance abuse disorders.

- Corrected QT interval (QTc) >450 milliseconds (msec) or QTc >480 msec for subjects
with Bundle Branch Block (BBB).

- There are further inclusion /exclusion criteria within the protocol that need to be
adhered to prior leukapharesis and lymphodepletion.

For Anti-PD1 Rescue with Pembrolizumab (Arm A only):

- Persistence of toxicities such as Cytokine Release Syndrome (CRS) => Grade 2 that
preclude treatment with pembrolizumab.