NY-ESO-1ᶜ²⁵⁹T for Advanced NSCLC

This is a single-arm study of genetically engineered NY-ESO-1ᶜ²⁵⁹T cells in HLA-A*02:01,
HLA-A*02:05 and/or HLA-A*02:06 positive subjects with advanced (Stage IIIb or IV) NSCLC.
Subjects with measurable disease will be screened for general health, performance status and
disease stage. Following screening, subjects meeting all eligibility will undergo a
large-volume leukapheresis to obtain cells for the manufacture of autologous NY-ESO-1ᶜ²⁵⁹ TCR
bearing T cells. When the NY-ESO-1ᶜ²⁵⁹T cells are available, subjects will receive
lymphodepleting chemotherapy with cyclophosphamide and fludarabine . Subjects will visit the
clinic for safety and efficacy assessments daily from T cell infusion (Day 1) through Day 5,
Days 8, 10, 12, and then weekly until week 6 and then at 8, 10, 12, 16, 20 and 24 weeks, and
every 3 months until 2 years and then every 6 months until progression of their disease (or
withdrawal of consent for the interventional portion of the study). Subjects who have a
confirmed response (or have stable disease for >4 months) but subsequent disease progression
following the initial infusion and whose tumor continues to express the appropriate antigen
target may be eligible for a second infusion. All subjects, completing or withdrawing from
the interventional portion of the study, will enter a 15-year long-term follow-up phase for
observation of delayed adverse events. All subjects will continue to be followed for overall
survival during the long-term follow-up phase.

Inclusion Criteria:

- Subject has voluntarily agreed to participate by giving written informed consent in
accordance with International Conference on Harmonization Good Clinical Practice (ICH
GCP) Guidelines and applicable local regulations.

- Subject has agreed to abide by all protocol required procedures including study
related assessments, and management by the treating institution for the duration of
the study and long-term follow up.

- Subject is >=18 years of age on the day of signing informed consent.

- Subject has a diagnosis of histologically or cytologically confirmed advanced
non-small cell lung cancer (Stage IIIB or IV) or recurrent disease.

- Subjects with known epidermal growth factor receptor (EGFR) mutations or 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.

- Subject has measurable disease according RECIST v1.1 criteria.

- Subject is HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.

- Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is
unavailable) has been pathologically reviewed by an Adaptimmune- / GSK-designated
central laboratory confirming NY-ESO-1 and/or LAGE-1a expression.

- Subject has Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 10.
Subject has an anticipated life expectancy >3 months.

- Subject has left ventricular ejection fraction >=50%.

- Subject 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. Male subjects: Male subjects are eligible to participate if they agree to the
following during the intervention period starting at the first dose of chemotherapy
for at least 12 months after receiving the T-cell infusion, or 4 months after there is
no evidence of persistence/ gene modified cells in the subject's blood, whichever is
longer. A) Refrain from donating sperm Plus either: B) 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 C) Must agree to use
contraception/barrier. Female subjects: A female subject is eligible to participate if
she is not pregnant or breastfeeding, and at least one of the following conditions
applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP who will agree
to use a barrier method (male condom) and use a contraceptive method that is highly
effective during the intervention period and for at least 12 months after receiving
the T-cell infusion, or 4 months after there is no evidence of persistence/ gene
modified cells in the subject's blood, whichever is longer. WOCBP should also agree
not to donate eggs (ova, oocytes) for the purpose of reproduction during this period.
The Investigator should evaluate the effectiveness of the contraceptive method in
relationship to the first dose of study intervention.

- Subject must have adequate organ function as indicated by the following laboratory
values: a) Absolute Neutrophil count (ANC) >=1.0 x10^9 per liter (/L) (without G-CSF
support); b) Platelets >= 75 x10^9/L; c) Hemoglobin >80 grams per deciliter (g/dL)
(without transfusion support within 7 days from start of leukapheresis); d)
Prothrombin Time or International Normalized Ratio (INR) <=1.5 times upper limit of
normal (ULN) unless receiving therapeutic anticoagulation. e) Partial Thromboplastin
Time (PTT) <=1.5 times upper limit of normal (ULN) unless receiving therapeutic
anticoagulation. f) Calculated or measured creatinine clearance >=40 milliliters per
minute (mL/min); g) Serum total bilirubin <=1.5 times ULN (unless subject had
documented Gilbert's Syndrome); h) Alanine aminotransferase (ALT)/Serum Glutamic
Pyruvic Transaminase (SGPT) <=2.5 times ULN.

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). Stable chronic liver disease should generally be defined
by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal
or gastric varices, persistent jaundice or cirrhosis.

- Subject who has had cytotoxic chemotherapy within 2 weeks prior to leukapheresis;
Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors) or
biological therapy with no wash-out times required; corticosteroids or any other
immunosuppressive therapy within 2 weeks prior to leukapheresis; tyrosine kinase
inhibitor (TKI) (e.g. erlotinib, gefitinib) and any other anti-cancer treatment within
1 week prior to leukapheresis; Investigational treatment within 4 weeks prior to
leukapheresis; 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 <=Grade 1 prior
to enrollment (except for non-clinically significant toxicities, e.g., alopecia,
vitiligo). Subjects with existing pneumonitis as a result of radiation are not
excluded; however, subjects cannot be oxygen dependent.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cyclophosphamide, fludarabine, or other agents used in the study.

- Subject has central nervous system (CNS) metastases except if, on a case by case basis
after risk-benefit evaluation in consultation with the Sponsor Medical Monitor or
designee (all below points apply): Low CNS disease burden; Asymptomatic; Clinically
stable; No history of bleeding within CNS metastases; No lesions in the brain stem;
Not requiring escalating anti-epileptic treatment; Not requiring treatment with
steroids; Not treated with whole brain radiotherapy within the prior 4 weeks; Not with
leptomeningeal disease or carcinomatous meningitis. Note: Treatment with focal
radiotherapy may be allowed (for example, gamma knife radiosurgery) with at least
2-week wash-out period

- Subject has active brain metastases or leptomeningeal metastases. Subjects with prior
history of brain metastasis who have undergone local therapy (i.e., metastatectomy
and/or radiation) and show no evidence of local recurrence or progression over the
past 3 months prior to Screening are eligible.

- Investigational treatment within 4 weeks prior to leukapheresis; 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.

- 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.

- Subject has active brain metastases or leptomeningeal metastases. Subjects with prior
history of brain metastasis who have undergone local therapy (i.e., metastasectomy
and/or radiation) and show no evidence of local recurrence or progression over the
past 3 months prior to Screening are eligible.

- Other active malignancies besides NSCLC within 3 years prior to Screening. Exceptions:
adequately treated malignancies not likely to require therapy (e.g., completely
resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma).
Subjects must be in complete remission from prior malignancy in order to be eligible
to enter the study.

- Unintended weight loss >10% in 6 months preceding study entry.

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

- Uncontrolled intercurrent illness including, but not limited to: a) Ongoing or active
infection; b) Clinically significant cardiac disease defined by chronic heart failure
(CHF) New York Heart Association (NYHA) Class >1; uncontrolled clinically significant
arrhythmia in last 6 months; Acute Coronary Syndrome (ACS) (angina or myocardial
infarction [MI]) in last 6 months. c) Inadequate pulmonary function with mechanical
parameters <40% predicted (forced expiratory volume in one second [FEV1], forced vital
capacity [FVC], total lung capacity [TLC], diffusing capacity of the lungs for carbon
monoxide [DLCO]). d) Interstitial lung disease (subjects with existing pneumonitis as
a result of radiation are not excluded, however, subjects cannot be oxygen dependent).

- Subjects 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) as minimally defined
below: a) Positive serology for HIV. b) Active hepatitis B infection as determined by
hepatitis B surface antigen. c) Active hepatitis C infection as determined by
hepatitis C RNA; A subject who is HCV antibody positive will be screened for HCV
ribonucleic acid (RNA) by any reverse transcriptase (RT) polymerase chain reaction
(PCR) or bDNA assay. If HCV antibody is positive, eligibility will be determined based
on a negative screening RNA value. d) Positive serology for HTLV 1 or 2.

- Subject is pregnant or breastfeeding. Furthermore and prior to lymphodepleting
chemotherapy, a subject meeting the following criteria is not eligible for
participation in the study: 1) Subject has received: Cytotoxic chemotherapy within 3
weeks prior to lymphodepleting chemotherapy; Immune therapy (including monoclonal
antibody therapy, checkpoint inhibitors) or biological therapy within 4 weeks prior
lymphodepleting chemotherapy; Corticosteroids or any other immunosuppressive therapy
within 2 weeks prior to lymphodepleting chemotherapy; Tyrosine kinase inhibitor (e.g.
erlotinib, gefitinib) and any other anti-cancer treatment within 1 week prior to
lymphodepleting chemotherapy; Major surgery within 4 weeks prior to lymphodepleting
chemotherapy; subjects must have recovered from any surgical-related toxicities in the
opinion of the Investigator; Radiotherapy that involves the lung or mediastinum within
3 months prior to lymphodepleting chemotherapy; however, electron beam radiotherapy to
superficial structures in the chest is permitted.