Clinical trial NCT02588612
Conditions: Neoplasms
Keywords: Letetresgene autoleucel Adoptive TCR T-cell therapy NY-ESO-1 T Cell Receptor Non-Small Cell Lung Cancer Leukapheresis
Sponsor: GlaxoSmithKline
Start date: 2016-02-01; Completion date: 2020-08-10
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Detailed description:
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.

Arms: arm 1: Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Interventions: intervention 1: letetresgene autoleucel (GSK3377794) intervention 2: Cyclophosphamide intervention 3: Fludarabine
Intervention descriptions: intervention 1: letetresgene autoleucel (GSK3377794) as an IV infusion. intervention 2: Cyclophosphamide will be used as a lymphodepleting chemotherapy. intervention 3: Fludarabine will be used as a lymphodepleting chemotherapy.

Protocol documents:
Prot_000.pdf: 
GlaxoSmithKline (GSK)
PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
Amendment 4
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Protocol Number GSK208749 (ADP-0011-004)
A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T 
Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects with Stage IIIb or 
Stage IV Non-Small Cell Lung Cancer (NSCLC)
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
Amendment 4
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INVESTIGATOR PROTOCOL AGREEMENT PAGE
Protocol Title: A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of 
Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects with 
Stage IIIb or Stage IV Non-Small Cell Lung Cancer(NSCLC)
I, the undersigned, have reviewed the protocol, including the appendices, and I will
conduct the clinical study as described and will adhere to International Conference
on Harmonization (ICH) tripartite guideline E6 (R1): Guideline for Good Clinical 
Practice (GCP) and all the ethical and regulatory considerations stated. I have 
read and understood the contents of the NY-ESO-1c259T Investigator Brochure.
Investigator Name
Investigator Title
Investigator Site and Address
Investigator Signature
Date
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
Amendment 4
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CLINICAL STUDY PROTOCOL
Title: A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of
Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in 
Subjects with Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC).
Product Name: NY-ESO-1c259T
Protocol Number: GSK208749 (ADP-0011-004)
IND Number: 14603
EudraCT Number: 2016-002517-21
Date of Original Protocol: 08-June-2015
Amendment 
Number
Date
Reason for Change
01
08-August-2016
This amendment was performed to address questions and 
comments from Institutional Review Boards and Regulatory 
Authorities. Additionally, revisions were made based on 
emerging data from Adaptimmune’s clinical program and due 
to Adaptimmune’s newly developed protocol template. 
Appendix 7 contains a summary of and rationale for all 
revisions for Amendment 01.
Key revisions included the following: Changed
phase of trial from Phase I/II to Pilot
Revised Background and Study Rationale sections to 
minimize information already provided in the NY-ESO-
1c259T Investigator Brochure
Revised primary, secondary, and exploratory endpoints to 
better characterize the safety and efficacy evaluations, and 
correlative studies to be performed in thisstudy
Changedlymphodepletingchemotherapyregimenfrom 
cyclophosphamide alone to cyclophosphamide and 
fludarabine based on emerging data from our ongoing 
clinical program
Removed human leukocyte antigen (HLA) and antigen 
expression screening since these tests will be performed in 
Adaptimmune’s Screening Protocol(ADP-0000-001)
Revised inclusion/exclusion criteria to provide more clarity on 
subject population
Added guidance on second T cell infusion, including 
eligibility criteria and Schedule of Procedures table
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
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Added text around the administration of cyclophosphamide 
and fludarabine, including dose adjustments, prophylactic 
and supportive treatments
Removedimmune-relatedResponseCriteria(irRC)criteria 
for tumor response assessments
Added several sections on supportive care guidance, 
including infection, hematologic and blood product 
support, autoimmunity, GVHD, and pancytopenia
02
16-July-2017
Subsequent to the licensing of Adaptimmune product NY-
ESO by GSK, the purpose of this protocol amendment is 
to:
- Delete or replace references to Adaptimmune or its staff 
with that of GlaxoSmithKline (GSK) and its authorized 
agents to align with the change of sponsorship;
- Make administrative changes to align with GSK 
processes and procedures;
- Update language relating to serious adverse event (SAE) 
reporting and safety monitoring;
- Changes to lymphodepletion regimenthroughout.
Appendix 7 contains a summary of revisions for 
Amendment 02.
03
17-October-2018
Changes made to the protocol were requested by the FDA 
as a result of safety events which included 2 reports of 
Guillain-Barré syndrome in subjects who have received 
chemotherapy and GSK3377794 during clinical trials.
Amendment 4
Overall Rationale for the Amendment:
The overall rationale for this amendment is to clarify patient management with regards to treatment regimen 
and evaluation of encephalopathy and modification of lymphodepleting regimen for older participants, 
modification of target dose range for NY-ESO transduced cells and changes related to Health Canada
requests including updates to both the Encephalopathy (now Immune Effector Cell-Associated 
Neurotoxicity or ICANS) and the CRS grading and management criteria.  
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
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Section # and Name
Description of Change
Brief Rationale
Synopsis
Section 3.1-Overall 
Study Design
Section 3.2.5-
Rationale for NY-
ESO-1c259 T Cell 
Dose
Removed the target dose and modify range to 1 
to 8 x109 transduced cells.
To align with other protocols 
across the GSK3377794 
program and to improve 
protocol clarity
Section 3.1 Figure 1
Updated figure to remove weeks 3, 5, 6, and 10 Changes were made to be 
consistent with changes in
Table 15 in the protocol
Section 3.5.1-Benefit 
Assessment
Section 3.5.2 -Risk 
Assessment 
Made changes to update safety profile for 
GSK3377794 based on GSK3377794 
Investigator’s Brochure 2019
Changes were made to align 
with GSK3377794 
Investigator’s Brochure 2019
Section 4.7 
Consideration for 
Temporary 
Suspension of 
Enrollment
Revised Study stopping and pausing rules
To align with other protocols 
across the GSK3377794 
program
Section 3.2.3
Section 5.2
Lymphodepleting 
Therapy
Added option to revise lymphodepleting 
therapy for participants with documented 
history of severe and prolonged cytopenia
To improve participants 
safety
Section 3.2.3
Section 5.2 Table 2 
Section 5.2.1
Lymphodepletion 
Dose Modification
Added lymphodepleting regimen adjustments 
for participants ≥60 years old and participants 
with severe cytopenia
To improve participants 
safety
Section 7.2 Table 4 
and 5 and Appendix 5 
Table 15 - Schedule 
of Activities (SoA)
Revised to include changes from CARTOX to 
ICE and clarify the collection of liquid biopsy
samples.
Changes were made to be 
consistent with changes in 
the text in the protocol and to 
align with other protocols 
across the GSK3377794 
program
Section 7.2 Schedule 
of Procedures Table 4 
(Interventional Phase 
1)
Added blood collection for cytokine analyses 
This cytokine sample is 
being included to determine a 
cytokine profile at time of 
biopsy & will also serve as 
'baseline' cytokine level, 
prior to lymphodepletion for 
the 2nd infusion.
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
Amendment 4
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Section # and Name
Description of Change
Brief Rationale
Section 7.2 Schedule 
of Procedures Table 5
(Long Term Follow-
up)
Revised text to be consistent with text in 
Section 7.2, including collection of delayed 
AEs.
To be consistent with 
changes elsewhere in this 
section
Section 7.4.8 Long 
Term Follow-up
Clarified when delayed AEs would be 
collected
To align with other protocols 
across the GSK3377794 
program
To improve protocol clarity 
and safety monitoring
Section 8.5 
Management of 
Cytokine Release 
Syndrome (CRS)
Revised guidelines to utilize the American 
Society for Transplantation and Cellular 
Therapy updated grading system [Lee, 2019]
Changes were based on 
Regulatory Agency feedback
8.9 Management of 
Immune Effector 
Cell-Associated 
Neurotoxicity 
Syndrome (ICANS)
And Table 11
Revised guidelines to utilize the American 
Society for Transplantation and Cellular 
Therapy updated grading system [Lee, 2019]
Changes were based on 
Regulatory Agency feedback
Section 8.10-
Management of 
Guillain-Barré 
Syndrome (GBS)
Added language to utilize diagnostic guidance 
for GBS [Fokke, 2014; Walgaard 2010; 
Walgaard 2011]
To align with other protocols 
across the GSK3377794 
program
To improve protocol clarity 
and safety monitoring
9.1 Time Period for 
Collecting AE and 
SAE Information
Added clarification to AEs collected during the 
various timepoints of the study 
To improve protocol clarity
9.4 Reporting Criteria 
During Long-Term 
Follow-Up (Years 1 -
15)
Added clarification to AEs collected during the 
various timepoints of the study 
To improve protocol clarity
Section 10.2
Mandated Study 
Pause Due to GBS
Revised language to utilize diagnostic 
guidance for GBS [Fokke, 2014]
To align with other protocols 
across the GSK3377794 
program
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
Amendment 4
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Section # and Name
Description of Change
Brief Rationale
Section 11.3 Study 
Populations
Removed text regarding leukapheresis date 
from the definition of the ITT population
To align with other protocols 
across the GSK3377794 
NSCLC program
Appendix 5, Table 15 
Schedule of 
Procedures
Removed Week 3, 5, 6, and 10 visits from the 
2nd Infusion Schedule of Procedures.  Added 
collection of liquid biopsies at D1, D8, W4 and 
W16.  Samples to evaluate persistence for 
research were added at Baseline and Week 16 
and Week 12 sample 
The evaluations atWeeks 3, 
5,6, and 10 are no needed 
based on prior experience in 
patients treated with t-cell 
infusions on this study. 
Persistence samples were 
added at Baseline and Week 
16 to correlate to second, 
confirmatory imaging and a 
sample at Week 12 sample 
for consistency with the first
infusion table
CONFIDENTIALITY STATEMENT
This document contains information which is the property of GSK LLC, and
therefore is provided in confidence for your review. It is understood that this
information will not be disclosed to others without written approval from GSK
LLC.
DECLARATION
This study will be conducted in compliance with ICH GCP, all applicable subject 
privacy requirements, and the guiding principles of the current version of the
Declaration of Helsinki (with amendments), and in accordance with local legal and
regulatory requirements.
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PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
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SYNOPSIS
Title: A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of 
Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects with 
Stage IIIb or Stage IV Non-Small Cell Lung Cancer(NSCLC).
Short Title
NY-ESO-1c259T for advanced NSCLC
Protocol Number
GSK208749 (ADP-0011-004)
Phase
Pilot
Methodology
This is an open-label clinical trial in subjects with locally 
advanced or metastatic NSCLC. Subjects with the HLA-
A*02:01,HLA-A*02:05,and/orHLA-A*02:06allele,whose 
tumor expresses the NY-ESO-1 and/or L antigen family
member-1a (LAGE-1a) tumor antigen, and who meet study entry 
criteria will be eligible to receive autologous genetically 
modified T-cells (NY-ESO-1c259T). The trial is conducted with 
outpatient procedures; however, subjects may be hospitalized for 
the lymphodepleting chemotherapy at the discretion of the 
Investigator. It is recommended that the T cell infusion is an 
inpatient procedure to allow for close monitoring of post-
infusion adverse events.
Upon enrollment, subjects will undergo leukapheresis for T cell 
collection, and their cells will be genetically engineered and 
expanded ex vivo. The manufacturing of T cells will take 
approximately 28 days. Prior to receiving T cells, subjects will 
undergolymphodepletingchemotherapywithcyclophosphamide 
and fludarabine on Day -7, Day -6, and Day – 5 followed by the 
cell infusion on Day 1.
Safety and tolerability as well as anti-tumor activity and 
biomarker assessments to be conducted at each visit are outlined 
in the Schedule of Procedures. Tumor response will be assessed 
according to Response Evaluation Criteria in Solid Tumors 
(RECIST) v 1.1 by Investigators and scans will be collected and 
stored at a central imaging laboratory for possible independent 
review. Tumor biopsies for research studies will be taken at 
Baseline, Week 8 and upon progression of disease. 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
Phase of the study, will enter a 15-year long-term follow-up 
phase for observation of delayed adverse events in accordance
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Investigational Product: NY-ESO-1c259
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with Food and Drug Administration (FDA) and European 
Medicines Agency (EMA) requirements for gene therapy clinical 
trials. All subjects will continue to be followed for overall 
survival during the long-term follow-up phase.
Study Duration
It is anticipated that this trial will take approximately 18-
24 months to enroll, with the study completion approximately 
24-30 months after initiation (approximately 6 months after the 
last subject is enrolled). Patients will be followed in the long-
term follow-up (LTFU) protocol for up to 15years.
Study Center(s)
This is a multi-center study, including approximately 15 sites in 
North America and Europe. Additional sites may be added at the 
discretion of the Sponsor.
Number of subjects
10 subjects
Objectives
Endpoints
Primary: To evaluate the safety and 
tolerability of autologous genetically 
modified T cells (NY-ESO-1c259T) in human 
leukocyte antigen (HLA) HLA-A*02:01, 
HLA-A*02:05 and/or HLA-A*02:06
positive subjects with NY-ESO-1 and/or 
LAGE-1a positive advanced NSCLC.
Adverse events (AE), including serious 
adverse events (SAE);
Change of laboratory assessments, 
including chemistry, hematology, and 
coagulation;
Cardiac and pulmonary assessments, 
includingelectrocardiogram(ECG)and 
pulmonary function (pulseoximetry).
Secondary: To evaluate the efficacy of NY-
ESO-1c259T
Overall Response Rate (ORR) per 
RECIST 1.1
Time to response 
Duration of response
Disease Control Rate (DCR)
Progression-free Survival (PFS)
Exploratory: To evaluate the persistence, 
phenotype and functionality of NY-ESO-
1c259T
Correlate persistence, phenotype and 
functionality of NY-ESO-1c259T in the 
peripheral blood and/or tumor with 
response to treatment
Correlate circulating cytokines with 
cytokine release syndrome (CRS)
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Investigational Product: NY-ESO-1c259
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Exploratory: To understand mechanisms of 
resistance to NY-ESO-1c259T
Correlatechangesinimmunosuppressive 
myeloid cells and Tregs in peripheral 
blood versus tumor
Correlatechangesinimmunosuppressive 
myeloid cells and Tregs in peripheral 
blood and tumor with treatment response
Investigate the immune contexture of each 
subjects' tumor over time and to 
understand mechanisms of tumor 
resistance, escape and treatment response
Determine whether loss of NY-ESO-1c259T 
expression in tumor is a resistance 
mechanism
Exploratory: To document the exposure 
andimmunogenicitywithNY-ESO-1c259T
Change of anti-NY-ESO-1c259T antibodies
Exploratory: To evaluate antigen 
spreading as a mechanism of response
Correlate clonal outgrowth of T cell
populations with response following T cell 
infusion
Exploratory: To evaluate the survival 
benefit of NY-ESO-1c259T
Overall Survival (OS)
Exploratory: To evaluate the efficacy of 
NY-ESO-1c259T per immune-related 
Response Evaluation Criteria in Solid 
Tumors (irRECIST)
Overall Response Rate (ORR) per 
irRECIST
Time to response (irRECIST)
Duration of response (irRECIST)
Progression-free Survival (PFS, 
irRECIST)
Key Inclusion
/Exclusion Criteria
Key eligibility include:

Subject has histologically or cytologically confirmed 
diagnosis of advanced non-small cell lung cancer (stage IIIB 
or IV) or recurrent disease.

Subject has failed at least one platinum-containing regimen 
and have disease progression. Subjects with known 
epidermal growth factor receptor (EGFR) mutations or 
anaplastic lymphoma kinase receptor (ALK) or ROS1 gene 
rearrangements must have also received failed prior EGFR or 
ALK or ROS1 tyrosine kinase inhibitor,respectively
(progressive disease [PD] or unacceptable toxicity). Subject
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may have received PD-1 or PDL-1 inhibitors. There is no 
limit on lines of prior anti-cancer therapy.

Subject has measurable disease according to RECIST v1.1 
criteria.

Subjectis 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 a designated central laboratory 
confirming NY-ESO-1 and/or LAGE-1aexpression.

Subject has an Eastern Cooperative Oncology Group 
(ECOG) Performance Status 0-1 and anticipated life 
expectancy >3 months.

Subjects with 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 are NOT eligible.

Prior or active demyelinating disease
Refer to protocol Section 4 for complete subject eligibility 
criteria for study entry.
Investigational 
Product, Dose, 
Route, Regimen
The product in this protocol is NY-ESO-1c259T (an autologous 
genetically modified T-cell product) and will be manufactured at 
a central manufacturing site.
Approximately 10 subjects will receive at least 1 x 109 
transduced cells and a maximum of 
8 x 109transduced cells. In the event the minimum cell dose (1 x 
109 transduced cells) cannot be achieved for a subject, that 
subject may be replaced with another subject. Up to two subjects 
may be replaced not to exceed a total of 12 subjects.
A second infusion of NY-ESO-1c259T cells may only be given to 
subjects who have documented progression of disease following 
an initial response and whose tumor continues to express the 
appropriate antigen target.
Comparator therapy
None
Statistical 
Methodology
Descriptive statistics will be provided for selected demographic, 
safety, response and correlative assessments as outlined in the 
statistical analysis plan. Descriptive statistics on continuous data
will include the mean, median, standard deviation, and ranges,
while categorical data will be summarized using frequency 
counts and percentages. Graphical summaries of the data may 
be presented.
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Investigational Product: NY-ESO-1c259
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TABLE OF CONTENTS
TABLE OF CONTENTS........................................................................................................................................... 13
LIST OF TABLES..................................................................................................................................................... 18
LIST OF FIGURES ................................................................................................................................................... 19
1
BACKGROUND AND RATIONALE............................................................................................... 20
1.1 Non-Small Cell Lung Cancer.............................................................................................................. 20
1.2 Background to Adoptive T Cell Therapy ........................................................................................... 20
1.3 Adoptive Immunotherapy with NY-ESO-1 Specific T Cells and Supporting data in NSCLC .......... 21
1.4 Rationale for NY-ESO-1c259T for NSCLC....................................................................................... 22
1.4.1
Optimization of Lymphodepleting ChemotherapyRegimen ............................................. 22
2
TRIAL OBJECTIVES AND ENDPOINTS ....................................................................................... 23
3
INVESTIGATIONAL PLAN............................................................................................................. 25
3.1 Overall Study Design.......................................................................................................................... 25
3.2.1
Screening for HLA and NY-ESO-1..................................................................................... 26
3.2.2
T Cell Manufacturing............................................................................................................ 27
3.2.3
Lymphodepletion .................................................................................................................. 27
3.2.4
T Cell Infusion ...................................................................................................................... 28
3.2.5
Rationale for NY-ESO-1c259 T CellDose ......................................................................... 28
3.3 Number of Subjects and Duration of Study........................................................................................ 28
3.4 Sites
28
3.5 Benefit: Risk Assessment ................................................................................................................... 30
3.5.1
Benefit Assessment............................................................................................................... 30
3.5.2
Risk Assessment ................................................................................................................... 30
3.5.3
Overall Benefit: Risk Conclusion ........................................................................................ 32
4
SELECTION OF STUDY POPULATION, WITHDRAWAL, COMPLETION AND 
STOPPING CRITERIA............................................................................................................................................. 33
4.1 Overview............................................................................................................................................. 33
4.2 Eligibility Criteria for Study Participation (Prior to Leukapheresis).................................................. 33
4.2.1
Inclusion Criteria................................................................................................................... 33
4.2.2
Exclusion Criteria ................................................................................................................. 35
4.3 Additional Eligibility Criteria (Prior to Lymphodepleting Chemotherapy)........................................ 38
4.4 Additional Eligibility Criteria (Prior to Second T-Cell Infusion) ...................................................... 39
4.5 Completion of the Interventional Phases............................................................................................ 39
4.6 Subject Withdrawal............................................................................................................................. 40
4.7 Consideration for Temporary Suspension of Enrollment................................................................... 40
4.8 Liver Safety: Required Actions and Follow-up Assessments ............................................................ 41
5
STUDY TREATMENTS ................................................................................................................... 44
5.1 Leukapheresis ..................................................................................................................................... 44
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5.2 Lymphodepleting Chemotherapy........................................................................................................ 44
5.2.1
Lymphodepletion Dose Modification.................................................................................. 46
5.2.2
Fludarabine dose adjustment for renal impairment ............................................................ 46
5.2.3
Mesna..................................................................................................................................... 46
5.3 T Cell Infusion.................................................................................................................................... 46
5.3.1
Premedication........................................................................................................................ 46
5.3.2
T Cell Infusion ...................................................................................................................... 46
5.4 Second T Cell Infusions (Interventional Phase 2) .............................................................................. 47
6
CONCOMITANT MEDICATION AND TREATMENT.................................................................. 48
6.1 Prohibited Concomitant Medication and Treatment........................................................................... 48
6.2 Permitted Concomitant Medication and Treatment............................................................................ 50
6.3 Contraception...................................................................................................................................... 50
7
SCHEDULE OF ASSESSMENTS AND PROCEDURES ................................................................ 53
7.1 HLA and Antigen Screening............................................................................................................... 53
7.2 Schedule of Procedures....................................................................................................................... 54
7.3 Screen Failures.................................................................................................................................... 62
7.4 Clinical Assessments and Procedures................................................................................................. 62
7.4.1
Medical history...................................................................................................................... 62
7.4.2
Physical Examination and Measurement of VitalSigns..................................................... 62
7.4.3
Performance Status ............................................................................................................... 62
7.4.4
Clinical Safety Assessments................................................................................................. 62
7.4.5
Laboratory Assessments....................................................................................................... 62
7.4.6
Cardiac and Other Assessments........................................................................................... 62
7.4.7
Tumor Response Assessments............................................................................................. 63
7.4.8
Long-Term Follow-up .......................................................................................................... 64
7.5 Correlative Studies and Research Assessments.................................................................................. 65
7.5.1
Pharmacogenetics Sample.................................................................................................... 65
7.5.2
Cytokine and Soluble Factors Analysis............................................................................... 66
7.5.3
Tumor Biopsies ..................................................................................................................... 66
7.5.4
NY-ESO-1c259 TCR+ Cell Persistence:................................................................................ 67
7.5.5
NY-ESO-1c259 TCR+ Cell Phenotype and Activity:............................................................ 67
7.5.6
Liquid Biopsy Collection and Analysis............................................................................... 67
7.5.7
Request for Autopsy for Death Following Administration of Gene Transfer Agents ........ 68
8
SUPPORTIVE CARE GUIDANCE................................................................................................... 68
8.1 T Cell Infusion Symptom Management.............................................................................................. 68
8.2 Infection.............................................................................................................................................. 68
8.2.1
Pneumocystis carinii Pneumonia ......................................................................................... 69
8.2.2
Herpes simplex and Varicella zoster.................................................................................... 69
8.2.3
Cytomegalovirus ................................................................................................................... 69
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8.2.4
Hepatitis B Prophylaxis........................................................................................................ 69
8.2.5
Syphilis .................................................................................................................................. 69
8.2.6
Other Anti-Microbial Prophylaxis ....................................................................................... 69
8.3 Hematologic and Blood Product Support ........................................................................................... 69
8.3.1
Irradiated Blood Product ...................................................................................................... 70
8.3.2
CMV Screened Blood Products ........................................................................................... 70
8.4 Management of Autoimmunity........................................................................................................... 70
8.5 Management of Cytokine Release Syndrome..................................................................................... 70
8.6 Management of Graft-versus-Host Disease (GVHD)......................................................................... 73
8.6.1
Diagnosis of GVHD.............................................................................................................. 73
8.6.2
Grading of GVHD................................................................................................................. 74
8.6.3
Management of GVHD......................................................................................................... 75
8.7 Management of Pancytopenia with Bone Marrow Failure / Aplastic Anemia................................... 76
8.8 Chemotherapy Symptom Management............................................................................................... 77
8.8.1
Management of Neutropenia................................................................................................ 77
8.9 Management of  Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) ................... 78
8.9.1
Management of ICANS........................................................................................................ 78
8.9.2
Monitoring for Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) .. 80
8.9.3
Grading of ICANS.................................................................................................................. 80
8.9.4
Monitoring for ICANS ........................................................................................................... 82
8.10 Management of Guillain-Barré Syndrome (GBS) .............................................................................. 82
8.10.1
Neurological Symptoms ....................................................................................................... 83
8.10.2
Brighton Key Diagnostic Criteria........................................................................................ 84
8.10.3
Erasmus GBS Respiratory Insufficiency Score (EGRIS) .................................................. 84
8.10.4
Modified Erasmus GBS Outcomes Score (mEGOS) ......................................................... 84
8.10.5
Summary of diagnosis and treatment for GBS....................................................................... 84
9
RECORDING ADVERSE EVENTS ................................................................................................. 86
9.1 Time Period for Collecting AE and SAE Information ....................................................................... 86
9.2 Definition of Adverse Event ............................................................................................................... 87
9.2.1
Assessment of Intensity........................................................................................................ 87
9.2.2
Assessment of Causality....................................................................................................... 88
9.3 Reporting Serious Adverse Events (SAEs)......................................................................................... 88
9.4 Reporting Criteria During Long-Term Follow-Up (Years 1 - 15)...................................................... 89
9.5 Progression of Underlying Malignancy.............................................................................................. 90
9.6 Regulatory Reporting Requirements for SAEs................................................................................... 91
9.7 Cardiovascular and Death Events ....................................................................................................... 91
9.8 Pregnancy............................................................................................................................................ 92
9.9 Pre-existing Condition ........................................................................................................................ 93
9.10 Laboratory Test Abnormalities as Adverse Events............................................................................. 93
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9.11 Timelines for Safety Reporting........................................................................................................... 93
10
SAFETY MONITORING................................................................................................................... 93
10.1 Safety Review Team........................................................................................................................... 93
10.2 Mandated Study Pause Due to GBS ................................................................................................... 94
10.3 Monitoring and Management of Replication-Competent Lentivirus (RCL) ...................................... 94
10.4 Testing for RCL in Clinical Studies ................................................................................................. 95
10.5 Safety Monitoring Results ................................................................................................................ 95
10.6 Persistence Testing and Monitoring for Insertional Oncogenesis...................................................... 95
10.7 Testing for Persistence of Gene Marked Cells in Clinical Studies ................................................. 96
10.8 Testing for Insertional Oncogenesis................................................................................................. 96
10.9 Monitoring and management for Demyelinating Neuropathy and other Neurological events........... 97
11.
STATISTICAL AND DATA ANALYSIS......................................................................................... 97
11.1 Study Populations .............................................................................................................................. 97
11.2 Sample Size Calculations................................................................................................................... 97
11.3 Interim Analyses................................................................................................................................. 97
11.4 Statistical Methods for Safety Endpoints............................................................................................ 97
11.5 Statistical Methods for Efficacy Endpoints ........................................................................................ 98
12.
CLINICAL SUPPLIES....................................................................................................................... 99
12.1 Packaging and Labelling..................................................................................................................... 99
12.2 Standard Policies and Product Return ................................................................................................ 99
12.3 Storage and Handling.......................................................................................................................... 99
12.4 Product Accountability ....................................................................................................................... 99
13.
DATA HANDLING AND RECORD KEEPING ............................................................................ 100
13.1 Data Management............................................................................................................................. 100
13.2 Case Report Forms............................................................................................................................ 100
13.3 Source Documents and Background Data ........................................................................................ 100
13.4 Data Retention and Availability ....................................................................................................... 101
14.
STUDY MONITORING .................................................................................................................. 101
14.1 Audit and Inspections ....................................................................................................................... 101
15.
REGULATORY AND ETHICAL CONSIDERATIONS................................................................ 102
15.1 Competent Authority Submissions ................................................................................................... 102
15.2 Independent Ethics Committees ....................................................................................................... 102
15.3 Local Regulations/ Declaration of Helsinki...................................................................................... 102
15.4 Informed Consent ............................................................................................................................. 102
15.5 Confidentiality .................................................................................................................................. 103
15.6 Protocol Adherence........................................................................................................................... 103
15.7 Completion of the Study and Study Termination ............................................................................. 103
15.8 Public Posting of Study Information................................................................................................. 103
15.9 Clinical Study Report........................................................................................................................ 103
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15.10
Publication Policy................................................................................................................. 104
16.
APPENDICES .................................................................................................................................. 105
APPENDIX 1.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS............................... 105
APPENDIX 2.
ECOG PERFORMANCE STATUS ............................................................................. 108
APPENDIX 3.
LOCAL LABORATORY TESTS AND ECG PARAMETERS.................................. 109
APPENDIX 4.
RECIST 1.1 CRITERIA FOR EVALUATING RESPONSE IN SOLID TUMORS.... 111
APPENDIX 5.
SCHEDULE OF PROCEDURES FOR SECOND T CELL INFUSION 
(INTERVENTIONAL PHASE 2) .................................................................................................... 117
APPENDIX 6.
LIST OF REFERENCES .............................................................................................. 123
APPENDIX 7.
PROTOCOL CHANGES.............................................................................................. 128
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LIST OF TABLES
Table 1 
Laboratory Values to Define Adequate Organ Function................................................... 35
Table 2:
Lymphodepleting Chemotherapy Treatment Regimen for GSK208749 (ADP-0011-
004)
45
Table 3:
Fludarabine Dose Adjustment........................................................................................... 46
Table 4
Schedule of Procedures (Interventional Phase 1).............................................................. 54
Table 5
Schedule of Procedures – Long Term Follow-up.............................................................. 60
Table 6:
Management Guidelines for Cytokine Release Syndrome................................................ 71
Table 7:
Overview of Clinical Findings/Symptoms of GVHD ....................................................... 74
Table 8:
Staging of Dermal, Gastrointestinal and Hepatic Involvement with Acute GVHD.......... 75
Table 9:
Grading of Acute GVHD................................................................................................... 75
Table 10:
Management Guidelines for GVHD.................................................................................. 76
Table 11:
Management of ICANS..................................................................................................... 79
Table 12:
Immune Effector Cell-Associated Encephalopathy (ICE) assessment tool...................... 81
Table 13:
Grading of Immune Effector Cell-Associated Neurotoxicity Syndrome 
(ICANS)Encephalopathy Syndrome.............................................................................................. 81
Table 14:
Grading of AEs Not Specified in CTCAE v4.0................................................................ 87
Table 15
: Schedule of Procedures for Second T Cell Infusion (Interventional Phase 2) .............. 117
Table 16
Summary of and Rationale for Protocol Changes ........................................................... 129
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LIST OF FIGURES
Figure 1
Schematic for Study GSK208749 (ADP-0011-004).................................................. 26
Figure 2
Diagnosis and Treatment of Guillain-Barré Syndrome (GBS) .................................. 85
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1
BACKGROUND AND RATIONALE
1.1
Non-Small Cell Lung Cancer
Lung cancer is the most common cancer worldwide and it is the leading cause of all
cancer- related deaths, responsible for approximately 1 in 5 cancer deaths. There 
were estimated to be 1.8 million new cases of lung cancer in 2012 (12.9% of the 
total) (Ferlay, 2013). In the United States, lung cancer is the second most 
common form of the cancer after prostate cancer in men and after breast cancer in 
women (US Cancer, 2015). In Europe, lung cancer is the second most common
cancer in men after prostate and the third most common cancer in women after 
breast and colorectal (Ferlay, 2013). One reason for the relatively poor prognosis
is initial diagnosis with advanced disease (only 15% of lung cancers are diagnosed 
at a localized stage).
Non-small cell lung cancer (NSCLC) accounts for 84% of lung cancer and may be
classified according to histology as adenocarcinoma (40%) which usually originate
in peripheral lung tissue, squamous-cell carcinoma (25%) typically occurring close
to large airways and large- cell carcinoma (10%) (NCI, 2016). Subsets of
adenocarcinomas can be further defined at the molecular level by the specific
mutations of genes coding, for example, for epidermal growth factor receptor
(EGFR) and anaplastic lymphoma kinase receptor (ALK).
For early stage NSCLC, surgery is the treatment of choice; however, subsequent 
relapse at distant sites has resulted in the use of additional chemotherapy or
radiotherapy. For subjects with advanced NSCLC that lack certain molecular
alterations, such as ALK translocation or EGFR mutations, recommended first-line 
treatment is with platinum-based doublet chemotherapy. This generally consists 
of cisplatin or carboplatin with another cytotoxic agent (pemetrexed, taxanes, 
gemcitabine, vinorelbine or camptothecins). Other agents, such as bevacizumab 
or cetuximab, may be added to the regime. Erlotinib or afatinib may be indicated 
for subjects with sensitizing EGFR mutations or crizotinib or ceritinib in subjects 
with ALK rearrangements. In subjects who experience disease progression, 
single-agent chemotherapy or appropriate targeted drugs may be indicated as
second- or third-line therapy. Furthermore, recent research into checkpoint 
inhibitors (e.g. anti-CTLA-4 and anti-PD-1 antibodies) have shown promising 
results in clinical trials with nivolumab, receiving marketing authorization in the
US for treatment of advanced NSCLC who had received prior platinum-based
chemotherapy.
1.2
Background to Adoptive T Cell Therapy
Adoptive T cell therapy (ACT) is a treatment that uses a cancer subject’s own T
lymphocytes with anti-tumor activity, expanded in vitro and re-infused into the 
subject. The ultimate objective of the process is the stimulation and expansion of
potent and antigen-specific T cell immunity. There are numerous recent 
publications and reviews of ACT (Kalos, 2013; Klebanoff, 2016; Maus, 2014;
Morgan, 2010; Robbins, 2011; Rosenberg, 2008).
The first observations that immune system engagement can lead to antitumor
effects are often attributed to William Coley, who observed regression of sarcoma
following severe bacterial infections in the 1890s. Further observations of the 
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spontaneous regression of malignant melanoma lesions initially led to the use of 
T cells isolated from tumor-infiltrating lymphocytes (TILs). Cell therapy using 
tumor-reactive TILs has resulted in approximately 50% objective clinical
regression in melanoma subjects (Besser, 2010; Dudley, 2005). This therapy;
however, has been limited by the requisite surgery to procure tumor-reactive TIL,
by ex vivo identification and expansion of these cells (TILs could be generated from
only 50% of resected samples) and by the failure to reproducibly isolate similar 
cells from other cancer types.
Adoptive transfer of bulk T lymphocytes, obtained from the periphery and
expanded ex vivo to generate large numbers of cells prior to reinfusion into 
subjects, is an alternative strategy for ACT (Rapoport, 2005). However, tumor 
cells are well known to be immunologically selected for low antigen presentation 
and, furthermore, the majority of tumor antigens are normally expressed self-
antigens. Hence, the natural T cell receptors (TCRs) that recognize self-tumor 
antigens are of low affinity. The high tolerance to tumor antigens with normal 
and/or developmental expression combined with the potent immunosuppressive 
microenvironment often present at the tumor site is manifest in most cases by 
suboptimal activation in terms of antitumor activity such that ‘‘native’’ T cells 
may not be sufficient to induce tumor cell death in most subjects with advanced 
malignancy. Higher affinity TCRs allow T cells to respond to lower levels of 
antigen; this is important for tumor immunotherapy where the tumor
microenvironment has adapted itself to reduce expression of antigen and also 
decrease expression of major histocompatibility complex (MHC) class I 
molecules (Baccala, 2005; Barrett, 2009; Marincola, 2000).
Therefore, gene-transfer-basedstrategies have been developed to overcome the
consequences of immune tolerance on the tumor-specific T cell repertoire. These 
approaches provide the potential to redirect T cells to effectively target tumors by 
the transfer of antigen-specific affinity-optimized T cell receptors. The majority 
of clinical approaches have employed T cells engineered to stably express 
transgenes via virus-based transduction. Virus-mediated gene transfer approaches
typically employ vectors that are derived from gamma retroviruses or more 
recently lentiviruses.
Rational high-throughput genetic mutagenesis approaches have resulted in the 
ability to molecularly engineer TCRs with substantially higher affinities for target
antigens. Affinity- enhanced TCR-based engineering approaches have certain
inherent biological advantages, most notably that essentially all cellular proteins
can be targeted because the approach is not limited to the targeting of cell surface 
epitopes, and the primary T cell activation signal is delivered in a physiological
context, which may be relevant for optimal functionality of the infused T cells.
Additional details are provided in the current NY-ESO-1c259T Investigator 
Brochure.
1.3
Adoptive Immunotherapy with NY-ESO-1 Specific T Cells and Supporting 
data in NSCLC
Although progress has been made in the treatment of lung cancer, improvements
have been modest leading to only 4% – 5% improvements in 5-year survival rates
for disease Stages I – III and prolongation of only months for Stage IV (Johnson,
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2014). In subjects with advanced NSCLC, new agent/ platinum combinations 
have generated overall response rates of approximately 25% – 35% which have 
plateaued. In addition, time to progression (4 – 6 months), median survival (8 –
10 months), 1 year survival rate (30% – 40%) and 2 year survival rate (10% –
15%) in fit subjects remain short.
However, NSCLC is now recognized as an immunologically targetable disease
(Chow, 2013). Recent research into checkpoint inhibitors (e.g. anti-CTLA-4 and
anti-PD-1 monoclonal antibodies) have shown promising results in clinical trials 
but have also demonstrated immune-related toxicities (skin, gastrointestinal, 
hepatic, endocrine and pneumonitis). Nivolumab received marketing
authorization in the USA for treatment of subjects with advanced NSCLC who had
received prior platinum-based chemotherapy (Bristol-Myers Squibb, 2016).
Published data indicates that NSCLC tumors express NY-ESO-1 (New York 
esophageal squamous cell carcinoma 1) with rates ranging approximately 11% to
43% of tumors (Grah, 2008; Gure, 2005). The Cancer Genome Atlas Ribonucleic
acid (RNA) sequencing database indicates a frequency of expression of NY-ESO-
1 in 12% in lung adenocarcinoma and 26% in squamous cell carcinoma and a 
frequency of expression of L antigen family member-1a (LAGE-1a) in 8.5% of
adenocarcinoma and 21% of squamous cell (NCI, 2016).
1.4
Rationale for NY-ESO-1c259T for NSCLC
Both the potential role for immunotherapies in NSCLC and the high unmet medical 
need in subjects with advanced disease provide strong rationale for the study of NY-
ESO SPEAR®T- cells (Specific Peptide Enhanced Affinity Receptor) in the subject
population.
1.4.1
Optimization of Lymphodepleting Chemotherapy Regimen
The most common lymphodepletion regimens used in ACT trials to date have
incorporated cyclophosphamide or cyclophosphamide and fludarabine (Dudley, 
2002; Dudley, 2005; Johnson, 2009; Robbins, 2011). The use of 
cyclophosphamide alone can achieve lymphodepletion without long-term 
immunosuppressive side effects. Therefore, in this study, cyclophosphamide 
alone was initially chosen forpreconditioning.
Recent studies in lymphoma, chronic leukemia and acute leukemia using a chimeric
antigen receptor (CAR) showed increased CD4+ and CD8+ CAR-T cell 
expansion, persistence and disease-free survival when fludarabine was added in to
a previously cyclophosphamide-only preparative regimen (Turtle, 2016). The 
cyclophosphamide was administered at 30 – 60 mg/kg x 1 day and fludarabine at
25 mg/m2/day x 3 – 5 days. Effective lymphodepletion has also been demonstrated
in other CAR-T cell studies using reduced cyclophosphamide dosing than 
previously used, together with fludarabine (Batlevi, 2016). The lymphodepleting 
regimen in which objective tumor responses have been observed in an ongoing
Adaptimmune clinical study in synovial sarcoma uses a cyclophosphamide dose 
of 1800 mg/m2/day for 2 days, in addition to fludarabine 30 mg/m2/day for 4 days 
(ClinicalTrials.gov Identifier: NCT01343043).
Based on the emerging data that the addition of fludarabine to cyclophosphamide
may play a role in homeostatic expansion, the protocol has been amended to
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evaluate cyclophosphamide and fludarabine as a lymphodepleting regimen. Refer 
to Section 3.2.3 for further rationale for lymphodepletion.
2
TRIAL OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To evaluate the safety and tolerability of 
autologous genetically modified T cells 
(NY-ESO-1c259T) in HLA-A*02:01, 
HLA-A*02:05  and/or HLA-A*02:06
positive subjects with NY-ESO-1 and/or 
LAGE-1a positive advanced NSCLC
Adverse events (AE), including serious adverse 
events (SAE);
Change of laboratoryassessments, including 
chemistry, hematology, andcoagulation;
Cardiacandpulmonaryassessments, including 
electrocardiogram (ECG) and pulmonary 
function (pulse oximetry).
Secondary
To evaluate the efficacy of NY-ESO-
1c259T
Overall Response Rate (ORR) per RECIST 1.1 
Time to response
Duration of response 
Disease Control Rate (DCR)
Progression-free Survival (PFS)
Exploratory
To evaluate the persistence, phenotype 
and functionality of NY-ESO-1c259T.
Correlate persistence, phenotype and 
functionality of NY-ESO-1c259T in the 
peripheral blood and/or tumor with response to 
treatment
Correlatecirculatingcytokines withcytokine 
release syndrome (CRS)
To understand mechanisms of resistance 
to NY-ESO-1c259T
Correlate changes in immunosuppressive 
myeloid cells and Tregs in peripheral blood 
versus tumor
Correlate changes in immunosuppressive 
myeloid cells and Tregs in peripheral blood and 
tumor with treatment response
Investigate the immune contexture of each 
subjects' tumor over time and to understand 
mechanisms of tumor resistance, escape and 
treatment response Determine whether loss
of NY-ESO-1c259T or antigen expression in 
tumor is a resistance mechanism
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To document the exposure and 
immunogenicity with NY-ESO-1c259T
Change of anti-NY-ESO-1c259T antibodies
To evaluate antigen spreading as a 
mechanism of response
Correlate clonal outgrowth of T cell
populations with response following T 
cellinfusion
To evaluate the survival benefit of NY-
ESO-1c259T
Overall Survival (OS)
To evaluate the efficacy of NY-ESO-
1c259T per immune-related Response 
Evaluation Criteria in Solid Tumors 
(irRECIST)
Overall Response Rate (ORR) per irRECIST 
Time to response (irRECIST)
Duration of response (irRECIST)
Progression-free Survival (PFS, 
irRECIST)
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3
INVESTIGATIONAL PLAN
3.1
Overall Study Design
This is a pilot, open-label study of genetically engineered NY-ESO-1c259T cells in HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 subjects with advanced NSCLC.
Approximately 10 subjects will be enrolled in thisstudy.
Subjects who have pre-screened for the relevant HLA alleles and NY-ESO-1 antigen will 
sign the study Informed Consent Form (ICF) and enter the Screening Phase in this protocol to 
determine eligibility for the study. The Screening Phase starts from the time the subject signs 
the ICF until leukapheresis. Eligible subjects then enter the Interventional Phase 1 of the 
study (first T cell infusion) which runs from the day of leukapheresis until progressive 
disease (PD).
Subjects will be screened for enrollment into the study according to the eligibility criteria in 
Section 4.2. Following Screening, subjects meeting all eligibility criteria will undergo 
leukapheresis to obtain cells for the manufacture of autologous NY-ESO-1c259TCR bearing T 
cells. Leukapheresis should be performed as soon as possible after the subject is determined 
to be eligible for study participation. Leukapheresis may also be performed in advance of a 
subject being eligible for treatment (i.e., before meeting the eligibility criteria prior to 
lymphodepleting chemotherapy).
When the NY-ESO-1c259T cells are available, subjects will undergo lymphodepleting 
chemotherapy with cyclophosphamide and fludarabine (Section 5.2), followed by infusion of 
NY-ESO-1c259transduced T cells in the range of 1 x 109 to 8 x 109transduced cells
(Section 5.3). Prior to the administration of lymphodepleting chemotherapy, subjects must 
have failed at least one prior platinum-containing regimen and have PD. All other eligibility 
criteria will be reconfirmed and baseline tumor measurements obtained. The 
lymphodepleting chemotherapy may be given as an outpatient procedure but subjects may be
hospitalized at the discretion of the Investigator. It is recommended that subjects receive 
granulocyte-colony stimulating factor (G-CSF) support starting 24 hours after 
lymphodepleting chemotherapy. It is recommended that the T cell infusion is an inpatient 
procedure to allow for close monitoring of post-infusion AEs. Subject may be hospitalized 
for follow-up care post T-cell infusion at the discretion of the Investigator. Section 8
provides guidance for supportive care during T-cell infusion.
The time point for administration of lymphodepleting chemotherapy and subsequent infusion 
of NY-ESO-1c259TCR bearing T cells will be staggered for the first 3 subjects enrolled.
Subjects may receive lymphodepleting chemotherapy as defined in Table 2 only after the 
previously enrolled subject has had a minimum safety observation period of 21 days 
following their NY-ESO-1c259T cell infusion. This 21-day observation period shall remain 
for the first 3 subjects enrolled. If 2 or more subjects among the first 3 subjects enrolled 
experience a severe study-related toxicity, enrollment will be paused for evaluation by the 
Sponsor and Investigators, otherwise, an additional 7 subjects will be entered. Refer to 
Section 4.7 for full details on the stopping rules for thisstudy.
Efficacy, safety, and biomarker assessments to be conducted at each visit are outlined in the 
Schedule of Procedures (Table 4). Efficacy will be assessed using RECIST v1.1 (Eisenhauer,
2009).
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Subjects who have PD following response to the initial infusion but whose tumors continue to 
express the appropriate antigen target will be eligible for a second infusion with engineered
T-cells pending they meet eligibility criteria defined in Section 4.4. Refer to Table 15 for 
Schedule of Procedures for Second Infusion (Interventional Phase2).
A subject will be considered to have completed the Interventional Phase of the study when 
he/she has PD or has died prior to PD, or 2 years after the latest NY-ESO-1c259 T cells 
infusion, whichever is shorter. A subject will be considered completing the Interventional 
Phase 2 of the study when he/she has PD, or has died prior to PD, or 6 months after the NY-
ESO-1c259T cell infusion, whichever is shorter. All subjects completing the Interventional 
Phase of the study will be rolled over to a long-term follow-up (LTFU) Protocol 
(GSK208750 [ADP-0000-002]) for observation of delayed AEs for 15 years post-infusion in 
accordance Food and Drug Administration (FDA) and European Medicines Agency (EMA) 
requirements for gene therapy clinical trials. All subjects will continue to be followed for 
overall survival during the LTFU phase. If LTFU protocol is not available when a subject 
completes the Interventional Phase, subject can be followed under this protocol until LTFU 
protocol becomes available.*
Figure 1 provides a schematic for the study.
Figure 1
Schematic for Study GSK208749 (ADP-0011-004)
*subjects, who have a confirmed response (or have stable disease for >4 months) and subsequently have documented PD and whose tumors 
continue to express NY-ESO-1 as verified by assay performed in biopsied tissue, can be considered for a second infusion with engineered 
T cells
3.2
Rationale for Components of Study Design
3.2.1
Screening for HLA and NY-ESO-1
The NY-ESO-1c259T specifically recognizes the HLA-A*02:01, HLA-A*02:05, and HLA- A*02:06-
restrictedNY-ESO-1peptideantigenHLA-A*02-SLLMWITQC. NY-ESO-1and LAGE-1a share the
same peptide sequence that is displayed in HLA-A*02:01 on the surface of tumor cells. Therefore, this 
protocol will select for subjects with these three HLA-A2 allelic variants and whose tumors express
2, 4, 8, 12, 16, 20, 24
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the NY-ESO-1and/or LAGE-1a antigens.
The prevalence of HLA sub-types varies from population to population. Information on the prevalence of 
HLA-A2 allelic variants is available in the Allele Frequency Net Database 
(www.allelefrequencies.net). It is recommended that Investigators review the database for HLA-A2
allelic variants relevant to the study population at their site.
3.2.2
T Cell Manufacturing
The Investigational Product (IP) is comprised of autologous CD4 and CD8 T cells that have been 
transduced with a self-inactivating (SIN) lentiviral vector expressing an affinity enhanced NY-ESO-1 
specific TCR. The product of this transduction is polyclonal T cells which are designed to target NY-
ESO-1 in tissue. The transfer vector is a SIN lentiviral vector which has been meticulously designed to 
contain only the minimal genetic elements required for function, and no vector proteins for maximum
biosafety (Dull, 1998). Lentiviral vectors are a subset of retroviral vectors thought to have an enhanced 
safety profile. Many reports provide evidence supporting the relative biosafety of SIN lentiviral vectors
in terms of genotoxicity, resulting primarily from the lack of enhancer activity in the lentivirus Long 
Terminal Repeat in comparison to the γ retroviral vectors (Maruggi, 2009; Modlich, 2009; Montini, 
2009; Montini, 2006).
Cell product typically is ready to be shipped to the site approximately 28 days after 
leukapheresis. Shipment to clinical sites will ideally be before the start of lymphodepleting 
chemotherapy; however, exceptions may be made for non-US sites that are unable to store 
genetically modified cells. In these cases, the cells may be shipped to the site immediately 
prior to the infusion and stored in the validatedcryoshipper.
After the ex vivo activation and expansion, the final cellular product is typically >90% T 
lymphocytes since the culture conditions do not support the growth of macrophages, natural 
killer or B cells. By the end of the culture period, B cells comprise <2%, natural killer cells
<2%, and macrophages <1% of the total culture. Additional details are provided in the NY-
ESO-1c259T Investigator Brochure.
3.2.3
Lymphodepletion
The incorporation of lymphodepletion prior to ACT may enhance immune reconstitution by 
the transferred cells and increase tumor specific responses. Immune reconstitution is 
enhanced through homeostatic mechanisms that facilitate expansion of T lymphocytes 
(Baccala, 2005) and facilitate trafficking of the engineered T cells (Pinthus, 2004).
Lymphodepletion also enhances the activity of the adoptively transferred cells via the 
removal of inhibitory factors such as regulatory T cells (Wolf, 2003) and can activate antigen 
presenting cells through the induction of inflammatory cytokines and induction of tumor 
apoptosis with resulting cross presentation of tumor antigens to T cells.
Recent evidence suggests that preparation for successful engraftment and expansion of gene 
modified ACT depends not just on the depth of cytoreduction but additionally on the specific 
action of some cytotoxic drugs. Recent studies in lymphoma, chronic leukemia and acute 
leukemia using ACT including a CAR showed increased T cell expansion, persistence and 
disease-free survival when fludarabine was added in a previously cyclophosphamide-only 
preparative regimen (Turtle, 2016).
Basedon our experienceusingcombinationfludarabine-cyclophosphamide lymphodepleting 
chemotherapy in a clinical study in synovial sarcoma and the increasing evidence that 
fludarabine may be a necessary component of the adoptive T cell therapy, the 
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lymphodepleting regimen in this study consists of fludarabine 30mg/m2/day at Days -8, -7, -6 
and -5 and cyclophosphamide 900mg/m2/day intravenously at Days -7, -6 and -5 (refer to
NY-ESO-1c259T Investigator Brochure).  For patients over 60 years of age, see dose 
modification in Section 5.2. For subjects with documented history of severe and prolonged 
cytopenia (anemia, thrombocytopenia, or leukopenia), the investigator should discuss with 
the sponsor’s medical monitor or designee to determine the need for dose modification of 
the lymphodepletion regimen.
3.2.4
T Cell Infusion
The investigational product in this study is the infusion of autologous T cells transduced with 
lentivirus encoding enhanced TCR specific for NY-ESO-1 (refer to Section 5.3 for 
administration details).
3.2.5
Rationale for NY-ESO-1c259 T Cell Dose
Activity seems to be indirectly related to dose administered (depending also on cell 
expansion and persistence) although high T cell doses may be associated with an increased 
risk of AE (e.g. cytokine release). Total T-cell doses up to ~100 x 109cells (median of 5 x 
1010 T transduced T cells with an anti-NY-ESO-1 TCR range of 1.6 x 109 to 130 x 109) 
(Robbins, 2011) have been used although the actual products may differ depending on 
manufacturing methods. Conversely, doses as low as 0.015 x 109(15 million) with CD19 
CAR-T cells may also be effective (Porter, 2011).
Current experience with NY-ESO-1c259T (n=100 subjects treated as of January 2019) is with 
total cell doses in the range of 0.4 x 109 – 3.47 x 1010 with a transduction level of ~18% –
78% (transduced cell dose range of 0.23 x 109 – 14.36 x 109). No untoward AEs have been 
observed in subjects who received higher transduced cell doses (>5 x 109 cells). Of the 5 
subjects who received <1 x 109 transduced cells, 3 subjects had poor expansion and 
persistence of transduced cells; meaningful clinical responses were not observed in 4 of the 5 
subjects. No clear dose response relationship has been observed to-date.
A range of 1 x 109to 8 x 109transduced cells will be administered by a single intravenous 
infusion on Day 1. If the transduced cell dose is less than the minimum dose of 1 x 109, 
manufacturing of additional transduced T cells from excess banked leukapheresis product 
will be undertaken to achieve a total dose in the target range. In the event that no banked 
leukapheresis product is available, a second leukapheresis may be performed to achieve a 
dose in the target range.
3.3
Number of Subjects and Duration of Study
The target enrollment for this trial is 10 subjects. In the event, a minimum dose of 
engineered cells (1 x 109transduced cells) cannot be achieved for a subject, that subject may 
be replaced with another subject. Up to two subjects may be replaced not to exceed a total of 
12 subjects.
Based on the anticipated positive screening rate, study enrollment is expected to continue for 
approximately 18-24 months. It is estimated that this study will take approximately 24-30
months to complete. The study will be considered complete once the last subject has 
transitioned to the LTFU protocol.
3.4
Sites
The protocol will be conducted in approximately 15 sites in North America and Europe. The 
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number of centers is necessary to ensure recruitment in this targeted population. Additional 
centers may be added at the discretion of theSponsor.
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3.5
Benefit: Risk Assessment
The results of clinical and non-clinical studies conducted with NY-ESO-1c259T are 
summarized in the Investigator Brochure. This section outlines the potential benefits, risks 
and the mitigation strategy for this study.
3.5.1
Benefit Assessment
The NY-ESO-1 cancer germline antigen is expressed by RNA sequencing in approximately 
12% of lung adenocarcinoma and 26% of squamous cell carcinoma and is highly restricted to 
the tumor and not expressed in normal healthy adult tissues (NCI, 2016). A subject’s T cells 
can be genetically engineered to recognize tumor antigens. The TCR approach to engineered 
T cell therapy is attractive because TCRs are capable of recognizing not only cell surface 
proteins (as is the case with CAR-T cells) but also any internal protein, since TCRs recognize 
peptide fragments in the context of HLA. In addition, the TCR approach mimics the natural 
function of the T cell by recruiting the endogenous signaling molecules and adhering to 
correct spatial orientation between the T cell and its target. These aspects may contribute to 
enhanced safety and activity of TCR engineered cells.
NY ESO-1c259T is the first Adaptimmune and GSK TCR to be studied in subjects with 
cancer. As of 27 January 2019, 100 subjects have been treated with NY-ESO-1c259T 
(engineered using a lentiviral vector) in five clinical trials in the indications of multiple
myeloma, synovial sarcoma, myxoid/round cell liposarcoma, melanoma, and ovarian cancer.
Objective responses have been observed in the on-going synovial sarcoma study, 
GSK208466 (formerly ADP-04511) and in the myeloma(transplant)study,209393 
(formerlyADP-01411[GSK3377794InvestigatorBrochure 2019;(Rapoport, 2015)].
Additionally, 38 subjects were treated in an Investigator sponsored study conducted by the
National Cancer Institute (NCI) (Robbins, 2008; Zhao, 2007), where the T cells were 
modified using a retroviral vector, expanded using NCI cell processing methods and 
administered in conjunction with IL-2. HLA-A2 subjects with melanoma and synovial 
sarcoma tumors expressing NY-ESO-1 were recruited. Eleven of 18 subjects (61%) with 
synovial sarcoma and 11 of 20 subjects (55%) with melanoma demonstrated objective 
clinical responses. The estimated overall 3 and 5-year survival rates for subjects with 
synovial cell sarcoma were 38% and 14% respectively, while the corresponding estimated 
survival rates for patients with melanoma were both 33% (Robbins, 2015). In addition, two 
subjects with gastroesophageal cancer have been treated in the ATTACK-OG clinical trial.
Thus, there is good evidence to support the potential therapeutic benefit of NY-ESO-1c259T 
cells in subjects with advanced or metastatic NSCLC.
3.5.2
Risk Assessment
The known safety profile of NY-ESO-1c259T is based on 100 treated subjects as of 27 
January 2019 (see GSK3377794 IB 2019). 
In the integrated sponsored trials, 100 subjects have received GSK3377794; fifteen (15) of 
these subjects [11 subjects in Study 208466 (formerly ADP-04511) and 4 subjects in 
Study 209393 (formerly ADP-01411)] have received a second infusion of GSK3377794 
after progressive disease following response (or prolonged stable disease) to their initial 
infusion.
Treatment-emergent adverse events (TEAEs) which occurred in ≥50% of subjects
following GSK3377794 infusion were nausea (82%), anemia/RBC decreased (79%),
neutropenia/neutrophil count decreased (79%), leukopenia/WBC decreased (78%),
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thrombocytopenia/platelet count decreased (75%), pyrexia (73%), fatigue (72%),
diarrhoea (58%), and lymphopenia/lymphocyte count decreased (50%). There were no apparent significant 
differences in reported TEAEs between subjects receiving 1 or 2 infusions
Treatment-emergent serious adverse events (SAEs) occurred in 58 (58%) subjects across
all studies. Treatment-emergent SAEs occurring in 2 or more subjects following
GSK3377794 cell infusion were febrile neutropenia (13%), pyrexia (13%), cytokine
release syndrome (CRS) (12%), neutropenia/neutrophil count decreased (10%), dyspnoea
(6%), thrombocytopenia/platelet count decreased (5%), dehydration (4%), diarrhoea
(4%), hypotension (4%), acute kidney injury (3%), atrial fibrillation (3%), hypoxia (3%),
pleural effusion (3%), rash/rash maculo-papular (3%), abdominal pain (2%),
anemia/RBC decreased (2%), back pain (2%), bone marrow failure (2%), chills (2%),
cough (2%), Guillain-Barré syndrome (2%), leukopenia/WBC decreased (2%), nausea
(2%), pneumonitis (2%), Staphylococcal infection (2%), and unspecified graft-versus
host disease (GVHD) - other (lung, bone marrow, not specified) (2%). The SAE profile
following a second infusion of GSK3377794 was consistent with that experienced for all
subjects infused. 
Three (3%) subjects experienced treatment emergent fatal SAEs:

one subject with synovial sarcoma died due to the treatment-related SAE of bone marrow failure on Day 
96, despite supportive care for pancytopenia with febrile neutropenia and bacteremia (blood cultures 
tested positive for Pseudomonas aeruginosa on Day 59 and for cytomegalovirus on Day 69; infections 
were ongoing at time of death); 

one subject with MRCLS was reported to die due to the treatment-related SAE of cardiac arrest on Day 
160. This subject had a Grade 3 cytokine release syndrome (CRS) complicated by supraventricular 
tachycardia and hypotension related to therapy immediately following infusion. He also had an anterior 
chest wall mass detected at baseline; contribution of this mass to the cardiac complications is unclear. 
GSK’s assessment of this report indicates that the exact cause of death remains unclear, but not likely 
related to the study treatment;

one subject with ovarian cancer died due to disease progression unrelated to treatment, which was 
reported as an SAE although death due to disease progression is generally excluded from the protocol 
SAE definition.
There were no fatal SAEs reported among subjects who received a second infusion of
GSK3377794.
To help Investigators manage CRS and GVHD, treatment guidance based on published 
literature was developed and is included in this protocol (refer to Section 8). Study sites are 
expected to have access to physicians with expertise in bone marrow transplant, and 
infectious diseases for consultation in the event of a subject developing either CRS or 
GVHD-like symptomatology. The protocol also includes guidance on the irradiation of 
transfused blood products to minimize the possibility of transfusion-related GVHD.
GSK are monitoring reports of recurrent pancytopenia after initial bone marrow recovery 
following pre-conditioning chemotherapy and NY-ESO-1c259T cell infusion. In order to 
manage this risk, the Sponsor has developed standard protocol guidance on the management 
of pancytopenia with bone marrow failure following initial bone marrow recovery.
Management of bone marrow failure (aplastic anemia) and related cytopenias is challenging, 
with no clearly established guidelines regarding immunosuppression. Therefore, treatment is 
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largely supportive, including transfusions and treatment of infections. Guidance includes a
recommendation to consult with physicians with expertise in the management of aplastic 
anemia and infectious diseases.
To manage the risk of CRS, GVHD, and pancytopenia in the NY-ESO-1c259T program, 
specific AE pages will be implemented in the electronic Case Report Form (eCRF) to 
carefully document these events to enable evaluation and identification of potential risk 
factors.
The potential risk of non-infectious encephalopathy, which may be due to the inflammation 
in the brain following TCR T-cell infusion, is mitigated by the exclusion of participants with 
brain metastases with features associated with such risk. Grading, monitoring and managing 
of encephalopathy syndrome (ES) are described in Section8.9.
The potential risks of replication competent lentivirus (RCL) and insertional oncogenesis 
(IO) are being monitored in accordance with FDA guidance (refer to Section 10).
Acute inflammatory demyelinating polyneuropathy / Guillain-Barré Syndrome (GBS) 
developed in two subjects who received the NY-ESO-1C259T cells following infusion. 
Therefore, subjects with prior or active demyelinating disease will be excluded from the 
study. Neurologic consultation is required for patients with Grade 2 or higher neurologic 
events of a ≥7 day duration. Additionally, any potential future recurrence of GBS will lead to 
a pause in study enrolment and stopping of treatment until further investigation.
Additional experience in clinical trials is required to confirm the incidence of these and other 
risks. The goal of the risk management measures is to maximize the chance of therapeutic 
benefit while mitigating and better understanding the risks of treatment with NY-ESO-1c259T 
cell therapy.
3.5.3
Overall Benefit: Risk Conclusion
Subjects with advanced or metastatic NSCLC who have progressed following other therapies, 
constitute a population with a high unmet medical need. Data from preclinical studies 
support the efficacy, specificity and safety of NY-ESO-1c259T cells. Clinical data from 
subjects summarized in the Investigator Brochure and the NCI study (Robbins, 2015,;
GSK3377794 IB 2019), demonstrate the safety and activity of NY-ESO-1c259T cells 
sufficiently to warrant clinical investigation in subjects with NSCLC.
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4
SELECTION OF STUDY POPULATION, WITHDRAWAL, 
COMPLETION AND STOPPING CRITERIA
4.1
Overview
Subjects will be assessed for eligibility for study participation prior to leukapheresis AND 
prior to lymphodepleting chemotherapy.
NOTE: Refer to Section 4.2.2 and Section 4.3 to understand the time restrictions (i.e., wash-
out period) required for therapies (anti-cancer treatments, radiotherapy, and corticosteroids) 
prior to leukapheresis and lymphodepleting chemotherapy, respectively, to ensure subject 
eligibility and proper timing of procedures.
Prior to leukapheresis and for qualification for the study, all subjects must meet all inclusion 
and exclusion criteria defined in Section 4.2.
4.2
Eligibility Criteria for Study Participation (Prior to Leukapheresis)
4.2.1
Inclusion Criteria
1. Subject has voluntarily agreed to participate by giving written informed consent in 
accordance with ICH GCP Guidelines and applicable local regulations.
2. 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.
3. Subject is ≥18 years of age on the day of signing informedconsent.
4. Subject has a diagnosis of histologically or cytologically confirmed advanced non-small 
cell lung cancer (Stage IIIB or IV) or recurrentdisease.
5. Subjects with known EGFR mutations or ALK or ROS1 gene rearrangements must have 
failed (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.
6. Subject has measurable disease according RECIST v1.1 criteria (Eisenhauer,2009).
7. Subject is HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.
8. 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-1aexpression.
9. Subject has Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
(Oken, 1982).
10. Subject has and anticipated life expectancy >3 months.
11. Subject has left ventricular ejection fraction ≥50%.
12. Subject is fit for leukapheresis and has adequate venous access for the cell collection.
13. 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.
a.
Male Participants:
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Male participants 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.
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 below
o
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 currentlypregnant
o
Agree to use male condom when engaging in any activity that allows for 
passage of ejaculate to another person
b. Female Participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditionsapplies:
14. Is not a woman of childbearing potential (WOCBP) as defined in Section 6.3 OR
o
Is a WOCBP (as defined in Section 6.3) who will agree to use a barrier
method (male condom) and use a contraceptive method that is highly 
effective (with a failure rate of <1% per year), as described in Section 6.3
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.
o
A WOCBP must have a negative highly sensitive pregnancy test (urine or
serum as required by local regulations) within 24 hours before the first 
dose of study intervention.
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be 
excluded from participation if the serum pregnancy result ispositive.
The Investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy
15. Subject must have adequate organ function as indicated by the following laboratory 
values in Table 1:
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Table 1
Laboratory Values to Define Adequate Organ Function
System
Laboratory Value
Hematological
Absolute Neutrophil count (ANC)
≥1.0 x 109/L (without G-CSF support)
Platelets
≥75 x 109/L
Hemoglobin
>80 g/L (without transfusion support within 7 
days from start of leukapheresis)
Coagulation
Prothrombin Time or International 
Normalized Ratio
≤1.5 x upper limit of normal (ULN) unless 
receiving therapeutic anticoagulation.
Partial Thromboplastin Time
≤1.5 x ULN unless receiving therapeutic 
anticoagulation.
Renal
Calculated or measured creatinine 
clearance 1
≥40 mL/min
Hepatic
Serum total bilirubin
≤1.5 x ULN (unless subject had documented 
Gilbert’s Syndrome)
Alanine aminotransferase (ALT)/Serum 
Glutamic Pyruvic Transaminase
≤2.5x ULN
1. In subjects <65 years of age creatinine clearance will be calculated using the Cockcroft-Gault Method:
(140 − age) × weight kg
Creatinine clearance = 72 × serum creatinine mg/dL (× 0.85 in females)
Subjects ≥65 years of age must have renal function measured either by 24-hour urine creatinine collection or by 
nuclear medicine ethylenediamineteraacetic acid (EDTA) glomerular filtration rate (GFR) measurement, 
according to standard practice at the treating Institution.
4.2.2
Exclusion Criteria
A subject meeting any of the following criteria are not eligible for participation in the study:
1. 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).
NOTE: Stable chronic liver disease should generally be defined by the
absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia,
oesophagealorgastric varices, persistent jaundice or cirrhosis.
2. Subject has received:

Cytotoxic chemotherapy within 2 weeks prior toleukapheresis;
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
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;
NOTE: recent or current use of inhaled or topical steroids is not exclusionary.

Tyrosine kinase inhibitor (e.g. erlotinib, gefitinib) and any other anti-cancer
treatment within 1 week prior to leukapheresis;

Investigational treatment within 4 weeks prior toleukapheresis;

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.
3. Subject has toxicity from previous anti-cancer therapy that has not recovered to
Grade ≤1 prior to enrolment (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. 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 Study Physician.
4. Subject has a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to cyclophosphamide, fludarabine, or other
agents used in the study.
5. 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 4weeks

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
6. 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
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radiation) and show no evidence of local recurrence or progression over the past
3 months prior to Screening are eligible.
7. Subject has 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.
8. Subject has unintended weight loss >10% in 6 months preceding study entry.
9. QTc > 450 msec or QTc > 480 msec for patients with Bundle Branch
Block (BBB). NOTES:

The QTc is the QT interval corrected for heart rate according to Bazett’s
formula (QTcB), Fridericia’s formula (QTcF), and/or another method, 
machine-read or manually over-read.

The specific formula that will be used to determine eligibility and
discontinuation for an individual subject should be determined prior to 
initiation of the study. In other words, several different formulae cannot
be used to calculate the QTc for an individual subject and then the 
lowest QTc value used to include or discontinue the subject from the
trial.

For purposes of data analysis, QTcB, QTcF, another QT correction
formula, or a composite of available values of QTc will be used as
specified in the Reporting and Analysis Plan (RAP).
10. Subject has uncontrolled intercurrent illness including, but not limitedto:

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;

Inadequate pulmonary function with mechanical parameters <40% predicted 
(forced expiratory volume in 1 second [FEV1], forced vital capcity [FVC],
transfer factor of the lung for carbon monoxide [TLC], diffusing capacity of
the lungs 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);

Prior or active demyelinating disease.
11. Subjects who in the opinion of the Investigator will be unlikely to fully
comply with protocol requirements.
12. Subject has active infection with human immonodeficicency virus (HIV),
hepatitis B virus (HBV), hepatitis C virus (HCV), or human lymphotropic 
virus (HTLV) as minimally defined below:
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
Positive serology for HIV;

Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result 
at screening or within 3 months prior to first dose of study treatment. For potent 
immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) 
should also be excluded.


Active hepatitis C infection as determined by hepatitis CRNA;

A subject who is HCV antibody positive will be screened for HCV RNA by any RT 
polymerase chain reaction (PCR) or bDNA assay. If HCV antibody is positive, 
eligibility will be determined based on a negative screening RNA value.

Positive serology for HTLV 1 or 2.
13. Subject is pregnant or breastfeeding.
4.3
Additional Eligibility Criteria (Prior to Lymphodepleting Chemotherapy)
Prior to lymphodepleting chemotherapy, all subjects must meet all the inclusion and 
exclusion in Section 4.2 and the following inclusioncriterion:
1. Subject has disease progression.
2. Subject has failed at least one prior platinum-containing regimen. Subject may have 
received PD-1 or PDL-1 inhibitors. There is no limit to lines of prior anti-cancer therapy.
Furthermore and prior to lymphodepleting chemotherapy, a subject meeting the following 
criteria is not eligible for participation in thestudy:
1. Subject has received:

Cytotoxic chemotherapy within 3 weeks prior to lymphodepletingchemotherapy;

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;
NOTE: A brief course of oral corticosteroids limited to less than 7 days is not 
exclusionary if completed 2 weeks prior to lymphodepleting chemotherapy; a recent or 
current use of inhaled or topical steroids is notexclusionary.

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 
lymphodepletingchemotherapy; however, electronbeamradiotherapytosuperficial 
structures in the chest is permitted.
NOTE: there is no washout period for palliative radiation to non-target organs other than
the lung and mediastinum. If radiation was to an intended target lesion within 3 months 
of baseline imaging studies, and the lesion is progressing within this time frame it may be 
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considered as a target lesion after review and discussion with the Sponsor.
4.4
Additional Eligibility Criteria (Prior to Second T-Cell Infusion)
Prior to receipt of a second T-cell infusion, all subjects must remain eligible to receive 
manufactured T-cell product as defined in Section 4.2 and Section 4.3 and meet the following 
inclusion criteria:
1. Subject has had a documented confirmed response [partial response (PR) or complete 
response (CR)] or stable disease >4 months followed by confirmed PD after the first T-
cell infusion.
2. A second T-cell infusion is recommended by theInvestigator.
3. Subject has a new tumor biopsy confirming NY-ESO-1 and/or LAGE-1a expression.
4. Subject has voluntarily agreed to receive a second T-cell infusion by giving written 
informed consent.
5. Subject has toxicity from first T-cell infusion that resolved to Grade ≤1.
6. Manufactured T-cell product must be available.

In cases where previously manufactured T-cell product is not available, any residual 
leukapheresis product from collections prior to receipt of the gene modified T cells will 
be utilized for a new product manufacture.

In cases where residual leukapheresed product is not available, subjects can agree to be 
re-leukapheresed for cells only in circumstances where there are no detectable gene 
modified cells.
Furthermore and prior to receipt of a second T-cell infusion, a subject meeting the following 
criterion is not eligible for a second T-cell infusion:
1. Subject with any Grade 4 CRS or clinically life-threatening (Grade 4) AEs deemed at 
least possibly related to the NY-ESO-1c259T cell product by the Investigator and study 
Sponsor reported during the first T-cell infusion.
NOTE: any subject meeting this exclusion criterion might be eligible to receive a 
second T-cell infusion after evaluation of all available subject data by the Sponsor and 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) and their 
subsequent approval.
4.5
Completion of the Interventional Phases
A subject will be considered completing the Interventional Phase 1 of the study when he/she 
has PD or has died prior to PD, or 2 years after the NY-ESO-1c259T cell infusion, whichever 
is shorter. A subject will be considered completing the Interventional Phase 2 of the study 
when he/she has PD, or has died prior to PD, or 6 months after the NY-ESO-1c259T cell 
infusion, whichever is shorter. All subjects completing the Interventional Phase of the study 
will enter the LTFU study for observation of delayed AEs during the 15 years post-infusion 
in accordance with FDA and EMA regulations (FDA, 2006a; EMEA, 2009). If LTFU 
protocol is not available when a subject completes the Interventional Phase, subject can be
followed under this protocol until LTFU protocol becomes available. This study 
(GSK208749 [ADP-0011-004]) will be considered complete when the last subject has rolled 
over into the LTFU protocol.
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4.6
Subject Withdrawal
A subject may withdraw from the study at any time for any reason without prejudice to their 
future medical care by the physician or Institution. However, the Investigator must make 
every reasonable effort to keep each subject on study for the whole duration of the trial. In 
cases where the subject is deemed ‘lost to follow-up’, the Investigator or designee must make 
every effort to regain contact with the subject; e.g., where possible, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods. These contact attempts should be documented in the subject’s medical records.
Should the subject continue to be unreachable, only then will he/she be considered to have 
withdrawn from the study with the primary reason as ‘Lost to Follow-up’.
If a participating subject withdraws consent, all final end of study assessments should be 
performed, if possible on the day the decision is made to take the subject off-study or as soon 
as possible thereafter. All the results of the evaluations and observations, together with a 
description of the reasons for study withdrawal, must be recorded in the medical records and 
eCRF. The following are some of the justifiable reasons for the Investigator to withdraw a 
subject from study:

Withdrawal of consent.

Did not receive any NY-ESO-1c259T cell (Refer to Section 9.1 and Section 9.2 for 
continued monitoring of AEs/SAEs following studyprocedures).
If a subject who has consented to participate in pharmacogenetics research withdraws from 
the clinical study for any reason other than lost to follow-up, the subject will be given the 
following options concerning the pharmacogenetics sample, if already collected:

Pharmacogenetics research continues as per the subject’s consent;or,

Any remaining sample is destroyed
If a subject withdraws consent from the pharmacogenetics research or requests sample 
destruction, the Investigator must complete the appropriate documentation to request sample 
destruction within the timeframe specified by GSK and maintain the documentation in the 
site study records. In either case, GSK will only keep study information collected/generated 
up and until that point.
If the subject voluntarily discontinues from treatment due to toxicity, ‘AE’ will be recorded 
as the primary reason for permanently discontinuation on the eCRF.
All subjects who discontinue from study treatment will have safety assessments at the time of 
discontinuation and during post-study treatment follow-up as specified in Schedule of 
Assessments Table (see Section 7).
4.7
Consideration for Temporary Suspension of Enrollment
Throughout the conduct of the study, all safety data will be closely monitored for each 
subject on an ongoing basis. Based on the severity of the AEs, the degree of T cell 
expansion, indicators of potential anti-tumor activity, and other factors, a recommendation
whether to suspend treatment, or continue enrollment will be made with input from the
Safety Review Team (SRT), Sponsor and Investigators. Final decisions to halt or modify 
the study will be made by the Sponsor.
Study will pause enrolment and stop treatment for all participants if any of the following 
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events occur pending submission to Regulatory Agencies and review by IRBs/ECs, and 
the Sponsor:

Any event of Guillain-Barre syndrome (GBS) as diagnosed by a neurologist according 
to diagnostic guidance for GBS [Fokke, 2014] (refer to Section 10.4).

A case of documented symptomatic progressive cerebral edema confirmed by an 
expert neurological examination and CT/MRI, that is not responding to treatment.

Any death occurs that is deemed to be at least possibly related to the NY-ESO-1c259T cell 
product by the Investigator and the Sponsor; or

Two or more Grade 4 autoimmune events deemed probably or definitely related to the 
NY-ESO-1c259T cell product by the Investigator and the Sponsor; or

A biologically functional positive Replication Competent Lentivirus (RCL) after 2 
confirmed positive tests by PCR
Following assessment by the Sponsor, enrollment and dosing may resume if agreed upon by 
the Sponsor, and Regulatory Authorities.
4.8
Liver Safety: Required Actions and Follow-up Assessments
Level 1 Monitoring
In the event that the subject develops elevations in liver function test (LFT) parameters as 
defined below, an increase to liver chemistry monitoring i.e. at weekly intervals, will apply.
Liver Chemistry Monitoring Criteria Level 1
Criteria
Actions
ALT ≥3x ULN but ALT <5x ULN and 
bilirubin <2xULN, without symptoms 
believed to be related to liver injury, 
or hypersensitivity

Notify the GSK medical monitor within 24 hours 
of learning of the abnormality to discuss 
participant safety.

Participant must return weekly for repeat liver 
chemistries (ALT, aspartate aminotransferase 
[AST],alkalinephosphatase,bilirubin) untilthey 
resolve, stabilise or return to within baseline

If, during monitoring, ALT increases to 5xULN , 
or remains ≥3x ULN for ≥4 weeks, or if total 
bilirubin increases to ≥2xULN, refer to Level 2 
monitoring guidance below.

If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice 
monthly until liver chemistries normalize or return 
to within baseline.
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Level 2 Monitoring
In the event that the subject develops elevations in LFT parameters as defined below, an 
increase to liver chemistry monitoring at more frequent intervals i.e. twice weekly, will 
apply.
Liver Chemistry Monitoring Criteria Level 2
ALT absolute
ALT 5xULN
ALT Increase
ALT 3xULN that persists for 4 weeks
Bilirubin1, 2
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)
International 
normalized 
ratio (INR)2
ALT 3xULN and INR>1.5
Symptomatic3
ALT 3xULN and associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity
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Required Actions and Follow up Assessments
Actions
Follow-Up Assessments

Report the event to GSK within 24 hours

Complete the CRF and complete an SAE data 
collection tool if the event also meets the 
criteria for an SAE2

Perform liver event follow-upassessments

Monitor the participant until liver chemistries 
resolve, stabilize, or return to within baseline 
(pre-Gene Therapy) (see MONITORING 
below)
MONITORING:
For bilirubin or INR criteria:

Repeatliver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin, INR) and 
perform liver event follow-up assessments 
within 24 hrs

Monitorparticipantstwice-weeklyuntilliver 
chemistries resolve, stabilize or return to 
within baseline (pre-Gene Therapy)

A specialist or hepatology consultation is 
recommended
For All other criteria:

Repeatliver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin, INR) and 
perform liver event follow-up assessments 
within 24-72 hrs

Monitor participants at least weekly until liver 
chemistries resolve, stabilize or return to 
within baseline (pre-Gene Therapy)

Viral hepatitis serology4

Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminasesvaluesshowdownward 
trend

Serumcreatinephosphokinaseandlactate 
dehydrogenase

Fractionate bilirubin, if total bilirubin2xULN

If possible, obtain peripheral blood for 
persistenceofgenetically modifiedcells

Obtaincomplete blood count with 
differentialtoassesseosinophilia

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications on 
the concomitant medications report form 
includingacetaminophen,herbalremedies, 
other over the countermedications

Record alcohol use on the liver event 
alcohol intake case reportform
For bilirubin or INR criteria:

Anti-nuclearantibody,anti-smoothmuscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG) or gamma 
globulins.

Liver imaging (ultrasound, magnetic 
resonance,orcomputerisedtomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy CRF forms
1.
Serum bilirubin fractionation should be performed if testing is available. Additionally, if serum bilirubin fractionation 
testing is unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin 
elevations and suggesting liver injury.
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2.
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, which may 
indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving anticoagulants.
3.
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia).
4.
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen (HbsAg) and Hepatitis B Core Antibody (IgM); Hepatitis
C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Hepatitis E IgM antibody.
5
STUDY TREATMENTS
5.1
Leukapheresis
Subjects who complete screening procedures and who meet all eligibility criteria defined in 
Section 4.2 will be eligible to undergo leukapheresis to obtain starting material for the 
manufacture of autologous NY-ESO-1c259T. Prior to leukapheresis, an absolute lymphocyte 
count of ≥0.5 x 109/L and the CD3 count ≥200/μL is recommended.
For collection of starting material, a large-volume non-mobilized peripheral blood 
mononuclear cell (PBMC) collection should be performed according to institutional standard 
procedures. 2-3 blood-volumes should be processed with a goal of collecting 1.0 x 108 
PBMC/kg body weight, and a minimum of 1.5 x 107PBMC/kg. In cases where the minimum 
number of PBMC is not collected or the T cells are not able to be infused back to the subject, 
a second leukapheresis may be performed. Citrate anticoagulant should be used. Prophylaxis 
and treatment (e.g. CaCl2 or MgSO4) for adverse effects of the citrate anticoagulant may be 
used at the discretion of the Investigator. The collected leukapheresis product will then be 
transported for manufacture as detailed in the Study Procedures Manual (SPM).
Once NY-ESO-1c259T cell product has been manufactured and received at the site, eligible 
subjects will proceed to have lymphodepleting chemotherapy and infusion of IP as detailed in 
Section 5.2 and Section 5.3, respectively.
5.2
Lymphodepleting Chemotherapy
Prior to the administration of lymphodepleting chemotherapy, all eligibility criteria will be 
reconfirmed and baseline tumor assessment obtained.
When the NY-ESO-1c259T cells have completed manufacture, have fulfilled release criteria, 
and are available for infusion at the site, fludarabine and cyclophosphamide will be 
administered as lymphodepleting chemotherapy as described in Table 2 to all subjects.  For 
subjects with documented history of severe and prolonged cytopenia (anemia, 
thrombocytopenia, or leukopenia), the investigator should discuss with the sponsor’s 
medical monitor or designee to determine the need for dose modification of the 
lymphodepletion regimen.
Cyclophosphamide and fludarabine will be supplied by the pharmacy of the participating 
Institution.
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Table 2:
LymphodepletingChemotherapyTreatmentRegimenfor GSK208749 (ADP-0011-004)
Lymphodepleting chemotherapy
Recommended prophylaxis 
and supportive medication
Day
Drug
Dose
Route
Administration1
Infection: on admission for 
lymphodepleting 
chemotherapy, commence 
anti-microbial and anti-fungal 
prophylaxis as recommended 
in Section 8.2 or in line with 
institutional standard practice.
Hydration: ensure adequate 
hydration and antiemetic 
provision prior to commencing 
cyclophosphamide infusions
Mesna: may be given to 
prevent urotoxicity per 
institutional guidelines or as 
recommended in Section 5.2.2.
G-CSF: recommend starting 
24 hours after the last 
cyclophosphamide infusion 
until resolution of neutropenia 
in accordance with ASCO 
guidelines (Smith , 2015) or 
institutional practice (refer to 
Section 8.8.1)5.
-8
Fludarabine2, 3
30 mg/m2
IV
in 50 – 100 ml 0.9% NaCl over 30 mins4
-7
Fludarabine2, 3
30 mg/m2
IV
in 50 – 100 ml 0.9% NaCl over 30 mins4
Cyclophosphamide3 900 mg/m2
IV
in 100 – 250 ml 0.9% NaCl over 1 hour
-6
Fludarabine2, 3
30 mg/m2
IV
in 50 – 100 ml 0.9% NaCl over 30 mins4
Cyclophosphamide3 900 mg/m2
IV
in 100 – 250 ml 0.9% NaCl over 1 hour
-5
Fludarabine2, 3
30 mg/m2
IV
in 50 – 100 ml 0.9% NaCl over 30 mins4
Cyclophosphamide3 900 mg/m2
IV
in 100 – 250 ml 0.9% NaCl over 1 hour
-4
start G-CSF6
-3
-2
-1
1
NY-ESO-1c259T cell infusion5
Abbreviations: ASCO = American Society of Clinical Oncology; IV = intravenous; NaCl = sodium chloride; G-CSF = granulocyte-colony stimulating factor
1
Or per institutional guidelines
2
Fludarabine dose will be adjusted in renal impairment as described in Section 5.2.1.
3
For subjects ≥ 60 years of age or for participants with documented history of severe and prolonged cytopenia, see Section 5.2.1..
4
Concentration ≤1mg/mL
5
Administration of NY-ESO-1c259T infusion is described in Section 5.3
6
Long-acting (pegylated) G-CSF may be given instead of short acting G-CSF according to institutional standard practice. If pegylated G-CSF is 
administered, give one dose 24 hours after the last chemotherapyadministered
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5.2.1
Lymphodepletion Dose Modification
For participants ≥ 60 years old, the recommended lymphodepleting regimen will be as follows:

Fludarabine at 30mg/m2 for 3 days (Day -7 to Day -5)

Cyclophosphamide at 600mg/m2 (Day -7 to Day -5)  
In case of participants with documented history of severe and prolonged cytopenia (anemia, 
thrombocytopenia, or leukopenia), the investigator should discuss with the sponsor’s medical monitor or 
designee the opportunity for potential lymphodepletion dose adjustment.
5.2.2
Fludarabine dose adjustment for renal impairment
Dose of fludarabine will be adjusted for subjects with renal dysfunction as described in 
Table 3:
Table 3:
Fludarabine Dose Adjustment
Creatinine clearance
Fludarabine dose
>80 mL/min
30 mg/m2
40 – 79 mL/min
20 mg/m2
5.2.3
Mesna
Mesna should be administered per institutional guidelines or as recommended below:

20% of cyclophosphamide dose (120 mg/m2) x 4 doses at times 0 (start of 
cyclophosphamide infusion) and then 3 hours, 6 hours and 9 hours after the start of 
each cyclophosphamide infusion.
5.3
T Cell Infusion
The autologous T cells transduced with lentivirus encoding enhanced TCR specific for 
cancer-testis antigen NY-ESO-1 is the investigational product in this study.
Subjects will receive a single dose of NY-ESO-1c259T five days after completing the
lymphodepleting chemotherapy. This is considered Day 1 and all procedures and 
assessments to be performed are listed in the Schedule of Procedures (Table 4).
5.3.1
Premedication
Thirty to sixty (30-60) minutes prior to cell infusion, subjects will be premedicated against 
potentialinfusionreactions withantihistaminesand acetaminophen(paracetamol)according 
to institutional practice. Steroids should not be administered as premedication for T cell 
infusion because they are lymphotoxic and inhibitory to the T-cell product.
5.3.2
T Cell Infusion
On Day 1, the subject will receive thawed NY-ESO-1c259T by intravenous infusion. Prior to 
infusion, two clinical personnel in the presence of the subject, will independently verify and 
confirm that the information on the infusion bag is correctly matched to the subject, as per the 
participating center’s blood bank procedures.
NY-ESO-1c259T must not be thawed until immediately prior to infusion. The cells can be 
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thawed either in a water bath at the subject’s bedside or in a centralized facility, according to 
institutional standard procedures. The cells must be infused without delay, and if thawed 
centrally, must be transported to the subject by appropriately trained clinical staff, to preserve 
the chain of custody. The cell product must not be washed or otherwise processed. It is 
expected that the infusion will commence within approximately 10 minutes of thawing and 
complete within 45 minutes of thawing to minimize exposure of the cell product to 
cryoprotectant. If the cells are provided in multiple bags, the second bag must not be thawed 
until half the first has been infused withoutreaction.
If after thawing the inner infusion bag is damaged or leaking, the Investigator and Sponsor 
should be notified and the cells should not beinfused.
NY-ESO-1c259T will be administered using a dual spike infusion set by gravity over 15-30 
minutes in the absence of reaction. It is recommended that the cells are infused without a 
filter, however if a filter is required by institutional practice the pore size must not be smaller 
than 170 µm. Infusion pumps must not be used. For administration of the cells, 100 - 250 ml 
of 0.9% sodium chloride should be connected to the second lumen of the infusion set, used to 
prime the line, and then the lumen closed. On completion of the infusion of a bag of NY-
ESO-1c259T, the main line should be closed and approximately 50 ml saline transferred into 
the cell bag, and then infused to minimize the loss of cells. This process should be repeated 
for each cell bag if multiple bags are provided. On completion of the cell infusion the set 
should be flushed using additional saline from the attachedbag.
In the event of adverse reaction to the cell infusion the infusion rate should be reduced and 
the reaction managed according to institutional standard procedures (refer to Section 8.1). 
Steroid treatment should be avoided unless medically required. In the event a subject 
develops a febrile episode following the infusion, appropriate cultures and medical 
management should be initiated, with attention to the initiation of empirical antibiotic 
treatment in the case of febrile neutropenia.
The day of T cell infusion may be delayed in subjects with significant complications of 
chemotherapy if according to the Investigator it is in the best interest of the subject. The 
timing of all assessments post-infusion will be calculated with reference to the T-cell infusion 
date. Subjects who have undergone leukapheresis but do not receive the T-cell infusion will 
be replaced. Cytopenias alone should not be a reason to delay T-cell infusion unless 
complications are present.
Vital signs will be recorded prior to the infusion, and at 5, 15, and 30 minutes, 1, 1.5, 2 and 4 
hours after the infusion has started.
5.4
Second T Cell Infusions (Interventional Phase 2)
Following the initial infusion, subjects, who have a confirmed response (or have stable 
disease for >4 months) and subsequently have documented PD and whose tumors continue to 
express NY-ESO-1 and/or LAGE-1a as verified by assay performed in biopsied tissue, can be 
considered for a second infusion with engineered T cells. Subjects must continue to meet all 
eligibility criteria for the study in addition to those specified in Section 4.4 prior to receiving 
a second infusion.
The second infusion may be given within 6 months of PD and after at least 12 weeks have 
elapsed from the time of previous infusion. During the period in which the subject is being 
considered for a second infusion, new or changes in AEs as defined in Section 9 must be 
recorded in the electronic data capture (EDC) system and blood for persistence (for safety) 
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and RCL monitoring must be collected at the time points noted in the Schedule of Procedures 
Table 4. However, no other clinical assessments or procedures are required until the subject 
is consented for the Interventional Phase 2.
Some subjects may need to have another leukapheresis. Prior to screening subjects for the 
Interventional Phase 2 (second T cell infusion), it should be determined if the subject has 
either 1) previously manufactured T cell product available or 2) any residual leukapheresis
product that can be utilized for a new T cell product manufacture. In cases where T cell 
product or leukapheresed product is not available, the subject can agree to undergo another 
leukapheresis for cells only in circumstances where there are no detectable gene modified 
cells. Table 15 provides the Schedule of Procedures for those subjects who will not require 
another leukapheresis collection of cells. For subjects who do require another leukapheresis, 
please follow the clinical procedures and assessments noted in the Screening phase, 
Leukapheresis, and Baseline visits as outlined in Table 4 with the exception of the following 
procedures, which are not required:

Demographics

Tobacco use

Blood sample for Pharmacogenetic analysis

Tumor biopsy at Baseline
NOTE: If a fresh biopsy was taken to confirm continued expression of NY-ESO-1 
and/or LAGE-1a at time of PD after the first T cell infusion and there is sufficient 
tumor sample left remaining, this sample may be used as the baseline sample for the 
Interventional Phase 2. This sample may also be used to assess tumor histology.  
Otherwise, the baseline biopsy may be collected anytime between two weeks prior 
to the start of lymphodepleting chemotherapy, with preference closer to the time of
infusion.
These subjects will then continue to follow the clinical assessment and procedures outlined in 
Table 15 from the Lymphodepleting Chemotherapy visitonward.
Subjects that qualify for a second infusion will receive the same lymphodepleting 
chemotherapy regimen and T cell infusion as received during the first T cell infusion.
6
CONCOMITANT MEDICATION AND TREATMENT
6.1
Prohibited Concomitant Medication and Treatment
The following treatments are prohibited during the Interventional Phase of the study: non-
protocol chemotherapy, immune therapy, biological therapy (including targeted therapies 
with tyrosine kinase inhibitors or monoclonal antibodies), or investigational anti-cancer 
therapy. Subjects should also not undergo other anticancer locoregional therapies, such as 
surgical resection or non-palliative radiation. Subjects should not require these therapies 
before confirmation of PD, and if used, will be considered as having met the PD criterion for 
efficacy and will rolled over to the LTFU Protocol and will not be eligible for a second T cell 
infusion.
Refer to Section 4.2.2 and Section 4.3 for details of washout and excluded treatments prior to 
leukapheresis and lymphodepleting chemotherapy, respectively.
The use of systemic steroids may abrogate the effects of the T cell therapy and therefore; use 
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is discouraged unless required to manage CRS (refer to Section 8.5 for CRS management) or 
other significant immune-mediated AEs. According to local standard of care or American 
Society of Clinical Oncology (ASCO) guidelines (Basch, 2010), steroids may be used as anti-
emetics before cyclophosphamide but must be discontinued no later than 3 days prior to 
infusion of the IP. Topical steroids for cutaneous application and inhaled steroidal treatments 
are permitted.
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6.2
Permitted Concomitant Medication and Treatment
Lesion sites previously requiring radiotherapy should be recorded prior to lymphodepleting 
chemotherapy. Palliative radiation for pain relief to non-measurable lesions or non-target 
lesions present at Baseline, in organs other than the chest, is permitted during the study.
However, lesion sites requiring radiotherapy after the T cell infusion should be evaluated as 
to whether that indicates disease progression.
Other treatment that the Investigator considers necessary for a subject’s welfare may be 
administered during the Interventional Phase of the study at the discretion of the Investigator 
in keeping with community standards of medical care and in adherence to the protocol.
Before immunizing a subject at high risk for vaccine-preventable disease (or member of the 
subject’s household), consult an Infectious Disease specialist or a guidance such as the CDC 
Clinical Practice Guideline for Vaccination of the Immunocompromised Host.
Allconcomitant medications includingall prescription, over-the-counter medications, and 
herbal remedies, will be recorded, including dose and frequency. The following will be 
recorded on the appropriate eCRF pages:

All prescription and nonprescription medication, vitamins, herbal and nutritional 
supplements taken by the subject during the 30 days prior to Screening will be recorded at 
the Screening Phase visit.

All prior anti-cancer treatments taken by the subject must be recorded regardless of time

All concomitant medications taken by the subject while in the Interventional Phase.

Use of any mutagenic agents or investigational agents must bereported
Any changes to concomitant medication regimens should be recorded throughout the study in 
the eCRF.
6.3
Contraception
NY-ESO-1c259T may have adverse effects on a fetus in utero. Furthermore, it is not known if 
NY-ESO-1c259T has transient adverse effects on the composition of sperm.
Definitions:
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP
1. Premenarchal
2.
Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy
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
Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (e.g., mullerian agenesis, androgen insensitivity), Investigator discretion 
should be applied to determining study entry.
Note: Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview.
3.
Postmenopausal female

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.

A high follicle stimulating hormone (FSH) level in the postmenopausal range 
(as per laboratory parameters for postmenopausal range) may be used to 
confirm a postmenopausal state in women not using hormonal contraception 
or hormonal replacement therapy (HRT) when postmenopausal status is in 
doubt. However, in the absence of 12 months of amenorrhea, confirmation 
with more than one FSH measurement is required.
Females on HRT and whose menopausal status is in doubt will be required to use one of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment.
Contraception:
Male Participants:
Male participants must 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.

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 below:
o
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 currentlypregnant.
Agree to use male condom when engaging in any activity that allows for passage of ejaculate 
to another person.
Female participants:
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WOCBP must 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.
For contraception, subjects who are WOCBP must use a barrier method (male condom) and 
should comply with one of the following:
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
Highly Effective MethodsbThat Have Low User Dependency Failure rate of <1% per year when 
used consistently and correctly.
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc
Intrauterine device (IUD)
Intrauterine hormone-releasing system (IUS)c
Bilateral tubal occlusion
Vasectomized partner
Note: Vasectomized partner is a highly effective contraceptive method provided that the partner 
is the sole sexual partner of the woman of childbearing potential and the absence of sperm 
has been confirmed. If not, an additional highly effective method of contraception should be 
used. Spermatogenesis cycle is approximately 90days.
Highly Effective Methods b That Are User Dependent Failure rate of <1% per year when used
consistently and correctly.
Combined(estrogen-andprogestogen-containing)hormonalcontraceptionassociatedwithinhibition 
of ovulationc
oral 
intravaginal 
transdermal
injectable
Progestogen-only hormone contraception associated with inhibition of ovulationc
oral 
injectable
Sexual abstinence
Note: Sexual abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the study 
intervention. The reliability of sexual abstinence needs to be evaluated in relation to the
duration of the study and the preferred and usual lifestyle of the participant.
a.
Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies.

Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those when 
used consistently and correctly.

Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with Clinical 
Trial Facilitation Group guidelines, acceptable contraceptive methods are limited to those which inhibit ovulation as 
the primary mode of action.
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7
SCHEDULE OF ASSESSMENTS AND PROCEDURES
The Schedule of Procedures is provided in Table 4 for Screening and the Interventional Phase 
1 of the study. On completion of the Interventional Phase, subjects transition to the LTFU 
Protocol.
Subjects will have been assigned a unique subject identification number upon signing the ICF 
for the Screening Protocol, ADP-0000-001. The number assigned will serve as the same 
subject ID upon qualification and enrollment into the Interventional Phase 1 of this study.
NOTE: A subject will have the same Subject ID in the Screening Protocol (ADP-0000-001), 
in this study (GSK208749 [ADP-0011-004]), and in the LTFU Protocol (GSK208750 [ADP-
0000-002]). Refer to the SPM for further details on assignment of Subject ID.
Study procedures performed as part of standard of care (laboratory assessments, radiologic 
imaging, including cardiac assessment) prior to signing informed consent can be used for 
screening if they were performed within the time period prior to leukapheresis as noted in 
Table 4.
7.1
HLA and Antigen Screening
Subjects identified by the Investigator as possible candidates for the trial must have 
completed screening under Screening Protocol, ADP-0000-001, to confirm that the subject is 
HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive and with NY-ESO-1 positive 
tumor prior to conducting the screening procedures in thisstudy.
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Male condom and 
female condom should not be used together (due to risk of failure with friction).
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7.2
Schedule of Procedures
Table 4
Schedule of Procedures (Interventional Phase 1)
Screen-
ing 
Phase1
Interventional Phase 1
Compl 
etion/ 
Withd 
rawal5
Leuka-
pheresis
Base-
line
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
- 28 D4
of   
Leuka-
pheresis
D -14
to -9
D
-8
D
-7
D
-6
D
-5
D1
D 
2
D 
3
D 
4
D 
5
D 
8
W 
2
W 
3
W 
4
W 
5
W 
6
W8
W 
10
W 
1
2
W 
1
6
W 
20
W 
24
Every 3 
Mos 
Until 
Yr 2.
Every 6 
Mos 
Thereafter
Visit Window
n/a
n/a
n/a
n/a
n/ 
a
n/a
n/a
±1 day
±3 days
±7 days
±14
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
8
19
20
2
1
2
2
23
24
25-30
31+
Clinical Assessments and Procedures6 (refer to Section 7.4 for details)
Informed Consent7
XEDC
Demographics
XEDC
Inclusion/ 
Exclusion
8
XEDC
X9
Medical History10, 
and Tobacco Use
X
X
Physical Exam
X
X
X
X
X
X
X
X
Prior/Concomi-
tant Medications11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs / 
Height/ Weight12
X
X
X13
X
X
X
X
X
X
X
ECG
X
X
X
X
X
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Screen-
ing 
Phase1
Interventional Phase 1
Compl 
etion/ 
Withd 
rawal5
Leuka-
pheresis
Base-
line
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
- 28 D4
of   
Leuka-
pheresis
D -14
to -9
D
-8
D
-7
D
-6
D
-5
D1
D 
2
D 
3
D 
4
D 
5
D 
8
W 
2
W 
3
W 
4
W 
5
W 
6
W8
W 
10
W 
1
2
W 
1
6
W 
20
W 
24
Every 3 
Mos 
Until 
Yr 2.
Every 6 
Mos 
Thereafter
Visit Window
n/a
n/a
n/a
n/a
n/ 
a
n/a
n/a
±1 day
±3 days
±7 days
±14
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
8
19
20
2
1
2
2
23
24
25-30
31+
ECHO/MUGA
4
XEDC
CT / MRI14
X4
X
X
X
X
X
X
X
Brain MRI 28
X
X
See footnote 28
ICE29
See footnote 29
Chest X-ray
X
PFTs15
XEDC
Lymphocyte 
Subset 
(CD3/CD4/CD8)
XEDC
Hematology
4
XEDC
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation Tests
X4
X
Pregnancy Test16
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X4
X
Infectious disease
markers17
XEDC
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Screen-
ing 
Phase1
Interventional Phase 1
Compl 
etion/ 
Withd 
rawal5
Leuka-
pheresis
Base-
line
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
- 28 D4
of   
Leuka-
pheresis
D -14
to -9
D
-8
D
-7
D
-6
D
-5
D1
D 
2
D 
3
D 
4
D 
5
D 
8
W 
2
W 
3
W 
4
W 
5
W 
6
W8
W 
10
W 
1
2
W 
1
6
W 
20
W 
24
Every 3 
Mos 
Until 
Yr 2.
Every 6 
Mos 
Thereafter
Visit Window
n/a
n/a
n/a
n/a
n/ 
a
n/a
n/a
±1 day
±3 days
±7 days
±14
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
8
19
20
2
1
2
2
23
24
25-30
31+
CMV IgG and 
PCR18
X
X
X
X
X
X
TSH with free 
T419
X
CRP20
X
X
X
X
X
X
Uric acid
X
X
`
GFR or 24h 
urine21
X
X
Adverse Events22
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vector Copies 
(Persistence for 
Safety)23
X
X
X
X23
X23
VSV-G DNA 
(RCL)24
X
X
X
X24
X24
Leukapheresis, Lymphodepleting Chemotherapy & Investigational Product Administration
Leukapheresis
X
Fludarabine
X
X
X
X
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Screen-
ing 
Phase1
Interventional Phase 1
Compl 
etion/ 
Withd 
rawal5
Leuka-
pheresis
Base-
line
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
- 28 D4
of   
Leuka-
pheresis
D -14
to -9
D
-8
D
-7
D
-6
D
-5
D1
D 
2
D 
3
D 
4
D 
5
D 
8
W 
2
W 
3
W 
4
W 
5
W 
6
W8
W 
10
W 
1
2
W 
1
6
W 
20
W 
24
Every 3 
Mos 
Until 
Yr 2.
Every 6 
Mos 
Thereafter
Visit Window
n/a
n/a
n/a
n/a
n/ 
a
n/a
n/a
±1 day
±3 days
±7 days
±14
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
8
19
20
2
1
2
2
23
24
25-30
31+
Cyclophos-
phamide
X
X
X
NY-ESO-1c259T
X
Correlative Studies and Research Assessments (refer to Section 7.5 for details)
Pharmacogenetic 
analysis
X25
Tumor biopsy26
X26a
X
X
Liquid 
biopsy26b
X
X
X
Cell phenotype 
and Functional 
Assays,
X
X
X
X
X
X
X
X
X
Cytokine 
Analyses20
& Humoral Anti-
Infused Cell 
Responses
X
X27
X
X
X
X
X
X
X
X
X2
7
X
X
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Screen-
ing 
Phase1
Interventional Phase 1
Compl 
etion/ 
Withd 
rawal5
Leuka-
pheresis
Base-
line
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
- 28 D4
of   
Leuka-
pheresis
D -14
to -9
D
-8
D
-7
D
-6
D
-5
D1
D 
2
D 
3
D 
4
D 
5
D 
8
W 
2
W 
3
W 
4
W 
5
W 
6
W8
W 
10
W 
1
2
W 
1
6
W 
20
W 
24
Every 3 
Mos 
Until 
Yr 2.
Every 6 
Mos 
Thereafter
Visit Window
n/a
n/a
n/a
n/a
n/ 
a
n/a
n/a
±1 day
±3 days
±7 days
±14
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
8
19
20
2
1
2
2
23
24
25-30
31+
Vector Copies 
(Persistence) for 
Research
X
X
X
X
X
X
X
X
X
X
Abbreviations:ICE = Immune Effector Cell-Associated Encephalopathy; CMV = cytomegalovirus; CRP = C-reactive protein; CRS = cytokine release syndrome; CT = computerized tomography;
ECG = electrocardiogra ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EDC = electronic data capture; FPCP = female patient of childbearing potential; GFR = glomerular filtration 
rate; MRI = magne resonance imaging; MUGA = multigated acquisition; n/a=not applicable; PCR = polymerase chain reaction; PFT = pulmonary function test; RCL = replication competent lentivirus; TSH 
= thyroid-stimulati hormone; VSV-G =vesicular stomatitis virus G protein
1. Subjects must have completed screening under Screening Protocol, ADP-0000-001, and confirmed as HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive and have NY-ESO-1 and/or LAGE-
positive tumor prior to conducting the procedures in this visit. All clinical assessments and procedures in this visit must be performed as indicated and recorded in source documents; however, only
thos assessments/procedures indicated with bold XEDC will be recorded in the EDC at thisvisit.
2. Refer to Section 5.2 for details on prophylaxis therapies, pre-medications, fludarabine dose adjustments according to renal function, and supportive treatments.
3. All samples will be collected and assessments performed prior to T-cell infusion, unless otherwise specified.
4. All clinical assessments required at the Screening visit must be performed within 28 days of leukapheresis, with the exception of lymphocyte subset (CD3/CD4/CD8), hematology, chemistry, 
coagulatio and urinalysis which must be done within 7 days of leukapheresis. ECHO/MUGA, MRI/CT scan and laboratory assessments performed as standard of care prior to study consent will be 
acceptable as long as assessment is done within required time period before leukapheresis.
5. If a subject withdraws consent or completes the Interventional Phase 1, all procedures and assessments listed at this visit must be performed, unless done within the previous 30 days.
6. All clinical assessments and procedures must be performed as indicated; however, any clinical assessment or procedure can be performed if clinically indicated at any time
7. Written subject informed consent must be obtained prior to performing any assessment or procedures, unless otherwise specified.
8. Subjects must meet all eligibility prior to leukapheresis as specified in Section 4.2.
9. Subjects must continue to meet all eligibility criteria (Section 4.2) in addition to meeting those prior to lymphodepleting chemotherapy specified in Section 4.3.
10. Medical history will be recorded in the EDC at Screening and Baseline visits; however, any changes in medical history must be recorded in source documents throughout the conduct of the study.
11. Includes all prescription, over-the-counter medications, and herbal remedies. Any use of mutagenic agents or investigational agents must also be reported.
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12. Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen saturation. Height will be collected at the Screening visit only.
13. Vital signs on day of T cell infusion should be taken pre-infusion, and at 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started
14. If a subject is found to have a tumor response or PD by imaging, a follow-up confirmation scan must be done no earlier than 4 weeks following the scan when response or PD first seen. A subject is 
not considered to have a response or PD until follow-up scan confirms the finding.
15. Includes FEV1, FVC, TLC, and DLCO parameters to determine eligibility as described in Exclusion criterion #10 .
16. FPCP must have a negative urine or serum pregnancy test.
17. Includes HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochaete bacterium). Refer to Exclusion criterion #12 for details on required testing for eligibility. Testing for infectious disease markers is 
required only at Screening and does not need to be repeated at Baseline to satisfy eligibility criteria.
18. Only subjects who are CMV IgG seropositive at Baseline will continue to be monitored for CMV viremia by CMV DNA PCR post Baseline.
19. A free T4 test should be performed in subjects who have an abnormal TSH function test (high or low).
20. If CRS is suspected, cytokine and C-reactive protein levels should be measured approximately every other day until symptoms are improving or an alternative diagnosis is confirmed.
21. Only to be done in subjects ≥65 years of age to measure renal function.
22. Adverse events should be reported as noted in Section 9.
23. Persistence of gene modified cells in subjects will be monitored at Months 3, 6, and 12 post-infusion, then every 6 months until 5 years post-infusion and annually from year 6-15 post infusion. 
If no gen modified cells are detected for 3 consecutive assessments post-infusion, and subject is ≥5 years post-infusion, then sample collection maystop.
24. If RCL tests are negative at all time points during the first year, then samples will be collected annually and archived for up to 15 years post infusion or until assessments for persistence have ended
However, if VSV-G DNA copies are detected at any time point in the first year post-infusion, refer to the safety monitoring procedures in Section 10.5.
25. If pharmacogenetic sample collection is not done at Baseline, it may be done at any other subsequent visit in the Interventional Phase 1. Collection of a pharmacogenetic sample is optional and all 
subjects must provide consent for sample collection and analysis.
26. Core needle biopsies for research are at Baseline, week 8, and at confirmation of PD, with the exception of subjects for whom there is no safely accessible tumor tissue. 26a.) If a fresh biopsy was 
taken for NY-ESO-1and/or LAGE-1a confirmation screening in Screening Protocol, ADP-0000-001, and there is sufficient tumor sample left remaining, this sample may be used as the baseline 
sample. Otherwise, the Baseline biopsy may be collected anytime two weeks prior to the start of lymphodepleting chemotherapy, with preference closer to the time of infusion. 26b.) Blood sample 
from which cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating tumor cells (CTC), and exosomes may be extracted should match tumor biopsy time points.
27. Pre-infusion and Week 8 blood collection is for both Cytokine and Humoral anti-infused cell responses, and is collected in one 3 ml tube.
28. Brain MRI (or CT Scan if MRI not feasible) should be obtained in all subjects at the time of screening. Baseline brain MRI should be repeated if more than 4 months have elapsed prior to 
lymphodepletion.
29. Immune Effector Cell-Associated Encephalopathy (ICE) should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving treatment and then at least through Day 8 according to the 
schedule of procedures. Subjects with know brain metastases should be monitored at least twice per day for the first 5 days following NY-ESO-1c259T cell infusion. If a subject is found to have 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), the ICE neurological assessment tool , should be used at least twice per day until resolution or stable. It can also be used at later 
visits if indicated.
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Table 5
Schedule of Procedures – Long Term Follow-up
Time post-infusion
Year 1
Year 2
Year 3
Year 4
Year 5
Years 6-15
Months
3
6
12
18
24
30
36
42
48
54
60
Annually
Visit window
± 2 weeks
± 3 month
± 6 months
Safety Assessments
Medical History and Physical Exam1
X
X
X
X
X
X
X
X
X
X
X
Mutagenic agents, other investigational agents or anti-cancer therapies
X
X
X
X
X
X
X
X
X
X
X
Delayed Adverse Events and Serious Adverse Events2
X
X
X
X
X
X
X
X
X
X
X
Pregnancy test for WOCBP3
<===========================X3===========================>
Hematology
X
X
X
X
X
X
X4
Serum chemistry
X
X
X
X
X
X
X4
Allogeneic SCT
X
X
X
X
X
Laboratory Assessments
VSV-G DNA (RCL) for safety
X
X
X
X
X
X
X
X4
Transgene Copies (Persistence) for safety
X
X
X
X
X
X
X
X
X
X
X
X
Other Assessments
Survival Status
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: RCL=replication competent lentivirus; SCT=stem cell transplant; VSV-G =vesicular stomatitis virus G protein
1.
New medical history/medications/chemotherapies.
2.
Delayed Adverse Event and Serious Adverse Event collection is limited to:

New malignancies

New incidence or exacerbation of a pre-existing neurologic disorder

New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder

New incidence of immune-related hematologic disorder

Serious infections (including opportunistic)

Unanticipated illness and/or hospitalization deemed related to gene modified celltherapy
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3.
For women of child bearing potential (WOCBP), pregnancy testing should be conducted during contraception period only as defined in Section 5.1. When pregnancy testing 
is performed at visits where hematology sample is collected, blood pregnancy testing will be done. At visits where hematology sample is not collected, urine pregnancy test 
is acceptable unless serum testing is required by local regulation or IRB/IEC.
4.
In year 6-15, these assessments are performed for as long as persistence is analyzed. If persistence samples are discontinued (Section 10.3) then laboratory assessments 
are discontinued.
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7.3
Screen Failures
A screen failure log documenting the Investigator’s assessment of each screened subject with 
regard to the protocol inclusion and exclusion criteria is to be maintained by the Investigator.
7.4
Clinical Assessments and Procedures
7.4.1
Medical history
A complete medical history (including demographics and tobacco use) will be recorded at 
Screening in the subject’s medical record and eCRF.
7.4.2
Physical Examination and Measurement of Vital Signs
At Screening, subjects will undergo a physical examination including weight, height and 
measurement of their vital signs (temperature, pulse, respirations, oxygen saturation, and 
blood pressure). The frequency of physical examination, weight and vital signs assessments 
at subsequent visits is specified in the Schedule of Procedures (Table 4).
7.4.3
Performance Status
At Screening, performance status will be measured using the ECOG performance scale (refer 
to Appendix 2). It is recommended, where possible, that a subject’s ECOG be assessed by 
the same person throughout the study. The frequency of the ECOG assessment is specified in 
the Schedule of Procedures (Table 4).
7.4.4
Clinical Safety Assessments
Subjects will be assessed for AEs throughout the study. AEs are to be graded by NCI 
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. All AEs must be 
recorded in the eCRF. Additionally, subjects will be monitored for RCL and persistence 
throughout the study as described in Section 10.1 and Section 10.3, respectively.
Details on assessing and reporting AEs and SAEs are described in Section 9.
7.4.5
Laboratory Assessments
All laboratory assessments will be performed locally at the site, and laboratory test reference 
ranges must be provided to the Sponsor before the studyinitiates.
Women subjects of childbearing potential must have a negative pregnancy test at Screening 
and prior to starting lymphodepleting chemotherapy.
Refer to Schedule of Procedures (Table 4) for information regarding the frequency of these 
assessments and Appendix 3 for details on these local laboratory tests.
7.4.6
Cardiac and Other Assessments
All assessments will be performed locally at the site and will be conducted in order to 
monitor subject safety:

An echocardiogram (ECHO) or multigated acquisition (MUGA) scan will be performed 
at Screening to determine eligibility. Additional scans will be performed only if clinically 
indicated.

NOTE: the same method of cardiac evaluation must be used consistently for any 
follow-up scans.
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
ECGs (refer to Appendix 3 for the ECG parameters required)

A chest x-ray will be performed at Baseline. Additional x-rays should be performed if 
clinically indicated.

Brain MRI will be performed at baseline for all participants and as clinically indicated 
thereafter (see Section 8.9.2).

ICE assessment as described in Section 8.9.2 at the timepoints indicated in the Schedule 
of Procedures.

Pulmonary function tests will be performed at Screening to determine eligibility (refer to 
Section 4.2.2 for the parameters required)
Please refer to Schedule of Procedures (Table 4 ) for information regarding the frequency of 
these assessments.
7.4.7
Tumor Response Assessments
Tumor assessments for response and PD will be evaluated at Baseline (within 1 week of 
lymphodepleting chemotherapy), Week 8, Week 16, Week 24, every 3 months until Year 2 
and then every 6 months thereafter until PD, according to RECIST v1.1 (refer to Appendix 4) 
(Eisenhauer, 2009).
Imaging scans of the chest, abdomen and pelvis should be performed at Baseline and all 
subsequent visits. Acceptable imaging modalities for this study include:

Diagnostic-quality computerized tomography (CT) scan with oral and/or IV iodinated 
contrast of the chest and abdomen/pelvis (CT is the preferred modality for tumor 
assessments);

Magnetic resonance imaging (MRI) of the abdomen/pelvis acquired before and after 
gadolinium contrast agent administration and a non-contrast enhanced CT of the chest, if 
a subject is contraindicated for contrast enhancedCT;

MRI of the extremities per site standard of care, if clinically indicated;

Digital photographs of skin lesions including a ruler for estimating the size of the lesion.
Throughout the study, the same imaging modality and image-acquisition protocol (including 
the use of IV contrast) should be used consistently across all time points for individual 
subjects to allow uniform comparison of lesions.
Investigators will assess tumor response according to RECIST v1.1 for clinical decision 
making. Tumor measurements for each subject should be performed by the same Investigator 
or radiologist (to the extent that this is feasible).
To allow time for the immune response to become apparent and for potential transient 
inflammatory reaction of the disease to the treatment (‘tumor flare’), response will not be 
assessed before 4 weeks post infusion of NY-ESO-1c259T unless there is unequivocal clinical 
evidence of deterioration. Responses or progression should be confirmed by repeat imaging 
scan performed not earlier than 4 weeks after the criteria for response or progression was first 
met. Determinations of PD will be based upon RECISTv1.1.
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For subjects who have new lesions, response by irRECIST (Nishino, 2013) will be assessed 
by the Investigator for exploratory purposes but will not be used to formally assess disease 
response or progression. For new lesions, information on whether the lesion is measurable or 
non-measurable will be recorded in the eCRF. The measurements of measurable lesions will 
also be recorded.
CT/MRI scans will be collected and stored at a central imaging vendor for a possible 
independent review at the discretion of the Sponsor. A Site Imaging Manual will be provided 
to sites to describe the imaging acquisition and standardized procedure for the transfer of
image data to the central imaging vendor. The Site Imaging Manual will also describe the 
procedures for CT/MRI data handling after the images have been received by the central 
vendor from the sites.
7.4.8
Long-Term Follow-up
Reporting Criteria During Long-Term Follow-Up (Years 1-15)
Due to the nature of the treatment, participants are required to be followed for up to 15 years 
after treatment with genetically modified T cells according to FDA and EMA guidance 
[FDA, 2006b, FDA, 2010]. Delayed AEs are defined as those events that fall into one or more 
of the 6 categories listed below and which occur either more than one year following 
GSK3377794 infusion or after disease progression, whichever occurs first.  In the event a 
subject has not progressed 1 year following GSK3377794 infusion, delayed AEs will be 
collected in Interventional Phase of study.  Delayed AEs which occur post progression will be 
collected as part of the LTFU phase of the current study or in the LTFU Study (208750), 
contingent upon formal transfer of subject to Study 208750.

New malignancies

New incidence or exacerbation of a preexisting neurologicaldisorder

New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder

New incidence of an immune-related hematologic disorder

Opportunistic and/or serious infections

Unanticipated illness or hospitalization deemed related to gene modified cell therapy
A detailed description of the event should include the date of diagnosis and the nature of the 
diagnosis. If the diagnosis is cancer, record the type and stage of the cancer. If the cancer is 
metastatic, list the metastatic sites. If a new malignancy is recorded in a vector target cell 
type, tumor cells will be evaluated for vector sequences. If the tumor is positive for vector 
sequences or the surrogate sample is positive for vector sequences and is confirmed in 
accordance to this protocol, clonality analysis will be performed. If no evidence of oligo-or 
monoclonality is observed, a summary report of any and all analysis for the pattern of vector 
integration will be assembled, and submitted within the annual report of the INDs listed on 
this protocol under which the participant(s) evaluated originally received their treatment. If 
evidence of oligo- or monoclonality is observed, an information amendment will be 
submitted within 30 days to the INDs listed on this protocol under which the participant(s) 
evaluated originally received their treatment. Suspected unexpected serious adverse reactions 
(SUSARs) deemed related to the gene modified cells will be reported to the Regulatory 
Agencies and shared with Investigators as necessary in the form of Investigator Notification 
Letters (INL).
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7.5
Correlative Studies and Research Assessments
Correlative studies and research assays will be performed during the trial with the aim of 
monitoring the biological parameters that influence treatment outcome, such as T cell 
phenotype, function, and persistence of the engineered infused cells, as well as evaluation of 
candidate biomarkers and their correlation with clinical response to treatment. Data from 
such studies will be correlated to clinical outcome. These studies will be performed on tumor 
biopsies, serum and fractionated PBMC plasma samples routinely collected according to the 
Schedule of Procedures (Table 4). All samples will be processed and/or frozen and analyzed 
by either central laboratory facilities contracted by the Sponsor or by the Sponsor at the 
Sponsor’s facilities.
Research studies conducted on blood samples may include:

Flow cytometry to analyze cell subsets and persistence of engineered T cells

Genomic sequencing to assess T cell clonality through TCR Vbeta and Valpha 
sequencing and integration site analysis

Luminex to measure serum cytokine levels
NOTE: As new technologies and data emerge, other assays relevant to the study objectives 
may be performed.
Biopsy research studies may include:

Protein, DNA and RNA analysis including PCR and in-situ hybridization to measure
infiltration of T cells

Genomic sequencing to assess T cell clonality through TCR Vbeta and/or Valpha 
sequencing

Tissue expression of the target antigen NY-ESO-1 and/orLAGE-1a

Tissue analysis for immune cell infiltrate and functional biomarkers and gene expression profile

Tissue analysis to determine the evolution of the mutation profile of the tumor over the 
course of the therapy
NOTE: As new technologies and data emerge, other assays relevant to the study objectives 
may be performed
If a subject has an AE, an additional biopsy (for example skin, gastroinstetinal tract, bone 
marrow, tumor) or blood (serum and PBMC) samples may be requested with the objective of 
gaining an understanding of the underlying etiology of the AE. For this purpose, the above 
described research tests may be performed on thesesamples.
7.5.1
Pharmacogenetics Sample
An optional whole blood sample for pharmacogenetic research may be obtained at any time 
throughout the study after eligibility is confirmed (refer to Table 4). The blood sample will 
be taken on a single occasion unless a duplicate sample is required due to inability to utilize 
the original sample. The blood sample can be taken at Baseline or at any point during the
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Interventional Phase of the study provided the subject has given written informed consent for 
pharmacogenetics research.
Specific genes will be selected from areas of the genome (e.g., candidate genes) including 
areas associated with mechanisms underlying AEs. The candidate genes that may be 
investigated in this study include transforming growth factor (TGF)-beta, tumor necrosis 
factor (TNF)-alpha, interleukin (IL)-6, IL10 and interferon(IFN)gamma.
7.5.2
Cytokine and Soluble Factors Analysis
Serum is collected at Baseline, and at each visit post infusion up to 12 weeks, to allow for 
measurement of cytokines in the blood. Serum is also collected from subjects with suspected 
CRS, with samples being taken approximately every other day until symptoms are improving 
or an alternative diagnosis is confirmed (refer to Section 8.5). Details regarding serum 
collection are provided in the Study Procedures Manual.
Cytokines, growth factors and soluble receptors including but not limited to IL-6, IFN-γ, 
TNF-α, IL-2Rα, IL-10, IL-13, IL-1Ra, IL-8, IL-12, IL-15, IL-2, and GM-CSF are measured
.
GLP measurement of the cytokine subset IL-1β, IL-10, IL-6, TNF-α, and IFN-γ is performed.
All other measurements are exploratory.
Serum samples may also be used to investigate the presence of antibodies to NY-ESO-1c259T.
7.5.3
Tumor Biopsies
The efficacy of cancer immunotherapy is conditioned by the infiltration of tumors by 
activated tumor-specific T cells. The activity of these T cells will in turn be affected by the 
presence in the tumor of an immunosuppressive environment (e.g. regulatory T cells).
Therefore, the direct evaluation of the “immune landscape” inside the tumor is of great value 
for understanding and optimizing cancer immunotherapy. For this reason, core needle 
biopsies are requested at Screening, Baseline (to evaluate the immune status of the tumor
before T cell infusion), Week 8 (at the expected time of an active anti-tumor response by 
infused T cells), and after disease progression is confirmed, with the exception of subjects
for whom there is no safely accessible tumor tissue.
Archival tissue may be used for the screening biopsy, although fresh tissue is preferred. If a 
fresh biopsy was taken for NY-ESO-1 and/or LAGE-1a confirmation screening in the 
Screening Protocol (ADP-0000-001), and there is sufficient tumor sample left remaining, this 
sample may be used as the Baseline sample for these correlative science studies. Otherwise, 
the baseline biopsy material may be collected anytime between two months and 2 weeks prior 
to the start of lymphodepleting chemotherapy, with preference for a biopsy to be taken closer 
to the time of infusion. Tumor tissue should either be taken from non-target lesions or from 
target lesions >2cm. When possible, the same lesion(s) should be biopsied at both Screening 
and subsequent time points. The apparent clinical or scan status of the lesion(s) biopsied 
should be documented at the time (e.g. decreased, stable, increased size or activity).
If feasible, biopsy material should be collected after disease progression has been confirmed 
and documented, ideally on lesions that have progressed.
Additional details regarding tumor biopsy collection are provided in the SPM.
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In subjects who have a pleural effusion or ascites, if there is a clinical requirement for 
removal of the effusion fluid at any time during the study, collection of samples for GSK 
translational research studies are requested.
NOTE: If available, pleural effusion or ascites fluid should be collected in addition to, and 
not instead of the requested tumor biopsies.
Clinically obtained pleural effusion/ascites samples have been shown to be a rich source of 
tumor cells, tumor infiltrating leukocytes and soluble factors, changes in which have been 
reported to correlate with disease prognosis and therapy response. Pleural effusions/ascites 
fluid collected in this protocol will be used to interrogate soluble and cellular components of 
the tumor microenvironment before and after T cell infusion to address mechanisms of 
sensitivity or resistance to therapy
7.5.4
NY-ESO-1c259 TCR+ Cell Persistence:
The primary research assays for the trial involve monitoring for the persistence of infused 
engineered cells in the subjects and for correlation of this with potential therapeutic effect. 
Persistence is also monitored as a long-term safety measure (refer to Section 10.3). Two well 
established methodologies will be used to measure thecells:

Quantitation of NY-ESO-1c259 TCR+cells by PCR of transgene from DNA extracted 
from frozen PBMC

Quantitation of NY-ESO-1c259 TCR+expression cells by flow cytometry from frozen 
PBMC
7.5.5
NY-ESO-1c259 TCR+ Cell Phenotype and Activity:
A range of assays will be performed to elucidate the phenotype and activity of the gene-
modified T cells (manufactured product) before and after infusion in the blood (and tumor if 
resection is performed). The assays performed will depend upon availability of sample and 
clinical / scientific significance. The following assays may be performed:

Phenotype analysis for determination of T cell lineages

Quantitation of the senescence and activation status of immune subsets from PBMC

Quantitation of soluble factors reflecting in vivo function of NY-ESO-1c259 TCR+ T cells

Anti-gene modified T cell immune responses (tertiary assay).

Ex-vivo activity of transduced cells at different time points to assess potential anergy of 
those cells.

Analysis of gene expression profile to reflect activity of thecells
NOTE: Analysis may not be limited to these assays; additional assays may be added as they 
become available
7.5.6
Liquid Biopsy Collection and Analysis
Recognizing that tumor biopsies cannot always be obtained safely, we set out to investigate 
whether alternative safer approaches can provide similarly valuable information. Therefore, 
in addition to tumor biopsies, liquid biopsies (peripheral blood plasma) will be collected in 
parallel, as well as at other timepoints as listed in the Schedule of Procedures, to extract cell-
free DNA (cfDNA) and exosomes to investigate:
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
Estimation and genetic profiling of the global tumor burden (including expression of NY-
ESO-1 and/or LAGE-1a mRNA and mutational profiling) from exosomes and cfDNA.

Systemic assessment of the immune response (gene expression by cytotoxic and 
regulatory immune cells) from exosomes.
7.5.7
Request for Autopsy for Death Following Administration of Gene 
Transfer Agents
In accordance with FDA and EMA guidance (FDA, 2006a; EMEA, 2009), all subjects 
enrolled in this trial are asked to consider an autopsy and autopsies will be requested of the 
families for all subjects who die during participation in studies after administration of gene 
transfer agents. To assure compliance, guidelines for performing an autopsy are provided in 
the Study Procedures Manual.
8
SUPPORTIVE CARE GUIDANCE
It is recommended that a specialist with experience in the administration of hematopoietic 
stem cell transplant and/ or other cell and gene therapy be involved in the care of study 
subjects. All subjects should be hospitalized for the T-cell infusion. Staff treating trial 
subjects should be experienced in acute post-transplant care and the management of 
associated toxicities (e.g. cytopenias, CRS, autologous graft versus host disease).
Subjects are at risk for the development of certain adverse effects for which recommended 
management strategies have been developed. Adverse effects are most likely to occur within 
the first month following T cell infusion, but may occur at later time points.
Supportive care treatments recommended herein, including tocilizumab, will be supplied by 
the pharmacy of the participating institution.
8.1
T Cell Infusion Symptom Management
Mild transient symptoms have been observed following infusion of engineered T cells. The 
management of these symptoms is suggested but should not necessarily be confined to the 
below.

Fever, chills, headache and temperature elevations will be managed with acetaminophen. 
It is recommended all subjects that develop fever or chills have a blood culture drawn.

Nausea and vomiting may be treated with a non-steroidal anti-emetic of choice.

Hypotension will initially be managed by intravenous fluid administration and further 
measures as dictated by standard medical practice.

Hypoxemia will initially be managed with supplemental oxygen and further measures as 
dictated by standard medical practice.
8.2
Infection
Additional measures to treat and prevent infection are outlined below. In particular, fever 
and neutropenia should be aggressively managed as well as preemptive influenza therapy and 
other standard therapies for immunocompromised hosts, in accordance with institutional 
guidelines.
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8.2.1
Pneumocystis carinii Pneumonia
Subjects should receive prophylaxis against PCP with drug, dose and duration according to 
institutional guidelines. Single strength trimethoprim sulfamethoxazole daily is the 
recommended first-line agent, starting at Day 28 post T cell infusion for one year. Other 
regimens, including atovaquone (1500mg daily with food) or aerosolized pentamidine 
(300mg every four weeks) are also acceptable (e.g. if sulfonamide allergy).
8.2.2
Herpes simplex and Varicella zoster
All subjects should receive prophylaxis with acyclovir (800mg twice daily) or valacyclovir 
(500mg twice daily) for one year, or in accordance with institutional guidelines.
8.2.3
Cytomegalovirus
All subjects will be screened for cytomegalovirus (CMV) IgG seropositivity at study entry. 
If CMV viremia is detected at Baseline, treatment should be initiated with evidence of viral 
clearance prior to lymphodepleting chemotherapy. All CMV IgG seropositive subjects will 
continue to be monitored as shown in Table 4 for CMV viremia by CMV DNA PCR until 60
days post infusion of NY-ESO-1c259T cell therapy. In the event CMV viremia is observed, an 
infectious diseases specialist should be consulted and treatment initiated if necessary 
according to institutional practice. Recommended regimens include ganciclovir based 
therapy if ANC ≥1000, and foscarnet if ANC <1000.
If a subject experiences prolonged or secondary pancytopenia or lymphopenia, additional 
monitoring for viral reactivation should be considered and treatment for viral infection 
initiated if necessary. A strategy for management of pancytopenia or bone marrow failure is 
described in Section 8.7.
8.2.4
Hepatitis B Prophylaxis
Subjects will be screened for hepatitis B virus (HBV) at study entry. Subjects who are 
hepatitis B core antibody positive must receive prophylaxis against viral reactivation using 
institutional protocols. Prophylaxis should be initiated prior to lymphodepleting 
chemotherapy and continued for 6 months. Acceptable regimens include lamivudine (300mg 
daily), entecavir (0.5mg daily), or tenofovir (300mg daily).
8.2.5
Syphilis
Subjects will be screened for syphilis at study entry. Subjects with positive screening results 
should be evaluated by an infectious diseases consultant. If determined to have syphilis 
infection, the subject should be treated before lymphodepleting chemotherapy.
8.2.6
Other Anti-Microbial Prophylaxis
Antibacterial and antifungal prophylaxis shouldfollow institutionalstandards for autologous 
bone marrow transplants.
8.3
Hematologic and Blood Product Support
Blood product support should be provided to maintain platelets >10 x 109/L, Hb >8.0 g/dL 
(or in accordance with institutional practice) and as clinically indicated. See AABB 
Guideline on platelet transfusion (Kaufman, 2015).
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8.3.1
Irradiated Blood Product
Bone marrow suppression can be a consequence of transfusion associated GVHD. To 
minimize the possibility of transfusion associated GVHD, all blood products transfused 
within 4 weeks prior to leukapheresis, within 4 weeks prior to initiation of lymphodepleting 
chemotherapy and following lymphodepleting chemotherapy until at least 6 months 
following IP infusion or until lymphocyte count returns to ≥1.0 x 109/L (whichever is longer) 
must be irradiated. In addition, if a subject requires systemic steroids or immunosuppression 
for the treatment of toxicity, irradiated blood products must be given until recovery of 
immune function.
8.3.2
CMV Screened Blood Products
Subjects will be screened for CMV seropositivity at study entry. In order to reduce the risk 
of primary CMV infection, all subjects (i.e. both CMV-positive and -negative subjects) 
should receive leukoreduced blood products where possible (excluding the IP infusion).
Where leukoreduced blood is not available, CMV negative subjects must only receive blood 
products from CMV-seronegative donors from study entry to study completion.
8.4
Management of Autoimmunity
Subjects should be monitored throughout the trial for potential autoimmune reactions in 
response to the genetically engineered T cells that could include skin toxicity, liver toxicity, 
colitis, eye toxicity etc. If autoimmunity is suspected, the Investigator should be contacted 
and every attempt should be made to biopsy the affected organ to clarify whether the 
symptoms are related to the NY-ESO-1c259T cell therapy. If the subject sustains persistent 
Grade 2, or Grade 3 or 4 autoimmunity, consideration should be given to administration of 
corticosteroid therapy, either topically (e.g. skin, eyes) or systemically as clinically indicated.
8.5
Management of Cytokine Release Syndrome
Cytokine release syndrome is a potentially life-threatening toxicity that has been observed 
following administration of antibodies and ACTs for cancer. It is defined clinically by 
symptoms many of which mimic infection, including pyrexia, nausea, diarrhea, headache, 
fatigue, tachycardia, hypotension, transaminitis, rash, and dyspnea. It is important to evaluate 
the subject for concurrent infections. Potentially life-threatening complications of CRS 
include cardiac dysfunction, adult respiratory distress syndrome, neurologic toxicity, renal 
and/or hepatic failure, and disseminated intravascular coagulation. CRS may also be 
associated with findings of macrophage activation syndrome or occur coincident with tumor 
lysis syndrome.
CRS caused a rapid rise in serum cytokine levels under conditions of immune activation and 
although cytokines will be assayed serially throughout the study, results of the assays will not 
be available in real time; therefore, CRS should be graded and managed with supportive and 
immunosuppressive interventions according to the severity of symptoms (Lee, 2014).
Table 6 provides the recommended management of CRS according to grade, which has been 
further adapted from CTCAE for use with immunotherapy and should be implemented in 
accordance with institutional guidelines. Symptoms can mimic those seen with infection.
The diagnosis of CRS is clinical, and is supported by the exclusion of infection as well as the 
presence of increased cytokine levels and other biomarkers. Assessment and treatment 
guidelines are provided below. If CRS is suspected, in addition to assessment for infection,
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cytokine levels as described Section 7.5.2 as well CRP levels should be measured 
approximately every other day until symptoms are improving or an alternative diagnosis is 
confirmed.
Table 6:
Management Guidelines for Cytokine ReleaseSyndrome
Grade
Clinical Presentation for Grading 
Assessment
Management Guidelines
1
Temperature ≥38.0 °C 

Vigilant supportive care1

Assess for infection and treat2
2
Temperature ≥38.0 °C 
with hypotension not requiring 
vasopressors 
and/or hypoxia requiring the use of 
oxygen delivered by low-flow nasal 
cannula (≤6 L/minute) or blow-by. 

Monitor cardiac and other organ 
function

Vigilant supportive care1

Assess for infection and treat2

Treat hypotension with fluid and 
pressors

Administer O2 forhypoxia

Consider administering 
tocilizumab ±corticosteroids3 
3
Symptoms require and respond to 
aggressive intervention
hypotension requires multiple pressors or 
high dose pressors
hypoxia requires ≥40% O2, Grade 3 organ 
toxicity or Grade 4 transaminitis

Monitor subject very closely for 
cardiac and other organ 
dysfunction. Most likely will 
require monitoring in an intensive 
care unit (ICU).

Vigilant supportive care1

Assess for infection and treat2

Treat hypotension with fluid and
pressors. Administer O2 for
hypoxia.

Administer tocilizumab± 
corticosteroids3
4
Life-threatening symptoms
Grade 4 organ toxicity (excluding 
transaminitis)

Manage subject in ICU

Intensive supportive care including 
mechanical ventilation, fluids, 
pressors, antibiotics and other 
measures as required

Administer tocilizumab± 
corticosteroids3
5
Death
1.
Fever is defined as temperature _38°C not attributable to any other cause. In patients who have CRS then receive 
antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent 
CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia.
2.
CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a patient with temperature of 39.5°C, hypotension requiring 1 vasopressor, and hypoxia requiring low-
flow nasal cannula is classified as grade 3 CRS.
3.
Low-flow nasal cannula is defined as oxygen delivered at ≤6 L/minute. Low flow also includes blow-by oxygen 
delivery, sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at >6 L/minute.
4.
Supportive care includes: monitor fluid balance, maintain adequate hydration and bloodpressure
5.
Assessment and treatment to include history and physical, blood and urine cultures, imaging studies, 
administration of antimicrobial agents for concurrent bacterial infections, and for treatment of fever and 
neutropenia as per institutional practice; and antipyretics, analgesics as needed.
6.
Given that prolonged fluid resuscitation without pressor use is associated with worse outcome and because early 
and aggressive supportive care, early use of vasopressors, and timely anti-cytokine therapy are paramount to 
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mitigating life-threatening CRS.
7.
Other immunosuppressor agents may be used, including TNFα and IL-1R inhibitors 
Source: (Lee, 2019)
Grade 1 CRS is defined as fever (≥38.0°C) with or without constitutional symptoms (Table 
6). The constitutional symptoms of CRS, such as myalgia, arthralgia, and malaise, are by 
themselves nonspecific; however, when coincident with fever in the expected timeframe, 
the etiology of CRS is more likely. 
Grade 2 CRS is defined as fever (≥38.0°C) with hypotension not requiring vasopressors 
and/or hypoxia requiring the use of oxygen delivered by low-flow nasal cannula (≤6 
L/minute) or blow-by (Table 6). 
Grade 3 CRS is defined as fever (≥38.0°C) with hypotension requiring 1 vasopressor with 
or without vasopressin and/or hypoxia requiring high-flow nasal cannula (>6 L/minute), 
facemask, nonrebreather mask, or venturi mask not attributable to any other cause (Table 
6). 
Grade 4 CRS is defined as fever (≥38.0°C) with hypotension requiring multiple 
vasopressors (excluding vasopressin) and/ or hypoxia requiring positive pressure [eg, 
Continuous airway positive pressure (CPAP), bilevel positive airway pressure, intubation, 
mechanical ventilation] not attributable to any other cause. Outside of vasopressin, adding 
a second agent is a strong indication that the patient remains hemodynamically unstable 
after the first intervention. Such a scenario would be consistent with grade 4 CRS. Any use 
of positive-pressure ventilation constitutes a grade 4 CRS. Intubation of a patient without 
hypoxia for the possible neurologic compromise of a patent airway alone or for a 
procedure is not, by definition, grade 4 CRS. By extension, a patient experiencing seizures 
in which a compromised airway affects oxygenation and intubation reverses such deficits 
is not considered to have grade 4 CRS, because the seizure rather than CRS is the cause of 
the hypoxia. Furthermore, a patient who remains intubated for a neurologic cause is not 
considered to have CRS when the other signs of CRS have resolved. 
By convention, grade 5 CRS is defined as death due to CRS in which another cause is not 
the principle factor leading to this outcome.
Subjects requiring immunosuppressive intervention may receive tocilizumab, steroids, or 
both (Davila, 2014; Lee, 2014; Lee 2019). Tocilizumab is a humanized anti-IL-6 receptor
antibody that has been used to manage severe CRS (although it is not approved for this
indication).
Anecdotally, tocilizumab has produced rapid and complete correction of CRS with single 
doses (Maude, 2014). Lee et al., recommended administration of tocilizumab 4mg/kg 
administered over 1 hour in adult subjects as the first-line treatment of severe CRS. Subjects 
may receive a repeat dose if clinical signs and symptoms do not improve within 24-48 hours.
Side effects attributed to chronic use of tocilizumab in rheumatologic disease include 
transaminitis, thrombocytopenia, elevated cholesterol and low-density lipoproteins, 
neutropenia and increased infections but acute infusional toxicities have not been reported in 
CRS use (Lee, 2014; Lee, 2019).
Subjects unresponsive to tocilizumab or experiencing severe neurological symptoms (e.g. 
confusion, delirium, seizure, etc.) may require treatment with steroids. Lee et al. [Lee, 2014; 
Lee, 2019], recommend steroids as second-line therapy for CRS as the response to 
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tocilizumab may be more rapid and owing to the potential of steroids to attenuate the anti-
tumor effects of the ACT. However, in subjects with Grade 3 or 4 CRS associated with
neurologic dysfunction without significant hemodynamic instability or other life-threatening
symptomatology, consideration may be given to the use of corticosteroids as a preferred 
first-line immunosuppressive therapy. High doses (e.g. 2 mg/kg/day prednisone equivalent) 
may be required.
If CRS is suspected, a physician with expertise in the management of subjects following bone 
marrow transplant should be consulted. If high-dose corticosteroids are required, treatment 
should generally be continued for at least 5 days followed by tapering doses over several 
weeks.
Please refer to the most recent version of the product label for tocilizumab.
8.6
Management of Graft-versus-Host Disease (GVHD)
Autologous GVHD has been described in association with adoptive transfer of ex-vivo 
expanded/co-stimulated autologous T cells (Rapoport, 2009), as well as infusion of T cells 
with engineered specificity for NY-ESO-1 and LAGE-1a (Garfall, 2013), following high-
dose chemotherapy and autologous stem cell transplant (ASCT) in subjects with multiple 
myeloma. There is the potential for subjects who receive lymphodepleting therapy followed 
by engineered autologous T-cell infusion to experience GVHD and/or autoimmune GVHD-
like symptomatology. Autologous GVHD is typically milder than classic (allogeneic) GVHD 
(Kline, 2008), and is usually manageable with treatment. However, severe cases (including 
fatalities) have been reported (Fidler, 2012). There are no published guidelines for the 
management of autologous GVHD. However, lessons can be drawn from published case 
reports and guidelines for the diagnosis and management of acute GVHD following 
allogeneic transplant (Dignan, 2012).
8.6.1
Diagnosis of GVHD
The diagnosis of GVHD is predominantly based on clinical findings and is often one of 
exclusion (Table 7). Many of these symptoms can also occur in the setting of the preparative 
regimen, high dose cyclophosphamide as well as with CRS. Any of these conditions 
including GVHD can be associated with fever. The skin is the most commonly involved 
organ, followed by the gastrointestinal tract and liver. A constellation of symptoms involving 
these organ systems may be helpful in establishing the diagnosis of GVHD. Diarrhea, rash, 
fever, and pancytopenia are common toxicities in the NY-ESO-1c259T program where we
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have the most clinical experience. Mild (Grade 1 or 2) transient transaminitis without 
cholestasis has been observed.
Table 7:
Overview of Clinical Findings/Symptoms of GVHD
Organ
Findings/Symptoms
Differential Diagnosis
Histopathology
Skin
Maculopapular rash 
involving the neck and 
shoulders as well as the 
palms and soles that spreads 
to include the rest of the 
body.
Drug reactions, viral 
exanthems, CRS, and 
effects of chemotherapy or 
radiation
Apoptosis at base of 
epidermal rete pegs, 
dyskeratosis, exocytosis of 
lymphocytes, satellite 
lymphocytes adjacent to 
dyskeratotic epidermal 
keratinocytes and 
perivascular  lymphocytic
infiltration in the dermis.
GI
Secretory diarrhea is most 
common but nausea, 
vomiting, anorexia, weight 
loss and abdominal pain can 
also occur. Diarrhea can be 
copious. Bleeding may 
result from mucosal
ulceration and ileus may 
ensue.
Side effects of 
chemotherapy or other 
drugs and infection of the 
gastrointestinal tract
Patchy ulcerations, apoptotic 
bodies at crypt bases, crypt 
ulceration and flattening of 
surface epithelium
Liver
Cholestatic pattern of liver 
injury including elevated 
conjugated bilirubin, alkaline 
phosphatase and gamma 
glutamyl transpeptidase 
(GGTP). Subjects may 
present with jaundice, with
pruritis in more severe cases.
Veno-occlusive disease of 
the liver, viral infections, 
drug toxicity and sepsis.
Endothelialitis, lymphocytic 
infiltration of the portal 
areas, pericholangitis and 
bile-duct destruction.
NOTE: Bone marrow suppression and related cytopenias have been described in the setting 
of acute GVHD. Management of this complication is challenging, with no clearly established 
guidelines regarding immunosuppression. Treatment may be largely supportive, including 
transfusions and treatment of infections.
Management should include consultation with a physician with expertise in the management 
of subjects following bone marrow transplant.
Bone marrow suppression is also a feature of transfusion-related GVHD. To minimize the 
possibility of transfusion-related GVHD, refer to Section 8.3.1 for guidance on irradiated 
blood products.
8.6.2
Grading of GVHD
Grading of acute GVHD is based on the stage of dermal, gastrointestinal, and hepatic 
involvement as described in Table 8 . Careful measurement of stool volume and assessment 
of percentage of body area covered by rash are important for proper grading and treatment.
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Table 8:
Staging of Dermal, Gastrointestinal and Hepatic Involvement with Acute
GVHD
Stage
Skin
Gut
Liver
1
Maculopapular rash <25% of body area
Diarrhea >500 ml/day
Bilirubin 2-3 mg/dl
2
Maculopapular rash 25%-50% of body
area
Diarrhea >1,000 ml/day
Bilirubin 3-6 mg/dl
3
Generalized erythroderma
Diarrhea>1,500 ml/day
Bilirubin 6-15 mg/dl
4
Desquamation and bullae
Diarrhea>2,000 ml/day or
pain or ileus
Bilirubin >15 mg/dl
With the addition of assessment of functional impairment, grading can be determined using 
Table 9 (Glucksberg, 1974).
Table 9:
Grading of Acute GVHD
Grade
Skin1
Gut1
Liver1
Functional status2
I
1-2
0
0
0
II
1-3
1
1
1
III
2-3
2-3
2-3
2
IV
1-4
2-4
2-4
3
1 Staging is described above
2 Mild, moderate, or severe decrease in performance status
8.6.3
Management of GVHD
Although the diagnosis of GVHD is predominantly based on clinical grounds, biopsy of 
affected organs can be helpful in excluding other causes and supporting the diagnosis of 
GVHD with consistent histopathologic findings. However, awaiting biopsy results should 
not delay the institution of appropriate therapy.
If GVHD is suspected:

A physician with expertise in the management of subjects following bone marrow 
transplant should be consulted

Consider biopsy of the affected organ(s)
Corticosteroids have been used as the standard first-line treatment for GVHD for several 
decades. Their effect is likely to be due to lympholytic effects and anti-inflammatory 
properties. In general, intestinal and liver GVHD require more prolonged steroid therapy 
than skin disease although response times vary.
Diarrhea should be managed with volume replacement, dietary restriction, and anti-diarrheal 
agents including the consideration of somatostatin for secretory diarrhea. Agents that slow 
motility should be used cautiously, ensuring that there is no evidence of ileus or toxic 
megacolon, and infectious causes of diarrhea should beexcluded.
General guidelines for first-line treatment based on grade are provided in Table 10, and 
should be considered in conjunction with input from the consulting physician with bone 
marrow transplant expertise.
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Table 10:
Management Guidelines for GVHD
Grade
Management Strategy
I
Subjects with Grade I disease are not likely to require systemic treatment. Cutaneous 
GVHD may respond to topical steroid creams. Antihistamines may be helpful in 
subjects with pruritis. Subjects should be reviewed frequently for other organ
manifestations of GVHD.
II
Treat skin symptoms with topical steroids. For GI symptoms - optimize anti-
diarrheal regimen, dietary restrictions, volume replacement and consider initiation of 
non-absorbable steroids. For refractory or progressive symptoms consider systemic
steroids as outlined below.
III
For more severe or progressive symptoms consider systemic corticosteroids (e.g.,
methylprednisolone one (1) mg/kg per day1)
IV
Methylprednisolone two (2) mg/kg per day1
1 The use of ‘nonabsorbable’ steroids (Budesonide and beclomethasone) can be considered for acute intestinal GVHD in 
order to reduce the dose of systemic steroids
If high dose corticosteroids are required, treatment should generally be continued for at least 
5 days followed by tapering doses over several weeks. A physician with expertise in 
infectious diseases in immunocompromised hosts should be consulted, and prophylactic 
antimicrobials should be considered.
Second-line treatment can be considered for subjects who have failed to respond for 5 days or 
have progressive symptoms after 3 days. There is no clear second-line agent that is preferred 
for steroid refractory GVHD. General guidelines for second-line treatment based on grade 
are provided below, and should be considered in conjunction with input from the consulting 
physician with bone marrow transplant expertise.
For steroid refractory skin rash, topical tacrolimus may also be useful.
Most of the allogeneic transplant subjects are concurrently receiving calcineurin inhibitors in 
part as prophylaxis against GVHD. Therefore, for Grade II-IV disease refractory to high 
dose steroids, the addition of a calcineurin inhibitor can be considered.
Otherwise, there are several additional second-line treatment options for which there is 
currently limited and/or evolving supporting data. Treating physicians can refer to the 
Haemato-oncology Task Force of the British Committee for Standards in Haematology and 
the British Society for Blood and Marrow Transplantation guideline for diagnosis and 
management of acute graft-versus-host disease (Dignan, 2012).
8.7
Management of Pancytopenia with Bone Marrow Failure / Aplastic
Anemia
Pancytopenia with bone marrow failure / aplastic anemia has been reported after initial bone 
marrow recovery from high-dose chemotherapy followed by infusion of NY-ESO-1c259T-
cells. Bone marrow recovery following lymphodepletion will be defined as:

ANC ≥1,000/μL for 2 consecutive measurements approximately seven days apart, and

Platelet count ≥20,000/μL without transfusion support for oneweek.
Aplastic anemia is a rare hematological disorder characterized by pancytopenia and a 
hypocellular marrow. Subjects are usually symptomatic on presentation but some are 
detected incidentally when unexpected cytopenias are found on a routine blood count. The
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diagnosis of severe aplastic anemia is made in the setting of a hypocellular bone marrow 
when 2 of the following 3 blood counts are met: ANC <500/μL, absolute reticulocyte count
<60,000/μL, and platelet count <20,000/μL, and myelodysplastic syndrome is ruled out. The 
clinical consequences of aplastic anemia are life-threatening bleeding from 
thrombocytopenia, and infection as a result of neutropenia. Bacterial and fungal infections 
are common and a significant cause of morbidity andmortality.
Management of bone marrow suppression and related cytopenias in aplastic anemia is 
challenging, with noclearlyestablished guidelines regardingimmunosuppression. Treatment 
is largely supportive, including transfusions and treatment of infections. If there is evidence 
of, or concern for the development of pancytopenia (decreasing hemoglobin, platelets or 
neutrophils, or increasing transfusion requirements) following initial bone marrow recovery 
the following measures should be implemented:

Consult a physician with expertise in the management of aplastic anemia

Increase the frequency of CBCs as clinically indicated.

Exclude other alternative etiologies such as other drugs, viral causes, etc.

An early bone marrow biopsy is recommended for clinical diagnosis, with a sample to be 
provided to the Sponsor for study. Details on tissue collections, kit use and shipment 
information can be found in the SPM and refer to Section7.5.

A matched peripheral blood sample should be collected in parallel with the bone marrow 
sample and provided to the Sponsor. Refer to Section7.5.

Initiate treatment with G-CSF

Consult an Infectious Diseases expert

Once alternative etiologies have been excluded, strongly consider immunosuppression 
(e.g. methylprednisolone 2mg/kg initial dose) or more aggressive regimens (e.g. 
antithymocyte globulin (ATG), cyclosporine, eltrombopag) as well as antimicrobial 
prophylaxis/therapy with the advice of your hematology/Infectious Diseases 
consultant(s). If high dose corticosteroids are initiated, continue for a minimum of 5 days 
and taper gradually with advice from expertconsultants.
Refer to Section 8.6 regarding bone marrow suppression as a feature of GVHD.
8.8
Chemotherapy Symptom Management
Cyclophosphamide and fludarabine are used as pre-conditioning lymphodepleting 
chemotherapy in this study. Symptoms associated with the use of cyclophosphamide and 
fludarabine are included in the product labels. Refer to the most current product labels, and 
Section 6.1 for details of prohibited medications.
8.8.1
Management of Neutropenia
The pre-conditioning chemotherapy is intended to cause lymphodepletion. However, 
neutropenia is also common. Prophylactic use of G-CSF is recommended in all subjects. G-
CSF (e.g., filgrastim) should be used for management of neutropenia according to ASCO 
guidelines (Smith, 2015). G-CSF should be should be given starting 24 hours after the
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administration of chemotherapy until resolution of neutropenia (reaching an ANC of at least 
2 × 109/L to 3 × 109/L or as per institutionalpractice).
Long-acting (pegylated) G-CSF may be given in preference to short acting daily G-CSF in 
accordance with institutional standard practice. Pegylated G-CSF will be given as one dose 
24 hours post the final dose of cyclophosphamide.
8.9
Management of Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS)
Encephalopathy has been described in association with chimeric antigen receptor (CAR) T 
therapy, and termed (CAR) T cell related encephalopathy syndrome, or CRES [Neelapu, 
2018]. CRES typically manifests as a toxic encephalopathy which is generally reversible. 
Early signs include diminished attention, language disturbance and impaired handwriting. 
Othersigns/symptoms includeconfusion, disorientation, agitation,aphasia, somnolence, and 
tremors. In severe cases of CRES (defined as grade >2), seizures, motor weakness, 
incontinence, mental obtundation, increasedintracranial pressure, papilledema, andcerebral 
edema may also occur.
CRES occurring within the first 5 days after immunotherapy may be concurrent with high 
fever and CRS symptoms. This form of CRES tends to be of shorter duration, lower grade 
(grade 1–2, see Table 2), and is generally reversible with anti-IL-6 therapy. CRES presenting 
as delayed neurotoxicity with seizures or episodes of confusion can occur three or four weeks 
after CART‑cell therapy, after the initial fever and CRSsubside.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) is a disorder 
characterized by a pathologic process involving the central nervous system following any 
immune therapy that results in the activation or engagement of endogenous or infused T 
cells and/or other immune effector cells. Symptoms or signs can be progressive and may 
include aphasia, altered level of consciousness, impairment of cognitive skills, motor 
weakness, seizures, and cerebral edema. ICANS may occur with other cancer 
immunotherapies, including TCRs. Cancer patients may also be at risk for ICANS
symptoms due to other causes ranging from mild to moderate somnolence and confusion as a
result of sedating medications, to seizures in relation to brain metastases. The possible 
contribution of other medications, underlying disease and/or co-morbidities should be 
evaluated when considering a diagnosis of ICANS in relation to T celltherapy.
8.9.1
Management of ICANS
The recommended management of ICANS should be based on toxicity grade. Table 11
provides guidance on the management of ICANS, and should be implemented in 
accordance with institutional guidelines.
Grade 1 ICANS is primarily managed with supportive care as outlined below. For subjects 
requiring intervention beyond supportive measures, anti-IL-6 therapy should be the first line 
treatment of for ICANS in the setting of CRS. In the setting of concurrent CRS, for Grades
1-3 ICANS additional doses of anti-IL-6 therapy should be considered before instituting 
corticosteroids since the use of systemic steroids may abrogate the effects of the T cell 
therapy. For subjects with neurologic symptoms refractory to an initial dose of anti-IL-6 
therapy, consider siltuximab for the second dose based on its mechanism of action directly 
against IL-6.
A neurology consultation should be obtained for all subjects with ICANS for thorough 
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neurological evaluation, and recommendations for further testing such as 
electroencephalogram (EEG) and neuroimaging as indicated.
Table 11:
Management of ICANS
ICANS
Grade
Treatment
1
• Vigilant supportive care; aspiration precautions; intravenous (IV) hydration
• Withhold oral intake of food, medicines, and fluids, and assess swallowing
• Convert all oral medications and/or nutrition to IV or enteral tube if swallowing isimpaired
• Avoid medications that cause central nervous system depression
• Evaluate for other contributing causes and treat accordingly
• Neurology consultation including fundoscopic exam to assess for papilloedema
• MRI of the brain with and without contrast (CT scan of the brain if MRI is not feasible). Further 
testing if indicated such as diagnostic lumbar puncture with measurement of opening pressure if 
increased intracranial pressure is suspected, or MRI of the spine if the subject has focal peripheral 
neurological deficits
• Institute levetiracetam therapy and consider EEG if seizure activity is suspected
• Consider anti‑IL‑6 therapy with tocilizumab 8 mg/kg1 IVor siltuximab 11 mg/kg IV, if Grade 1 
persists beyond 24 hours, or worsening and associated with concurrent CRS
2
• Supportive care and neurological work‑up as described for grade 1 ICANS
• Anti-IL-6 therapy if associated with concurrent CRS
• Consider Dexamethasone 10 mg IV every 6 h or methylprednisolone 1 mg/kg IV every 12 h if 
refractory to anti‑IL‑6 therapy, or for ICANS without concurrent CRS; once initiated continue 
corticosteroids until improvement to grade 1 ICANS and then taper
• Consider transferring patient to intensive-care unit (ICU) if ICANS associated with grade ≥2CRS
3
• Supportive care and neurological work‑up as indicated for grade 1 ICANS
• ICU transfer is recommended
• Anti‑IL‑6 therapy if associated with concurrent CRS if not administeredpreviously
• Corticosteroids as outlined for grade 2 ICANS if symptoms worsen despite anti‑IL‑6 therapy, or
for ICANS without concurrent CRS; continue corticosteroids until improvement to grade 1 ICANS
and then taper
• Stage 1 or 2 papilloedema with cerebrospinal fluid (CSF) opening pressure <20 mmHg should be 
treated corticosteroid regimen as per Grade 4 below.
• Consider repeat neuroimaging (CT or MRI) every 2–3 days if patient has persistent grade ≥3 ICANS
4
• Supportive care and neurological work‑up as indicated for grade 1 ICANS
• Consider neurosurgical consultation for patients with evidence ofincreased intracranial pressure
• ICU monitoring; consider mechanical ventilation for airway protection
• Anti‑IL‑6 therapy and repeat neuroimaging as described for grade 3 ICANS
• High-dose corticosteroids continued until improvement to grade 1 ICANS and then taper; for
example, methylprednisolone IV 1 g/day for 3 days, followed by rapid taper at 250 mg every 12 h for
2 days, 125 mg every 12 h for 2 days, and 60 mg every 12 h for 2 days
1 Maximum amount of tocilizumab per dose is 800 mg
Grade 1 ICANS. Grade 1 ICANS is defined as a score of 7-9 on the ICE assessment (Table 8). A patient 
with grade 1 ICANS may have a delay in responses or disorientation to time or place, mild inattention with 
difficulty in counting numbers backwards, or impairment of handwriting. There may be drowsiness, but 
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patients awaken spontaneously, and when prompted, the patient should be able to complete most of the ICE 
assessment. Grade 1 ICANS may be seen during CRS waxing and waning with febrile episodes.
Grade 2 ICANS. Grade 2 ICANS is defined as a score of 3-6 on the ICE assessment (Table 8).  
Expressive aphasia is the most specific first sign of severe neurotoxicity and early signs during grade 2 
include paraphasic errors (the production of unintended syllables and words during attempts to speak) and 
verbal perseveration with patients repeating the same words over and over. Patients with grade 2 ICANS are 
able to communicate their needs but it is effortful. Patients may have depressed level of consciousness but 
are arousable to voice and the responses may be slowed.
Grade 3 ICANS. Grade 3 ICANS is defined as a score of 0-2 on the ICE assessment (Table 8).  Patients 
with grade 3 ICANS have severe global aphasia and are not speaking or following commands even when 
wide awake and therefore may be unable to complete any of the ICE questions. Alternatively, they may 
have excessive drowsiness and need tactile stimulus to attend to examiner. Any clinical seizure whether 
simple partial, complex partial or generalized, and any electrographic seizures would also meet criteria for 
grade 3 ICANS (Table 12, Table 13). If neuroimaging shows new focal or local edema this would also be 
categorized as grade 3 ICANS (Table 12, Table 13). However, intracranial hemorrhage due to coagulopathy 
or other causes with or without associated edema is not considered a neurotoxicity feature and is excluded 
from ICANS grading.
Grade 4 ICANS.  Grade 4 ICANS is defined as patients who have a score of 0 on the ICE assessment 
(Table 8) due to being unarousable and unable to perform the ICE assessment.  Stupor and coma may be 
seen; the stuporous patient only responds by grimacing or drawing away from vigorous or repetitive tactile
stimuli and the comatose patient is unarousable and/or unresponsive. This depressed level of consciousness 
should be attributable to no other cause (e.g. no sedating medication), which is often a complicating factor 
in sick patients with CRS. Some patients may require intubation for airway protection. In addition, any 
patient having prolonged or repetitive clinical or subclinical electrographic seizures without return to 
baseline in between, or deep focal motor weakness such as hemiparesis or paraparesis would be considered 
to have Grade 4 ICANS. Patients with symptoms and signs of elevated ICP such as projectile vomiting with 
headache, depressed consciousness, cranial nerve VI palsies, papilledema, Cushing's triad of bradycardia, 
hypertension and respiratory depression, decerebrate or decorticate posturing, or diffuse cerebral edema on 
head imaging would also be considered to have grade 4 ICANS. 
Grade 5 ICANS. By convention, Grade 5 ICANS is defined as death due to ICANS where another cause is 
not the principle factor leading to this outcome.
8.9.2
Monitoring for Immune Effector Cell-Associated Neurotoxicity Syndrome 
(ICANS)
Brain MRI (or CT Scan if MRI not feasible) should be obtained in all subjects at the time of 
screening. Baseline brain MRI should be repeated if more than 4 months have elapsed prior 
to lymphodepletion.
ICE should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving
treatment and then at least through Day 8 according to the schedule of procedures. Subjects
with known brain metastases should be monitored at least twice per day for the first 5 days 
following NY-ESO-1c259T cell infusion. If a subject is found to haveICANS, the 
ICEshould be used at least twice per day until resolution or stable. It can also be used at 
later visits if indicated.
8.9.3
Grading of ICANS
[Lee, 2019] have developed a new grading system for ICAN which incorporates use of a 
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modified version of the CARTOX 10‑point neurological assessment termed Immune Effector 
Cell-Associated Encephalopathy(ICE) tool, see Table 12. Points are assigned for each of the
tasks in Table 12 which are performed correctly. Normal cognitive function is defined by 
an overall score of 10.
The ICE should be used to monitor all subjects for ICANS.  The ICE score is used in grading of ES as 
presented in Table 28.
Table 12:
Immune Effector Cell-Associated Encephalopathy (ICE) assessment 
tool
Task
ICE Points
Scoring: 10, no impairment; 7-9; grade 1 ICANS; 3-6, grade 2 ICANS; 0-2, grade 3 ICANS; 0 due to 
patient unarousable and unable to perform ICE assessment, grade 4 ICANS
The ICE score is used in grading of ICANS as presented in Table 13.
Table 13:
Grading of Immune Effector Cell-Associated Neurotoxicity Syndrome 
(ICANS)Encephalopathy Syndrome
Neurotoxicity 
Domain
Grade 1
Grade 2
Grade 3
Grade 4
ICE score
Depressed level of 
consiousness2
Elevated ICP/ 
cerebral edema
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Motor findings5
Seizure
ICANS= Immune Effector Cell-Associated Neurotoxicity Syndrome; ICE = Immune Effector Cell-Associated Encephalopathy; ICP = Intracranial Pressure; N/A = not 
applicable. 
1. See Table 12 for ICE.  A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but 
a patient with an ICE score of 0 may be classified as grade 4 ICANS if unarousable.
2. Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication)
3. Papilloedema grading is performed according to the modified Frisén scale.
4. Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from ICANS 
grading. 
5. Tremors and myoclonus associated with immune effector cell therapies do not influence ICANS grading.
This table is based on Lee, 2019.
8.9.4
Monitoring for ICANS
Brain MRI (or CT Scan if MRI not feasible) should be obtained for all participants at the time of 
screening.  Baseline brain MRI should be obtained within 4 weeks prior to lymphodepletion.
ICE should be measured on the day of NY-ESO-1c259T infusion prior to receiving treatment and then 
at least through Day 8 according to the schedule of procedures.  If a participant is found to have 
ICANS, the ICE should be used at least twice per day until resolution or stable.  It can also be used at 
later visits if indicated.
8.10
Management of Guillain-Barré Syndrome (GBS)
Please obtain a neurology consultation for all participants with signs or symptoms suggestive of GBS 
for thorough neurological evaluation, and for expert recommendations on further diagnostic workup 
including EMG, lumbar puncture, infectious panel to guide management and follow up.
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Case assessment for possible Guillain Barre Syndrome using diagnostic and prognostic tools 
supported by medical diagnosis and/or medical treatment
*Please refer to algorithm for treatment described in Figure 2.
8.10.1
Neurological Symptoms
The following features should be considered as suggestive of a GBS diagnosis in clinical practice and 
the use of the Brighton criteria [Fokke, 2014] together with further neurological evaluation will be the 
basis for confirmation of diagnosis:
Progressive weakness in legs and arms (sometimes initially only in legs)
•
Areflexia (or decreased tendon reflexes) in weak limbs
Additional symptoms
• 
Progressive weakness phase lasts 2 to 4 weeks (often 2 weeks)
• 
Relative symmetry of weakness
• 
Cranial nerve involvement, especially bilateral weakness of facial muscles
• 
Autonomic dysfunction
Peripheral 
neuropathy
Symptoms 
suggestive of 
GBS/AIDP
Treatment according 
to guidelines/clinical 
practice
GBS Diagnostic tool:
Brighton Criteria
At hospital admission
Indicator of prognosis
EGRIS tool
At hospital 
admission*
mEGOS tool
At hospital admission and Day 7
Yes
Confirmatory assessment 
targeted within 7 days from 
hospital admission
Suspected 
GBS
Strength of diagnosis includes 
clinical assessment and CSF and 
NCV measures. Some tests may not 
be available until several days after 
hospital admission.

Confirmed GBS required to 
implement mEGOS. 

At hospital admission (data 
that supports Brighton level 1 
or 2) may not be available. 

Level 1 or 2 assessment 
required before mEGOS 
assessment i.e. Day 7
Neurology 
consultation
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• 
Pain
8.10.2
Brighton Key Diagnostic Criteria
At admission and confirmation within 7 days of admission:
•
Bilateral and flaccid weakness of limbs
•
Decreased or absent deep tendon reflexes in weak limbs
•
Monophasic course and time between onset – nadir 12 hours to 28 days
•
CSF cell count < 50/µl
•
CSF protein concentration > normal value
•
Nerve conduction studies findings consistent with one of the subtypes of GBS
•
Absence of alternative diagnosis for weakness
8.10.3
Erasmus GBS Respiratory Insufficiency Score (EGRIS)
Probability of acute risk first week following hospital admission of respiratory insufficiency 
[Walgaard, 2010]. 
Parameters required at hospital admission:
•
Days between  onset of weakness and admission
•
Facial and/or bulbar weakness at admission
•
Medical Research Council sum score
8.10.4
Modified Erasmus GBS Outcomes Score (mEGOS)
Parameters required at hospital admission and 7 days later [Walgaard, 2011]: 
•
Age at onset
•
Preceding diarrhoea (in 4 weeks preceding onset of weakness)
•
Medical Research Council sum score
Summary of diagnosis and treatment for GBS
Additional information on the diagnosis and management of GBS (Figure 2) can be found in a review 
article on GBS [Willison, 2016].
8.10.5
Summary of diagnosis and treatment for GBS
Additional information on the diagnosis and management of GBS (Figure 2) can be found in a review 
article on GBS [Willison, 2016].
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Figure 2
Diagnosis and Treatment of Guillain-Barré Syndrome (GBS)
Abbreviations: EGRIS = Erasmus GBS Respiratory Insufficiency Score; GBS = Guillain-Barré Syndrome; 
ICU = intensive care unit; IVIg = intravenous immunoglobulin; TRF = treatment related fluctuation.
Source with permission: Willison, 2016.
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9
RECORDING ADVERSE EVENTS
Timely, accurate and complete reporting and analysis of safety information from clinical 
studies are crucial for the protection of subjects and is mandated by regulatory agencies 
worldwide. The Sponsor has established standard operating procedures in conformity with 
regulatory requirements worldwide to ensure appropriate reporting of all safety information; 
all clinical studies conducted by the Sponsor or its affiliates will be conducted in accordance 
with those procedures. The Investigator and their designees are responsible for detecting, 
documenting and reporting events that meet the definition of an AE or SAE. Individual AEs 
should be evaluated by the Investigator and should be reported to the Sponsor as appropriate. 
This includes the evaluation of its intensity, the causality between the investigational product 
and/or concomitant therapy and the AE and seriousness.
The Sponsor has to keep detailed records of all AEs reported by the Investigator(s) and to 
perform an evaluation with respect to causality, seriousness, and expectedness.
9.1 Time Period for Collecting AE and SAE Information
AEs and SAEs will be collected at the time points specified in the Schedule of Procedures 
(Table 4) and as described herein:

SAEs or AEs assessed as related to study participation (e.g., study intervention, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or 
leading to early withdrawal will be collected in the AE section of the CRF from the 
time a participant signs the informed consent form until leukapheresis.  All other 
relevant events that begin before the start of leukapheresis but after obtaining 
informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the case report form (CRF) not the AE section..

From leukapheresis until the lymphodepletion, all SAEs and other reportable safety 
events that could affect patient eligibility or study participation (e.g., protocol-
specified intervention, including but not limited to, wash-out or discontinuation of 
usual therapy, diet, or a procedure) will be collected.

All AEs and SAEs will be collected from the start of lymphodepleting chemotherapy until 
the end of the study. Refer to Section 9.4 for details on emerging clinical conditions that 
must be reported post-infusion.

All SAEs have to be reported to Sponsor within 24 h of Investigator learning about them.

All pregnancies and exposure during breastfeeding, from the start of chemotherapy 
(lymphodepletion regimen) through the contraception period (see Section 9.8) must be 
reported by the Investigator. 

Additionally, any SAE brought to the attention of an Investigator at any time outside of the 
time period specified above must be reported immediately to the Sponsor if the event is 
considered to be drug-related.

AEs and SAEs occurring after the participant rolls over to the LTFU study (GSK Study 208750) will be 
collected and reported in the LTFU protocol database.

During LTFU for subjects who do not enroll in the LTFU study, subjects will only
be monitored for those emerging clinical conditions defined in Section 9.4.
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9.2 Definition of Adverse Event
In accordance with the ICH, an AE is any untoward medical occurrence in a subject or 
clinical investigation subject who receives a pharmaceutical product, regardless of causality. 
An AE is therefore any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not considered related to the medicinal (investigational) 
product. Pre-existing conditions which worsen during the study are to be reported as AEs.
For guidance on reporting laboratory test abnormalities as AEs, refer to Section 9.10.
Adverse events or abnormal laboratory findings should be recorded in the eCRF using a 
diagnosis or possible diagnosis, and rated for intensity, causality and seriousness. In the 
absence of a diagnosis, individual symptoms or findings may be recorded and the eCRF 
updated to reflect a final diagnosis once additional information becomes available. If 
photographs are requested by the Sponsor (e.g. a rash AE), the subject will sign a Medical 
Photograph Release prior to any photographs being taken.
All AEs should be followed until:

Resolved or improved to baseline.

Investigator confirms no further improvement can be expected.

Death
On completion of the subject from the Interventional Phase of the study, or withdrawal from 
the study, serious or severe AEs will be followed until one of the above criteria is met. SAEs 
related to NY-ESO 1c259T will continue to be recorded and monitored into long-term follow-
up (refer to Section 9.4).
9.2.1
Assessment of Intensity
AEs will be graded according to the CTCAE v 4.0. The Investigator will assess intensity of 
all AEs using this five point scale (Grade 1-5) and record on the eCRF.
AEs not specifically listed on the CTCAE should be graded according to Table 14:
Table 14:
Grading of AEs Not Specified in CTCAE v4.0
CTCAE Grade
Equivalent to
Definition
Grade 1
Mild
Discomfort noticed but no disruption of normal daily activity
Grade 2
Moderate
Discomfort sufficient to reduce or affect daily activity; 
minimal medical intervention is indicated.
Grade 3
Severe
Incapacitating with inability to work or perform normal daily 
activity; treatment or medical intervention is indicated in 
order to improve the overall well-being or symptoms; 
delaying the onset of treatment is not putting the survival of 
the subject at direct risk.
Grade 4
Life threatening/ 
disabling
An immediate threat to life that requires urgent medical 
intervention
Grade 5
Death
AE resulting in death.
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9.2.2
Assessment of Causality
The Investigator will assess the causal relationship between the AE and NY-ESO-1c259T 
product according to his/her best clinical judgement. An assessment of 
possibly/probably/definitely related is meant to convey there is evidence of a causal 
relationship, not that a relationship cannot be ruled out. The Investigator should consider 
alternative causes such as natural history of the underlying disease, lymphodepleting 
chemotherapy, concomitant medications and other risk factors when making an assessment. 
The following scale will be used as guidance:

Not related – The subject did not receive the investigational product; the temporal 
sequence of the AE onset relative to administration of the investigational product is not 
reasonable; or there is another obvious cause of theAE.

Possibly related – There is evidence of exposure to the investigational product; the 
temporal sequence of the AE onset relative to T cell infusion is plausible; or the AE could 
have been due to another equally likely cause.

Probably related – There is evidence of exposure to the investigational product; the 
temporal sequence of the AE onset relative to T cell infusion is plausible; the AE shows a 
pattern consistent with previous knowledge of the investigational product; or the AE is 
more likely explained by the investigational product than any other cause.

Certainly related – There is evidence of exposure to the investigational product; the 
temporal sequence of the AE onset relative to T cell infusion is plausible; the AE shows a 
pattern consistent with previous knowledge of the investigational product, or the AE is 
most likely explained by the investigational product and any other cause is improbable.
The Investigator may change his/her opinion of causality if additional information is 
received, and amend the AE eCRF accordingly. The Investigator causality assessment is one 
of the criteria the Sponsor uses to determine regulatory reporting requirements for an SAE.
9.3 Reporting Serious Adverse Events (SAEs)
An SAE is any AE that:

Results in death (NOTE: death is the outcome, not theevent).

Is life-threatening (NOTE: the term “Life-threatening” refers to an event in which the 
subject was at immediate risk of death at the time of the event; it does not refer to an 
event which could hypothetically have caused a death had it been more severe).

Requires hospitalization or prolongation of existinghospitalization.

Results in persistent or significant disability.

Is a congenital anomaly/birth defect.

Is clinically significant or requires intervention to prevent one of the outcomes listed 
above.
Medical and scientific judgment should be exercised in deciding if an AE is of significant 
enough medical importance to be classified as serious outside the above definitions.
Important medical events are those that may not be immediately life threatening but are 
clearly of major clinical significance. They may jeopardize the subject and may require 
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intervention to prevent one of the other serious outcomes noted above. For example, drug 
overdose or abuse, a seizure that did not result in in-patient hospitalization or intensive 
treatment of bronchospasm in an emergency department would typically be considered 
serious. In this case event will be reported using the serious criteria of clinically significant or 
requires intervention.
Additional protocol-defined criteria

Any Grade ≥3 cytokine release syndrome or GVHD, and all cases of Guillain-Barré 
syndrome or acute demyelinating neuropathy must be reported as an SAE within 24 hours 
(Section 9.6).
The study will comply with all local regulatory requirements and adhere to the full 
requirements of the ICH Guideline for Clinical Safety Data Management, Definitions and 
Standards for Expedited Reporting, Topic E2.
All SAEs have to be reported to Sponsor within 24 h of Investigator learning about them.An 
SAE must be recorded by completing the SAE eCRF form within EDC systemIn addition, an
SAE Worksheet must be completed and submitted to GSK within 24 hours by e-mail to 
and
(or fax:
).
NOTE: The SAE eCRF within the EDC system is the primary method for reporting SAEs. 
The SAE Worksheet should only be used if the EDC system is unavailable.
The SAE eCRF must be completed by the Investigator with as much information as is 
available. The minimum reporting criteria include:

Identifiable subject (Subject ID)

Serious adverse event

Suspect investigational product

Identifiable reporting source (PI acknowledgment of the report and signature are 
required)

Relationship to investigational product.
The Investigator will assess the causal relationship between the SAE and investigational 
product according to his/her best clinical judgement. The Investigator will also assess the
causal relationship between the SAE and the lymphodepleting chemotherapy.
Please refer to the SPM for the back-up SAE Worksheet.
9.4 Reporting Criteria During Long-Term Follow-Up (Years 1 - 15)
Due to the nature of the treatment, subjects are required to be followed for up to 15 years 
after treatment with genetically modified T cells for observation of delayed AEs 
according to FDA and EMA guidance (FDA, 2006a; FDA, 2010; EMEA, 2009). Subjects
with delayed AEs will be followed until disease progression and then will continue to be 
monitored in the LTFU protocol. Emergence of any of the following new clinical 
conditions reported or observed and the action taken will be reported to the Sponsor:

New malignancies

New incidence or exacerbation of a pre-existing neurologicaldisorder
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
New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder

New incidence of an immune-related hematologic disorder

Serious infections (including opportunistic)

Unanticipated illness or hospitalization deemed related to gene modified cell therapy
A detailed description of the event should include the date of diagnosis and the nature of the 
diagnosis. If the diagnosis is cancer, record the type and stage of the cancer. If the cancer is 
metastatic, list the metastatic sites. If a new malignancy is recorded in a vector target cell 
type, tumor cells will be evaluated for vector sequences. If the tumor is positive for vector 
sequences or the surrogate sample is positive for vector sequences and is confirmed in 
accordance to this protocol, clonality analysis will be performed. If no evidence of oligo-or 
monoclonality is observed, a summary report of any and all analysis for the pattern of vector 
integration will be assembled, and submitted within the annual report of the Investigational 
New Drugs (INDs) listed on this protocol under which the subject(s) evaluated originally 
received their treatment. If evidence of oligo- or monoclonality is observed, an information
amendment will be submitted within 30 days to the INDs listed on this protocol under which 
the subject(s) evaluated originally received their treatment. Suspected unexpected serious 
adverse reactions (SUSARs) deemed related to the gene modified cells will be reported to the 
Regulatory Agencies and shared with Investigators as necessary in the form of Investigational 
new drug safety reports (INDSRs).
All the above listed AEs should be followed until:

Resolved or improved to baseline.

Investigator confirms no further improvement can beexpected.

Death.
9.5 Progression of Underlying Malignancy
Progression of underlying malignancy and related symptoms are not reported as an AE if it is 
clearly consistent with the suspected progression of the underlying cancer. Clinical 
symptoms of progression may be reported as AEs if the symptom cannot be determined as 
exclusively due to the progression of the underlying malignancy, or does not fit the expected 
pattern of progression for the disease under study.
If there is any uncertainty about an AE being due only to the disease under study, it should be 
reported as an AE or SAE.
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9.6 Regulatory Reporting Requirements for SAEs
The Sponsor has legal obligations for expedited reporting of certain events to Regulatory 
Authorities, IRBs/ Independent Ethics Committees (IEC) and other study participants. GSK 
will comply with all GCP and country specific regulatory requirements relating to safety 
reporting to the Regulatory Authorities, IRBs/IECs andInvestigators.
Investigator safety reports for SUSARs are prepared and distributed according to local 
regulatory requirements and GSK policy. These safety reports are forwarded to Investigators 
as necessary in the form of INDSRs.
An Investigator who receives an INDSR describing a SAE(s) or other specific safety 
information (e.g. summary or listing of SAEs) from GSK will file it with the IB and notify 
their IRB/IEC if appropriate, in accordance with localrequirements.
On request of a Competent Authority in whose territory the clinical trial is being conducted, 
the Sponsor will submit detailed records of all AEs which are reported to him by the relevant 
Investigator(s).
9.7 Cardiovascular and Death Events
For any cardiovascular events detailed below and all deaths, whether or not they are 
considered SAEs, specific Cardiovascular (CV) and Death sections of the CRF will be 
required to be completed. These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovasculardeath.
The CV CRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary of Regulatory Activites (MedDRA) terms. The CV information should be
recorded in the specific cardiovascular section of the CRF within one week of receipt of a CV 
Event data query prompting its completion.
The Death CRF is provided immediately after the occurrence or outcome of death is reported. 
Initial and follow-up reports regarding death must be completed within one week of when the 
death is reported.
Definition of Cardiovascular Events
Cardiovascular Events (CV) Definition:
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs:

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization
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9.8 Pregnancy
There is no pre-clinical or clinical trial data of NY-ESO-1c256T in pregnant women; however, 
there is a reasonable but unproven likelihood that this intervention may be significantly 
embryotoxic or even an abortifacient given the underlying biology of the target. The effects 
on breast milk are unknown; therefore, breastfeeding should be discontinued for the duration 
of the study starting at the first dose of chemotherapy and for at least 12 months after 
receiving the investigational product, or 4 months after there is no evidence of 
persistence/gene modified cells in the subject’s blood, whichever is longer.
Pregnancy (or pregnancy of a male subject’s partner) is not considered an AE/SAE unless 
there is reason to believe that the pregnancy may be the result of failure of the contraceptive 
being used due to interaction with the investigational product. However, the Investigator 
shall report all pregnancies immediately to the Sponsor. A woman who becomes pregnant 
and remains pregnant during the study will be discontinued from the Interventional Phase as 
exposure to radiation from imaging studies would be contraindicated in this setting. The 
subject would be rolled over to the LTFU protocol. The outcome of the pregnancy must also 
be reported to the Sponsor. The contraception guidelines in the inclusion criteria of the 
parent protocol should continue to be followed duringLTFU.
If a pregnancy is reported, the Investigator should inform GSK within 24 hours of learning of 
the pregnancy.
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9.9 Pre-existing Condition
A pre-existing condition is one that is present at the start of the study during Screening. A 
pre-existing condition should be recorded as an AE if the frequency, intensity, or the 
character of the condition worsens during the InterventionalPhase.
9.10  Laboratory Test Abnormalities as Adverse Events
Out-of-range laboratory test results meeting the following criteria should be reported as AEs.

Any CTCAE laboratory value Grade ≥3 should be recorded as an AE. Grade 1 and 2 
laboratory abnormalities do not require reporting unless the Investigator considers the 
event is clinically significant.

Any Grade 4 CTCAE laboratory value based solely on numerical criteria (e.g. white 
blood cells decreased) should be reviewed to determine whether it should be reported as a 
SAE.
9.11  Timelines for Safety Reporting
Initial Reports
Follow-up Information on a Previous
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours
SAE data collection
tool
24 hours
Updated SAE data
collection tool
“CV events” and/or 
“death”
Initial and follow 
up reports to be 
completedwithin 
one week of 
when the 
cardiovascular 
event or deathis
reported
“CV events” and/or 
“death” data 
collection tool(s) if 
applicable
Initial and follow up 
reports to be 
completed within 
one week of when 
the cardiovascular 
event or death is 
reported
Updated “CV events” 
and/or “death” data 
collection tool(s) if 
applicable
Pregnancy
24 Hours
Pregnancy
Notification Form
2 Weeks
Pregnancy
Followup- Form
10 SAFETY MONITORING
10.1  Safety Review Team
A SRT will be implemented in this study. In line with routine pharmacovigilance, a GSK 
SRT will review blinded safety data, including clinical laboratory parameters and AEs, at 
appropriate intervals during the period of study conduct. Recommendations on study 
modification, halting the study and/or pausing enrollment will be provided by the SRT. A 
SRT charter, defining roles and accountabilities and the process for safety review and 
meeting frequency, will be available.
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10.2  Mandated Study Pause Due to GBS
The occurrence of any event of GBS will mandate a pause in enrollment and stopping 
treatment for all participant within the GSK3377794studies.  The case must be diagnosed 
by a neurologist as GBS according to diagnostic guidance for GBS [Fokke, 2014].
10.3  Monitoring and Management of Replication-Competent Lentivirus (RCL)
Replication competent lentivirus (RCL) is a theoretical risk associated with the use of 
lentiviral vectors; no RCL has ever been detected in vitro or in vivo. The risk is derived from 
the detection of replication competent retrovirus (RCR) during the use of early γ retroviral 
vector packaging systems which were inadequately designed to avoid recombination events 
between the vector and packaging components (Miller, 1990). Updated γ retroviral 
packaging systems have not been associated with RCR. However in a study with Rhesus 
monkeys, three out of 10 animal died of lymphomas at around 6 months after transplantation 
of vector transduced bone marrow cells contaminated with replication-competent virus 
(Donahue, 1992). Therefore, RCR/L must continue to be rigorously evaluated in vector and 
cell lots, and in subjects post infusion with any product involving a retrovirus (FDA, 2006a; 
FDA, 2006b; FDA, 2010; EMEA, 2009).
A RCL may be generated during the production phase or subsequently after introduction of 
vector transduced cells into the subject. RCL may be generated between homologous or non-
homologous recombination between the transfer vector and packaging elements, or 
endogenous retroviral elements (Chong, 1998; Garrett, 2000). A RCL resulting from the 
production phase of the lentivirus used in this trial is highly unlikely since elements are 
incorporated in the design of the vector system that minimize vector recombination and 
generation of RCL. Nevertheless, generation of a RCL by recombination with an 
endogenous virus (i.e., HIV) in the subject following infusion of the vector product remains a 
theoretical possibility. The consequences of such recombination events could be neutral, 
could reduce the replication rate or pathogenicity of the subject's virus, or could increase the 
replication rate or pathogenicity of the subject's virus. Since the development of a strain with 
increased pathogenicity would pose greater risk to both the subject and their close contact(s), 
periodic monitoring for RCL is conducted during the course of the trial and during the 15 
year follow up.
Regulatory Agencies and the gene therapy community have previously discussed measures to 
be taken should an RCL be confirmed in a subject (FDA, 2006a; FDA, 2006b; EMEA, 2009). 
However, because the probability and characteristics of an RCL are unknown, no concrete 
plans have been put in place. As of the writing of this protocol, it is agreed that the subject 
must be isolated and no additional subjects treated with NY-ESO-1c259T cells until an action 
plan is agreed upon as outlined in Section 10.5.
The following approaches have been discussed for subject management:

Provide targeted antiretroviral therapies based on genotyping of theRCL.

Intensive follow up of subject in consultation with FDA, and other Regulatory 
Authorities, National Institute of Health, gene therapy experts, study Investigators, and 
HIV physicians.
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10.4  Testing for RCL in Clinical Studies
RCL will be monitored using a PCR-based assay that detects and measures copies of the gene 
coding for the vector’s envelope protein, namely Vesicular Stomatitis Virus G protein (VSV-
G) that is necessary for the assembly of pseudotyped infectious lentiviral particles but absent 
from the vector’s backbone. RCL testing and monitoring will take place on:

The cell product, whereby RCL testing will be performed by or under the direction of the 
manufacturing facility responsible for manufacturing and release of the vector.

Subject PBMCs will be collected prior to infusion of transduced T cells and then at 3, 6, 
and 12 months post treatment. If these tests are negative at all time points during the first 
year, PBMC samples will be collected annually until assessments for persistence have 
discontinued (Section 10.7) or until Year 15, whichever comes first. Samples will be 
archived at GSK’s centralized biorepository.

If VSV-G DNA copies are detected at any time point in the first year post-infusion, the 
safety monitoring protocol (Section 10.5) will be triggered. Subject samples will 
continue to be tested for VSV-G DNA copies until VSV-G DNA copies are not detected 
for 3 consecutive annual assessments, then subject samples will be collected annually
until year 15 and archived at GSK’s centralized biomarker repository or until assessments 
for persistence have discontinued (Section 10.7).
10.5  Safety Monitoring Results
If a positive VSV G DNA signal is obtained, the Investigator will be informed and the subject 
scheduled for a retest as soon as possible and no later than one month after the initial positive 
result was reported to the Sponsor. A review by the Sponsor will take place.
If the second test is positive, infusions for all subjects receiving cells modified with the same 
vector lot will be postponed. The subject with the confirmed positive VSV G signal will be 
scheduled for leukapheresis and a biological RCL performed on the leukapheresis product. 
The biological RCL test assesses whether there is active production of infectious viral 
particles from the leukapheresis product (Manilla, 2005).
If the biological RCL is positive, all NY-ESO-1c259T cell infusions will be halted. An action 
plan will be discussed with FDA and other Regulatory Authorities and experts as appropriate. 
Additional subjects will not be treated until such time as a plan is agreed upon, completed, 
and reviewed.
10.6  Persistence Testing and Monitoring for Insertional Oncogenesis
Monitoring for insertional oncogenesis follows the recommendations set forth in the FDA 
and EMA guidance’s (FDA, 2006a; FDA, 2006b; EMEA, 2009). Insertional oncogenesis is a 
theoretical risk in T cells transduced with a lentiviral vector. T cells appear resistant to 
transformation by integrating viruses (Cattoglio, 2010; Newrzela, 2008). However, there are 
cases of oncogenesis with γ-retroviral transduced stem cells. Four of nine subjects with X-
linked severe combined immunodeficiency (SCID-X1) treated with retrovirus transduced 
stem cells were found to have insertion near the LMO2 proto-oncogene promoter, leading to 
aberrant transcription and expression of LMO2 which resulted in acute T-cell lymphoblastic 
leukemia (Hacein-Bey-Abina, 2003; Hacien-Bey-Abina, 2014). Additionally, two subjects
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treated for X-linked chronic granulomatous disease (X-CGD) with retroviral transduced stem 
cells demonstrated insertional activation of the EVI1 transcription factor which resulted in 
genetic instability, monosomy 7 and clonal progression toward myelodysplasia (Stein, 2010).
10.7  Testing for Persistence of Gene Marked Cells in Clinical Studies
Peripheral blood mononuclear cell samples will be collected and used as the “surrogate 
sample” for monitoring persistence of gene modified cells in subjects prior to infusion of 
transduced T cells and at 3, 6 and 12 months post-infusion, then every 6 months until 5 years 
post-infusion and every year from year 6 to 15 post infusion in accordance with the FDA and 
EMA guidance’s (FDA, 2006a; FDA, 2006b; EMEA, 2009). The samples will be tested 
using a PCR-based method to detect the presence of the Psi gene, which is part of the 
lentiviral vector used to transduce T cells. Detection of Psi DNA copies reflects persistence 
of the genetically modified T cells. If at 1 year or beyond post-infusion greater than 1% 
PBMCs test positive for the vector sequence, the subject’s PBMCs will be evaluated for 
integration site analysis (see Section 10.8). If no gene modified cells are detected for three 
consecutive assessments post-infusion, and the subject is ≥5 years post-infusion (for example, 
negative persistence assessments at year 4, 4.5 and 5), no further monitoring of PBMCs is 
required and collection of samples for persistence may be discontinued. All other laboratory 
assessments such as RCL, hematology and chemistry may also be discontinued. Subject will 
continue to be followed by the Investigator by phone call or survey for up to 15 years post-
infusion. The Investigator will be the primary physician responsible for continued follow up 
of the subject for the duration of LTFU, whenever possible. If contact with the Investigator 
becomes no longer feasible, follow up can be transitioned to a local physician, preferably an 
oncologist.
10.8  Testing for Insertional Oncogenesis
If persistence, as detected by the presence of a vector sequence (Psi DNA copies), is present 
in >1% of PBMC at 1 year or beyond post-infusion, DNA from the subject’s PBMCs will be 
sent for sequencing for integration site analysis. Integration site analysis assesses clonality
and the possibility of insertional oncogenesis. This integration site analysis method, used in 
previous clinical trials (Hacein-Bay, 2015), uses sonic length quantitation, an accurate
method of measuring relative clonal abundance (Berry, 2012).
If there is clonal dominance in the genetically modified T cell population (either 
monoclonality or oligoclonality) the persistence assessment will be repeated within 3 months 
on a new sample. If the repeated analysis demonstrates: 1) persistent monoclonality, 2) 
evidence of insertional oncogenesis or 3) clonal expansion (an increase in percent 
predominance of a clone), there will be a review by the Sponsor to develop a monitoring plan 
specific to the health care risk, and strategies to inform appropriate subjects, investigators, 
FDA, and other regulators of the findings.
If the integration site analysis indicates polyclonality of the genetically modified T cell 
population, then screening will continue as scheduled.
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10.9  Monitoring and management for Demyelinating Neuropathy and other 
Neurological events
Obtain a neurological consultation for participants with Grade 2 or higher neurologic events 
of a ≥ 7 day duration. Participants who develop signs and symptoms consistent with GBS 
must be evaluated by a neurologist to provide expert recommendations to guide appropriate 
diagnostic workup such as EMG, lumbar puncture, infectious panel to guide management and 
follow up.
11.
STATISTICAL AND DATA ANALYSIS
The objectives and endpoints for this study are described in Section 2. Section 11 focuses on 
key aspects for the analysis and reporting of the primary and secondary efficacy and safety 
endpoints. Details for the analysis of all endpoints including subgroups, sensitivity analyses 
and missing value imputations, such as censoring, where applicable, will be provided in the 
Reporting and Analysis Plan (RAP).
11.1
Study Populations
Intent-to-Treat (ITT) population: all participants who were enrolled in the trial and met 
all eligibility criteria.The ITT population is the primary population for the safety of the
end-to-end autologous T cell therapy procedure.
Modified Intent-to-Treat (mITT) population: all subjects in the ITT population who 
receive at least one NY-ESO-1c259T cell infusion.
If the mITT and ITT populations are identical, only analyses associated to the ITT population 
will be reported.
Detailed criteria for inclusion in these populations will be prospectively specified in the RAP. 
Further exploratory analysis populations may be defined according to the correlative studies.
11.2
Sample Size Calculations
Ten (10) subjects are planned for treatment with NY-ESO 1c259 T. The sample size in this 
study has been based on clinical judgement. This is a small pilot study to describe the safety 
and tolerability where efficacy endpoints are secondary and will be summarized using 
estimation methods such as exact 95% confidence intervals. The study is not powered to 
conduct statistical hypothesis testing.
11.3
Interim Analyses
No formal statistical interim analyses for efficacy or futility are planned for this study.
11.4
Statistical Methods for Safety Endpoints
Safety endpoints will be summarized by time periods as described in Section 9.1. Descriptive 
statistics will be provided for selected demographic, safety, imaging, and cytokine 
assessments by dose and time as appropriate. Descriptive statistics on continuous data will 
include means, medians, standard deviations, and ranges, while categorical data will be 
summarized using frequency counts and percentages. Graphical summaries of the data may 
be presented.
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The safety profile will be based on AEs reported, vital signs measurements, clinical 
laboratory measurements, ECG recordings, and physical examination results. AEs associated 
with the first or the second infusion will be reportedseparately.
Adverse Events – All AEs will be listed and coded by MedDRA. The number and percent of 
subjects reporting any AEs will be tabulated by system organ class and preferred term and 
categorized by dose. AEs will be further classified by severity, relationship to treatment, and 
seriousness in tabulation. Tables and/or narratives of any on-study death, or serious or 
significant AEs, including early withdrawals because of AEs, will be provided should they 
occur.
Vital Signs – Vital signs will be listed and reviewed for each subject. Depending on the size 
and the scope of changes, summaries of vital signs data over time and/or changes from day 1 
pre-dose value over time may be provided.
Electrocardiogram – Electrocardiogram data will be listed and reviewed for each subject. 
Fridericia’s and Bazett’s correction will be used to adjust QT for RR. Summaries of ECG 
intervals and/or the change from Baseline will be provided. Baseline ECG parameters will be 
based on the mean of the Screening and pre-dose ECG assessments.
Anti-NY-ESO-1c259TAntibodies–Thesubjectincidenceofanti-NY-ESO-1c259Tantibody 
formation will be computed and the anti- NY-ESO-1c259T antibody results will be listed.
T cell Phenotype and Cytokines–The results will be listed.
Clinical Laboratory Tests– Clinical chemistry, hematology, and urinalysis data will be listed 
for each subject. Values outside the normal laboratory reference ranges will be flagged as 
high or low on the listings. Laboratory abnormalities will be graded using CTCAE version 4. 
Each subject’s maximum post-Baseline grade will be computed for each laboratory parameter 
and referred to as their worst grade for that laboratory parameter. For each parameter shift 
tables from Baseline to worst grade may be presented.
11.5
Statistical Methods for Efficacy Endpoints
To determine the effect of the treatment of NY-ESO-1c259T cell infusion on tumor response 
and progression, summaries of efficacy will be based ORR; best overall response; time to and 
duration of response; duration of stable disease; PFS; and OS. Details will be described in 
the RAP.
The primary efficacy endpoint is ORR defined as the proportion of subjects with a confirmed 
CR or PR per RECIST v1.1 relative to the total number of subjects in the corresponding 
analysis population. The ORR will be based on confirmed responses from the Investigator 
assessment of overall response. The 95% exact confidence intervals (CI) for ORR will be 
calculated.
Key Secondary Analyses - The duration of response based on RECIST v1.1 will be 
summarized descriptively for subjects for each cohort using Kaplan-Meier Product Limit 
methods for quartile estimates. Duration of response is defined, for the subset of subjects 
with a confirmed CR or PR, as the time from first documented evidence of CR or PR until 
first documented disease progression or death due to anycause.
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Disease Control Rate (DCR), defined as the percentage of participants with a confirmed SD 
or better as the BOR (i.e., PR, CR, or SD ≥12 weeks), as assessed by the investigator per 
RECIST 1.1 Criteria.
In addition, PFS, defined as the interval between the date of T-cell infusion day and the 
earliest date of disease progression or death due to any cause, and PFS will be summarized 
using Kaplan-Meier Product Limit Method for quartile estimates if data warrant.
Further details about the efficacy analyses for these and other secondary endpoints, such as, 
how missing values will be handled and rules for censoring, will be provided in the statistical 
analysis plan.
12.
CLINICAL SUPPLIES
12.1
Packaging and Labelling
Selected, qualified manufacturing sites will manufacture, package and label cell product for 
each individual subject in accordance with applicable regulatory requirements.
Labels will include batch number, protocol number, number of transduced cells, the subject’s 
unique study identification number and any other applicablerequirements.
12.2
Standard Policies and Product Return
Investigational product must be received by a designated person at the site, handled and 
stored safely and properly, and kept in a secure location to which only the Investigator and 
designated assistants have access. Investigational product is to be dispensed only in 
accordance with the protocol. The Investigator is responsible for keeping accurate records of 
the investigational product received from the Sponsor, the amount dispensed to and any 
unused investigational product at the conclusion of the study. Contact the Sponsor or 
designee regarding any questions concerning the investigational product.
Sites should contact the Sponsor or designee for specific instructions for investigational 
product returns or destruction and appropriate documentation for drug accountability.
12.3
Storage and Handling
The subject’s T cell product received at the site from the manufacturer will be stored below
—135°C until being ordered by the Investigator (or designee) to be infused. The cells will be 
thawed and infused as specified in Section 5.3.
12.4
Product Accountability
The investigational product provided for this study is for use only as directed in the protocol. 
It is the Investigator/Institution’s responsibility to establish a system for handling the 
investigational product to ensure:

Deliveries of the investigational product are correctly received by a responsible person

Such deliveries are recorded

Investigational product is handled and stored safely and properly as stated on the label

Investigational product is only dispensed to study subjects in accordance with the 
protocol
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
Any unused product is accounted for in the site’s records before returning to the Sponsor 
(or designee)
At the end of the study, it must be possible to reconcile delivery records with records of usage 
and destroyed stock. Records of usage should include the identification of the person to 
whom the investigational product was dispensed, the quantity, and date of dispensing. This 
record is in addition to any investigational product accountability information recorded on the 
eCRF. Any discrepancies must be accounted for on the appropriate forms.
13.
DATA HANDLING AND RECORD KEEPING
13.1
Data Management
An EDC system will be used to collect data pertaining to this trial. Trial data will be 
captured through an eCRF. Within the EDC system the eCRF data will be entered by the site 
staff and all source document verification and data cleaning will be performed by the Sponsor 
or designee [e.g. Contract Research Organization (CRO)].
The specifications for the EDC system will be documented and approved before the EDC 
system is released for live use. The validation of the eCRF data will be defined in a Data 
Management Plan. As data are entered into the eCRF, the validation checks will be 
performed and where necessary, queries will be raised. All queries raised will be held in the 
EDC database.
The EDC system is a validated software program that has been designed to comply with 
CFR21 Part 11 requirements. All users will access the system using their user name and 
password. A full audit history of all actions performed within the system is maintained. User 
accounts ensure that each user can only perform the tasks applicable to their role and only 
have access to the data applicable to their role.
Standard coding dictionaries, WHO Drug and MedDRA will be used to code medications and 
AEs.
When all data have been entered and all data cleaning is complete the data will be locked and 
made available for analysis and reporting.
On completion of the study, all eCRF data, including all associated queries and audit history, 
will be made available in PDF format to both the Sponsor and the sites.
13.2
Case Report Forms
For each subject enrolled, the completed eCRF must be reviewed and signed by the Principal 
Investigator or authorized delegate. If a subject withdraws from the study, the reason must be 
noted on the eCRF.
The Investigator should ensure the accuracy, completeness, legibility, and timeliness of the 
data reported to the Sponsor in the eCRFs and in all required reports.
13.3
Source Documents and Background Data
The Investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified. These 
documents are classified into two different categories: (1) Investigator Site File (ISF) and (2) 
subject specific source documents.
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The Investigator is responsible for maintaining a complete and accurate ISF containing 
essential documents as required by ICH GCP.
Source documents contain the results of original observations and activities of a clinical 
investigation. Source documents include but are not limited to subject medical 
records/progress notes, appointment book, original laboratory reports, ECG printouts, 
CT/MRI scans, pathology and special assessment reports, signed informed consents. In no 
case is the eCRF to be considered as source data for this trial.
The Investigator must ensure the availability of source documents from which the 
information on the eCRF was derived.
The Investigator must permit authorized representatives of the Sponsor, the respective 
national, local or foreign Regulatory Authorities, the IRB/IEC and auditors to inspect 
facilities and to have direct access to the ISF and all source documents relevant to this study 
regardless of the type of media.
13.4
Data Retention and Availability
The Investigator must keep all essential study documents including source data on file for at 
least 25 years after completion or discontinuation of the Study. After that period of time the 
documents may be destroyed, subject to localregulations.
The Investigator will not dispose of any records relevant to this study without written 
permission from the Sponsor. If the Investigator cannot guarantee the archiving requirement 
at the investigational site for any or all of the documents, such study records may be 
transferred upon request to the Sponsor or its designee.
Should the Investigator wish to assign the study records to another party or move them to 
another location, the Sponsor must be notified in writing in advance.
Study documentation is subject to inspection by the Sponsor, its representatives and 
Regulatory Agencies and must be stored in such a way that it can be accessed/retrieved 
within a reasonable timeframe at a later date.
14. STUDY MONITORING
Study Monitoring will be completed by the Sponsor or designated CRO.
It is understood the responsible monitor will contact and visit the Investigator regularly and 
will be allowed, on request, to inspect the various records of the trial (e.g., eCRFs ISF, and 
source documents) provided that subject confidentiality is maintained in accordance with 
local requirements.
It will be the monitor’s responsibility to inspect the eCRFs at regular intervals throughout the 
study, to verify the adherence to the protocol and the completeness, consistency and accuracy 
of the data being entered. The monitor should have direct access to subject source documents 
to verify the entries on the eCRF. The Investigator (or designee) agrees to cooperate with the 
monitor to ensure that any discrepancies detected areresolved.
14.1
Audit and Inspections
The Sponsor or its representatives may conduct audits at investigative sites including, but not 
limited to, facilities where the study is being conducted, investigational product handling and
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accountability, presence of required documents, the informed consent process and 
comparison of eCRFs with source documents.
All study documentation including source data must be available for audit.
The Investigator agrees to cooperate fully with audits conducted at a convenient time in a 
reasonable manner.
Regulatory Agencies may also inspect investigative sites during or after the study. The 
Investigator (or designee) should contact the Sponsor immediately if this occurs, and provide 
copies of correspondence relating to requests for an inspection of the site facilities.
15.
REGULATORY AND ETHICAL CONSIDERATIONS
15.1
Competent Authority Submissions
GSK or its authorized representatives will be responsible for ensuring that appropriate 
Competent Authority approvals are obtained according to local country requirements. 
Competent Authority approval (or notification as applicable) will be obtained before 
initiation of the study.
15.2
Independent Ethics Committees
The final study protocol and subject informed consent documentation will be approved by the 
IRB/IEC and any other site level committee deemed appropriate by the Institution. Approval 
from each applicable committee will be received in writing before initiation of the study.
Protocol amendments must also be approved by the IRB/IEC (and other committees as 
applicable) before implementation, except in the case of changes made to protect subjects 
from immediate hazard, which will be implementedimmediately.
15.3
Local Regulations/ Declaration of Helsinki
The Investigator will ensure this study is conducted in full compliance with the principals of 
the “Declaration of Helsinki” or with the laws and regulations of the country in which the 
research is conducted, whichever, affords the greater protections to the subject. The study 
must fully adhere to the principles outlined in “Guideline for Good Clinical practice” ICH 
Tripartite Guideline (January 1997) or with local law if it affords greater protection to the 
subject.
15.4
Informed Consent
It is the responsibility of the Investigator to obtain written informed consent from all study 
subjects prior to any study related procedures being performed. All consent documentation 
must be in accordance with applicable regulations and ICH GCP. Documentation must 
include the dated signature of both the subject (or the subject’s parents or legally authorized 
representative as applicable) and the person conducting the consent discussion. If the subject 
is illiterate, an impartial witness should be present during the consent discussion, and the 
consent signed and dated by the witness, the subject, and the person conducting the consent 
discussion. The consent form should be translated and communicated to the subject in a 
language that is understandable to the subject. Certified translations of the informed consent 
documentation will be provided as applicable.
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A copy of the signed and dated informed consent should be provided to the subject before 
participation in the study.
Tests performed as standard of care prior to documentation of consent may be used for 
screening results as appropriate.
15.5
Confidentiality
The confidentiality of records that may identify subjects will be protected in accordance with 
applicable laws, regulation and guidelines.
The Investigator must ensure that each subject’s anonymity is maintained and protected from 
unauthorized parties. On the eCRFs or other documents submitted to the Sponsor, subjects 
must not be identified by their names, but by a unique identification code allocated to them to 
ensure confidentiality on all study documentation. Subjects will retain this unique number 
throughout the study.
The Investigator will keep a subject enrollment log showing subject unique identification 
codes, names and addresses in the ISF.
The Sponsor and/or its representatives accessing subject records and data at site will take all 
reasonable precautions to maintain subject confidentiality.
15.6
Protocol Adherence
The Investigator must sign the protocol to confirm acceptance and willingness to comply 
with the study protocol.
The Investigator or designee will not deviate from the protocol unless necessary to eliminate 
an apparent immediate hazard to the safety, rights or welfare of any study subject. In the 
event of a protocol deviation for any reason, the Investigator will promptly report the 
deviation to the Sponsor in writing.
15.7
Completion of the Study and Study Termination
The Sponsor may suspend or terminate the study at any time for any reason. If the study is 
suspended or terminated, the Sponsor will ensure applicable sites, Regulatory Agencies and 
IRBs/IECs are notified as appropriate.
If the Investigator stops/terminates the study at their site the Sponsor must be notified. The 
Sponsor will ensure Regulatory Agencies and IRBs/IECs are notified as appropriate.
The Sponsor will ensure End of Study declarations are made to the relevant Regulatory
Agencies/IECs in accordance with local regulations.
15.8
Public Posting of Study Information
The Sponsor is responsible for posting appropriate study information on applicable clinical 
study registry websites. Information included in clinical study registries may include 
participating Investigator’s names and contact information.
15.9
Clinical Study Report
The results of the study will be presented in an integrated Clinical Study Report (CSR) 
according to ICH guideline E3: Structure and Content of Clinical Study Reports.
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15.10
Publication Policy
The Investigator may not submit the results of the study for publication or present the results 
of the study without the prior written agreement of the Sponsor in accordance with the 
Clinical Trial Agreement. The results of this study will be published as a whole once all 
subjects have completed the study and the study results have been analyzed. Interim 
publications of data from the study may be made if mutually agreed between the Sponsor and 
the Investigators. Agreement will not be provided by the Sponsor where in the Sponsor’s 
view interim publications would introduce bias or lead to any misrepresentation or 
inaccuracies in data.
Authorship will be determined in conformance with the International Committee of Medical 
Journal Editors (ICMJE) guidelines and/or publication guidelines if applicable.
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16.
APPENDICES
APPENDIX 1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
The following abbreviations and specialist terms are used in this study protocol.
Abbreviations and Specialist Terms
ACT 
AE 
ALK 
ALT 
ANC 
ASCO 
AST 
ATG 
CAR
cfDNA 
CMV 
CNS 
CR 
CRO 
CRS 
CSF 
CT 
CTCAE 
CV 
DCR 
DLCO 
DNA 
DSUR 
EBV 
ECG 
ECHO 
ECOG 
eCRF 
EDC 
EDTA 
EEG 
EGFR 
EMA 
EMG 
FDA
FDG-PET
FEV1
Adoptive T cell Therapy 
Adverse Event
Anaplastic lymphoma kinase receptor 
Alanine amintransferase
Absolute neutrophil count
American Society of Clinical Oncology 
Aspartate aminotransferase 
Antithymocyte globulin
Chimeric antigen receptor
Cell-free DNA
Cytomegalovirus 
Central nervous system 
Complete response
Contract Research Organization 
Cytokine release syndrome 
Cerebrospinal fluid
Computerized tomography
CommonTerminologyCriteriaforAdverseEvents 
Cardiovascular
Disease Control Rate
Diffusingcapacityofthe lungs for carbon monoxide 
Deoxyribonucleic acid
Developmental Safety Update Report 
Epstein-Barr virus
Electrocardiogram 
Echocardiogram
Eastern Cooperative Oncology Group 
Electronic Case Report Form 
Electronic Data Capture 
Ethylenediamineteraacetic acid 
Electroencephalogram
Epidermal growth factor receptor 
European Medicines Agency 
Electromyography 
Food and Drug Administration
18-fluorodeoxyglucose positron emission tomography 
Forced expiratory volume in 1 second
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FSH 
FVC 
GBS 
GCP 
G-CSF 
GFR 
GGTP 
GVHD
HBcAb 
HBsAg 
HBV 
HCV 
HIV 
HLA 
HRT 
HTLV
ICE
ICF 
ICH 
ICMJE 
ICU 
IEC 
IFN
IL
IND 
INDSR 
IO
irRC 
irRECIST 
IND
INR 
IRB 
ISF 
IV
LAGE-1a 
LFT 
LTFU
MedDRA 
MHC 
MRI 
MUGA 
NCI
NE 
NSCLC 
NYHA
Follicle-stimulating hormone 
Forced vital capacity 
Guillain-Barré Syndrome 
Good Clinical Practice
Granulocyte-colony stimulating factor 
Glomerular filtration rate
Gamma glutamyl transpeptidase 
Graft-Versus-Host Disease 
Hepatitis B core antibody 
Hepatitis B surface antigen 
Hepatitis B virus
Hepatitis C virus
Human immunodeficiency virus 
Human leukocyte antigen 
Hormone replacement therapy 
Human lymphotropic virus 
Immune Effector Cell-associated Encephalopathy
Informed Consent Form
International Conference on Harmonization 
InternationalCommitteeofMedicalJournalEditors 
Intensive care unit
Independent Ethics Committee 
Interferon
Interleukin 
Investigational New Drug
InvestigationalNewDrugSafetyReport 
Insertional oncogenesis
Immune-related Response Criteria
Immune-relatedResponseEvaluationCriteriainSolidTumors 
Investigational new drug
International normalized ratio 
Institutional Review Board 
Investigator Site File 
Intravenous
L antigen family member-1a 
Liver function test
Long-term follow-up
MedicalDictionaryofRegulatoryActivities 
Major histocompatibility complex 
Magnetic resonance imaging
Multigated acquisition scan 
National Cancer Institute 
Not evaluable
Non-small cell lung cancer 
New York Heart Association
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OS
ORR 
PBMC 
PCR 
PD 
PFS 
PR 
QTcB 
QTcF 
RAP 
RCL 
RCR
RECIST 
RNA 
SAE 
SCT 
SD
SIN 
SPM 
SUSAR 
TCR 
TGF 
TIL 
TLC 
TNF 
ULN 
US 
VSV-G 
WBC
WOCBP
Overall survival
Overall response rate
Peripheral blood mononuclear cell 
Polymerase chain reaction 
Progressive disease
Progression-free survival 
Partial response
QT interval corrected according to Bazett’s formula
QTintervalcorrectedaccordingtoFridericia’sformula 
Reporting and Analysis Plan
Replication competent lentivirus 
Replication competent retrovirus
ResponseEvaluationCriteriainSolidTumors 
Ribonucleic acid
Serious adverse event 
Stem cell transplant 
Stable Disease
Self-inactivating
Study Procedures Manual
Suspectedunexpectedseriousadversereactions 
T cell receptor
Tumor growth factor
Tumor-infiltrating lymphocyte
Tranferfactorof the lung forcorbon monoxide 
Tumor necrosis factor
Upper limits of normal 
Ultrasound
Vesicular stomatitis virus G protein 
White blood cell
Woman of child-bearing potential
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APPENDIX 2. ECOG PERFORMANCE STATUS
Grade
ECOG
Source: (Oken, 1982)
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APPENDIX 3. LOCAL LABORATORY TESTS AND ECG PARAMETERS
Clinical Chemistry:
Calcium 
Phosphorus 
Magnesium 
Albumin 
Bilirubin
Alanine aminotransferase 
Aspartate aminotransferase 
Alkaline phosphatase 
Lactic acid dehydrogenase 
Sodium
Potassium 
Bicarbonate 
Creatinine* 
Chloride 
Glucose 
Urea
* In subjects <65 years of age creatinine clearance will be calculated 
using the Cockcroft-Gault Method:
*Subjects ≥65 years of age must have renal function measured either by 
24-hour urine creatinine collection or by nuclear medicine EDTA GFR 
measurement, according to standard practice at the treating institution.
Coagulation Screen:
Prothrombin time or International Normalized Ratio 
Activated partial tissue thromboplastin time
ECG Parameters:
Heart Rate 
Heart Rhythm 
PR Interval 
RR Interval 
QRS Interval
QTc Interval (Fridericia’s or Bazett’s correction)
Hematology:
Red cell count 
Hemoglobin 
Hematocrit
Mean cell volume
Mean corpuscular hemoglobin
Mean corpuscular hemoglobin concentration 
Platelet count
White blood cell count & differential count (percent & 
absolute)
Lymphocyte subset
Absolute cell count and percentage of CD3, CD4, and CD8
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Pregnancy Test:
Serum beta-HCG or Urine test
Thyroid Function Tests:
TSH with reflex free T4
Urinalysis:
Glucose 
Ketones 
Specific gravity 
Protein
Blood 
Microscopy 
Bilirubin
pH
Infectious disease markers:
HIV 1+2 antibody
Hepatitis B core antibody – if positive, test for HBV DNA 
Hepatitis C antibody – if positive, test for HCV RNA 
HTLV 1+2 IgG
CMV IgG / DNA PCR
Epstein-Barr virus (EBV) (EBNA)
Syphilis (spirochaete bacterium) rapid plasma regain
Other Tests:
Uric Acid
C-reactive protein
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APPENDIX 4. RECIST 1.1 CRITERIA FOR EVALUATING RESPONSE IN SOLID 
TUMORS
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. CT is the best currently
available and reproducible method to measure lesions selected for response assessment. MRI 
is also acceptable in certain situations (e.g., for body scans but not for lung). Ultrasound (US) 
should not be used to measure tumor lesions. The same modality should be used when 
comparing or making efficacy assessments.
Lesions on a chest X-ray may be considered measurable lesions if they are clearly defined 
and surrounded by aerated lung. However, CT is preferable. Clinical lesions will only be 
considered measurable when they are superficial and ≥10 mm in diameter as assessed using 
calipers. For the case of skin lesions, documentation by color photography, including a ruler 
to estimate the size of the lesion, is recommended.
Tumor markers alone cannot be used to assess response. If markers are initially above the 
upper normal limit, they must normalize for a subject to be considered in complete response.
Cytology and histology can be used in rare cases (e.g., for evaluation of residual masses to 
differentiate between Partial Response and Complete Response or evaluation of new or 
enlarging effusions to differentiate between Progressive Disease and Response/Stable 
Disease).
Use of endoscopy and laparoscopy is not advised. However, they can be used to confirm 
complete pathological response.
All baseline evaluations should be performed as closely as possible to the beginning of 
treatment and never more than 4 weeks before the beginning of the treatment.
Measurable lesions
Must be accurately measured in at least one dimension (longest diameter in the plane of 
measurement is to be recorded) with a minimum sizeof:

10 mm by CT scan (CT scan slice thickness no greater than 5 mm; when CT scans have 
slice thickness >5 mm, the minimum size should be twice the slice thickness).

10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded asnon-measurable).

20 mm by chest X-ray.
Measurable lesions

Malignant lymph nodes to be considered pathologically enlarged and measurable, a 
lymph node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice 
thickness is recommended to be no greater than 5 mm). At baseline and in follow-up, 
only the short axis will be measured andfollowed.

Lytic bone lesions or mixed lytic-blastic lesions with identifiable soft tissue 
components that can be evaluated by cross-sectional imaging techniques such as CT or 
MRI can be considered measurable if the soft tissue component meets the definition of 
measurability described above.
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
‘Cystic lesions’ thought to represent cystic metastases can be considered measurable if 
they meet the definition of measurability described above. However, if non-cystic lesions 
are present in the same subject, these are preferred for selection as target lesions.
Non-measurable lesions
Non-measurable lesions are all other lesions, including small lesions (longest diameter <10 
mm or pathological lymph nodes with 10 to <15 mm short axis), as well as truly non-
measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic 
involvement of skin or lung, abdominal masses/abdominal organomegaly identified by 
physical exam that is not measurable by reproducible imaging techniques.

Blastic bone lesions are non-measurable.

Lesions with prior local treatment, such as those situated in a previously irradiated area 
or in an area subjected to other loco-regional therapy, are usually not considered 
measurable unless there has been demonstrated progression in the lesion. Study protocols 
should detail the conditions under which such lesions would be considered measurable.
Target Lesions

All measurable lesions up to a maximum of two lesions per organ and five lesions in 
total, representative of all involved organs, should be identified as target lesions and 
recorded and measured at baseline.

Target lesions should be selected on the basis of their size (lesions with the longest 
diameter) and be representative of all involved organs, as well as their suitability for 
reproducible repeated measurements.

All measurements should be recorded in metric notation using calipers if clinically 
assessed. A sum of the diameters (longest for non-nodal lesions, short axis for nodal 
lesions) for all target lesions will be calculated and reported as the baseline sum 
diameters, which will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease. If lymph nodes are to be included 
in the sum, only the short axis will contribute.
Non-target Lesions
All lesions (or sites of disease) not identified as target lesions, including pathological lymph 
nodes and all non-measurable lesions, should be identified as non-target lesions and be 
recorded at baseline. Measurements of these lesions are not required and they should be 
followed as ‘present’, ‘absent’ or in rare cases, ‘unequivocal progression’.
Evaluation of Target Lesions
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) must have reduction in short axis to <10 mm
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target 
lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is
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the smallest on study). In addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more 
new lesions is also considered progressions) Note: determination of PD will not be made 
prior to the Week 8 evaluation.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
Evaluation of Non-Target Lesions
Complete Response (CR): Disappearance of all non-target lesions and normalization of 
tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis)
NOTE: If tumor markers are initially above the upper normal limit, they must normalize for 
a subject to be considered in complete clinicalresponse.
Non-CR/Non-PD (Stable Disease, SD): Persistence of one or more non-target lesion(s) 
and/or maintenance of tumor marker level above the normal limits.
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions. Unequivocal progression should not normally 
trump target lesion status. It must be representative of overall disease status change, not a 
single lesion increase.
Special notes on the assessment of target lesions

Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded even if the nodes regress to below 10 mm on study. When lymph 
nodes are included as target lesions, the ‘sum’ of lesions may not be zero even if 
complete response criteria are met since a normal lymph node is defined as having a short 
axis of <10 mm.

Target lesions that become ‘too small to measure’. While on study, all lesions (nodal 
and non-nodal) recorded at baseline should have their actual measurements recorded at 
each subsequent evaluation, even when very small. However, sometimes lesions or lymph 
nodes become so faint on a CT scan that the radiologist may not feel comfortable 
assigning an exact measure and may report them as being ‘too small to measure’, in 
which case a default value of 5 mm should be assigned. Lesions that split or coalesce on 
treatment. When non-nodal lesions ‘fragment’, the longest diameters of the fragmented 
portions should be added together to calculate the target lesion sum. Similarly, as lesions 
coalesce, a plane between them may be maintained that would aid in obtaining maximal 
diameter measurements of each individual lesion. If the lesions have truly coalesced such 
that they are no longer separable, the vector of the longest diameter in this instance should 
be the maximal longest diameter for the ‘coalescedlesion’.
Special notes on the assessment of non-target lesions

When subject has measurable disease. To achieve ‘unequivocal progression’ on the 
basis of the non-target disease, there must be an overall level of substantial worsening in 
non-target disease such that, even in presence of SD or PR in target disease, the overall
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tumor burden has increased sufficiently to merit discontinuation of therapy. A modest 
‘increase’ in the size of one or more non-target lesions is usually not sufficient to qualify 
for unequivocal progression status.

When subject has only non-measurable disease. There is no measurable disease 
assessment to factor into the interpretation of an increase in non-measurable disease 
burden. Because worsening in non-target disease cannot be easily quantified, a useful test 
that can be applied is to consider if the increase in overall disease burden based on change 
in non-measurable disease is comparable in magnitude to the increase that would be 
required to declare PD for measurable disease. Examples include an increase in a pleural 
effusion from ‘trace’ to ‘large’ or an increase in lymphangitic disease from localized to 
widespread.
New lesions
The appearance of new malignant lesions denotes disease progression:

The finding of a new lesion should be unequivocal (i.e., not attributable to differences in 
scanning technique, change in imaging modality or findings thought to represent 
something other than tumor, especially when the subject’s baseline lesions show partial or 
complete response).

If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm 
there is definitely a new lesion, then progression should be declared using the date of the 
initial scan.

A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and diseaseprogression.
It is sometimes reasonable to incorporate the use of 18-fluorodeoxyglucose positron emission 
tomography (FDG-PET) scanning to complement CT in assessment of progression 
(particularly possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be 
identified according to the following algorithm:
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up - is PD based on a 
new lesion.
No FDG-PET at baseline and a positive FDG-PET at follow-up:

If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by 
CT, this is PD.

If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan).

If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT 
that is not progressing on the basis of the anatomic images, this is not PD.
Summary of the overall response status calculation at each time point:
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Target Lesions
Non-Target 
Lesions
New Lesions
Overall 
Response
Best Overall Response when 
Confirmation is Required*
CR
CR
No
CR
>4 wks. Confirmation**
CR
Non-CR 
Non-PD
No
PR
>4 wks. Confirmation**
CR
Not evaluated
No
PR
PR
Non-CR 
Non-PD
Not evaluated
No
PR
SD
Non-CR 
Non-PD
Not evaluated
No
SD
Documented at least once >4 
wks. from baseline**
PD
Any
Yes or No
PD
No prior SD, PR or CR
Any
PD***
Yes or No
PD
Any
Any
Yes
PD
*See RECIST 1.1 manuscript for further details on what is evidence of a new lesion.
**Only for non-randomized trials with response as primary endpoint.
***In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression
Confirmation
In non-randomized trials where response is the primary endpoint, confirmation of PR and CR 
is required to ensure responses identified are not the result of measurement error. This will 
also permit appropriate interpretation of results in the context of historical data where 
response has traditionally required confirmation in suchtrials.
In the case of SD, measurements must have met the SD criteria at least once after study entry 
at a minimum interval (in general not less than 6–8 weeks) that is defined in the study 
protocol.
Missing Assessments and Inevaluable Designation
When no imaging/measurement is done at all at a particular time point, the subject is not 
evaluable (NE) at that time point. If only a subset of lesion measurements are made at an 
assessment, usually the case is also considered NE at that time point, unless a convincing
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argument can be made that the contribution of the individual missing lesion(s) would not 
change the assigned time point response. This would most likely happen in the case of PD.
https://www.eortc.be/Recist/documents/RECISTGuidelines.pdf
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APPENDIX 5. SCHEDULE OF PROCEDURES FOR SECOND T CELL INFUSION (INTERVENTIONAL PHASE 2)
Table 15
:
Schedule of Procedures for Second T Cell Infusion (Interventional Phase2)
Baseline1
Interventional 
Phase 2
Completion/
Withdrawal5
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell 
Infusion
Day (D) / 
Week (W)
-28 D4 of
Chemo-
therapy
D
-8
D
-7
D
-6
D
-5
D1
D2
D3
D4
D5
D8
W 
2
W 
4
W 
8
W 
12
W 
16
W 
20
W 
24
Every 3 
Mos 
Until Yr 
2.
Every 6 Mos 
Thereafte r
Visit Window
n/a
n/a
n/a
n/a
n/a
±1 
day
±3 days
±7 days
±14 
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
14
17
19
20
21
22
23-28
29+
Clinical Assessments and Procedures6 (refer to Section 7.4 for details)
Informed Consent7
X
Inclusion/ 
Exclusion
X8
Medical History9
X
Physical Exam
X
X
X
X
Prior/Concomi-
tant Medications10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs / 
Height/ Weight11
X
X12
X
X
X
X
X
X
X
ECG
X
X
X
X
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Baseline1
Interventiona
l Phase 2
Completion/
Withdrawal5
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
-28 D4 of
Chemo-
therapy
D
-8
D
-7
D
-6
D
-5
D1
D2
D3
D4
D5
D8
W 
2
W 
4
W 
8
W 
12
W 
16
W 
20
W 
24
Every 3 
Mos Until 
Yr 2.
Every 6 Mos 
Thereafte r
Visit Window
n/a
n/a
n/a
n/a
n/a
±1 day
±3 days
±7 days
±14 days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
14
17
19
20
21
22
23-28
29+
ECHO/MUGA
X
CT / MRI 13
X
X
X
X
X
X
X
Brain MRI
X
See footnote 27
ICE29
                                                                                                     See footnote 28
Chest X-ray
X
PFTs14
X
Lymphocyte 
subset 
(CD3/CD4/CD8)
X
Hematology
X4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation Tests
X4
Pregnancy Test15
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X4
Infectious disease 
markers16
X
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Baseline1
Interventional Phase 2
Completion/ 
Withdrawal5
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) / 
Week (W)
-28 D4 of
Chemo-
therapy
D
-8
D
-7
D
-6
D
-5
D1
D2
D3
D4
D5
D8
W 
2
W 
4
W 
8
W 
12
W 
16
W 
20
W 
24
Every 3 
Mos 
Until 
Yr 2.
Every 6 
Mos 
Thereaft
er
Visit Window
n/a
n/a
n/a
n/a
n/a
±1 day
±3 
days
±7 days
±14 
days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
14
17
19
20
21
22
23-28
29+
CMV IgG and 
PCR17
X
X
X
X
X
X
TSH with free 
T418
X
CRP19
X
X
X
X
X
X
Uric acid
X
X
GFR or 24h 
urine20
X
Adverse Events21
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vector Copies 
(Persistence for 
Safety)22
X
X
X22
X22
VSV-G DNA 
(RCL)23
X
X
X
X23
X23
ICE24
See footnote 24
Lymphodepleting Chemotherapy2 & Investigational Product Administration
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Baseline1
Interventional 
Phase 2
Completion/ 
Withdrawal5
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell Infusion
Day (D) 
/ Week 
(W)
-28 D4 of
Chemo-
therapy
D
-8
D
-7
D
-6
D
-5
D1
D2
D3
D4
D5
D8
W 
2
W 
4
W 
8
W 
12
W 
16
W 
20
W 
24
Every 3 
Mos Until 
Yr 2.
Every 6 
Mos 
Therea
fter
Visit Window
n/a
n/a
n/a
n/a
n/a
±1 day
±3
days
±7 
days
±14 days
±3 
mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
14
17
19
20
21
22
23-28
29+
Fludarabine
X
X
X
X
Cyclophos
- phamide
X
X
X
NY-ESO-1c259T
X
Correlative Studies and Research Assessments (refer to Section 7.5 for details)
Tumor biopsy25
X25a
X
X
Liquid 
biopsy25
X
X
X
X
X
X
X
Cell 
phenotype and 
Functional 
Assays,
X
X
X
X
X
X
X
X
Cytokine 
Analyses1
9
& Humoral 
Anti- Infused 
Cell Responses
X26
X
X
X
X
X
X
X
X26
X
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Baseline1
Interventio
nal Phase 2
Completion/ 
Withdra
wal5
Lymphodepleting 
Chemotherapy2
T-cell 
in-
fusion3
Post-T-cell 
Infusion
Day (D) / 
Week (W)
-28 D4 of
Chemo-
therapy
D
-8
D
-7
D
-6
D
-5
D1
D2
D3
D4
D5
D8
W
2
W 
4
W 
8
W 
12
W 
16
W 
20
W 
24
Every 3 Mos 
Until Yr 2.
Every 6 
Mos 
Thereafter
Visit Window
n/a
n/a
n/a
n/a
n/a
±1 day
±3 days
±7 days
±14 days
±3 mos
n/a
Visit
1
2
3
4
5
6
7
8
9
10
11
12
14
17
19
20
21
22
23-28
29+
Vector Copies 
(Persistence) for 
Research
X1
X
X
X
X
X
X
X
X
X
X
Subjects must have been considered eligible for a second infusion (refer to Section 4.4) before initiating any screening procedures or assessments for Interventional Phase 2. 
Refer to Section 5.2 for details on prophylaxis therapies, pre-medications, fludarabine dose adjustments according to renal function, and supportive treatments.
All samples will be collected and assessments performed prior to T-cell infusion, unless otherwise specified.
Clinical procedures or assessments do not need to be repeated at this Baseline visit if they were be performed within 28 days of planned leukapheresis, with the exception of lymphocyte subset 
(CD3/CD4/CD8), hematology, chemistry, coagulation and urinalysis which must be done within 7 days of leukapheresis.
If a subject withdraws consent or completes the Interventional Phase 2, all procedures and assessments listed at this visit must be performed, unless done within the previous 30 days. 
All clinical assessments and procedures must be performed as indicated; however, any clinical assessment or procedure can be performed if clinically indicated at any time.
An additional written subject informed consent for a second infusion must be obtained prior to performing any Baseline assessments or procedures, unless otherwise specified. 
Subjects must continue to meet all eligibility criteria (Section 4.2 and Section 4.3) in addition to meeting those prior to second infusion specified in Section 4.4).
Any new or changes in medical history will be recorded in the EDC at Baseline visit; however, any additional changes in medical history must be recorded in source documents throughout the 
conduct of the study.
Includes all prescription, over-the-counter medications, and herbal remedies. Any use of mutagenic agents or investigational agents must also be reported. 
Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen saturation. Height will be collected at the Screening visit only.
Abbreviations: CMV = cytomegalovirus; CRP = C-reactive protein; CRS = cytokine release syndrome; CT = computed tomography; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern 
Cooperative Oncology Group; FPCP = female patient of childbearing potential; MRI = magnetic resonance imaging; n/a=not applicable; PCR = polymerase chain reaction; PFT = pulmonary function test; RCL
= replication competent lentivirus; TSH = thyroid-stimulating hormone; VSV-G =vesicular stomatitis virus G protein
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12. Vital signs on day of T cell infusion should be taken pre-infusion, and at 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started.
13. If a subject is found to have a tumor response or PD by imaging, a follow-up confirmation scan must be done no earlier than 4 weeks following the scan when response or PD first seen. A subject is 
not considered to have a response or PD until follow-up scan confirms the finding.
14. Includes FEV1, FVC, TLC, and DLCO parameters to determine eligibility as described in Exclusion criterion #10.
15. FPCP must have a negative urine or serum pregnancy test.
16. Includes HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochaete bacterium). Refer to Exclusion criterion #12 for details on required testing for eligibility.
17. Only subjects who are CMV IgG seropositive at baseline will continue to be monitored for CMV viremia by CMV DNA PCR post baseline.
18. A free T4 test should be performed in subjects who have an abnormal TSH function test (high or low).
19. If CRS is suspected, cytokine and C-reactive protein levels should be measured approximately every other day until symptoms are improving or an alternative diagnosis is confirmed.
20. Only to be done in subjects ≥65 years of age to measure renal function.
21. Adverse events should be reported as noted in Section 9.
22. Persistence of gene modified cells in subjects will be monitored at Months 3, 6, and 12 post-infusion, then every 6 months until 5 years post-infusion and annually from year 6-15 post infusion. If no 
gene modified cells are detected for 3 consecutive assessments post-infusion, and subject is >5 years post-infusion, then sample collection may stop.
23. If RCL tests are negative at all time points during the first year, then samples will be collected annually and archived for up to 15 years post or until assessments for persistence have ended  However, 
if VSV-G DNA copies are detected at any time point in the first year post-infusion, refer to the safety monitoring proceduresin Section 10.5.
24. Immune Effector Cell-Associated Encephalopathy (ICE) should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving treatment and then at least through Day 8 according to the 
schedule of procedures. Subjects with know brain metastases should be monitored at least twice per day for the first 5 days following NY-ESO-1c259T cell infusion. If a subject is found to have 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), the ICE neurological assessment tool, should be used at least twice per day until resolution or stable. It can also be used at later 
visits if indicated  .
25.  Core needle biopsies are at baseline, week 8, and at confirmation of PD, with the exception of subjects for whom there is no safely accessible tumor tissue.  24a.) If a fresh biopsy was taken to 
confirm continued expression of NY-ESO-1 and/or LAGE-1a at the time of PD after the first T cell infusion and there is sufficient tumor sample left remaining, this sample may be used as the 
baseline sample. Otherwise, the baseline biopsy should be collected anytime two weeks prior to the start of lymphodepleting chemotherapy, with preference closer to the time of infusion. 24b.) 
Exosome/cfDNA samples should match tumor biopsy timepoints.
26. Pre-infusion and Week 8 blood collection is for both Cytokine and Humoral anti-infused cell responses, and is collected in one 3 ml tube.
27. Brain MRI will be performed at baseline for all participants and as clinically indicated thereafter (see Section 8.9.2).
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APPENDIX 6. LIST OF REFERENCES
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15. Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following 
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23. Fidler C, Klumpp T, Mangan K, et al. Spontaneous graft versus host disease 
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26. Garrett E, Miller AR, Goldman JM, Apperley JF, Melo JV. Characterization of 
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with clinical-pathological features. Coll Antropol. 2008; 32(3), 731-736.
29. Gure AO, Chua R, Williamson B, et al. Cancer-testis genes are coordinately 
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30. Hacein-Bey Abina S, Gaspar HB, Blondeau J, et al. Outcomes following gene 
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2015; 313: 1550-1563.
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proliferation in two patients after gene therapy for SCID-X1. Science. 2003;302: 415-
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32. Hacien-Bey-Abina S, Pai S, Gaspar HB, et al. A modified γ-retrovirus vector for X-
Linked severe combined immunodeficiency. N Engl J Med. 2014;371:1407-1417.
33. Johnson DH, Schiller JH, Bunn PA, Jr. Recent clinical advances in lung cancer 
management. Journal of clinical oncology. 2014. 32(10): 973-982.
34. Johnson LA, Morgan RA, Dudley ME, etal. Gene therapy with human and mouse T-
cell receptors mediates cancer regression and targets normal tissues expressing 
cognate antigen. Blood. 2009;114(3)
35. Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of 
synthetic biology. Immunity. 2013;39(1): 49-60.
36. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical 
practice guideline from the AABB. Ann Intern Med. 2015; 162(3):205-213.
37. Klebanoff CA, Rosenberg SA, Restifo NP. Prospects for gene-engineered T cell 
immunotherapy for solid cancers. Nature Med.2016;22(1):26-36.
38. Kline J, Subbiah S, et al. Autologous graft-versus-host disease: harnessing anti-tumor 
immunitythroughimpairedself-tolerance. BoneMarrow Transplant.2008;41:505-13.
39. Lee DW, Gardner R. Current concepts in the diagnosis and management of cytokine 
release syndrome. Blood. 2014;124(2), 188-195.
40. Lee DW, Santomasso BD, Locke FL,  ASTCT Consensus Grading for Cytokine 
Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.  
Biology of Blood and Marrow Transplantation.  2019;25:625-38.
41. Manilla P, Rebello T, Afable C, et al. Regulatory Considerations for Novel Gene 
Therapy Products: A Review of the Process Leading to the First Clinical Lentiviral
Vector. Human Gene Therapy. 2005; 16:17–25.
42. Marincola FM, Jaffee EM, et al. Escape of human solid tumors from T-cell 
recognition: molecular mechanisms andfunctionalsignificance. Advances in 
Immunology. 2000;74:181-273.
43. Maruggi G, Porcellini S, Facchini G, et al. Transcriptional enhancers induce 
insertional gene deregulation independently from the vector type and design. 
Molecular therapy: the journal of the American Society of Gene Therapy, 2009;17(5): 
851-856.
44. Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome 
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associated with novel T cell-engaging therapies. Cancer J. 2014;20(2): 119-122.
45. Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take 
the front seat for hematologic malignancies. Blood. 2014;123(17): 2625-2635.
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47. Modlich U, Navarro S, Zychlinski D, et al.. Insertional transformation of 
hematopoieticcells byself-inactivatinglentiviraland gammaretroviral vectors. 
Molecular therapy: the journal of the American Society of Gene Therapy. 
2009;17(11): 1919-1928.
48. Montini E, Cesana D, Schmidt M, et al. The genotoxic potential of retroviral vectors 
is strongly modulated by vector design and integration site selection in a mouse model 
of HSC gene therapy. Journal Clin Investigation. 2009;119(4): 964-975.
49. Montini E, Cesana D, Schmidt M, et al. Hematopoietic stem cell gene transfer in a 
tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. 
Nature biotechnology. 2006;24(6): 687-696.
50. Morgan RA, Yang JC, Kitano M, et al. Case report of a serious adverse event 
following the administration of T cells transduced with a chimeric antigen receptor 
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51. National Cancer Institute website (http://www.cancer.gov).
52. Neelapu, S. S., et al. (2018). "Chimeric antigen receptor T-cell therapy-
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53. Newrzela S, Cornils K, Li Z. Resistance of mature T cells to oncogene 
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Eastern Cooperative Oncology Group. Am J Clin Oncol, 1982;5(6): 649-655.
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APPENDIX 7. PROTOCOL CHANGES
Amendment 01 Changes
The original Protocol dated, 08 June 2015, was replaced by Amendment No. 01, Protocol, 
dated 08 August 2016. This amendment applied to all participating investigative sites.
The following protocol changes were implemented by Adaptimmune as a result of emerging 
data from Adaptimmune’s clinical development program as well as comments received by 
the participating investigative sites and Regulatory Authorities.
Additionally, protocol changes were made to align with Adaptimmune’s standard protocol 
language. Due to these revisions, the section numbering changed. The previous section 
number has been noted in the table below.
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Table 16
Summary of and Rationale for Protocol Changes
Section of Protocol
Changes
Rationale for Changes
Title and Clinical Study 
Protocol pages
Changed from Phase I/II to Pilot
Added Eudra Number
To better reflect the aim of the trial which is to test a drug or treatment in a 
small group of people in a new indication (NSCLC) for the first time to 
evaluate its safety and identify side effects.
To reflect study participation in EU countries
Investigator Signature and 
Sponsor Signature/ 
Information Pages 
(previously Section 16 in
original protocol)
Moved to two separate pages after the title 
page
To adhere to Adaptimmune’s recently developed standard protocol template
Synopsis
Revised to reflect changes made throughout
protocol as described herein
To ensure consistency with protocol following amendment
Section 1 Background and Study Rationale (previously Section 2 in original protocol)
Section 1.2: Background to 
Adoptive T Cell Therapy 
(previously Section 2.1 in
original protocol)
Text was deleted and reference to NY-ESO-
1c259T Investigator Brochure added
To minimize information provided in the MAGE-A10c796T Investigator 
Brochure.
Section 2.3 through Section
2.7 in original protocol
Sections deleted
To minimize information provided in the MAGE-A10c796T Investigator
Brochure.
Section 1.3: Adoptive 
Immunotherapy with NY-
ESO-1 Specific T Cells and 
Supporting Data in NSCLC 
and Section 1.4 Rationale 
for NY-ESO-1c259T for 
NSCLC (previously Section
2.8 in original protocol)
Section headings split (from 2.8 to 1.3 and 
1.4)
Added expression rates for LAGE-1a in 
NSCLC
To adhere to Adaptimmune’s recently developed standard protocol template
LAGE-1a and NY-ESO-1 share the same peptide sequence that is displayed in 
HLA*02:01 on the surface of tumor cells; therefore, subjects will be screened 
for LAGE-1a in addition to NY-ESO-1 in the Screening Protocol (ADP-0000-
001) to determine eligibility for this study. To provide information on LAGE1a 
in this this patient population, the expression rates in various histology was
added.
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Section 1.4.1: Optimization 
of Lymphodepleting 
Chemotherapy Regimen (not 
previously part of original
protocol)
Section added to provide rationale for 
change in lymphodepleting chemotherapy 
regimen
Based on emerging data from CAR-T cell clinical studies and Adaptimmune’s 
ongoing clinical program, the lymphodepleting chemotherapy regimen was 
changed from cyclophosphamide alone to cyclophosphamide plus fludarabine. 
Data indicates that the addition of fludarabine to cyclophosphamide may play a
role in homeostatic expansion.
Section 2: Trial Objectives and Endpoints (previously Section 3 in original protocol)
Primary endpoint
Added anti-NY-ESO-1c259T antibodies, 
persistence, and circulating cytokines as
safety endpoints
To better characterize the comprehensive safety evaluation to be performed for 
this study. Previously these were listed as separate secondary objectives of the
study.
Secondary objective: To 
evaluate the efficacy of NY-
ESO-1c259T
Removed text defining secondary efficacy 
endpoints;
Deleted clinical benefit rate and added 
overall best response as secondary efficacy 
endpoint
Text was removed to minimize information provided in the Statistical Analysis 
Plan and Section 11.5 of the protocol
To more clearly define an evaluation of tumor response by using the standard 
overall best response as assessed by RECIST 1.1.
Secondary and Exploratory 
objectives/endpoints
Revised text around correlative science 
objectives and re-classified them as 
exploratory objectives
To better characterize the correlative studies and research assessments to be 
performed in this study.
To properly denote objectives as exploratory and to ensure alignment with
Adaptimmune’s recently developed standard protocol template.
Section 3: Investigational Plan (previously Section 4 in original protocol)
Section 3.1 Overall Study 
Design (previously Section 4 
and Section 4.2 in original 
protocol)
Added text providing guidance on patient 
management in terms of hospitalization
Removed language around HLA and 
antigen testing as screening tests for this 
study and added text to denote that HLA 
and antigen testing will have been 
conducted in the Screening Protocol (ADP-
0000-001).
To ensure the safety of subjects, language was added noting that hospitalization 
for lymphodepleting chemotherapy is at the discretion of the Investigator; 
however, inpatient hospitalization was recommended for T cell infusion to 
allow for close monitoring.
To ensure subjects will have completed testing for HLA subtype and antigen 
expression in the context of the Screening Protocol and that HLA and antigen 
expression satisfies the requirements of this protocol before undergoing written 
informed consent and screening procedures associated with this study.
Additional revisions to language was made to adhere to Adaptimmune’s
recently developed standard protocol template.
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Section 3.2.1: Screening for 
HLA and NY-ESO-1 (ADP-
0000-001) (previously 
Section 2.9 in original
protocol)
Revised language in accordance with 
protocol template
To adhere to Adaptimmune’s recently developed standard protocol template.
Section 3.2.2: T Cell 
Manufacturing (previously 
Section 2.6 in original 
protocol)
Revised text to concisely and at a high-level
describe the T cell manufacturing process 
Text was revised around the timing of when 
manufactured T cells would be shipped to 
the sites
To minimize information provided in the NY-ESO-1c259T Investigator Brochure 
and to adhere to Adaptimmune’s recently developed standard protocol template. 
To acknowledge that the manufacturer will now ship the T cell product after the 
14-day (not 7-day) sterility testing is complete and the release specification 
acceptance criterion is confirmed to have been met. Therefore, T cells will 
arrive approximately 28 days after leukapheresis instead of 21-28 days.
Furthermore, to accommodate ex-US sites which may not have sufficient 
storage facility for the T cell product, shipment will occur immediately before
the scheduled infusion and may be stored in the cryoshipper.
Section 3.2.3: 
Lymphodepletion 
(previously Section 4.1.1. in 
original protocol)
Revised text to provide rationale for change 
in lymphodepleting chemotherapy regimen
Based on emerging data from CAR-T cell clinical studies and Adaptimmune’s 
ongoing clinical program, the lymphodepleting chemotherapy regimen was 
changed from cyclophosphamide alone to cyclophosphamide plus fludarabine. 
Data indicates that the addition of fludarabine to cyclophosphamide may play a
role in homeostatic expansion.
Section 3.2.4.: T Cell 
Infusion (previously Section
6.2 in original protocol)
Moved section to be part of Rationale for 
Components of Study Design
To adhere to Adaptimmune’s recently developed standard protocol template.
Section 3.2.5.: Rationale for 
NY-ESO-1c259T Cell Dose
(previously Section 4.1.2. in 
original protocol)
Updated text to include cell dose ranges 
from current NY-ESO-1c259T cell ongoing 
studies
To provide current information from our ongoing clinical program which 
continue to provide support for the cell dose ranges being explored in this 
study.
Section 4.1.3 and Section
4.1.4 in original protocol
Sections deleted
To remove repetitive language around tumor assessment criteria (RECIST v1.1)
and Correlative studies which is covered elsewhere in the protocol
Section 3.3.: Number of 
Subjects and Duration of 
Study (previouslySection
4.4 in original protocol)
Added estimation of study enrolment and 
study completion
To provide context around the duration of the study in terms of enrolment and 
completion
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Section 3.4 Sites (previously
Section 4.5 in original 
protocol)
Increased number of sites 15 and noted 
region as North America and Europe
To reflect an increase in the number of sites globally needed to recruit this 
patient population
Section 3.5: Benefit: Risk 
Assessment (not previously
part of original protocol)
Section added
Based on pre-clinical and clinical studies of NY-ESO-1c259T, this section 
provides the potential benefits and risks of NY-ESO-1c259T and the mitigation
strategy for this study
Section 4.: Selection of Study Population, Withdrawal, Completion and Stopping Criteria (previously Section 5 in original protocol)
Section 4.1 Overview 
(previously Section 5.1 in
original protocol
Deleted text
To remove repetitive language (patient population and participation in 
pharmacogenetics research) previously presented in other sections of the
protocol
Section 4.2.1. Inclusion 
criteria (previously Section
5.2.1 in original protocol)
Added text around ROS1 gene 
rearrangements in inclusion criterion #5 
(previously #3).
Added the following criterion: #12. 
“Subject is fit for leukapheresis and has 
adequate venous access for the cell 
collection”
Revised text around effective birth control 
in inclusion criterion #13 (previously #9)
Revised laboratory values defining adequate 
organ function for eligibility in inclusion 
criterion #14 (previously #10)
Given the additional indication of crizotinib for patients with metastatic 
NSCLC whose tumor are ROS1 positive, text was added to clarify that such 
subjects should have received this standard of care treatment when appropriate.
To ensure the safety of subjects by selecting those who can undergo the process 
of leukapheresis, including the appropriate venous access to obtain the required 
cells for manufacturing.
To ensure female subjects are using the appropriate birth control for a defined 
time period after cell infusion (12 months) or after there is no evidence of 
persistence/gene modified cells in the blood (4 months). To ensure male 
subjects are using the appropriate birth control for a defined time period after 
chemotherapy according to the current available label. Also added a definition 
for abstinence for clarity of this means of birth control.
To more accurately reflect the baseline status of subjects with advanced 
NSCLC, certain laboratory values which define adequate organ function have 
been revised. Acceptable baseline values for ANC, hemoglobin, and platelets 
were lowered; however, remain in a safe range (i.e., subjects are not at risk for 
infection or spontaneous bleeding). A required white blood cell countwas
removed because a minimum WBC is not needed to determine eligibility if a
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minimum ANC is specified. Creatinine clearance rate has been lowered from
≥50 mL/min to ≥40 mL/min to be in line with the fludarabine administration 
guidelines. Alkaline phosphate was removed from the eligibility criteria 
because it is a non-specific test that can be out of normal range for a variety of 
reasons, including due to advanced malignancy, and does not impact ability to
tolerate T cell therapy.
Section 4.2.2. Exclusion 
criteria (previously Section
5.2.2. in original protocol)
Revised wash-out interval for immune 
therapy from 3 weeks to 4 weeks prior to 
leukapheresis in exclusion criterion #1
Revised exclusion criterion #2 to allow 
subjects with stable or irreversible Grade 2 
toxicities to be enrolled on a case-by-case 
basis with prior consultation and agreement 
with the Sponsor Study Physician.
Revised exclusion criterion #3 to include 
fludarabine.
Removed bullet from exclusion criterion
#10: “Clinically significant psychiatric 
illness/social situations that would limit 
compliance with study requirement” and 
replaced with wording “Subjects who in the 
opinion of the Investigator will be unlikely 
to fully comply with protocol requirements”
Revised text around exclusion criterion #11
regarding active infections, including the 
addition of HTLV 1 and 2 testing
The average half-life of most monoclonal antibodies is 3 to 4 weeks; therefore, 
to allow for a sufficient wash-out for monoclonal antibodies that have longer 
half-lives, this interval was increased
To enable subjects with stable pre-existing toxicity the opportunity to enroll 
onto the study following the appropriateconsultation
To ensure safety of subjects by excluding those who have a history of allergic 
reactions to fludarabine which has been added to the lymphodepleting 
chemotherapy regimen
To broaden the scope of excluding those subjects who will be most likely be 
noncompliant according to Investigator’s assessment
To provide clarity on the serology testing required to rule active hepatitis B and 
C infection. FDA guidance states that whole blood and blood components 
intended for use in transfusion and leukocytes intended for manufacturing use
should be screened for antibodies to HTLV-I. Only units from donors found to
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be negative on screening test(s) for antibodies to both HTLV-I should be 
released for use in transfusion; therefore screening for HTLV was added.
Section 4.3 Additional 
Eligibility Criteria (Prior to 
Lymphodepleting 
Chemotherapy) (previously 
Section 5.3 in original
protocol)
Added text to allow prior treatment with 
PD-1 and PD-LI inhibitors in inclusion 
criterion #1
Given the recent approval and availability of treatment with PD-1 and PD-L1 
inhibitors, text was added to clarify that prior treatment with such therapy was 
allowed
Section 4.4. Additional 
Eligibility Criteria (Prior to 
Second T-Cell Infusion) (not
previously part of original 
protocol)
Added eligibility criteria for subjects to 
meet prior to second T cell infusion
To ensure consistency across our clinical studies in NSCLC, inclusion and 
exclusion criteria were added to this protocol allowing for a rigorous evaluation 
of eligibility before a subject receives a secondinfusion.
Section 4.5. Completion of 
the Interventional Phases 
and Section 4.6: Subject 
Withdrawal (previously 
Section 7.3 in original
protocol)
Revised text around subject completion to 
also include subjects who died prior to 
disease progression
To clarify that subjects who have disease progression or die prior to disease 
progression are considered to have completed thestudy
Section 4.7: Consideration 
for Temporary Suspension 
of Enrollment (previously 
Section 11.1 in original 
protocol)
Revised text around stopping rules by 
changing two or more Grade 4 events to two 
or more Grade 4 autoimmune events and 
added text for an additional criteria around 
positive RCL
To clarify that the clinically significant events must be autoimmune in nature 
and a confirmed positive RCL can be either through positive PBMCs or 
biological to trigger a temporary pause in enrolment to allow for a 
comprehensive assessment by Adaptimmune’s Safety Governance Board.
Additional revisions to language was made to adhere to Adaptimmune’s
recently developed standard protocol template.
Section 5: Study Treatments (previously Section 6 in original protocol)
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Section 5.1.: Leukapheresis
(not previously part of 
original protocol)
Section added
To provide instructional language on how to obtain starting material for the 
manufacture of autologous NY-ESO-1c259T.
Section 5.2: 
Lymphodepleting 
Chemotherapy (previously 
Section 6.1 in original 
protocol)
Revised text to provide information on the 
administration of cyclophosphamide and 
fludarabine
Added sections to provide information on
recommended prophylaxis and supportive 
medication, including Mesna
To provide comprehensive information on how to administer 
cyclophosphamide and fludarabine in terms of days, route and dosage, 
including dose adjustment of fludarabine according to renal function.
To provide detailed information on prophylactic treatment for infection, pre-
medication, including hydration and anti-emetics, administration of Mesna and 
G-CSF.
Section 5.3: T Cell Infusion
(previously Section 6.2 in 
original protocol)
Revised text to provide information on the 
infusion of the T cell product
To provide comprehensive information on how to infuse the NY-ESO-1c259T
cell product, including pre-medication, thawing and transport instructions, use 
of dual spike infusion set, and handling of adversereactions.
Section 5.4: Second T Cell 
Infusion (previously Section
6.3 in original protocol)
Revised text to provide information around 
a second T cell infusion, now defined as
Interventional Phase 2
To provide comprehensive information on the eligibility requirements for a 
second T cell infusion as well as the assessments required in-between infusions
and at the time of Screening for Interventional Phase 2 (second T cell infusion)
Section 6: Concomitant Medication and Treatment (previously Section 7 in original protocol)
Section 6.1: Prohibited 
concomitant medication and 
treatment (previously 
Section 7.1 in original
protocol)
Deleted text
Corrected text regarding the administration 
of steroids as anti-emetics
To remove repetitive language (prohibited anti-cancer treatments and required 
wash-out intervals) previously presented in other sections of the protocol.
To clarify that steroid administration is started before (not after) chemotherapy 
in accordance with ASCO guidelines
Section 6.2.: Permitted 
Concomitant Medication and 
Treatment (previously 
Section 7.2 in original
protocol)
Added text on the use of vaccines
Added text defining concomitant 
medications
To provide guidance on the immunization of a high-risk subject (or member of 
the subject’s household)
To provide instructions on the data collection requirements for concomitant 
medications regarding type and the timeframe ofinterest
Section 7.3 in original 
protocol
Moved section regarding completion of and 
withdrawal from the study to Section 4.5 
and Section 4.6, respectively
To adhere to Adaptimmune’s recently developed standard protocol template
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Section 7: Schedule of Assessments and Procedures (previously Section 8 in original protocol)
Section 7: Schedule of 
Assessments and Procedures 
(previously Section 8.1,
including 8.1.1 and 8.1.2 in
original protocol)
Deleted text regarding screening number 
and subject identification number
To remove repetitive language (subject eligibility) previously presented in other 
sections of the protocol
To provide clarification that subjects are assigned one unique 5-digit subject 
identification number that is assigned at the Screening Protocol and will serve
as the same Subject ID for this study; this is a new process for Adaptimmune
Section 7.1.:HLA and 
Antigen Screening (to be 
conducted in Screening 
Protocol, ADP-0000-001)
(previously Section 8.1 in 
original protocol)
Revised text to denote that HLA subtype 
and antigen expression screening is required 
in the Screening Protocol (ADP-0000-001)
To ensure subjects will have completed testing for HLA subtype and antigen 
expression in the context of the Screening Protocol and that HLA and antigen 
expression satisfies the requirements of this protocol before undergoing written 
informed consent and screening procedures associated with this study.
7.2.:  Schedule of
Procedures, Table 5 
(previously Section 4.2 in 
original protocol)
Added the following assessments to the 
Schedule of Procedures table:

Tobacco use as part of medical 
history

Chest x-ray

Pregnancy test

CMV IgG and PCR

GFR or 24hr urine

TSH and freeTS4
To obtain adequate evaluations in this patient population to ensure eligibility 
and define a pre-infusion baseline value
Added the collection of liquid biopsies
(exosomes and cfDNA) to table.
To provide an alternative safer approach to tumor biopsies as an additional way 
to address the correlative research objectives of thestudy
Added local lymphocyte subset panel 
(CD3/CD4/CD8) to table
To provide guidance on absolute lymphocyte count and CD3 subset prior to 
leukapheresis
Removed the following assessments from 
the Schedule of Procedures table:

HLA testing
To remove assessments (HLA and antigen expression testing) that will no
longer be performed as part of this study or no longer thought to be necessary 
for the evaluation of safety (ferritin and cardiactroponin)
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
Antigen expression testing

Ferritin

Cardiac troponin
Added window intervals around visits 
where applicable
Added visits at Week 5, Week 6, Week 10 
and Week 20 to table.
Changed frequency of post-infusion follow 
up visits and ensured assessments required 
for long-term follow up were accounted for 
in Schedule of Procedures (previously 
Section 4.3 in original protocol) and in
accordance with FDA and EMA guidance.
To provide flexibility for procedures to be performed as required for each visit
To allow for close monitoring of bone marrow suppression and related 
cytopenias following lymphodepletion and T cell infusion, additional visits for 
collection of blood for local hematology were added.
To decrease the frequency of visits (every 3 months instead of every 2 months) 
for subjects who have not progressed 6 months after T cell infusion; thereby, 
aligning with standard of care
Section 7.4: Clinical 
Assessments and Procedures 
(previously Section 8.3 in 
original protocol)
Revised text throughout section regarding 
the safety and efficacy assessments to be 
performed on study
Revised Section 7.4.7 Tumor Response 
Assessments to include irRECIST for 
exploratory purposes (previously Section
8.3.6 in original protocol)
Deleted Section 8.3.6.1 (in original 
protocol) regarding immune-related 
response criteria (irRC)
To ensure alignment with the assessments and timing of assessments presented 
in the Schedule of Procedures, Table 4 and to adhere to Adaptimmune’s 
recently developed standard protocol template
To provide an opportunity for new lesions to be assessed by the Investigator 
using irRECIST criteria for exploratory purposes; tumor response for 
assessment of efficacy will be according to RECISTv1.1
Nishino and colleagues [Clin Cancer Res; 19(14); 3936–43)] concluded that 
using unidimensional measurements (as required with RECIST criteria) yielded 
highly concordant response assessment compared with bidimensional 
measurements (as required with irRC), with less measurement variability.
Therefore, to simplify the collection of tumor measurements and subsequent
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Investigator assessment of tumor response, irRC was removed from this study;
tumor response for assessment of efficacy will be according to RECIST v1.1
Section 7.5: Correlative 
Studies and Research 
Assessments (previously 
Section 8.4 in original
protocol)
Revised text to provide details on the 
research on blood and biopsy samples
To provide more detailed information on the type of analyses to be performed 
and the objective of each analysis and to adhere to Adaptimmune’s recently 
developed standard protocol template.
Section 7.5.1.: 
Pharmacogenetics Sample 
(previously Section 8.4.1 in
original protocol)
Deleted text
To minimize information provided in the NY-ESO-1c259T SPM and to adhere to 
Adaptimmune’s recently developed standard protocoltemplate.
Section 7.5.2.:Cytokine and
Soluble Factors analysis (not 
in original protocol)
Section added
To provide detailed information on the analyses planned for cytokines, growth 
factors and soluble receptors.
Section 8.4.3: Screening 
Assay in original protocol
Section deleted
To remove information no longer relevant for this study since antigen 
expression testing will be performed in the Screening Protocol (ADP-0000-001)
Section 7.5.3. Tumor 
biopsies (previously Section
8.4.23 in original protocol)
Revised text around tumor tissue collection
Added text on collection of pleural effusion 
or ascites fluid
To clarify that the biopsy required at screening will be obtained and tested in 
the Screening Protocol (ADP-0000-001) and to provide additional details on the 
time points for biopsies
Pleural effusion/ascites samples can be a rich source of tumor cells, tumor
infiltrating leukocytes and soluble factors; therefore, text was added to allow for 
the collection of such samples for translational research studies.
Section 7.5.6: Liquid 
Biopsy Collection and 
Analysis (not in original
protocol)
Section added
To provide an alternative safer approach to tumor biopsies as an additional way 
to address the correlative research objectives of thestudy
Section 7.5.7: Request for 
Autopsy for Death 
Following Administration of
Gene Transfer Agents
Corrected text regarding guidance for 
autopsy
To clarify that autopsy can be requested in accordance with FDA and EMA 
guidance which is no longer mentioned in NIH RACguidelines
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(previously Section 8.4.6 in
original protocol)
Section 8: Supportive Care Guidance (previously Section 9 in original protocol)
Section 8: Supportive Care 
Guidance
Added text
To ensure the safety of subjects treated on this study, guidance was provided 
such that hospitalization is recommended for T cell infusion and treating staff 
should be experienced in the administration of hematopoietic stem cell
transplant and/ or other cell and gene therapy
Section 8.2 Infection (not in
original protocol)
Section added
To ensure the safety of subjects treated on this study, information on measures
to treat and prevent infection was provided
Section 8.3: Hematologic
and Blood Product Support 
(not in original protocol)
Section added
To ensure the safety of subjects treated on this study, information on the use of 
blood products while on study was provided
Section 8.4: Management of 
Autoimmunity (not in
original protocol)
Section added
To ensure the safety of subjects treated on this study, information on 
autoimmune reactions was provided
Section 8.6: Management of 
Graft-versus-Host Disease 
(GVHD) (not in original
protocol)
Section added
To ensure the safety of subjects treated on this study, information on the 
diagnosis, grading, and management of GVHD wasprovided.
Section 8.7: Management of 
Pancytopenia with Bone 
Marrow Failure / Aplastic 
Anemia (not in original
protocol)
Section added
To ensure the safety of subjects treated on this study, information on the 
management of pancytopenia was provided.
Section 8.8.1. Management 
of Neutropenia (previously 
Section 9.3 in original
protocol)
Revised text
To clarify that G-CSF should be administered 24 (not 24 to 72) hours after 
chemotherapy and to provide flexibility in management by allowing use of 
long-acting (pegylated) G-CSF.
Section 9.4 Management of 
Cytokine Release Syndrome
(in original protocol)
Section deleted and moved to Section 8.5
To delete information previously provided in other sections of the protocol due 
to Adaptimmune’s recently developed standard protocoltemplate
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Section 9: Recording Adverse Events (previously Section 9 in original protocol)
Section 9.1: Time Period for 
Collecting AE and SAE 
Information (not in original
protocol)
Section added
To provide guidance on the nature of AEs/SAEs to be recorded in the EDC over 
the course of the study (i.e., during screening phase, Interventional Phase and 
LTFU)
Section 9.2.2. Assessment of 
Causality (previously 
Section 10.2.2. in original
protocol)
Added text to define the scales of causal 
relationship 
(possibly/probably/definitely)
To provide guidance to the Investigator when determining the causal relation 
between the AE/SAE and NY-ESO-1c259T.
Section 9.3. Reporting 
Serious Adverse Events 
(previously Section 10.3 in 
original protocol)
Revised definition of SAE
Corrected method of reporting an SAE
To ensure consistency of the definition of a SAE with the “Code of Federal 
Regulations Title 21 Section 312.32: IND SafetyReporting”
To clarify that SAEs must be reported to Adaptimmune by completing the SAE 
eCRF form (not a paper SAE worksheet)
Section 9.6: Regulatory 
Reporting Requirements for 
SAEs (previously Section
10.3.1. in original protocol)
Previous section on Standards for Expedited 
Reporting (SUSARs) (Section 10.3.1.) has 
been replaced
To provide a concise overview of Sponsor obligations for reporting SAEs to 
regulatory authorities and to adhere to Adaptimmune’s recently developed 
standard protocol template.
Section 10.3.2. Reporting 
Guidelines for Other 
Observations in original
protocol
Section deleted
To delete information previously provided in other sections of the protocol or 
that are no longer relevant
Section 10.8:
Hospitalization, Prolonged 
Hospitalization or Surgery
Section deleted
To delete information previously provided in other sections of the protocol
Section 9.9: Laboratory 
Test Abnormalities as 
Adverse Events (previously 
Section 10.9 in original 
protocol)
Revised definition regarding laboratory 
abnormalities to be reported as AEs
To clarify and simplify that only Grade ≥3 laboratory value should be reported 
as an AE and provide additional guidance on numerical lab values which reach 
Grade 4.
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Section 10: Safety Monitoring (previously Section 11 in original protocol)
Section 10.1: Monitoring 
and Management of 
Replication Competent 
Lentivirus (previously 
Section 11.2 in original
protocol)
Revised text
To ensure compliance with FDA and EMA guidance on the monitoring and 
management of RCL and to adhere to Adaptimmune’s recently developed 
standard protocol template.
Section 10.2: Persistence 
Testing and Monitoring for 
Insertional Oncogenesis 
(previously Section 11.3 in
original protocol)
Revised text
To ensure compliance with FDA and EMA guidance on the monitoring and 
management of persistence and to adhere to Adaptimmune’s recently developed 
standard protocol template.
Section 11: Statistical and Data Analysis (previously Section 12 in original protocol)
Section 11.1: Study 
Populations (previously 
Section 12.3 in original
protocol)
Revised definitions of populations
To clarify that the ITT population will be the primary population for safety and 
efficacy analyses (not just safety) and to remove the minimum target and per 
protocol patient populations which were thought to be not relevant for this
small, Phase 1 study with the objective of defining safety of NY-ESO-1c259T.
Section 11.2 : Sample Size 
Calculations (previously 
Section 12.1 in original
protocol)
Revised text
To provide further justification on the sample size of the study
Section 11.3: Interim 
Analyses (not in original
protocol)
Section added
To clarify that no formal interim analyses are planned for this study
Section 12: Clinical Supplies (previously Section 13 in original protocol)
Section 12
Revised text
To adhere to Adaptimmune’s recently developed standard protocol template 
regarding the Investigational Product, including packaging/labelling, 
storage/handling and accountability
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GlaxoSmithKline (GSK)
PROTOCOL NUMBER: GSK208749 (ADP-0011-004)
Investigational Product: NY-ESO-1c259
Amendment 4
Confidential                  
Page 142
Section 13: Data Handling and Record Keeping (previously Section 14.1, Section 15.4, and Section 15.2 in original protocol)
Section 13
Revised and compiled sections
To adhere to Adaptimmune’s recently developed standard protocol template 
regarding data management, including case report forms, source documents,
and data retention
Section 14: Study Monitoring (previously Section 14.2 and Section 14.3 in original protocol)
Section 14
Revised text and compiled sections
To adhere to Adaptimmune’s recently developed standard protocol template
regarding site monitoring and audits
Section 15: Regulatory and Ethical Considerations (previously Section 14.4, 14.5, 14.7, 14.8, 14.9, 14.10, and 14.12, in original protocol)
Section 15
Revised text and compiled sections
To adhere to Adaptimmune’s recently developed standard protocol template
regarding regulatory and ethical considerations for the study
Section 16: Appendices (previously Section 17 in original protocol)
Appendix 1 List of 
Abbreviations (previously 
Section 1 in original
protocol)
Revised text
To align with abbreviations used throughout the revised protocol
Appendix 3: Local 
laboratory Tests and ECG 
Parameters (previously 
Section17.2 in original
protocol)
Revised table
To align with all laboratory and ECG requirements of the revised protocol
Section 17.3: Total Blood 
Volumes Collection Table
in original protocol
Section deleted
To remove information that will now be presented in the SPM
Section 17.4: Immune-
related Response Criteria in 
original protocol
Section deleted
To remove information no longer applicable to the conduct of the study
Appendix 5: Schedule of 
Procedures for Second T cell 
infusion (not in original
protocol)
Section added
To provide comprehensive schedule of procedures for those subjects deemed 
eligible for a second T cell infusion
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PR
Amendment 4
Confidential                  
Page 143
Amendment 02 Changes 
Primary reason for amendment
Protocol Amendment No. 01, dated 08 August 2016 is replaced by Protocol Amendment No. 
02.
Subsequent to the licensing of Adaptimmune product NY-ESO by GSK, the purpose of this 
protocol amendment is to:
-
Delete or replace references to Adaptimmune or its staff with that of GlaxoSmithKline 
(GSK) and its authorized agents to align with the change of sponsorship;
-
Make administrative changes to align with GSK processes and procedures;
-
Update language relating to serious adverse event (SAE) reporting and safety 
monitoring;
-
Update of lymphodepletion regimen throughout.
Section of Amendment No. 2.0
Change
RESPONSIBLE SPONSOR STUDY 
PHYSICIAN/SPONSOR 
INFORMATION PAGE, and
Responsible Study Physician/SAE 
Contact Information
Updated as applicable
Throughout the document
•
GSK study numbers added to former Adaptimmune 
study numbers
•
Adaptimmune replaced by GSK / “the Sponsor” where 
appropriate
•
“Adaptimmune’s Safety Review Team and Safety 
Governance Board” replaced with “the Sponsor” where 
appropriate.
•
Statistical Analysis Plan (SAP) replaced by Reporting 
and Analysis Plan (RAP)
•
Update of lymphodepleting regimen
Objectives
Primary, secondary and exploratory objectives updated.
Section 3.1 Overall Study Design
Study design amended to update screening requirements, 
and definition of interventional phase completion, and to 
describe follow-up of subjects. Study design schematic 
updated.
Section 3.2.2 Lymphodepletion
Lymphodepleting regimen for the study updated.
Section 3.5.2 Risk Assessment
Information on known safety profile updated. Potentila risk 
of non-infection encephalopathy added.
Section 4.2.1 Inclusion Criteria
Contraceptive requirements updated.
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Amendment 4
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Section of Amendment No. 2.0
Change
Section 4.2.2, Exclusion Criteria
Exclusion of subjects with active liver or biliary disease 
added, prior/concomitant medication exclusion criteria 
amended, exclusion of subjects with CNS metastases added, 
and QTc criteria and details of hepatitis B and C tests 
amended.
Section 4.5 Completion of the 
Interventional Phases
Definition of completion of interventional phases amended.
Section 4.6, Subject Withdrawal
Details of follow-up attempts amended, and information 
with regards to subjects who voluntarily discontinued 
added.
Section 4.7, Consideration for 
Temporary Suspension of Enrollment
Text amended to match standard GSK procedures.
Sections 4.8 Liver Safety: Required 
Actions and Follow-up Assessments
New section added on liver safety requirements
Section 5.2 Lymphodepleting 
Chemotherapy
Lymphodepleting chemotherapy regimen for the study 
updated.
Section 6.3 Contraception
New contraceptive requirements added.
Section 7.1 HLA and Antigen 
Screening
HLA and antigen screening requirement amended.
Schedule of Procedures
Updated to add Brain MRI and CARTOX
Section 7.4.6 Cardiac and Other 
Assessments
Brain MRI and CARTOX 10 added
Section 7.4.8 Long-Term Follow-up
Long-term follow-up requirements updated.
Section 8.9 Management of 
Encephalopathy Syndrome
New section added to describe management of 
encephalopathy syndrome
Section 9.1 Time Period for Collecting 
AE and SAE Information
Time period for AE and SAE monitoring and reporting 
updated.
Section 9.2.2 Assessment of causality
Wording amended to GSK standard
Section 9.3, Reporting of SAEs
Wording amended to GSK standard. Procedure for SAE 
reporting updated.
Section 9.4 Reporting Criteria During 
Long-Term Follow-up (Years 1 to 15)
Reporting criteria amended
Section 9.6 Regulatory Reporting for 
SAEs
Wording amended to GSK standard
Section 9.7 Cardiovascular and Death 
Events
New section added to describe details of reporting deaths 
and cardiovascular events
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Amendment 4
Confidential                  
Page 145
Section of Amendment No. 2.0
Change
Section 9.8 Pregnancy
Timing of reporting pregnancy to GSK by Investigator 
added.
Section 9.11 Timelines for safety 
reporting
New section detailing timelines for safety reporting added.
Section 11.5 Statistical Methods for 
Efficacy Endpoints
Description of key secondary analyses updated in line with 
updated objectives.
Appendix 1 List of abbreviations and 
definitions of terms
Updated abbreviation list
Appendix 5 – Schedule of Procedures 
for Second T Cell Infusion 
(Interventional Phase 2)
Brain MRI added
Amendment 03 Changes
Protocol Amendment No. 02 is replaced by Protocol Amendment No. 
03.
Primary reason for amendment:
Changes made to the protocol were requested by the FDA as a result of safety events which 
included 2 reports of Guillain-Barré syndrome in subjects who have received 
chemotherapy and GSK3377794 during clinical trials.
Section of Amendment No. 3.0
Change
Synopsis
Key Inclusion/Exclusion 
Criteria
Addition of ‘Prior or active 
demyelinating disease as an exclusion 
criterion’.
3.5.2 Risk Assessment
Update to risk assessment to add 
additional risk of Guillain-Barré 
syndrome and other demyelinating
neuropathies.
4.2.2 Exclusion Criteria (#10)
Addition of ‘Prior or active demyelinating 
disease as an exclusion criterion’.
9.3 Reporting Serious 
Adverse Events (SAEs)
Addition of all cases of Guillain-Barré 
syndrome or acute demyelinating 
neuropathy as a reportable SAE within 24
hours.
10. 1 Safety Review Team
Addition of GSK SRT.
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Amendment 4
Confidential                  
Page 146
10.1.1. Mandated Study Pause 
Due to GBS
Addition of Mandated Study Pause due to 
GBS
10.4
Monitoring and management for 
Demyelinating Neuropathyand
other Neurological events
Addition of Monitoring and Management 
for Demyelinating Neuropathy and other 
Neurological events
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SAP_001.pdf: 
 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
208749 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for A Pilot Open-Label Clinical 
Trial Evaluating the Safety and Efficacy of Autologous T Cells 
Expressing Enhanced TCRs Specific for NY-ESO-1 in 
Subjects with Stage IIIb or Stage IV Non-Small Cell Lung 
Cancer (NSCLC) 
Compound Number  : GSK3377794 
Effective Date  
: Refer to Document Date 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol GSK208749 
• 
This RAP is intended to describe the final analyses required for the study.  
• 
This RAP will be provided to the study team members to convey the content of the 
Statistical Analysis Complete (SAC) deliverable. 
 
RAP Author(s): 
Author 
Date 
 
16-SEP-2020 
Statistician (Oncology Clinical Statistics) 
 
 
 
 
Copyright 2020 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
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RAP Team Reviewer (Method: Email) 
Clinical Statistics and Clinical Programming Line Approvals: (Method: Pharma 
TMF eSignature) 
Approver 
Date 
 
Refer to Document 
Date  
Statistics Director (Oncology Clinical Statistics) 
On behalf of 
 (Senior Statistics Director Oncology 
Clinical Statistics) 
 
Refer to Document 
Date 
Programming Manager (Oncology Clinical Programming) 
 
 
 
Reviewer 
Date 
 
17-SEP-2020 
VP Clinical Development, Cell & Gene Therapy (Oncology 
Clinical) 
 
16-SEP-2020 
Programming Manager (Oncology Clinical Programming) 
 
16-SEP-2020 
Clinical Biomarker Lead (Translational Research and 
Development) 
 
16-SEP-2020 
Quantitative Clinical Pharmacology Director (Oncology 
CPMS) 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 7 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 8 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 8 
2.2. 
Study Objective(s) and Endpoint(s)............................................................... 9 
2.3. 
Study Design .............................................................................................. 11 
2.4. 
Statistical Analyses ..................................................................................... 12 
3. 
PLANNED ANALYSES .......................................................................................... 13 
3.1. 
Primary Analyses ........................................................................................ 13 
3.2. 
Final Analyses ............................................................................................ 13 
4. 
ANALYSIS POPULATIONS ................................................................................... 13 
4.1. 
Protocol Deviations ..................................................................................... 14 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 15 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 15 
5.2. 
Baseline Definitions .................................................................................... 15 
5.3. 
Multicenter Studies ..................................................................................... 16 
5.4. 
Examination of Covariates, Other Strata, and Subgroups ........................... 16 
5.5. 
Multiple Comparison and Multiplicity ........................................................... 16 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 16 
6. 
STUDY POPULATION ANALYSES ....................................................................... 18 
6.1. 
Overview of Planned Study Population Analyses ........................................ 18 
6.2. 
Disposition of Participants ........................................................................... 18 
6.3. 
Protocol Deviations ..................................................................................... 18 
6.4. 
Demographic and Baseline Characteristics ................................................. 19 
6.5. 
Study Treatment Exposure ......................................................................... 19 
6.6. 
Anti-Cancer Therapy and Surgery............................................................... 20 
6.7. 
Concomitant Medications ............................................................................ 20 
7. 
EFFICACY ANALYSES .......................................................................................... 21 
7.1. 
Secondary Efficacy Analyses ...................................................................... 21 
7.1.1. 
Endpoint / Variables ..................................................................... 21 
7.1.2. 
Summary Measure ...................................................................... 28 
7.1.3. 
Population of Interest ................................................................... 29 
7.1.4. 
Strategy for Intercurrent Events ................................................... 29 
7.1.5. 
Statistical Analyses / Methods ..................................................... 29 
7.2. 
Exploratory Efficacy Analyses ..................................................................... 30 
7.2.1. 
Overall Survival............................................................................ 30 
7.2.2. 
Summary Measure ...................................................................... 30 
7.2.3. 
Population of Interest ................................................................... 30 
7.2.4. 
Strategy for Intercurrent Events ................................................... 30 
7.2.5. 
Statistical Analyses / Methods ..................................................... 30 
8. 
SAFETY ANALYSES ............................................................................................. 31 
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8.1. 
Adverse Events Analyses ........................................................................... 31 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 32 
8.2.1. 
Cytokine Release Syndrome (CRS) and Graft versus Host 
Disease (GvHD) ........................................................................... 33 
8.3. 
Deaths and Serious Adverse Events ........................................................... 34 
8.4. 
Clinical Laboratory Analyses ....................................................................... 34 
8.4.1. 
Analyses of Liver Function Tests (LFT) ........................................ 37 
8.5. 
Other Safety Analyses ................................................................................ 38 
8.5.1. 
Performance Status ..................................................................... 38 
8.5.2. 
ECG ............................................................................................. 38 
8.5.3. 
Vital Signs .................................................................................... 39 
8.5.4. 
Pregnancies ................................................................................. 39 
8.5.5. 
Replication Competent Lentivirus (RCL) and Persistence 
of NY-ESO-1c259T ......................................................................... 39 
9. 
BIOMARKER ANALYSES ...................................................................................... 40 
9.1. 
Exploratory Biomarker Analyses ................................................................. 40 
9.1.1. 
Endpoint / Variables ..................................................................... 40 
9.1.2. 
Summary Measure ...................................................................... 40 
9.1.2.1. 
Persistence of NY-ESO-1c259T .................................... 40 
9.1.2.2. 
Cytokines ................................................................... 41 
9.1.3. 
Population of Interest ................................................................... 41 
10. PHARMAKOKINETIC ANALYSES ......................................................................... 41 
11. POPULATION PHARMACOKINETIC (POPPK) ANALYSES .................................. 41 
12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES ................................. 42 
13. REFERENCES ....................................................................................................... 43 
14. APPENDICES ........................................................................................................ 44 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 44 
14.2. 
Appendix 2: Schedule of Activities .............................................................. 45 
14.2.1. 
Protocol Defined Schedule of Events Interventional Phase 
I ................................................................................................... 45 
14.2.2. 
Protocol Schedule of Events Interventional Phase II .................... 51 
14.2.3. 
Protocol Defined Schedule of Events Long Term Follow-
up ................................................................................................ 56 
14.3. 
Appendix 3: Assessment Windows ............................................................. 58 
14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 59 
14.4.1. 
Study Phases .............................................................................. 59 
14.4.1.1. Study Phases for Concomitant Medications ............... 59 
14.4.1.2. Study Phases for Anti-Cancer Therapy/Surgery ......... 59 
14.4.2. 
Treatment Emergent Flag for Adverse Events ............................. 59 
14.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 60 
14.5.1. 
Reporting Process ....................................................................... 60 
14.5.2. 
Reporting Standards .................................................................... 60 
14.6. 
Appendix 6: Derived and Transformed Data ............................................... 62 
14.6.1. 
General ........................................................................................ 62 
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14.6.2. 
Study Population .......................................................................... 63 
14.6.3. 
Efficacy ........................................................................................ 63 
14.6.4. 
Safety .......................................................................................... 64 
14.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 65 
14.7.1. 
Premature Withdrawals ................................................................ 65 
14.7.2. 
Handling of Missing Data ............................................................. 65 
14.7.2.1. Handling of Missing and Partial Dates ........................ 65 
14.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 68 
14.8.1. 
Laboratory Values ........................................................................ 68 
14.8.2. 
ECG Parameters ......................................................................... 68 
14.8.3. 
Vital Signs .................................................................................... 69 
14.9. 
Appendix 9: Abbreviations & Trade Marks .................................................. 71 
14.9.1. 
Abbreviations ............................................................................... 71 
14.9.2. 
Trademarks ................................................................................. 72 
14.10. Appendix 10: List of Data Displays.............................................................. 73 
14.10.1. Mock Example Shell Referencing ................................................ 73 
14.10.2. Data Display Numbering .............................................................. 73 
14.10.3. Deliverables ................................................................................. 73 
14.10.4. Study Population Tables .............................................................. 74 
14.10.5. Efficacy Tables ............................................................................ 80 
14.10.6. Efficacy Figures ........................................................................... 82 
14.10.7. Safety Tables ............................................................................... 83 
14.10.8. Safety Figures ............................................................................. 91 
14.10.9. Biomarker Tables ......................................................................... 91 
14.10.10. Biomarker Figures ....................................................................... 92 
14.10.11. ICH Listings ................................................................................. 99 
14.10.12. Non-ICH Listings ........................................................................ 109 
14.11. Appendix 11: Example Mock Shells for Data Displays .............................. 112 
14.11.1. POP_T1 Exposure Mock-Up Summary ...................................... 112 
14.11.2. EFF_F1 Spider Plot Mock-Up Figure ......................................... 113 
14.11.3. SAFE_F1 Prior Therapy Mock-Up Figure................................... 114 
14.11.4. SAFE_F2 Study Duration Mock Up Figure ................................. 115 
14.11.5. BIO_F3 Persistence Profile Mock-Up Figure .............................. 116 
14.11.6. BIO_F4 Cytokine Spider Plot Mock-Up Figure ........................... 117 
14.11.7. BIO_F5 Cytokine Box Plot Figure .............................................. 118 
14.11.8. SAFE_L1 CRS Mock-Up Listing ................................................ 119 
14.11.9. BIO_T1 Summary of Peak Persistence ...................................... 121 
14.11.10. BIO_T2 Summary of Time to Peak Persistence ......................... 122 
14.11.11. SAFE_T3 Summary of Replication Competent Lentivirus 
Positive ...................................................................................... 123 
14.11.12. BIO_L1 Listing of Persistence .................................................... 124 
14.11.13. POP_L1 Listing of Exposure to T-cell Infusion ........................... 126 
14.11.14. POP_L2 Listing of Exposure to Cyclophosphamide/Mesna ....... 127 
14.11.15. POP_L3 Listing of Leukapheresis, Lymphodepletion, and 
T-cell Infusion Dates .................................................................. 128 
14.11.16. POP_L4 Listing of Disease Characteristics at Screening ........... 130 
14.11.17. POP_L5 Subject Status Mock-Up Listing ................................... 131 
14.11.18. EFF_T1 Summary of Time to Response by Investigator 
(RECIST 1.1  Criteria) ................................................................ 132 
14.11.19. SAFE_T1 Summary of Time to Resolution ................................. 133 
14.11.20. POP_T2 Summary of Subject Status ......................................... 134 
14.11.21. POP_T3 Summary of Subject Status- End of Study ................... 135 
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14.11.22. SAFE_L2 Listing of Symptoms, Concomitant Medications, 
and Procedures Related to Cytokine Release Syndrome ........... 136 
14.11.23. BIO_L2 Listing of Immunohistochemistry Data .......................... 137 
14.12. Appendix 12: Combined Preferred Terms ................................................. 138 
14.13. Appendix 13: AE Collapsing Rules............................................................ 140 
 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol:  
Revision Chronology: 
ADP-0011-004 
08-JUN-2015 
Original protocol was provided by Adaptimmune  
ADP-0011-004 
Amendment 01 
08-AUG-2016 
This amendment was performed to address questions 
and comments from Institutional Review Boards and 
Regulatory Authorities.  Additionally, revisions were 
made based on emerging data from Adaptimmune’s 
clinical program and due to Adaptimmune’s newly 
developed protocol template. Appendix 8 in the 
protocol contains a summary of and rationale for all 
revisions for Amendment 01. 
Key revisions included the following: 
Changed phase of trial from Phase I/II to Pilot 
Revised Background and Study Rationale sections to 
minimize information already provided in the NY-ESO-
1c259T Investigator Brochure 
Revised primary, secondary, and exploratory endpoints 
to better characterize the safety and efficacy 
evaluations, and correlative studies to be performed in 
this study 
Changed lymphodepleting chemotherapy regimen from 
cyclophosphamide alone to cyclophosphamide and 
fludarabine based on emerging data from our ongoing 
clinical program 
Removed HLA and antigen expression screening since 
these tests will be performed in Adaptimmune’s 
Screening Protocol (ADP-0000-001) 
Revised inclusion/exclusion criteria to provide more 
clarity on participant population 
Added guidance on second T cell infusion, including 
eligibility criteria and Schedule of Procedures table 
Added text around the administration of 
cyclophosphamide and fludarabine, including dose 
adjustments, prophylactic and supportive treatments 
Removed irRC criteria for tumor response assessments 
Added several sections on supportive care guidance, 
including infection, hematologic and blood product 
support, autoimmunity, GVHD, and pancytopenia 
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GSK208749 
Amendment 02 
16-July-2017 
Subsequent to the licensing of Adaptimmune product 
NY-ESO by GSK, the purpose of this protocol 
amendment is to: 
 Delete or replace references to Adaptimmune or its 
staff with that of GlaxoSmithKline (GSK) and its 
authorized agents to align with the change of 
sponsorship; 
 Make administrative changes to align with GSK 
processes and procedures; 
 Update language relating to serious adverse event 
(SAE) reporting and safety monitoring. 
- Changes to lymphodepletion regimen throughout 
 
GSK208749 
Amendment 03 
17-October-
2018 
Changes made to the protocol were requested by the 
FDA as a result of safety events which included 2 
reports of Guillain-Barré syndrome in participants who 
have received chemotherapy and GSK3377794 during 
clinical trials.  
 
GSK208749 
Amendment 04 
26-September-
2019 
The overall rationale for this amendment is to clarify 
patient management with regards to treatment regimen 
and evaluation of encephalopathy and modification of 
lymphodepleting regimen for older participants, 
modification of target dose range for NY-ESO 
transduced cells and changes related to Health Canada 
requests including updates to both the Encephalopathy 
(now Immune Effector Cell-Associated Neurotoxicity or 
ICANS) and the CRS grading and management criteria. 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1.  
Table 1 
Changes to Protocol Defined Analysis Plan 
According to GSK standards, Listing of Race (DM9) is required. Due to differences in 
Adaptimmune data collection, only Listing of Demographic Characteristics (DM2) will 
be displayed which will include race information.  
Protocol 
Reporting & Analysis Plan 
Statistical Analysis Plan 
Statistical Analysis Plan 
Rationale for Changes 
None 
None 
None 
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2.2. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• To evaluate the safety and 
tolerability of autologous 
genetically modified T cells (NY-
ESO-1c259T) in human leukocyte 
antigen (HLA) HLA-A*02:01, HLA-
A*02:05 and/or HLA-A*02:06 
positive participants with NY-ESO-
1 and/or LAGE-1a positive 
advanced NSCLC. 
• Adverse events (AE), including serious adverse 
events (SAE);  
• Change of laboratory assessments, including 
chemistry, hematology, coagulation 
• Cardiac and pulmonary assessments, including 
electrocardiogram (ECG) and pulmonary function 
(pulse oximetry); 
Secondary Objectives 
Secondary Endpoints 
• To evaluate the efficacy of NY-
ESO-1c259T 
• Investigator-Assessed Overall Response Rate 
(ORR)  
• Time to response  
• Duration of response  
• Disease Control Rate (DCR)  
• Progression-free Survival (PFS) 
Exploratory Objectives 
Exploratory Endpoints 
• To evaluate the persistence, 
phenotype and functionality of NY-
ESO-1c259T 
• Correlate persistence, phenotype and functionality of 
NY-ESO-1c259T in the peripheral blood and/or tumor 
with response to treatment 
• Correlate circulating cytokines with cytokine release 
syndrome (CRS) 
• To understand mechanisms of 
resistance to NY-ESO-1c259T 
• Correlate changes in immunosuppressive myeloid 
cells and Tregs in peripheral blood versus tumor 
• Correlate changes in immunosuppressive myeloid 
cells and Tregs in peripheral blood and tumor with 
treatment response 
• Investigate the immune contexture of each 
participants' tumor over time and to understand 
mechanisms of tumor resistance, escape and 
treatment response 
• Determine whether loss of NY-ESO-1c259T 
expression in tumor is a resistance mechanism 
• To evaluate antigen spreading as a 
mechanism of response 
• Correlate clonal outgrowth of T cell populations with 
response following T cell infusion 
• To document the exposure and 
immunogenicity with NY-ESO-
1c259T 
• Change of anti-NY-ESO-1c259T antibodies 
 
• To evaluate the survival benefit of 
NY-ESO-1c259T   
• Overall Survival (OS) 
• To evaluate the efficacy of NY-
ESO-1c259T per immune-related 
• Overall Response Rate (ORR) per irRECIST 
• Time to response (irRECIST) 
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Objectives 
Endpoints 
Response Evaluation Criteria in 
Solid Tumors (irRECIST) 
• Duration of response (irRECIST) 
• Progression-free Survival (PFS, irRECIST) 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
 
*participants, who have a confirmed response (or have stable disease for >4 months) and subsequently have documented 
PD and whose tumors continue to express NY-ESO-1 as verified by assay performed in biopsied tissue, can be considered 
for a second infusion with engineered T cells 
Design 
Features 
• 
This is a pilot, open-label study of genetically engineered NY-ESO-1c259T cells in HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 participants with advanced NSCLC.  
Approximately 10 participants will be enrolled in this study. Sample size was chosen based 
on clinical judgement and the study is not powered to conduct statistical hypothesis testing. 
• 
Participants will have been screened for the presence HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 and have NY-ESO-1 and/or LAGE-1a expression on the tumor to be eligible 
to enrol in the study. Prior to the administration of lymphodepleting chemotherapy, 
participants must have failed at least one prior platinum-containing regimen and have PD. 
All other eligibility criteria will be reconfirmed and baseline tumor measurements obtained. 
• 
The Screening Phase starts from the time the participant signs the ICF until leukapheresis. 
Eligible participants then enter the Interventional Phase 1 of the study (first T cell infusion) 
which runs from the day of leukapheresis until progressive disease (PD), death, or followed 
for 2 years post- T-cell infusion, whichever is shorter 
• 
Following Screening, participants meeting all eligibility criteria will undergo leukapheresis to 
obtain cells for the manufacture of autologous NY-ESO-1c259 TCR bearing T cells.  
• 
When the NY-ESO-1c259T cells are available, participants will receive lymphodepleting 
chemotherapy with cyclophosphamide and fludarabine, followed by infusion of NY-ESO-
1c259 transduced T cells in the range of 1 x 109 to 6 x 109 transduced cells.  
• 
The time point for administration of lymphodepleting chemotherapy and subsequent 
infusion of NY-ESO-1c259 TCR bearing T cells will be staggered for the first 3 participants 
enrolled. Participants may receive lymphodepleting chemotherapy as defined in Table 2 (in 
protocol) only after the previously enrolled participant has had a minimum safety 
observation period of 21 days following their NY-ESO-1c259 T cell infusion. This 21-day 
observation period shall remain for the first 3 participants enrolled.  If 2 or more participants 
among the first 3 participants enrolled experience a severe study-related toxicity, 
enrollment will be paused for evaluation by the Sponsor and Investigators, otherwise, an 
additional 7 participants will be entered. 
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Overview of Study Design and Key Features 
• 
A participant will be considered completing the Interventional Phase 1 of the study when 
he/she has PD or has died prior to PD, or 2 years after the NY-ESO-1c259T cell infusion, 
whichever is shorter.  A participant will be considered completing the Interventional Phase 
2 of the study when he/she has PD, or has died prior to PD, or 6 months after the NY-ESO-
1c259T cell infusion, whichever is shorter.  All participants completing the Interventional 
Phase of the study will be rolled over to a long-term follow-up (LTFU) Protocol 
(GSK208756) for observation of delayed AEs for 15 years post-infusion in accordance 
Food and Drug Administration (FDA) and European Medicines Agency (EMA) 
requirements for gene therapy clinical trials.  
• 
Following the initial infusion, participants, who have a confirmed response (or have stable 
disease for >4 months) and subsequently have documented PD and whose tumors 
continue to express NY-ESO-1 and/or LAGE-1a as verified by assay performed in biopsied 
tissue, can be considered for a second infusion with engineered T cells.   
Dosing 
• 
When the NY-ESO-1c259T cells are available, participants will undergo lymphodepleting 
chemotherapy with cyclophosphamide and fludarabine, followed by infusion of NY-ESO-
1c259 transduced T cells in the range of 1 x 109 to 6 x 109 transduced cells. The 
lymphodepleting regimen in this study consists of fludarabine 30mg/m2/day at Days -8, -7, -
6 and -5 and cyclophosphamide 900mg/m2/day intravenously at Days -7, -6, and -5. 
• 
Participants that qualify for a second infusion will receive the same lymphodepleting 
chemotherapy regimen and T cell infusion as received during the first T cell infusion 
Time & 
Events 
• 
[Refer to Appendix 2: Schedule of Activities] 
Treatment 
Assignment 
• 
This is a single arm open-label unblinded study treated with autologous T cells transduced 
with lentivirus encoding enhanced TCR specific for NY-ESO-1. 
Interim 
Analysis 
• 
No formal interim analyses for efficacy or futility are planned for this study. 
 
2.4. 
Statistical Analyses 
The study is not powered to conduct any hypothesis testing on either primary and 
secondary endpoints. All analyses will be descriptive in nature. Continuous data will be 
summarized including means, medians, standard deviations, and ranges. Categorical data 
will be summarized using frequency counts and percentages. Graphical summaries of the 
data will be presented as appropriate. Time-to-event endpoints will be summarized as the 
median, and the 25th and 75th percentiles and displayed graphically using Kaplan-Meier 
method if data warrant. 
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3. 
PLANNED ANALYSES 
3.1. 
Primary Analyses 
The primary analyses will be performed after the completion of the following 
sequential steps: 
1. 
All participants who have received the first NY-ESO-1c259T cell infusion have 
progressed, or have died, or have been followed for 2 years, or the last participant 
who has received the second NY-ESO-1c259T cell infusion has been followed 6 
months after the NY-ESO-1c259T cell infusion, progressed, or has died, whichever 
is later.  
2. All required database cleaning activities have been completed and database release 
(DBR) and database freeze (DBF) has been declared by Data Management 
If the primary analyses are expected to occur shortly before the final analyses, the study 
team may decide to conduct only the final analyses. 
3.2. 
Final Analyses 
The final analyses will be performed after the completion of the following sequential 
steps. If the primary analysis and final analysis occurs at the same time, only final 
analysis will be performed.  
1. All participants who have received the first NY-ESO-1c259T cell infusion have 
progressed, have died, have been followed 2 year after the first NY-ESO-1c259T cell 
infusion, or have withdrawn from the study; the last participant who has received the 
second NY-ESO-1c259T cell infusion either has been followed until disease 
progression or withdraws from the study. If LTFU protocol is not available when a 
participant completes the Interventional Phase, participant can be followed under this 
protocol until LTFU protocol becomes available. The final analyses will be conducted 
when all participants are off-study. 
 
2. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management. 
 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened 
• 
All participants that signed screening informed consent  • 
Screen Failures 
Intent-to-Treat 
(ITT) 
• 
All participants who were enrolled in the trial and 
met all eligibility criteria  
 
• 
Primary Study 
Population 
• 
Primary Safety 
• 
Sensitivity 
Efficacy (ORR 
and DCR) 
Modified Intent-
To-Treat (mITT) 
• 
All participants in the ITT population who receive NY-
ESO-1c259T cell infusion. 
• 
Sensitivity Study 
Population 
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Population 
Definition / Criteria 
Analyses Evaluated 
• 
Primary Safety 
(where 
appropriate) 
• 
Sensitivity Safety 
(where 
appropriate) 
• 
Primary Efficacy 
Modified Intent-to 
Treat 2 (mITT2) 
• 
All participants that received a second T cell infusion 
• 
Efficacy 
• 
Safety 
• 
Study Population 
 
4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, participant management or participant assessment) will be 
summarized and all protocol deviations, including both major and minor will be listed. 
 
Protocol deviations will be tracked in accordance with the Protocol Deviation 
Specification Form by the study team throughout the conduct of the study and sent to 
Data Manger and Biostatistics Lead in a spreadsheet. There will be no data-driven 
protocol deviation tracked.  
 
A separate summary and listing of all inclusion/exclusion criteria deviations will also 
be provided. This summary will be based on data as recorded on the 
inclusion/exclusion page of the eCRF. 
 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions 
Data Displays for Reporting 
Description 
Order in TLF 
GSK794 
1 
 
Note that all data displays (Tables, Figures, and Listings) will use the term “Subject” 
which reflects CDISC and GSK Data Display Standards terminology. 
5.2. 
Baseline Definitions 
Unless specified otherwise, baseline measurements should be the most recent value prior 
to initiating lymphodepletion and should occur within 7 days prior to initiating 
lymphodepletion. Initiation of lymphodepletion should start on Day -8, but may start on 
Day -7 if the participant was treated before consenting to Protocol Amendment 2 or after 
amendment 4 and is ≥ 60 years old. If an assessment is not available, then the last 
assessment prior to that visit would be used even if it occurred more than 7 days prior to 
initiation lymphodepletion. If time is not collected, assessments taken on the day of 
lymphodepleting chemotherapy are assumed to be taken prior to lymphodepletion and 
used as baseline. 
For laboratory data, baseline will be defined as the most recent, non-missing value from a 
central laboratory within 7 days prior to the lymphodepleting chemotherapy. If there are 
no central labs collected for a participant and a lab test prior to the lymphodepletion, the 
most recent, non-missing value from a local laboratory within 7 days prior to the 
lymphodepletion will be defined as the baseline values. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
For participants who did not receive lymphodepleting chemotherapy during the study, 
baseline will be defined as the latest, non-missing collected value.  
For participants that receive a second T-cell infusion, a second baseline associated with 
second lymphodepletion and infusion will be derived and used for all Second Infusion 
Phase displays. For all endpoints, except laboratory data, the window for baseline will be 
<=28 days prior to the initiation of second lymphodepletion chemotherapy, instead of 7 
days. For laboratory data (lymphocyte subset (CD3/CD4/CD8), hematology, chemistry, 
coagulation and urinalysis), baseline will be within 7 days of lymphodepletion as 
described above for the first infusion. 
 
 
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Parameter 
Study Assessments Considered as Baseline 
Screening Informed 
Consent 
Within 7 days prior to initiating 
lymphodepletion 
Target and Non-target 
lesions 
 
X 
Hematology, 
Chemistry, C-reactive 
protein (CRP), CMV 
PCR, Additional Lab 
 
X 
Vital Signs, Physical 
Exam, ECOG 
 
X 
Electrocardiograms 
 
X 
Cytokines 
 
X 
Demography 
X 
 
5.3. 
Multicenter Studies 
Data from all participating centers that enrol and treat patients will be pooled prior to 
analysis. 
It is anticipated that participant accrual will be spread thinly across centers and 
summaries of data by center would be unlikely to be informative and will not, therefore, 
be provided 
5.4. 
Examination of Covariates, Other Strata, and Subgroups 
No covariates or strata will be use in analysis and no subgroup analysis will be 
performed. 
5.5. 
Multiple Comparison and Multiplicity 
No formal statistical testing will be performed; therefore, no adjustments for multiple 
comparisons or multiplicity are planned.  
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: Note that all data displays (Tables, Figures, and Listings) will use the term 
“Subject” which reflects CDISC and GSK Data Display Standards terminology. 
Section 
Component 
14.3 
Appendix 3: Assessment Windows 
14.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
14.5 
Appendix 5: Data Display Standards & Handling Conventions 
14.6 
Appendix 6: Derived and Transformed Data 
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Section 
Component 
14.7 
Appendix 7: Reporting Standards for Missing Data 
14.8 
Appendix 8: Values of Potential Clinical Importance 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the ITT population, unless otherwise 
specified. The mITT population is the secondary analysis population. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, concomitant medications, disease 
characteristics at initial diagnosis and at screening, prior and on-study anti-cancer 
therapy, surgical/medical procedures, substance use, and study treatment exposure will be 
based on GSK Core and Oncology Data Standards. Study population listings will include 
second infusion data. Details of the planned displays are presented in Appendix 10: List 
of Data Displays. 
6.2. 
Disposition of Participants 
A summary of the number of participants in each of the analysis populations described in 
Section 4 will be provided. A listing of participants excluded from analysis populations 
will also be provided. 
A summary and listing of screening status and screen failures will be provided using the 
screened population.  
Reason for discontinuation, completion of study, and primary reason for study 
withdrawal will be summarized in the order they are displayed in the eCRF. Participant 
status will be displayed with the categories and subcategories Completed study (death, 
progressive disease, completed 2 years of follow-up), Ongoing or did not complete study 
with reasons from the CRF.  A summary of end of study status for ITT participants will 
be produced with the reasons Death, Moved to LTFU study, withdrew consent, lost-to-
follow-up and death. For participants that are not dosed, end of study reason is equivalent 
to end of treatment phase reason. Participants dosed and that have a death date in the 
database are classified with end of study reason=Death. Otherwise, end of treatment 
phase reason is used as the end of study reason, unless end of treatment phase reason is 
Progression. If end of treatment phase reason is Progression, then End of Study reasons is 
not available. 
Listing of reasons for study withdrawal for both Interventional Phase 1 and 2 will be 
provided. A listing of subject status will be generated, including participant number, 
lymphodepletion, date and dose of T cell infusion, study completion, and date and reason 
of discontinuation/completion of interventional phase. 
6.3. 
Protocol Deviations 
Only important protocol deviations will be summarized and listed and will include 
inclusion/exclusion deviations as well as other deviations. Protocol deviations will be 
classified as ‘major’ and ‘minor’ based on Protocol Deviation Specifications. 
A separate summary and listing of inclusion/exclusion deviations will also be provided 
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6.4. 
Demographic and Baseline Characteristics 
Disease characteristics at initial diagnosis, time since initial diagnosis in months, stage of 
lung cancer at initial diagnosis, disease stage at enrolment, and histology will be 
summarized and listed. In addition to those stated above, date of initial diagnosis will be 
listed. Refer to Section 14.6.2 for time since initial diagnosis derivation rules. 
Disease characteristics at screening, tumor type, anatomical location, number of prior 
radiotherapy regimens, number of prior systemic therapy regimens,  NY-ESO-1 status 
and HLA status will be summarized and listed. In addition to those stated above, date of 
blood collection date of biopsy for antigen testing will be listed. 
A summary of disease burden at baseline, including number of organs involved and 
location of disease at baseline, will be produced. Both target and non-target lesions at 
baseline will be included. 
The demographic characteristics at baseline (e.g., race, age, ethnicity, sex, height, body 
weight, and body mass index (kg/m^2)) will be summarized and listed. Age, height, 
weight, and bmi will be summarized using the mean, standard deviation, minimum, 
median and maximum. Age will be summarized by GSK IDSL standard as ≤18, 19-64, 
≥65. The count and percentage will be computed for sex and ethnicity. Age at T-cell 
infusion will be reported for MITT subjects. If date of T-cell infusion is not available, age 
at study eligibility is reported for ITT subjects. 
In a separate summary, age will also be categorized and summarized by 18-64, 65-84 and 
≥85 using EudraCT. 
Medical conditions will be listed and summarized.  
A summary of substance use will be presented, including smoking history, years smoked, 
and packs per day. A supporting listing will be provided. 
6.5. 
Study Treatment Exposure 
Number and percentage of participants receiving apheresis procedure, lymphodepleting 
therapy, and T cell infusion will be summarized for the first T-cell infusion. 
A listing of study treatment will be provided, including participant number, total number 
of transduced cells, percent of cells transduced, T-cell infusion date, study day, start time 
and end time for first and second T-cell infusion.  
The total number of first infusion transduced T cells will be summarized using mean, 
standard deviation, median and range.  Also, the total number of transduced T cells will 
be categorized into < 1, >=1 to <=8, and >8 (x 109 cells). 
All dose administration data for lymphodepletion, including cyclophosphamide/mesna 
and fludarabine, will be presented by participant in a data listing for first and second T-
cell infusion. 
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6.6. 
Anti-Cancer Therapy and Surgery 
Prior, bridging, and on-study anti-cancer therapy will be coded using GSK Drug coding 
dictionary. Anti-cancer therapy and cancer-related surgeries will be reported by the three 
classifications prior, bridging, and on-study, defined in Section 14.4.1.2. 
All prior anti-cancer therapy will be summarized by therapy type using the ITT and mITT 
population. A summary of the number of prior anti-cancer therapy regimens will be 
provided. Prior anti-cancer surgeries, medications, and therapies will be summarized and 
anti-cancer therapy, radiotherapy, and surgeries will be listed. Listings of radiotherapy 
and surgeries will include all procedures that occur before lymphodepletion, and within 
the listings, bridging procedures will be flagged per Section 14.4.1.2. Prior anti-cancer 
therapy will be listed and bridging anti-cancer therapy will be provided in a separate 
listing. 
On-study anti-cancer therapies will be summarized using the mITT population. A 
summary of the number of on-study anti-cancer therapy regimens will be provided. On-
study anti-cancer surgeries, medications, and therapies will be summarized, and time 
from T-cell infusion to first post-treatment anti-cancer therapy will be included. On-study 
anti-cancer therapy and surgeries will be listed. On-study therapies occurring after second 
infusion, defined as start date on or after second lymphodepletion chemotherapy, will be 
flagged in the listings. 
Tumor biopsies will be listed. 
6.7. 
Concomitant Medications 
Concomitant medications will be coded using GSK Drug coding dictionary, and will be 
summarized and listed. The summary of concomitant medications will show the number 
and percentage of participants taking concomitant medication by Ingredient. Multi-
ingredient products will be summarized by their separate ingredients rather than as a 
combination of ingredients. Anatomical Therapeutic Chemical (ATC) classification 
Level 1 (Body System) information will be included in the dataset created but will not 
appear on the listing or summary.  
In the summary of concomitant medications, each participant is counted once within each 
unique ingredient. For example, if a participant takes Amoxycillin on two separate 
occasions, the participant is counted only once under the ingredient ‘Amoxycillin’. In the 
summary of concomitant medications, the ingredients will be summarized by the base 
only. 
Concomitant medications and blood products will also be listed. Concomitant 
medications and blood products occurring after second infusion, defined as start date on 
or after second lymphodepletion chemotherapy, will be flagged in the listings. 
Definition of concomitant medication study phases are provided in Section 14.4.1.1. 
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7. 
EFFICACY ANALYSES 
Lesion assessment method and timing, evaluation of disease, disease progression and 
response criteria for all efficacy analyses will be conducted according to RECIST 
(version 1.1) [Eisenhauer , 2009]. 
To be assigned a status of SD, follow-up disease assessment must have met the SD 
criteria at least once after T-cell infusion at a minimum of 7 weeks (49 days).  
If a participant is found to have a tumor response by imaging, a follow-up confirmation 
scan must be done no earlier than 28 days following the scan when response or disease 
progression first seen. 
Independent review of scans may be performed for participants at the sponsor’s 
discretion. Analysis of independent reviewer data will not be included in the RAP, but 
may be conducted as an ad hoc exploratory analysis. 
Anti-cancer therapy for efficacy censoring includes systemic therapy, radiotherapy, anti-
cancer surgery, and tumor biopsy resections. 
The efficacy analyses will be based on the mITT population, unless otherwise specified. 
Both ORR and DCR will also be summarized based on the ITT population. Analysis of 
ORR will also occur for second infusion efficacy based on the mITT2 population.  
Second infusion efficacy displays will summarize efficacy on or after second infusion 
baseline. 
7.1. 
Secondary Efficacy Analyses 
7.1.1. 
Endpoint / Variables 
ORR 
Overall Response Rate (ORR) is defined as the percentage of participants with a 
confirmed PR or CR as the BOR, as assessed by the RECIST 1.1 Criteria. 
 
Best Overall Response (BOR) is defined as the best confirmed response (Complete 
Response (CR) > Partial Response (PR) > Stable Disease (SD) > Progressive Disease 
(PD) > Not Evaluable (NE)) from T cell infusion date until disease progression or 
initiation of new anti-cancer therapy, whichever is earlier, as assessed by the RECIST 1.1 
Criteria. 
DCR 
Disease Control Rate (DCR), defined as the percentage of participants with a SD or better 
as the BOR (i.e., Confirmed PR, confirmed CR, or SD ≥ 12 weeks, as assessed by the 
RECIST 1.1 Criteria). 
A status of SD durability will be assigned if follow-up disease assessment has met the SD 
criteria at least once after the first dose at a minimum of 12 weeks. 
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DOR 
Duration of response (DoR), defined as the interval of time in months from first 
documented evidence of PR or better to the time when disease progression is documented 
as assessed by the RECIST 1.1, or death due to any cause among participants with a 
confirmed PR or CR as the BOR. Censoring rule will follow those for PFS as specified in 
Table 2. 
 
TTR  
Time to response (TTR), defined as the interval of time (in months) between the date of 
T-cell infusion and the first documented evidence of response (PR or CR) in the subset of 
participants with a confirmed PR or CR as the BOR as assessed by the RECIST 1.1.  
 
PFS  
Progression-free survival (PFS), defined as the interval of time (in months) between the 
date of T-cell infusion and the earlier of the date of disease progression as assessed by the 
investigator per RECIST 1.1 criteria and the date of death due to any cause. 
Determination of dates of PFS events and dates for censoring are described in Table 2. 
 
If a participant has neither progressed nor died nor started new anti-cancer therapy, PFS 
will be censored at the date of the last adequate disease assessment. The acceptable 
imaging modalities for this study are: 
• 
Diagnostic-quality computerized tomography (CT) scan with oral and/or IV 
iodinated contrast of the chest and abdomen/pelvis (CT is the preferred modality for 
tumor assessments); 
• 
Magnetic resonance imaging (MRI) of the abdomen/pelvis acquired before and after 
gadolinium contrast agent administration and a non-contrast enhanced CT of the 
chest, if a participant is contraindicated for contrast enhanced CT; 
• 
MRI of the extremities per site standard of care, if clinically indicated; 
• 
Digital photographs of skin lesions including a ruler for estimating the size of the 
lesion. 
For participants who receive subsequent anti-cancer therapy the following rules will 
apply: 
• 
If anti-cancer therapy is started without documented disease progression or is started 
prior to documented disease progression, PFS will be censored at the date of the last 
adequate disease assessment that is no later than the date of initiation of anti-cancer 
therapy (i.e. if an assessment occurs on the same day as the start of new anti-cancer 
therapy the assessment will be used, as it will be assumed the assessment occurred 
prior to the administration of new anti-cancer therapy).  
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• 
If a participant has only a baseline visit or does not have an adequate disease 
assessment that is no later than the date of initiation of subsequent anti-cancer 
therapy, PFS will be censored at the date of T cell infusion. 
• 
If the start date of the subsequent anti-cancer therapy is partial (i.e. either missing the 
day but has the month and year available or missing both day and month), the 
imputation rules described in Section 14.7.2 will be applied. No imputation will be 
made for completely missing dates. 
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Table 2 
Assignments of Progression and Censoring Dates for PFS Analysis 
Scenario 
Date of Event (Progression/Death) or Censored  
Event 
(Progression/Death) 
Or Censored 
No baseline assessments4 and the participant has not 
died 
Day 1 ( NY-ESO-1c259T cell infusion) 
Censored 
No adequate post-baseline assessments before start 
of new anti-cancer therapy and the participant has 
not died 
Day 1 ( NY-ESO-1c259T cell infusion) 
Censored 
Progression documented between scheduled visits 
Date of assessment of progression1 
Event 
With adequate post-baseline assessment but no 
progression (or death)  
Date of last ‘adequate’ assessment of response2 
Censored 
With adequate post-baseline assessment and new 
anticancer treatment started (prior to documented 
disease progression).3 
Date of last ‘adequate’ assessment of response2 (on or prior to 
starting anti-cancer therapy)  
Censored 
Death before first scheduled assessment  
Date of death 
Event 
Death (regardless of having baseline assessment) 
before missing two scheduled assessments and no 
progression  
Date of death (Use rule below to determine missing two scheduled 
assessments)  
Event 
Death (regardless of having baseline assessment) or 
progression after more than two missed scheduled 
assessment 
Day 1 ( NY-ESO-1c259T cell infusion) if there is no adequate post-
baseline assessment or date of last ‘adequate’ assessment of response 
(Prior to missed assessments): 
As the assessment schedule changes through the course of the protocol 
(i.e. every 8 weeks until week 24, then every 3 months from month 9 to 
month 24, and then every 6 months thereafter), the following rules will 
be used for identifying extended loss to follow up or extended time 
without an adequate assessment (i.e. two or more missed assessments). 
• 
If PFS event is on or prior to week 24 + 7 days (Day 175), then 
a participant will be identified as an extended loss to follow up 
if the participant did not have an adequate disease assessment 
Censored 
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Scenario 
Date of Event (Progression/Death) or Censored  
Event 
(Progression/Death) 
Or Censored 
during the time period of 126 days (16 weeks+7 days+7 days) 
prior to PFS event; 
• 
Else if PFS event is after week 24 + 7 days (Day 175) and on or 
prior to the first scheduled disease assessment date (month 9 + 
14 days, day 288), then a participant will be identified as an 
extended loss to follow up if the participant missed both week 
16 and week 24 disease assessments: 
o 
 If PFS event is after week day 175 (week 24 + 7 days) 
and on or prior to day 203 (week 28 + 7 days), then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 126 days 
(16 weeks+7 days+7 days) prior to PFS event; 
o 
Else if PFS event is after day 203 (week 28 + 7 days) 
and on or prior to day 231 (week 32 + 7 days) then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 154 days 
(20 weeks+7 days + 7 days) prior to PFS event; 
o 
Else if PFS event is after day 231 (week 32 + 7 days)  
and on or prior to day 288 (month 9 + 14 days)  then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 183 days 
(24 weeks+7 days + 7 days) prior to PFS event; 
• 
Else if PFS event is after day 288 (month 9 + 14 days) and on or 
prior to the second scheduled disease assessment date (month 
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Scenario 
Date of Event (Progression/Death) or Censored  
Event 
(Progression/Death) 
Or Censored 
12 + 14 days, day 379), then a participant will be identified as 
an extended loss to follow up if the participant missed both 
week 24 and month 9 disease assessments: 
o 
If PFS event is after day 288 (month 9 + 14 days) and 
on or prior to day 318 (month 10 + 14 days), then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 168 days 
(8 weeks + 3 months+7 days + 14 days) prior to PFS 
event; 
o 
Else if PFS event is day 318 (month 10 + 14 days) and 
on or prior to day 349 (month 11 + 14 days), then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 199 days 
(8 weeks + 4 months+7 days + 14 days) prior to PFS 
event; 
o 
Else if PFS event is after day 349 (month 11 + 14 days) 
and on or prior to day 379 (month 12 + 14 days), then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 219 days 
( (9mon-24 weeks=106 days) + 3 months +7 days + 14 
days) prior to PFS event; 
• 
Else if PFS event is after day 379 (month 12 + 14 days) and on 
or prior to day 745 (month 24 + 14 days), then a participant will 
be identified as an extended loss to follow up if the participant 
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Scenario 
Date of Event (Progression/Death) or Censored  
Event 
(Progression/Death) 
Or Censored 
did not have an adequate disease assessment during the time 
period of 211 days (6 months+14 days + 14 days); 
• 
Else if PFS event is after day 745 (month 24 + 14 days) then a 
participant will be identified as an extended loss to follow up if 
they missed 1 visit 
o 
Else if PFS event is day 745 (month 24 + 14 days) and 
on or prior to day 776 (month 27 +14 days),then a 
participant will be identified as an extended loss to 
follow up if the participant did not have an adequate 
disease assessment during the time period of 211 days 
(6 months + 14 days + 14 days) prior to PFS event; 
o 
Else if PFS event is after day 776 (month 27 + 14 
days), then a participant will be identified as an 
extended loss to follow up if the participant did not 
have an adequate disease assessment during the time 
period of 274 days (6 months + 3 months) prior to PFS 
event; 
PFS will be censored at the date of last adequate disease assessment of 
response or Day 1, whatever is later, prior to PD/death.  
1 The earliest of (i) Date of radiological assessment showing new lesion (if progression is based on new lesion); or (ii) Date of radiological assessment showing unequivocal progression 
in non-target lesions, or (iii) Date of last radiological assessment of measured lesions (if progression is based on increase in sum of measured lesions) 
2 An adequate assessment is defined as an assessment where the Investigator determined response is CR, PR, or SD. 
3 If PD and New anti-cancer therapy occur on the same day assume the progression was documented first e.g., outcome is progression and the date is the date of the assessment of 
progression).  
4 No baseline assessment defined as baseline scan performed outside of the protocol defined window (>7 days before start of lymphodepletion) or no baseline scan at all. 
 
 
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7.1.2. 
Summary Measure 
ORR 
The number and percentage of participants with the BOR in the following response 
categories will be summarized: CR, PR, SD, PD, NE and overall response (CR+PR), The 
exact 95% CI for ORR will also be provided. Participants with unknown or missing 
responses will be treated as non-responders, i.e., these participants will be included in the 
denominator when calculating percentages of response. ORR will be summarized for the 
ITT, mITT, and mITT2 population. 
Change in target lesions from baseline over time will be shown in a spider plot. A 
waterfall plot showing the maximum percent reduction from baseline in tumor 
measurement will be also produced. 
ORR will be listed.  
DCR  
The number and percentage of participants with the BOR in the following response 
categories will be summarized: Confirmed CR, PR, or SD ≥ 12 weeks, clinical benefit 
response (Confirmed CR+PR+SD ≥ 12 weeks), PD and NE. The corresponding exact 
95% CI for DCR will also be provided. Participants with unknown or missing responses 
will be treated as non-responders, i.e., these participants will be included in the 
denominator when calculating percentages of DCR. DCR will be summarized for the ITT 
and mITT population. 
DOR 
If there are sufficient number of responses at time of primary or final analysis, 
distribution of DOR will be summarized using the Kaplan-Meier method. The median, 
25th and 75th percentiles of DOR will be estimated and corresponding 95% confidence 
intervals will be estimated using the Brookmeyer-Crowley method [Brookmeyer, 1982].  
TTR 
If there are sufficient number of responses at time of primary or final analysis, time to 
response at will be summarized descriptively using median, min, max and quartiles in the 
subset of participants with a confirmed response of PR or CR as the BOR.  
PFS  
The distribution of PFS will be estimated using the Kaplan-Meier method if data warrant. 
The median, 25th and 75th percentiles of PFS will be estimated and corresponding 95% 
confidence intervals will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982].  
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For DOR and PFS, Kaplan-Meier quantiles along with two-sided 95% CIs will be listed 
and summarized in months if data warrant. A Kaplan-Meier curve will be produced with 
95% confidence bands, if data warrant. 
7.1.3. 
Population of Interest  
The secondary efficacy analyses will be based on the mITT population. The ITT is the 
sensitivity analysis population for Disease Control Rate (DCR) and ORR. If the mITT 
and ITT populations are identical, only results associated with the mITT population will 
be reported. 
7.1.4. 
Strategy for Intercurrent Events 
For ORR, participants who are not evaluable or have missing response will be treated as 
non-responders; i.e. they will be included in the denominator when calculating the 
percentage 
For PFS and DOR: 
Intercurrent events, such as use of protocol prohibited medication, switching to a 
different treatment, or withdrawal of consent, are expected. Refer to Table 2 for 
censoring rules and intercurrent event strategy. 
 
7.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.1.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
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7.2. 
Exploratory Efficacy Analyses 
The only exploratory efficacy endpoint that will be reported is overall survival (OS). 
Endpoints per irRECIST will not be reported. 
7.2.1. 
Overall Survival  
Overall Survival (OS), defined as the interval of time (in months) from T-cell infusion to 
the date of death due to any cause. For participants who have not died at the time of 
analysis they will be treated as censored and the last date of known contact derived per 
Section 14.6.3. 
7.2.2. 
Summary Measure 
The distribution of OS will be estimated using the Kaplan-Meier method if data warrant. 
The median, 25th and 75th percentiles of OS will be estimated and corresponding two-
sided 95% confidence intervals will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982]. 
Kaplan-Meier quantiles along with two-sided 95% CIs will be listed and summarized in 
months if data warrant. A Kaplan-Meier curve will be produced with 95% confidence 
bands, if data warrant. 
7.2.3. 
Population of Interest 
The exploratory efficacy analyses will be based on the mITT population.  
7.2.4. 
Strategy for Intercurrent Events 
Intercurrent events, such as use of protocol prohibited medication, switching to a 
different treatment, or withdrawal of consent, are expected. If a participant has an 
intercurrent event that precludes observation of the endpoint death, the patient will be 
censored at the date of last contact. If the patient has an intercurrent even that does not 
preclude the observation of the endpoint death, the patient’s event will be included in the 
analysis and the intercurrent event will not be accounted for. 
7.2.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the Intent-To-Treat population except for displays 
that are treatment dependent. In those cases, the modified Intent-To-Treat population will 
be the primary safety, as detailed in Appendix 10: List of Data Displays. The mITT is the 
secondary analysis population.   
8.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs) 
and other significant AEs will be based on GSK Core Data Standards. Details on 
treatment emergent AEs are provided in Section 14.4.2. The details of the planned 
displays are provided in Appendix 10: List of Data Displays. 
AEs will be graded by the investigator according to the National Cancer Institute- 
Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v4.03. AEs will be coded 
to the Preferred Term (PT) level using the Medical Dictionary for Regulatory Affairs 
(MedDRA) V23.0. Per Protocol V4 effective 26-Sept-2019, CRS events are graded using 
the American Society for Transplantation and Cellular Therapy grading system [Lee, 
2019]. Previous versions of the protocol collected CRS events graded using 2014 criteria 
[Lee, 2014]. 
Per the request of the clinical team, various Preferred Terms were combined and will be 
reported together as one term. The combined terms for MedDRA Version 23.0 are listed 
in Appendix 12: Combined Preferred Terms. Changes to the MedDRA dictionary may 
occur between the start of the study and the time of reporting and/or emerging data from 
on-going studies may highlight additional combined terms, therefore the list of combined 
preferred terms will be based on the safety review team (SRT) agreements in place at the 
time of reporting. Tables that summarize AEs by SOC and PT will use MedDRA 
preferred terms, as well as any adverse event tables required for disclosure. Most other 
AE tables will summarized AEs by the combined terms in Appendix 12: Combined 
Preferred Terms, as detailed in the programming notes in Appendix 10: List of Data 
Displays. 
Tables will summarize all AEs for the ITT population and Treatment Emergent AEs for 
the mITT population. 
A summary of non-serious AEs that occurred in strictly 5% of the participants or above 
will be provided (no rounding for the percentage will be used in terms of 5% threshold, 
e.g. events with 4.9% incidence rate should not be included in this table). This summary 
will contain the number and percentage of participants and the number of occurrences of 
common non-serious adverse events. The summary table will be displayed by System 
Organ Class (SOC) and Preferred Term (PT). 
A summary of number and percentage of participants with any AEs by maximum grade 
will be produced. AEs will be sorted by PT in descending order of total incidence. The 
summary will use the following algorithms for counting the participant: 
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• 
Preferred term row: Participants experiencing the same AE preferred term several 
times with different grades will only be counted once with the maximum grade. 
• 
Any event row: Each participant with at least one AE will be counted only once at 
the maximum grade no matter how many events they have. 
In addition, the frequency and percentage of AEs (all grades) will be summarized and 
displayed in descending order of total incidence by SOC and PT. In the SOC row, the 
number of participants with multiple events under the same system organ class will be 
counted once.  
Three separate summaries will be provided for the study treatment related AEs displays. 
One table will be produced for each of the following: Lymphodepletion-related, T-cell 
related, and Any Study Treatment-related. A study treatment-related AE is defined as an 
AE for which the investigator classifies the relationship to study treatment as “Yes”, 
which includes “Definitely Related”, “Probably Related” or “Possibly Related”. A worst-
case scenario approach will be taken to handle missing relatedness data, i.e. the summary 
table will include events with the relationship to study treatment as ‘Yes’ or missing. The 
summary tables by maximum grade will be displayed in descending order of total 
incidence by PT only.  
Second infusion adverse events are defined in Section 14.4.2 and will be identified with a 
flag in AE listings. 
A listing of delayed AEs as-adjudicated by GSK will be provided. GSK adjudicated AEs 
will be provided as an additional data source.  
All AEs will be listed. Additionally, a listing of participant IDs for each individual AE 
will be produced. Time from second T-cell infusion, Study Day 2, will be included in 
listings that list data Post-Second Infusion. Study Day 2 is defined in Section 14.6.1 
8.2. 
Adverse Events of Special Interest Analyses 
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event including use of all SMQs where applicable. Changes to the MedDRA 
dictionary may occur between the start of the study and the time of reporting and/or 
emerging data from on-going studies may highlight additional adverse events of special 
interest, therefore the list of terms to be used for each event of interest and the specific 
events of interest will be based on the safety review team (SRT) agreements in place at 
the time of reporting. A focused and a comprehensive list of MedDRA terms was 
developed to identify the following AESIs. The details of the planned displays are 
provided in Appendix 10: List of Data Displays. 
The events of special interest include the following categories 
• 
Graft versus host disease 
• 
Guillain-Barre syndrome 
• 
Haematopoietic cytopenias (including pancytopenia and aplastic anaemia) 
• 
Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS) 
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• 
Cytokine release syndrome  
• 
Pneumonitis 
 
AESI tables will be reported for the mITT population. All tables below will be 
summarized using the focused list for all AESI and for the Haematopoietic cytopenia 
AESI using both the comprehensive and focused list of preferred terms. 
For each AESI, time from T cell infusion to first onset (in days) and duration of first 
occurrence and last occurrence will be summarized for all AESIs. 
 
The number and percentage of participants with these events will be summarized by 
categories of AESI and preferred term in one table. The summary of event characteristics 
for each category of AESI will also be provided, including number of participants with 
any event, number of events, number of participants with any event that is serious, 
number of participants with any event that is related to study treatment, the outcome of 
the event, maximum grade and the action taken for the event. The percentage will be 
calculated in two ways, one with number of participants with event as the denominator 
and the other with total number of participants as the denominator. The worst-case 
approach will be applied at participant level for the event outcome and maximum grade, 
i.e. a participant will only be counted once as the worst-case from all the events 
experienced by the participant. For action taken to an event, participant will be counted 
once under each action. 
A summary of onset and duration of the first occurrence and last occurrence of all AESIs 
will be created for each AESI separately. A summary of time to resolution will also be 
created for each AESI separately. The time to resolution displays summarizes participants 
with an AESI occurring before study day 28. Among all AESIs occurring before study 
day 28, the worst-case study day of resolution will be summarized. Additionally, the 
worst-case AESI duration of all recurrent AESIs will be summarized. Recurrent AESI is 
defined as additional occurrences of AESIs after initial occurrence before study day 28. 
Duration is defined as end date-start date+1. 
Characteristics, Onset and Duration, and Time to Resolution summaries will not be 
created if there are 0 or 1 AESI. 
8.2.1. 
Cytokine Release Syndrome (CRS) and Graft versus Host 
Disease (GvHD)  
Refer to Section 8.5 and Section 8.6 of the Protocol for the definitions and the grading of 
CRS and GvHD. Listing for participants experiencing AE of GVHD will be provided, 
which will include leukapheresis date, chemo start date, T cell infusion date, AE start 
date, time since infusion (days), AE end date, SAE code, severity, relationship to T cell 
infusion, and outcome of event. Listing for participants experiencing AE of CRS will also 
include time from infusion to first CRS (days) and time from infusion to max CRS 
(days). If data warrant, time from infusion to first occurrence and duration of CRS (days) 
will be summarized using mean, standard deviation, median, and range. The mock-up 
shells are in Appendix 11: Example Mock Shells for Data Displays. 
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8.3. 
Deaths and Serious Adverse Events  
In the event that a participant has withdrawn consent, no data after the withdrawal of 
consent date from this participant including death is supposed to appear in the database, 
which should be part of the data cleaning process. All deaths will be summarized based 
on the number and percentage of participants. This summary will classify participants by 
time of death relative to the date of T cell infusion as a categorical (>30 days or 30 
days) and primary cause of death (disease under study, treatment related toxicity, or 
other).  A supportive listing will be generated to provide participant-specific details on 
participants who died.  
All SAEs will be tabulated based on the number and percentage of participants who 
experienced the event. Summaries will be displayed by System Organ Class (SOC) and 
Preferred Term (PT). Another table will summarize the frequency and percentage of fatal 
AEs in descending order of total incidence by PT only.  
Three separate summaries will be provided for the study treatment related SAEs displays. 
One table will be produced for each of the following: Lymphodepletion-related, T-cell 
related, and Any Study Treatment-related. These three summaries will also be reported 
for Fatal Adverse Events if there are at least 5 participants with fatal study treatment-
related AEs. A study treatment-related SAE is defined as an SAE for which the 
investigator classifies the relationship to study treatment as “Yes”, which includes 
“Definitely Related”, “Probably Related” or “Possibly Related”. A worst-case scenario 
approach will be taken to handle missing data, i.e. the summary table will include events 
with the relationship to study treatment as ‘Yes’ or missing.  
SAEs are included in the listing of all adverse events. Separate supportive listings with 
participant-level details will be generated for 
• 
Fatal SAEs  
• 
Non-fatal SAEs. 
A plot of study duration including study days of any SAE, death, progression, and 
response will be produced. 
8.4. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analyses of Chemistry laboratory tests, Hematology 
laboratory tests, Urinalysis, and liver function tests will be based on GSK Core Data 
Standards. The details of the planned displays are in Appendix 10: List of Data Displays. 
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Clinical Chemistry: 
Calcium 
Phosphorus 
Magnesium 
Albumin 
Bilirubin 
Alanine aminotransferase 
Aspartate aminotransferase 
Alkaline phosphatase 
Lactic acid dehydrogenase 
Sodium 
Potassium 
Bicarbonate 
Creatinine* 
Chloride 
Glucose 
Urea 
* In participants <65 years of age creatinine clearance will be 
calculated using the Cockcroft-Gault Method: 
*Participants ≥65 years of age must have renal function 
measured either by 24-hour urine creatinine collection or by 
nuclear medicine EDTA GFR measurement, according to 
standard practice at the treating institution. 
Coagulation Screen: 
Prothrombin time or International Normalized Ratio 
Activated partial tissue thromboplastin time 
ECG Parameters: 
Heart Rate 
Heart Rhythm 
PR Interval  
RR Interval 
QRS Interval 
QTc Interval (Fridericia’s or Bazett’s correction) 
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Hematology: 
Red cell count 
Hemoglobin 
Hematocrit 
Mean cell volume 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Platelet count 
White blood cell count & differential count (percent & 
absolute) 
Lymphocyte subset 
Absolute cell count and percentage of CD3, CD4, and 
CD8 
Pregnancy Test: 
Serum beta-HCG or Urine test 
Thyroid Function Tests: 
TSH with reflex free T4 
Urinalysis: 
Glucose 
Ketones 
Specific gravity 
Protein 
Blood 
Microscopy 
Bilirubin 
pH 
Infectious disease markers: 
HIV 1+2 antibody 
Hepatitis B core antibody – if positive, test for HBV 
DNA 
Hepatitis C antibody – if positive, test for HCV RNA 
HTLV 1+2 IgG 
CMV IgG / DNA PCR 
Epstein-Barr virus (EBV) (EBNA) 
Syphilis (spirochaete bacterium) rapid plasma regain 
Other Tests: 
Uric Acid 
C-reactive protein 
 
Laboratory grades will be reported using the CTCAE v4.03.  
Summary of the post-baseline change of lab values for each visit (including 
cytomegalovirus (CMV) by polymerase chain reaction (PCR), and C-reactive protein 
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(CRP)) using mean, median, standard deviation, minimum, and maximum will be 
provided. Labs that do not have post-baseline values will not be included in the table. 
Summaries of worst case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v4.03. These summaries will display the number 
and percentage of participants with a maximum post-baseline grade increasing from their 
baseline grade. Missing baseline grade will be assumed as grade 0. For laboratory tests 
that are graded for both low and high values, summaries will be done separately and 
labeled by direction, e.g. sodium will be summarized as hyponatremia and 
hypernatremia. 
For lab tests that are not gradable by CTCAE v4.03, summaries of worst-case changes 
from baseline with respect to normal range will be generated. The worst case will be 
chosen from all available tests, including scheduled and unscheduled visits. Decreases to 
low, changes to normal or no changes from baseline, and increases to high will be 
summarized for the worst case post-baseline. If a participant has a decrease to low and an 
increase to high during the same time interval, then the participant is counted in both the 
“Decrease to Low” categories and the “Increase to High” categories.  
Separate summary tables for hematology, chemistry, urinalysis, and other laboratory tests  
will be produced. Unless otherwise specified, the denominator in percentage calculation 
at each scheduled visit will be based on the number of participants with non-missing 
value at each particular visit. 
A supporting listing of laboratory data for participants with any value outside normal 
range or any value of potential clinical importance will be provided. All laboratory 
values, including pre-baseline values, will be included in the listing. A separate listing of 
laboratory data with character values will also be provided. 
Detailed derivation of baseline assessment is specified in Section 5.2. 
Second infusion lab assessments will be excluded from “worst-case post baseline” in 
tables. Lab tables will only summarize first-infusion lab values. First infusion displays 
will summarize lab assessments before second infusion baseline.  All listings will include 
first infusion and second infusion assessments. 
8.4.1. 
Analyses of Liver Function Tests (LFT) 
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided.  
Possible Hy’s law cases are defined as any elevated (ALT≥3×ULN and total 
bilirubin≥2×ULN (with direct bilirubin 35% of total bilirubin, if direct bilirubin is 
measured)) OR (ALT ≥3×ULN and INR >1.5, if INR is measured). Note that INR 
measurement is not required and the threshold value stated will not apply to participants 
receiving anticoagulants. 
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A scatter plot of maximum total bilirubin versus maximum ALT will be generated. Also 
a scatter plot of maximum vs baseline for ALT will be produced. Both plots will be 
produced for first infusion only. 
8.5. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs, pregnancies, and vital 
signs will be based on GSK Core Data Standards, unless otherwise specified. 
Performance status will be summarized and listed based on GSK Oncology Data 
Standard. The details of the planned displays are presented in Appendix 10: List of Data 
Displays. 
Second infusion assessments will be excluded from “worst-case post baseline” in tables. 
Tables will be produced for first infusion only. First infusion displays will summarize 
safety assessments before second infusion baseline. All listings will include first infusion 
and second infusion assessments. 
8.5.1. 
Performance Status 
ECOG performance status will be summarized at baseline and last-assessment for first 
infusion. Summaries will use frequency and percentage of participants at each planned 
assessment time. A summary of change from baseline by scheduled visits will be 
performed, as well as the worst case post-baseline and the best case post-baseline changes 
during the study (improved, no change, deteriorated). 
A supporting listing will also be provided that includes both first infusion and second 
infusion visits. 
8.5.2. 
ECG 
A summary of the number and percentage of participants who had normal and abnormal 
(clinically significant and not clinically significant) ECG findings will be displayed by 
scheduled visits as well as for the worst case post-baseline.  The worst case will be 
chosen from all available ECG findings, including scheduled and unscheduled visits. 
A summary of change from baseline in ECG values will be produced. QtcB and QtcF will 
be summarized separately. 
The number of participants with maximum QTc values (i.e., worst case) post-baseline 
relative to baseline will be summarized by test (e.g., QTcF Interval, Aggregate) and 
category. Also, a summary by a categorization of participants’ maximum increase (i.e., 
worst case) in QTc value (e.g., QTcF Interval, Aggregate) post-baseline relative to 
baseline will be produced. Both QTcB and QTcF are collected, and will be summarized 
separately. 
Listings of abnormal ECG findings and a listing of ECG values of PCI will be provided. 
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8.5.3. 
Vital Signs 
A summary of change from baseline in vital signs will be provided. Also, a summary of 
worst case vital signs results by CTCAE criteria and normal range post-baseline relative 
to baseline will be generated.  
A listing of all vital signs data for participants with any value of PCI will be provided. 
Also there will be a listing of vital signs of PCI. 
8.5.4. 
Pregnancies 
Pregnancy (or pregnancy of a male participant’s partner) is not considered an AE/SAE 
unless there is reason to believe that the pregnancy may be the result of failure of the 
contraceptive being used due to interaction with the study drug. However, the 
investigator shall report all pregnancies immediately to the Sponsor. If participants or 
participants’ partner become pregnant while on the study, the information will be 
included in the narratives and no separate table or listing will be produced. 
8.5.5. 
Replication Competent Lentivirus (RCL) and Persistence of NY-
ESO-1c259T 
The proportion of participants showing >1% gene marked PBMCs one year post-first 
infusion or one year post-second infusion will be summarized. Only persistence 
measurements collected before occurrence of second infusion will be considered for one 
year post-first infusion derivation. 
For any patient who has greater than 1% gene marked PBMCs at at least 1 year or 
beyond post-infusion, integration site analysis will be performed on PBMCs to assess 
clonality and possible insertional oncogenesis. The proportion of participants who are 
RCL positive will also be summarized, if data warrant.  
The proportion of participants who are RCL positive will also be summarized for all 
infusions. 
RCL results will also be presented in a data listing. 
 
 
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9. 
BIOMARKER ANALYSES 
9.1. 
Exploratory Biomarker Analyses 
9.1.1. 
Endpoint / Variables 
Persistence, cytokines, and immunohistochemistry data described in this RAP will be 
reported if data warrant. Any additional exploratory biomarker, including anti-NY-ESO 
antibodies, and persistence analyses will not be included in this RAP, but may be 
described in a separate RAP and included in the CSR if data warrant. 
9.1.2. 
Summary Measure 
9.1.2.1. 
Persistence of NY-ESO-1c259T  
Spider plots will be used to graphically summarize persistence (copies/µg DNA)  over 
time for each participant by responders and non-responders for first infusion and second 
infusion separately. Maximum persistence during the study and time to maximum 
persistence will be summarized overall and for responders and non-responders using 
descriptive statistics and boxplots for first infusion. If the reported result is Negative, then 
the value 0 will be used for values deemed < lower limit of quantitation or > upper limit 
of quantitation. If the reported result is Detectable, Laboratory specified lower limit of 
quantitation, and upper limit of quantitation values will be used for values deemed < 
lower limit of quantitation or > upper limit of quantitation. 
The following calculations will be performed: 
copies/cell is calculated with the following formula: 
copies/cell=(copies/µg)x(0.0000063 µg DNA/cell) 
Percent gene marked peripheral blood mononuclear cells (PBMCs) =(copies/cell) *100 
The final reported result of copies/µg DNA is calculated as follows: 
copies/µg DNA=copies per well/µg DNA per well 
A listing of persistence will be provided and will include coefficient of variation, number 
of positive replicates, copies/cell, copies/DNA, percent gene marked PBMCs (%), 
detectable result and time to loss of 25%/50%/75% peak persistence, and duration of 
detectable persistence. Time to loss of 25% of peak persistence will be calculated as the 
time since T-cell infusion corresponding to observing at least 25% loss of peak 
persistence. If time to 25% loss of peak persistence is not observed, the last observed 
time is reported with a “+” appended to the numerical result. The same procedure will be 
followed for 50% and 75%. Duration of detectable persistence is derived as time from T-
cell infusion until persistence is no longer detectable (persistence falls below the 
detection limit and interpretive result is “Negative”). If persistence remains detectable for 
the given participant on study, the last observed time is reported with a “+” appended to 
the numerical result. Peak persistence, duration of detectable persistence and time to loss 
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of peak persistence will be derived separately for second infusion and presented in the 
listing. 
First infusion figures and tables will summarize persistence collected before second 
infusion baseline and second infusion figures will summarize persistence on or after 
second infusion baseline.   
9.1.2.2. 
Cytokines 
If data warrant, boxplots of the maximum post-baseline value and spider plots for select 
cytokines including but not limited to IL-1β, IL-10, IL-6, TNF-α, and IFN-γ will be 
provided for participants with none or non-serious CRS vs. serious CRS for the overall 
cohort and for responders vs. non-responders if data warrant. Boxplots and spider plots 
by responders vs. non-responders will also be created for cytokines IL-7 and IL-15. One 
spider plot and boxplot will be presented per cytokine.  
Cytokine results will be presented by participant in a data listing if data warrant. Pre-
baseline cytokines will also be included in the listing. Participants with an adverse event 
of serious CRS will be flagged in the listing. If the reported result is “Fail QC” or 
“CV>25%”, then the value will be set to missing for values deemed < lower limit of 
quantitation or > upper limit of quantitation. If the reported result is “<LLOQ (ex. 
<0.25)”, the laboratory specified lower limit of quantification/3 will be used. If the 
reported result is “>ULOQ (ex >2.5)”, the laboratory specified upper limit of 
quantification will be used. If there are multiple baseline values, the value analyzed first 
will be used as the baseline value. 
Only cytokine associated with first infusion will be plotted. 
9.1.3. 
Population of Interest 
The primary biomarker analyses will be based on the mITT population, unless otherwise 
specified. 
10. 
PHARMAKOKINETIC ANALYSES 
N/A 
 
11. 
POPULATION PHARMACOKINETIC (POPPK) 
ANALYSES 
N/A 
 
 
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12. 
PHARMACOKINETIC / PHARMACODYNAMIC 
ANALYSES 
N/A 
 
 
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13. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics. 1982;38:29-41.  
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
European Journal of Cancer. 2009;45(2):228-247.  
 
Lee DW, Gardner R. Current concepts in the diagnosis and management of cytokine 
release syndrome. Blood. 2014;124(2):188-195.  
 
Lee DW, Santomasso BD, Locke FL. ASTCT Consensus Grading for Cytokine Release 
Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of 
Blood and Marrow Transplantation. 2019;25:625-38.  
 
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14. 
APPENDICES 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Protocol Deviation Specification document. 
 
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14.2. 
Appendix 2: Schedule of Activities 
14.2.1. 
Protocol Defined Schedule of Events Interventional Phase I 
Table 3 
Schedule of Procedure (Interventional Phase 1) 
Screen- 
ing 
Phase1 
Interventional Phase 1 
Comp 
etion/ 
Withd 
rawal5
Leuka- 
pheresis 
Base- 
line 
Lymphodepleting 
Chemotherapy2 
T-cell 
in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
- 28 D4 
of   
Leuka- 
pheresis 
D -14 
to -9 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D 2 D 3 D 4 D 5 D 8 W 2W 3 W 4 W 5 W 
6 
W8 W 
10 
W 
1 
2 
W 
1 
6 
W 
20 
W 
24 
Every 3 
Mos 
Until Yr 
2. 
Every 6 
Mos 
Thereafter 
Visit Window 
n/a 
n/a 
n/a n/a 
n/ a n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 
days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 14 15 16 17 1 
8 
19 
20 
2 
1 
2 
2 
23 24 25-30 
31+ 
Clinical Assessments and Procedures6 (refer to Section 7.4 in the Protocol for details) 
Informed 
Consent7 
XEDC 
Demographics 
XEDC 
Inclusion/ 
Exclusion 
8 
XEDC 
X9 
Medical 
History10, and 
Tobacco Use 
X 
X 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomi- 
tant 
Medications11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
X X 
X 
X 
X 
X 
ECOG 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
Vital Signs / 
Height/ Weight12 
X 
X 
X13 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
X 
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Screen- 
ing 
Phase1 
Interventional Phase 1 
Compl 
etion/ 
Withd 
rawal5
Leuka- 
pheresis 
Base- 
line 
Lymphodepleting 
Chemotherapy2 
T-cell 
in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
- 28 D4 
of   
Leuka- 
pheresis 
D -14 
to -9 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D 2 D 3 D 4 D 5 D 8 W 
2 
W 3 W 4 W 5 W 
6 
W8 W 
10 
W 
1 
2 
W 
1 
6 
W 
20 
W 
24 
Every 3 
Mos 
Until Yr 
2. 
Every 6 
Mos 
Thereafter 
Visit Window 
n/a 
n/a 
n/a n/a 
n/ a n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 
days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 14 15 16 17 1 
8 
19 
20 
2 
1 
2 
2 
23 24 25-30 
31+ 
ECHO/MUGA 
4 
XEDC 
CT / MRI14 
X4 
X 
X 
X 
X 
X 
X 
X 
Brain MRI 28 
X 
X 
See footnote 28 
ICE29 
See footnote 29 
Chest X-ray 
X 
PFTs15 
XEDC 
Lymphocyte 
Subset 
(CD3/CD4/CD8) 
XEDC 
Hematology 
4 
XEDC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
X X 
X 
X 
X 
X 
Chemistry 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
Coagulation Tests X4 
X 
Pregnancy Test16 X 
X 
X 
X 
X 
X 
X X 
X 
X 
X 
X 
Urinalysis 
X4 
X 
Infectious disease 
markers17 
XEDC 
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Screen- 
ing 
Phase1 
Interventional Phase 1 
Compl 
etion/ 
Withd 
rawal5
Leuka- 
pheresis 
Base- 
line 
Lymphodepleting 
Chemotherapy2 
T-cell 
in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
- 28 D4 
of   
Leuka- 
pheresis 
D -14 
to -9 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D 2 D 3 D 4 D 5 D 8 W 
2 
W 3 W 4 W 5 W 
6 
W8 W 
10 
W 
1 
2 
W 
1 
6 
W 
20 
W 
24 
Every 3 
Mos 
Until Yr 
2. 
Every 6 
Mos 
Thereafter 
Visit Window 
n/a 
n/a 
n/a n/a 
n/ a n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 
days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 14 15 16 17 1 
8 
19 
20 
2 
1 
2 
2 
23 24 25-30 
31+ 
CMV IgG and 
PCR18 
X 
X 
X 
X 
X X 
TSH with free 
T419 
X 
CRP20 
X 
X 
X 
X 
X 
X 
Uric acid 
X 
X 
` 
GFR or 24h 
urine21 
X 
X 
Adverse Events22 X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X X 
X 
X X X 
X 
X 
X 
X 
Vector Copies 
(Persistence for 
Safety)23 
X 
X 
X 
X23 
X23 
VSV-G DNA 
(RCL)24 
X 
X 
X 
X24 
X24 
Leukapheresis, Lymphodepleting Chemotherapy & Investigational Product Administration 
Leukapheresis 
X 
Fludarabine 
X 
X 
X 
X 
 
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Screen- 
ing 
Phase1 
Interventional Phase 1 
Compl 
etion/ 
Withd 
rawal5 
Leuka- 
pheresis 
Base- 
line 
Lymphodepleting 
Chemotherapy2 
T-cell 
in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
- 28 D4 
of   
Leuka- 
pheresis 
D -14 
to -9 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D 2 D 3 D 4 D 5 D 8 W 
2 
W 3 W 4 W 5 W 
6 
W8 W 
10 
W 
1 
2 
W 
1 
6 
W 
20 
W 
24 
Every 3 
Mos 
Until Yr 
2. 
Every 6 
Mos 
Thereafter
Visit Window 
n/a 
n/a 
n/a n/a 
n/ a n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 
days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 
14 15 16 17 1 
8 
19 
20 
2 
1 
2 
2 
23 24 25-30 
31+ 
Cyclophos- 
phamide 
X 
X 
X 
NY-ESO-1c259T 
X 
Correlative Studies and Research Assessments (refer to Section 7.5 in the protocol for details) 
Pharmacogenetic 
analysis 
X25 
Tumor biopsy26 
X26a 
X 
X 
Liquid biopsy26b 
X 
X 
X 
Cell phenotype 
and Functional 
Assays, 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cytokine 
Analyses20 
& Humoral Anti- 
Infused Cell 
Responses 
X 
X27 
X 
X 
X 
X 
X 
X 
X 
X 
X2 
7 
X 
X 
 
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Screen- 
ing 
Phase1 
Interventional Phase 1 
Compl 
etion/ 
Withd 
rawal5
Leuka- 
pheresis 
Base- 
line 
Lymphodepleting 
Chemotherapy2 
T-cell 
in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
- 28 D4 
of   
Leuka- 
pheresis 
D -14 
to -9 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D 2 D 3 D 4 D 5 D 8 W 
2 
W 3 W 4 W 5 W 
6 
W8 W 
10 
W 
1 
2 
W 
1 
6 
W 
20 
W 
24 
Every 3 
Mos 
Until Yr 
2. 
Every 6 
Mos 
Thereafter 
Visit Window 
n/a 
n/a 
n/a n/a 
n/ a n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 
days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 11 12 13 14 15 16 17 1 
8 
19 
20 
2 
1 
2 
2 
23 24 25-30 
31+ 
Vector Copies 
(Persistence) for 
Research 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Abbreviations: CARTOX = CAR T-Cell Treatment Toxicities ; CMV = cytomegalovirus; CRP = C-reactive protein; CRS = cytokine release syndrome; CT = computerized 
tomography; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EDC = electronic data capture; FPCP = female patient of 
childbearing potential; GFR = glomerular filtration rate; MRI = magnetic resonance imaging; MUGA = multigated acquisition; n/a=not applicable; PCR = polymerase chain 
reaction; PFT = pulmonary function test; RCL = replication competent lentivirus; TSH = thyroid-stimulating hormone; VSV-G =vesicular stomatitis virus G protein 
1. 
Participants must have completed screening under Screening Protocol, ADP-0000-001, and confirmed as HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive and 
have NY-ESO-1 and/or LAGE-1a positive tumor prior to conducting the procedures in this visit.  All clinical assessments and procedures in this visit must be performed as 
indicated and recorded in source documents; however, only those assessments/procedures indicated with bold XEDC will be recorded in the EDC at this visit. 
2. 
Refer to Section 5.2 (in protocol) for details on prophylaxis therapies, pre-medications, fludarabine dose adjustments according to renal function, and supportive treatments.   
3. 
All samples will be collected and assessments performed prior to T-cell infusion, unless otherwise specified. 
4. 
All clinical assessments required at the Screening visit must be performed within 28 days of leukapheresis, with the exception of lymphocyte subset (CD3/CD4/CD8), 
hematology, chemistry, coagulation and urinalysis which must be done within 7 days of leukapheresis.  ECHO/MUGA, MRI/CT scan and laboratory assessments performed as 
standard of care prior to study consent will be acceptable as long as assessment is done within required time period before leukapheresis. 
5. 
If a participant withdraws consent or completes the Interventional Phase 1, all procedures and assessments listed at this visit must be performed, unless done within the previous 
30 days. 
6. 
All clinical assessments and procedures must be performed as indicated; however, any clinical assessment or procedure can be performed if clinically indicated at any time 
7. 
Written participant informed consent must be obtained prior to performing any assessment or procedures, unless otherwise specified.   
8. 
Participants must meet all eligibility prior to leukapheresis as specified in Section 4.2 (in protocol). 
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9. 
Participants must continue to meet all eligibility criteria (Section 4.2 (in protocol)) in addition to meeting those prior to lymphodepleting chemotherapy specified in Section 4.3 
(in protocol) 
10. 
Medical history will be recorded in the EDC at Screening and Baseline visits; however, any changes in medical history must be recorded in source documents throughout the 
conduct of the study. 
11. 
Includes all prescription, over-the-counter medications, and herbal remedies.  Any use of mutagenic agents or investigational agents must also be reported. 
12. 
Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen saturation.  Height will be collected at the Screening visit only. 
13. 
Vital signs on day of T cell infusion should be taken pre-infusion, and at 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started  
14. 
If a participant is found to have a tumor response or PD by imaging, a follow-up confirmation scan must be done no earlier than 4 weeks following the scan when response or 
PD first seen.  A participant is not considered to have a response or PD until follow-up scan confirms the finding. 
15. 
Includes FEV1, FVC, TLC, and DLCO parameters to determine eligibility as described in Exclusion criterion #23. 
16. 
FPCP must have a negative urine or serum pregnancy test.  
17. 
Includes HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochaete bacterium).  Refer to Exclusion criterion #25 for details on required testing for eligibility. Testing for 
infectious disease markers is required only at Screening and does not need to be repeated at Baseline to satisfy eligibility criteria. 
18. 
Only participants who are CMV IgG seropositive at Baseline will continue to be monitored for CMV viremia by CMV DNA PCR post Baseline. 
19. 
A free T4 test should be performed in participants who have an abnormal TSH function test (high or low). 
20. 
If CRS is suspected, cytokine and C-reactive protein levels should be measured approximately every other day until symptoms are improving or an alternative diagnosis is 
confirmed. 
21. 
Only to be done in participants ≥65 years of age to measure renal function.  
22. 
Adverse events should be reported as noted in Section 9 (in protocol) 
23. 
Persistence of gene modified cells in participants will be monitored at Months 3, 6, and 12 post-infusion, then every 6 months until 5 years post-infusion and annually from year 
6-15 post infusion. If no gene modified cells are detected for 3 consecutive assessments post-infusion, and participant is ≥5 years post-infusion, then sample collection may 
stop. 
24. 
If RCL tests are negative at all time points during the first year, then samples will be collected annually and archived for up to 15 years post infusion or until assessments for 
persistence have ended  However, if VSV-G DNA copies are detected at any time point in the first year post-infusion, refer to the safety monitoring procedures in Section 
10.1.2 (in protocol) 
25. 
If pharmacogenetic sample collection is not done at Baseline, it may be done at any other subsequent visit in the Interventional Phase 1.  Collection of a pharmacogenetic 
sample is optional and all participants must provide consent for sample collection and analysis. 
26. 
Core needle biopsies for research are at Baseline, week 8, and at confirmation of PD, with the exception of participants for whom there is no safely accessible tumor tissue.  
26a.) If a fresh biopsy was taken for NY-ESO-1and/or LAGE-1a confirmation screening in Screening Protocol, ADP-0000-001, and there is sufficient tumor sample left 
remaining, this sample may be used as the baseline sample.   Otherwise, the Baseline biopsy may be collected anytime between two months and two weeks prior to the start of 
lymphodepleting chemotherapy, with preference closer to the time of infusion. 26b.) Exosome/cfDNA samples should match tumor biopsy time points. 
27. 
Pre-infusion and Week 8 blood collection is for both Cytokine and Humoral anti-infused cell responses, and is collected in one 3 ml tube. 
28. 
Brain MRI (or CT Scan if MRI not feasible) should be obtained in all participants at the time of screening.  Baseline brain MRI should be repeated if more than 4 months have 
elapsed prior to lymphodepletion. 
29. 
CARTOX-10 should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving treatment and then at least through Day 8 according to the schedule of 
procedures.  Participants with known brain metastases should be monitored at least twice per day for the first 5 days following NY-ESO-1c259T cell infusion.  If a participant is 
found to have ES, the CARTOX-10 should be used at least twice per day until resolution or stable.  It can also be used at later visits if indicated. 
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14.2.2. 
Protocol Schedule of Events Interventional Phase II 
Table 4 
Schedule of Procedures for Second T Cell Infusion (Interventional Phase 2) 
Baseline1 
Interventional Phase 2 
Completion/ 
Withdrawal5 
Lymphodepleting 
Chemotherapy2 
T-cell in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
-28 D4 of 
Chemo- 
therapy 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D2 D3 D4 D5 D8 W 2 W 4 W 8 W 
12 
W 
16 
W 20 W 24 Every 3 
Mos Until 
Yr 2. 
Every 6 Mos 
Thereafte r 
Visit Window 
n/a n/a 
n/a 
n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
14 
17 
19 
20 
21 
22 
23-28 
29+ 
Clinical Assessments and Procedures6 (refer to Section 7.4 of the protocol for details) 
Informed 
Consent7 
X 
Inclusion/ 
Exclusion 
X8 
Medical History9 X 
Physical Exam 
X 
X 
X 
X 
Prior/Concomi- 
tant 
Medications10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs / 
Height/ Weight11 
X 
X12 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
X 
X 
X 
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Baseline1 
Interventional Phase 2 
Completion/ 
Withdrawal5 
Lymphodepleting 
Chemotherapy2 
T-cell in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
-28 D4 of 
Chemo- 
therapy 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D2 
D3 
D4 
D5 
D8 
W 2 W 4 W 8 W 12 W 16 W 20 W 24 Every 3 
Mos Until 
Yr 2. 
Every 6 Mos 
Thereafter 
Visit Window 
n/a 
n/a 
n/a 
n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
14 
17 
19 
20 
21 
22 
23-28 
29+ 
ECHO/MUGA 
X 
CT / MRI 13 
X 
X 
X 
X 
X 
X 
X 
Brain MRI 
X 
See footnote 27 
Chest X-ray 
X 
PFTs14 
X 
Lymphocyte 
subset 
(CD3/CD4/CD8) 
X 
Hematology 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry 
X4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation Tests X4 
Pregnancy Test15 X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X4 
Infectious disease 
markers16 
X 
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Baseline1 
Interventional Phase 2 
Completion/ 
Withdrawal5 
Lymphodepleting 
Chemotherapy2 
T-cell in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
-28 D4 of 
Chemo- 
therapy 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D2 
D3 
D4 
D5 
D8 
W 2 W 4 W 8 W 12 W 16 W 20 W 24 Every 3 Mos 
Until Yr 2. 
Every 6 
Mos 
Thereafter
Visit Window 
n/a 
n/a 
n/a 
n/a 
n/a 
±1 day 
±3  days 
±7 days 
±14 days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
14 
17 
19 
20 
21 
22 
23-28 
29+ 
Fludarabine 
X 
X 
X 
X 
Cyclophos- 
phamide 
X 
X 
X 
NY-ESO-1c259T 
X 
Correlative Studies and Research Assessments (refer to Section 7.5 of the Protocol for details) 
Tumor biopsy25 X25a 
X 
X 
Liquid biopsy25 X 
X 
X 
X 
X 
X 
X 
Cell phenotype 
and Functional 
Assays, 
X 
X 
X 
X 
X 
X 
X 
X28 
X28 
X 
Cytokine 
Analyses19 
& Humoral Anti- 
Infused Cell 
Responses 
X26 
X 
X 
X 
X 
X 
X 
X 
X26 X 
X28 
X28 
X 
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Baseline1 
Interventional Phase 2 
Completion/ 
Withdra 
wal5 
Lymphodepleting 
Chemotherapy2 
T-cell in- 
fusion3 
Post-T-cell Infusion 
Day (D) / Week 
(W) 
-28 D4 of 
Chemo- 
therapy 
D 
-8 
D 
-7 
D 
-6 
D 
-5 
D1 
D2 
D3 
D4 
D5 
D8 
W 2 W 4 W 8 W 12 W 16 W 20 W 24 Every 3 Mos 
Until Yr 2. 
Every 6 Mos 
Thereafter 
Visit Window 
n/a 
n/a 
n/a n/a 
n/a 
±1 day 
±3 days 
±7 days 
±14 days 
±3 mos 
n/a 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
14 
17 
19 
20 
21 
22 
23-28 
29+ 
Vector Copies 
(Persistence) for 
Research 
X1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Abbreviations: CMV = cytomegalovirus; CRP = C-reactive protein; CRS = cytokine release syndrome; CT = computed tomography; ECG = electrocardiogram; ECHO = 
echocardiogram; ECOG = Eastern Cooperative Oncology Group; FPCP = female patient of childbearing potential; MRI = magnetic resonance imaging; n/a=not applicable; PCR = 
polymerase chain reaction; PFT = pulmonary function test; RCL = replication competent lentivirus; TSH = thyroid-stimulating hormone; VSV-G =vesicular stomatitis virus G protein 
1. 
Participants must have been considered eligible for a second infusion (refer to Section 4.4 (in protocol)) before initiating any screening procedures or assessments for 
Interventional Phase 2. 
2. 
Refer to Section 5.2 (in protocol)  for details on prophylaxis therapies, pre-medications, fludarabine dose adjustments according to renal function, and supportive 
treatments.   
3. 
All samples will be collected and assessments performed prior to T-cell infusion, unless otherwise specified. 
4. 
Clinical procedures or assessments do not need to be repeated at this Baseline visit if they were be performed within 28 days of planned leukapheresis, with the exception 
of lymphocyte subset (CD3/CD4/CD8), hematology, chemistry, coagulation and urinalysis which must be done within 7 days of leukapheresis.  
5. 
If a participant withdraws consent or completes the Interventional Phase 2, all procedures and assessments listed at this visit must be performed, unless done within the 
previous 30 days. 
6. 
All clinical assessments and procedures must be performed as indicated; however, any clinical assessment or procedure can be performed if clinically indicated at any 
time. 
7. 
An additional written participant informed consent for a second infusion must be obtained prior to performing any Baseline assessments or procedures, unless otherwise 
specified.   
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8. 
Participants must continue to meet all eligibility criteria (Section 4.2 and Section 4.3 (in protocol)) in addition to meeting those prior to second infusion specified in 
Section 4.4 (in protocol)). 
9. 
Any new or changes in medical history will be recorded in the EDC at Baseline visit; however, any additional changes in medical history must be recorded in source 
documents throughout the conduct of the study. 
10. 
Includes all prescription, over-the-counter medications, and herbal remedies.  Any use of mutagenic agents or investigational agents must also be reported. 
11. 
Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen saturation.  Height will be collected at the Screening visit only. 
12. 
Vital signs on day of T cell infusion should be taken pre-infusion, and at 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started. 
13. 
If a participant is found to have a tumor response or PD by imaging, a follow-up confirmation scan must be done no earlier than 4 weeks following the scan when 
response or PD first seen.  A participant is not considered to have a response or PD until follow-up scan confirms the finding. 
14. 
Includes FEV1, FVC, TLC, and DLCO parameters to determine eligibility as described in Exclusion criterion #23. 
15. 
FPCP must have a negative urine or serum pregnancy test.  
16. 
Includes HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochaete bacterium).  Refer to Exclusion criterion #25 for details on required testing for eligibility. 
17. 
Only participants who are CMV IgG seropositive at baseline will continue to be monitored for CMV viremia by CMV DNA PCR post baseline. 
18. 
A free T4 test should be performed in participants who have an abnormal TSH function test (high or low). 
19. 
If CRS is suspected, cytokine and C-reactive protein levels should be measured approximately every other day until symptoms are improving or an alternative diagnosis is 
confirmed. 
20. 
Only to be done in participants ≥65 years of age to measure renal function.  
21. 
Adverse events should be reported as noted in Section 9 (in protocol). 
22. 
Persistence of gene modified cells in participants will be monitored at Months 3, 6, and 12 post-infusion, then every 6 months until 5 years post-infusion and annually 
from year 6-15 post infusion. If no gene modified cells are detected for 3 consecutive assessments post-infusion, and participant is >5 years post-infusion, then sample 
collection may stop. 
23. 
If RCL tests are negative at all time points during the first year, then samples will be collected annually and archived for up to 15 years post or until assessments for 
persistence have ended  However, if VSV-G DNA copies are detected at any time point in the first year post-infusion, refer to the safety monitoring procedures in Section 
10.1.2 (in protocol). 
24. 
CARTOX-10 should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving treatment and then at least through Day 8 according to the schedule of 
procedures.  Participants with known brain metastases should be monitored at least twice per day for the first 5 days following NY-ESO-1c259T cell infusion.  If a 
participant is found to have ES, the CARTOX-10 should be used at least twice per day until resolution or stable.  It can also be used at later visits if indicated. 
25. 
Core needle biopsies are at baseline, week 8, and at confirmation of PD, with the exception of participants for whom there is no safely accessible tumor tissue.  24a.) If a 
fresh biopsy was taken to confirm continued expression of NY-ESO-1 and/or LAGE-1a at the time of PD after the first T cell infusion and there is sufficient tumor sample 
left remaining, this sample may be used as the baseline sample.   Otherwise, the baseline biopsy may be collected anytime between two months and two weeks prior to the 
start of lymphodepleting chemotherapy, with preference closer to the time of infusion. 24b.) Exosome/cfDNA samples should match tumor biopsy time points.   
26. 
Pre-infusion and Week 8 blood collection is for both Cytokine and Humoral anti-infused cell responses, and is collected in one 3 ml tube. 
27. 
Brain MRI will be performed at baseline for all participants and as clinically indicated thereafter (see Section 8.9.2 (in protocol)). 
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14.2.3. 
Protocol Defined Schedule of Events Long Term Follow-up 
Table 5 
Schedule of Procedures – Long Term Follow- up 
Time post-infusion 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Years 6-15 
Months 
3 
6 
12 
18 
24 
30 
36 
42 
48 
54 
60 
Annually 
Visit window 
± 2 weeks 
± 3 month 
± 6 months 
Safety Assessments 
Medical History and Physical Exam1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mutagenic agents, other investigational agents or anti-cancer 
therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Delayed adverse Events and Serious Adverse Events2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test for WOCBP3 
<===========================X3===========================> 
Hematology 
X 
X 
X 
X 
X 
X 
X4 
Serum chemistry 
X 
X 
X 
X 
X 
X 
X4 
Allogeneic SCT 
X 
X 
X 
X 
X 
Laboratory Assessments 
VSV-G DNA (RCL) for safety 
X 
X 
X 
X 
X 
X 
X 
X4 
Transgene Copies (Persistence) for safety 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Other Assessments 
Survival Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: RCL=replication competent lentivirus; SCT=stem cell transplant; VSV-G =vesicular stomatitis virus G protein 
1. 
New medical history/medications/chemotherapies. 
2. 
Delayed adverse Event and Serious Adverse Event collection is limited to: 
 New malignancies 
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 New incidence or exacerbation of a pre-existing neurologic disorder 
 New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder 
 New incidence of immune-related hematologic disorder 
 Serious infections (including opportunistic) 
 Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy 
3. 
For women of child bearing potential (WOCBP), pregnancy testing should be conducted during contraception period only as defined in Section 5.1 
(in protocol). When pregnancy testing is performed at visits where hematology sample is collected, blood pregnancy testing will be done. At visits 
where hematology sample is not collected, urine pregnancy test is acceptable unless serum testing is required by local regulation or IRB/IEC. 
4. 
In year 6-15, these assessments are performed for as long as persistence is analyzed. If persistence samples are discontinued (Section 10.3 (in 
protocol)) then laboratory assessments are discontinued 
 
 
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14.3. 
Appendix 3: Assessment Windows 
Assessment windows will not be used. 
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14.4. 
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events 
14.4.1. 
Study Phases 
14.4.1.1. 
Study Phases for Concomitant Medications 
Study Phase 
Definition 
Prior 
End date of medication is not missing and is before the start date of lymphodepletion 
OR lymphodepletion start date is missing 
Concomitant  
Medication is not a prior 
NOTES:  
• 
Please refer to Appendix 7: Reporting Standards for Missing Datafor handling of missing and partial dates for 
concomitant medication. Use the rules in this table if concomitant medication date is missing. 
 
14.4.1.2. 
Study Phases for Anti-Cancer Therapy/Surgery 
Study Phase 
Definition 
Prior 
Start date is prior to first day of leukapheresis or leukapheresis start date is 
missing 
Bridging 
Start date is on or after the day of apheresis to the day before initiation of 
lymphodepletion chemotherapy 
On-Study 
Start date is on or after the first day of lymphodepletion chemotherapy 
NOTES:  
• 
Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial dates for 
anti-cancer therapy 
 
14.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent  
• 
If AE onset date is on or after first lymphodepletion chemotherapy start date. 
(Lymphodepletion Start Date ≤ AE Start Date) until end of study, include AEs 
onset on or after the second lymphodepletion for participants who receive a 
second T-cell infusion. 
• 
Treatment emergence for second infusion will be defined as: If AE onset date is 
on or after second lymphodepletion chemotherapy start date. 
(Lymphodepletion Start Date ≤ AE Start Date) until end of study. 
• 
If AE onset date is missing and AE end date is before the lymphodepletion start 
date, then the AE will not be classified as Treatment-Emergent. If AE onset date 
is missing and AE end date is either missing or on or after lymphodepletion start 
date, then the AE will be classified as treatment-emergent  
• 
Missing AE Start Date will be imputed following rules in Section 14.7.2.1 for 
determining Treatment Emergent AEs. 
 
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14.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
14.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: arprod\GSK3377794\mid208749 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.1]. 
Generation of RTF Files 
• 
RTF files will be generated for SAC upon request. 
14.5.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings 
Formats 
• 
GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
o Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
o The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
o Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
o Unscheduled or unplanned readings will be presented within the participant’s listings.  
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Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables and/or figures, except in cases where 
worse-case post-baseline is calculation. 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
 
 
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14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented. 
• 
For character variables, if multiple assessments on different days are reported for the same 
scheduled assessment, then the worst case assessment for that scheduled assessment will be 
analyzed 
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance 
summary tables. 
Study Day 
• 
Calculated as the number of days from T cell infusion date: 
o Ref Date = Missing              → Study Day = Missing  
o Ref Date < T cell infusion Date → Study Day = Ref Date – T cell infusion Date 
o Ref Data ≥ T cell infusion Date → Study Day = Ref Date – T cell infusion Date + 1  
Second study day (Study Day 2) will be calculated for participants with second T-cell infusion as below 
o Ref Date = Missing              → Study Day = Missing  
o Ref Date < Second T cell infusion Date → Study Day = Ref Date – Second T cell infusion Date 
o Ref Data ≥Second T cell infusion Date → Study Day = Ref Date – Second T cell infusion Date 
+ 1  
Change from Baseline 
• 
Change from Baseline = Post-Baseline Visit Value – Baseline 
• 
% Change from Baseline= 100 x (Post-Baseline Visit Value – Baseline) / Baseline 
• 
Maximum Increase/Decrease from Baseline = maximum (Increase/Decrease from Baseline) 
• 
If either the Baseline or Post-Baseline Visit Value is missing, Change from Baseline and % Change 
from Baseline is set to missing 
Date of Response 
• For post-baseline disease assessments, the date of response (PR,CR) is assigned to the latest date 
of disease assessments; for other response categories (SD, NE, PD), the date of response is 
assigned to the earliest date of disease assessments.    
Date of New On-study Anti-Cancer Therapy 
• 
Derived as the earliest date of new on-study anti-cancer therapy, radiotherapy (where applicable) or 
cancer-related surgical procedure (where applicable) 
• Missing or partial dates will be imputed for derivation of new anti-cancer therapy following rules 
specified in Section 14.7.2.1. 
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14.6.2. 
Study Population 
Age 
• 
For participants with a T-cell infusion date, age is derived using T-cell infusion date as the reference 
date. For ITT participants without a T-cell Infusion date, date of eligibility for apheresis is used as the 
reference date. 
BMI 
• 
(Weight in kg) / (Height in meters)2 
Time from Screening to Initial Diagnosis 
• 
Calculated as the number of months from the Date of Initial Diagnosis: 
o Informed Consent Date = Missing           → Elapse Time = Missing  
o Date of Initial Diagnosis = Completely/partially Missing       → Elapse Time = Missing  
• 
Otherwise       → Elapse Time = (Informed Consent Date – Date of Initial Diagnosis + 1)/30.4375         
 
14.6.3. 
Efficacy 
Refer to Section 7 for endpoint derivation information. 
Overall Survival 
Date of Last Contact 
• 
Last date in all SDTM domains 
• 
If patient died, the last contact date should be death date. 
• 
Dates after date of death will be excluded. Future dates will be excluded. 
• 
SDTM domain SE and SUPPBE will be excluded and SDTM variables DM.BRTHDTC, 
MH.MHSTDTC, SV.SVENDTC, SV.SVSTDTC,  DM.RFPENDTC,  _ALL_.ANALDTC, DV.DVDTC, 
DV.DVSTDTC,and RS.RSDTC where RSEVAL=’INDEPENDENT ASSESSOR’ will be excluded 
• 
Partial and missing dates will not be imputed for the purpose of deriving date of last contact 
 
 
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14.6.4. 
Safety 
Adverse Events 
AE’S of Special Interest 
• Cytokine Release Syndrome 
• Pneumonitis 
• Graft vs Host Disease 
• Haematopoietic cytopenias (including pancytopenia and aplastic anaemia) 
• Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS) 
• Guillain-Barre Syndrome  
Duration of AE 
• 
Calculated as the number of days from AE Start Date to AE Stop Date: 
o AE Start Date = Missing              → Elapse Time = Missing  
o AE Stop Date = Missing              → Elapse Time = Missing 
Otherwise                                    → Elapsed Time = AE Stop Date – AE Start Date + 1     
Imputed dates will not be used to calculated AE duration 
Corrected Calcium for Albumin 
• 
Corrected Calcium [mg/dL]= Total Calcium [mg/dL] + 0.8 * (4.0 – serum albumin [g/dL]) 
• 
Corrected Calcium [mmol/L] =  
Total Calcium [mmol/L] / .2495 + 0.8 * .2495 * (4.0 - serum albumin [g/L]/10)  
 
 
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14.7. 
Appendix 7: Reporting Standards for Missing Data 
14.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Participant study completion (i.e. as specified in the protocol) was defined as when 
he/she has PD or has died prior to PD, or 2 years after the NY-ESO T-cell infusion, 
whichever is shorter for participants that receive one T-cell infusion. For participants 
that receive a second T-cell infusion, study completion is defined as when he/she has 
PD or has died prior to PD, or 6 months after the second T-cell infusion, whichever is 
shorter. 
• 
Withdrawn participants were not replaced in the study. 
• 
All available data from participants who were withdrawn from the study will be listed 
and all available planned data will be included in summary tables and figures, unless 
otherwise specified.  
14.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank 
fields on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant listing 
displays. Unless all data for a specific visit are missing in which case the data 
is excluded from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
14.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. However, 
where necessary, display macros may impute dates as temporary variables for 
sorting data in listings only. In addition, partial dates may be imputed for ‘slotting’ 
data to study phases (see Section 14.4.1) or for specific analysis purposes as 
outlined below. 
• 
Imputed partial dates will not be used to derive study day, duration (e.g., duration 
of adverse events), or elapsed time variables unless otherwise specified. In 
addition, imputed dates are not used for deriving the last contact date in overall 
survival analysis dataset. 
• 
Imputed partial dates for anti-cancer therapy, surgery, and radiotherapy will be 
used for plotting therapies in Figure 3.010, only if the day is missing. 
Adverse Events 
• 
Imputations in the adverse events dataset are used for slotting events to the 
appropriate study time periods and for sorting in data listings. 
o This includes identifying an AESI as first or last occurrence. 
• 
Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
 
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Element 
Reporting Detail 
Missing start day 
• 
If lymphodepletion start date is missing (i.e. participant did 
not start lymphodepletion), then set start date = 1st of 
month. 
• 
Else if lymphodepletion start date is not missing: 
o 
If month and year of start date = month and year of 
lymphodepletion start date then 
▪ 
If stop date contains a full date and stop date is 
earlier than lymphodepletion start date then set 
start date= 1st of month. 
▪ 
Else set start date = lymphodepletion start date. 
o Else set start date = 1st of month. 
Missing start day 
and month 
• 
If lymphodepletion start date is missing (i.e. participant did 
not start lymphodepletion), then set start date = January 
1. 
• 
Else if lymphodepletion start date is not missing: 
o 
If year of start date = year of lymphodepletion start 
date then 
▪ 
If stop date contains a full date and stop date is 
earlier than lymphodepletion start date then set 
start date = January 1. 
▪ 
Else set start date = lymphodepletion start 
date.       
o Else set start date = January 1. 
Missing stop day  
Last day of the month will be used. 
Missing stop day 
and month 
No Imputation 
Completely 
missing start/end 
date 
No imputation. 
Concomitant 
Medications 
• 
These imputation rules will be used for classifying a medication as prior or 
concomitant 
• 
Completely missing start dates will not be imputed 
• 
Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
• 
Rules will be applied for second infusion separately 
 
Missing start day 
• 
If lymphodepletion start date is missing (i.e. participant 
did not receive lymphodepletion), then set start date = 1st 
of month. 
• 
Else if lymphodepletion start date is not missing: 
o 
If month and year of start date = month and year of 
lymphodepletion start date then 
▪ 
If stop date contains a full date and stop date is 
earlier than lymphodepletion start date then set 
start date= 1st of month. 
▪ 
Else set start date = lymphodepletion start date. 
o Else set start date = 1st of month. 
Missing start day 
and month 
• 
If lymphodepletion start date is missing (i.e. participant 
did not receive lymphodepletion), then set start date = 
January 1. 
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Element 
Reporting Detail 
• 
Else if lymphodepletion start date is not missing: 
o 
If year of start date = year of lymphodepletion start 
date then 
▪ 
If stop date contains a full date and stop date is 
earlier than lymphodepletion start date then set 
start date = January 1. 
▪ 
Else set start date = lymphodepletion start 
date.       
• 
Else set start date = January 1. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on the 
month and year)  
Missing end day 
and month 
A '31' will be used for the day and 'Dec' will be used for the 
month. 
Completely 
missing start/end 
date 
No imputation 
Anti-Cancer 
Therapy and 
Radiotherapy 
• 
Completely missing start or end dates will remain missing, with no imputation 
applied. 
• 
If partial start date contains a year only set to January 1st. 
• 
If partial start date contains a month and year set to the 1st of the month. 
• 
No imputation for partial end dates will be performed. 
Surgical 
Procedures 
• 
No Imputation for completely missing dates 
• 
If partial date contains a year only set to January 1st. 
• 
If partial date contains a month and year set to the 1st of the month 
New On-study 
Anti-Cancer 
Therapy/ 
Radiotherapy/ 
Surgical 
Procedures for 
Efficacy 
Evaluation  
• 
Start dates for on-study anti-cancer therapy, radiotherapy (where applicable), and 
surgical procedures (where applicable) will be temporarily imputed in order to 
define event and censoring rules for progression-free survival, response rate, or 
duration of response (i.e. start date for new anti-cancer therapy). Dates will only 
be imputed when a month and year are available but the day is missing. The 
following rules will be used to impute the date when partial start dates are present 
on anti-cancer therapy radiotherapy, and/or surgical procedures datasets. 
• 
Completely missing start dates will remain missing, with no imputation applied; 
• 
Partial start dates will be imputed using the following convention: 
• 
If both month and day are missing, no imputation will be applied; 
• 
If only day is missing:  
o If the month of partial date is the same as the month of T-cell infusion, 
minimum of (T-cell infusion + 1, last day of the month) will be used for the 
day; 
o If the month of partial date is the same as the month of last disease 
assessment and the last disease assessment is PD, minimum of (last 
date of disease assessment + 1, last day of the month) will be used for 
the day; 
o If both conditions above are met, the later date will be used for the day; 
o Otherwise, a ‘01’ will be used for the day; 
• 
Completely or partial missing end dates will remain missing, with no imputation 
applied; 
Rules will be applied for second infusion separately 
 
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14.8. 
Appendix 8: Values of Potential Clinical Importance 
To identify laboratory values of potential clinical importance, National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03) will be used to 
assign grades for laboratory parameters including clinical chemistry, hematology, liver 
function tests, thyroid function tests, pancreatic enzyme tests, QTc (Bazett’s or 
Fridericia’s) values, and vital signs (heart rate, blood pressure, temperature).  
14.8.1. 
Laboratory Values 
Reference ranges for all laboratory parameters collected throughout the study are 
provided by the laboratory. A laboratory value that is outside the reference range is 
considered either high abnormal (value above the upper limit of the reference range) or 
low abnormal (value below the lower limit of the reference range). Note: a high abnormal 
or low abnormal laboratory value is not necessarily of clinical concern. The laboratory 
reference ranges will be provided on the listings of laboratory data. Clinical laboratory 
test results outside of the reference range will be flagged in the listings. 
To identify laboratory values of potential clinical importance, National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) will be used to 
assign grades to the relevant laboratory parameters. NCI-CTCAE v4.03 can be found at 
http://ctep.cancer.gov/reporting/ctc.html.  
For laboratory data which are not listed in the NCI CTCAE v4.03, a summary of values 
outside the normal range will be provided. 
 For lab test values that can be graded, values of grade 1 or above are defined as values of 
potential clinical concern. For lab test values that cannot be graded, values out of the 
normal range are defined as values of potential clinical concern. Abnormal, clinically 
significant Urinalysis labs will be also be considered PCI values. 
14.8.2. 
ECG Parameters  
To identify QTc (Bazett’s or Fridericia’s) values of potential clinical importance, NCI-
CTCAE v4.03 will be used to assign grades (see adverse event ‘Electrocardiogram QT 
corrected interval prolonged’). The CRF collects either QTcB or QTcF. Note that there is 
a slight inconsistency between CTCAE v4.03 and ICH E14 (Absolute QTc interval 
prolongation). It was decided to align with CTCAE for the oncology standard categories. 
 
The following criteria will be used to flag electrocardiogram (ECG) values that are values 
of potential clinical importance:  
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PCI Flag 
Potential Clinical Importance (PCI) Range 
 
High (H) 
Grade 2 or Higher (QTc>480)  
or  
QTc increase from baseline of >30msec 
 
 
14.8.3. 
Vital Signs 
To identify heart rate values of potential clinical importance, NCI-CTCAE v4.03 will be 
used to assign categories that align with the grades for ‘Sinus bradycardia’, ‘Sinus 
tachycardia’, ‘Supraventricular tachycardia’, and ‘Ventricular tachycardia’. 
The following criteria will be used to flag vital sign values that are values of potential 
clinical importance: 
Vital Sign Parameter 
Potential Clinical Importance (PCI) Range 
Unit 
Decrease from baseline 
Heart Rate 
Decrease to <60 
bpm 
Increase from baseline 
Heart Rate 
Increase to >100 
bpm 
 
To identify blood pressure values of potential clinical importance, NCI-CTCAE v4.03 
will be used to assign categories that align with the grades for ‘Hypertension’. 
Vital Sign Parameter 
Potential Clinical Importance (PCI) Range 
Unit 
Increase from baseline 
Systolic Blood Pressure 
120 to <140 (Grade 1) 
140 to <160 (Grade 2) 
160 (Grade 3) 
mmHg 
Increase from baseline 
Diastolic Blood 
Pressure 
80 to <90 (Grade 1) 
90 to <100 (Grade 2) 
100 (Grade 3) 
mmHg 
 
To identify temperature values of potential clinical importance, NCI-CTCAE v4.03 will 
be used to assign categories that align with the grades for ‘Hypothermia’ and ‘Fever’. 
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Vital Sign Parameter 
Potential Clinical Importance (PCI) Range 
Unit 
Increase from baseline 
temperature 
Increase to 38 
Degrees 
C 
Decrease from baseline 
Diastolic Blood 
Pressure 
Decrease to 35 
Degrees 
C 
 
To identify oxygen saturation values of potential clinical importance, NCI-CTCAE v4.03 
will be used to assign categories that align with “Hypoxia” 
Vital Sign Parameter 
Potential Clinical Importance (PCI) Range 
Unit 
Decrease for baseline 
oxygen saturation 
Decrease to <88 
% 
 
 
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14.9. 
Appendix 9: Abbreviations & Trade Marks 
14.9.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
A&R 
Analysis and Reporting  
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CRS 
Cytokine Release Syndrome 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
CTCAE 
Common Toxicity Criteria for Adverse Events 
CTR 
Clinical Trial Register 
DBF 
Database Freeze 
DBR 
Database Release 
DOR 
Duration of Response 
DP 
Decimal Places 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Record Form 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure Requirements 
GSK 
GlaxoSmithKline 
GvHD 
Graft versus Host Disease 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
IP 
Investigational Product 
ITT 
Intent-To-Treat 
LVEF 
Left Ventricular Ejection Fraction 
MedDRA 
Medical Dictionary for Regulatory Affairs 
ORR 
Overall Response Rate 
OS 
Overall Survival 
PCI 
Potential Clinical Importance  
PFS 
Progression Free Survival 
PP 
Per Protocol 
PT 
Preferred Term 
QC 
Quality Control 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
SAC 
Statistical Analysis Complete 
SDTM 
Study Data Tabulation Model 
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Abbreviation 
Description 
SOC 
System Organ Class 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
TTR 
Time to Response 
WHO 
World Health Organization 
14.9.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
NONE 
 
SAS 
 
 
 
 
 
 
 
 
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14.10. 
Appendix 10: List of Data Displays 
14.10.1. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 11: Example Mock Shells for Data Displays. Shells are 
subject to some minor formatting modifications post RAP approval. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Biomarker 
BIO_Fn 
BIO_Tn 
BIO_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
 
14.10.2. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.010 to 1.320 
NA 
Efficacy 
2.010 to 2.080 
2.010 to 2.050 
Safety 
3.010 to 3.670 
3.010 to 3.040 
Pharmacodynamic and / or Biomarker 
6.010 to 6.020 
6.010 to 6.290 
Section 
Listings 
ICH Listings 
10 to 580 
Other Listings 
590 to 680  
 
14.10.3. 
Deliverables 
Delivery  
Description 
SAC 
 Statistical Analysis Complete 
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14.10.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Subject Disposition 
1.010. 
ITT 
POP_T2 
Summary of Subject Status- Interventional Phase 1 (ITT 
Population) 
ICH E3, FDAAA, EudraCT 
 
 
SAC 
1.020. 
mITT 
POP_T2 
Summary of Subject Status- Interventional Phase 1 (mITT 
Population) 
ICH E3, FDAAA, EudraCT 
  
SAC 
1.030. 
ITT 
POP_T3 
Summary of Subject Status- End of Study  
ICH E3, FDAAA, EudraCT 
 
SAC 
1.040. 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
Journal Requirements 
Add a footnote that we only have data 
from about 40 subjects and x subjects 
were screened under Adaptimmune 
and why 
SAC 
1.050. 
ITT 
NS1 
Summary of Number of Subject by Country and Site ID 
EudraCT/Clinical Operations 
Include Site Name  
SAC 
1.060. 
ITT 
Non-Standard 
Summary of Apheresis, Lymphodepletion, and T cell Infusion 
Use POP_T1 
SAC 
Protocol Deviation 
1.070. 
ITT 
DV1 
Summary of Important Protocol Deviations 
ICH E3 
SAC 
Population Analysed 
1.080. 
ITT 
SP1A 
Summary of Study Populations  
IDSL 
ITT, mITT, Second T-cell Infusion 
SAC 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Demographic and Baseline Characteristics 
1.090. 
ITT 
DM1  
Summary of Demographic Characteristics (ITT Population) 
ICH E3, FDAAA, EudraCT 
Report baseline height, weight, and 
BMI, 
Report Race not Race Detail 
SAC 
1.100. 
mITT 
DM1  
Summary of Demographic Characteristics (mITT Population) 
ICH E3, FDAAA, EudraCT 
Report screening height, weight, and 
BMI 
Report Race not Race Detail 
SAC 
1.110. 
ITT 
DM11 
Summary of Age Ranges 
EudraCT 
SAC 
Prior and Concomitant Medications 
1.120. 
ITT 
MH1 
Summary of Medical Conditions (ITT Population) 
ICH E3  
 
SAC 
1.130. 
mITT 
MH1 
Summary of Medical Conditions (mITT Population) 
ICH E3  
 
SAC 
1.140. 
mITT 
CM8 
Summary of Concomitant Medications 
 ICH E3 
Use GSKDRUG 
SAC 
Exposure and Treatment Compliance 
1.150. 
mITT 
OEX1 
Summary of Total Transduced T cells (First Infusion) 
Report total number of transduced T 
cells in 10^9 cells and categorize it into  
< 1, >=1 to <=8, and >8 
 
SAC 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Disease Characteristics 
1.160. 
ITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis (ITT 
Population) 
ICH E3 
Time since initial diagnosis in months 
Stage of lung cancer at initial diagnosis 
Histology 
SAC 
1.170. 
mITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis (mITT 
Population) 
ICH E3 
Time since initial diagnosis in months 
Stage of lung cancer at initial diagnosis 
Histology 
SAC 
1.180. 
ITT 
DC2 
Summary of Disease Characteristics at Screening (ITT 
Population) 
ICH E3  
Disease stage at enrolment  
Tumor type 
Anatomical location 
NY-ESO-1 status 
HLA status 
Number of prior radiotherapy regimens 
(prior to leukapheresis – see study 
phase) 
Number of prior systemic therapy 
regimens (prior to leukapheresis- see 
study phase) 
SAC 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
1.190. 
mITT 
DC2 
Summary of Disease Characteristics at Screening (mITT 
Population) 
ICH E3  
Disease stage at enrolment  
Tumor type 
Anatomical location 
NY-ESO-1 status 
HLA status 
Number of prior radiotherapy regimens 
(prior to leukapheresis – see study 
phase) 
Number of prior systemic therapy 
regimens (prior to leukapheresis- see 
study phase) 
SAC 
1.200. 
mITT 
LA1 
Summary of Disease Burden at Baseline-First Infusion 
ICH E3 
Include target and non target lesions 
SAC 
Anti-Cancer Therapy 
1.210. 
ITT 
AC1  
 
Summary of Prior Anti-Cancer Therapy (ITT Population) 
IDSL 
Therapy before leukapheresis-see 
study phase 
SAC 
1.220. 
mITT 
AC1  
Summary of Prior Anti-Cancer Therapy (mITT Population) 
IDSL 
Therapy before leukapheresis-see 
study phase 
SAC 
1.230. 
mITT 
FAC1 
Summary of On-Study Anti-Cancer Therapy 
IDSL 
Add time from T-cell infusion to first 
post-treatment anti-cancer therapy, 
min, 25th Q, median, 75th Q, max 
SAC 
1.240. 
ITT 
CM1 
Summary of Prior Dictionary Coded Anti-Cancer Therapy (ITT 
Population) 
IDSL 
Therapy before leukapheresis-see 
study phase 
SAC 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
1.250. 
mITT 
CM1 
Summary of Prior Dictionary Coded Anti-Cancer Therapy 
(mITT Population) 
IDSL 
Therapy before leukapheresis-see 
study phase 
SAC 
1.260. 
mITT 
CM1 
Summary of On-Study Dictionary Coded Anti-Cancer Therapy 
IDSL 
 
SAC 
1.270. 
ITT 
AC3 
Summary of Number of Anti-Cancer Therapy Regimens Prior to 
Leukapheresis (ITT Population) 
IDSL 
Therapy before leukapheresis-see 
study phase 
SAC 
1.280. 
mITT 
AC3 
Summary of Number of Anti-Cancer Therapy Regimens Prior to 
Leukapheresis (mITT Population) 
IDSL 
Therapy before leukapheresis-see 
study phase 
SAC 
Surgical/Medical Procedures 
1.290. 
ITT 
OSP1 
Summary of Prior Cancer-Related Surgical Procedures (ITT 
Population) 
IDSL 
Summarize like below; 
Any surgery 
 
Surgery Intent 
   Curative,diagnostic,palliative, other 
 
Site of surgery 
    Lobectomy,etc,other. 
 
Surgery before leukapheresis 
SAC 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
1.300. 
mITT 
OSP1 
Summary of Prior Cancer-Related Surgical Procedures (mITT 
Population) 
IDSL 
Summarize like below; 
Any surgery 
 
Surgery Intent 
   Curative,diagnostic,palliative, other 
 
Site of surgery 
    Lobectomy,etc,other. 
 
Surgery before leukapheresis 
SAC 
1.310. 
mITT 
OSP1 
Summary of On-Study Cancer-Related Surgical Procedures 
IDSL 
Summarize like below; 
Any surgery 
 
Surgery Intent 
   Curative,diagnostic,palliative, other 
 
Site of surgery 
    Lobectomy,etc,other. 
 
SAC 
Substance Use 
1.320. 
mITT 
SU1 
Summary of Substance Use  
IDSL 
Cigarette use: smoking history, years 
smoked, packs per day 
SAC 
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14.10.5. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response Rate  
2.010. 
mITT 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria) (mITT Population) – First 
Infusion 
First infusion 
Do not keep:  Best Response-Non-
CR/Non-PD , Response Rate-p-value, 
or the last three sections (response 
rate, odds ratio, test for homogeneity). 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
2.020. 
ITT 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria) (ITT Population)– First 
Infusion 
First infusion 
Do not keep:  Best Response-Non-
CR/Non-PD , Response Rate-p-value, 
or the last three sections (response 
rate, odds ratio, test for homogeneity). 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
2.030. 
mITT 
RE1c 
Summary of Investigator-Assessed Disease Control Rate with 
Confirmation (RECIST 1.1 Criteria) (mITT Population)– First 
Infusion 
First infusion 
Do not keep any optional sections: 
Non-CR/Non-PD, P-value, or last 3 
sections 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.040. 
ITT 
RE1c 
Summary of Investigator-Assessed Disease Control Rate with 
Confirmation (RECIST 1.1 Criteria) (ITT Population)– First 
Infusion 
First infusion 
Do not keep any optional sections: 
Non-CR/Non-PD, P-value, or last 3 
sections 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
Time-to-Event Endpoints 
2.060. 
mITT 
TTE1 
Summary of Progression-Free Survival by Investigator 
(RECIST 1.1 Criteria)– First Infusion 
Only present Endpoint(Event) and 
Censored, do not include follow-up 
ended/ongoing.  Remove hazard ratio, 
and log rank sections. 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
2.080. 
mITT 
TTE1 
Summary of Overall Survival 
Only present Endpoint(Event) and 
Censored, do not include follow-up 
ended/ongoing.  Remove Event 
summary, hazard ratio, and log rank 
sections. 
SAC 
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14.10.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response Rate 
2.010. 
mITT 
RE8b 
Investigator-Assessed Maximum Percent Reduction from 
Baseline in Tumor Measurement (RECIST 1.1 Criteria)– First 
Infusion 
Label with subject ID 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
2.020. 
mITT 
Non-Standard 
Spider Plot of Percent Change from Baseline in Target Lesion 
Diameter– First Infusion 
Label with subject ID 
Use EFF_F1 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
Time-to-Event Endpoints 
2.030. 
mITT 
TTE10 
Graph of Kaplan Meier Survival Curves of Progression-Free 
Survival with 95% Confidence Bands (RECIST 1.1 Criteria) – 
First Infusion 
 
Include footnote identify subject that 
does not have target lesion at baseline 
SAC 
2.050. 
mITT 
TTE10 
Graph of Kaplan Meier Survival Curves of Overall Survival with 
95% Confidence Bands  
 
SAC 
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14.10.7. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
3.010 
ITT 
AE1 
Summary of All Adverse Events by System Organ Class and 
Preferred Term  
ICH E3 
Do not use combined PT Terms 
SAC 
3.020 
mITT 
AE1 
Summary of All Treatment Emergent Adverse Events by 
System Organ Class and Preferred Term  
ICH E3 
Do not use combined PT Terms 
SAC 
3.030 
ITT 
AE1 
Summary of Adverse Events Grouped by Similarity of Preferred 
Terms  
Only include combined PT term AEs  
-Remove “Any Event” row 
-SOC from AE1 should be Combined 
Term 
-PT term from AE1 should Preferred 
Term 
Label column “Synoymn/Preferred 
Term” 
If combined AE does not appear, 
include a 0 count. 
SAC 
3.040 
ITT 
OAE07 
Summary of All Adverse Events by Maximum Grade  
Use Combined PT list 
FOR ALL COMBINED PT TABLES  
FOOTNOTE=Adverse Events are 
combined as showed in Table 3.40” 
COLUMN LABEL=Adverse Events 
All tables by maximum grade 
should only include Grade 3+4+5 
column as in OAE01, not Grade 3+4 
columns 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.050 
mITT 
OAE07 
Summary of All Treatment Emergent Adverse Events by 
Maximum Grade  
Use Combined PT list 
SAC 
3.060 
mITT 
OAE07 
Summary of All Study-Treatment Related Adverse Events by 
Maximum Grade  
ICH E3 
Use Combined PT list  
Treatment related including all 
lymphodepletion regimens and T-cell 
Infusion 
SAC 
3.070 
mITT 
OAE07 
Summary of All T-Cell Related Adverse Events by Maximum 
Grade  
ICH E3 
Use Combined PT list  
SAC 
3.080 
mITT 
OAE07 
Summary of All Lymphodepletion-Related Adverse Events by 
Maximum Grade  
ICH E3 
Use Combined PT list  
SAC 
3.090 
ITT 
AE15 
Summary of All Common (>=5%) Non-serious Adverse Events 
by System Organ Class and Preferred Term (Number of 
Subject and Occurrences) 
FDAAA, EudraCT 
Do not combine PT Terms 
SAC 
3.100 
mITT 
AE3 
Summary of All Non-Serious Study-Treatment Related AEs by 
Overall Frequency 
Do not combine PT Terms 
SAC 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events of Special Interest 
3.110 
mITT 
ESI1 
Summary of Characteristics of Cytokine Release Syndrome-
First Infusion 
Use Focused Scope List 
Report for all subjects and for all 
subjects with event 
Report characteristics, outcome, 
number of occurrences and max grade 
Do not create if 1 or less people have 
event, default to listing 
Footnote – “Preferred terms identified 
in the Focused list are summarized” 
Exclude AEs after second 
lymphodepletion 
SAC 
3.140 
mITT 
ESI1 
Summary of Characteristics of Haematopoietic Cytopenias  
 (Comprehensive List)-First Infusion 
Use Comprehensive Scope List 
Footnote – “Preferred terms identified 
in the Comprehensive list are 
summarized “ 
See above 
SAC 
3.180 
mITT 
ESI2a 
Summary of Onset and Duration of the First Occurrence of 
Cytokine Release Syndrome-First Infusion 
Time to onset (days) (-8- -1, 1-14, 15-
28, 29-56, >56) Remove subject at risk 
Duration (days) (1-28, 29-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or less people have 
event, default to listing 
Focused Scope reporting list 
Footnote – “Preferred terms identified 
in the Focused list are summarized 
SAC 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.210 
mITT 
ESI2a 
Summary of Onset and Duration of the First Occurrence of 
Haematopoietic Cytopenias (Comprehensive List)-First Infusion 
See note above- use comprehensive 
list 
Footnote – “Preferred terms identified 
in the Comprehensive list are 
summarized 
SAC 
3.270 
mITT 
ESI2a 
Summary of Onset and Duration of the Last Occurrence of 
Haematopoietic Cytopenias (Comprehensive List)-First Infusion 
See note above- use comprehensive 
list 
Footnote – “Preferred terms identified 
in the Comprehensive list are 
summarized 
SAC 
3.290 
mITT 
SAFE_T1 
Summary of Time to Resolution of Grade 3 and Above 
Cytokine Release Syndrome-First Infusion 
Do not create if 1 or less people have 
event, default to listing 
Focused list 
SAC 
3.320 
mITT 
SAFE_T1 
Summary of Time to Resolution of Grade 3 and Above 
Haematopoietic Cytopenias (Comprehensive List)-First Infusion 
Do not create if 1 or less people have 
event, default to listing 
SAC 
3.360 
mITT 
OAE01 
Summary of All Treatment Emergent Adverse Event of Special 
Interest by Maximum Grade (Focused List)-All Infusions 
Replace SOC with AESI category 
Use Combined PT 
SAC 
3.370 
mITT 
OAE01 
Summary of All Treatment Emergent Adverse Event of Special 
Interest by Maximum Grade (Comprehensive List)-All Infusions 
Replace SOC with AESI category 
Use preferred term, not combined PT 
SAC 
Serious and Other Significant Adverse Events 
3.380 
ITT 
AE16 
Summary of All Serious Adverse Events by System Organ 
Class and Preferred Term (Number of Subjects and 
Occurrences)  
FDAAA, EudraCT 
Do not use Combined PT term 
SAC 
3.390 
ITT 
OAE07 
Summary of All Serious Adverse Events by Maximum Grade 
Use Combined PT  
SAC 
3.400 
mITT 
OAE07 
Summary of All Treatment Emergent Serious Adverse Events 
by Maximum Grade   
Use Combined PT 
SAC 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.410 
mITT 
OAE07 
Summary of All Study Treatment Related Serious Adverse 
Events by Maximum Grade  
Use Combined PT 
Treatment related including all 
lymphodepletion regimens and T-cell 
Infusion 
 
SAC 
3.420 
mITT 
OAE07 
Summary of All T-cell Related Serious Adverse Events by 
Maximum Grade  
Use Combined PT 
SAC 
3.430 
mITT 
OAE07 
Summary of All Lymphodepletion-Related Serious Adverse 
Events by Maximum Grade  
Use Combined PT 
SAC 
3.440 
ITT 
AE3 
Summary of Fatal Adverse Events 
Use Combined PT 
Don’t produce if <5 subjects have 
fatal AE 
SAC 
3.450 
mITT 
AE3 
Summary of Study-Treatment Related Fatal Adverse Events  
Don’t produce if < 5 subjects have 
study treatment related fatal AE 
Use Combined PT 
SAC 
3.460 
mITT 
AE3 
Summary of All Serious Study-Treatment Related AEs by 
Overall Frequency 
Don’t use Combined PT 
SAC 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Deaths 
3.470 
mITT 
DD1 
Summary of Deaths 
IDSL 
Only report Alive at Last Contact, not 
follow up ended/ongoing 
Report as collected on the CRF 
-Disease Under study 
-Treatment related toxicity 
-Other 
 
Report time from T-cell infusion to 
death with median, min, max, 1st Q, 3rd 
Q in months, >30 days or <=30 days 
SAC 
Laboratory: Chemistry  
3.480 
mITT 
LB1 
Summary of Chemistry Changes from Baseline (First Infusion) 
ICH E3 
SAC 
3.490 
mITT 
OBL9A 
Summary of Worst Case Chemistry Results by Maximum 
Grade Increase Post-Baseline Relative to Baseline (First 
Infusion) 
ICH E3 
Do not report by visit 
For labs that are gradeable by 
CTCAEv4.03 
SAC 
3.500 
mITT 
OLB11A 
Summary of Worst Case Chemistry Results Relative to Normal 
Range Post-Baseline Relative to Baseline (First Infusion) 
ICH E3 
Do not report by visit 
For labs that are not gradeable by 
CTCAE 
 
SAC 
Laboratory: Hematology 
3.510 
mITT 
LB1 
Summary of Hematology Changes from Baseline (First 
Infusion) 
ICH E3 
SAC 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.520 
mITT 
OBL9A 
Summary of Worst Case Hematology Results by Maximum 
Grade Increase Post-Baseline Relative to Baseline (First 
Infusion) 
ICH E3 
Do not report by visit 
For labs that are gradeable by 
CTCAEv4.03 
SAC 
3.530 
mITT 
OLB11A 
Summary of Worst Case Hematology Results Relative to 
Normal Range Post-Baseline Relative to Baseline (First 
Infusion) 
ICH E3 
Do not report by visit 
For labs that are not gradeable by 
CTCAE 
 
SAC 
Laboratory: Other Tests 
3.540 
mITT 
LB1 
Summary of Urinalysis Laboratory Changes from Baseline 
(First Infusion) 
ICH E3 
SAC 
ECG 
3.570 
mITT 
EG1 
Summary of ECG Findings (First Infusion) 
IDSL 
“Clinically significant change from 
baseline” in this standard shell is not 
collected in this study so cannot be 
reported: drop from display. 
SAC 
3.580 
mITT 
OECG1A 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category (First Infusion) 
IDSL 
Do not report by visit 
QTcF and QTcB reported in one table 
 
SAC 
3.590 
mITT 
EG2 
Summary of Change from Baseline in ECG Values by Visit 
(First Infusion) 
IDSL 
QTcF and QTcB reported separately 
SAC 
3.600 
mITT 
OECG2A 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category (First Infusion) 
IDSL 
Do not report by visit 
QTcF and QTcB in one table 
SAC 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Vital Signs 
3.610 
mITT 
VS1 
Summary of Change from Baseline in Vital Signs (First 
Infusion) 
ICH E3 
Include weight, bmi, temp, BP, pulse 
rate, respiratory rate, oxygen 
saturation 
SAC 
3.620 
mITT 
OVT1A 
 
Summary of Worst Case change in Heart Rate Relative to 
Normal Range Post-Baseline Relative to Baseline (First 
Infusion) 
IDSL 
Do not summarize by visit 
 
SAC 
3.630 
mITT 
OVT2A 
 
Summary of Worst Case Increase in Blood Pressure by 
Maximum Grade Increase Post-Baseline Relative to Baseline 
(First Infusion) 
IDSL 
Do not summarize by visit 
SAC 
Performance Status 
3.640 
mITT 
 
PS1A  
 
Summary of ECOG Performance Status (First Infusion) 
ICH E3 
Just summarize at baseline and last-
assessment 
SAC 
3.650 
mITT 
PS3A 
Summary of Change in ECOG Performance Status from 
Baseline (First Infusion) 
ICH E3 
Include best and worst case 
SAC 
Replication Competent Lentivirus Positive (RCL) 
3.660 
mITT 
SAFE_T3 
Summary of Replication Competent Lentivirus Positive 
All infusions 
SAC 
3.670 
mITT 
SAFE_T3 
Summary of Subjects Showing >1%  Gene Marked PBMCs 1 
Year Post-treatment 
Label- >1% Gene Marked PBMCs 1 
Year Post-treatment 
All infusions 
SAC 
 
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14.10.8. 
Safety Figures 
 
 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Duration Plots 
3.010. 
mITT 
SAFE_F1 
Plot of Prior Therapy Information 
. 
SAC 
3.020. 
mITT 
SAFE_F2 
Plot of Duration on Interventional Phase 1 
. 
SAC 
Laboratory 
3.030. 
mITT 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT (First Infusion) 
IDSL 
SAC 
3.040. 
mITT 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
eDISH (First Infusion) 
IDSL 
SAC 
14.10.9. 
Biomarker Tables 
Biomarker: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Persistence of NY-ESO-1c259T  
6.010. 
mITT 
BIO_T1 
Summary of Peak Persistence (First Infusion) 
Only report maximum persistence (i.e. 
not by scheduled visits). 
Report overall cohort and by 
responders vs. non-responders 
SAC 
6.020. 
 mITT 
BIO_T2 
Summary of Time to Peak Persistence (First Infusion) 
Report overall cohort and by 
responders vs. non-responders 
SAC 
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14.10.10. Biomarker Figures 
Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Cytokines 
6.010. 
mITT 
BIO_F4 
Profile of IL-6 by CRS Status and Subject (First Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Make CRS start red triangle, make 
CRS stop red square. Add legend 
labels for start and stop of CRS event. 
Add label of CRS start and stop date 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
6.020. 
mITT 
BIO_F4 
Profile of IL-6 by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
6.030. 
mITT2 
BIO_F4 
Profile of IL-6 by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use Log10 for y axis and same x axis 
length as first infusion display 
SAC 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.040. 
mITT 
BIO_F4 
Profile of IL-10 by CRS Status and Subject (First Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Make CRS start red triangle, make 
CRS stop red square. Add legend 
labels for start and stop of CRS event. 
Add label of CRS start and stop date 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
6.050. 
mITT 
BIO_F4 
Profile of IL-10 by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
6.060. 
mITT2 
BIO_F4 
Profile of IL-10 by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use Log10 for y axis and same x axis 
length as first infusion display 
SAC 
6.070. 
mITT 
BIO_F4 
Profile of TNF-alpha by CRS Status and Subject (First Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Make CRS start red triangle, make 
CRS stop red square. Add legend 
labels for start and stop of CRS event. 
Add label of CRS start and stop date 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.080. 
mITT 
BIO_F4 
Profile of TNF-alpha by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
6.090. 
mITT2 
BIO_F4 
Profile of TNF-alpha by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use Log10 for y axis and same x axis 
length as first infusion display 
SAC 
6.100. 
mITT 
BIO_F4 
Profile of IFN-gamma by CRS Status and Subject (First 
Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Make CRS start red triangle, make 
CRS stop red square. Add legend 
labels for start and stop of CRS event. 
Add label of CRS start and stop date 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis 
SAC 
6.110. 
mITT 
BIO_F4 
Profile of IFN-gamma by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
Use Log10 for y axis. 
SAC 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.120. 
mITT2 
BIO_F4 
Profile of IFN-gamma by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use Log10 for y axis and same x axis 
length as first infusion display 
SAC 
6.130. 
mITT 
BIO_F4 
Profile of IL-1beta by CRS Status and Subject (First Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Make CRS start red triangle, make 
CRS stop red square. Add legend 
labels for start and stop of CRS event. 
Add label of CRS start and stop date 
Add dot at each cytokine measurement 
One color per subject 
SAC 
6.140. 
mITT 
BIO_F4 
Profile of IL-1beta by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
 
SAC 
6.150. 
mITT2 
BIO_F4 
Profile of IL-1beta by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use same x axis length as first infusion 
display 
SAC 
6.151 
mITT 
BIO_F4 
Profile of IL-7 by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
SAC 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.152 
mITT2 
BIO_F4 
Profile of IL-7 by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use same x axis length as first infusion 
display 
SAC 
6.153 
mITT 
BIO_F4 
Profile of IL-15 by Response and Subject (First Infusion) 
By responder and non-responder per 
investigator-assessed best response 
with confirmation. Include footnote per 
mock programming note. 
Add dot at each cytokine measurement 
One color per subject 
SAC 
6.154 
mITT2 
BIO_F4 
Profile of IL-15 by Subject (Second Infusion) 
Do not separate by responder status 
Add dot at each cytokine measurement 
Use same x axis length as first infusion 
display 
SAC 
6.160. 
mITT 
BIO_F5 
Peak Cytokine Expression of IL-6 by CRS Status (First 
Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Add mean in legend 
SAC 
6.170. 
mITT 
BIO_F5 
Peak Cytokine Expression  of IL-6 by Response (First Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
6.180. 
mITT 
BIO_F5 
Peak Cytokine Expression of IL-10 by CRS Status (First 
Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Add mean in legend 
SAC 
6.190. 
mITT 
BIO_F5 
Peak Cytokine Expression  of IL-10 by Response (First 
Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
6.200. 
mITT 
BIO_F5 
Peak Cytokine Expression of TNF-alpha by CRS Status (First 
Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Add mean in legend 
SAC 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.210. 
mITT 
BIO_F5 
Peak Cytokine Expression  of TNF-alpha by Response (First 
Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
6.220. 
mITT 
BIO_F5 
Peak Cytokine Expression of IFN-gamma by CRS Status (First 
Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Add mean in legend 
SAC 
6.230. 
mITT 
BIO_F5 
Peak Cytokine Expression  of IFN-gamma by Response (First 
Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
6.240. 
mITT 
BIO_F5 
Peak Cytokine Expression of IL-1beta by CRS Status (First 
Infusion) 
By CRS (None or Non-Serious CRS 
vs. Serious CRS) 
Add mean in legend 
SAC 
6.250. 
mITT 
BIO_F5 
Peak Cytokine Expression of IL-1beta by Response (First 
Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
6.251 
mITT 
BIO_F5 
Peak Cytokine Expression of IL-7 by Response (First Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
6.252 
mITT 
BIO_F5 
Peak Cytokine Expression of IL-15 by Response (First Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
Persistence of NY-ESO-1c259T 
6.260. 
mITT 
BIO_F3 
Persistence Profile by Subject (First Infusion) 
Do not separate responder and non-
responder 
Create a new display for each subject  
All subjects should not be on the same 
plot. Use same x and y axis for all plots 
SAC 
6.270. 
mITT 
BIO_F3 
Persistence Profile by Subject and Responder Status (First 
Infusion) 
Separate by responder and non-
responder 
All subjects in the same display 
SAC 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.271 
mITT 
BIO_F3 
Persistence Profile by Subject and Responder Status 
Truncated at 6 Months (First Infusion) 
Separate by responder and non-
responder 
All subjects in the same display 
Truncate at day 180 and show tick 
mark every 30 days 
SAC 
6.280. 
mITT2 
BIO_F3 
Persistence Profile by Subject (Second Infusion) 
Do not separate by responder-non-
responder 
Use x axis length in display 6.260 
SAC 
6.290. 
mITT 
BIO_F5 
Distribution of Peak Persistence (First Infusion) 
By responder and non-responder 
Add mean in legend 
SAC 
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14.10.11. ICH Listings 
Add mITT and mITT2 flags to all ITT listings and mITT2 flags to all mITT listings. 
Replace Study Day in all listings to Time from 1st Infusion/ Time from 2nd Infusion 
ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
10.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
Journal Guidelines 
Only include subjects that were 
screen failures 
Do not include “Type of Failure” 
SAC 
20.  
ITT 
ES2 
Listing of Reasons for Study Withdrawal (Interventional 
Phase 1) 
ICH E3 
Do not include columns “Reason 
Term(s)”, “Was a follow-up phone 
contact attempted 3 times?” & “ 
Was a follow-up certified letter 
mailed?” from GSK standard mock 
as not collected in this study. 
SAC 
30.  
Second T-
cell 
Infusion 
ES2 
Listing of Reasons for Study Withdrawal (Interventional 
Phase 2) 
ICH E3Do not include columns 
“Reason Term(s)”, “Was a follow-
up phone contact attempted 3 
times?” & “ 
Was a follow-up certified letter 
mailed?” from GSK standard mock 
as not collected in this study. 
 
SAC 
40.  
mITT 
POP_L5 
Listing of Subject Status 
 
SAC 
Protocol Deviations 
50.  
ITT 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
SAC 
60.  
ITT 
IE3  
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
ICH E3 
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Populations Analysed 
70.  
 Screened 
SP3 
Listing of Subjects Excluded from Any Population 
ICH E3 
ITT, mITT, mITT2 
SAC 
Demographic and Baseline Characteristics 
80.  
ITT 
DM2 
Listing of Demographic Characteristics 
ICH E3 
Add BMI and Race 
SAC 
Prior and Concomitant Medications 
90.  
ITT 
BP4 
Listing of Blood Products 
IDSL 
Include flag for blood product 
occurring on or after second 
lymphodepletion 
SAC 
100. 
ITT 
CM3 
Listing of Medications 
IDSL 
Include all collected medications, 
do not subset on concomitant 
medications study phase 
Replace “Started Pre-Trial” 
column with “Prior / Concomitant”  
Include flag for conmed occurring 
on or after second 
lymphodepletion 
SAC 
Exposure and Treatment Compliance 
110. 
ITT 
Non-standard/POP_L3 
Listing of Leukapheresis, Lymphodepletion, and T-cell 
Infusion Dates 
ICH E3 
Include both first and second 
infusion exposures  
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
120. 
ITT 
POP_L1 
Listing of Exposure to T-cell Infusion 
ICH E3 
Start date, study day, start time, 
end time, total cell dose, total 
number of transduced cells, 
percentage of cells transduced, lot 
number. Report cell dose as 10^9 
Include both first and second 
infusion exposures 
SAC 
130. 
ITT 
POP_L2 
Listing of Exposure to Lymphodepletion Chemotherapy 
ICH E3 
Include both first and second 
infusion exposures 
SAC 
Response 
140. 
ITT 
RE5 
Listing of Investigator-Assessed Responses at Each Visit 
with Confirmation (RECIST 1.1 Criteria)- First Infusion 
Include Target and Non-Target 
Lesion column 
Do not keep measureable disease 
at baseline ,CA, or organs of PD 
columns 
 
Include footnote identify subject 
that does not have target lesion at 
baseline 
SAC 
150. 
mITT2 
RE5 
Listing of Investigator-Assessed Responses at Each Visit 
with Confirmation (RECIST 1.1 Criteria)- Second Infusion 
Include Target and Non-Target 
Lesion column 
Do not keep measureable disease 
at baseline ,CA, or organs of PD 
columns 
 
SAC 
160. 
mITT 
TTE9 
Listing of Time To Response -First Infusion 
Change randomization date to T-
cell Infusion Date,  
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
170. 
mITT 
TTE9 
Listing of Time To Response -Second Infusion 
Change randomization date to 2nd 
T-cell Infusion Date,  
SAC 
180. 
mITT 
TTE9 
Listing of Progression-Free Survival-First Infusion 
Use T-cell infusion date 
 
Include footnote identify subject 
that does not have target lesion at 
baseline 
SAC 
190. 
mITT 
TTE9 
Listing of Progression-Free Survival-Second Infusion 
Use T-cell infusion date 
SAC 
200. 
mITT 
TTE9 
Listing of Duration of Response-First Infusion 
Change randomization date to T-
cell Infusion Date. Add date of 
confirmed response 
SAC 
210. 
mITT 
TTE9 
Listing of Duration of Response-Second Infusion 
Change randomization date to 2nd 
T-cell Infusion Date. Add date of 
confirmed response 
SAC 
220. 
mITT 
TTE9 
Listing of Overall Survival 
Change randomization date to T-
cell Infusion Date.  
SAC 
Adverse Events 
230. 
ITT 
AE8  
Listing of Adverse Events 
ICH E3 
Use “Time Since 1st T-Cell 
Infusion/Time Since 2nd T-cell 
Infusion” 
MITT flag 
Include all AEs on study and 
display flag for second infusion 
treatment emergent AE (Y/N) 
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
240. 
mITT 
SAFE_L1 
Listing of Delayed Adverse Events 
ICH E3 
Use “Time Since 1st T-Cell 
Infusion/Time Since 2nd T-cell 
Infusion” 
Display second infusion treatment 
emergent AE flag 
SAC 
250. 
ITT 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
All AEs 
SAC 
260. 
ITT 
AE2 
Listing of Relationship Between Adverse Event System 
Organ Classes, Preferred Terms, and Verbatim Text 
IDSL 
SAC 
Adverse Events of Special Interest 
270. 
mITT 
SAFE_L1 
Listing of Cytokine Release Syndrome Adverse Events 
Focused scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2 
Add column 
Medications/Procedures   
SAC 
280. 
mITT 
SAFE_L2 
Listing of Symptoms, Concomitant Medications, and 
Procedures Related to Cytokine Release Syndrome 
 
SAC 
290. 
mITT 
SAFE_L1 
Listing of Graft versus Host Disease Adverse Events 
Focused scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2   
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
300. 
mITT 
SAFE_L1 
Listing of Immune Effector-Cell Associated Neurotoxicity 
Syndrome (ICANS)- Adverse Events 
Focused scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2   
SAC 
310. 
mITT 
SAFE_L1 
Listing of Haematopoietic Cytopenias Adverse Events 
(Focused List) 
Focused scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2   
SAC 
320. 
mITT 
SAFE_L1 
Listing of Haematopoietic Cytopenias Adverse Events 
(Comprehensive List) 
Comprehensive scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2   
SAC 
330. 
mITT 
SAFE_L1 
Listing of Guillain-Barre Syndrome Adverse Events 
Focused scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2   
SAC 
340. 
mITT 
SAFE_L1 
Listing of Pneumonitis Adverse Events 
Focused scope 
Sort by USUBJID, AEDECOD, 
ASTDT, AENDT 
Display all AESIs, 1st and 2nd inf. 
Display start and end study day 2   
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Serious and Other Significant Adverse Events 
350. 
ITT 
AE8  
Listing of Fatal Serious Adverse Events 
ICH E3 
Use “Time Since 1st T-Cell 
Infusion/Time Since 2nd T-cell 
Infusion” 
Display all AEs  
MITT Flag 
Display second infusion treatment 
emergent AE flag 
SAC 
360. 
ITT 
AE8  
Listing of Non-Fatal Serious Adverse Events 
ICH E3 
Use “Time Since 1st T-Cell 
Infusion/Time Since 2nd T-cell 
Infusion” 
MITT Flag 
Display all AEs  
Display second infusion treatment 
emergent AE flag 
SAC 
370. 
ITT 
AE14 
Listing of Reasons for Considering as a Serious Adverse 
Event 
ICH E3 
Display second infusion treatment 
emergent AE flag 
SAC 
371. 
ITT 
PAN12 
Listing of Covid-19 Assessments and Symptoms 
Assessments 
If data exists 
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Deaths 
380. 
ITT 
DTH3 
Listing of Deaths 
ICH E3 
Include “Time from 1st T-cell 
infusion/ Time from 2nd T-cell 
infusion”  
MITT Flag 
Exclude “No. of Cycles/ Last Dose 
(unit)”. 
SAC 
381 
ITT 
DD3 
Death Profile 
ICH E3 
MITT Flag 
If data warrant 
SAC 
Hepatobiliary (Liver) 
390. 
ITT 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting 
IDSL 
Update columns “Time Since First 
Dose”, “Time Since Last Dose 
(days)” of LIVER5 mock with 
“Time Since First T-Cell Infusion” 
& “Time Since Second T-Cell 
Infusion”. 
SAC 
400. 
mITT 
LIVER13 
Listing of Subjects Meeting Hepatobiliary Laboratory 
Criteria Post-Baseline 
IDSL 
SAC 
410. 
ITT 
LIVER15 
Liver Stopping Event Profile 
IDSL 
Date of Start of Treatment and 
Date of End of Treatment change 
to Date of First T-cell Infusion, 
Date of Second T-cell Infusion 
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
All Laboratory 
420. 
ITT 
LB5A 
Listing of All Chemistry Data for Subjects with Any Value of 
Potential Clinical Importance/Outside Normal Range 
ICH E3 
 
SAC 
430. 
ITT 
LB5A 
Listing of All Hematology Data for Subjects with Any Value 
of Potential Clinical Importance/Outside Normal Range 
ICH E3 
SAC 
440. 
ITT 
LB5A 
Listing of All Other Laboratory Data for Subjects with Any 
Value of Potential Clinical Importance/Outside Normal 
Range 
ICH E3 
SAC 
450. 
ITT 
LB5A 
Listing of Chemistry Values of Potential Clinical Importance  
SAC 
460. 
ITT 
LB5A 
Listing of Hematology Values of Potential Clinical 
Importance 
 
SAC 
470. 
ITT 
LB5A 
Listing of Other Laboratory Values of Potential Clinical 
Importance 
 
SAC 
480. 
ITT 
LB14 
Listing of Laboratory Data with Character Results 
ICH E3 
SAC 
490. 
ITT 
UR2A 
Listing of Urinalysis Data  
ICH E3 
 
SAC 
500. 
 mITT 
LB5 
Listing of Cytokine Data  
Include flag for subjects with 
serious CRS event 
Include all infusions 
SAC 
510. 
mITT 
BIO_L1 
Listing of Persistence Data 
Raw and Derived 
All infusions included with second 
infusion info derived separately 
SAC 
520. 
mITT 
LB5 
Listing of VSV-G DNA (RCL) Data 
 
SAC 
531. 
mITT 
LB5 
Listing of ICE Score 
Date, Time, ICE Points 
SAC 
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ICH: Listings 
No. 
Population 
IDSL / Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
532. 
ITT 
BIO_L2 
Listing of Immunohistochemistry Data 
 
SAC 
ECG 
540. 
ITT 
EG3 
Listing of All ECG Values for Subjects with Any Value of 
Potential Clinical Importance 
IDSL 
SAC 
550. 
ITT 
EG5  
 
Listing of All ECG Findings for Subjects with an Abnormal 
ECG Finding 
IDSL 
Remove clinically significant 
change from baseline and 
clinically significant abnormality 
SAC 
560. 
ITT 
OECG5A 
Listing of QTc Values of Potential Clinical Importance 
Specify if Bazett’s or Fridericia 
SAC 
Vital Signs 
570. 
ITT 
OVT7A 
Listing of Vital Signs with any Value of Potential Clinical 
Importance 
Add oxygen saturation column 
with category defined in PCI 
section 
SAC 
Performance Status 
580. 
ITT 
PS5A 
Listing of ECOG Performance Status 
 
SAC 
 
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14.10.12.  Non-ICH Listings 
Add mITT and mITT2 flags to all ITT listings and mITT2 flags to all mITT listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Disease Characteristics 
590. 
ITT 
DC3 
Listing of Disease Characteristics at Initial Diagnosis 
Date of diagnosis/ time from 
diagnosis to screening (months), 
stage of lung cancer at initial 
diagnosis, type of histology 
SAC 
600. 
ITT 
POP_L4 
Listing of Disease Characteristics at Screening 
Number of prior systemic therapy 
regimens before enrolment, number 
of radiotherapy therapy before 
enrolment,*, stage of lung cancer at 
time of enrolment, Tumor Type, 
Anatomical Location, HLA Allele 1 
status, HLA Allele 2 status, NY-ESO-
1 status 
 
 
 
SAC 
Anti-Cancer Therapy 
610. 
ITT 
AC6 
Listing of Prior Anti-Cancer Therapy 
Include amount/scheduled or 
cumulative dose, regimen number, 
and best response per mock 
Therapy before leukapheresis-see 
study phase 
SAC 
611. 
ITT 
AC6 
Listing of Bridging Anti-Cancer Therapy 
Include amount/scheduled or 
cumulative dose and regimen 
number, and best response per mock 
SAC 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
see study phase for definition of 
bridging therapy 
620. 
mITT 
FAC3 
Listing of On-Study Anti-Cancer Therapy 
Include flag for on-study anti-cancer 
therapy occurring on or after second 
lymphodepletion 
Include amount/scheduled or 
cumulative dose and regimen 
number per mock 
SAC 
630. 
ITT 
AC7 
Listing of Prior and Bridging Anti-Cancer Radiotherapy 
Include prior and bridging and flag 
bridging therapy 
SAC 
Medical Conditions 
640. 
ITT 
MH2 
Listing of Medical Conditions 
Remove Past/Current category and 
replace with “Ongoing?” flag 
SAC 
Surgical Procedures 
650. 
ITT 
OSP3 
Listing of Prior and Bridging Cancer-Related Surgical 
Procedures 
List Surgery Intent and Site and Date 
of Surgery 
Include prior and bridging and flag 
bridging therapy 
SAC 
660. 
mITT 
OSP3 
Listing of On-Study Cancer-Related Surgical Procedures 
List Surgery Intent and Site and Date 
of Surgery 
Include flag for on-study surgery 
occurring on or after second 
lymphodepletion 
SAC 
661. 
ITT 
OSP3 
Listing of Tumor Biopsies 
Use listing 650 as mock and remove 
timepoint, classification, and bridging 
therapy column. 
Rename “Surgery Intent”=”Type of 
Sample Obtained”, “Site of Surgery” 
SAC 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
= “Anatomical Location” 
Substance Use 
670. 
ITT 
SU2 
Listing of Substance Use 
List cigarette use, years smoked, 
packs per day 
SAC 
Responses 
680. 
mITT 
LA5 
Listing of Investigator-Assessed Lesion Assessments 
(RECIST 1.1 Criteria) 
Include second infusion lesion 
assessments 
SAC 
 
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14.11. 
Appendix 11: Example Mock Shells for Data Displays  
14.11.1. 
POP_T1 Exposure Mock-Up Summary 
Example POP_T1 
Protocol: 208479                                                                                   Page 1 of 1 
Population: Intent-To-Treat                                                    (Data as of: 24APR2018) 
Table X.X 
Summary of Exposure 
 
 
GSK794 
(N=15) 
 
 
Apheresis Performed 
13 (87%) 
Received Lymphodepleting Therapy 
12 (80%) 
Received T-cell Infusion 
10 (67%) 
Received Second T-cell Infusion 
2 (13%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 
1: ITT population comprises of all subjects who enrolled in the trial and met all eligibility criteria.. 
 
 
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14.11.2. 
EFF_F1 Spider Plot Mock-Up Figure 
Example EFF_F1 
Protocol: 208479                                                                              Page 1 of 1 
Population: Modified Intent-to-Treat                                                (Data as of: 24APR2018) 
Figure X 
Spider Plot of Percent Change from Baseline in Target Lesion Diameter 
 
 
Note: 
1: mITT population includes all ITT subjects who received T cell infusion. 
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14.11.3. 
SAFE_F1 Prior Therapy Mock-Up Figure 
 
 
 
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14.11.4. 
SAFE_F2 Study Duration Mock Up Figure 
 
 
 
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14.11.5. 
BIO_F3 Persistence Profile Mock-Up Figure 
Example BIO_F3 
Protocol: 208479                                                                                Page 1 of 1 
Population: Modified Intent-to-Treat                                                   (Data as of: 24APR2018) 
Figure X 
Persistence Profile by Subject 
 
Note: 
1: mITT population includes all ITT subjects who received T cell infusion. 
 
 
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14.11.6. 
BIO_F4 Cytokine Spider Plot Mock-Up Figure 
Example BIO_F4 
Protocol: 208479                                                                                Page 1 of 1 
Population: Modified Intent-to-Treat                                                   (Data as of: 24APR2018) 
Figure X 
IL-6 Profile by Subject 
 
Note: 
1: mITT population includes all ITT subjects who received T cell infusion 
Where plotting split by responder and non-responder include footnote “Note: Responders are subjects with 
investigator-assessed best response with confirmation (per RECIST 1.1 criteria) of Partial Response or 
Complete Response.” 
 
 
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14.11.7. 
BIO_F5 Cytokine Box Plot Figure 
Example BIO_F5 
Protocol: 208479                                                                                Page 1 of 1 
Population: Modified Intent-to-Treat                                                   (Data as of: 24APR2018) 
Figure X 
Peak Cytokine Expression by CRS Status 
 
Note: 
1: mITT population includes all ITT subjects who received T cell infusion 
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14.11.8. 
SAFE_L1 CRS Mock-Up Listing 
Example SAFE_L1 
Protocol: GSK208479                                                                             Page 1 of n 
Population: Intent-to-Treat                                                          (Data as of: 24APR2018) 
Listing XX 
Listing of Adverse Events of Special Interest 
Treatment: GSK794 
Infusion: First Infusion 
 
 
Site Id./ 
Unique 
Subject Id. 
Date of 
Apheresis/ 
Date of 
Lymphodepletio
n/ 
Date of T-cell 
Infusion 
Preferre
d Term 
Total 
Event 
Duratio
n 
(Days) 
AE Start 
Date/Star
t Study 
Day/ 
AE End 
Date/End 
Study 
Day/ 
Event 
Duration 
(Days) 
SAE Code 
Grad
e 
Relationshi
p to Study 
Treatment 
Outcome of Event 
 
 
 
 
 
 
 
 
 
/ 
/ 
/ 
 
Cytokine 
release 
syndrome 
9 
/ 3 
/ 10/ 
8 
 
Not applicable Grad
e 2 
Yes: T-
Cell 
Recovered/resolv
ed 
 
 
 
 
/ 5 
/ 11 
7 
 
Not applicable Grad
e 3  
Yes: T-
Cell 
Recovered/resolv
ed 
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/ 6 
/ 11/ 
6 
Not applicable Grad
e 1  
Yes: T-
Cell 
Recovered/resolv
ed 
 
 
 
 
 
 
 
 
 
 
 
Cytokine 
release 
syndrome 
3/ 
Y 
/ 379 
/ 380/ 
2 
 
Not applicable Grad
e 1  
Yes: T-
Cell 
Recovered/resolv
ed 
 
 
 
 
/ 380 
/ 381/ 
2 
 
Not applicable Grad
e 3 
Yes: T-
Cell 
Recovered/resolv
ed 
 
 
 
 
 
 
 
 
 
/ 
/ 
/ 
 
Cytokine 
release 
syndrome 
8/ 
N 
/ 5 
/ 12/ 
8 
Hospitalizatio
n 
Grad
e 3  
Yes: T-
Cell 
Recovered/ 
resolved 
Note:  
1: ITT population comprises of all subjects who enrolled in the trial and met all eligibility criteria. 
2: The second infusion section of the listing includes all AE starting after second lymphodepletion. In the 
section, the study day is in reference to second T-cell infusion, and the apheresis, lymphodepletion, and T-
cell dates are for second infusion.  
USER ID:directory/program.sas  01JAN2002 12:01 
 
 
 
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14.11.9. 
BIO_T1 Summary of Peak Persistence 
Example BIO_T1 
Protocol: 208749                                                                             Page 1 of 1 
Population: Modified Intent-to-Treat 
 
 
 
 
 
 
 
(Data as of: 24APR2018) 
Table X 
Summary of Peak Persistence  
 
 
Test (units)           
 
Group      
 
N    
 
n   
 
Mean 
 
     SD   
 
Median 
 
Min. 
 
Max. 
 
 
 
 
 
 
 
 
 
Peak Persistence 
Overall  
202   180 
 74.3 
    9.82 
     74 
51 
96 
(Cell number/ μL)             
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
Non-
Responders 
100 
90 
70.4 
8.51 
62 
51 
80.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Responders 
102 
90 
80.4 
6.41 
92 
30 
96 
 
 
 
 
 
Note: 
1: mITT population comprises of all subjects in the ITT population that received T-cell infusion 
 
 
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14.11.10. BIO_T2 Summary of Time to Peak Persistence 
Example: BIO_T2 
Protocol: 208749                                                                          Page 1 of 1 
Population: Modified Intent-to-Treat 
 
 
 
 
 
 
(Data as of: 24APR2018) 
Table X 
Summary of Time to Peak Persistence 
 
 
 
 
Time (Days) to Peak Persistence (Cell number/ μL)   
Group 
N 
n 
Mean 
 SD 
Median 
Min. 
Max. 
 
 
 
 
 
 
 
 
Overall 
100 
99 
25.0 
4.52 
25.0 
20 
34 
Non-Responders 
50 
49 
21.0 
3.25 
22.0 
20 
28 
Responders  
50 
50 
30.0 
3.51 
29.5 
36 
34 
 
 
 
 
 
Note: 
1: mITT population comprises of all subjects in the ITT population that received T-cell infusion 
 
 
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14.11.11. SAFE_T3 Summary of Replication Competent Lentivirus Positive 
Example: BIO_T3 
Protocol: 208749                                                                          Page 1 of 1 
Population: Modified Intent-to-Treat 
 
 
 
 
 
 
(Data as of: 24APR2018) 
 
 
Table X 
Summary of Replication Competent Lentivirus Positive 
 
                      
 
GSK794 
(N=40) 
 
 
Replication Competent Lentivirus Positive 
 
    n 
4 
    Count 
2 (50%) 
 
 
 
 
 
 
 
Note: 
1: mITT population comprises of all subjects in the ITT population that received T-cell infusion 
 
 
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14.11.12. BIO_L1 Listing of Persistence 
Example: BIO_L1 
Listing of Persistence Results 
 
Treatment=Treatment A 
 
Age 
(YEARS
)/ 
Sex/ 
Race  
 
 
 
 
 
 
 
 
 
Site 
ID/Subject ID 
Planne
d 
Time 
Date/Stu
dy Day 
Total 
Number 
of 
Transduc
ed Cells 
(10^9 
cells) 
Coefficie
nt of 
Variation
/ Number 
of 
Positive 
Replicate
s 
Copie
s per 
Cell/ 
Perce
nt 
gene 
marke
d 
PBMCs 
(%) 
Copes 
per 
ug 
DNA 
Interpreti
ve 
Result 
Peak 
Persistenc
e/ Time to 
Peak 
Persistenc
e (days) 
Time to 25% 
Loss of Peak 
Persistence 
(days)/50%/7
5%/ 
Duration of 
Detectable 
Persistence 
 
 
 
 
 
 
 
 
 
 
 
/ 
65/ 
F/ 
MULTIP
LE 
Baseli
ne 
 -11 
 
N/A/ 
1 
<.000
3/ 
0% 
<50.0 NEGATIVE 
67852.7/ 
2 
3/ 
14/ 
14/ 
28+ 
 
 
Day 1 
/ 1 
 
N/A/ 
1 
<.001
6 
<250.
0 
NEGATIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
/ 2 
 
.2/ 
2 
.4275
/ 
42.75
% 
67852
.7 
POSITIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Day 4 
/ 4 
 
.1/ 
4 
.2544
/ 
25.44
% 
40383
.5 
POSITIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
/ 8 
 
.2/ 
8 
.4226
/ 
42.26
% 
67080
.7 
POSITIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
/ 14 
 
.3/ 
14 
.0173
/ 
1.73% 
2742.
5 
POSITIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 4 
/ 28 
 
.2/ 
28 
.0041
/ 
.41% 
644.2 POSITIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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14.11.13. POP_L1 Listing of Exposure to T-cell Infusion 
Example: POP_L1 
Protocol: 208749                                                                          Page 1 of 1 
Population: Intent-to-Treat 
 
 
 
 
 
 
 
 
(Data as of: 24APR2018) 
 
Listing X 
Listing of Exposure to T-cell Infusion 
 
Treatment: GSK794 
 
 
Centre 
Id./ 
Subject 
 
 
Start 
Date/Start 
Time/ 
Study Day 
 
 
Stop 
Date/Stop 
Time/ 
Study Day 
 
 
Total Number of 
Transduced Cells 
(10^9 cells) 
 
 
Percentage of 
Cells Transduced 
(%)  
 
 
 
 
 
/ 
 
/ 
14:30/ 
1 
/ 
15:30/ 
1 
1.21 
35.4 
 
 
 
 
 
 
 
 
 
 
/ 
 
/ 
10:30/ 
1 
/ 
13:15/ 
1 
2.52 
28.3 
 
 
 
 
 
Note:  
1: ITT population comprises of all subjects who enrolled in the trial and met all eligibility criteria. 
USER ID:directory/program.sas  01JAN2002 12:01 
 
 
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14.11.14. POP_L2 Listing of Exposure to Cyclophosphamide/Mesna  
Example: POP_L2 
Protocol: 208749                                                                          Page 1 of 1 
Population: Intent-to-Treat 
 
 
 
 
 
 
 
 
(Data as of: 24APR2018) 
Listing X 
Listing of Exposure to Lymphodepletion Chemotherapy Medicine 
 
Treatment: LOW LYMPHO DOSE + GSK794 
 
Centre 
Id./Uniq
ue 
Subject 
Age 
Visit 
Cyclophosphamide 
Administration 
 
Fludarabine Administration 
 
Infusion 
Date/Study 
Day 
Dose/Unit 
Infusion 
Date/Study 
Day 
Dose/Unit 
 
 
 
 
 
 
 
 
 
 
/ 
 
 
/ 
-7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
1: ITT population comprises of all participants who enrolled in the trial and met all eligibility criteria. 
USER ID:directory/program.sas  01JAN2002 12:01 
 
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14.11.15. POP_L3 Listing of Leukapheresis, Lymphodepletion, and T-cell Infusion Dates 
Example: POP_L3 
Protocol: 208749                                                                          Page 1 of 1 
Population: Intent-to-Treat 
 
 
 
 
 
 
 
 
(Data as of: 24APR2018) 
Listing X 
Listing of Leukapheresis, Lymphodepletion, and T-cell Infusion Dates 
 
Treatment: GSK794  
 
 
Centre Id./ 
Subject 
 
 
 
Visit 
 
 
 
Treatment 
 
 
 
Date / 
Study Day 
 
 
 
 
/ 
 
Screening 
APHERESIS 
/ -60 
 
 
FLUDARABINE 
/ -8 
 
 
FLUDARABINE 
/ -7 
 
 
CYCLOPHOSPHAMIDE 
/ -7 
 
 
MESNA 
/ -7 
 
 
FLUDARABINE 
/ -6 
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CYCLOPHOSPHAMIDE 
/ -6 
 
 
MESNA 
/ -6 
 
 
FLUDARABINE 
/ -5 
 
 
CYCLOPHOSPHAMIDE 
/ -5 
 
 
MESNA 
/ -5 
 
 
T-CELL 
/ 1 
Note:  
1: ITT population comprises of all subjects who enrolled in the trial and met all eligibility criteria. 
USER ID:directory/program.sas  01JAN2002 12:01 
 
 
 
 
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14.11.16. POP_L4 Listing of Disease Characteristics at Screening 
Example: POP_L4 
Protocol: 208749                                                                          Page 1 of 1 
Population: Intent-to-Treat 
 
 
 
 
 
 
 
 
(Data as of: 24APR2018) 
 
Listing X 
Listing of Disease Characteristics at Screening 
 
Treatment: GSK794 
 
 
Centre 
Id./ 
Subject 
Number of 
Prior Anti-
Cancer 
Therapy 
Regimens[1] 
 
 
Stage of 
Lung 
Cancer at 
Time of 
Enrollment 
 
 
Tumor Type 
Anatomical 
Location 
Date of 
Blood 
Collection 
for HLA 
Testing 
 
 
HLA Allele 
1 
HLA Allele 2 
Date of 
Biopsy 
for 
Antigen 
Testing 
NY-ESO-1 
Status 
 
 
 
 
 
 
 
 
 
 
/ 
 
2 
STAGE IIIB METASTATIC LUNG 
 HLA-
A*02:01 
OTHER, NOT 
HLA-A*02 
 POSITIVE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
/ 
 
3 
STAGE 4 
PRIMARY 
LUNG 
 HLA-
A*02:01 
HLA-A*02:01 
 NEGATIVE 
 
 
 
 
 
 
 
 
Note:  
1: Number of regimens includes all regimens before start of lymphodepleting chemotherapy 
USER ID:directory/program.sas  01JAN2002 12:01 
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14.11.17. POP_L5 Subject Status Mock-Up Listing 
Example POP_L5 
Protocol: GSK208749                                                                             Page 1 of n 
Population: Intent-to-Treat 
Listing XX 
Listing of Subject Status 
 
Site Id./ 
Unique Subject 
Id. 
Lymphodepletio
n (Y/N) 
1st T Cell 
Infusion 
Date/Time 
between 
Leukapheresi
s and 1st T-
cell 
Infusion/ 
2nd T Cell 
Infusion 
Date 
1st 
Transduce
d Dose 
(10^9 
cells)/ 
2nd 
Transduce
d Dose 
(10^9 
cells) 
 
Completed 
Interventiona
l Phase 1/ 2 
(Y/N) 
Date of 
Discontinuatio
n or 
Completion of 
Interventional 
Phase 1/ 2 
Reason for 
Discontinuatio
n or 
Completion of 
Interventional 
Phase 1/ 2 
End of 
Study 
Reason 
 
 
 
 
 
 
 
 
/ 
Y 
/ 
 
4.52/ 
    3.24 
Y/ 
N 
/ 
 
Progressive 
disease/ 
Death 
Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
/ 
Y 
 
6.24 
N 
 
Withdrew 
consent 
Withdre
w 
consent 
 
 
 
 
 
 
 
 
 
 
 
 
Note: 
1: ITT population comprises of all subjects who enrolled in the trial and met all eligibility criteria.. 
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14.11.18. EFF_T1 Summary of Time to Response by Investigator (RECIST 1.1  Criteria) 
Example EFF_T1 
Protocol: 208749                                                                             Page 1 of 1 
Population: eg, Intent to Treat/Safety/Other Study Specific                     
Table X 
Summary of Time to Response by Investigator (RECIST 1.1 Criteria) 
 
 
GSK749 
 (N=100) 
 
 
Number of Subjects with Confirmed  
Response 
   50/100 (50%) 
 
 
 
 
Time to Response (months) 
 
  Min 
    3 
  1st Quartile 
    4.3 
  Median 
    5.4 
  3rd Quartile 
   10.8 
  Max. 
   12 
 
 
Note:  
1: mITT population comprises of all subjects in the ITT population that received T-cell infusion 
 
 
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14.11.19. SAFE_T1 Summary of Time to Resolution  
SAFE_T1 
                                           Table 3.5610 
           Summary of Time to Resolution of Grade 3 and Above Adverse Event of Special Interest - 
                      Haematopoietic Cytopenias (Comprehensive List - First Infusion) 
 
                                       GSK749      
                                       (N=5)          
 ------------------------------------------------ 
 Initial Occurence  n                  4              
 <= Study Day 28 
                    <= Study Day 28    4 (100%)       
                    Study Day 29 - 90  0              
                    Study Day >90      0              
                    Unresolved         0              
 
 Recurrence >       n                  0              
 Study Day 28 
                    <= 28 Days         0              
                    29 - 90 Days       0              
                    >90 Days           0              
                    Unresolved         0              
 
Segment 1: Any subject with events starting on or before Day 28 are considered for the first segment. 
Time to resolution in relation to T-cell infusion is being summarized 
Ex: Subject with one AE starting on Study Day 27 that resolved on Study Day 29 will be summarized in 
the "Study Day 29-90" row. 
Segment 2: Recurrent events starting after Day 28 for those subset of subjects in segment 1 
Time to resolution in relation to overall duration of the event is summarized 
If a subject has multiple events that fall within the time of interest, the worst case is summarized. 
Unresolved is worst case. 
Modified Intent-to-Treat population includes all subjects who received T-cell infusion. 
 
 
 
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14.11.20. POP_T2 Summary of Subject Status 
Example POP_T2 
Protocol: 208749                                                                                   Page 1 of 1 
Population: Intent-to-Treat                                                    (Data as of: 24APR2018) 
Table X.X 
Summary of Subject Status 
 
 
 GSK794 (N=300) 
 
 
INTERVENTIONAL PHASE 1 STATUS 
 
    COMPLETED 
XX (XX%) 
NOT PROGRESSED AT 2 YEARS POST T-CELL INFUSION 
XX (XX%) 
PROGRESSIVE DISEASE 
XX (XX%) 
     DIED 
XX (XX%) 
    ONGOING 
XX (XX%) 
    DID NOT COMPLETE 
XX (XX%) 
WITHDREW CONSENT 
XX (XX%) 
FAILED 
TO 
MEET 
ELIGIBILITY 
PRIOR 
TO 
CYTOREDUCTIVE CHEMOTHERAPY 
XX (XX%) 
FAILED 
TO 
MEET 
ELIGIBILITY 
PRIOR 
TO 
LEUKAPHERESIS 
XX (XX%) 
LOST TO FOLLOW-UP 
XX (XX%) 
INVESTIGATOR DISCRETINOY 
XX (XX%) 
STUDY TERMINATED BY SPONSOR 
XX (XX%) 
DID NOT RECEIVE T-CELL INFUSION 
XX (XX%) 
DEATH (PRIOR TO T-CELL INFUSION) 
XX (XX%) 
OTHER 
 
 
XX (XX%) 
 
 
 
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14.11.21. POP_T3 Summary of Subject Status- End of Study 
Example POP_T2 
Protocol: 208749                                                                                   Page 1 of 1 
Population: Intent-to-Treat                                                    (Data as of: 24APR2018) 
Table X.X 
Summary of Subject Status 
 
 
 GSK794 (N=300) 
 
 
 
 
DEATH 
XX (XX%) 
WITHDREW CONSENT 
XX (XX%) 
MOVED TO LTFU STUDY 
XX (XX%) 
LOST TO FOLLOW-UP 
XX (XX%) 
OTHER 
XX (XX%) 
 
 
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14.11.22. SAFE_L2 Listing of Symptoms, Concomitant Medications, and Procedures Related to Cytokine Release 
Syndrome 
Example SAFE_L2 
Protocol: GSK208749                                                                       Page 1 of n 
Population: Modified Intent-to-Treat                                            (Data as of: 24APR2018) 
Listing XX 
Listing of Concomitant Medications and Procedures Related to Cytokine Release Syndrome 
 
 
Site Id./ 
Unique 
Subject 
Id. 
Date of 
Apheresis/ 
Date of 
Lymphodepleti
on/ 
Date of T-
cell Infusion 
Date CRS 
Assessed / 
Time from 1st 
T-cell 
Infusion/ Time 
from 2nd T-cell 
Infusion 
Symptoms 
Medications 
Procedures  
 
 
 
 
 
 
/ 
/ 
/ 
 
/ 3/  HYPOXIA, OTHER: 
ventricular 
tachycardia 
IV FLUIDS, 
OTHER:ACETAMINOPHEN 
VENTILATION ASSISTANCE 
/ 
/ 
/ 
 
/ 5/ 
 
CORTICOSTEROIDS, 
TOCILIZUMAB, 
OTHER:ACETAMINOPHEN
, POTASSIUM 
CHLORIDE 
 
/ 
 
 
/ 5/ 
 
 
OXYGEN 
 
Note: Modified Intent-to-Treat (mITT) population includes all enrolled subjects who were dosed 
Note: Medications and procedures as recorded on "CYTOKINE RELEASE SYNDROME" form. 
USER ID:directory/program.sas  01JAN2002 12:01 
 
 
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14.11.23. BIO_L2 Listing of Immunohistochemistry Data 
 
Listing of Persistence Results 
 
Treatment=Treatment A 
 
Age 
(YEARS)/ 
Sex/ 
Race  
 
 
 
 
Site ID/Subject 
ID 
Planned 
Time 
Date/Study 
Day 
Location 
of 
Biopsy 
Interpretation Percentage of Cells with 
0 Intensity Staining/ 
1+/ 2+/ 3+ 
 
 
 
 
 
 
 
/ 
65/ 
F/ 
MULTIPLE 
Baseline 
/ -11 
OTHER: 
Liver 
POSTIIVE 
0/ 
30/ 
10/ 
5 
 
 
Completion/Withdrawal 
 
/ 1 
OTHER: 
Liver 
POSTIIVE 
0/ 
30/ 
10/ 
5 
 
 
 
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14.12. 
Appendix 12: Combined Preferred Terms 
Combined Term 
MedDRA Preferred term 
PT Code 
MedDRA version 23.0 for PT codes  
 Anemia/Red blood cell count decreased 
Anemia  
10002034 
  
Red blood cell count decreased 
10038153 
  
  
  
Cytokine Release Syndrome (CRS)  
Cytokine release syndrome  
10052015 
  
Cytokine storm  
10050685 
  
  
  
Acute GVHD - Skin% 
Acute graft versus host disease in skin 
10066262 
Acute GVHD - Gut (Liver and Intestine)% 
Acute graft versus host disease in liver 
10066263 
  
Acute graft versus host disease in intestine 
10066264 
Acute GVHD  - Other (Lung, Bone Marrow, not specified)% 
Acute graft versus host disease 
10066260 
  
  
  
Chronic GVHD -  Skin% 
Chronic graft versus host disease in skin 
10072159 
Chronic GVHD - Gut (Liver and Intestine)% 
Chronic graft versus host disease in liver 
10072160 
  
Chronic graft versus host disease in intestine 
10072158 
Chronic GVHD Other -  (Lung, Bone Marrow, not specified)% 
Chronic graft versus host disease 
10066261 
  
  
  
Unspecified GVHD - Skin% 
Graft versus host disease in skin 
10064675 
Unspecified GVHD - Gut (Liver and Intestine)% 
Graft versus host disease in liver 
10064676 
  
Graft versus host disease in gastrointestinal tract 
10075160 
Unspecified GVHD - Other (Lung, Bone Marrow, not specified)% 
Graft versus host disease 
10018651 
  
Graft versus host disease in eye 
10074563 
  
Graft versus host disease in lung 
10067742 
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Combined Term 
MedDRA Preferred term 
PT Code 
MedDRA version 23.0 for PT codes  
  
Prophylaxis against graft versus host disease 
10053239 
  
Transfusion associated graft versus host disease 
10070895 
  
Engraftment syndrome  
10050684 
  
  
  
 Leukopenia/White blood cell decreased  
White blood cell count decreased 
10047942 
  
Leukopenia 
10024384 
  
  
  
Lymphopenia/Lymphocyte count decreased  
Lymphocyte count decreased 
10025256 
  
CD4 lymphocytes decreased  
10007839 
  
CD8 lymphocytes decreased  
10056283 
  
Lymphopenia 
10025327 
  
  
  
Neutropenia/Neutrophil count decreased  
Neutrophil count decreased 
10029366 
  
Neutropenia 
10029354 
  
  
  
Rash/Rash maculo-papular 
Rash maculo-papular 
10037868 
  
Rash 
10037844 
  
Rash erythematous 
10037855 
  
  
  
Thrombocytopenia/Platelet count decreased  
Platelet count decreased 
10035528 
  
Thrombocytopenia 
10043554 
* Preferred Term  "RBC decreased" originally from MedDRA version 18 in Adaptimmune IB version 7 . Not in current MedDRA versions 
 
 
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14.13. 
Appendix 13: AE Collapsing Rules 
Segments with a Common AE Preferred Term (PT) into Unique Events based on the Start and End Dates  
For each unique subject, the AE records (segments) with the same AE preferred term will be collapsed into one unique AE event based on 
the start and end dates below. 
Step 1 : Multiple AE Segments with Overlapped or Continuous Start/End Dates 
Multiple AE segments with a common preferred term (PT, variable=ADAE.AEDECOD) that occurred around the same time; 
defined as: 
If a segment starts no more than one day (i.e., ≤ 1 day) prior, on, or after the previous segment’s end date, it is considered as an 
‘event’.   
If the gap between the start date of a segment and the end date of previous segment is greater than one complete day (i.e., > 1 day), 
then consider these segments as different events.  
If partial start or end dates for any AE segments, then consider these segments as separate events. 
*** NOTE: Handling of partial dates or completely missing dates 
Partial dates or completely missing dates will not be imputed.  
The reason for not using imputed dates is due to the small number of partial / or completely missing dates.  Furthermore, using 
imputed dates might create additional error of up to 30 days off for the AE start or AE end dates, and can be up to 60 days off for 
the duration of AE. 
Step 2: Sort Adverse Events (AE)  
For any AE event identified above: 
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Sort the AEs segments by study ID (ADAE.STUDYID), unique subject ID (ADAE.USUBJID), AE preferred term 
(ADAE.AEDECOD), AE start date (ADAE.AESTDTC), and AE end date (ADAE.AEENDTC). The sorting will include all AE 
segments with complete or partial start / end dates. 
Step 3: Create Derived Variables in ADAE ADaM SAS Dataset 
Based on the ADAE dataset sorted above under Step 2 for each unique subject, create the following derived variables in the 
ADAE ADaM SAS data set: 
1) 
ANL01FL: Flag for the unique AE 
a) Collapsed AE Segments 
For collapsed AE segments. based on the ADAE data set sorted above under Step 2:  
• derive the flag variable: ANL01FL=”Y” on the first record for each collapsed AE (i.e. the earliest 
segment within each collapsed AE with the same ADAE.AEDECOD) . In case if the AE segment of 
the collapsed AEs started before Lymphodepletion and ending after it, then populate the ANL01FL=’Y’ 
on very first Treatment emergent record. If there is only one record (segment) which started before 
lymphodepletion and ended after lymphodepletion then populate ANL01FL=’Y’ on that record only.  
• Otherwise ANL01FL=”” (Missing) 
 
b) AE Events Comprised of a Single Row (No Collapsing Needed) 
• derive the flag variable: ANL01FL=”Y” for each single segment AE event. 
 
2) 
EVTSEQ: Sequence number of each unique AE with the same PT 
Create a sequence number, EVTSEQ, for each unique AE within the same ADAE.AEDECOD. 
For each unique subject within each unique AE preferred term, this variable will be recorded as the sequential 
number to identify all unique adverse events (including both single segment events (i.e., no collapsing 
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needed) and collapsed events from multiple segments) based on the sorting order chronologically addressed 
above under Step 2.  
a) Collapsed AE Segments 
Each collapsed AE and its corresponding composed segments will have the same sequence numbers (i.e., if 
multiple segments/records are qualified for being collapsed into one unique AE (i.e., all those records will have 
same value for the derived variable EVTSEQ for that corresponding subject within the same collapsed AE). 
b) Single Segment AE Records 
Each single segment AE event (i.e., un-collapsed event) will have different unique sequence number separately  
c) AE Segments with partial start or end dates  
Each AE segment with partial start or end dates will have different unique sequence number starting from 
99XXX, where XXX=001, 002, ...  
  * NOTE: 
     For those subjects who received 2 T-cell infusions, the sequential number will be based on both infusion periods combined  
     (i.e., the assigned sequential number will be independent of T-cell infusion periods). 
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Signature Page for  208749 TMF-2069301 v1.0
Signature Page for TMF-2069301 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 01-Oct-2020 17:56:16 GMT+0000
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 01-Oct-2020 23:19:25 GMT+0000
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