Clinical trial NCT03709706
Conditions: Neoplasms
Keywords: GSK3377794 Pembrolizumab T Cell Receptors Adoptive T-cell therapy Non-Small Cell Lung Cancer Immuno-oncology NY-ESO-1 LAGE-1a Leukapheresis Letetresgene autoleucel
Sponsor: GlaxoSmithKline
Start date: 2018-12-31; Completion date: 2022-11-04
Enrollment: 34 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.

Detailed description:
New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and 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 (TCR) engineered T-cells. This is a multi-arm, open-label study of letetresgene autoleucel (lete-cel, GSK3377794) in Human Leukocyte Antigen (HLA)-A\*02:01, HLA-A\*02:05 and/or HLA-A\*02:06 positive adults whose tumors express NY-ESO-1 and/or LAGE-1a. This study will enroll participants who have unresectable Stage IIIb or Stage IV NSCLC.

Arms: arm 1: In Arm A, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel monotherapy. Participants who subsequently progress by Week 25 will be offered pembrolizumab. arm 2: In Arm B, participants with NSCLC (lacking actionable genetic aberrations) will receive lete-cel followed by pembrolizumab. arm 3: In Arm C, participants with NSCLC (with actionable genetic aberrations) will receive lete-cel followed by pembrolizumab.
Interventions: intervention 1: Lete-cel intervention 2: Pembrolizumab
Intervention descriptions: intervention 1: lete-cel will be administered to eligible participants. intervention 2: Pembrolizumab will be administered to eligible participants.

Protocol documents:
Prot_000.pdf: 
TMF-14132100 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
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TITLE PAGE 
Protocol Title: A Phase 1b/2a Pilot Study to Evaluate the Safety and Tolerability of 
Autologous T-Cells Expressing Enhanced TCRs (T-Cell Receptors) Specific for NY-
ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination with Pembrolizumab in 
HLA-A2+ Participants with NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent 
Non-Small Cell Lung Cancer 
Protocol Number: 208471 / Amendment 07    
Compound Number: 
GSK3377794 (letetresgene autoleucel, lete-cel) 
 
Study Phase: Phase 1b/2a  
Short Title: Pilot immunotherapy study with letetresgene autoleucel (lete-cel, 
GSK3377794) T-Cells in NY-ESO-1/LAGE-1a-positive advanced NSCLC either alone 
or in combination with pembrolizumab. 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline LLC 
5 Crescent Drive 
Philadelphia, PA 19112 
US  
 
Medical Monitor Name and Contact Information: To be provided separately OR can 
be found in the Study Reference Manual 
Regulatory Agency Identifying Number(s):  
IND: 14603 
EudraCT: 2018-003949-42 
 
 
Approval Date: 04-NOV-2021 
 
 
Copyright 2021 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorized copying or use of this information is prohibited.


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SPONSOR SIGNATORY: 
Protocol Title: A Phase 1b/2a Pilot Study to Evaluate the Safety and Tolerability of 
Autologous T-Cells Expressing Enhanced TCRs (T-Cell Receptors) Specific for NY-
ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination with Pembrolizumab in 
HLA-A2+ Participants with NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent 
Non-Small Cell Lung Cancer 
Protocol Number: 208471 / Amendment 07 
Compound Number 
or Name: 
GSK3377794 
 
 
 
 
 
 
Carsten Goessl, MD 
Vice President, Clinical Development 
Synthetic Lethality and Cell and Gene Therapies 
Oncology Research & Development 
GlaxoSmithKline 
 
The signed page is a separate document 
 
Date 
 
 
 
Medical Monitor Name and Contact Information refer to Study Reference Manual 
 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 07 
04-NOV-2021 
TMF-14132100 
Amendment 06-GBR-2 
21-JUL-2021 
TMF-13894889 
Amendment 06-NET-2 
19-MAY-2021 
TMF-13775495 
Amendment 06-GBR-1 
19-MAY-2021 
TMF-13775509 
Amendment 06-SPA-1 
19-MAY-2021 
TMF-13775486 
Amendment 06 
17-MAY-2021 
TMF-12466596 
Amendment 05-NET-1 
27-MAR-2020 
2018N358002_11 
Amendment 05-UK-1 
26-MAR-2020 
2018N358002_10 
Amendment 05-SPA-1 
26-MAR-2020 
2018N358002_09 
Amendment 05 
21-FEB-2020 
2018N358002_08 
Amendment 02-NET-1 
29-OCT-2019 
2018N358002_07 
Amendment 04 
29-OCT-2019 
2018N358002_06 
Amendment 03 
01-OCT-2019 
2018N358002_05 
Amendment 02-SPA-1 
16-SEP-2019 
2018N358002_04 
Amendment 02-UK-1 
03-SEP-2019 
2018N358002_03 
Amendment 02 
13-FEB-2019 
2018N358002_02 
Amendment 01 
17-OCT-2018 
2018N358002_01 
Original Protocol 
11-JUL-2018 
2018N358002_00 
 
 
 


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Amendment 07: 04-NOV-2021 
Overall Rationale for the Amendment:  
The overall rationale for this amendment is to: 
• Implementation of additional safety monitoring measures in accordance with a 
recent Dear Investigator Letter and safety events for lete-cel. 
• For participants treated as of protocol amendment 7, the upper end of the target 
dose range of transduced T cells was increased from to 8×109 to 15×109 in order 
to maximize the delivery of cells for participants whose manufacture yields 
>8×109 transduced T cells. 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the 
protocol 
Made administrative changes and corrected 
clerical errors. 
For clarity and consistency 
Section 1.1 Synopsis 
Section 4.3.2 
Justification of Lete-
cel dose 
Section 6.4.2 Lete-cel 
dose 
The upper end of the lete-cel dose was 
expanded from 8×109 transduced T cells to 
15×109 transduced T cells for participants 
treated under protocol amendments 7 and 
beyond. 
In Section 4.3.2, added justification of 
changed lete-cel dose  
The lete-cel dose range was 
expanded in order to maximize 
the use of cells in participants 
whose manufacture yields 
>8×109 transduced T cells.   
Section 1.3 
Schedule of Activities 
(SoAs) 
Modified time window for the assessment of 
infectious disease markers: must be 
completed within 28 days prior to 
leukapheresis (Table 2, Note 16) 
 
Added thyroid function tests to the Schedule 
of Activities in Part 4 (Table 5) 
 
Clarified that brain MRI prior to 
lymphodepletion would need to show 
stability/reduction of CNS metastases if 
radiotherapy was administered after the MRI 
performed prior to leukapheresis (Table 3, 
footnote 13) 
 
Clarified that CMV infection will be assessed 
if GBS is suspected (Table 3, footnote 17) 
 
 
EoT visit is to be completed by participants 
who withdraw from the interventional phase 
and have not withdrawn from the study. If EoT 
assessments are completed sooner than what 
is indicated in Table 7, only need to repeat 
assessments not performed as part of the last 
visit. (Table 7, Note 1.) 
In alignment with relevant 
regulations [Implementing 
Directive 2004/23/EC, 2006] 
 
 
For accuracy 
 
 
For participant safety 
 
 
 
 
 
For participant safety and in 
alignment with other protocols 
across the lete-cel program 
 
In alignment with changes in 
Section 4.4.1 
 
 
 
 
 
 


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Section # and Name 
Description of Change 
Brief Rationale 
 
Added information about ECHO/MUGA at 
onset of Grade ≥2 CRS, about continuous 
cardiac telemetry monitoring (per Section 
10.9.5) and cardiologist evaluation in 
participants with increased burden of 
cardiovascular risk factors (per Section 8.2.3). 
(Table 3, Footnotes 9 and 10, respectively) 
In alignment with changes 
incorporated into Section 10.9.5 
and Section 8.2.3, respectively 
  
Section 2.3.1 Risk 
Assessment 
Added risks of cardiac arrest and 
haemorrhage secondary to thrombocytopenia 
Updated information for risk of ICANS 
In accordance with a recent Dear 
Investigator Letter and safety 
events for lete-cel 
Section 4.4.1 
End of Interventional 
Phase/Study for 
Individual Participants 
Added language to clarify the difference 
between end of interventional phase and end 
of study for individual participants (in 
alignment with incorporation of Part 5 in 
protocol amendment 6)  
For clarity, since end of 
intervention and end of study for 
individual participants might vary 
now that study includes Part 5 
Section 5.2 
Exclusion Criteria 
Modified language on treatments not 
permitted prior to the study 
 
 
Under active infection, added a sub-bullet for 
active CMV infection 
 
Included additional details under CNS 
metastases exclusion criterion 
 
Moved exclusion criterion, about radiotherapy 
that involves lung or mean heart dose 
>20 Gy, from prior to leukapheresis to prior to 
lymphodepletion to meet intent of criterion 
and eliminate unnecessary burden to patient. 
Added clarifying language on radiotherapy 
exclusion criterion, intent has not changed. 
 
Modified text in exclusion criterion concerning 
irradiated measurable lesions, intent has not 
changed. Moved note to exclusion criterion 
#19, due to relevance. 
For clarity / accuracy, in 
alignment with other protocols 
across the lete-cel program 
 
For clarity and accuracy, this 
sub-bullet was missing 
 
For participant safety 
 
 
For clarity, to eliminate 
redundancy  
 
 
 
 
 
 
 
For clarity 
Section 5.2 Exclusion 
Criteria 
 
 
Section 10.9.2 
Infection 
Sectionn 10.9.2.6 
Other Anti-Microbial 
Prophylaxis/Treatment 
Included additional information on existing 
exclusion criterion to exclude participants with 
ongoing systemic fungal infections 
 
Added information on surveillance for 
indwelling central lines (Section 10.9.2) and 
risk of cardiac toxicity with use of anti-
microbial treatments (Section 10.9.2.6) 
 
For participant safety 
 
 
 
 


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Section # and Name 
Description of Change 
Brief Rationale 
Added recommendations in case of prolonged 
leukopenia or gross hematuria (Section 
10.9.2.6) 
Section 6.3  
Lymphodepleting 
Chemotherapy 
and  
Section 10.9.10 
Lymphodepleting 
Chemotherapy 
Symptom 
Management  
Use of prophylactic G-CSF should be 
approximately 24 hours after last dose of 
chemotherapy 
At investigator’s discretion and in 
alignment with other lete-cel 
protocols  
Section 6.9.1 
Prohibited 
Concomitant 
Medication and 
Treatment 
Clarified language on the administration of 
locoregional therapies during the 
interventional portion of the study. 
 
Eliminated the following sentence due to 
redundancy: "Exceptions to the above rule 
can be made if a participant has progressive 
disease and cannot be treatment-free" 
For clarity  
 
 
 
For clarity, redundant language 
  
Section 8.2.3 
Cardiac Assessments 
This section was revised to include a 
definition of participants with increased 
burden of cardiovascular risk. Those 
participants with increased burden are 
required to undergo a cardiology evaluation 
prior to lymphodepletion and continuous 
cardiac telemetry for a minimum of 3 days 
post T-cell infusion (moved from earlier 
portion of Section 8.2.3) 
This revision was made to 
mitigate cardiac complications in 
participants with high risk factors 
Section 8.2.4 
Pulmonary 
Assessments 
(New Section) 
This section recommends pulmonary 
consultation for any participant with any 
history or known lung metastases. Also, 
closer monitoring is recommended for at least 
3 days post T-cell infusion and in case of 
suspected CRS and should include frequent 
chest radiograms, fluid balance monitoring 
and continuous cardiac telemetry.  
Participants with compromised airway should 
be assessed prior to lymphodepletion 
(consider speech and swallow evaluation, as 
well as anaesthesia consult)  
This section was added to 
recommend pulmonary 
assessments for participants with 
known lung metastases (active 
or previously treated) 
Section 8.3.5 Testing 
for Persistence of 
Transduced T cells 
and Insertional 
Oncogenesis 
Participants with a persistence of transduced 
T cells at first instance of >1% PBMCs and 
who have already been tested for Integration 
Site Analysis with a result of ‘polyclonal’, will 
only be retested if: 
Clarify conditions for monitoring 
and retesting of participants who 
have already been tested for 
Integration Site Analysis with a 
result of ‘polyclonal’ 
 


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Section # and Name 
Description of Change 
Brief Rationale 
persistence of transduced T cells has 
suddenly increased; OR 
in case of suspected/reported hematological 
malignancy    
 
Added “In all cases of SAE that occur after T 
cell infusion, a transgene copy (persistence) 
sample must be obtained if feasible.” 
 
 
 
 
 
For safety purposes and in 
alignment with other lete-cel 
protocols 
Section 1.3 Schedule 
of Activities (Table 4 
and 6)  
Section 8.9 
Biomarkers 
Removal of plan to collect stool sample to 
assess gut microbial community; deleted 
Section 8.9.9: Stool Collection for Microbiome 
Analysis 
 
Removal of plan to investigate cell free RNA  
Assays deprioritized 
Section 9.2 Sample 
Size Determination 
 
 
 
Section 9.2 Sample 
Size Determination 
Change in sample size language to clarify 
that the study aims to enrol approximately 18 
patients per arm to dose approximately 15 
patients per arm.  
 
Clarified that participants to be included in 
statistical analyses need to meet “evaluable” 
criteria, as indicated in Section 9.3 
For clarity 
 
 
 
 
For clarity 
Section 10.9.2.3 
Cytomegalovirus 
Clarified that CMV screening will happen at 
study entry and at baseline 
Correction for accuracy, in 
alignment with Schedule of 
Activities 
Section 10.9.3 
Hematologic and 
Blood Support 
 
Clarified that blood support should be 
provided to maintain platelets >10 x 109/L in 
the in-patient and >20 x 109/L in the out-
patient settings. Made small modifications to 
existing language to indicate: or as clinically 
indicated in the judgement of the Investigator, 
or in accordance with institutional practice. 
For clarity and safety purposes 
Section 10.9.5 
Management of 
Cytokine Release 
Syndrome 
Participants with increased cardiovascular 
risk factors (per Section 8.2.3) might need 
earlier intervention with tocilizumab and/or 
steroids at the onset of CRS.  
If CRS ≥Grade 2 is suspected, an 
ECHO/MUGA is required at onset 
If CRS ≥Grade 2, additional monitoring 
should include: 
• Continuous cardiac telemetry monitoring 
• ECHO/MUGA as clinically indicated 
• Local tests 
Section was revised to specify 
management of patient with an 
increased burden of 
cardiovascular risk factors 
 
 
 
 
 
 
 
 
 
 


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Section # and Name 
Description of Change 
Brief Rationale 
o Daily troponin and N-terminal pro B-type 
natriuretic peptide (NT-proBNP) or BNP 
tests 
 
Added language on organ toxicity grade per 
CTCAE V5.0, in alignment with Section 
10.3.4. 
 
 
For clarity and in alignment with 
Section 10.3.4 
 
 


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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY ........................................................................................ 17 
1.1. 
Synopsis ..................................................................................................... 17 
1.2. 
Schema ...................................................................................................... 20 
1.3. 
Schedules of Activities (SoAs) .................................................................... 21 
2. 
INTRODUCTION .................................................................................................... 38 
2.1. 
Study Rationale .......................................................................................... 38 
2.2. 
Background ................................................................................................ 38 
2.2.1. 
Lete-cel ........................................................................................ 39 
2.2.2. 
Pembrolizumab ............................................................................ 39 
2.2.2.1. 
Pharmaceutical and Therapeutic Background ............ 40 
2.2.2.2. 
Pre-clinical Data ......................................................... 41 
2.2.3. 
Rationale for the Combination Regimen ...................................... 41 
2.3. 
Benefit/Risk Assessment ............................................................................ 41 
2.3.1. 
Risk Assessment ......................................................................... 42 
2.3.2. 
Benefit Assessment ..................................................................... 48 
2.3.2.1. 
Benefit for Lete-cel ..................................................... 48 
2.3.2.2. 
Benefit for Pembrolizumab ......................................... 49 
2.3.2.3. 
Benefit for the Combination Regimen ......................... 49 
2.3.3. 
Overall Benefit - Risk Conclusion ................................................. 49 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 50 
4. 
STUDY DESIGN .................................................................................................... 51 
4.1. 
Overall Design ............................................................................................ 51 
4.1.1. 
Part 1: Screening ......................................................................... 55 
4.1.1.1. 
Screening under other GSK studies ........................... 55 
4.1.2. 
Part 2: Leukapheresis/Manufacture ............................................. 56 
4.1.3. 
Part 3: Lymphodepletion/Treatment (Interventional Phase) ......... 57 
4.1.4. 
Part 4: Pembrolizumab Therapy Following Disease 
Progression after Lete-cel Infusion (for Arm A ONLY) .................. 58 
4.1.5. 
Part 5: Long-Term Follow-Up (LTFU) ........................................... 58 
4.2. 
Scientific Rationale for Study Design .......................................................... 58 
4.3. 
Justification of Dose .................................................................................... 58 
4.3.1. 
Justification of Lymphodepleting Regimen ................................... 58 
4.3.2. 
Justification of Lete-cel Dose ....................................................... 59 
4.3.3. 
Justification of Pembrolizumab Dose ........................................... 59 
4.3.3.1. 
Justification for Administration of First Dose of 
Pembrolizumab on Day 22 Following Lete-cel 
Infusion ....................................................................... 60 
4.4. 
End of Study Definition ............................................................................... 61 
4.4.1. 
End of Interventional Phase/Study for Individual 
Participants .................................................................................. 61 
5. 
STUDY POPULATION ........................................................................................... 62 
5.1. 
Inclusion Criteria ......................................................................................... 62 
5.1.1. 
Target Expression Screening ....................................................... 62 


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5.1.2. 
Leukapheresis Eligibility Screening .............................................. 63 
5.1.3. 
Lymphodepletion Eligibility Screening .......................................... 66 
5.1.3.1. 
Treatment Fitness ...................................................... 67 
5.1.4. 
Pembrolizumab Therapy Following Disease Progression 
after Lete-cel Infusion (Arm A ONLY, Part 4) ............................... 68 
5.2. 
Exclusion Criteria ........................................................................................ 68 
5.2.1. 
Target Expression Screening ....................................................... 68 
5.2.2. 
Leukapheresis Eligibility Screening .............................................. 68 
5.2.3. 
Lymphodepletion Eligibility Screening .......................................... 72 
5.2.3.1. 
Treatment Fitness ...................................................... 73 
5.2.4. 
Pembrolizumab Therapy Following Disease Progression 
after Lete-cel Infusion (Arm A ONLY, Part 4) ............................... 73 
5.3. 
Lifestyle Considerations .............................................................................. 73 
5.3.1. 
Meals and Dietary Restrictions .................................................... 73 
5.3.2. 
Activity ......................................................................................... 74 
5.3.3. 
Contraception .............................................................................. 74 
5.3.3.1. 
Definitions .................................................................. 74 
5.3.3.2. 
Contraception ............................................................. 75 
5.3.4. 
Use in Pregnancy ........................................................................ 77 
5.3.5. 
Use in Nursing Women ................................................................ 77 
5.4. 
Screen Failures........................................................................................... 77 
6. 
STUDY INTERVENTION ........................................................................................ 77 
6.1. 
Leukapheresis ............................................................................................ 77 
6.2. 
Supportive Therapy and/or SoC Therapy Before Lymphodepletion............. 78 
6.3. 
Lymphodepleting Chemotherapy ................................................................ 78 
6.3.1. 
Lymphodepletion Dose Modification ............................................ 79 
6.3.2. 
Fludarabine Dose Adjustment for Renal Impairment .................... 81 
6.3.3. 
Cyclophosphamide Dose Adjustment .......................................... 81 
6.3.4. 
Mesna .......................................................................................... 82 
6.4. 
T-cell (Lete-cel) Infusion ............................................................................. 82 
6.4.1. 
Premedication .............................................................................. 82 
6.4.2. 
Lete-cel Dose .............................................................................. 82 
6.4.3. 
Lete-cel Administration ................................................................ 82 
6.4.4. 
Pembrolizumab Therapy Following Disease Progression 
after Lete-cel Infusion (Part 4, Arm A Only) .................................. 83 
6.5. 
Pembrolizumab Infusion in Arms B and C and Part 4 Arm A ....................... 83 
6.5.1. 
Schedule Modification Guidelines for Pembrolizumab 
(Arms B and C and Part 4 of Arm A) ............................................ 84 
6.6. 
Preparation/Handling/Storage/Accountability .............................................. 85 
6.7. 
Measures to Minimize Bias: Randomization and Blinding ........................... 85 
6.8. 
Study Intervention Compliance ................................................................... 86 
6.9. 
Concomitant Therapy.................................................................................. 86 
6.9.1. 
Prohibited Concomitant Medication and Treatment ...................... 86 
6.9.2. 
Permitted Concomitant Medication and Treatment ...................... 88 
6.9.3. 
Rescue Medications and Supportive Care ................................... 89 
6.10. 
Dose Modification ....................................................................................... 89 
6.10.1. 
Modification Guidelines for Lete-cel (All Treatment Arms) ............ 89 
6.10.2. 
Guidelines for Pembrolizumab Withholding and 
Discontinuation ............................................................................ 89 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 1  
 
7.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ..................................................................... 9 6  
7. 1.  
Di s c o nti n u ati o n of St u d y I nt er v e nti o n  .......................................................... 9 6  
7. 1. 1.  
Li v er C h e mi str y M o nit ori n g Crit eri a  .............................................. 9 7  
7. 1. 1. 1.  
Li v er E v e nt M o nit ori n g  ................................................ 9 8  
7. 1. 1. 2.  
St u d y I nt er v e nti o n R e st art or R e c h all e n g e aft er 
Li v er St o p pi n g Crit eri a Ar e M et  ................................. 1 0 0  
7. 1. 2.  
Q T c F St o p pi n g Crit eri a  .............................................................. 1 0 0  
7. 1. 3.  
T e m p or ar y Di s c o nti n u ati o n  ........................................................ 1 0 1  
7. 2.  
P arti ci p a nt Di s c o nti n u ati o n/ Wit h dr a w al fr o m t h e St u d y  ............................. 1 0 1  
7. 3.  
L o st t o F oll o w -u p  ...................................................................................... 1 0 2  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ................................................... 1 0 2  
8. 1.  
Effi c a c y A s s e s s m e nt s  ............................................................................... 1 0 3  
8. 1. 1.  
T u m or R e s p o n s e A s s e s s m e nt s  ................................................. 1 0 3  
8. 1. 2.  
L o n g -T er m F oll o w -u p  ................................................................. 1 0 4  
8. 2.  
S af et y A s s e s s m e nt s  ................................................................................. 1 0 6  
8. 2. 1.  
P h y si c al E x a mi n ati o n s  ............................................................... 1 0 6  
8. 2. 2.  
Vit al Si g n s  .................................................................................. 1 0 6  
8. 2. 3.  
C ar di a c A s s e s s m e nt s  ................................................................ 1 0 6  
8. 2. 4.  
P ul m o n ar y A s s e s s m e nt s  ........................................................... 1 0 7  
8. 2. 5.  
Cli ni c al S af et y L a b or at or y A s s e s s m e nt s  .................................... 1 0 8  
8. 3.  
S af et y M o nit ori n g  ...................................................................................... 1 0 8  
8. 3. 1.  
S af et y R e vi e w T e a m ( S R T)  ....................................................... 1 0 9  
8. 3. 1. 1.  
M a n d at e d St u d y P a u s e D u e t o G B S  ........................ 1 0 9  
8. 3. 2.  
Tr e at m e nt Li miti n g T o xi citi e s D efi niti o n  ...................................... 1 0 9  
8. 3. 3.  
Tr e at m e nt Li miti n g T o xi citi e s f or P e m br oli z u m a b  ....................... 1 1 0  
8. 3. 4.  
M o nit ori n g a n d M a n a g e m e nt of R e pli c ati o n -C o m p et e nt 
L e nti vir u s  ................................................................................... 1 1 0  
8. 3. 4. 1.  
T e sti n g f or R C L i n Cli ni c al St u di e s  ........................... 1 1 1  
8. 3. 4. 2.  
S af et y M o nit ori n g R e s ult s  ......................................... 1 1 2  
8. 3. 5.  
T e sti n g f or P er si st e n c e of Tr a n s d u c e d T c ell s a n d 
I n s erti o n al O n c o g e n e si s ............................................................ 1 1 2  
8. 3. 6.  
M o nit ori n g a n d M a n a g e m e nt f or D e m y eli n ati n g 
N e ur o p at h y a n d Ot h er N e ur ol o gi c al E v e nt s  ............................... 1 1 3  
8. 4.  
A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s  ........................................... 1 1 3  
8. 4. 1.  
Ti m e P eri o d a n d Fr e q u e n c y f or C oll e cti n g A E a n d S A E 
I nf or m ati o n ................................................................................. 1 1 3  
8. 4. 2.  
M et h o d of D et e cti n g A E s a n d S A E s  ........................................... 1 1 4  
8. 4. 3.  
F oll o w -u p of A E s a n d S A E s  ....................................................... 1 1 4  
8. 4. 4.  
A d v er s e E v e nt s of S p e ci al I nt er e st ( A E SI s)  ............................... 1 1 5  
8. 4. 5.  
R e p orti n g Crit eri a d uri n g L o n g -T er m F oll o w -U p ( Y e ar s 1 
t hr o u g h 1 5) ................................................................................ 1 1 6  
8. 4. 6.  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s  ........................... 1 1 7  
8. 4. 7.  
Pr e g n a n c y  ................................................................................. 1 1 7  
8. 4. 8.  
C ar di o v a s c ul ar a n d D e at h E v e nt s  .............................................. 1 1 8  
8. 4. 9.  
Pr o gr e s si o n of U n d erl yi n g M ali g n a n c y  ....................................... 1 1 8  
8. 5.  
Tr e at m e nt of O v er d o s e  ............................................................................. 1 1 9  
8. 6.  
P h ar m a c o ki n eti c s  ..................................................................................... 1 1 9  
8. 7.  
P h ar m a c o d y n a mi c s  .................................................................................. 1 1 9  
8. 9.  
Bi o m ar k er s  ............................................................................................... 1 2 0  
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T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 2  
 
8. 9. 1.  
C yt o ki n e a n d S ol u bl e F a ct or s A n al y si s  ...................................... 1 2 1  
8. 9. 2.  
T u m or Bi o p si e s  .......................................................................... 1 2 2  
8. 9. 3.  
Tr a n s g e n e p er si st e n c e f or P K a s s e s s m e nt  ................................ 1 2 4  
8. 1 0.  R e q u e st f or A ut o p s y f or D e at h F oll o wi n g A d mi ni str ati o n of G e n e 
 
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ...................................................................... 1 2 7  
9. 1.  
St ati sti c al H y p ot h e s e s ............................................................................... 1 2 7  
9. 2.  
S a m pl e Si z e D et er mi n ati o n  ...................................................................... 1 2 7  
9. 3.  
P o p ul ati o n s f or A n al y s e s  .......................................................................... 1 2 9  
9. 4.  
St ati sti c al A n al y s e s  ................................................................................... 1 2 9  
9. 4. 1.  
Effi c a c y A n al y s e s  ....................................................................... 1 2 9  
9. 4. 1. 1.  
Pri m ar y Effi c a c y A n al y si s  ......................................... 1 2 9  
9. 4. 1. 2.  
S e c o n d ar y Effi c a c y A n al y si s  ..................................... 1 3 0  
9. 4. 2.  
S af et y A n al y s e s  ......................................................................... 1 3 0  
9. 4. 2. 1.  
A d v er s e E v e nt s  ........................................................ 1 3 1  
9. 4. 2. 2.  
Cli ni c al L a b or at or y E v al u ati o n s  ................................ 1 3 1  
9. 4. 2. 3.  
Ot h er S af et y M e a s ur e s  ............................................. 1 3 1  
9. 4. 3.  
Ot h er A n al y s e s  .......................................................................... 1 3 1  
9. 5.  
I nt eri m A n al y s e s ....................................................................................... 1 3 1  
1 0.  S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  
C O N SI D E R A TI O N S  ............................................................................................. 1 3 3  
1 0. 1.  A p p e n di x 1: R e g ul at or y, Et hi c al, a n d St u d y O v er si g ht 
C o n si d er ati o n s  .......................................................................................... 1 3 3  
1 0. 1. 1.  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  ...................................... 1 3 3  
1 0. 1. 2.  
Fi n a n ci al Di s cl o s ur e  ................................................................... 1 3 3  
1 0. 1. 3.  
I nf or m e d C o n s e nt Pr o c e s s ........................................................ 1 3 4  
1 0. 1. 4.  
D at a Pr ot e cti o n  .......................................................................... 1 3 4  
1 0. 1. 5.  
Di s s e mi n ati o n of Cli ni c al St u d y D at a  ......................................... 1 3 5  
1 0. 1. 6.  
D at a Q u alit y A s s ur a n c e  ............................................................. 1 3 5  
1 0. 1. 7.  
S o ur c e D o c u m e nt s  .................................................................... 1 3 6  
1 0. 1. 8 . 
St u d y a n d Sit e Cl o s ur e  .............................................................. 1 3 6  
1 0. 1. 9.  
P u bli c ati o n P oli c y  ....................................................................... 1 3 6  
1 0. 2.  A p p e n di x  2: Cli ni c al L a b or at or y T e st s  ....................................................... 1 3 8  
1 0. 3.  A p p e n di x 3: A d v er s e E v e nt s: D efi niti o n s a n d Pr o c e d ur e s f or 
R e c or di n g, E v al u ati n g, F oll o w -u p, a n d R e p orti n g  ..................................... 1 4 1  
1 0. 3. 1.  
D efi niti o n of A E  .......................................................................... 1 4 1  
1 0. 3. 2.  
D efi niti o n of S A E  ........................................................................ 1 4 2  
1 0. 3. 3.  
D efi niti o n of C ar di o v a s c ul ar E v e nt s  ........................................... 1 4 3  
1 0. 3. 4.  
R e c or di n g a n d F oll o w -U p of A E a n d S A E  .................................. 1 4 3  
1 0. 3. 5.  
R e p orti n g of S A E t o G S K  ........................................................... 1 4 5  
C CI
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T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 3  
 
1 0. 4.  A p p e n di x 4: C o ntr a c e pti v e G ui d a n c e a n d C oll e cti o n of Pr e g n a n c y 
I nf or m ati o n ................................................................................................ 1 4 6  
1 0. 4. 1.  
D efi niti o n s:  ................................................................................. 1 4 6  
1 0. 4. 2.  
C o ntr a c e pti o n G ui d a n c e  ............................................................ 1 4 7  
1 0. 4. 3.  
C oll e cti o n of Pr e g n a n c y I nf or m ati o n:  ......................................... 1 4 7  
1 0. 5.  A p p e n di x  5: G e n eti c s  ................................................................................ 1 4 9  
1 0. 5. 1.  
S cr e e n a n d B a s eli n e F ail ur e s  .................................................... 1 4 9  
1 0. 5. 2.  
G er mli n e C o ntr ol  ........................................................................ 1 5 0  
1 0. 6.  A p p e n di x 6: Li v er S af et y  ........................................................................... 1 5 1  
1 0. 7.  A p p e n di x 7: C o u ntr y -S p e cifi c R e q uir e m e nt s  ............................................. 1 5 2  
1 0. 8.  A p p e n di x 8: A b br e vi ati o n s a n d Tr a d e m ar k s  .............................................. 1 5 3  
1 0. 9.  A p p e n di x 9: S u p p orti v e C ar e G ui d a n c e  .................................................... 1 5 9  
1 0. 9. 1.  
T -c ell I nf u si o n S y m pt o m M a n a g e m e nt  ....................................... 1 5 9  
1 0. 9. 2.  
I nf e cti o n ..................................................................................... 1 5 9  
1 0. 9. 2. 1.  P n e u m o c y sti s c ari nii P n e u m o ni a ( P C P)  ................... 1 5 9  
1 0. 9. 2. 2.  H er p e s Si m pl e x a n d V ari c ell a Z o st er  ........................ 1 6 0  
1 0. 9. 2. 3.  C yt o m e g al o vir u s  ....................................................... 1 6 0  
1 0. 9. 2. 4.  H e p atiti s B Pr o p h yl a xi s  ............................................. 1 6 0  
1 0. 9. 2. 5.  S y p hili s  ..................................................................... 1 6 0  
1 0. 9. 2. 6.  Ot h er A nti -Mi cr o bi al Pr o p h yl a xi s/ Tr e at m e nt .............. 1 6 0  
1 0. 9. 3.  
H e m at ol o gi c a n d Bl o o d Pr o d u ct S u p p ort  ................................... 1 6 1  
1 0. 9. 3. 1.  Irr a di at e d Bl o o d Pr o d u ct ........................................... 1 6 1  
1 0. 9. 3. 2.  C M V S cr e e n e d Bl o o d Pr o d u ct s  ................................ 1 6 1  
1 0. 9. 4.  
M a n a g e m e nt of A ut oi m m u nit y  ................................................... 1 6 1  
1 0. 9. 5.  
M a n a g e m e nt of C yt o ki n e R el e a s e S y n dr o m e  ............................ 1 6 2  
1 0. 9. 6.  
M a n a g e m e nt of Gr aft -v er s u s -H o st Di s e a s e ( G V H D)  .................. 1 6 5  
1 0. 9. 6. 1.  Di a g n o si s of G V H D  .................................................. 1 6 5  
1 0. 9. 6. 2.  Gr a di n g of G V H D  ..................................................... 1 6 6  
1 0. 9. 6. 3.  M a n a g e m e nt of G V H D  ............................................. 1 6 7  
1 0. 9 . 7. 
M a n a g e m e nt of P a n c yt o p e ni a wit h B o n e M arr o w F ail ur e / 
A pl a sti c A n e mi a  ......................................................................... 1 6 9  
1 0. 9. 8.  
M a n a g e m e nt of I m m u n e Eff e ct or C ell -A s s o ci at e d 
N e ur ot o xi cit y S y n dr o m e (I C A N S)  ............................................... 1 7 0  
1 0. 9. 8. 1.  Gr a di n g of I C A N S  ..................................................... 1 7 0  
1 0. 9. 8. 2.  M o nit ori n g f or I m m u n e Eff e ct or C ell -A s s o ci at e d 
N e ur ot o xi cit y S y n dr o m e  (I C A N S) .............................. 1 7 2  
1 0. 9. 8. 3.  M a n a g e m e nt of I m m u n e Eff e ct or C ell -
A s s o ci at e d N e ur ot o xi cit y S y n dr o m e  (I C A N S)............ 1 7 2  
1 0. 9. 9.  
G uill ai n -B arr é S y n dr o m e  ............................................................ 1 7 4  
1 0. 9. 9. 1.  N e ur ol o gi c al s y m pt o m s  ............................................ 1 7 5  
1 0. 9. 9. 2.  Bri g ht o n k e y di a g n o sti c crit eri a  ................................. 1 7 6  
1 0. 9. 9. 3.  Er a s m u s G B S R e s pir at or y I n s uffi ci e n c y S c or e 
( E G RI S) .................................................................... 1 7 6  
1 0. 9. 9. 4.  M o difi e d Er a s m u s G B S O ut c o m e s S c or e 
( m E G O S) ................................................................. 1 7 6  
1 0. 9. 9. 5.  S u m m ar y of di a g n o si s a n d tr e at m e nt f or G B S  .......... 1 7 6  
1 0. 9. 1 0.  L y m p h o d e pl eti n g C h e m ot h er a p y S y m pt o m M a n a g e m e nt  .......... 1 7 7  
1 0. 1 0.  A p p e n di x 1 0: G ui d eli n e s f or A s s e s s m e nt of Di s e a s e, Di s e a s e 
Pr o gr e s si o n, a n d R e s p o n s e Crit eri a  ......................................................... 1 7 9  
1 0. 1 0. 1.  R E CI S T v 1. 1 G ui d eli n e s  ............................................................ 1 7 9  
1 0. 1 1.  A p p e n di x 1 1: Pr ot o c ol A m e n d m e nt Hi st or y  ............................................... 1 9 0  
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11. REFERENCES ..................................................................................................... 209 
 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
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1 5  
 
LI S T O F T A B L E S  
P A G E  
T a bl e 1  
O bj e cti v e s a n d E n d p oi nt s  ....................................................................... 1 7  
T a bl e 2  
S c h e d ul e of A c ti viti e s –  S cr e e ni n g ( P art 1) a n d L e u k a p h er e si s 
( P art 2) ................................................................................................... 2 1  
T a bl e 3  
S c h e d ul e of A cti viti e s –  L y m p h o d e pl eti o n/ Tr e at m e nt 
(I nt er v e nti o n al P h a s e) ( P art 3) ............................................................... 2 4  
T a bl e 5  
S c h e d ul e of A cti viti e s –  P e m br oli z u m a b T h er a p y F oll o wi n g 
Di s e a s e Pr o gr e s si o n aft er L et e -c el I nf u si o n  ( P art 4 -Ar m  A o nl y)  ............ 3 1  
T a bl e 7  
S c h e d ul e of A cti viti e s –  E n d of Tr e at m e nt/ E n d of I nt er v e nt i o n al 
P h a s e  ..................................................................................................... 3 4  
T a bl e 8  
S c h e d ul e of A cti viti e s –  L o n g T er m F oll o w -u p aft er Di s e a s e 
Pr o gr e s si o n or C o m pl eti o n of I nt er v e nti o n al P h a s e ( P art 5 or 
St u d y 2 0 8 7 5 0)  ........................................................................................ 3 6  
T a bl e 9  
S u m m ar y of Ri s k s a n d Ri s k -Miti g ati o n Str at e gi e s R el at e d t o 
St u d y Tr e at m e nt s  ................................................................................... 4 2  
T a bl e 1 0  
O bj e cti v e s a n d E n d p oi nt s  ....................................................................... 5 0  
T a bl e 1 1  
A d e q u at e Or g a n F u n cti o n  ...................................................................... 6 4  
T a bl e 1 2  
C o n c o mit a nt Tr e at m e nt s a n d W a s h o ut P eri o d s  ..................................... 7 3  
T a bl e 1 3  
C o ntr a c e pti v e s All o w e d D uri n g t h e St u d y ............................................... 7 6  
T a bl e 1 4  
L y m p h o d e pl eti n g C h e m ot h er a p y  ............................................................ 7 9  
T a bl e 1 5  
D o s e M o difi c ati o n G ui d eli n e s a n d T o xi cit y M a n a g e m e nt 
G ui d eli n e s f or I m m u n e -R el at e d A d v er s e E v e nt s A s s o ci at e d wit h 
St u d y Tr e at m e nt ..................................................................................... 9 1  
T a bl e 1 6  
P e m br oli z u m a b I nf u si o n R e a cti o n D o s e M o difi c ati o n a n d 
Tr e at m e nt G ui d eli n e s  ............................................................................. 9 5  
T a bl e 1 7  
Li v er C h e mi str y M o nit ori n g Crit eri a L e v el 1  ............................................ 9 8  
T a bl e 1 8  
Li v er C h e mi str y M o nit ori n g Crit eri a L e v el 2  ............................................ 9 9  
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
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1 6  
 
T a bl e 1 9  
O p er ati n g C h ar a ct eri sti c s f or I nt eri m a n d Fi n al A n al y s e s f or Ar m s 
A, B, a n d C  ........................................................................................... 1 2 8  
T a bl e 2 0  
Effi c a c y E n d p oi nt s a n d St ati sti c al M et h o d s  .......................................... 1 2 9  
T a bl e 2 1  
D e ci si o n -M a ki n g Crit eri a f or F utilit y f or Ar m s A, B, a n d C at t h e 
I nt eri m A n al y si s C o n d u ct e d wit h 1 0 E v al u a bl e P arti ci p a nt s/ Ar m  .......... 1 3 2  
T a bl e 2 2  
Pr ot o c ol -R e q uir e d S af et y L a b or at or y A s s e s s m e nt s  ............................. 1 3 9  
T a bl e 2 3  
C o ntr a c e pti v e s All o w e d D uri n g t h e St u d y ............................................. 1 4 7  
T a bl e 2 4  
M a n a g e m e nt G ui d eli n e s f or C yt o ki n e R el e a s e S y n dr o m e  .................... 1 6 3  
T a bl e 2 5  
O v er vi e w of Cli ni c al Fi n di n g s/ S y m pt o m s of G V H D  ............................... 1 6 5  
T a bl e 2 6  
St a gi n g of D er m al, G a str oi nt e sti n al, a n d H e p ati c I n v ol v e m e nt 
wit h A c ut e G V H D  ................................................................................. 1 6 6  
T a bl e 2 8  
M a n a g e m e nt G ui d eli n e s f or G V H D  ...................................................... 1 6 8  
T a bl e 2 9  
I m m u n e Eff e ct or C ell-A s s o ci at e d E n c e p h al o p at h y (I C E) ‑ T o ol  ............. 1 7 1  
T a bl e 3 1  
M a n a g e m e nt of I m m u n e Eff e ct or C ell -A s s o ci at e d N e ur ot o xi cit y 
S y n dr o m e  (I C A N S) ............................................................................... 1 7 3  
T a bl e 3 2  
E v al u ati o n of O v er all R e s p o n s e f or P arti ci p a nt s wit h M e a s ur a bl e 
Di s e a s e at B a s eli n e  ............................................................................. 1 8 3  
T a bl e 3 3  
I m a gi n g a n d Tr e at m e nt aft er Fir st R a di ol o gi c E vi d e n c e of 
Pr o gr e s si v e Di s e a s e  ............................................................................ 1 8 8  
LI S T O F FI G U R E S  
P A G E  
Fi g ur e 1  
St u d y S c h e m a  ........................................................................................ 2 0  
Fi g ur e 2  
St u d y S c h e m a  ........................................................................................ 5 2  
Fi g ur e 3  
P arti ci p a nt Fl o w ...................................................................................... 5 4  
Fi g ur e 4  
Di a g n o si s a n d Tr e at m e nt of G uill ai n -B arr é S y n dr o m e ( G B S)  ............... 1 7 7  
Fi g ur e 5  
I m a gi n g a n d Tr e at m e nt f or Cli ni c all y St a bl e P arti ci p a nt s Aft er t h e 
Fir st R a di ol o gi c E vi d e n c e of P D a s A s s e s s e d b y t h e I n v e sti g at or  ........ 1 8 9  
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 1b/2a Pilot Study to Evaluate the Safety and Tolerability of 
Autologous T-Cells Expressing Enhanced TCRs (T-Cell Receptors) Specific for NY-
ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination with Pembrolizumab in 
HLA-A2+ Participants with NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent 
Non-Small Cell Lung Cancer 
Short Title: Pilot immunotherapy study with letestregene autoleucel (lete-cel, 
GSK3377794) T-Cells in NY-ESO-1/LAGE-1a-positive advanced NSCLC either alone 
or in combination with pembrolizumab. 
Rationale: Adoptive T-cell therapy (ACT) is a therapeutic approach that uses a cancer 
patient’s own T lymphocytes obtained by leukapheresis, engineered to express a tumor-
specific T-cell receptor (TCR), expanded ex vivo, and re-infused into the patient, with the 
aim of generating an anti-tumor T-cell immune response.  New York esophageal 
squamous cell carcinoma 1 (NY-ESO-1) and cancer testis antigen 2 (LAGE-1a) antigens 
are tumor-associated proteins that have been found in several tumor types, including non-
small cell lung cancer (NSCLC).  Previous clinical trials using ACT with T-cells directed 
against NY-ESO-1/LAGE-1a have shown objective responses between 40% to 60% in 
participants with synovial sarcoma, metastatic melanoma, and multiple myeloma.   
Pembrolizumab is a monoclonal antibody that acts specifically on tumor-targeting T-cells 
to block programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) 
interaction and increase T-cell anti-tumor function; pembrolizumab will be used in 
combination with NY-ESO-1/LAGE-1a TCR engineered patient T-cells, lete-cel, to 
potentially further improve therapy for patients. 
Table 1 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To evaluate the safety and tolerability of 
autologous genetically modified T-cells 
(lete-cel) 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 alone [Arm A] or lete-cel in 
combination with pembrolizumab in 
participants with NSCLC lacking actionable 
genetic aberrations [Arm B] and 
participants with NSCLC with an actionable 
genetic aberration [Arm C] 
• 
Frequency and severity of AEs, serious 
adverse events (SAEs) and AEs of 
special interest (AESIs; as defined in 
protocol) 
• 
AE/SAEs leading to dose delays 
and/or withdrawals in participants who 
received lete-cel alone or in 
combination with pembrolizumab 
 
• 
To determine the response to lete-cel alone 
[Arm A] or lete-cel in combination with 
pembrolizumab in participants with NSCLC 
lacking actionable genetic aberrations [Arm 
B] and participants with NSCLC with 
actionable genetic aberrations [Arm C] 
• 
Overall Response Rate (ORR) 
(investigator assessed according to 
RECIST v1.1) 


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O bj e cti v e s  
E n d p oi nt s  
S e c o n d ar y - Effi c a c y  
•  
T o f urt h er i nv esti g at e t h e a nti -t u m or activity 
of l et e-c el al o n e or l et e -c el i n c o m bi n ati o n 
wit h p e m br oliz u m a b acc or di n g t o R E CI S T 
v1. 1 crit eri a  
•  
Pr o gr essi o n -Fr e e S urviv al ( P F S)  
•  
Dis e as e C o ntr ol R at e ( D C R)  
•  
D ur ati o n of R es p o ns e ( D o R)  
•  
Ti m e t o R es p o ns e ( T T R)  
S e c o n d ar y  - P h ar m a c o ki n eti c s  
•  
T o c h ar act eriz e i n viv o c ell ul ar P K pr ofil e 
(l ev els, ex p a nsi o n, p ersist e nc e) of 
N Y -E S O -1  s p ecific (c 2 5 9) T c ells 
•  
M axi m u m tr a ns g e n e ex p a nsi o n 
( C m ax) 
•  
T i m e t o C m ax ( T m ax) 
•  
A r e a u n d er t h e ti m e c urv e fr o m z er o t o 
ti m e t A U C( 0-t), as d at a p er mit  
C CI


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A b br evi ati o ns:  
; A E = a dv ers e ev e nt/s; A E SI = a dv ers e ev e nt of s p eci al i nt er est; AL K/ R O S 1 =  a n a pl astic 
ly m p h o m a ki n as e/c-r os o nc o g e n e 1; A U C( 0 -t) = ar e a u n d er t h e ti m e c urv e fr o m z er o t o ti m e t; C m ax = m axi m u m 
p ersist e nc e ; C R S = cyt oki n e r el e as e sy n dr o m e; D C R = dis e as e c o ntr ol r at e; D o R = d ur ati o n of r es p o ns e  (i D o R = D o R 
b as e d o n  
) ; E C G =  el ectr oc ar di o gr a m; E C O G  P S  =  E ast er n C o -o p er ativ e O nc ol o gy Gr o u p p erf or m a nc e 
st at us; e C R F = el ectr o nic c as e r e p ort f or m; E G F R  =  e pi d er m al gr o wt h f act or r ec e pt or; F D G = fl u or o d e oxy gl uc os e; 
G -C S F  =  gr a n ul ocyt e c ol o ny sti m ul ati n g f act or; H L A  =  h u m a n l e uk ocyt e a nti g e n; I L = i nt erl e uki n;
L A G E -1 a  = ca nc er  testis a nti g e n 2; N S C L C  =  n o n -sm all cell lu n g ca nc er; N Y -E S O -1  = N e w Y ork es o p h a g e al 
s q u a m o us c ell c arci n o m a 1; O R R = ov er all r es p o ns e r at e  (
); 
; P E T  =  p ositr o n e missi o n t o m o gr a p hy; P F S  =  pr o gr essi o n -fr e e s urviv al 
; R E CI S T =  R es p o ns e Ev al u ati o n Crit eri a I n S oli d T u m ors  
 
); 
; 
S A E  =  s eri o us a dv ers e ev e nt; T C R  =  T -c ell r ec e pt or; 
 T m ax = ti m e t o C m ax; 
 
; T T R = ti m e t o r es p o ns e; W T = wil d -ty p e. 
 
O ver all Desi g n : 
T his is a m ulti -ar m, o pe n -la bel st u d y of letestre ge ne a ut ole ucel (lete-cel, G S K 3 3 7 7 7 9 4 ) 
i n H L A-A * 0 2: 0 1, H L A -A * 0 2: 0 5 a n d/ or H L A -A * 0 2: 0 6 p ositi ve a d ults w h ose t u m ors 
e x press N Y -E S O -1 a n d/ or L A G E -1 a.   
T his st u d y will e nr oll partici pa nts w h o ha ve u nresecta ble Sta ge III b or Sta ge I V N S C L C 
a n d als o fit criteri a  o utli ne d i n eli gi bilit y.   
Discl os ur e St ate me nt :  
T his is a m ulti -c o h ort, o pe n -la bel, e x pa nsi o n c o h ort st u d y wit h 3  ar ms w h ose pri mar y 
p ur p ose is t o e val uate cli nical acti vit y a n d safet y f or eac h ar m.  
N u m ber of P artici p a nts:  
A p pr o xi matel y  5 4 p artici pa nts will be e nr olle d t o ac hie ve at least 1 5 e v al ua ble 
partici pa nts per ar m. At l east  3 0 partici pa nts  ( 1 5 per eac h ar m) wit h N S C L C lac ki n g 
acti o na ble ge n etic a berrati o ns will be assi g ne d t o lete-cel al o ne ( Ar m A) or i n 
c o m bi nati o n wit h pe m br oliz u ma b ( Ar m B). As si g n me nt of partici pa nts t o Ar m A or B 
will be deter mi ne d  b y  t he S p o ns or a n d will be assi g ne d t o Ar m A first a n d t he n t o Ar m 
B.     
At least  1 5 e val ua ble p artici pa nts wit h N S C L C wit h  a n acti o na ble ge netic  a berrati o n  (e. g. 
B R A F, A L K/ R O S 1 or a n y ot her p er N C C N g ui deli nes) will be assi g n e d t o treat me nt wit h 
lete-cel i n c o m bi nati o n wit h pe m br oliz u ma b ( Ar m C).  Partici pa nts wit h acti o na ble 
ge n etic a b errati o n s ma y recei ve treat me nt as p art of Ar m C o nl y f oll o wi n g treat me nt w it h 
tar gete d sta n dar d of care t hera p y ( N C C N or or e q ui vale nt c o u ntr y -g ui deli nes (e. g. , 
E S M O, NI C E, etc.) , as a p plica ble). 
I nter ve nti o n Gr o u ps a n d D ur ati o n: 
I n Ar m A, lete-cel will b e a d mi nistere d as a si n gl e i ntra ve n o us (I V) i nf usi o n of 1 t o 
1 5  x  1 0 9 tra ns d uce d cells.  T here will be n o re-tr eat me nt wit h lete -cel i n t his st u d y.  
Partici pa nts w h o s u bse q u e ntl y pr o gress ma y  o pti o nall y recei v e t hera p y wit h 
pe m br oliz u ma b  2 0 0 m g o nce e v er y 3 wee ks ( Q 3 W ) f or u p t o 3 5 c ycles, u ntil disease 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


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progression or until early withdrawal, at which point participants will then be entered into 
a separate long-term follow-up (LTFU) protocol (GSK Study 208750). 
In Arms B and C, participants will receive a single IV infusion of lete-cel on Day 1 
followed by pembrolizumab 200 mg starting on Day 22 (Week 4 Day 1).  
Pembrolizumab will be administered for up to 35 cycles Q3W, until disease progression 
or until early withdrawal, at which point participants will be entered into the LTFU 
protocol (GSK Study 208750). If not yet enrolled in the LTFU protocol, participants will 
be followed per LTFU schedule under this protocol (Part 5) until enrolled in LTFU 
protocol. 
Data Monitoring Committee: No 
1.2. 
Schema 
Figure 1 
Study Schema 
 
Abbreviations: ALK/ROS1 = anaplastic lymphoma kinase/c-ros oncogene 1; BRAF = B-Raf; EGFR = epidermal growth 
factor receptor; EoT = end of treatment; HLA = human leukocyte antigen; LAGE-1a = cancer testis antigen 2; 
NCCN = National Comprehensive Cancer Network; NSCLC = non-small cell lung cancer; NTRK = Neurotrophic 
Tropomyosin-Related Kinase; NY-ESO-1 = New York esophageal squamous cell carcinoma 1; 
PD-1 = programmed death protein 1; PD-L1 = PD-1 ligand; LTFU = long-term follow-up. 
 
1. NSCLC patients with an actionable genetic aberration may receive treatment as part of Arm C only following 
treatment with targeted standard of care therapy (NCCN or equivalent country guidelines (e.g., ESMO, NICE, etc.), 
as applicable). 
2.  Option of pembrolizumab therapy at time of disease progression following Lete-cel administration and based on 
benefit-risk evaluation with Sponsor’s Medical Monitor (or designee) approval.  
3.  LTFU requires participant enrollment in a dedicated LTFU protocol (GSK Study 208750). If not yet enrolled in the 
LTFU protocol, participants will be followed per LTFU schedule under this protocol (Part 5) until enrolled in the 
separate LTFU protocol (see Table 8). 
 


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1.3. 
Schedules of Activities (SoAs) 
Table 2 
Schedule of Activities – Screening (Part 1) and Leukapheresis (Part 2) 
 
Screening Phase1 
Leuka-
pheresis4 
Notes 
Day (D) / 
Week (W)  
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening 
(Within 42 days 
prior to 
Leukapheresis) 3 
 
 
Informed Consent for Screening 
X 
 
 
1. 
Written informed consent must be obtained prior to performing any study 
assessments or procedures, except for those collected as SoC and considered 
acceptable for the study (footnote 11) or as part of other GSK studies (per Section 
4.1.1). 
2. 
Target Expression Screening may be performed under a separate protocol, if 
applicable, per Section 4.1.1. 
3. 
Participants must be HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive and 
have NY-ESO-1/LAGE-1a positive tumor prior to conducting leukapheresis 
eligibility screening procedures. 
4. 
Participants must meet all eligibility requirements prior to leukapheresis, as 
specified in Section 5. 
5. 
If an archival tumor specimen is not available, then a fresh tumor tissue biopsy 
may be considered at the discretion of the investigator. See Section 8.9.2. 
6. 
Only collect this sample if optional Liquid Biopsy Consent has been signed by the 
participant as part of the Informed Consent for Screening. Sample may be 
collected any time from signature of optional consent until leukapheresis. 
7. 
Medical history will be recorded in the eCRF at Target Expression Screening and 
at Lymphodepletion Screening/Baseline visits; however, any changes in medical 
history must be recorded in source documents throughout the conduct of the 
study. 
8. 
Includes all prescriptions, over-the-counter medications, and herbal remedies.  Any 
use of mutagenic agents or investigational agents must also be reported. 
Informed Consent for 
Leukapheresis and Treatment 
 
X 
 
Inclusion/Exclusion for Screening 
X 
 
 
Inclusion/Exclusion for 
Leukapheresis 
 
X 
 
Demographics 
X 
 
 
HLA -A*02:01, A*02:05 and 
A*02:06 genotyping1 
X 
 
 
Tumor expression of NY-ESO-1/ 
LAGE-1a5 
X 
 
 
Liquid Biopsy (blood)6 
X 
 
 
Medical History7 
X 
X 
 
Prior/Concomitant Medications8 
X 
X 
X 
ECOG 
X 
X 
 
Physical Exam10 
 
X 
 
Vital Signs / Height / Weight15  
 
X 
 
12-lead ECG9  
 
X 
 
ECHO/MUGA11 
 
X 
 
CT / MRI11,12 
 
X 
 
Brain MRI11 
 
X 
 
Lymphocyte Subset 
(CD3/CD4/CD8)10,11,13 
 
X 
 
Hematology10,11 
 
X 
 


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Screening Phase1 
Leuka-
pheresis4 
Notes 
Day (D) / 
Week (W)  
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening 
(Within 42 days 
prior to 
Leukapheresis) 3 
 
 
Clinical Chemistry10,11 
 
X 
 
9. 
Collect a single ECG.  If QTc is >480 msec, collect 2 more ECGs 5 minutes apart 
and use the average of those QT values to determine eligibility. If the average QTc 
is >480 msec, obtain a manual overread of the triplicate. 
10. All clinical assessments required at Leukapheresis Eligibility Screening must be 
performed within 42 days prior to leukapheresis, except for vital signs, weight, 
lymphocyte subset (CD3/CD4/CD8), hematology, clinical chemistry, coagulation 
tests, physical exam and urinalysis which must be done within 7 days prior to 
leukapheresis. 
11. ECHO/MUGA, CT/MRI scan, brain MRI 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.  
12. Any FDG PET/CT performed as part of clinical routine within the required time 
period before leukapheresis will also be collected centrally but will not replace CT 
scans. 
13. CD3 count prior to leukapheresis should be preferably performed within 24 hours 
from leukapheresis procedure. 
14. WOCBP must have a negative urine or serum pregnancy test at Screening and 
again prior to leukapheresis. 
15. Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen 
saturation.  Height will be collected at the Screening visit only. FEV1, FVC, TLC, 
and DLCO will be measured to determine eligibility as described in Section 5. 
16. Includes HIV, HBV, HCV, HTLV, EBV, CMV, and syphilis (spirochete bacterium).  
Must be completed within 28 days prior to leukapheresis. Testing is required at 
Screening and needs to be repeated at Baseline (see Table 3) to satisfy eligibility 
criteria. 
17. Adverse events (AEs) should be collected and reported as noted in Section 8.4. 
18. Arm assignment should occur before leukapheresis. 
 
 
Coagulation Tests10,11 
 
X 
 
Pregnancy Test14 
 
X14 
X14 
Urinalysis10,11 
 
X 
 
PFTs15 
 
X 
 
Infectious Disease Markers11,16 
 
X 
 
Creatinine clearance by GFR or 24-
h Urine Collection 
 
X 
 
Adverse Events17 
X 
X 
X 
Leukapheresis18 
 
 
X 


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Abbreviations: CMV = cytomegalovirus; CT = computed tomography; DLCO =  pulmonary diffusing capacity for carbon monoxide; EBV = Epstein-Barr virus; ECG = electrocardiogram; 
ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; eCRF = electronic case report form; FDG PET = fluorodeoxyglucose positron emission tomography; 
FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; GFR = glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; HLA = human leukocyte antigen; HTLV = human T lymphotropic virus; LAGE-1a = cancer testis antigen 2; MRI = magnetic resonance imaging; 
MUGA = multigated acquisition; NY-ESO-1 = New York esophageal squamous cell carcinoma 1; PFT = pulmonary function test; SoC = standard of care; TLC = total lung capacity; 
WOCBP = women of child-bearing potential. 


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Table 3 
Schedule of Activities – Lymphodepletion/Treatment (Interventional Phase) (Part 3) 
 
Base- 
line 
Lymphodepletion 
Lete-cel 
Infusion1 
Post-T-cell Infusion 
Day (D) / Week (W) 
Day 
-17 to -9 
Day 
Week2 
 
 
-8 
-7 
-6 
-5 
1 
2 
3 
4 
5 
2 
3 
4 
5 
6 
7 
10 to 25 
Q3W 
Arm A: 34-106 Q12W  
Arms B & C: 28-106 Q3W 
Visit Window 
n/a 
 
 
 
 
n/a 
±1 day 
±3 days 
±3 days 
Treatment Fitness 
and 
Lymphodepletion 
Eligibility 
Screening3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med. History4  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Neurological 
assessments5 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ICE5 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Prior/Concomitant 
Medications6 
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 
Vital Signs7,8  
X 
 
 
 
 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECHO/MUGA9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG10 
X 
 
 
 
 
X 
 
 
X 
 
X 
 
 
 
 
 
 
 
Body CT/MRI11,12 
X11,12 
 
 
 
 
See footnotes 11 and 12 
RECIST evaluation 
X11 
 
 
 
 
See footnote 11 
Brain MRI13 
X13 
 
 
 
 
See footnote 13 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ferritin15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Troponin and NT-
proBNP/BNP15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation 
Tests14,15 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
2 5  
 
 
B a s e - 
li n e 
L y m p h o d e pl eti o n  
L et e -c el 
I nf u si o n1 
P o st -T -c ell I nf u si o n  
D a y ( D) / W e e k ( W)  
D a y  
-1 7 t o -9 
D a y  
W e e k 2 
 
 
-8  
-7  
-6  
-5  
1  
2  
3  
4  
5  
2  
3  
4  
5  
6  
7  
1 0 t o 2 5  
Q 3 W  
Ar m A: 3 4 -1 0 6  Q 1 2 W  
Ar m s B & C: 2 8 -1 0 6  Q 3 W  
Vi sit  Wi n d o w  
n/ a  
 
 
 
 
n/ a  
± 1 d a y  
± 3 d a y s  
± 3 d a y s  
Pr e g n a ncy T est 1 6 
X 1 6 
 
 
 
 
X 1 6  
 
 
 
 
 
 
X  
 
 
X  
X  
X  
Uri n aly sis 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I nf ecti o us Dis e as e 
M ark ers  
( HI V, H B V, H C V, 
H T L V, E B V, a n d 
sy p hilis)   
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C M V I g G a n d 
P C R 1 7 
X  
 
 
 
 
X  
 
 
 
 
X  
 
X  
 
X  
X  
 
 
T S H wit h Fr e e T 4 1 8 
X  
Se e f o ot n ot e 1 8  
C R P 1 5 
X  
 
 
 
 
X  
 
 
X   
X  
X  
X  
X  
X  
X  
X  
X  
Uric Aci d  
X  
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
G F R or 2 4 -h uri n e 
c oll ecti o n 1 9 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A dv ers e Ev e nts 2 0 
X  
X  
X  
X  
X  
X  
X  X  X  X  
X  
X  
X  
X  
X  
X  
X  
X  
V ect or C o pi es 
( P ersist e nc e) f or 
S af ety (bl o o d )2 1  
X  
 
 
 
 
 
F or c oll ecti o n, s e e  
f o ot n ot e 2 1  
V S V -G D N A ( R C L) 
f or S af ety (bl o o d )2 2  
X  
 
 
 
 
 
F or c oll ecti o n, s e e  
f o ot n ot e 2 2  
L y m p h o d e pl eti o n  
Fl u d ar a bi n e  
 
X  
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycl o p h os p h a mi d e  
 
 
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
I n v e sti g ati o n al Pr o d u ct A d mi nistrati o n 
L et e -c el 
 
 
 
 
 
X 2 3  
 
 
 
 
 
 
 
 
 
 
 
 
P e m br oliz u m a b  
Se e f o ot n ot e 2 4  
S e e T a bl e 4  f or P K, I m m u n o g e ni cit y, a n d Bi o m ar k ers S a m pl e s 
G e n etic s a m pl e  
X 2 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
2 6  
 
 
B a s e - 
li n e 
L y m p h o d e pl eti o n  
L et e -c el 
I nf u si o n1 
P o st -T -c ell I nf u si o n  
D a y ( D) / W e e k ( W)  
D a y  
-1 7 t o -9 
D a y  
W e e k 2 
 
 
-8  
-7  
-6  
-5  
1  
2  
3  
4  
5  
2  
3  
4  
5  
6  
7  
1 0 t o 2 5  
Q 3 W  
Ar m A: 3 4 -1 0 6  Q 1 2 W  
Ar m s B & C: 2 8 -1 0 6  Q 3 W  
Vi sit  Wi n d o w  
n/ a  
 
 
 
 
n/ a  
± 1 d a y  
± 3 d a y s  
± 3 d a y s  
 
A b br evi ati o ns:  
A E = a dv ers e ev e nt; B N P = B -ty p e n atri ur etic p e pti d e; C M V  =  cyt o m e g al ovir us; C R P =  C -r e activ e pr ot ei n; C R S =  cyt oki n e r el e as e sy n dr o m e; C T = c o m p ut e d t o m o gr a p hy; C T C A E = 
C o m m o n T ec h nic al Crit eri a f or A dv ers e Ev e nts; D N A  =  d e oxyri b o n ucl eic aci d; E B V = E pst ei n -Barr vir us; E C G = el ectr oc ar di o gr a m; E C H O = ec h oc ar di o gr a m; E C O G = E ast er n C o -
o p er ativ e O nc ol o gy Gr o u p; e C R F = el ectr o nic c as e r e p ort f or m;  Eo T = e n d of tr e at m e nt; F D G P E T = fl u or o d e oxy gl uc os e p ositr o n e missi o n t o m o gr a p hy; G F R  =  gl o m er ul ar filtr ati o n 
r at e; H B V = h e p atitis B vir us; H C V =  h e p atitis C vir us; HI V = h u m a n i m m u n o d efici e ncy vir us; 
; H T L V = h u m a n T ly m p h otr o pic vir us; I CA N S =I m m u n e 
Eff ect or C ell -Ass oci at e d N e ur ot oxicity Sy n dr o m e; I C E = I m m u n e Eff ect or C ell-Ass oci at e d E nc e p h al o p at hy ; I g G = i m m u n o gl o b uli n G; M RI = m a g n etic r es o n a nc e i m a gi n g; M U G A = 
m ulti g at e d ac q uisiti o n; N T -pr o B N P = N -t er mi n al pr o B -ty p e n atri ur etic p e pti d e; P C R = p oly m er as e c h ai n r e acti o n; P D = pr o gr essiv e dis e as e; P K  =  p h ar m ac oki n etic; P M B C = p eri p h er al 
bl o o d m o n o n ucl e ar c ell; Q 3 W = o nc e ev ery 3  w e eks; Q 6 W = o nc e ev ery six w e eks; Q 9 W = o nc e ev ery 9  w e eks; Q 1 2 W = o nc e ev ery 1 2  w e e ks; R C L =  r e plic ati o n c o m p et e nt l e ntivir us; 
R E CI S T = R es p o ns e Ev al u ati o n Crit eri a I n S oli d T u m ors; T 4 = t hyr oxi n e; T S H = t hyr oi d sti m ul ati n g h or m o n e; V S V -G  =  v esic ul ar st o m atitis vir us G.  
1. O n D ay 1, a ll s a m pl es will b e c oll ect e d a n d ass ess m e nts p erf or m e d pri or t o L et e -c el i nf usi o n ( wit hi n 2 4 h), u nl ess ot h er wis e s p ecifi e d. 
2. W e ek N visit f or N > 1 is sc h e d ul e d o n 1st d ay of t h e w e ek ; D ay = 7 N -6  
3 . Tr e at m e nt fit n ess will b e ev al u at e d acc or di n g t o S ecti o n 5  a n d d et er mi n e d i n c o ns ult ati o n wit h M e dic al M o nit or .  
4 . M e dic al hist ory, i ncl u di n g hist ory of t o b acc o us e, will b e r ec or d e d i n t h e e C R F at Scr e e ni n g a n d B as eli n e visits; h o w ev er, a n y c h a n g es i n m e dic al hist ory m ust b e r ec or d e d i n s o urc e 
d oc u m e nts t hr o u g h o ut t h e c o n d uct of t h e st u dy   
5 . N e ur ol o gic al ass ess m e nt s ar e t o b e p erf or m e d f or p ati e nts wit h br ai n m et ast as es a n d p ati e nts wit h n e ur ol o gical  a dv ers e ev e nts u p t o 1 2 w e eks p ost r es ol uti o n of t h e ev e nt . I C E 
s h o ul d b e m e as ur e d o n t h e d ay of L et e -c el i nf usi o n pri or t o tr e at m e nt. F oll o wi n g i nf usi o n, I C E s h o ul d b e m e as ur e d acc or di n g t o i nstr ucti o ns i n S ecti o n 1 0. 9. 8. 2 .  
6 . I ncl u d es all pr escri pti o ns, ov er-t h e-c o u nt er m e dic ati o ns a n d h er b al r e m e di es.  A ny us e of m ut a g e nic a g e nts or i nv esti g ati o n al a g e nts m ust als o b e r e p ort e d.   It als o i ncl u d es us e of 
a nti bi otics a n d pr o bi otics t ak e n 6 0 d ays pri or t o ly m p h o d e pl eti o n  a n d u p t o W e ek 7 visit . 
7 . I ncl u d es t e m p er at ur e, bl o o d pr ess ur e, p uls e r at e, r es pir at ory r at e, oxy g e n s at ur ati o n a n d w ei g ht.  H ei g ht will b e c oll ect e d at t h e Scr e e ni n g visit o nly.   
8 . Vit al si g ns o n d ay of L et e -c el i nf usi o n s h o ul d b e t ak e n pr e-i nf usi o n, a n d at 5, 1 5, a n d 3 0 mi n ut es, a n d 1, 1. 5, 2, a n d 4 h o urs aft er t h e i nf usi o n h as st art e d.  O n p e m br oliz u m a b 
i nf usi o n d ays, vit al si g ns s h o ul d b e t ak e n pr e- a n d p ost -i nf usi o n. 
9. If p artic i p a nt's E C H O/ M U G A at l e uk a p h er esis eli gi bility scr e e ni n g m et eli gi bility f or l eft v e ntric ul ar ej ecti o n fr acti o n ≥4 5 % as s p ecifi e d i n S ecti o n 5. 1. 2 , a n d if pri or E C H O/ M U G A w as 
o bt ai n e d wit hi n 9 0 d ays pri or t o t h e first d ay of ly m p h o d e pl eti o n, t h e n a r e p e at E C H O/ M U G A will n ot b e r e q uir e d.  R e p e at E C H O / M U G A at b as eli n e s h o ul d b e o bt ai n e d as cli nic ally 
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
2 7  
 
i n dic at e d. If s us p ect e d C R S Gr a d e ≥2, a n E C H O/ M U G A is r e q uir e d at o ns et of Gr a d e ≥2 C R S. Ad diti o n al m o nit ori n g m ust b e c o n d uct e d (i ncl u di n g i n p ati e nt c o nti n u o us c ar di ac 
t el e m etry m o nit ori n g) f or a mi ni m u m of 3 d ays p ost o ns et a n d as l o n g as d e e m e d n ec ess ary by t h e I nv esti g at or (r ef er t o S ecti o n 1 0. 9. 5 ) 
1 0. C oll ect a si n gl e E C G at b as eli n e.   If Q Tc is > 4 8 0 ms ec, c oll ect 2 m or e E C Gs 5 mi n ut es a p art a n d us e t h e av er a g e of t h os e Q T v al u es t o d et er mi n e eli gi bility.  If t h e av er a g e Q Tc is 
> 4 8 0 ms ec, o bt ai n a m a n u al ov err e a d of t h e tri plic at e. Si n gl e E C Gs will b e c oll ect e d at all ot h er ti m e p oi nts t h at r e q uir e E C Gs . E C G c a n als o b e p erf or m e d at ot h er ti m e p oi nts if 
m e dic ally i n dic at e d. P artici p a nts wit h cli nic ally si g nific a nt c ar di ov asc ul ar risk f act ors ( p er S ecti o n 8. 2. 3 ) will u n d er g o ev al u ati o n by a c ar di ol o gist pri or t o ly m p h o d e pl eti o n. 
1 1. Di a g n ostic q u ality C T sc a n of c h est/ a b d o m e n/ p elvis wit h c o ntr ast is r e q uir e d at B as eli n e ( wit hi n 2 w e eks pri or t o ly m p h o d e pl eti o n),  W e ek 7 ( ± 7 d ays), W e ek 1 3 ( ± 7 d ays), W e ek  1 9 
( ± 7 d ays), W e ek 2 5 ( ± 7 d ays), W e ek 3 4 ( ± 7 d ays), a n d Q 1 2 W ( ± 7 d ays) t h er e aft er, u ntil E o T.  If a p artici p a nt is f o u n d t o h av e a t u m or r es p o ns e by i m a gi n g, a f oll o w -u p c o nfir m at ory 
sc a n m ust b e d o n e n o e arli er t h a n 4 w e eks a n d n o l at er t h a n t h e n ext sc h e d ul e d i m a gi n g ti m e p oi nt aft er t h e i niti al sc a n s h o wi n g r es p o ns e.  If a p artici p a nt is f o u n d t o h av e pr o gr essiv e 
dis e as e by  i m a gi n g, a f oll o w -u p c o nfir m at ory sc a n m ust b e d o n e n o e arli er t h a n 4 w e eks a n d n o l at er t h a n 8 w e eks  aft er t h e i niti al sc a n s h o wi n g P D .  I nv esti g at or ass ess e d R E CI S T  
v 1. 1
 ev al u ati o n m ust b e d o n e f oll o wi n g i nstr ucti o ns i n Ap p e n dix 1 0 .  
1 2. A ny F D G P E T/ C T p erf or m e d as p art of cli nic al r o uti n e will b e c oll ect e d c e ntr ally b ut will n ot r e pl ac e C T sc a ns.  
1 3. Br ai n M RI ( or C T Sc a n if M RI n ot f e asi bl e) s h o ul d b e p erf or m e d at Bas eli n e ( wit hi n 4 w e eks pri or t o ly m p h o d e pl eti o n) if m or e t h a n 4 m o nt hs h av e el a ps e d fr o m l ast br ai n M RI. A 
r e p e at br ai n M RI pri or t o ly m p h o d e pl eti o n w o ul d n e e d t o s h o w st a bility or r e d ucti o n of C N S m et ast as es if a ny r a di ot h er a py w as a d mi nist er e d aft er t h e M RI p erf or m e d f or l e uk o p h er esis 
eli gi bility scr e e ni n g. Br ai n M RI s h o ul d b e p erf or m e d as cli nic ally i n dic a t e d t h er e aft er (s e e S ecti o n 1 0. 9. 8 ).  
1 4. C o a g ul ati o n t ests i ncl u d e I N R, P T T or a P T T a n d fi bri n o g e n. C o a g ul ati o n t ests s h o ul d b e t ak e n at b as eli n e , D ay 1, 2, 3, 4, 5, 8 a n d 1 5.  
1 5 . If C R S a n d/ or I C A N S  is s us p ect e d, c h e mistry, h e m at ol o gy, f erriti n, c o a g ul ati o n a n d C R P t ests s h o ul d b e p erf or m e d l oc ally ev ery d ay f or t h e first w e ek a n d ev ery  ot h er d ay 
t h er e aft er u ntil sy m pt o ms ar e i m pr ovi n g or a n alt er n ativ e di a g n osis is c o nfir m e d . I n a d diti o n, if C R S is s us p ect e d, cyt oki n e s a m pl es will b e c oll ect e d f or c e ntr al a n alysis f oll o wi n g s a m e 
sc h e d ul e, as d et ail e d i n T a bl e 4 . Tr o p o ni n a n d N T -pr o B N P / B N P t ests s h o ul d b e m o nit or e d f or p artici p a nts wit h C R S G r a d e ≥2 as cli nic ally i n dic at e d. 
1 6. W O C B P m ust h av e a n e g ativ e uri n e or s er u m pr e g n a ncy t est ( hi g hly s e nsitiv e) at Bas eli n e ( wit hi n 2 4 h o urs pri or t o ly m p h o d e pl eti o n), pri or t o L et e -c el i nf usi o n, a n d t h er e aft er will 
n e e d t o h av e pr e g n a ncy t ests p erf or m e d at all visits i n dic at e d i n t h e t a bl e f or t h e d ur ati o n of t h e c o ntr ac e pti o n p eri o d (s e e S ecti o n 5. 3. 3. 2  a n d S ecti o n 8. 4. 7 ). 
1 7. O nly p artici p a nts w h o ar e C M V I g G s er o p ositiv e at Bas eli n e will c o nti n u e t o b e m o nit or e d f or C M V vir e mi a by C M V D N A P C R p ost B as eli n e.  C M V will als o b e ass ess e d if G B S is 
s us p ect e d. 
1 8.  T hyr oi d t ests m ust b e p erf or m e d Q 6 W d uri n g p e m br oliz u m a b a d mi nistr ati o n. Se e f o ot n ot e 2 4  f or first p e m br oliz u m a b a d mi nistr ati o n. 
1 9. S e e T a bl e 1 1  f or s p ecifics o n r e n al ass ess m e nt. 
2 0. A dv ers e ev e nts s h o ul d b e c oll ect e d a n d r e p ort e d as n ot e d i n S ecti o n 8. 4 . 
2 1. P B M Cs f or P ersist e nc e will b e c oll ect e d at B as eli n e ( D ay -1 7 t o D ay - 9)  a n d at We ek 1 3, W e ek 2 5, a n d ev ery 6 m o nt hs t h er e aft er ( e. g., 1 2 m o nt hs, 1 8 m o nt hs, 2 4  m o nt hs, etc.) 
u ntil 5  y e ars p ost L et e -c el i nf usi o n, t h e n o nc e a y e ar f or u p t o 1 5 y e ars. Aft er W e ek 2 2, t h e visit wi n d o w f or this ass ess m e nt will b e ± 3 m o nt hs. S o m e of t h es e s a m pl es m ay b e t ak e n 
aft er t h e p artici p a nt e nt ers t h e L T F U pr ot oc ol ( G S K St u dy 2 0 8 7 5 0) or st u dy P art 5 ( T a bl e 8 ). P B M Cs f or P ersist e nc e m ay b e c oll ect e d i n a d diti o n al ti m e p oi nts as cli nic ally i n dic at e d. If 
v ect or p ersist e nc e  is u n d et ect e d f or t w o c o ns ec utiv e visit ass ess m e nts a n d t h e p artici p a nt is ≥2 y e ars p ost-i nf usi o n, s a m pl es f or p ersist e nc e of g e n e m o difi e d c ells will b e 
disc o nti n u e d.  
2 2. P B M Cs f or R C L will b e c oll ect e d at B as eli n e ( D ay -1 7 t o D ay - 9)  a n d at We ek 1 3, We ek 2 5, a n d ev ery 6 m o nt hs t h er e aft er ( e. g., 1 2 m o nt hs, 1 8 m o nt hs, 2 4  m o nt hs, etc.) u ntil 
5  y e ars p ost L et e -c el i nf usi o n, t h e n o nc e a y e ar f or u p t o 1 5 y e ars.  Aft er W e ek 2 2, t h e visit wi n d o w f or t his ass ess m e nt will b e ±  3 m o nt hs. S o m e of t h es e s a m pl es m ay b e t ak e n aft er 
t h e p artici p a nt e nt ers t h e L T F U pr ot oc ol ( G S K St u dy 2 0 8 7 5 0). If v ect or p ersist e nc e is u n d et ect e d f or t w o c o ns ec utiv e  visit ass ess m e nts a n d t h e p artici p a nt is ≥2 y e ars p ost -i nf usi o n, 
s a m pl es f or R C L will b e disc o nti n u e d. 
2 3. P artici p a nts will b e h os pit aliz e d o n t h e d ay of T -c ell i nf usi o n ( D ay 1) a n d m ay b e i n t h e h os pit al f or f oll o w -u p c ar e u ntil D ay 3 as cli nic ally i n dic at e d. P artici p a nts will b e i n cl os e 
pr oxi mity t o t h e h os pit al f or at l e ast 7 d ays p ost i nf usi o n. Ad diti o n al h os pit aliz ati o n m ay b e w arr a nt e d b as e d u p o n cli nic al n e e d.  
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
2 8  
 
2 4. Ar ms B a n d C o nly. First p e m br oliz u m a b a d mi nistr ati o n o n D ay 2 2 ( W e ek 4 D ay 1), t h e n Q 3 W f or u p t o 3 5 cycl es.  If t oxiciti es t h at pr ecl u d e p e m br oliz u m a b tr e at m e nt, s uc h as C R S 
Gr a d e ≥2, ar e pr es e nt at D ay  2 2, t h e first i nf usi o n of p e m br oliz u m a b will b e o n W e ek 7 D ay 1, i n w hic h c as e, Cycl e 3 5 will occ ur o n W e ek 1 0 9 D ay 1. If A Es  d o n o t r es olv e by W e ek 7 
D ay 1 t o ≤ Gr a d e 1, p e m br oliz u m a b will n ot b e a d mi nist er e d, a n d t h e p artici p a nt will b e ev al u at e d u ntil dis e as e pr o gr essi o n o r E o T. Pe m br oliz u m a b m ay b e a d mi nist er e d u p t o 3 d ays 
b ef or e or aft er t h e sc h e d ul e d D ay 1 of e ac h cycl e d u e t o a d mi nistr ativ e r e as o ns.  
2 5. F or bi o m ark er a n alysis, if g e n etic s a m pl e c oll ecti o n is n ot d o n e at Bas eli n e, it m ay b e d o n e at a ny ot h er s u bs e q u e nt visi t i n t h e I nt erv e nti o n al P h as e. C oll ecti o n of a g e n etic s a m pl e 
is o pti o n al a n d all p artici p a nts m ust pr ovi d e c o ns e nt f or s a m pl e c oll ecti o n a n d a n alysis pri or t o s a m pli n g.  
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
2 9  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
3 0  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
3 1  
 
T a bl e 5  
S c h e d ul e of A cti viti e s –  P e m br oli z u m a b T h er a p y F oll o wi n g Di s e a s e Pr o gr e s si o n aft er L et e -c el I nf u si o n (P art  4 -
Ar m  A o nl y)  
P e m br oliz u m a b ( P) W e e k ( W)  
P B L  
P W 1  P W 2  
P W 4  
P W 7  
P W1 0 
t o 
P W1 0 3  
( Q3 W) 
N ot e s  
1. W e ek N visit f or N > 1 is sc h e d ul e d o n 1st day of t h e w e ek ; Day = 7 N -6.  
2. B as eli n e ass ess m e nts re q uir e d o nly if t h e ass ess m e nts h av e n ot b e en p erf or m e d wit hi n 2 8 d ays 
pri or t o first p e m broliz u ma b a d mi nistr ati o n.  
3. S e e S ecti o n 5. 1. 4 . 
4. Ne urol o gic al ass ess m e nt f or p artici p ants wit h br ai n met ast as es a n d t hos e wit h n e urol o gic al 
a dv ers e ev e nts u p t o 1 2 w e eks p ost r es ol uti o n of t h e ev e nt.  
5. Si n gl e E C G o n t h e d ays of p e m broliz u ma b a d mi nistrati o n, pri or t o i nf usi o n.  
6. P e m broliz u ma b B as eli n e C T/ M RI pri or t o p e mbroliz u ma b t h era py m ust b e o bt ai n e d wit hi n 4 we eks 
pri or t o first p e m broliz u ma b a d mi nistr ati o n. If t h e C T/ M RI h as b e e n o bt ai n e d at P D wit hi n 4 we eks 
pri or t o p e mbroliz u ma b t h era py i niti ati o n, t his c a n b e c o nsi d er e d as b as eli n e m e as ure me nt. 
Di a g n ostic q u ality C T sc a n of c h est/ a b do me n/ p elvis wit h c o ntrast is re q uir e d ev ery 6 we eks ( ± 7 d ays) 
u ntil P W 2 5, at P W 3 4, a n d t h e n ev ery 1 2 we eks ( ± 7 d ays) t here aft er, until E o T f or p e m broliz u ma b. If 
a p artici p a nt is f o u n d t o h av e a t u m or res p o ns e by i m a gi n g, a f oll o w -u p c o nfir m at ory sc a n m ust be 
d o n e n o e arli er t h a n 4 we eks a n d n o l at er t ha n t h e n ext sc h ed ul e d i m a gi n g ti m e p oi nt aft er t h e i niti al 
sc a n s h o wi n g res p o ns e.  If a p artici p a nt is f ou nd t o h av e pro gressiv e dis e as e by i m a gi n g, a f oll o w-u p 
c o nfir m at ory sc a n m ust b e d o n e n o e arli er t ha n 4 w e eks a n d n o l at er t h an 8 we eks aft er t he i niti al 
sc a n s h o wi n g P D.  I nv esti g at or ass ess e d R E CI S T  v 1. 1
 ev al u ati o n m ust be d o ne f oll o wi n g 
i nstructi o ns i n A p p e n dix 1 0 . A ny F D G P E T/ C T p erf or m e d as p er cli nic al ro uti n e will b e c oll ect e d 
c e ntrally b ut will n ot r e pl ac e C T sc a ns. 
7. W O C B P will n e e d t o h av e pre g n a ncy t ests (hi g hly s e nsitiv e) p erf or m e d at all vi sits i n dic at e d i n t h e 
t a bl e f or t h e d urati o n of t h e c o ntrac e pti o n p eri o d (s e e S ecti o n 5. 3. 3. 2  a nd S ecti o n 8. 4. 7 ). 
8. O nly p artici p a nts wh o are C M V I g G s ero positiv e at P B L will c o nti n ue t o b e m o nit ore d f or C M V 
vire mi a by C M V D N A P C R p ost P B L. 
9. T hyroi d t ests m ust b e p erf or m e d Q 6 W d uri n g p e m brol iz u ma b a d mi nistrati o n.   
1 0 . If C R S a n d/ or I C A N S  is s us p ect e d, c h e mistry, he m at ol o gy, f erriti n, c o a g ul ati o n a n d C R P t ests 
s h o ul d b e p erf or m e d l oc ally ev ery d ay f or t he first we ek a n d ev ery ot h er d ay t here aft er u ntil 
sy m pt o ms are i m provi n g or a n alt ern ativ e di a g n osis is c o nfir m e d . I n a d diti o n, if C R S is s us p ect e d, 
cyt oki n e s a m pl es will b e c oll ect e d f or c e ntral a nalysis f oll o wi n g s a m e sc h e d ul e , as d et ail e d i n T a bl e 
6. Tro p o ni n a n d N T -pro B N P / B N P t ests s h oul d be m o nit ore d f or p artici p a nts wit h C R S G ra de ≥2 as 
cli nic ally i n dic at e d. 
1 1 . P B M Cs f or P ersist e nc e a n d R C L t esti n g will b e c oll ect e d at P W 13, P W 2 5, an d ev ery 6 m o nt hs 
u ntil E o T f or p e m broliz u ma b or dis e as e pro gressi o n, whic h ev er c o m es first.  Dat a c oll ect e d at 
B as eli n e ( D ay -1 4 t o D ay - 9)  pri or t o l et e-cel will b e us e d as b as eli n e.  
1 2 . If v ect or p ersist e nc e is u n d et ect e d f or t wo c o ns ec utiv e visit ass ess m e nts a nd t h e p artici p ant is ≥2 
y e ars p ost-i nf usi o n, s a m pl es f or R C L a n d p ersist e nc e of g e n e m o difi e d c ells will b e disc o nti n ue d.  
H o wev er, if V S V -G D N A c o pi es are d et ect e d at a ny ti m e p oi nt d uri n g y e ar 1, ref er t o t h e s af ety 
m o nit ori n g proc e d ures i n S ecti o n  8. 3. 5. 
Vi sit Wi n d o w 1 
-2 8  
d a y s 2 
±1 
d a y  
±3  
d a y s  
±3  
d a y s  
P e m br olizu m a b Eligibility 3 
X  
 
 
 
 
 
P hysical Exa m  
X  
X  
X  
X  
X  
X  
N e ur olo gical Exa m 4 a n d  I C E 
X  
S e e n ot e 4  
Pri or/ C o nc o mit a nt M e dicati o ns  
X  
X  
X  
X  
X  
X  
E C O G  
X  
X  
X  
X  
X  
X  
Vit al Sig ns  
X  
X  
X  
X  
X  
X  
E C G 5 
X  
X  
 
X  
 
 
C T/ M RI 6 
X  
 
 
 
X 6  
X  
R E CI S T  Evalu atio n 6 
X  
 
 
 
X  
X  
H e m at olo gy 9 
X  
X  
X  
X  
X  
X  
C h e mistry 9 
X  
X  
X  
X  
X  
X  
Pr e g n a ncy T est 7 
X  
S e e n ot e 7  
C M V I g G a n d P C R 8 
S e e n ot e 8  
T S H wit h Fr e e T 4 9 
S e e n ot e 9  
C R P 1 0 
 
X  
X  
X  
X  
X  
F erritin 1 0 
S e e n ot e 1 0  
C o a g ul atio n T ests 1 0 
S e e n ot e 1 0  
Tr o p o nin a n d N T -pr o B N P/ B N P 1 0 
S e e n ot e 1 0  
A dverse Eve nts  
 
X  
X  
X  
X  
X  
V ect or C o pi es ( P ersist e nce f or 
S af ety)  [ blo o d] 
S e e n ot es 1 1  a n d 1 2  
V S V -G D N A ( R C L)  [ blo o d] 
S e e n ot es 1 1  a n d 1 2  
P e m br oliz u m a b 
a d mi ni str ati o n  
 
X  
 
X  
X  
X  
C CI


TMF-14132100 
CONFIDENTIAL 
 
 
 
208471 
 
32 
 
See Table 6 for PK, Immunogenicity, and Biomarker Samples 
 
EoT = end of treatment; FDG PET = fluorodeoxyglucose positron emission tomography; IgG = immunoglobulin G; MRI = magnetic resonance imaging; PBL = Pembrolizumab Baseline; 
PCR = polymerase chain reaction; PD = progressive disease; PK = pharmacokinetics; PW = Pembrolizumab Week; Q3W = once every 3 weeks; RCL = replication competent 
lentivirus; RECIST = Response Evaluation Criteria In Solid Tumors; VSV-G = vascular stomatitis virus G.  
Note: Pembrolizumab therapy is only allowed in case of disease progression within the first 25 weeks after lete-cel infusion.  Pembrolizumab therapy will not be allowed if disease 
progression occurs after the Week 25 scan.  Pembrolizumab treatment will be administered for up to 35 cycles Q3W at 200 mg or until subsequent disease progression. 
 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
3 3  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
3 4  
 
T a bl e 7  
S c h e d ul e of A cti viti e s –  E n d of Tr e at m e nt /E n d of I nt er v e nti o n al P h a s e 
D a y ( D) /  
W e e k ( W)  
C o m pl eti o n/ 
Wit h dra w al 1 
N ot e s  
Cli ni c al A s s e s s m e nt s a n d Pr o c e d ure s 2 
1.  P artici p a nts will c o m pl et e t h e Eo T visit aft er c o m pl eti n g i nt erv e nti o n al p orti o n of t h e st u dy 
( Parts 3 or 4; s e e S ecti o n 4. 4. 1 ), disc o nti n u ati o n of p e m br oliz u m a b (if r el ev a nt)  or e arly 
wit h dr a w al fr o m t h e i nt erv e nti o n al p h as e . E o T visit is t o b e c o m pl et e d o nly o nc e f or e ac h 
p artici p a nt. All pr oc e d ur es a n d ass ess m e nts, as i n dic at e d, s h o ul d b e p erf or m e d pr ef er a bly 4 
w e eks a n d n o l at er t h a n 6 0  d ays fr o m l ast p e m br oliz u m a b tr e at m e nt or visit, as r el ev a nt.  If 
p erf or m e d s o o n er , o nly c o m pl et e ass ess m e nts n ot alr e a dy p erf or m e d  as p art of l ast 
p e m br oliz u m a b tr e at m e nt or visit . Eo T visit m ust b e c o m pl et e d pri or t o i niti ati n g n o n -pr ot oc ol 
a nti -c a nc er t h er a py, if r el ev a nt ( S e e S ecti o n 6. 9. 1 ). 
2.  S e e S ecti o n 8  f or d et ails. 
3.  I ncl u d es all pr escri pti o ns, ov er -t h e-c o u nt er m e dic ati o ns, a n d h er b al r e m e di es.  A ny us e of 
m ut a g e nic a g e nts or i nv esti g ati o n al a g e nts m ust als o b e  r e p ort e d. 
4.  I ncl u d es t e m p er at ur e, bl o o d pr ess ur e, p uls e r at e, r es pir at ory r at e, a n d oxy g e n s at ur ati o n.   
5.  If cli nic ally n e e d e d.  
6.  If a p artici p a nt is f o u n d t o h av e a t u m or r es p o ns e or pr o gr essiv e dis e as e by i m a gi n g vi a 
R E CI S T v 1. 1, a f oll o w -u p c o nf ir m ati o n sc a n m ust b e d o n e n o e arli er t h a n 4 w e eks a n d n o l at er 
t h a n 8 w e eks f oll o wi n g t h e sc a n w h e n r es p o ns e or dis e as e pr o gr essi o n w as first s e e n.  A 
p artici p a nt is n ot c o nsi d er e d t o h av e a r es p o ns e or pr o gr essi o n u ntil a f oll o w -u p sc a n c o nfir ms 
t h e fi n di n g.  Any F D G P E T/ C T p erf or m e d as p er cli nic al r o uti n e will b e c oll ect e d c e ntr ally b ut 
will n ot r e pl ac e C T sc a ns.  
7.  If a C T / M RI ass ess m e nt h as b e e n c o m pl et e d wit hi n t h e l ast 4 w e eks, a d diti o n al C T / M RI 
ass ess m e nts ar e n ot r e q uir e d as p art of E o T visit , u nl ess it is c o nfir m at ory sc a n ( wit hi n t h e 
sc h e d ul e i n N ot e #6, a b ov e).  
8.  If dis e as e pr o gr essi o n h as b e e n c o nfir m e d pri or t o Eo T visit, a d diti o n al C T / M RI 
ass ess m e nts ar e n ot r e q uir e d as p art of E o T visit.  
9.  A dv ers e ev e nts s h o ul d b e r e p ort e d as n ot e d i n S ecti o n 8. 4 . 
Pri or/ C o nc o mit a nt M e dic ati o ns 3 
X  
P hysic al Ex a m  
X  
E C O G  
X  
Vit al Si g ns / H ei g ht / W ei g ht 4  
X  
E C G  
X 5 
C T / M RI 6,7,8 
X  
H e m at ol o gy  
X  
C h e mistry  
X  
A dv ers e Ev e nts 9 
X  
C orrel ati v e St u di e s a n d R e s e ar c h A s s e s s m e nt s  
1 1.  Bi o psi es f or r es e arc h ar e t ak e n at B as eli n e, W e ek 7, a n d at c o nfir m ati o n of P D, wit h t h e 
exc e pti o n of p artici p a nts f or w h o m t h er e is n o s af ely acc essi bl e t u m or tiss u e.   
1 2.  Li q ui d Bi o psy s a m pl es s h o ul d m atc h t u m or bi o psy a n d/ or C T/ M RI ass ess m e nt ti m e p oi nts.  
Se e f o ot n ot e 6 f or C T/ M RI ass ess m e nt.  
T u m or bi o psy 1 1 
X  
Li q ui d Bi o psy ( bl o o d) 1 2   
X  
Bl o o d f or C ell P h e n oty p e a n d F u ncti o n al Ass ays  
X  
Cyt oki n e A n alys es  
X  
C CI


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Abbreviations: cfDNA = cell-free DNA; CT = computed tomography; CTCAE = Common Technical Criteria for Adverse Events; D = Day; DNA = deoxyribonucleic acid; 
ECG = electrocardiogram; ECOG = Eastern Co-operative Oncology Group; EoT = end of treatment; FDG PET = fluorodeoxyglucose positron emission tomography; MRI = magnetic 
resonance imaging; PD = Progressive Disease;  W = Week. 
 
 


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Table 8 
Schedule of Activities – Long Term Follow-up after Disease Progression or Completion of Interventional Phase 
(Part 5 or Study 208750) 
 
 
 
 
 
 
Allo-SCT = allogeneic stem cell transplant; CBC = complete blood cell (count); RCL = replication competent lentivirus; VSV-G = vesicular stomatitis virus G 
 
1. 
If a site visit is not feasible, then medical evaluation of participants may take place via telemedicine (e.g., phone call or video conferences) where country and/or local 
regulations allow. Where applicable country and local regulations; and infrastructure for home healthcare allow, upon approval by the sponsor home healthcare may take 
place at a location other than the clinical trial site to perform study assessments, which may include medical history, physical exam, collection of blood samples, 
measurement of height and weight. Remote visits may be performed upon approval by the sponsor at the participant’s home by qualified study personnel or at a local medical 
facility, unless the Investigator deems that a site visit is necessary. 
2. 
Collect new medical history/medications and chemotherapies and/or radiotherapy.   
3. 
All participants who received pembrolizumab will be followed for 24 months after their last dose to ascertain if they are candidates to receive an allogeneic- stem cell 
transplant (allo-SCT). Participants who receive an allo-SCT within the 24-month follow-up period will be monitored for 18 months for post allo-SCT complications as described 
in Section 8.4.5. 
4. 
Delayed adverse event collection is limited to: 
• 
New malignancies 
• 
New incidence or exacerbation of pre-existing neurologic disorder 
Time post-infusion1 
 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Year 6-159 
 
Months 
3 
6 
12 
18 
24 
30 
36 
42 
48 
54 
60 
Annually 
Unscheduled 
Visit7 
Visit Window 
±2 weeks 
±3 months 
±6 months 
 
Medical History2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Subsequent anti-cancer therapies 
or allogeneic stem cell transplant 
(allo-SCT)2,3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Delayed Adverse Events4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X5 
 
CBC with differential and Serum 
Chemistry6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
VSV-G DNA (RCL) and vector 
copies (Persistence) for safety 
(blood)6,7  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Survival Status8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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• 
New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder 
• 
New incidence of a hematologic disorder 
• 
New incidence of infection (potentially related to gene modified cell therapy)  
• 
Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy 
• 
Specific events outlined in Section 8.3 for participants who received pembrolizumab and had allo-SCT  
5. 
During years 6-15 of annual follow-up period, AEs and SAEs will be entered in the CRF if reported by the patient or investigator.     
6. 
If a visit for medical evaluation is conducted via telemedicine, a site visit to collect a blood samples should be performed as soon as practicable.  
7. 
If vector persistence is undetected for two consecutive visit assessments and the participant is ≥2 years post-infusion, samples for RCL and persistence of gene modified 
cells will be discontinued. 
8. 
If a participant is contacted between the scheduled visits, the date of last contact should be recorded as an unscheduled visit.    
9. 
Subjects who do not have persistence of gene modified cells may be followed remotely during years 6-15. 
 


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2. 
INTRODUCTION 
2.1. 
Study Rationale 
Adoptive T-cell therapy (ACT) is a therapeutic approach that uses a patient’s own 
T lymphocytes, obtained by leukapheresis, engineered to express a tumor-specific T-cell 
receptor (TCR), expanded ex vivo, and re-infused into the patient, with the aim of 
generating an anti-tumor T-cell immune response.  The New York esophageal squamous 
cell carcinoma 1 (NY-ESO-1) and cancer testis antigen 2 (LAGE-1a) antigens are tumor-
associated proteins that have been found in several tumor types, including non-small cell 
lung cancer (NSCLC).  Previous clinical trials using ACT with T-cells directed against 
NY-ESO-1/LAGE-1a have shown objective responses between 40% to 60% in 
participants with synovial sarcoma, metastatic melanoma, and multiple myeloma 
[Robbins, 2011; Robbins, 2015; Rapoport, 2015]. 
Pembrolizumab (KEYTRUDA) is a monoclonal antibody that acts specifically on 
tumor-targeting T-cells to block the interaction of programmed death protein 1 (PD-1) 
and its ligand (PD-L1) interaction and increase the anti-tumor function of T-cells.  In this 
study, pembrolizumab will be used in combination with NY-ESO-1/LAGE-1a TCR 
engineered patient T-cells (lete-cel) to potentially further improve the therapeutic effect.  
2.2. 
Background 
Lung cancer is the most common cause of cancer death, accounting for 1.69 million 
deaths worldwide [WHO, 2018].  Although the incidence and mortality rates attributed to 
cancer vary across regions globally, lung cancer remains the leading cause of cancer 
death in men and the second leading cause of cancer death in women [Torre, 2015].  
Non-small cell lung cancer accounts for the majority of lung cancer cases (up to 85%) 
with disease stage, histological subtype (viz., adenocarcinoma, squamous, and large cell) 
and molecular features playing the principal role in the selection of the course of 
treatment.  
In advanced-stage metastatic NSCLC that is determined positive for a specific molecular 
alteration (such as epidermal growth factor receptor (EGFR), anaplastic lymphoma 
kinase (ALK), c-ros oncogene 1 (ROS1), and BRAF), targeted single-agent approaches 
are recommended [NCCN, 2017; Postmus, 2017].  For metastatic non-squamous NSCLC 
who present with either wild-type (WT) or Kirsten rat sarcoma viral oncogene (KRAS) 
mutated tumors, the incorporation of an anti-PD-1 inhibitor, such as, pembrolizumab, to 
the pemetrexed/carboplatin backbone is an option for some patients as first-line treatment 
through the recent accelerated approval of this triplet combination by the Food and Drug 
Administration (FDA) [Langer, 2016].  An alternative current standard for NSCLC is 
pembrolizumab as a single-agent for the first-line treatment of patients with metastatic 
NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] 
≥50%) or, in subsequent lines of therapy as a single-agent for the treatment of metastatic 
NSCLC expressing PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with 
disease progression on or after platinum-containing chemotherapy [Reck, 2016].  
Additional subsequent-line treatment options include other single-agent anti-PD-1/PD-L1 
inhibitors (for example, nivolumab, atezolizumab) if not administered in the first line 


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[Brahmer, 2015; Rittmeyer, 2017].  Older therapies such as pemetrexed for non-
squamous NSCLC (if not used as part of the platinum-based chemotherapy doublet), 
gemcitabine for squamous NSCLC, or docetaxel for all NSCLC sub-types have been 
relegated to later lines and can be selected, based on a patient’s treatment history, disease 
characteristics, and performance status.  The clinical activity of older single-agent 
chemotherapies such as docetaxel for second-line treatment in NSCLC is limited with 
response rates in the range of 9% to 24% [Shepherd, 2000; Hanna, 2004].  Thus, patients 
with NSCLC that has failed anti-PD-1/PD-L1 blockers (alone or in combination with 
chemotherapy) have a high unmet medical need for treatment advances that improve 
progression-free survival (PFS) and overall survival (OS). 
2.2.1. 
Lete-cel 
Lete-cel consists of autologous T cells transduced with lentiviral vectors to express the 
affinity enhanced TCR (c259) and is being investigated in multiple GSK sponsored pilot 
clinical trials in participants with metastatic synovial sarcoma, advanced myxoid/round 
cell liposarcoma, and/or relapsed refractory multiple myeloma who are HLA-A*02+ and 
whose tumors express NY-ESO-1 and/or LAGE-1a.  NY-ESO-1 and LAGE-1a are 
members of the cancer-testis family of tumor associated antigens.  Published data 
indicate that approximately 11% to 43% of NSCLC tumors express NY-ESO-1 [Grah, 
2008; Gure, 2005].  The Cancer Genome Atlas Ribonucleic Acid (TCGA RNA) 
sequencing database indicates a frequency of expression of NY-ESO-1 of 12% in lung 
adenocarcinoma and 26% in squamous cell carcinoma and a frequency of expression of 
LAGE-1a in 8.5% of adenocarcinoma and 21% of squamous cell carcinoma.  An 
HLA-A2 binding peptide (SLLMWITQC), corresponding to amino acids 157 to 165 in 
both NY-ESO-1 and LAGE-1a, that can be recognized by NY-ESO-1 reactive T-cells has 
been identified.  Lete-cel is a product of genetically engineered T-cells with an enhanced 
affinity T-cell receptor toward the SLLMWITQC peptide bound to HLA-A*02.   
Most clinical protocols with TCR gene therapy have incorporated conditioning of the 
patient with a lymphodepleting chemotherapy regimen prior to T-cell infusion [Rohaan, 
2019].  As of 15 May 2018, 3 participants with NSCLC have received lete-cel in 
combination with lymphodepleting chemotherapy (Section 6.3) in an ongoing trial (Study 
208749).  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], facilitate trafficking of the engineered T-cells [Pinthus, 
2004] and also improve the persistence of infused T-cells.  Lymphodepletion can also 
enhance 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. 
2.2.2. 
Pembrolizumab 
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody 
(mAb) with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction 
with PD-L1 and programmed death protein 2 ligand (PD-L2).  Based on in vitro 


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preclinical data, pembrolizumab has high affinity and potent receptor blocking activity 
for PD-1.  Pembrolizumab is indicated for the treatment of patients across a number of 
indications.  Pembrolizumab has an acceptable preclinical safety profile and is in clinical 
development as an intravenous (IV) immunotherapy for other advanced malignancies.  
Refer to the Investigator’s Brochure (IB)/approved labeling for detailed background 
information on pembrolizumab. 
2.2.2.1. 
Pharmaceutical and Therapeutic Background  
The importance of intact immune surveillance function in controlling neoplastic 
transformations has been known for decades [Disis, 2010].  Accumulating evidence 
shows a correlation between tumor-infiltrating lymphocytes in cancer tissue and a 
favorable prognosis in various malignancies.  In particular, the presence of CD8+ T-cells 
and a high ratio of CD8+ effector T-cells/FoxP3+ regulatory T-cells (T-regs) correlates 
with improved prognosis and long-term survival in solid malignancies, such as ovarian, 
colorectal, and pancreatic cancer; hepatocellular carcinoma; malignant melanoma; and 
renal cell carcinoma.  Tumor-infiltrating lymphocytes can be expanded ex vivo and 
reinfused, inducing durable objective tumor responses in cancers such as melanoma 
[Dudley, 2005; Hunder, 2008]. 
The PD-1 receptor-ligand interaction is a major pathway that is hijacked by tumors to 
suppress immune control.  The normal function of PD-1, expressed on the cell surface of 
activated T-cells under healthy conditions, is to down-modulate unwanted or excessive 
immune responses, including autoimmune reactions.  PD-1 (encoded by the gene Pdcd1) 
is an immunoglobulin (Ig) superfamily member related to cluster of differentiation 28 
(CD28) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) that has been shown 
to negatively regulate antigen receptor signaling upon engagement of its ligands (PD-L1 
and/or PD-L2) [Greenwald, 2005; Okazaki, 2001]. 
The structure of murine PD-1 has been resolved [Zhang, 2004].  PD-1 and its family 
members are type I transmembrane glycoproteins containing an immunoglobulin 
variable–type (IgV) domain responsible for ligand binding and a cytoplasmic tail 
responsible for the binding of signaling molecules.  The cytoplasmic tail of PD-1 contains 
2 tyrosine-based signaling motifs, an immunoreceptor tyrosine-based inhibition motif, 
and an immunoreceptor tyrosine-based switch motif.  Following T-cell stimulation, PD-1 
recruits the tyrosine phosphatases, Src homology 2 containing phosphatases 1 and 2 
(SHP-1 and SHP-2), to the immunoreceptor tyrosine-based switch motif within its 
cytoplasmic tail, leading to the dephosphorylation of effector molecules such as CD3 zeta 
(CD3ζ), protein kinase C-theta (PKCθ), and zeta-chain-associated protein kinase 
(ZAP70), which are involved in the CD3 T-cell signaling cascade [Okazaki, 2001; 
Chemnitz, 2004; Sheppard, 2004; Riley, 2009].  The mechanism by which PD-1 down-
modulates T-cell responses is similar to, but distinct from, that of CTLA-4, as both 
molecules regulate an overlapping set of signaling proteins [Parry, 2005; Francisco, 
2010].  As a consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic 
intervention in NSCLC.  


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2.2.2.2. 
Pre-clinical Data 
Therapeutic studies in mouse models have shown that administration of antibodies 
blocking PD-1/PD-L1 interaction enhances infiltration of tumor-specific CD8+ T-cells 
and ultimately leads to tumor rejection, either as a monotherapy or in combination with 
other treatment modalities [Hirano, 2005; Blank, 2004; Weber, 2010; Strome, 2003; 
Spranger, 2014; Pilon, 2010].  Anti-mouse PD-1 or anti-mouse PD-L1 antibodies have 
demonstrated antitumor responses in models of squamous cell carcinoma, pancreatic 
carcinoma, melanoma, acute myeloid leukemia and colorectal carcinoma [Strome, 2003; 
Curran, 2010; Pilon, 2010; Nomi, 2007; Zhang, 2004].  In such studies, tumor infiltration 
by CD8+ T-cells and increased IFN-γ, granzyme B and perforin expression were 
observed, indicating that the mechanism underlying the antitumor activity of PD-1 
checkpoint inhibition involved local infiltration and activation of effector T-cell function 
in vivo [Curran, 2010].  Experiments have confirmed the in vivo efficacy of anti-mouse 
PD-1 antibody as a monotherapy, as well as in combination with chemotherapy, in 
syngeneic mouse tumor models (Refer to pembrolizumab IB/approved labeling). 
2.2.3. 
Rationale for the Combination Regimen 
The immunomodulatory molecule PD-L1 is expressed on both tumor cells and immune 
cells within the tumor microenvironment.  Furthermore, the expression of PD-1 is 
upregulated on activated T-cells.  The expression of immunosuppressive receptors such 
as PD-1 is one mechanism by which the efficacy of ACT could be inhibited.  In a 
xenograft model of NSCLC, it was observed that PD-1 expression was significantly 
upregulated on NY-ESO-1 specific T-cells following infiltration into the tumor.  In vivo 
synergy was observed between NY-ESO-1 specific T-cells and anti PD-1, resulting in 
significantly enhanced control of tumor growth over NY-ESO-1-specific T-cells alone 
[Moon, 2016].  Therefore, the combination of lete-cel and pembrolizumab could result in 
a synergistic effect due to the inhibition of PD-1 on lete-cel.  This combination is 
currently under clinical investigation for the treatment of multiple myeloma 
(NCT03168438 [ADP-0011-004]). 
Thus, patients with NSCLC that has failed PD-1/PD-L1 checkpoint blockade therapy 
(alone or in combination with chemotherapy), as well as patients with NSCLC that has 
relapsed following standard of care (SoC) tyrosine kinase inhibitors (TKIs), have a high 
unmet medical need for treatment advances to improve PFS and OS. 
2.3. 
Benefit/Risk Assessment 
The results of clinical and non-clinical studies of lete-cel are summarized in the IB 
(GlaxoSmithKline Document Number RPS-CLIN-015027).  Likewise, the results of 
pembrolizumab studies are summarized in the KEYTRUDA prescribing information.   
It cannot be guaranteed that participants in clinical trials will directly benefit from 
treatment during participation, as these studies are designed to provide information about 
the safety and effectiveness of investigational medicines.  The potential benefits, risks 
and risk mitigation strategy for this study are outlined in this section.  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 lete-cel alone or in combination with 
pembrolizumab. 


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2.3.1. 
Risk Assessment 
Table 9 
Summary of Risks and Risk-Mitigation Strategies Related to Study 
Treatments 
Risks of Clinical Significance 
(Identified or Potential) 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Lymphodepleting Chemotherapy (Fludarabine/Cyclophosphamide) 
• 
Myelosuppression 
• 
Immunosuppression 
• 
Bone marrow failure and 
infection 
• 
Cardiotoxicity 
• 
Pulmonary toxicity 
• 
Urinary tract and renal 
toxicity 
• 
Veno-occlusive disease 
• 
Secondary malignancy 
• 
Hyponatremia 
• 
Neurotoxicity 
Cases were reported with both 
drugs. 
Please refer to the prescribing 
information of fludarabine and 
cyclophosphamide and Appendix 9 
(Section 10.9.9) 
• 
Autoimmune hemolytic 
anemia 
• 
Autoimmune 
thrombocytopenia 
• 
Decreased vision 
• 
Peripheral neuropathy 
Cases were reported with 
fludarabine 
Please refer to the prescribing 
information of fludarabine. 
Lete-cel 
Cardiac arrest 
Potential risk associated with 
lymphodepletion chemotherapy 
and TCR T-cell infusion. There 
have been 2 reports of unexpected 
fatal cardiac arrest. The first 
occurred 5 months after T-cell 
infusion and was confounded by 
hypotension due to poor oral intake 
and concurrent renal insufficiency. 
The second occurred 
approximately 1 week after T-cell 
infusion in the setting of a recent 
fungal catheter line infection, 
concurrent treatment with 
caspofungin and multifocal 
pneumonia / edema seen on chest 
CT. 
Participants with significant cardiac 
risk factors or with CRS ≥Grade 2 
will receive close cardiac 
monitoring (Section 8.2.3 and 
Section 10.9.5).  
Participants with lung metastases 
should be considered for 
pulmonary consultation prior to 
lymphodepletion; participants 
deemed at high risk of pulmonary 
complications should be monitored 
closely (Section 8.2.4). 
Central lines should be closely 
monitored for infection (Section 
10.9.2). 
Systemic fungal infections are 
excluded (Exclusion criterion #8) 
Monitoring of risk of increased 
cardiac toxicity with the use of anti-
microbials (Section 10.9.2.6) 
Cytokine Release Syndrome (CRS) 
Identified risk due to TCR T-cell 
infusion, considered an adverse 
event of special interest (AESI) 
Participants with pre-existing 
autoimmune disorders are 
excluded (Section 5.1 and Section 
5.2).  See management for CRS, 
Appendix 9 (Section 10.9.5).  
Events ≥ Grade 3 must be reported 
as SAEs and submitted to GSK 
within 24 hours.  


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Risks of Clinical Significance 
(Identified or Potential) 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Pneumonitis 
Potential risk associated with TCR 
T-cell infusion, considered an AESI 
I/E criteria exclude participants with 
pre-existing autoimmune disorders 
(Section 5.2.1).  See Appendix 9 for 
Supportive Care Guidance. 
Graft-versus-Host disease (GVHD) 
Identified risk associated with TCR 
T-cells reacting against normal 
tissues and organs, considered an 
AESI  
Participants with pre-existing 
autoimmune disorders are 
excluded (Section 5.1 and Section 
5.2).  See management for GVHD, 
Appendix 9 (Section 10.9.6) 
Haematopoietic cytopenias (including 
Pancytopenia with bone marrow 
failure/aplastic anemia) 
Identified risk associated with 
lymphodepletion chemotherapy 
and TCR T-cell infusion, 
considered an AESI 
Participants with cytopenias are 
excluded.  See management for 
pancytopenia, Appendix 9 (Section 
10.9.7) 
Haemorrhage secondary to 
thrombocytopenia  
Identified risk associated with 
lymphodepletion chemotherapy 
and TCR T-cell infusion. There 
have been reports of haemorrhage 
(including intracranial and 
pulmonary) in participants with 
severe, prolonged 
thrombocytopenia 
Protocol guidance on Blood product 
support provides recommendation 
on platelets levels to be maintained 
in the in-patient setting and the out-
patient setting, as per Section 
10.9.3 
Hypersensitivity  
Identified risk due to lete-cel 
infusion. Hypersensitivity reactions 
(including anaphylaxis) may be due 
to the 5% (v/v) DMSO in lete-cel. 
Participants with history of allergic 
reactions to any agents used in the 
study are excluded. See Section 
5.2.2 for details. 
Participants will be premedicated 
against potential infusion reactions 
with antihistamines on the day of 
lete-cel infusion. See Section 6.4.1 
for details. 


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Risks of Clinical Significance 
(Identified or Potential) 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Reactivation of previous viral 
infections after prolonged leukopenia 
Identified risk associated with 
lymphodepletion chemotherapy 
and TCR T-cell infusion 
Participants who have received 
radiation to bone marrow that 
would predispose them to 
prolonged cytopenia after 
lymphodepletion (in the 
investigator’s opinion) are 
excluded. See Section 5.2 for 
details. 
Lymphodepletion dose will be 
modified in participants with 
potentially reduced bone marrow 
reserve. See Section 6.3.1 for 
details. 
Participants with active infection 
are excluded. Participants with 
CMV seropositivity will be 
monitored regularly for viral 
reactivation. For herpes simplex 
virus and varicella zoster virus 
prophylaxis, participants will 
receive acyclovir or valacyclovir for 
one year from LD.  Prophylaxis will 
be given to those with HBV 
seropositivity. See Section 5.2 and 
Section 10.9.2 for details. 
Neutropenia (including fatal 
neutropenia) 
Identified risk associated with 
lymphodepletion chemotherapy 
and TCR T-cell infusion 
Patients are excluded based on 
absolute neutrophil counts (Section 
5.1.2). Investigator must discuss 
with Medical Monitor or designee to 
determine the need for dose 
modification of the lymphodepletion 
regimen in participants at risk 
(Section 6.3.1). 
G-CSF to be administered in 
accordance with ASCO guidelines 
or institutional practice (Section 6.3 
and Section 10.9).  
Dose modifications for fludarabine 
and cyclophosphamide (Section 
6.3) 
Grade 4 Neutropenia events lasting 
≥28 days must be submitted to 
GSK within 24 hours (Section 
8.4.4). 
Decreased Vision 
Potential risk: There was a report 
of decreased vision in a patient 
who received lete-cel following 
lymphodepletion with fludarabine 
and cyclophosphamide. 
Dose reductions for fludarabine for 
renal impairment. Investigator must 
discuss with Medical Monitor or 
designee to determine the need for 
dose modification of the 
lymphodepletion regimen in 
patients at risk (Section 6.3) 


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Risks of Clinical Significance 
(Identified or Potential) 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Guillain-Barré Syndrome (GBS)/Acute 
inflammatory demyelinating 
polyneuropathy 
Potential risk associated with TCR 
T-cell infusion.  Two participants 
who received lete-cel developed 
GBS. 
Participants with prior or active 
demyelinating disease will be 
excluded (Section 5).  Neurologic 
consultation is required for patients 
with Grade 2 or higher neurologic 
events of a ≥7-day duration.  Any 
potential future recurrence of GBS 
will lead to a pause in study 
enrollment until further 
investigation. 
Treatment-related inflammatory 
response at tumor site(s) 
Potential risk associated with TCR 
T-cell infusion 
Routine monitoring and testing as 
clinically required. 
Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) 
Potential risk associated with 
inflammation in the brain following 
TCR T-cell infusion. There have 
been reports of ICANS in 
participants who received lete-cel. 
Participants with brain metastases 
with features associated with 
increased risk of ICANS are 
excluded (Section 5.1.3).  
Monitoring criteria for ICANS are 
described in Section 10.9.8.and 
Table 15, respectively. 
Insertional oncogenesis 
Potential risk in T-cells transduced 
with lentiviral vector 
Routine pharmacovigilance (PV).  
To be monitored in the LTFU 
Protocol (GSK Study 208750) or 
LTFU portion of this study (Part 5).  
Monitoring to follow the 
recommendations set forth in the 
FDA guidance [FDA, 2020a].  
PBMC samples are used as a 
surrogate sample for monitoring 
insertional oncogenesis by 
polymerase chain reaction (PCR) 
for gene modified cells in the blood. 
Replication competent lentivirus (RCL) 
Potential risk associated with use 
of lentivirus 
Routine PV.  To be monitored in 
the LTFU Protocol (GSK Study 
208750) or LTFU portion of this 
study (Part 5).  Samples will be 
tested for the presence of VSV-G 
DNA copies (Section 8.3.5) 
On/Off-Target Off-Tumor Risks 
Potential risk associated with use 
of lentivirus  
To be monitored in the LTFU 
Protocol (GSK Study 208750) or 
LTFU portion of this study (Part 5).  
Protocol includes eligibility criteria 
(Section 5.1 and Section 5.2), 
routine PV (Section 8.3), and 
management strategies as 
appropriate to limit, diagnose, 
characterize and treat toxicities 
related to potential risks  
(Appendix 9). 
Pembrolizumab 
Immune related reactions  
• 
Pneumonitis 
• 
Colitis 
• 
Nephritis 
• 
Neuritis 
• 
Hepatitis 
Identified risks caused by an 
excessive T-cell immune activation 
and potential expansion and 
activation of T-cell clones against 
normal tissues 
Please refer to Appendix 9, 
Section 10.9. 


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Risks of Clinical Significance 
(Identified or Potential) 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
• 
Skin inflammation 
• 
Endocrinopathies 
Infusion reaction (pembrolizumab) 
Identified risk associated with 
pembrolizumab infusion 
Please refer to the KEYTRUDA 
prescribing information. 
Interaction with lete-cel 
Theoretical risk that anti-PD-1 
treatment with pembrolizumab 
could exacerbate or trigger 
potential lete-cel and 
pembrolizumab-related side effects 
listed above. 
The participants treated with the 
combination regimen of lete-cel and 
pembrolizumab will be carefully 
monitored through frequent visits 
and AE monitoring (Appendix 9 and 
Table 15) 
Study Procedures 
Tumor biopsy 
Bleeding, pain, swelling associated 
with the procedure 
Biopsies are performed by trained 
personnel.  Image-guided when 
necessary, and performed only if 
deemed safe 
Leukapheresis 
Electrolyte imbalance and bleeding 
at the site of phlebotomy 
Refer to local site procedures and 
guidelines. 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; CRS = cytokine release syndrome;  
DSUR = development safety update report; FDA = Food and Drug Administration; GBS = Guillain-Barré Syndrome; 
GSK = GlaxoSmithKline (Sponsor); GVHD = graft versus host disease; I/E = inclusion/exclusion; ICANS = Immune 
Effector Cell-Associated Neurotoxicity Syndrome; KEYTRUDA = pembrolizumab; LTFU = long-term follow-up; 
PD-1 = programmed death protein 1; PV = pharmacovigilance; RCL = replication competent lentivirus; SAE = serious 
adverse event; TCR = T-cell receptor; VSV-G = Vesicular Stomatitis Virus G. 
 
Risk Assessment for Lete-cel  
The known safety profile of lete-cel is based on 166 participants who have undergone 
leukapheresis, of which 125 have been treated as of 27 January 2021 (GSK Document 
Number RPS-CLIN-015027).   
In the integrated sponsored trials, 125 subjects have received both lymphodepletion and 
lete-cel; sixteen (16) of these subjects [11 subjects with synovial sarcoma, 4 subjects with 
multiple myeloma, and 1 with NSCLC] have received a second infusion of lete-cel 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 lete-cel infusion were leukopenia/white blood cell (WBC) decreased (81%), 
neutropenia/neutrophil count decreased (80%), nausea (78%), anemia/ red blood cell 
(RBC) decreased (78%), thrombocytopenia/platelet count decreased (77%), fatigue 
(70%), pyrexia (66%), diarrhea (57%), and lymphopenia/lymphocyte count decreased 
(54%). Overall, there were no apparent significant differences in reported TEAEs 
between subjects receiving 1 or 2 infusions. 
 
Treatment-emergent serious adverse events (SAEs) occurred in 74 (59%) subjects across 
all studies. Treatment-emergent SAEs occurring in 2 or more subjects following 
lete-cel cell infusion were cytokine release syndrome (CRS) (15%); febrile neutropenia 
and pyrexia (11%); neutropenia/neutrophil count decreased (10%); 


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thrombocytopenia/platelet count decreased (6%); dyspnea and rash/rash maculo-papular 
(5%); hypotension (4%); dehydration, diarrhea, and pleural effusion (3%); and acute 
kidney injury, anemia/RBC decreased, atrial fibrillation, hypoxia, nausea, pancytopenia, 
pneumonia, bone marrow failure, chills, cough, Guillain-Barré syndrome, hemoptysis, 
leukopenia/WBC decreased, pneumonitis, pulmonary hemorrhage, Staphylococcal 
infection, tumor pain, unspecified graft-versus host disease (GVHD) - other (lung, bone 
marrow, not specified), and vomiting (2%). The SAE profile following a second infusion 
of lete-cel was consistent with that experienced for all subjects infused.  
 
Four (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 161. 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 on Day 138 due to disease progression unrelated 
to treatment, which was reported as an SAE; 
• one subject with synovial sarcoma was reported as having died on Day 58 due to 
Grade 5 hemoptysis unrelated to study treatment and which was reported as an SAE 
before the data cut-off for GSK3377794 IB, 2021 (GSK Document Number RPS-
CLIN-015027). Following the data cut-off for the IB update and after autopsy report 
the site clarified that the primary cause of death was disease progression; hemoptysis 
was a concomitant event. 
There were no fatal SAEs reported among subjects who received a second infusion of 
lete-cel. 
 
Refer to the most recent Investigator’s Brochure (IB) for lete-cel for detailed information. 
 
Risk Assessment for Pembrolizumab  
Pembrolizumab monotherapy was discontinued due to adverse reactions in 8% of 682 
participants with metastatic NSCLC in the KEYNOTE-010 trial (a Phase 3 randomized 
controlled clinical trial with pembrolizumab versus docetaxel in previously treated, 
PD-L1-positive, advanced NSCLC [Herbst, 2016] (NCT01905657).  The most common 
AE resulting in permanent discontinuation of pembrolizumab was pneumonitis (1.8%).  
Adverse reactions leading to treatment interruption occurred in 23% of participants; the 
most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme 
elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%).  The most common 
AEs (occurring in at least 20% of participants and at a higher incidence than with 


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docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea 
(20% vs 18%).   
See Section 6.10.2 for pembrolizumab dose modification guidelines. 
Risk Assessment for the Lete-cel Plus Pembrolizumab Combination 
The combination of lete-cel and pembrolizumab is currently being tested in participants 
with multiple myeloma [NCT03168438].  The current NSCLC study is the first time that 
a single-dose of lete-cel will be given to participants prior to pembrolizumab treatment.  
The theoretical risk is that anti-PD-1 treatment with pembrolizumab could exacerbate or 
trigger potential lete-cel-related side effects listed above.  To mitigate this risk, 
participants treated with the combination regimen of lete-cel and pembrolizumab will be 
carefully monitored through frequent visits and for AEs. 
2.3.2. 
Benefit Assessment 
2.3.2.1. 
Benefit for Lete-cel 
The TCR approach to engineered T-cell therapy is attractive because TCRs can recognize 
not only cell surface proteins (as is the case with chimeric antigen receptor T-cells 
[CAR-T]) 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. 
As of 27 January 2020, 103 participants have been treated with lete-cel (engineered using 
a lentiviral vector) in 5 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, 208466 (formerly 
ADP-04511, and in the myeloma (transplant) study, 209393 (formerly ADP-01411 [GSK 
Document Number RPS-CLIN-015027].  Additionally, 38 participants 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 
participants with melanoma and synovial sarcoma tumors expressing NY-ESO-1 were 
recruited.  Eleven of 18 participants (61%) with synovial sarcoma and 11 of 20 
participants (55%) with multiple myeloma demonstrated objective clinical responses.  
The estimated overall 3- and 5-year survival rates for participants with synovial cell 
sarcoma were 38% and 14% respectively, while the corresponding estimated survival 
rates for participants with melanoma were both 33% [Robbins, 2015].  In addition, 2 
participants with gastroesophageal cancer have been treated in the ATTACK-OG clinical 
trial. 
Thus, there is good evidence to support the potential therapeutic benefit of lete-cel in 
participants with advanced or metastatic NSCLC. Refer to the most recent Investigator’s 
Brochure (IB) for lete-cel for detailed background information. 


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2.3.2.2. 
Benefit for Pembrolizumab 
Pembrolizumab has shown to prolong OS and have a favorable benefit-risk profile in 
patients with previously treated, PD-L1-positive, advanced NSCLC.  The Keynote-010 
trial enrolled 1034 participants with previously treated NSCLC with PD-L1 expression 
on at least 1% of tumor cells.  In the total population, the median OS was 10.4 months 
with pembrolizumab 2 mg/kg, 12.7 months with pembrolizumab 10 mg/kg, and 
8.5 months with docetaxel.  The OS was significantly longer for pembrolizumab 2 mg/kg 
versus docetaxel (HR 0.71, 95% CI 0.58–0.88; p=0.0008) and for pembrolizumab 
10 mg/kg versus docetaxel (0.61, 0.49–0.75; p<0.0001).  The median PFS was 
3.9 months with pembrolizumab 2 mg/kg, 4.0 months with pembrolizumab 10 mg/kg, 
and 4.0 months with docetaxel, with no significant difference for pembrolizumab 
2 mg/kg versus docetaxel (0.88, 0.74–1.05; p=0.07) or for pembrolizumab 10 mg/kg 
versus docetaxel (HR 0.79, 95% CI 0.66–0.94; p=0.004).  Grade 3 to 5 treatment-related 
AEs were less common with pembrolizumab than with docetaxel (13% with 2 mg/kg, 
16% with 10 mg/kg, and 35% with docetaxel). 
2.3.2.3. 
Benefit for the Combination Regimen 
There is evidence of clinical benefit from each of the individual agents in multiple tumor 
types to support the investigation of the potential augmented activity of lete-cel in 
combination with pembrolizumab in advanced or recurrent NSCLC (see Study Rationale, 
Section 2.1). 
2.3.3. 
Overall Benefit - Risk Conclusion 
Patients with advanced or metastatic NSCLC positive for NY-ESO-1 and LAGE-1a 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 lete-cel.  Clinical data from participants summarized in the Investigator Brochure and 
the NCI and UPENN studies [Robbins, 2015; Rapoport, 2015; GSK Document Number 
RPS-CLIN-015027] demonstrate the safety and activity of lete-cel sufficiently to warrant 
further clinical investigation in participants with NSCLC. 
Based on the known clinical activity of pembrolizumab in patients with NSCLC, the 
addition of lete-cel to pembrolizumab in participants with tumors positive for NY-ESO-1 
and LAGE-1a may further improve clinical benefit. 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
5 0  
 
3.  
O B J E C TI V E S A N D E N D P O I N T S 
T a bl e 1 0  
O bj e cti v e s a n d E n d p oi nt s  
O bj e cti v e s  
E n d p oi nt s  
Pri m ar y  
•  
T o ev al u at e t h e s af ety a n d t ol er a bility of 
a ut ol o g o us g e n etic ally m o difi e d T -c ells 
(let e -c el) i n h u m a n l e uk ocyt e a nti g e n ( H L A) 
H L A -A*0 2: 0 1, H L A -A*0 2: 0 5 a n d/ or H L A -
A*0 2: 0 6 p ositiv e p artici p a nts wit h N Y -E S O -
1 a n d/ or L A G E 1 a -p ositiv e a dv a nc e d 
N S C L C al o n e [ Ar m  A] or let e -c el i n 
c o m bi n ati o n wit h p e m br oliz u m a b i n 
p artici p a nts wit h N S C L C l acki n g  acti o n a bl e 
g e n etic a b err ati o ns [ Ar m B] a n d 
p artici p a nts wit h N S C L C wit h a n acti o n a bl e 
g e n etic a b err ati o n [ Ar m C]  
•  
Fr e q u e ncy a n d s ev erity of A Es, s eri o us 
a dv ers e ev e nts ( S A Es) a n d A Es of 
s p eci al i nt er est ( A E SIs; as d efi n e d i n 
pr ot oc ol)  
•  
A E/ S A Es l e a di n g t o d os e d el ays 
a n d/ or wit h dr a w als i n p artici p a nts w h o 
r ec eiv e d let e -c el al o n e or i n 
c o m bi n ati o n wit h p e m br oliz u m a b  
•  
T o d et er mi n e t h e r es p o ns e t o let e -c el al o n e 
[ Ar m A] or let e -c el i n c o m bi n ati o n wit h 
p e m br oliz u m a b i n p artici p a nts wit h N S C L C  
l acki n g acti o n a bl e g e n etic a b err ati o ns [ Ar m 
B] a n d p artici p a nts wit h N S C L C wit h 
acti o n a bl e g e n etic a b err ati o n s [ Ar m C] 
•  
Ov er all R es p o ns e R at e ( O R R) 
(i nv esti g at or ass ess e d acc or di n g t o 
R E CI S T v1. 1)  
S e c o n d ar y - Effi c a c y  
•  
T o f urt h er i nv esti g at e t h e a nti -t u m or activity 
of let e -c el al o n e or l et e -c el i n c o m bi n ati o n 
wit h p e m br oliz u m a b acc or di n g t o R E CI S T 
v1. 1 crit eri a  
•  
Pr o gr essi o n -Fr e e S urviv al ( P F S)  
•  
Dis e as e C o ntr ol R at e ( D C R)  
•  
D ur ati o n of R es p o ns e ( D o R)  
•  
Ti m e t o R es p o ns e ( T T R)  
S e c o n d ar y - P h ar m a c o ki n eti c s  
•  
T o c h ar act eriz e i n viv o c ell ul ar P K pr ofil e 
(l ev els, ex p a nsi o n, p ersist e nc e) of 
N Y -E S O -1  s p ecific (c 2 5 9) T c ells 
•  
M axi m u m tr a ns g e n e ex p a nsi o n 
( C m ax) 
•  
Ti m e t o C m ax ( T m ax)  
•  
Ar e a u n d er t h e ti m e c urv e fr o m z er o t o 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
5 1  
 
O bj e cti v e s  
E n d p oi nt s  
A b br evi ati o ns:  
 A E = a dv ers e ev e nt/s; A E SI = a dv ers e ev e nt of s p eci al i nt er est; A U C( 0 -t) = ar e a u n d er t h e 
ti m e c urv e fr o m z er o t o ti m e t; C m ax = m axi m u m p ersist e nc e; C R S = cyt oki n e r el e as e sy n dr o m e; D C R = dis e as e 
c o ntr ol r at e; D o R = d ur ati o n of r es p o ns e (i D o R = D o R b as e d o n  
); E C G  =  el ectr oc ar di o gr a m; 
E C O G  P S  =  E ast er n C o o p er ativ e O nc ol o gy Gr o u p p erf or m a nc e st at us; e C R F = el ectr o nic c as e r e p ort f or m; F D G = 
fl u or o d e oxy gl uc os e; G-C S F  =  gr a n ul ocyt e c ol o ny sti m ul ati n g f act or ; H L A =  h u m a n l e uk ocyt e a nti g e n; I L = i nt erl e uki n; 
L A G E -1 a  = c a nc er t estis a nti g e n 2; N S C L C  =  n o n -s m all c ell l u n g c a nc er; N Y-E S O -1 = N e w 
Y ork es o p h a g e al s q u a m o us c ell c arci n o m a 1; O R R = ov er all r es p o ns e r at e (i O R R = O R R b as e d o n 
); 
P D -L 1  =  pr o gr a m m e d d e at h pr ot ei n 1 li g a n d; P E T  =  p ositr o n e missi o n t o m o gr a p hy; 
P F S  =  pr o gr essi o n -fr e e s urviv al 
 P R O-C T C A E  = Pati e nt -R e p ort e d O utc o m es v ersi o n 
of C o m m o n T er mi n ol o gy Crit eri a f or A dv ers e Ev e nts; R E CI S T  =  R es p o ns e Ev al u ati o n Crit eri a I n S oli d T u m ors 
); 
 
; S A E =  s eri o us a dv ers e ev e nt; T C R =  T -c ell r ec e pt or; 
 T m ax = 
ti m e t o C m ax; 
 
; T T R = ti m e t o r es p o ns e; W T = wil d-ty p e. 
4.  
S T U D Y D E SI G N  
4. 1.  
O v er all D e si g n  
T his is a m ulti -ar m, o pe n -la bel st u d y of lete-cel i n H L A -A * 0 2: 0 1, H L A -A * 0 2: 0 5 , a n d/ or 
H L A -A * 0 2: 0 6  p o siti ve a d ults  w h ose t u m or s e x press N Y -E S O -1 a n d/ or L A G E -1a .  T h e 
a bilit y t o ac hie v e o bjecti ve res p o nses i n di verse t u m or t y pes s u p p orts a h y p ot hesis t hat 
H L A a n d a nti ge n e x pressi o n are bi o mar kers t hat i de ntif y a p o p ulati o n of p artici pa nts w h o  
ma y b e nefit fr o m let e-cel. 
T his st u d y will e nr oll partici pa nts w h o ha ve u nresecta ble Sta ge III b or Sta ge I V N S C L C 
a n d als o fit st u d y eli gi bilit y criteria ( See Secti o n 5 ).  
T he st u d y will c o nsist of  3  ar ms –  Ar m s A , B, a n d C  (Fi g ure 2 ): 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


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Figure 2 
Study Schema 
 
Abbreviations: EoT = end of treatment; HLA = human leukocyte antigen; LAGE-1a = cancer testis antigen 2; 
NCCN = National Comprehensive Cancer Network; NSCLC = non-small cell lung cancer; NY-ESO-1 = New York 
esophageal squamous cell carcinoma 1; PD-1 = programmed death protein 1; PD-L1 = PD-1 ligand; 
LTFU = long--term follow--up. 
 
1. NSCLC patients with actionable genetic aberrations may receive treatment as part of Arm C only following treatment 
with targeted standard of care therapy (NCCN or equivalent country-guidelines (e.g., ESMO, NICE, etc.), as 
applicable).  
2. Option of pembrolizumab therapy at time of disease progression following lete-cel administration and based on 
benefit-risk evaluation with Sponsor’s Medical Monitor (or designee) approval.  
3. LTFU requires participant enrollment in a dedicated LTFU protocol (GSK Study 208750). If not yet enrolled in the 
LTFU protocol, participants will be followed per LTFU schedule under this protocol (Part 5) until enrolled in the 
separate LTFU protocol (see Table 8). 
 
The investigational treatment is intended for patients with NSCLC lacking actionable 
genetic aberrations that has failed PD-1/PD-L1 checkpoint blockade therapy (Arms A or 
B) or patients with NSCLC with actionable genetic aberrations (e.g., BRAF, ALK/ROS1, 
etc.) that has failed SoC targeted therapies as per NCCN or equivalent country-guidelines 
(e.g., ESMO, NICE, etc.), as applicable (Arm C).   
Arms A and B: 
Participants with NSCLC lacking actionable genetic aberrations will be assigned to 
receive either lete-cel monotherapy single infusion (Arm A) or receive a single IV 
infusion of lete-cel on Day 1 followed by pembrolizumab to be initiated on Day 22 
(Week 4 Day 1) and continued for up to 35 cycles, or until disease progression, or 
intolerable toxicity, whichever occurs first (Arm B). There will be no re-treatment with 
lete-cel in this study.  
In Arm A, participants who progress within 25 weeks following lete-cel infusion may be 
offered anti-PD-1 therapy with pembrolizumab following benefit-risk evaluation and 
approval by the Sponsor’s Medical Monitor (or designee).  Pembrolizumab treatment will 
be administered for up to 35 cycles or until subsequent disease progression or intolerable 
toxicity. Pembrolizumab therapy will not be allowed if disease progression occurs after 
the 25-week scan. 


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Assignment of participants to Arm A or B will be determined by the Sponsor. 
Participants will be assigned to Arm A first and then to Arm B.   
Enrollment will aim to include approximately 5 squamous cell carcinoma (SCC) NSCLC 
participants lacking actionable genetic aberrations. 
Arm C: 
Participants with NSCLC with actionable genetic aberrations will be assigned to Arm C 
and receive the same treatment as participants in Arm B. There will be no re-treatment 
with lete-cel in this study. 
Participant Flow  
Figure 3 summarizes the participant flow in the study.   
 
 
 


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Figure 3 
Participant Flow 
Abbreviations: CRS = cytokine release syndrome; EoT = end of treatment; HLA = human leukocyte antigen; 
ICF = informed consent form; I/E = inclusion/exclusion; LAGE-1a = cancer testis antigen 2; NSCLC = non-small cell 
lung cancer; NY-ESO-1 = New York esophageal squamous cell carcinoma 1; PD = progressive disease; Q3W = once 
every 3 weeks; RT = radiotherapy; SoC = standard of care. 
1. 
Screening may start at any time after diagnosis of advanced Stage IIIb or IV or recurrent NSCLC. 
2. 
Leukapheresis may start once the eligibility criteria are fulfilled.  Wash-out times as indicated in Table 12 may 
apply. 
3. 
Lymphodepletion starts at clinical and / or radiographic disease progression. Wash-out times as indicated in  
Table 12 may apply.  
4. 
Participants will receive a single dose of lete-cel five (5) days after completing the lymphodepleting chemotherapy 
(this is considered Day 1). 
5. 
Participants in Arm A who have PD following treatment with lete-cel at or before the scheduled Week 25 scan may 
be offered pembrolizumab therapy (Part 4) following assessment of eligibility for pembrolizumab treatment, 
benefit-risk evaluation, and approval by the Sponsor’s Medical Monitor (or designee). (see Section 6.4.4).    
6. 
In Arms B and C, the first pembrolizumab administration is on Day 22 (Week 4 Day 1). If toxicities that preclude 
pembrolizumab treatment, including such as CRS Grade ≥2, are present at Day 22, infusion of pembrolizumab 
will start on Week 7 Day 1. In either case, pembrolizumab will then be administered Q3W up to 35 cycles or PD as 
described in Section 6.5.  
7. 
LTFU requires participant enrollment in a dedicated LTFU protocol (GSK Study 208750). If not yet enrolled in the 
LTFU protocol, participants will be followed per LTFU schedule under this protocol (Part 5) until enrolled in the 
LTFU protocol (see Table 8). 
 
 
Note: Dashed boxes and arrows indicate activities that may be performed based on clinical need. 
The study consists of 5 parts: 
Part 1 (Screening) 
Part 2 (Leukapheresis) 


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Part 3 (Interventional Phase: Lymphodepletion/Treatment) 
Part 4 (Pembrolizumab Therapy Following Disease Progression after Lete-cel Infusion, 
for Arm A ONLY) 
Part 5 (Long-Term Follow-Up) 
 
4.1.1. 
Part 1: Screening 
Part 1 (Screening) will consist of 2 phases: target expression screening and leukapheresis 
eligibility screening. 
Target Expression Screening 
Target expression screening may proceed once informed consent has been obtained and 
patient is deemed eligible based on inclusion / exclusion criteria for target expression 
screening, as listed in Section 5.  
A blood sample will be collected from each participant for testing the presence of HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06. NY-ESO-1 and, when feasible, LAGE-1a 
expression will also be evaluated on tumor tissue from a formalin-fixed and paraffin-
embedded (FFPE) archival (most recent preferred) or fresh biopsy (see Section 8.9.2 for 
more details). Please refer to Study Reference Manual for additional information on 
target expression screening procedures.  
Participants screened or enrolled in other GSK studies may be considered for enrollment 
to this study, where it is IRB/IEC approved, on a case-by-case scenario following 
risk/benefit evaluation between the Investigator and Sponsor Medical Monitor (or 
designee). See Section 4.1.1.1 for details.   
Leukapheresis Eligibility Screening 
Once participants are deemed positive for HLA and tumor antigen expression, they will 
sign the main study informed consent to undergo screening for leukapheresis within 42 
days prior to the day of the scheduled leukapheresis procedure. Patient must be deemed 
eligible based on inclusion / exclusion criteria for leukapheresis eligibility screening 
listed in Section 5. 
4.1.1.1. 
Screening under other GSK studies 
Participants screened or enrolled in other GSK studies may be considered for enrollment 
to this study, where it is IRB/IEC approved, on a case-by-case scenario following 
risk/benefit evaluation between the Investigator and Sponsor Medical Monitor (or 
designee).  
Where a participant was previously tested for HLA and/or NYESO-1 expression under a 
different GSK-sponsored protocol, testing of HLA and/or NY-ESO-1 for 208471 may not 
be required dependent on the test platform(s) used and whether they meet the 208471 
protocol requirements. If the 208471 requirements are not met, repeat test(s) may be 


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required. The repeat test(s) may be possible without requiring new sample collection. 
Other screening/baseline assessments or procedures (e.g., biopsy collection, imaging) 
performed under a separate GSK sponsored protocol may be acceptable, in consultation 
with the Sponsor. Additionally, if lete-cel is already manufactured for these participants, 
leukapheresis and/or re-manufacture process may not be necessary, in consultation with 
the Sponsor.  
4.1.2. 
Part 2: Leukapheresis/Manufacture 
Participants who fulfill the leukapheresis eligibility criteria (Section 5) can undergo 
leukapheresis. The initiation of leukapheresis procedure constitutes enrollment in the 
study. 
Disease progression may be present but is not mandatory for leukapheresis.  In addition, 
leukapheresis may occur before, during or upon completion of a prior line of therapy, if 
appropriate washout periods are followed (See Table 12).  
Upon development of progressive disease in metastatic cancer patients, the disease may 
have a rapid course, and any treatment delay can limit the treatment effect.   
Because of this, the potential for early leukapheresis is justified based on the following: 
• Early leukapheresis permits the manufacture of T cells prior to progression of 
disease from prior therapy.  This then permits timely treatment of the patient.   
• Leukapheresis product collected prior to intense chemotherapy treatment may 
contain T cells that have higher proliferative potential thereby providing higher 
yield of a fitter T-cell product.  
• Manufacturing failures can be communicated ahead of time, thereby, minimizing 
delays for further treatment if product is not available in time for the patient.   
Consult with Sponsor for current shelf-life specifications of the cryopreserved T-cell 
product from leukapheresis and the cryopreserved drug product, lete-cel. 
Following leukapheresis, lete-cel manufacture can be undertaken by the Sponsor as 
production slots become available. Additional details are provided in the Apheresis 
Manual. 
Supportive local therapy (e.g., radiotherapy, cryotherapy), chemotherapy, or other 
systemic treatments such as, but not limited to, PD-1/PD-L1 checkpoint blockers may be 
administered between leukapheresis and treatment if a participant has progressive disease 
and cannot be treatment-free.  In this case, mandatory wash-out periods (Table 12) must 
be respected.  
An intermediate SoC line of therapy between leukapheresis (Part 2) and treatment (Part 
3) at the time of disease progression is allowed if all of the conditions in Section 6.2 are 
met. 


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4.1.3. 
Part 3: Lymphodepletion/Treatment (Interventional Phase) 
In Arms A and B, lete-cel will be infused after having failed at least one line of PD-1/PD-
L1 checkpoint blockade therapy.   
For participants in Arm C, lete-cel will be infused after having failed SoC targeted 
therapies (per NCCN or equivalent country guidelines [e.g., ESMO, NICE, etc.], as 
applicable).   
Following clinical and/or radiographic evidence of disease progression, participant’s 
fitness for lymphodepletion will be assessed, lymphodepletion eligibility criteria will be 
confirmed, and baseline tumor assessments (scan and biopsy) obtained prior to initiating 
the lymphodepleting chemotherapy.  A baseline scan demonstrating measurable disease 
is required prior to lymphodepletion and before the participant will receive lete-cel; 
thereafter, the tumor will be followed as per RECIST v1.1, starting at Week 7 per 
protocol.  
Once the manufactured lete-cel product has been received and the integrity of the bag(s) 
has/have been verified by the site, each participant will undergo lymphodepletion with 
cyclophosphamide and fludarabine (Section 6.3) in preparation for infusion of lete-cel on 
Day 1 (Section 6.4).  Participants should receive Granulocyte-Colony Stimulating Factor 
(G-CSF) support and Mesna (Refer to Table 14 and Appendix 9). 
On the day of lete-cel infusion, participants will be premedicated against potential 
infusion reactions with antihistamines and acetaminophen (paracetamol). Follow 
institutional guidance for dosage and specific medications (see Section 6.4.1 for details). 
In Arms B and C, the first pembrolizumab administration is on Day 22 (Week 4 Day 1), 
then Q3W up to 35 cycles or disease progression, as described in Section 6.5. If 
pembrolizumab cannot be started at Week 4 due to an AE, participants assigned to Arm B 
or Arm C may receive their first dose of pembrolizumab on Week 7 Day 1, as long as 
permitted per Table 15. 
The second dose of pembrolizumab will be administered 3 weeks later if the participant is 
not experiencing AEs as described in Section 6.5. 
Participants will be frequently monitored for any unexpected ≥ Grade 3 AE / SAE; 
participants treated in Arms B and C will also be monitored for pembrolizumab treatment 
limiting toxicities (TLTs) as outlined in Section 8.3.2. 
Participants in Arm A who have PD following treatment with lete-cel at or before the 
scheduled Week 25 scan may be offered pembrolizumab therapy (Part 4) following 
assessment of eligibility for pembrolizumab treatment, benefit-risk evaluation, and 
approval by the Sponsor’s Medical Monitor (or designee). 
Participants who are not eligible for study treatment by the time NY-ESO-1 specific 
(c259) T cells expire, will be withdrawn from the study and will not undergo 
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For participants who withdraw from the study or die prior to receiving GSK3377794, any 
remaining apheresis or drug product from the participant will be stored by the Sponsor 
for up to 15 years (or according to local regulations) following the participant’s 
withdrawal from the study or death. During this time, these materials may be used for 
scientific research at the Sponsor’s discretion. After 15 years of storage, any materials 
which have not been used may be destroyed. 
4.1.4. 
Part 4: Pembrolizumab Therapy Following Disease Progression 
after Lete-cel Infusion (for Arm A ONLY) 
Participants in Arm A who have PD following treatment with lete-cel at or before the 
scheduled Week 25 scan, may be offered pembrolizumab therapy (Part 4) following 
assessment of eligibility for pembrolizumab treatment, benefit-risk evaluation, and 
approval by the Sponsor’s Medical Monitor (or designee). 
4.1.5. 
Part 5: Long-Term Follow-Up (LTFU) 
Upon completing the interventional phase of the study (Part 3 or 4) but no sooner than 90 
days post T-cell infusion (in order to capture enough safety information) or upon early 
withdrawal from the interventional phase, participants will be entered into a separate 
long-term follow-up (LTFU) protocol (GSK study 208750) and will be monitored for the 
observation of delayed AEs and survival during the 15 years post-infusion, in accordance 
with FDA regulations [FDA, 2020b] (Section 8.1.2). If not yet enrolled in Study 208750, 
there is a short-term provision (≤6 months) to follow participants according to the LTFU 
schedule under this protocol (reproduced on Table 8) until enrolled in the 208750 study. 
Participants who fail to consent to the 208750 study within this period will be withdrawn 
from Study 208471.    
4.2. 
Scientific Rationale for Study Design 
The study will employ an adaptive design to compare experimental therapy alone, or in 
combination with pembrolizumab, using Bayesian methods to provide probability of 
success estimates.  The design provides efficiencies in the evaluation of experimental 
therapy by discontinuing arms that meet pre-defined futility thresholds at interim time-
points while continuing enrollment to arms that may be more efficacious and 
subsequently graduate to Phase 3 confirmatory studies.   
4.3. 
Justification of Dose 
4.3.1. 
Justification of Lymphodepleting Regimen 
The planned lymphodepleting regimen is fludarabine, 30 mg/m2/day x 4 days and 
cyclophosphamide, 900 mg/m2/day x 3 days, with lete-cel infusion on Day 1.  This 
regimen is based on prior experience with lete-cel in participants with synovial sarcoma 
and melanoma, where fludarabine-containing regimens were associated with optimal 
responses [Mackall, 2016; Robbins, 2015]. For participants ≥60 years old, the 
lymphodepleting regimen should be adjusted as described in Section 6.3. For subjects 
with a prior history of severe and prolonged cytopenia (anemia, thrombocytopenia, or 
leukopenia) or other risk factors, the investigator should discuss with the sponsor’s 


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medical monitor or designee to determine the need for dose modification of the 
lymphodepletion regimen (see Section 6.3). 
4.3.2. 
Justification of Lete-cel Dose 
Lete-cel has achieved objective responses without significant toxicity, a dose range of 
1 x 109 to 8 x109 total transduced T cells, in participants with metastatic synovial 
sarcoma, metastatic melanoma [Robbins, 2015] and multiple myeloma [Rapoport, 2015] 
whose tumors expressed the NY-ESO-1 or LAGE-1a antigens and who met the HLA 
inclusion criteria.  This cell dose range was included in prior protocol amendments for 
Study 208471.  
 
Optimization of the dose range: 
A cell dose of 15 × 109 transduced T cells represents the updated upper end of what is 
logistically deemed feasible to manufacture. 
As such, the upper end of the target dose range of transduced T cells is increased from 
8 × 109  to 15 × 109 in order to maximize the delivery of cells for participants whose 
manufacture yields >8 × 109  transduced T cells.   
 
Patients have previously been treated at this upper end of the revised dose range: in 2 
older pilot studies (synovial sarcoma Study 208466 and multiple myeloma Study 
209393), 3 patients received doses >8 ×109 (up to 14.4 × 109) transduced T cells with no 
safety signals identified.  
Other TCR T cells have been reported safe at even higher doses: in a first-in-human, 
phase 1 clinical trial of 12 participants, genetically engineered T cells with a TCR 
targeting human papilloma virus-associated epithelial cancer HPV-16 E7 (E7 TCR) did 
not show any dose limited by toxicity with a maximum administered dose of 100 × 109 
engineered T cells [Nagarsheth , 2021]. 
Since no dose-toxicity relationship has been established to date on 125 patients dosed 
with lete-cel (GlaxoSmithKline Document Number: RPS-CLIN-015027), it is anticipated 
that the safety profile in patients who receive doses up to the theoretical 15 × 109 
transduced cells will remain comparable to the current safety profile. 
• For participants treated as of protocol amendment 7, any released manufactured 
product counting between (1-15) × 109 transduced cells will be shipped in its 
entirety for infusion as a single dose.   
Due to the sample size and tight control over product release, participants receiving doses 
>8 ×109 will be closely monitored with ongoing review by the internal Safety Review 
Team (SRT).  
  
4.3.3. 
Justification of Pembrolizumab Dose 
The planned dose of pembrolizumab for this study is 200 mg Q3W, which is the current 
approved dose and schedule for pembrolizumab.  Based on the totality of data generated 
in the pembrolizumab development program, 200 mg Q3W is the appropriate dose of 


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pembrolizumab for adults across all indications and regardless of tumor type.  This dose 
is justified by: 
• clinical data from 8 randomized studies demonstrating flat dose- and exposure-
efficacy relationships from 2 mg/kg Q3W to 10 mg/kg every 2 weeks (Q2W),  
• clinical data showing meaningful improvement in benefit-risk including overall 
survival at 200 mg Q3W across multiple indications, and 
• pharmacology data showing full target saturation in both systemic circulation 
(inferred from pharmacokinetic [PK] data) and tumor (inferred from 
physiologically-based PK [PBPK] analysis) at 200 mg Q3W. 
Among the 8 randomized dose-comparison studies, a total of 2262 participants were 
enrolled with melanoma and NSCLC, covering different disease settings (treatment 
naïve, previously treated, PD-L1 enriched, and all-comers) and different treatment 
settings (monotherapy and in combination with chemotherapy).  Five studies compared 
2 mg/kg Q3W versus 10 mg/kg Q2W (KN001 Cohort B2, KN001 Cohort D, KN002, 
KN010, and KN021), and 3 studies compared 10 mg/kg Q3W versus 10 mg/kg Q2W 
(KN001 Cohort B3, KN001 Cohort F2 and KN006).  All of these studies demonstrated 
flat dose- and exposure-response relationships across the doses studied representing an 
approximate 5- to 7.5-fold difference in exposure.  The 2 mg/kg (or 200 mg fixed-dose) 
Q3W provided similar responses to the highest doses studied.  Subsequently, flat dose-
exposure-response relationships were also observed in other tumor types including head 
and neck cancer, bladder cancer, gastric cancer and classical Hodgkin Lymphoma, 
confirming 200 mg Q3W as the appropriate dose independent of the tumor type.  These 
findings are consistent with the mechanism of action of pembrolizumab, which acts by 
interaction with immune cells, and not via direct binding to cancer cells. 
Additionally, pharmacology data clearly show target saturation at 200 mg Q3W.  First, 
PK data in KN001 evaluating target-mediated drug disposition (TMDD) conclusively 
demonstrated saturation of PD-1 in systemic circulation at doses much lower than 
200 mg Q3W.  Second, a PBPK analysis was conducted to predict tumor PD-1 saturation 
over a wide range of tumor penetration and PD-1 expression.  This evaluation concluded 
that pembrolizumab at 200 mg Q3W achieves full PD-1 saturation in both blood and 
tumor. 
Finally, population PK analysis of pembrolizumab, which characterized the influence of 
body weight and other participant covariates on exposure, has shown that the fixed-
dosing provides similar control of PK variability as weight-based dosing, with 
considerable overlap in the distribution of exposures from the 200 mg Q3W fixed dose 
and 2 mg/kg Q3W dose.  Supported by these PK characteristics and given that fixed-dose 
has advantages of reduced dosing complexity and reduced potential of dosing errors, the 
200 mg Q3W fixed-dose was selected for evaluation across all pembrolizumab protocols.  
4.3.3.1. 
Justification for Administration of First Dose of Pembrolizumab on 
Day 22 Following Lete-cel Infusion 
In Arms B and C, pembrolizumab administration starts on Day 22 (if deemed safe), and 
repeated Q3W for up to 35 cycles or disease progression (see Section 6.5).  The rationale 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
6 1  
 
f or starti n g pe m br oliz u ma b a d mi nistrati o n o n Da y 2 2 is t o mi ni mize t he ris k of C R S a n d 
e ns ure a d e q uate b o n e marr o w rec o ver y f oll o wi n g l y m p h o de pleti o n.   
4. 4.  
E n d of St u d y D efi niti o n  
T he c o m pleti o n of t he i nter ve nti o nal p has e of t he st u d y is defi ne d as t he dat e w he n a t 
least 7 0 % of all partici pa nts w h o recei v e d lete-cel i nf usi o n ( mI T T) ha ve pr o gresse d , d ied  
or ha ve bee n l ost t o f oll o w -u p . 
T he st u d y e n ds w he n all partici pa nts w h o recei ve d lete -cel i nf usi o n ( mI T T) ha ve m o ve d 
t o t he se parat e L T F U pr ot oc ol , decli ne d L T F U, ha ve bee n l ost t o f oll o w -u p, wit h dre w 
earl y, or die d.  
4. 4. 1.  
E n d of I nt er v e nti o n al P h a s e / St u d y f or I n di vi d u al P arti ci p a nt s 
E n d of i nterve nti o n al p h ase f or i n divi d u al p artici p a nts  
Partici pa nts  w h o d o n ot recei ve p e m br oliz u ma b will be c o nsi dere d t o ha ve c o m plete d t he 
i nter ve nti o nal p hase of t h e st u d y  ( Part 3 or 4) after bei n g o n st u d y u ntil W ee k 1 0 6 p ost 
lete-cel i nf usi o n (ap pr o xi matel y 2 years) , c o nfir m e d disease pr o gressi o n  (as defi ne d b y 
), or deat h  ( w hi c he ver occ urs first) i n or der t o all o w f or t he pri mar y a nal ysis t o 
occ ur. Partici p a nts w h o r ecei ve p e m br oliz u ma b i n A r ms B or C, or i n Ar m A f oll o wi n g 
disease pr o gressi o n after lete-cel i nf usi o n ( Part 4), will be c o nsi dere d o n t h e 
i nter ve nti o nal p hase of t h e st u d y u ntil c o m pleti o n of 3 5 c ycles of pe m br oliz u ma b, 
c o nfir me d diseas e  pr o gressi o n i n Ar ms B a n d C  (as defi ne d b y 
), f urt her 
c o nfir me d diseas e pr o gressi o n i n Ar m A Part 4  (as defi ne d b y 
), or  deat h  
( w hic he ver occ urs first).If partici pa nt disc o nti n ues t he i nter ve nti o nal p hase f or reas o ns 
n ot liste d a b o ve a n d d oes n ot wit h dra w fr o m t he st u d y, t he y will be c o nsi dere d as ha vi n g 
wit h dra w n fr o m t he i nter ve nti o nal p orti o n of t he st u d y.  
Partici pa nts will c o m plete a n E n d of Treat me nt visit, as detaile d i n Ta ble 7 , u nless 
wit h dra w n fr o m t he st u d y .  
U p o n c o m pleti n g t he i nter ve nti o nal p hase of t h e st u d y ( Part 3 or 4) b ut n o s o o ner t ha n 9 0 
da ys p ost T -cell i nf usi o n (i n or der t o ca pt ure e n o u g h safet y i nf or mati o n) or u p o n earl y 
wit h dra wal fr o m t he i nter ve nti o nal p hase, p artici p a nts will be e ntere d i nt o a se parate 
l o n g-ter m f oll o w-u p ( L T F U) pr ot o c ol ( G S K S t u d y 2 0 8 7 5 0) a n d will be m o nit ore d f or t he 
o bser vati o n of dela ye d A Es a n d s ur vi val d uri n g t he 1 5  years p o st-i nf usi o n, i n acc or da nce 
wit h F D A  re g ulati o ns [F D A , 2 02 0 b ] ( Secti o n 8. 1. 2 ).  If n ot yet e nr olle d i n t he L T F U 
pr ot oc ol, partici pa nts w h o ha ve n ot wit h dra w n fr o m t his st u d y will  be f oll o we d per 
L T F U sc h e d ule u n der t his pr ot oc ol ( Part 5) u ntil e nr olle d i n L T F U pr ot o c ol (see Ta bl e 
8 ). 
 
E n d of st u dy f or i n divi d u al p artici p a nts 
T he st u d y e n ds f or a n e nr olle d partici pa nt w he n t h e y h a ve tr a nsferre d t o t he se parat e 
L T F U pr ot o c ol ( G S K S t u d y 2 0 8 7 5 0), d ecli ne d c o nse nti n g t o t he se p arate L T F U pr ot o c ol, 
c o m plete d L T F U re q uir e me nt i n t his st u d y, ha v e bee n l ost t o f oll o w -u p, wit h dra w n  fr o m 
t he st u d y, or die d.  
C CI
C CI
C CI


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Discontinuation of pembrolizumab does not represent withdrawal from the interventional 
phase or withdrawal from the study. Refer to Section 7.1 for more information. 
5. 
STUDY POPULATION 
This Phase 1b/2a study aims to evaluate safety and clinical activity of lete-cel, alone 
(Arm A) or in combination with pembrolizumab (Arms B and C) in participants with 
cytologically or histologically confirmed advanced Stage IIIb or IV or recurrent NSCLC.  
Prospective approval of protocol deviations from recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, are not permitted. 
5.1. 
Inclusion Criteria 
Inclusion/Exclusion criteria are grouped into 4 parts and eligibility screening will take 
place in the following 4 steps: 
• Target expression screening: A set of criteria permitting participants’ blood to be 
screened for HLA-type and tumor sample to be screened for the expression of NY-
ESO-1/LAGE-1A. 
• Leukapheresis eligibility screening: To be fulfilled prior to performing 
leukapheresis procedure.  
• Lymphodepletion eligibility screening: To be fulfilled prior to performing 
lymphodepletion procedure. 
o Treatment fitness: To be evaluated prior to commencing 
lymphodepleting chemotherapy and administration of lete-cel. 
• Pembrolizumab treatment screening (Arm A ONLY, Part 4): To be fulfilled prior 
to commencing pembrolizumab treatment among patients in Arm A who progress 
following administration of lete-cel. 
 
5.1.1. 
Target Expression Screening  
Participants are eligible to be screened for target expression (HLA-A*02:01, A*02:05, or 
A*02:06 and NY-ESO-1/LAGE-1a) only if all of the following criteria apply: 
 
1. The participant (or legally acceptable representative if applicable) provides written 
informed consent for the screening process described as “Target Expression 
Screening” in the SoA (Section 1.3). 
2. Age ≥18 years on the day of signing informed consent. 
3. Medical Monitor (or designee) approval has been obtained if participants are 
enrolled or to be enrolled in other experimental interventional clinical studies during 
the screening and leukapheresis stages of this study (GSK208471). 
4. Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV 
NSCLC.  
a. Arms A and B: Participants with NSCLC lacking actionable genetic aberrations 
(i.e., wild type) per NCCN guidelines, based on SoC diagnostic test. 


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b. Arm C: Participants with NSCLC with actionable genetic aberrations (e.g., 
sensitizing EGFR mutation ALK translocation, etc.) per NCCN guidelines, based 
on SoC diagnostic test. 
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 
6. Tumor tissue sample with associated pathology report is available to perform tumor 
antigen expression analysis (NY-ESO-1 or, if tested, LAGE-1a), in alignment with 
Section 8.9.2.  
Note: Participants may not need to repeat certain screening/baseline assessments or 
procedures if performed as part of other GSK studies (see Section 4.1.1.1).  
 
5.1.2. 
Leukapheresis Eligibility Screening 
All screening criteria described in Section 5.1.1 must be reviewed and fulfilled along 
with all the following criteria prior to leukapheresis. Leukapheresis process may not be 
necessary for participants for which lete-cel cell product is already manufactured. 
Additionally, participants may not need to repeat certain screening/baseline assessments 
or procedures if performed as part of other GSK studies (see Section 4.1.1.1). 
7. The participant has successfully completed the HLA and target expression 
evaluations.  
a. 
Participant is positive for any of the following alleles: HLA-A*02:01, 
HLA-A*02:05, and/or HLA-A*02:06 by a validated test.  
b. Participant’s tumor has been reviewed by the GSK-designated laboratory and 
confirmed as meeting the pre-defined threshold for expression of NY-ESO-1 
and/or, if tested, LAGE-1a.  
After HLA allele genotyping and tumor antigen expression have been found positive, an 
eligible participant must fulfill all the following inclusion criteria: 
8. Participant (or legally acceptable representative if applicable) provides written 
informed consent for the trial. 
9. Participant must have adequate organ function and blood cell counts as indicated by 
the laboratory values in Table 11 and within the appropriate time windows per 
Schedule of Activities Table 2 (and per Table 3 for Treatment fitness assessment).  


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Table 11 
Adequate Organ Function 
System 
Laboratory Values 
Hematologica,b,c 
Absolute neutrophil count (ANC) 
1.5 x 109/L (without granulocyte colony-stimulating factor) 
Absolute lymphocyte count (ALC) 
≥0.5 x 109/L 
Hemoglobin 
9 g/dL or ≥5.6 mmol/L (not achieved by transfusion) 
Platelets 
100 x 109/L (not achieved by transfusion) 
Hepatic 
Albumin 
≥3.5 g/dL 
Total bilirubin 
Participants with Gilbert’s Syndrome (only if direct 
bilirubin 35%) 
1.5 x upper limit of normal (ULN)  
(isolated bilirubin ≥1.5 x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
Alanine aminotransferase (ALT) 
2.5 x ULN (or 5 x ULN if documented history of liver 
metastases)  
Renal 
Calculated creatinine clearance (CrCl) 
≥50 mL/min 
• 
Participants who are ≥18 and <65 years of age must be assessed either:  
o 
by 24-hour urine creatinine collection   OR 
o 
by using Serum Creatinine (Scr) via an estimated creatinine clearance calculated as outlined below 
by using the Chronic kidney disease Epidemiology Collaboration (CKD-EPI) equation and adjusting 
the result by multiplying with (BSA/1.73) to obtain a CrCl in mL/min.  
Step 1: estimated glomerular filtration rate (GFR) to be obtained from the CKD-EPI formula [Levey, 
2009]:  
Estimated GFR (mL/min/1.73m2) =  
                141 × min (Scr/κ, 1)α × max (Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black]  
where:  
Scr is serum creatinine in mg/dL,  
κ is 0.7 for females and 0.9 for males,  
 is -0.329 for females and -0.411 for males,  
min(Scr/κ,1) indicates the minimum of Scr/κ or 1,  
max(Scr/κ,1) indicates the maximum of Scr/κ or 1, and  
Age is in years. 
Step 2: correction factor to be applied per the American National Kidney Foundation in order to 
obtain the estimated creatine clearance in mL/min 
Estimated CrCl (mL/min) = Estimated GFR (mL/min/1.73 m2) × BSA (m2) / 1.73  
To calculate the BSA for fludarabine dosing, use actual body weight. An adjusted body weight may 
be required for cyclophosphamide, see Section 6.3 for further details.  
• 
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. 
Coagulationd 
International normalized ratio (INR) OR prothrombin 
time (PT) / Activated partial thromboplastin time 
(aPTT) 
≤1.5 × ULN unless participant is receiving anticoagulant 
therapy as long as PT or aPTT is within therapeutic range 
of intended use of anticoagulants 
a. 
No platelet transfusions within 14 days.  
b. 
No red blood cell transfusions to meet minimum hematologic values for eligibility. 
c. 
Organ function will be reassessed prior to lymphodepletion: if, upon consultation with the Medical Monitor, 
there is evidence from laboratory values that recovery from last anti-cancer treatment is underway, 
hematology labs may be considered acceptable and requirements waved to proceed with lymphodepletion. 
d. 
Prior to lymphodepletion, please refer to Section 6.9.2 for guideline on use of anticoagulant medications.  


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10. Predicted life expectancy that is ≥24 weeks from leukapheresis.  
11. Participant has left ventricular ejection fraction ≥45%.   
12. Participant is fit for leukapheresis and has adequate venous access for leukapheresis. 
13. 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: 
Male participants are eligible to participate if they agree to the following during 
the intervention period starting at the first dose of chemotherapy 
(lymphodepletion regimen) for at least 12 months after receiving the T-cell (lete-
cel) infusion, or until persistence of gene modified cells in the participant’s blood 
is below the level of detection for 2 consecutive assessments, whichever is 
longer:   
• If receiving pembrolizumab, must use effective contraception for at least 
4 months after the last dose of pembrolizumab if this time frame is longer than 
the duration of contraception required in the context of chemotherapy 
(lymphodepletion regimen) and gene modified cells.  
• Refrain from donating sperm, PLUS, EITHER:  
o Abstain 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 
o Must agree to use contraception/barrier as detailed below: 
▪ Agree to use a male condom and should also be advised of the benefit 
for a female partner to use a highly effective method of contraception 
as a condom may break or leak when having sexual intercourse with a 
woman of childbearing potential who is not currently pregnant 
▪ Agree to use a male condom when engaging in any activity that allows 
for passage of ejaculate to another person 
b. Female Participants:  
Female participants are eligible to participate if they are not pregnant or 
breastfeeding, and, at least 1 of the following conditions applies: 
• Is not a woman of childbearing potential (WOCBP) as defined in 
Section 5.3.3, 
OR 
• Is a WOCBP (as defined in Section 5.3.3) 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 5.3.3, during the 
intervention period and for at least 12 months after receiving the T-cell (lete-
cel) infusion, or until persistence of gene modified cells in the participant’s 
blood is below the level of detection for 2 consecutive assessments, whichever 
is longer.  If the participant is planned to receive pembrolizumab, she must 


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use a barrier method (male condom) and a highly effective contraception 
(with a failure rate of <1% per year) for at least 4 months after the last dose of 
pembrolizumab if this time frame is longer than the duration of contraception 
required in the context of chemotherapy (lymphodepletion regimen) and gene 
modified cells.  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. 
• 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.  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 is positive. 
5.1.3. 
Lymphodepletion Eligibility Screening 
The following criteria must be confirmed within protocol pre-specified timelines (see 
Table 3). 
14. Prior therapies 
a. All participants with NSCLC lacking actionable genetic aberrations (i.e., wild 
type), per NCCN guidelines (Arms A and B), need to have received at least 
one line of PD-1/PD-L1 checkpoint blockade therapy. For participants in the 
metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been 
received either alone, in combination or sequentially with platinum-containing 
chemotherapy (adjuvant therapy will count as a regimen if completed within 6 
months before the relapse).   
OR 
b. All participants with NSCLC with actionable genetic aberrations (e.g., 
sensitizing EGFR mutation ALK translocation, etc.), per NCCN guidelines 
(Arm C only), should have received appropriate targeted therapy following 
NCCN or equivalent country-level guidelines (e.g., ESMO, NICE, etc.). These 
participants could have received and failed PD-1/PD-L1 checkpoint blockade 
therapy.  
OR 
c. Medical Monitor (or designee) approval has been obtained if prior SoC therapy 
is refused by the participant (following discussion between participant and 
Investigator about benefits and risks) 
OR 
d. Participants not eligible for SoC anti-cancer therapy OR have terminated prior 
treatment due to intolerable side effects. Participants "intolerant" to an anti-
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OR have developed Grade ≥3 toxicity necessitating discontinuation of therapy, 
or dose modification, and/or Grade ≥3 unplanned hospitalization to alleviate 
effects of toxicity. 
e. Experimental systemic regimens are allowed. 
15. Disease progression: 
a. Lymphodepleting regimen may start after clinical AND/OR radiographic disease 
progression without second confirmatory imaging, based upon benefit-risk 
evaluation in agreement with the Medical Monitor (or designee). 
b. Following treatment with a PD-1/PD-L1 checkpoint blockade therapy 
administered either as monotherapy or in combination with other checkpoint 
inhibitors or other therapies, progression is defined by meeting all of the 
following criteria: 
o Received at least 2 doses of an approved PD-1/PD-L1 checkpoint 
blockade therapy  
o Demonstrated progression after PD-1/PD-L1 therapy as defined by 
RECIST v1.1.  In cases where pseudoprogression is suspected, the initial 
evidence of disease progression should be confirmed by a second 
assessment no less than 4 weeks and no more than 8 weeks after the date 
of the first documented progression, in the absence of rapid clinical 
progression [Seymour, 2017].  Confirmatory imaging may not be required 
based upon a benefit-risk evaluation in agreement with the Medical 
Monitor (or designee).  
c. An intermediate SoC line of therapy between leukapheresis (Part 2) and treatment 
(Part 3) at the time of disease progression is allowed if all of the conditions in 
Section 6.2 are met. 
16. Measurable disease per RECIST v1.1 as assessed by local site investigator/radiology.   
Measurable disease, i.e., presenting with at least one measurable lesion per RECIST 
v1.1.  See Section 10.10.1 for definition of a measurable lesion.  
Note: Lesions situated in a previously irradiated area are considered measurable if 
progression has been demonstrated in such lesions. 
17. Participant has undergone mandatory washout periods (Table 12) if receiving 
supportive therapy (e.g., radiotherapy, cryotherapy, chemotherapy, or other systemic 
treatments).  
18. A hematologist has been consulted prior to lymphodepletion in participants who 
have had a serious/significant bleeding/thrombosis history. 
 
5.1.3.1. 
Treatment Fitness 
Given potential changes in clinical status between screening/enrollment and the start of 
conditioning chemotherapy, safety assessments from Section 5.1.1 and Section 5.1.2 will 
be reassessed prior to lymphodepletion. If the results of any assessments or procedure are 


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outside of the eligibility criteria, please consult with the GSK Medical Monitor prior to 
proceeding with lymphodepletion.  
5.1.4. 
Pembrolizumab Therapy Following Disease Progression after 
Lete-cel Infusion (Arm A ONLY, Part 4) 
Participants who have received lete-cel in Arm A are eligible for therapy with 
pembrolizumab 200 mg flat dose Q3W if they fulfill all the following criteria: 
19. Radiographically confirmed progressive disease following treatment with lete-cel at 
or before the scheduled Week 25 scan. 
20. Any toxicity must be ≤ Grade 1 CTCAE (v4.03) at the time of first/dose (except for 
non-clinically significant toxicities, e.g., alopecia, vitiligo).  Participants with 
Grade 2 toxicities that are deemed stable or irreversible (e.g., non-demyelinating 
peripheral neuropathy) can be enrolled on a case-by-case basis with prior 
consultation and agreement with the Sponsor’s Medical Monitor (or designee).  
21. Pembrolizumab treatment is permitted, following benefit-risk evaluation between the 
Investigator and Sponsor’s Medical Monitor (or designee). 
5.2. 
Exclusion Criteria 
5.2.1. 
Target Expression Screening  
Participants are not eligible to be screened for target expression if any of the following 
criteria apply: 
1. Prior treatment: 
a. Previous treatment with genetically engineered NY-ESO-1-specific T-cells.  
b. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. 
c. Prior gene therapy using an integrating vector. 
d. Previous allogeneic hematopoietic stem cell transplant. 
2. Prior malignancy other than NSCLC, with the following exceptions: 
a. Participants with a history of basal cell carcinoma of the skin, superficial 
bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or 
has undergone potentially curative therapy with no evidence of that disease 
recurrence for 5 years since initiation of that therapy. 
3. Participant has undergone prior allogeneic/autologous bone marrow or solid organ 
transplantation.   
5.2.2. 
Leukapheresis Eligibility Screening  
Participants are not eligible for leukapharesis if any of the Exclusion criteria in Section 
5.2.1 apply. Please note that mandatory washout period restrictions must be respected 
(Table 12) before starting leukapheresis. In addition, participants are not eligible for 
leukapheresis if any of the following criteria apply: 


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4. Participant has a history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to cyclophosphamide, fludarabine, 
dimethylsulfoxide (DMSO) or other agents used in the study (participants with 
vitiligo or resolved childhood asthma/atopy are an exception to this rule). 
5. Participant has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of 
its excipients. 
6. Participant has an active autoimmune disease that has required systemic treatment in 
past 2 years (i.e., with use of disease modifying agents, corticosteroids or 
immunosuppressive drugs).  Replacement therapy (e.g., physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency) is not considered a form 
of systemic treatment and is allowed. 
7. Participant has a history of chronic or recurrent (within the last year prior to 
enrollment) severe autoimmune or active immune-mediated disease requiring 
steroids or other immunosuppressive treatments. 
8. Uncontrolled intercurrent illness including, but not limited to: 
a. Ongoing or active infection (including but not limited to systemic fungal 
infections) 
b. Clinically significant cardiac disease defined by congestive heart failure New 
York Heart Association (NYHA) Class >1 
c. Uncontrolled clinically significant arrhythmia in last 6 months 
d. Acute coronary syndrome (angina or myocardial infarction) in last 6 months 
e. Severe aortic stenosis, symptomatic mitral stenosis 
f. Inadequate pulmonary function with mechanical parameters <40% predicted 
(forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], 
total lung capacity [TLC], pulmonary diffusing capacity for carbon monoxide 
[DLCO]) 
g. Interstitial lung disease (participants with existing pneumonitis as a result of 
radiation are not excluded; however, participants cannot be oxygen dependent) 
Note: Post-radiation changes in the lung related to prior radiotherapy and/or 
asymptomatic radiation-induced pneumonitis not requiring treatment may be 
permitted if agreed upon by the Investigator and Sponsor’s Medical Monitor 
(or designee). 
h. Prior or active demyelinating disease 
i. Current unstable liver or biliary disease per Investigator assessment defined by 
the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, 
esophageal or gastric varices, persistent jaundice, or cirrhosis. 
9. Participant has active infection with HIV, HBV, HCV, EBV, CMV, syphilis, or 
HTLV as defined below: 
a. Positive serology for human immunodeficiency virus (HIV).  
b. Active hepatitis B infection as demonstrated by test for hepatitis B surface 
antigen. Participants who are hepatitis B surface antigen negative but are 


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hepatitis B core antibody positive must have undetectable hepatitis B DNA and 
receive prophylaxis against viral reactivation.  
c. Active hepatitis C infection as demonstrated by hepatitis C RNA test. 
Participants who are HCV antibody positive will be screened for HCV RNA 
by any RT PCR or bDNA assay.  If HCV antibody is positive, eligibility will 
be determined based on a negative Screening RNA value. 
d. Positive serology for human T lymphotropic virus 1 or 2 (HTLV-1 or -2). 
e. Positive serology for Epstein-Barr virus (EBV). Participants with positive EBV 
serology will undergo additional tests/assessments in order to rule out active 
infection. 
f. Active CMV infection. Participants with positive CMV serology need to 
undergo additional tests/assessments in order to rule out active infection. 
g. Positive test for syphilis (spirochete bacterium). 
10. Participant is pregnant or breastfeeding. 
11. Participant has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the study, interfere with the 
participant's participation for the full duration of the study, or is not in the best 
interest of the participant to participate, in the opinion of the treating Investigator and 
in agreement with the Sponsor’s Medical Monitor (or designee). 
12. Participant has known psychiatric or substance abuse disorders that would interfere 
with cooperating with the requirements of the study 
13. QTc >480 msec. 
Notes:  
a. Collect a single ECG.  If QTc is >480 msec, collect 2 more ECGs 5 minutes 
apart and use the average of those QTc values to determine eligibility. If the 
average QTc is >480msec get a manual overread of the triplicate.   
b. QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), or another method, machine-read or 
manually over-read. 
c. The specific formula that will be used to determine eligibility and 
discontinuation for an individual participant 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 participant and then the lowest QTc 
value used to include or discontinue the participant from the trial. 
d. 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). 
14. Prior/Concomitant Therapy: 
a. Toxicity from previous anti-cancer therapy that has not recovered to CTCAE 
v4.03 Grade ≤1 prior to enrollment (except for non-clinically significant 
toxicities, e.g., alopecia, vitiligo).  Participants with existing pneumonitis 


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because of radiation are not excluded; however, participants cannot be oxygen-
dependent.  Participants 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 Medical Monitor 
(or designee). 
b. Other standard of care lines of therapy are allowed only if guidelines and 
washout periods are followed as described in Table 12. 
15. Investigational treatment within 4 weeks or 5 half-lives (whichever is shorter) prior 
to leukapheresis (or lymphodepletion).  Investigational vaccines (other than NY-
ESO-1 vaccines that are not allowed) must follow the washout period specified in 
Table 12 Exceptions to this rule must be evaluated by the Investigator in agreement 
with the Sponsor’s Medical Monitor (or designee). 
16. Symptomatic or untreated central nervous system (CNS) metastases.  
Participants with treated asymptomatic CNS metastases (supratentorial or cerebellar) 
may be eligible after discussion and agreement with the Sponsor Medical Monitor 
(or designee), and if they meet all the following criteria:  
a. 
Clinically stable  
b. No history of bleeding within CNS metastases 
c. 
No lesions in the brain stem, midbrain, pons, medulla or spinal cord 
d. No leptomeningeal metastases  
e. 
No spinal cord compression 
f. 
Not requiring escalating anti-epileptic treatment 
g. Not requiring ongoing treatment with steroids for CNS disease 
h. Adhere to a 2-week washout period for focal radiotherapy (e.g. gamma knife 
radiosurgery) 
i. 
Adhere to a 4-week washout period for whole brain radiotherapy 
j. 
Adhere to a 3-month washout period for therapy to any CNS metastases if 
they are to be considered as target lesions  
k. A repeat brain MRI prior to lymphodepletion would need to show stability or 
reduction of CNS metastases if any radiotherapy was administered after the 
screening MRI 
Participants who develop oligometastatic CNS metastasis (supratentorial or 
cerebellar) after leukapheresis and prior to the start of lymphodepletion may be 
eligible to continue with lymphodepletion after discussion and agreement with the 
Sponsor Medical Monitor (or designee), and they meet all of the following criteria:   
a. Asymptomatic 
b. Small volume disease (defined as no more than 3 lesions, each ≤0.5 cm)  
c. Not requiring steroids or anti-epileptic treatment  
d. Treatment of the lesions is not clinically indicated 


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5.2.3. 
Lymphodepletion Eligibility Screening 
Please note that mandatory washout period restrictions must be respected (see Table 12) 
before starting lymphodepletion. In addition, participants meeting any of the following 
exclusion criteria cannot proceed with lymphodepleting chemotherapy and subsequent 
lete-cel treatment: 
17. Manufactured T cells have expired their shelf life (consult with Sponsor for current 
shelf life specifications). 
18. Participant has received treatment/therapy within the required washout periods listed 
in Table 12.  
a. Participants must have recovered from all AEs due to previous therapies to 
≤ Grade 1 or baseline.  Participants with ≤ Grade 2 non-demyelinating 
neuropathy are eligible. 
Note: If participant received major surgery, they must have recovered adequately 
from the toxicity and/or complications from the intervention prior to starting study 
treatment. 
19. Radiotherapy that involves the lung (V20 exceeding 30% lung volume or mean heart 
dose >20Gy) within 3 months 
OR 
Radiotherapy (including but not limited to palliative radiotherapy) to 
lung/mediastinum with V20 less than 30% lung volume and with mean heart 
dose ≤20Gy within 4 weeks (3 days) 
Note: Electron beam radiotherapy to superficial structures in the chest is permitted. 
There is no wash-out period for palliative radiation to non-target lesions other than 
the lung and mediastinum.  
20. Participant has received ≥50 Gy radiotherapy to a significant volume of the pelvis, 
long bones or spine, or a cumulative dose of radiation that, in the investigator’s 
opinion would predispose patients to prolonged cytopenia after lymphodepletion. 
21. All of the participant’s measurable lesions have been irradiated within 3 months 
before lymphodepletion.  
Note: An irradiated measurable lesion with unequivocal progression following 
irradiation may be considered a target lesion regardless of time from last 
radiotherapy dose.  
22. Participant has undergone major surgery 28 days before the first dose of study 
treatment. 
23. Active infection requiring intravenous systemic therapy. 
 


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Table 12 
Concomitant Treatments and Washout Periods 
Treatment/Therapy1 
Required Washout prior to leukapheresis and 
lymphodepletion 
Cytotoxic chemotherapy 
2 weeks 
Immune therapy (including monoclonal antibody 
therapy) 
No wash-out for PD-1/PD-L1 checkpoint blockade agents. 
For all others, case by case evaluation between Investigator 
and Sponsor’s Medical Monitor (or designee). 
Anticancer Vaccine 
2 months 
The participant should be excluded if the Investigator 
considers the participant’s disease to be responding to an 
experimental vaccine given within 6 months. 
Live-virus vaccination (seasonal flu vaccines that 
do not contain live virus are acceptable). 
4 weeks 
 
Systemic corticosteroids or any other 
immunosuppressive therapy  
NOTE:  Use of inhaled or topical steroids or 
physiologic corticosteroid replacement therapy for 
adrenal or pituitary insufficiency is acceptable. 
2 weeks 
Investigational treatment  
4 weeks or 5 half-lives2 
Tyrosine kinase inhibitors 
1 week3 
Radiotherapy 
See exclusion criteria #19, #20 and #21, prior to 
lymphodepletion4 
Herbal medications and other dietary supplements 
2 weeks (see Section 6.9 for details) 
Abbreviation: PD-1/PD-L1 = programmed death protein 1/PD-1 ligand. 
1. 
Permission and washout for any other anticancer therapies must be discussed with the Sponsor’s 
Medical Monitor (or designee). 
2. 
Washout period of 4 weeks or 5 half-lives, whichever is shorter. 
3. 
One-week washout period for tyrosine kinase inhibitors prior to lymphodepletion. No required washout 
period prior to leukapheresis. 
4. 
No required washout period prior to leukapheresis. 
5.2.3.1. 
Treatment Fitness 
Given potential changes in clinical status between screening/enrollment and the start of 
conditioning chemotherapy, safety assessments from Section 5.2.1 and Section 5.2.2 will 
be reassessed prior to lymphodepletion. If the results of any assessments or procedure are 
outside of the eligibility criteria, please consult with the GSK Medical Monitor prior to 
proceeding with lymphodepletion. 
5.2.4. 
Pembrolizumab Therapy Following Disease Progression after 
Lete-cel Infusion (Arm A ONLY, Part 4) 
24. Persistence of toxicities such as CRS ≥ Grade 2 that preclude treatment with 
pembrolizumab. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Participants should maintain a normal diet unless modifications are required to manage 
an AE such as diarrhea, nausea, or vomiting. 


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5.3.2. 
Activity 
Participants will abstain from strenuous exercise for 24 hours before each blood 
collection for clinical laboratory tests.  Participants may participate in light recreational 
activities during studies (e.g., watching television, reading, walking slowly, sitting at a 
computer, making the bed, eating, preparing food, and washing dishes). 
5.3.3. 
Contraception 
Participants should be informed that treatment with fludarabine, cyclophosphamide, lete-
cel and/or pembrolizumab may have adverse effects on a fetus in utero.  Furthermore, 
while it is not known if such treatment has transient adverse effects on the composition of 
sperm, the investigator should advise fertile male participants to consider collecting and 
storing viable sperm prior to undergoing lymphodepletion, given that cyclophosphamide 
may result in partial (oligospermia) or total (azoospermia) sterility.   
5.3.3.1. 
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: 
I. 
Premenarchal female 
II. 
Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• 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. 
III. 
Postmenopausal female: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
o 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 


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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. 
5.3.3.2. 
Contraception  
Male Participants 
Male participants must agree to the following during the intervention period starting at 
the first dose of chemotherapy (lymphodepletion regimen) for at least 12 months after 
receiving the T-cell infusion, or until persistence of gene modified cells in the 
participant’s blood is below the level of detection for 2 consecutive assessments , 
whichever is longer.  If assigned to Arm B or Arm C or participating in Part 4 Arm A, 
participants must use effective contraception for at least 4 months after the last dose of 
pembrolizumab if this time frame is longer than the duration of contraception required in 
the context of chemotherapy (lymphodepletion regimen) and gene modified cells.   
• 
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 currently pregnant 
o Agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person. 
 
Female Participants 
For contraception, participants who are WOCBP must use a barrier method (male 
condom) and should comply with one of the following: 


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Table 13 
Contraceptives Allowed During the Study 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User-Dependency Failure rate of <1% per year when used 
consistently and correctly. 
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
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 90 days. 
Highly Effective Methodsb That Are User-Dependent Failure rate of <1% per year when used consistently and 
correctly. 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationc 
o 
Oral 
o 
Intravaginal 
o 
Transdermal 
o 
Injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
o 
Oral 
o 
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. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Male 
condom and female condom should not be used together (due to risk of failure with friction). 
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. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those when 
used consistently and correctly. 
c. Male condoms must be used in addition to hormonal contraception.  If locally required, in accordance with Clinical 
Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those which inhibit 
ovulation as the primary mode of action. 
Participants should be informed that taking the study medication may involve unknown 
risks to the fetus (unborn baby) if pregnancy were to occur during the study.  In order to 
participate in the study, participants of childbearing potential must adhere to the 
contraception requirement (described above) from the day of study medication initiation 
(or 14 days prior to the initiation of study medication for oral contraception) throughout 
the study period up to 12 months after receiving T-cell infusion, or until persistence of 
gene modified cells in the participant’s blood is below the level of detection for 2 
consecutive assessments, whichever is longer.  Participants assigned to Arm B or Arm C 
or participating in Part 4 Arm A must also use effective contraception for at least 4 
months after the last dose of pembrolizumab if this time frame is longer than the duration 
of contraception required in the context of chemotherapy (lymphodepletion regimen) and 
gene modified cells.  If there is any question that a participant of childbearing potential 


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will not reliably comply with the requirements for contraception, that participant should 
not be entered into the study. 
5.3.4. 
Use in Pregnancy 
If a participant inadvertently becomes pregnant while on treatment with lete-cel or 
pembrolizumab, the participant will immediately be removed from the study.  The site 
will contact the participant at least monthly and document the participant’s status until 
the pregnancy has been completed or terminated.  The outcome of the pregnancy will be 
reported to the Sponsor without delay and within 24 hours if the outcome is a serious 
adverse experience (e.g., death, abortion, congenital anomaly, or other disabling or life-
threatening complication to the mother or newborn).  The Investigator will make every 
effort to obtain permission to follow the outcome of the pregnancy and report the 
condition of the fetus or newborn to the Sponsor.  Any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. 
5.3.5. 
Use in Nursing Women 
It is unknown whether lete-cel or pembrolizumab is excreted in human milk.  Since many 
drugs are excreted in human milk, and because of the potential for serious adverse 
reactions in the nursing infant, participants who are breastfeeding are not eligible for 
enrollment. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently enrolled in the study.  A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any SAEs. 
Individuals who do not meet the criteria for participation in this study (any screen failure 
except for HLA) may be rescreened 1 additional time.  Rescreened participants should be 
assigned a new participant number. 
6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Leukapheresis 
Participants who complete screening procedures and meet all eligibility criteria will be 
eligible to undergo leukapheresis to obtain the starting material for the manufacture of 
autologous lete-cel.   


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For collection of the starting material, a large-volume non-mobilized peripheral blood 
mononuclear cell (PBMC) collection should be performed according to institutional 
standard procedures and as detailed in the Apheresis Manual.  In cases where the 
minimum number of PBMCs is not collected or the manufactured lete-cel product cannot 
be infused back to the participant, a second leukapheresis may be performed. The 
collected leukapheresis product will then be transported for manufacture as detailed in the 
Apheresis Manual. 
6.2. 
Supportive Therapy and/or SoC Therapy Before 
Lymphodepletion 
Supportive local therapy (e.g., radiotherapy, cryotherapy, etc.), chemotherapy, or other 
systemic treatments may be administered between Screening and leukapheresis, and 
between leukapheresis and the start of lymphodepletion (bridging therapy) if a participant 
has progressive disease and cannot be treatment-free, but mandatory washout periods 
(Table 12, Section 5.1 and Section 5.2) must be respected.  For therapies not described in 
this protocol, wash-out periods should be around 4 weeks or 5 half-lives (whichever is 
shorter), in consultation with Medical Monitor for the study. 
A SoC line of therapy may be administered to participants before lymphodepletion based 
on the Investigator’s evaluation of benefits and risks, in accordance with local regulatory 
requirements and standards, and in agreement with the Sponsor’s Medical Monitor (or 
designee). 
An intermediate SoC line of therapy between leukapheresis (Part 2) and treatment 
(Part 3) at the time of disease progression is allowed if it is based on benefit-risk 
assessment and/or local regulatory requirements and following agreement with Sponsor’s 
Medical Monitor (or designee). 
Note: SAEs related to study participation and other clinical observations affecting 
treatment eligibility need to be reported in this study database. 
Note: Participants receiving a line of systemic SoC treatment can start 
lymphodepletion after disease progression. 
6.3. 
Lymphodepleting Chemotherapy 
Once lete-cel has been manufactured and received at the site, eligible participants will 
proceed to have lymphodepleting chemotherapy and infusion of lete-cel as detailed in this 
section. 
Prior to the administration of lymphodepleting chemotherapy, participant’s fitness for 
lymphodepletion will be assessed together with the Medical Monitor and baseline tumor 
assessments (scan and biopsy) obtained (See Section 1.3 for Schedule of Activities).  
When the lete-cel cells have been manufactured, have fulfilled release criteria, and are 
available for infusion at the site, lymphodepleting fludarabine and cyclophosphamide can 
be administered as described in Table 14.  Cyclophosphamide and fludarabine will be 
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Table 14 
Lymphodepleting Chemotherapy 
Lymphodepleting chemotherapy 
Recommended prophylaxis and 
supportive medication 
Day 
Drug 
Dose,b 
mg/m2 
Route 
Administrationd 
Infection: On admission for 
lymphodepleting chemotherapy, 
commence anti-microbial and anti-fungal 
prophylaxis as recommended in Section 
10.9.2 or in line with institutional standard 
practice. 
 
Hydration: Ensure adequate hydration and 
antiemetic provision prior to commencing 
cyclophosphamide infusions. 
 
Mesna: Should be given to prevent 
urotoxicity per institutional guidelines or as 
recommended in Section 6.3.4. 
 
G-CSF: Must start ~24 hours after the last 
cyclophosphamide infusion (i.e. on Day -4) 
until resolution of neutropenia in 
accordance with ASCO guidelines (Smith, 
2015) or in line with institutional practice. 
-8 
Fludarabinea 
30 
IV 
In 50 to 100 mL 
0.9% NaCl over 
30 minsc 
-7 
Fludarabinea 
30 
IV 
In 50 to 100 mL 
0.9% NaCl over 
30 minsc 
Cyclophosphamide 
900 
IV 
In 100 to 250 mL 
0.9% NaCl over 
1 hour  
-6 
Fludarabinea 
30 
IV 
In 50 to 100 mL 
0.9% NaCl over 
30 minsc 
Cyclophosphamide 
900 
IV 
In 100 to 250 mL 
0.9% NaCl over 
1 hour 
-5 
Fludarabinea 
30 
IV 
In 50 to 100 mL 
0.9% NaCl over 
30 minsc 
Cyclophosphamide 
900 
IV 
In 100 to 250 mL 
0.9% NaCl over 
1 hour 
-4 
Start G-CSFd 
 
-3 
 
-2 
 
-1 
 
1 
Lete-cel infusione 
Abbreviations: ASCO = American Society of Clinical Oncology; IV = intravenous; NaCl = sodium chloride; 
G-CSF = granulocyte-colony stimulating factor. 
a. 
Fludarabine dose will be adjusted in renal impairment as described in Section 6.3.2. This adjustment needs 
to be applied to all doses, on top of the age-related modification. Fludarabine dose will not be adjusted by 
body weight per ASBMT guidelines that recommend dosing based upon body surface area (BSA) using total 
body weight [Bubalo, 2014], unless required otherwise by institutional guidelines. 
b. 
Lymphodepleting regimen will be adjusted in participants ≥60 years old as described in Section 6.3.1. 
c. 
Concentration ≤1 mg/mL. 
d. 
Long-acting (pegylated) G-CSF may be given instead of short acting G-CSF per institutional standard 
practice. If using pegylated G-CSF, give one dose ~24 hours after the last chemotherapy administered.  
e. 
Administration of lete-cel is described in Section 6.4. 
 
6.3.1. 
Lymphodepletion Dose Modification 
Dose and regimen for lymphodepleting chemotherapy is adjusted for participants ≥60 
years old, as follows: 
• Fludarabine at 30 mg/m2 for 3 days (Day -7 to Day -5) 
• Cyclophosphamide at 600 mg/m2 (Day -7 to Day -5)   


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Baseline assessments may be completed between Day -17 and Day -8 among participants 
who initiate the lymphodepleting regimen on Day -7.  
The investigator must discuss with the sponsor’s medical monitor or designee to 
determine the need for dose modification of the lymphodepletion regimen in situations 
such as but not limited to the following: 
- 
participants with documented history of severe and prolonged cytopenia (anemia, 
thrombocytopenia, or leukopenia),  
- 
participants with 3 or more prior lines of therapies, 
- 
participants with documented extensive prior radiation of the pelvis, long bones or 
spine,  
- 
participants with documented history of intensive chemotherapy that could reduce 
bone marrow reserve, 
- 
participants with documented low albumin (≤3.5 g/dL),  
If during the course of lymphodepletion a participant experiences toxicity and is unable 
to complete the lymphodepletion regimen, participant may proceed with infusion in 
agreement with Medical Monitor.  
If the infusion of lete-cel is delayed >2 weeks, in general lymphodepleting chemotherapy 
should be repeated. The Investigator is expected to discuss the participant’s condition and 
the treatment plan with the Medical Monitor. 
Lymphodepletion dose calculation 
For Investigators with patients approaching lymphodepletion, GSK requires that you 
review your Creatinine Clearance and Lymphodepletion dose calculations with the 
medical monitor or designee.  Before lymphodepletion, site must provide Sponsor with 
intended doses (in mg/day) of fludarabine and cyclophosphamide, patient’s height, 
weight, gender, ethnicity, baseline serum creatinine(s) and creatinine clearance (CrCl, 
estimated or measured).  Any significant discrepancy that would lead to a change in dose 
will be discussed with Investigator prior to commencing lymphodepletion. 
Calculations methods are provided in Section 5.1.2 Table 11 Definitions of Adequate 
Organ Function, Renal for CKD-EPI and BSA (e.g. DuBois), but institutions may use 
their own BSA calculator (e.g., Mosteller), if required per local institutional practice.  
If there is variability in pre-leukapheresis and pre-lymphodepletion serum creatinine by 
30%, institution must consider more formal/accurate measure rather than rely on 
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6.3.2. 
Fludarabine Dose Adjustment for Renal Impairment 
This adjustment needs to be applied to all doses, on top of the age-related modification. 
The dose of fludarabine will be adjusted for participants with renal dysfunction as 
follows: 
Creatinine clearance 
Fludarabine dose 
>80 mL/min 
30 mg/m2 
>50 to 80 mL/min 
20 mg/m2 
30 to 50 mL/min 
15 mg/m2 
Note: to estimate CrCl (in mL/min) please use Table 11 (Adequate Organ Function) for calculation steps 
before comparing to the thresholds given above. 
If estimating CrCl using the CKD-EPI equation, adjust the result by multiplying by 
(BSA/1.73) to obtain a CrCl in mL/min. For fludarabine dosing with this BSA 
calculation, use actual body weight.   
Creatinine clearance must be reassessed prior to lymphodepletion for use in these 
calculations. 
6.3.3. 
Cyclophosphamide Dose Adjustment   
This adjustment needs to be applied to all doses, on top of the age-related modification.  
If the participant’s weight is greater than 175% Ideal Body Weight (IBW), then calculate 
cyclophosphamide dose based on Body Surface Area (BSA) calculated using the 
Adjusted Body Weight (ABW). 
Calculating Ideal Body Weight 
 
Estimated ideal body weight (IBW) in kg 
Males 
IBW = (0.9 × height in cm) −88  
Females 
IBW = (0.9 × height in cm) −92  
Estimation of Ideal Body Weight may be performed per local institutional guidelines instead. 
 
Calculating Adjusted Body Weight 
If the actual body weight is greater than 175% of the calculated IBW, calculate the ABW:  
ABW = IBW + 0.4 × (actual weight −IBW) 
Estimation of Adjusted Body Weight may be performed per local institutional guidelines 
instead. 
The IBW and ABW are used to calculate medication dosages when the participant is 
obese. This formula only applies to persons 152 cm or taller.  Use ABW in the 
calculation for body surface area. 


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6.3.4. 
Mesna 
Mesna should be administered per institutional guidelines or as recommended below:  
• 20% of cyclophosphamide dose (180 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. 
6.4. 
T-cell (Lete-cel) Infusion 
Lete-cel, autologous T-cells transduced with a self-inactivating lentiviral vector encoding 
an affinity enhanced TCR specific for NY-ESO-1/LAGE-1a, is one of the IPs in this 
study. 
Participants will receive a single-dose of lete-cel 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 Assessments (Section 1.3). 
6.4.1. 
Premedication 
Thirty (30) to 60 minutes prior to lete-cel infusion, participants will be premedicated 
against potential infusion reactions with antihistamines and acetaminophen 
(paracetamol). Follow institutional guidance for dosage and specific medications.  It is to 
be noted that steroids should not be administered as premedication for T-cell 
infusion because they are lymphotoxic and inhibitory to the T-cell product. 
6.4.2. 
Lete-cel Dose 
A dose range of 1 x 109 to 15 x 109 total transduced cells will be administered by a single 
IV 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.  If after a second leukapheresis,  
manufacturing has still not produced at least the minimum target dose of 1 x 109 cells, 
and the patient still would like to be treated with their cells, the participant may be 
allowed to receive lete-cel following review and approval by the local IRB, regulatory 
agency, Investigator and Sponsor’s Medical Monitor, if deemed clinically acceptable. In 
such cases however, it is expected that at least 5 x 108 cells would need to be available. 
These participants will be included in the safety population, but not in the Modified ITT 
(mITT) Population or All Evaluable Population (see Section 9.3). 
6.4.3. 
Lete-cel Administration 
Vital signs will be recorded prior to infusion (Table 3). 
On Day 1, the participant will receive thawed lete-cel by IV infusion.  Prior to infusion, 
two clinical personnel will independently verify and confirm in the presence of the 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
8 3  
 
partici pa nt  t hat t he i nf or mati o n o n t he i nf usi o n ba g is c orrectl y matc h e d t o t he 
partici pa nt , as per t he S p o ns or’s  a n d cli nical site’s pr oce d ures.  
A le u k ore d ucti o n filter m ust n ot be use d f or t he i nf usi o n of t he T -cell pr o d u ct . T he 
s pecific i nstr ucti o ns f or t he pre parati o n a n d a d mi nistrati o n of lete-cel are f o u n d i n t he 
Dr u g Pr o d uct a n d I nf usi o n Ma n ual. A n y de viati o ns fr o m t he pr oce d ure d etaile d i n t he 
Dr u g Pr o d uct a n d I nf usi o n Ma n ual s h o ul d be rec or de d a n d re p orte d acc or di n gl y.  
I n t he e ve nt of a n a d v ers e reacti o n t o cell i nf usi o n , t he i nf usi o n rate s h o ul d be re d uce d or 
st o p pe d a n d t he reacti o n ma na ge d acc or di n g t o i nstit uti o nal sta n dar d pr oce d ures 
( Secti o n 1 0. 9. 1 ).  Ster oi d treat me nt s h o ul d be a v oi de d u nless me dicall y re q uire d.  I n t he 
e ve nt a partici pa nt de vel o ps a fe brile e pis o de f oll o wi n g t he i nf usi o n, a p pr o priate c ult ures 
a n d me dical ma na ge me nt s h o ul d be i nitiate d, wit h atte nti o n t o t he i nitiati o n of e m pirical 
a nti bi otic treat me nt i n t he case of fe brile ne utr o p e nia . 
T he da y of let e-cel i nf usi o n ma y b e dela ye d i n a p artici pa nt wit h si g nifica nt 
c o m plicati o ns of c he m ot hera p y if , acc or di n g t o t h e I n vesti gat or , it is i n t he best i nterest 
of t he partici pa nt.  T h e ti mi n g of all assess me nts p ost -i nf usi o n will be calc ulate d wit h 
refere nce t o t he lete-cel i nf usi o n date.  C yt o pe ni as al o ne s h o ul d n ot be a reas o n t o dela y 
lete-cel i nf usi o n u nless c o m plicati o ns are pres e nt. 
Partici pa nts w h o ha ve u n der g o ne le u ka p heresis b ut d o n ot recei ve t he l ete-cel i nf usi o n 
will be re place d.   
6. 4. 4.  
P e m br oli z u m a b T h er a p y F oll o wi n g Di s e a s e Pr o gr e s si o n aft er 
L et e -c el I nf u si o n (P art 4, Ar m A  O nl y )  
Partici pa nts i n Ar m A w h o ha ve P D  f oll o wi n g treat ment wit h  lete-cel at or bef ore t h e 
sc he d ule d Wee k 2 5 sca n ma y  b e offere d p e m br oliz u ma b  t hera p y f oll o wi n g assess me nt of 
eli gi bilit y f or pe m br oliz u ma b treat me nt, be n efit -ris k e val uati o n , a n d a p pr o val b y t he 
S p o ns or’s Me dical M o nit or  ( or desi g nee).  Pe m br oliz u ma b treat me nt will be 
a d mi nistere d at 2 0 0 m g Q 3 W f or u p t o 3 5 c ycles or u ntil s u bse q ue nt disease pr o gressi o n.  
T he  first da y of pe m br oliz u ma b a d mi nistrati o n will be c o nsi dere d Da y 1 of t he 
pe m br oliz u ma b t hera p y p hase ( Pe m br oliz u ma b Wee k 1 Da y 1).  Ge neral i nf or mati o n 
re gar di n g p e m br oliz u ma b i nf usi o n ( Secti o n 6. 5 ) is als o a p plica ble t o partici pa nts i n 
Part  4 of Ar m A.  
T he S o A f or partici pa nts t hat recei v e pe m br oliz u ma b f oll o wi n g dise ase pr o gressi o n after 
lete-cel i nf usi o n i n Ar m A  is prese nte d i n Ta bl e 5 . 
6. 5.  
P e m br oli z u m a b I nf u si o n  i n Ar m s  B  a n d C  a n d P art 4 Ar m A  
I n Ar ms B  a n d C , the first pe m br oliz u ma b a d mi nistrati o n is o n Da y 2 2  ( Wee k 4 Da y 1), 
a n d t he n it is a d mi nistere d Q 3 W f or u p t o 3 5 c ycles  ( u p t o W ee k 1 0 6) or u ntil disease 
pr o gressi o n , w hic he v er occ urs first.   
C CI


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If toxicities are observed at Day 22 that preclude the administration of pembrolizumab 
treatment (such as CRS Grade ≥2 or GVHD), infusion of pembrolizumab will start on 
Week 7 Day 1 and continue Q3 weeks for up to 35 cycles (up to Week 109).  If AEs do 
not resolve by Week 7 Day 1 (see Table 15 for details), pembrolizumab will not be 
administered and the participant will be evaluated until disease progression or EoT. 
Participants who do not receive pembrolizumab by Week 7 must be discussed by the 
Investigator and the Sponsor’s Medical Monitor (or designee) prior to initiating 
pembrolizumab at a later date; enrollment can continue until at least 15 participants are 
assigned in Arm B and have received pembrolizumab by Week 7 and at least 
15 participants are assigned to Arm C and have received pembrolizumab by Week 7. 
The following general information regarding pembrolizumab infusion is applicable to 
participants in Arms B and C and Part 4 of Arm A: 
• Pembrolizumab may be administered up to 3 days before or after the scheduled 
Day 1 of each cycle due to administrative reasons.  
• Pembrolizumab will be administered as a dose of 200 mg using a 30-minute IV 
infusion.  Sites should make every effort to target infusion timing to be as close to 
30 minutes as possible.  However, given the variability of infusion pumps from 
site to site, a window between -5 minutes and +10 minutes is permitted (i.e., 
infusion time is 30 [-5/+10] minutes). 
• The Pharmacy Manual contains specific instructions for the preparation of the 
pembrolizumab infusion and administration of the infusion solution.   
6.5.1. 
Schedule Modification Guidelines for Pembrolizumab (Arms B 
and C and Part 4 of Arm A) 
AEs (both non-serious and serious) associated with pembrolizumab exposure may 
represent an immunologic etiology.  These AEs may occur shortly after the first dose or 
several months after the last dose of treatment.  Table 15 lists severe or life-threatening 
AEs and conditions that preclude the start of pembrolizumab treatment or require that 
pembrolizumab treatment be withheld for drug-related toxicities.  If pembrolizumab 
cannot be started at Week 4 Day 1 due to an AE, participants assigned to Arm B or to 
Arm C may receive their first dose of pembrolizumab on Week 7 Day 1, as long as 
permitted per Table 15.  When pembrolizumab is given after progressive disease in Arm 
A, the day of the first pembrolizumab dose is designated as Pembrolizumab Week 1 Day 
1. See Appendix 9 for supportive care guidelines for management of pembrolizumab 
toxicities. 
Dosing interruptions are permitted in cases of medical/surgical events or logistical 
reasons not related to study therapy (e.g., elective surgery, unrelated medical events, 
participant vacation, and/or holidays).  Participants should be placed back on study 
therapy by the next scheduled infusion 3 weeks later, unless otherwise discussed with the 
Sponsor.  The reason for interruption should be documented in the participant’s study 
record. 


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6.6. 
Preparation/Handling/Storage/Accountability 
It is the Investigator/institution’s responsibility to establish a system for handling both IPs 
(lete-cel and pembrolizumab) to ensure that: 
1. Deliveries of the IP are correctly received by a responsible person.  Deliveries are 
recorded. 
2. The Investigator (or designee) must confirm appropriate temperature conditions have 
been maintained during transit for all IP received and any discrepancies are reported 
and resolved before use of the IP. 
3. The participant’s T-cell product (lete-cel) received at the site from the manufacturer 
will be stored at ≤ -130°C until ordered by the Investigator (or designee) to be 
infused. 
4. Only participants enrolled in the study may receive IP and only authorized site staff 
may supply or administer IP.  All IP must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled 
storage conditions with access limited to the Investigator and authorized site staff. 
5. The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for IP accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records). 
6. Further guidance and information for the final disposition of unused IP are provided 
in the SRM and/or Drug Product and Infusion Manual.  
• 
Under normal conditions of handling and administration, IP is not expected 
to pose significant safety risks to site staff.  Take adequate precautions to 
avoid direct eye or skin contact and the generation of aerosols or mists.  In 
the case of unintentional occupational exposure notify the monitor, Medical 
Monitor, and/or GSK study contact. 
• 
A Material Safety Data Sheet (MSDS)/equivalent document describing 
occupational hazards and recommended handling precautions will either be 
provided to the Investigator, where this is required by local laws, or is 
available upon request from GSK. 
Precaution will be taken to avoid direct contact with the IP.   
6.7. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label (unblinded) study.  This study does not include randomization. 
Upon completion of the required screening assessments, eligible participants will be 
registered into the Registration and Medication Ordering System (RAMOS), the GSK 
Interactive Response Technology (IRT), by the investigator or authorized site staff.  
RAMOS allows study sites to register and assign participants.  Arm assignment will be 
done centrally using an assignment schedule generated by the GSK Clinical Statistics 
Department, which will assign all participants with NSCLC lacking actionable genetic 
aberrations into Arm A or Arm B and all participants with NSCLC with actionable 
genetic aberrations (per NCCN guidelines), to Arm C.   


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6.8. 
Study Intervention Compliance 
Lete-cel and pembrolizumab will be intravenously administered to participants at 
investigational sites by trained personnel.  Administration will be documented in source 
documents and reported in the electronic case report form (eCRF). 
6.9. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter [OTC] or prescription medicines, 
vitamins, probiotics, and/or herbal supplements) that the participant is receiving at the 
time of enrollment or receives during the study must be recorded in the eCRF along with: 
• 
the reason for use 
• 
dates of administration including start and end dates 
• 
the dose and frequency 
The Medical Monitor (or designee) should be contacted if there are any questions 
regarding concomitant or prior therapy. 
Participants must abstain from taking prescription or non-prescription drugs (including 
vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a 
potential enzyme-inducer) or 5 half-lives (whichever is longer) before the start of study 
intervention until completion of the follow-up visit, unless, in the opinion of the 
Investigator and Sponsor, the medication will not interfere with the study.  
Paracetamol / acetaminophen at doses of 2 grams/day is permitted for use any time 
during the study, unless prohibited by the Investigator.  
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement 
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic 
treatment and is allowed.  
An intermediate SoC line of therapy between leukapheresis (Part 2) and treatment 
(Part 3) at the time of disease progression is allowed if all of the conditions in Section 6.2 
are met. 
Other concomitant medication may be considered on a case-by-case basis by the 
Investigator in consultation with the Medical Monitor (or designee). 
6.9.1. 
Prohibited Concomitant Medication and Treatment 
The following anti-cancer 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 therapy.   
Participants should also not undergo anti-cancer locoregional therapies, such as surgical 
resection or non-palliative radiation. In the case of participants with mixed responses 
(e.g. shrinking target lesions with new non-target lesion, mixed response, etc.), the use of 


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anti-cancer locoregional therapies should be discussed with the GSK medical monitor.  If 
any non-protocol anti-cancer therapies are used before confirmation of disease 
progression, the participant will be considered as having met the primary endpoint for 
efficacy and will be rolled over to the LTFU study (GSK Study 208750) or to Part 5 of 
this study (if not yet enrolled in the LTFU study).  
Supportive chemo- or local therapy (e.g., radiotherapy, cryotherapy, etc.) may be 
administered between leukapheresis and the start of lymphodepletion.  In this case, 
mandatory wash-out periods (Table 12) must be respected. 
An intermediate SoC line of therapy between leukapheresis (Part 2) and treatment 
(Part 3) at the time of disease progression is allowed if all of the conditions in Section 6.2 
are met. 
Systemic steroids may abrogate the effects of the T-cell therapy (lete-cel) and, therefore, 
are discouraged unless required to manage CRS (Section 10.9.5) or other significant 
immune-mediated AEs.  According to local SoC or American Society of Clinical 
Oncology guidelines [Basch, 2011], steroids may be used as anti-emetics before 
cyclophosphamide but must be discontinued no later than 3 days prior to infusion of lete-
cel.  Topical steroids for cutaneous application, inhaled steroidal treatments, and 
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency are 
permitted. 
Participants may receive other medications that the Investigator deems to be medically 
necessary in agreement with the Sponsor’s Medical Monitor (or designee). 
See Section 5.2 for wash-out and excluded treatments prior to leukapheresis or 
lymphodepleting chemotherapy.  
Medications or vaccinations specifically prohibited in the exclusion criteria (Section 5.2) 
are not allowed during this trial.  Administration of live vaccine during the period of 
infusion of fludarabine, cyclophosphamide or lete-cel, and for at least three months after 
last dose of any of these agents is prohibited. If there is a clinical indication for any 
medication specifically prohibited during the trial, discontinuation from trial therapy may 
be required.  The Investigator should discuss any questions regarding this aspect with the 
Sponsor.  The final decision on any supportive therapy or vaccination rests with the 
Investigator and/or the participant's primary physician.  However, the decision to 
continue the participant on study treatment requires the mutual agreement of the 
Investigator, the Sponsor, and the participant. 
All concomitant medications received within 28 days prior to the first dose of 
pembrolizumab and up to 30 days after the last dose of study treatment should be 
recorded.  Concomitant medications administered beyond 30 days after the last dose of 
study treatment should be recorded if given as treatment for SAEs and AEs of special 
interest (AESIs) as defined in Section 8.4.4.  


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6.9.2. 
Permitted Concomitant Medication and Treatment 
Lesion sites previously requiring radiotherapy should be recorded prior to 
lymphodepleting chemotherapy.  Palliative radiation (e.g., for pain relief to non-
measurable lesions, non-target lesions present at Baseline, etc.) is permitted during the 
study.  However, lesion sites requiring radiotherapy after lete-cel infusion should be 
evaluated as to whether that indicates disease progression. 
Other treatment that the Investigator considers necessary for a participant’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 participant at high risk for vaccine-preventable 
disease (or member of the participant’s household), consult an infectious disease 
specialist or guidance such as the Centers for Disease Control and Prevention (CDC) 
Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Before 
immunizing a participant against SAR-CoV-2 (COVID-19) it is requested that you 
contact the study Sponsor. 
The following will be recorded on the appropriate eCRF pages: 
• All prescription and non-prescription medications, vitamins, herbal and nutritional 
supplements taken by the participant during the 30 days prior to Screening will be 
recorded at the Screening Phase visit. 
• All prior anti-cancer treatments taken by the participant must be recorded 
regardless of time. 
• All concomitant medications taken by the participant while in the Interventional 
Phase. 
• Use of any mutagenic agents or investigational agents must be reported. 
Any changes to concomitant medication regimens should be recorded throughout the 
study in the eCRF.  
Recommendations for participants on therapeutic anticoagulants: 
• Before proceeding with lymphodepletion, participants on therapeutic anticoagulants 
should be switched from long-acting to short-acting formulations, wherever possible. 
Long-acting anticoagulants can significantly potentiate bleeding risk during CRS. 
• If platelet counts drop below 100,000/μL in participants undergoing study treatment, 
dual-acting anticoagulants should be discontinued. 
• If platelet counts drop below 50,000/μL in participants undergoing study treatment, all 
anticoagulants should be discontinued unless a patient has a recent thrombosis. 
• If platelet counts drop below 50,000/μL in participants undergoing study treatment and 
the patient has a recent thrombosis, anticoagulants may be continued, but the dose should 
be reduced or platelet transfusions should be administered. 


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6.9.3. 
Rescue Medications and Supportive Care 
Participants should receive appropriate supportive care measures as deemed necessary by 
the treating Investigator.  Suggested supportive care measures for the management of 
AEs with potential immunologic etiology are outlined along with the dose modification 
guidelines in Section 6.10.  Where appropriate, these guidelines include the use of oral or 
IV treatment with corticosteroids, as well as additional anti-inflammatory agents if 
symptoms do not improve with administration of corticosteroids.  Note that several 
courses of steroid tapering may be necessary as symptoms may worsen when the steroid 
dose is decreased.  For each disorder, attempts should be made to rule out other causes 
such as metastatic disease or bacterial or viral infection, which might require additional 
supportive care.  The treatment guidelines are intended to be applied when the 
Investigator determines the events to be related to study treatment.  
It may be necessary to perform conditional procedures such as bronchoscopy, endoscopy, 
or skin photography as part of evaluation of the event.  
6.10. 
Dose Modification 
6.10.1. 
Modification Guidelines for Lete-cel (All Treatment Arms) 
Because lete-cel is administered as a single infusion in all treatment arms, dose 
modification is not applicable to lete-cel.  
6.10.2. 
Guidelines for Pembrolizumab Withholding and Discontinuation 
Pembrolizumab may cause severe or life-threatening infusion reactions including severe 
hypersensitivity or anaphylaxis.  Signs and symptoms usually develop during or shortly 
after drug infusion and generally resolve completely within 24 hours after completion of 
infusion.  Dose modification and toxicity management guidelines on pembrolizumab 
associated infusion reaction are provided in Table 15. 
AEs (both non-serious and serious) associated with pembrolizumab exposure may 
represent an immunologic etiology.  These AEs may occur shortly after the first dose or 
several months after the last dose of treatment.  Table 15 lists severe or life-threatening 
AEs and conditions that preclude starting pembrolizumab treatment or require that 
pembrolizumab treatment be withheld for toxicities related to lete-cel or pembrolizumab.  
If pembrolizumab cannot be started at Week 4 Day 1 due to an AE, participants assigned 
to Arm B or to Arm C may receive their first dose of pembrolizumab on Week 7 Day 1, 
as long as permitted per Table 15.  For participants in Part 4 of Arm A, the day of first 
pembrolizumab infusion is designated as Pembrolizumab Week 1 Day 1.  See Appendix 
9 for supportive care guidelines for management of pembrolizumab toxicities. 
Pembrolizumab may be interrupted for situations other than treatment-related AEs. 
Dosing interruptions are permitted in the case of medical/surgical events or logistical 
reasons not related to study therapy (e.g., elective surgery, unrelated medical events, 
participant vacation, and/or holidays).  Participants should be placed back on study 
therapy by the next scheduled infusion 3 weeks later, unless otherwise discussed with the 
Sponsor.  The reason for interruption should be documented in the participant's study 


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record.  The treatment restart ICF will be signed only by participants who restart 
pembrolizumab after a temporary discontinuation.


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Table 15 
Dose Modification Guidelines and Toxicity Management Guidelines for Immune-Related Adverse Events 
Associated with Study Treatment 
General instructions: 
1. 
Corticosteroid taper should be initiated upon AE improving to Grade 1 or less; the taper should take at least 4 weeks. 
2. 
For situations in which pembrolizumab has been withheld, pembrolizumab can be resumed after the AE has been reduced to Grade 1 or 0 and the corticosteroid has been 
tapered. Pembrolizumab should be permanently discontinued if the AE does not resolve within 12 weeks after the last dose or if corticosteroids cannot be reduced to ≤10 mg 
prednisone or equivalent per day within 12 weeks.  
3. 
For severe and/or life-threatening immune-related AEs (irAEs), IV corticosteroid should be initiated and then followed by oral steroid. Other immunosuppressive 
treatment should be initiated if irAEs cannot be controlled by corticosteroids. 
Immune-related AEs 
Toxicity Grade or 
condition (CTCAE 
v4.03) 
Action taken with regard to 
pembrolizumab 
irAE management with 
corticosteroid and/or 
other therapies  
Monitoring and follow-up  
Pneumonitis  
Grade 2 
Withhold  
Administer corticosteroids 
(initial dose of 1 to 2 mg/kg 
prednisone or equivalent) 
followed by taper. 
 
Monitor participant for signs and symptoms of 
pneumonitis. 
Evaluate participant with suspected 
pneumonitis with radiographic imaging and 
initiate corticosteroid treatment. 
Add prophylactic antibiotics for opportunistic 
infections. 
Grade 3 or 4, or 
recurrent Grade 2 
Permanently discontinue 
Diarrhea / Colitis  
Grade 2 or 3 
Withhold 
Administer corticosteroids 
(initial dose of 1 to 2 mg/kg 
prednisone or equivalent) 
followed by taper. 
 
Monitor participant for signs and symptoms of 
enterocolitis (i.e., diarrhea, abdominal pain, 
blood or mucus in stool with or without fever). 
Monitor participant for signs and symptoms of 
bowel perforation (i.e., peritoneal signs and 
ileus). 
GI consultation and endoscopy to rule out 
colitis should be considered for participant with 
≥ Grade 2 diarrhea if colitis is suspected.  
Participant with diarrhea/colitis should be 
advised to drink liberal quantities of clear 
fluids.  If sufficient oral fluid intake is not 
feasible, fluid and electrolytes should be given 
via IV infusion. 
Grade 4, or recurrent 
Grade 3 
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Immune-related AEs 
Toxicity Grade or 
condition (CTCAE 
v4.03) 
Action taken with regard to 
pembrolizumab 
irAE management with 
corticosteroid and/or 
other therapies  
Monitoring and follow-up  
AST / ALT elevation or 
Increased bilirubin 
Grade 2 
Withhold 
Administer corticosteroids 
(initial dose of 0.5 to 1 mg/kg 
prednisone or equivalent) 
followed by taper. 
Monitor with liver function tests (weekly or 
more frequently until liver enzyme value 
returns to Baseline or is stable). 
Grade 3 or 4  
Permanently discontinue 
Administer corticosteroids 
(initial dose of 1 to 2 mg/kg 
prednisone or equivalent) 
followed by taper. 
Type 1 diabetes mellitus 
(T1DM) or hyperglycemia 
 
New onset T1DM or 
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of -cell 
failure 
Withhold 
Initiate insulin replacement 
therapy for participant with 
T1DM.  
Administer anti-
hyperglycemic to participant 
with hyperglycemia. 
Monitor participant for hyperglycemia or other 
signs and symptoms of diabetes. 
Hypophysitis 
Grade 2 
Withhold 
Administer corticosteroids 
and initiate hormonal 
replacements as clinically 
indicated.   
Monitor participant for signs and symptoms of 
hypophysitis (including hypopituitarism and 
adrenal insufficiency).  
Grade 3 or 4  
Withhold or permanently discontinue1  
Hyperthyroidism  
Grade 2 
Continue  
Treat with non-selective beta-
blockers (e.g., propranolol) or 
thionamides as appropriate.  
Monitor participant for signs and symptoms of 
thyroid disorders.  
Grade 3 or 4  
Withhold or permanently discontinue1 
Hypothyroidism 
Grade 2, 3, or 4 
Continue  
Initiate thyroid replacement 
hormones (e.g., 
levothyroxine or liothyroinine) 
per SoC. 
Monitor participant for signs and symptoms of 
thyroid disorders.  
Nephritis and Renal 
dysfunction 
Grade 2 
Withhold  
Administer corticosteroids 
(prednisone 1 to 2 mg/kg or 
equivalent) followed by taper. 
Monitor participant for changes in renal 
function. 
Grade 3 or 4  
Permanently discontinue 
Neurological Toxicities 
Grade 2 
Withhold  
Based on severity of AE, 
administer corticosteroids. 
Ensure adequate evaluation of the participant 
to confirm etiology and/or exclude other 
causes. 
Grade 3 or 4  
Permanently discontinue 
Myocarditis 
Grade 1  
Withhold 


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Immune-related AEs 
Toxicity Grade or 
condition (CTCAE 
v4.03) 
Action taken with regard to 
pembrolizumab 
irAE management with 
corticosteroid and/or 
other therapies  
Monitoring and follow-up  
Grade 2, 3 or 4 
Permanently discontinue 
Based on severity of AE, 
administer corticosteroids. 
Ensure adequate evaluation of the participant 
to confirm etiology and/or exclude other 
causes. 
Exfoliative Dermatologic 
Conditions 
Suspected SJS, TEN, 
or DRESS 
Withhold  
Based on severity of AE, 
administer corticosteroids. 
Ensure adequate evaluation of the participant 
to confirm etiology and/or exclude other 
causes. 
Confirmed SJS, TEN, or 
DRESS 
Permanently discontinue 
All other irAEs 
Intolerable/persistent 
Grade 2 
Withhold 
Based on type and severity 
of AE, administer 
corticosteroids.  
Ensure adequate evaluation of the participant 
to confirm etiology and/or exclude other 
causes. 
 
Grade 3 
Withhold or discontinue based on the 
type of event.  Events that require 
discontinuation include, but are not 
limited to, encephalitis and other 
clinically important iRAEs (eg. vasculitis 
and sclerosing cholangitis). 
Grade 4 or recurrent 
Grade 3  
Permanently discontinue 
Cytokine release 
syndrome (CRS) 
Grade 2 or 3 
Withhold until Grade ≤1 
See Table 24 
See Table 24 
Grade 4 
 
 
 
Permanently discontinue 
 
 
 Immune Effector Cell-
Associated Neurotoxicity 
Syndrome (ICANS) 
Grade 1 persisting 
beyond 24 hrs or 
associated with 
concurrent Grade 2 
CRS 
Withhold until resolution 
See Section 10.9.8 
See Section 10.9.8 
Grade 3 or 4 
Permanently discontinue 
Pancytopenia/aplastic 
anemia 
See Section 10.9.7 
See Section 10.9.7 
See Section 10.9.7 
See Section 10.9.7 


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Immune-related AEs 
Toxicity Grade or 
condition (CTCAE 
v4.03) 
Action taken with regard to 
pembrolizumab 
irAE management with 
corticosteroid and/or 
other therapies  
Monitoring and follow-up  
Insertional oncogenesis 
See Section 8.3.5 
See Section 8.3.5 
See Section 8.3.5 
See Section 8.3.5 
Replication competent 
lentivirus (RCL) 
See Section 8.3.5 
See Section 8.3.5 
See Section 8.3.5 
See Section 8.3.5 
1. Withhold or permanently discontinue pembrolizumab at the discretion of the Investigator or treating physician.   
NOTE: When withholding of pembrolizumab is required because of Grade 3 or 4 immune-related endocrinopathy, pembrolizumab may be resumed when AE resolves to ≤ Grade 2 
and is controlled with hormonal replacement therapy (or metabolic control is achieved in the case of T1DM).   
 
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CRS = cytokine release syndrome; CTCAE = Common Terminology Criteria 
for Adverse Events; DRESS=Drug Rash with Eosinophilia and Systemic Symptoms; GI = gastrointestinal; ICANS=Immune Effector Cell-Associated Neurotoxicity Syndrome; irAE = 
immune-related AE; IV = intravenous; RCL = replication competent lentivirus; SJS=Stevens-Johnson Syndrome; SoC = standard of care; T1DM = type 1 diabetes mellitus; TEN=Toxic 
Epidermal Necrolysis.  


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Table 16 
Pembrolizumab Infusion Reaction Dose Modification and Treatment Guidelines 
NCI CTCAE Grade (v4.03) 
Treatment 
Premedication at 
Subsequent Dosing 
Grade 1 
Mild reaction; infusion interruption not 
indicated; intervention not indicated 
Increase monitoring of vital signs as medically indicated until the participant is deemed medically 
stable in the opinion of the Investigator. 
None 
Grade 2 
Requires therapy or infusion interruption but 
responds promptly to symptomatic treatment 
(e.g., antihistamines, NSAIDs, narcotics, IV 
fluids); prophylactic medications indicated for 
≤24 hrs 
Stop Infusion. 
Additional appropriate medical therapy may include, but are not limited to, the following: 
IV fluids; Antihistamines; NSAIDs; Acetaminophen; Narcotics. 
Increase monitoring of vital signs as medically indicated until the participant is deemed medically 
stable in the opinion of the Investigator. 
If symptoms resolve within 1 hour of stopping drug infusion, the infusion may be restarted at 50% of 
the original infusion rate (e.g., from 100 mL/hour to 50 mL/hour). Otherwise, dosing will be held until 
symptoms resolve and the participant should be premedicated for the next scheduled dose. 
Participants who develop Grade 2 toxicity despite adequate premedication should be permanently 
discontinued from further study drug treatment. 
At 1.5 hours 
(±30 minutes) prior to 
infusion of 
pembrolizumab, the 
participant may be 
premedicated with 
diphenhydramine 50 mg 
po (or equivalent dose of 
antihistamine). 
Also, acetaminophen 500 
to 1000 mg po (or 
equivalent dose of 
analgesic) may be given. 
Grades 3 or 4 
Grade 3: 
Prolonged (i.e., not rapidly responsive to 
symptomatic medication and/or brief 
interruption of infusion); recurrence of 
symptoms following initial improvement; 
hospitalization indicated for other clinical 
sequelae (e.g., renal impairment, pulmonary 
infiltrates) 
Grade 4: 
Life-threatening; pressor or ventilator support 
indicated 
Stop Infusion. 
Additional appropriate medical therapy may include, but are not limited to, the following: 
Epinephrine**; IV fluids; Antihistamines; NSAIDs; Acetaminophen; Narcotics; Oxygen; Pressors, 
Corticosteroids. 
Increase monitoring of vital signs as medically indicated until the participant is deemed medically 
stable in the opinion of the Investigator. 
Hospitalization may be indicated. 
Participant is permanently discontinued from further study drug treatment. 
 
**In cases of anaphylaxis, epinephrine should be used immediately. 
 
No subsequent dosing 
Appropriate resuscitation equipment should be available at the bedside, and a physician must be readily available during pembrolizumab infusion. For further information, please 
refer to the CTCAE (v4.03) at http://ctep.cancer.gov. 
 
Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; IV = intravenous; NCI = National Cancer Institute; NSAID = non-steroidal anti-inflammatory drug. 


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In accordance with the FDA and European Medicines Agency (EMA) requirements for 
gene therapy clinical trials, all participants completing the Interventional Phase of the 
study will be rolled over to a LTFU protocol (GSK Study 208750) for observation of 
delayed AEs and survival for 15 years post lete-cel infusion. If not yet enrolled in the 
LTFU protocol, participants will be followed per LTFU schedule under this protocol 
(Part 5) until enrolled in LTFU protocol (see Table 8). 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
Lete-cel is administered as a single infusion and as such individual stopping rules apply 
only to those participants receiving pembrolizumab treatment. 
Discontinuation of pembrolizumab does not represent withdrawal from the study. 
Participants will receive pembrolizumab treatment as described in Section 6.4.4 and 
Section 6.5, unless one of the following events occurs: disease progression (as 
determined by RECIST v1.1), death, or unacceptable toxicity, including meeting stopping 
criteria for liver chemistry abnormalities defined in Section 7.1.1, and QTc prolongation 
defined in Section 7.1.2. 
In addition, study treatment may be permanently discontinued for any of the following 
reasons: 
a. 
Deviation(s) from the protocol 
b. Withdrawal of consent by participant (or proxy) 
c. 
Discretion of the Investigator 
d. Participant is lost to follow-up 
e. 
Closure or termination of the study 
f. 
Intercurrent illness that prevents further administration of study treatment(s) 
g. Recurrent Grade 2 pneumonitis 
h. Discontinuation of treatment may be considered for participants who have attained a 
confirmed complete response (CR) and have been treated for at least 8 cycles (at 
least 24 weeks), receiving at least 2 doses of pembrolizumab beyond the date when 
the initial CR was declared.   
Treatment will be considered complete after 35 cycles (approximately 2 years) of 
pembrolizumab administration unless any of the above events occur.  
Note: The number of treatments is calculated starting with the first dose of 
pembrolizumab. 
The primary reason for permanent discontinuation of study treatment must be 
documented in the participant’s medical records and eCRF.  All participants who 


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discontinue study treatment will have safety assessments at the time of discontinuation, at 
the EoT visit (Table 7), and during additional follow-up in the LTFU protocol (GSK 
Study 208750) or Part 5 of this study (LTFU).  See the SoA (Section 1.3) for data to be 
collected at the time of discontinuation of study intervention, and at the EoT visit. 
Permanently discontinued participants will not remain in the study and will be rolled over 
into the LTFU protocol (GSK Study 208750) or Part 5 of this study (LTFU).    
Group Pausing Criteria 
Throughout the study, safety data will be reviewed on an ongoing basis by the internal 
SRT (Section 8.3.1).   
All SAEs and ≥ Grade 3 AEs possibly associated with either lete-cel or pembrolizumab 
will be closely monitored.  Additionally, periodic safety reviews will be undertaken by 
the Sponsor. 
It is expected that AEs will occur frequently in this population due to the underlying 
disease and that these can be serious.  The review of AEs, and any decision to 
prematurely stop participant enrollment, will be determined by the SRT and reviewed by 
the relevant IRB. 
Study will pause enrollment and stop treatment for all participants if any of the following 
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]. 
• A case of documented symptomatic progressive cerebral edema confirmed by an 
expert neurological examination and CT/MRI, that is not responding to 
treatment.  
• A biologically functional positive Replication Competent Lentivirus (RCL) after 
2 confirmed positive tests by PCR. 
• Death directly attributed to lete-cel by the Investigator  
Premature study termination may occur if: 
• The Investigator, Sponsor, Medical Monitor, SRT, or any independent review 
board or regulatory body decides for any reason that participant safety may be 
compromised by continuing the study. 
• Premature study termination may occur if the Sponsor decides to discontinue the 
development of the intervention used in this study. 
7.1.1. 
Liver Chemistry Monitoring Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
participant safety and to evaluate liver event etiology.  Liver stopping criteria for 
participants who have received pembrolizumab either as study treatment in Arms B or C 


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or as pembrolizumab therapy received after disease progression after lete-cel infusion in 
Arm A (Figure 1) are described in Table 15, Section 6.10.2. 
Refer to Table 15 for stopping and monitoring details. 
The following Level 1 and Level 2 monitoring are required for all participants in all 
treatment arms.   
7.1.1.1. 
Liver Event Monitoring 
Level 1 Monitoring 
In the event that a participant develops elevations in liver function test (LFT) parameter 
values as defined below, an increase in liver chemistry monitoring (i.e., at weekly 
intervals) will apply.  
Table 17 
Liver Chemistry Monitoring Criteria Level 1 
Liver Chemistry Monitoring Criteria Level 1 
Criteria 
Actions 
ALT ≥3x ULN and ≥1.5x baseline value but 
ALT <5x ULN and <2x baseline value 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, AST, alkaline phosphatase, bilirubin) until they 
resolve, stabilize, or return to within baseline.  
• 
If, during monitoring, ALT increases to 5xULN and 2x 
baseline value, or remains ≥3x ULN and ≥1.5x baseline 
value 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. 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; GSK = GlaxoSmithKline 
(Sponsor); ULN = upper limit of normal. 
 
Level 2 Monitoring 
In the event that the participant develops elevations in LFT parameters as defined below, 
an increase in liver chemistry monitoring to more frequent intervals (i.e., twice weekly) 
will apply.  


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Table 18 
Liver Chemistry Monitoring Criteria Level 2 
Liver Chemistry Monitoring Criteria Level 2 
ALT Absolute 
Both ALT 5xULN and 2x baseline value 
ALT Increase 
Both ALT 3xULN and ≥1.5x baseline value that persists for 4 weeks 
Bilirubin1, 2 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INR2  
ALT 3xULN and INR >1.5 
Symptomatic3 
ALT 3xULN and 1.5x baseline value associated with symptoms (new or worsening) believed 
to be related to liver injury or hypersensitivity 
Required Actions and Follow-Up Assessments  
Actions 
Follow-Up Assessments 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event eCRF and complete an 
SAE data collection tool if the event also meets the 
criteria for an SAE2 
• 
Perform liver event follow-up assessments  
• 
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:  
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, bilirubin, INR) and perform liver event 
follow-up assessments within 24 hrs 
• 
Monitor participant twice weekly until liver 
chemistries resolve, stabilize or return to within 
baseline (pre-Gene Therapy) 
• 
A specialist or hepatology consultation is 
recommended 
For all other criteria:  
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, bilirubin, INR) and perform liver event 
follow-up assessments within 24 to 72 hrs  
• 
Monitor participant 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 transaminase values show 
downward trend 
• 
Serum CPK and LDH 
• 
Fractionate bilirubin, if total bilirubin 2xULN 
• 
If possible, obtain peripheral blood to check for 
persistence of genetically modified cells 
• 
Obtain CBC with differential to assess 
eosinophilia 
• 
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 including 
acetaminophen, herbal remedies, and other over 
the counter medications 
• 
Record alcohol use on the liver event alcohol 
intake eCRF 
For bilirubin or INR criteria: 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total IgG or gamma 
globulins. 
• 
Liver imaging (ultrasound, magnetic resonance, or 
computed tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver Imaging 
and/or Liver Biopsy eCRFs. 
 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood cell (count); 
CPK = creatine phosphokinase; eCRF = electronic case report form; GSK = GlaxoSmithKline (Sponsor); 
HBsAg = hepatitis B surface antigen; IgG = immunoglobulin G; IgM = immunoglobulin M; INR = international 
normalized ratio; LDH = lactate dehydrogenase; RNA = ribonucleic acid; SAE = serious adverse event; 
ULN = upper limit of normal. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for the subject if ALT  3xULN and bilirubin  2xULN. 
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; 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); and Hepatitis E IgM antibody. 
7.1.1.2. 
Study Intervention Restart or Rechallenge after Liver Stopping Criteria 
Are Met 
If a participant meets liver chemistry stopping criteria, do not restart/rechallenge 
participant with study intervention unless: 
GSK Medical Governance approval is granted 
Ethics and/or IRB approval is obtained, if required, and 
Separate consent for intervention restart/rechallenge is signed by the participant 
Refer to Table 15 for details.  
If GSK Medical Governance approval to restart/rechallenge participant with study 
treatment is not granted, then participant must permanently discontinue study 
treatment and roll over into the LTFU study (GSK Study 208750) or Part 5 of this 
study (LTFU) for additional follow-up assessments. 
 
7.1.2. 
QTcF Stopping Criteria 
The stopping and restarting criteria for QTcF abnormalities described in this section will 
be applicable only to participants who have received pembrolizumab either as study 
treatment (Arms B or C) or after disease progression after lete-cel infusion (Arm A; see 
Figure 1) because lete-cel is administered as a single dose. 
In case of need to confirm QTcF prolongations, the QTcF should be based on the average 
of triplicate ECG readings obtained over a brief (e.g., 5 to 10 minutes) recording period.   
If a participant meets the corrected QTcF interval duration criteria below, study 
treatment(s) will be discontinued: 
• QTcF >530 msec (with or without underlying Bundle Branch Block),  
OR, 
• QTcF change from baseline of >60 msec 
See the SoA (Section 1.3) for data to be collected at the time of intervention and 
discontinuation.  After discontinuation from the study, the participant enters the LTFU 
protocol (GSK Study 208750) or Part 5 of this study (LTFU). 


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7.1.3. 
Temporary Discontinuation 
Lete-cel is administered as a single dose via IV infusion.  In the event of severe reactions 
potentially associated with liver toxicities during infusion, the infusion may be 
interrupted.  Please refer to the current Drug Product and Infusion Manual for details of 
dose administration. Please refer to Section 8 for safety assessments and monitoring; 
Section 10.3 for reporting of adverse events; and Section 10.9 for supportive care 
guidance on T-cell infusion, CRS and other potential risks.  
Infusion-related reactions Grade 3 or higher during infusion should be reported to 
Sponsor promptly: 
- 
GSK CGT Patient Supply Coordinator by e-mail (GSK.CELL@gsk.com) or  
by phone +1-833-GSK-CELL (+1 833-475-2355) or +44 800-026-6295 (for 
European countries);  
- 
Medical Monitor or designee (contact information provided in SRM).  
In participants with infusion-related reaction ≤ Grade 2, infusion may be restarted once 
resolved to < Grade 1, following instructions in the Drug Product and Infusion Manual.  
Refer to 6.10.2 for information about pembrolizumab dosing interruptions.  
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the study at any time at his/her own request or 
may be withdrawn at any time at the discretion of the Investigator for safety, 
behavioral, compliance or administrative reasons.  This is expected to be 
uncommon. 
• At the time of discontinuing from the interventional portion of the study, if 
possible, an End of Treatment / Interventional Phase visit should be conducted, as 
shown in the SoA.  See the SoA (Section 1.3) for data to be collected at the time 
of discontinuation from the interventional portion of the study and for any further 
evaluations that need to be completed at EoT.  After discontinuation from the 
interventional portion of the study, the participant enters the LTFU study (GSK 
Study 208750) or, if not yet enrolled in 208750, Part 5 of this study (LTFU). See 
Section 4.1.5 for details. 
• The participant will be permanently discontinued from the study once enrolled in 
the separate LTFU study (GSK Study 208750). Participants who fail to consent to 
the 208750 study within 6 months of completing the End of Treatment / 
Interventional Phase visit will be withdrawn from Study 208471.    
• If the participant withdraws consent for disclosure of future information, the 
Sponsor may retain and continue to use any data collected before the withdrawal 
of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the site 
study records. 


T M F -1 4 1 3 2 1 0 0  
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1 0 2  
 
7. 3.  
L o st t o F oll o w -u p  
A partici pa nt  will be c o nsi dere d l ost t o f oll o w -u p if he or s he re peate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.  
T he f oll o wi n g acti o ns m ust be ta ke n if a p artici pa nt fails t o ret ur n t o t he cli nic f or a 
re q uire d st u d y visit: 
•  T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ul e t he misse d visit as 
s o o n as p ossi ble a n d c o u nsel t he partici pa nt o n t h e i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ul e a n d ascert ai n w het her or n ot t he partici pa nt wis hes t o 
a n d/ or s h o ul d c o nti n ue i n t he st u d y. 
•  Bef ore a p artici pa nt is dee me d l ost t o f oll o w-u p , t he I n vesti gat or ( or desi g nee) 
m ust ma ke e ver y eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 
tele p h o ne calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n 
maili n g a d dress or l ocal e q ui vale nt met h o ds) .  T h ese c o ntact atte m pts s h o ul d be 
d oc u me nte d i n t he partici pa nt’s me dical r ec or d.  
•  S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o 
ha ve wit h dra w n fr o m t he st u d y.  
Disc o nti n uati o n of s pecific sites or of t he st u d y as a w h ole are ha n dle d as  d escri be d i n 
A p pe n di x 1 . 
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  
All st u d y assess me n ts a n d t heir ti mi n gs are s u m m arize d i n Secti o n 1. 3 : 
Ta ble 2 : Scree ni n g  
Ta ble 3 : L y m p h o d e pleti o n a n d Treat me nt : I nter ve nti o nal P hase  
Ta ble 5 : Pe m br oliz u ma b T hera p y F oll o wi n g Disease Pr o gressi o n after Lete -cel I nf usi o n 
(Part 4 Ar m A O nl y)  
Ta ble 7 : E n d of Treat me nt  
Ta ble 8 : L o n g -Ter m F ol l o w-U p  
A d here n ce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A, is 
esse ntial a n d re q uire d f or st u d y c o n d u ct. Pr ot oc ol wai vers or e x e m pti o ns are n ot all o we d 
e x ce pt f or i m me diate safet y c o ncer ns.  
I m me diat e safet y c o ncer ns s h o ul d be disc usse d wit h t he S p o ns or u p o n occ urre nce or 
a ware ness t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y treat me nt.  
C CI
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1 0 3  
 
All scree ni n g e v al uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y criteria. T h e I n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all parti ci pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.  
I nf or me d c o ns e nt m ust be si g ne d b y a partici pa nt bef ore a n y st u d y re q uir e d pr oce d ures 
are perf or m e d . H o we v er, pr oce d ures c o n d u cte d as part of t he r o uti ne cli nical 
ma na ge me nt (e. g., i ma gi n g st u dies) a n d c o n d ucte d pri or t o si g ni n g of t he st u d y i nf or me d 
c o nse nt ma y be use d f or scree ni n g/ bas el i ne assess me nts pr o vi de d t he pr oce d ure f ulfills 
t he pr ot oc ol defi ne d s p ecificati o ns a n d has bee n p erf or me d wit hi n t he pr ot oc ol i n dicate d 
ti mefra me.  
If assess me nts are sc h e d ule d f or t he sa me n o mi nal ti me, t he n t he assess me nts s h o ul d 
occ ur i n t he f oll o wi n g or der:  
1.  1 2 -lea d E C G  
2.  Vital si g ns  
3.  Bl o o d dra ws  
Re peat or u nsc h e d ule d sa m ples ma y be t a ke n f or safet y reas o ns or f or tec h nical iss ues 
wit h t he sa m ples.  
8. 1.  
Effi c a c y A s s e s s m e nt s  
8. 1. 1.  
T u m or R e s p o n s e A s s e s s m e nt s  
T u m or assess me nts f or res p o nse a n d pr o gressi o n  will be e val uate d acc or di n g t o 
R E CI S T  v 1. 1 [Eise n ha uer , 2 0 0 9] a n d 
 [Se y m o ur , 2 0 1 7] (see S ecti o n 1 0. 1 0. 2 ). 
Dia g n ostic q u alit y C T sca n of c hest/a b d o m e n/ pel vis wit h  c o ntrast is re q uir e d as detaile d 
i n Secti o n 1. 3 . 
I ma gi n g s ca ns of t he c hest, a b d o me n, a n d pel vis s h o ul d be perf or me d at b aseli ne (i.e., 
wit hi n 2 wee ks bef ore l y m p h o de pleti o n) a n d all s u bse q ue nt visits  as i n dicate d i n S o A 
( Secti o n 1. 3 ).  Brai n i ma gi n g is re q uir e d f or all partici pa nts  at baseli ne ( wit hi n 4 wee ks 
bef ore l y m p h o de pl eti o n) a n d as cli nicall y i n dicate d  t hereafter (refer t o S ecti o n 1 0. 9. 8 ).  
Acce pt a ble i ma gi n g m o dalities f or t his st u d y i ncl u de:  
•  Dia g n ostic -q ualit y C T sca n wit h oral a n d/ or I V i o di nate d c o ntrast of t he c h est a n d 
a b d o me n/ pel vis ( C T is t he preferre d m o dalit y f or t u m or assess me nts)  
•  M RI of t he a b d o me n/ pel vis ac q uire d bef ore a n d after ga d oli ni u m c o ntrast a ge nt 
a d mi nistrati o n  
•  N o n -c o ntrast e n ha nce d C T of c hest/a b d o me n/ pel vis if a partici pa nt is 
c o ntrai n dicate d f or b ot h C T a n d M RI c o ntrast or if t he y h a ve re nal c o m pr o mise  
•  A d diti o nal sca ns ( C T/ M RI) s h o ul d be ac q uir e d f or a n y ot her areas of 
s us pecte d/ k n o w n diseas e per site S o C, if cli nicall y i n dicate d  
•  Di gital p h ot o gra p hs of s ki n lesi o ns i ncl u di n g a r ul er f or esti mati n g t he size of t he 
lesi o n 
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1 0 4  
 
T hr o u g h o ut t he st u d y, t h e sa me i ma gi n g m o dalit y a n d i ma ge -ac q uisiti o n pr ot oc ol 
(i ncl u di n g t he us e of I V c o ntrast) s h o ul d be use d c o nsiste ntl y acr oss all ti me p oi nts f or a n 
i n di vi d ual partici pa nt  t o all o w u nif or m c o m paris o n of lesi o ns.   
I n v esti gat ors will assess t u m or res p o nse acc or di n g t o 
 f or cli nical decisi o n 
ma ki n g  (A p pe n di x 1 0 , S ecti o n 1 0. 1 0. 2 ) a n d f or e x pl orat or y e val u ati o ns .  T u m or 
meas ure me nts f or eac h p artici pa nt  s h o ul d be perf or me d b y t h e sa me I n v esti gat or or 
ra di ol o gist (t o t he e xte nt t hat t his is feasi ble).   
T o all o w ti me f or t he i m m u ne res p o nse t o bec o me a p pare nt a n d f or p ote ntial tra nsie nt 
i nfla m mat or y reacti o n of t he disease t o t he treat me nt (‘t u m or flare’), res p o nse will n ot be 
assesse d bef ore 4 w ee ks p ost i nf usi o n of lete-cel u nless t here is u ne q ui v ocal cli nical 
e vi de nce of deteri orati o n.  Res p o nses s h o ul d be c o nfir me d b y re p eat i ma gi n g sca n 
perf or me d n ot earlier t ha n 4 wee ks a n d n ot later t ha n t he ne xt sc he d ule d i ma gi n g sca n 
after t he criteria f or res p o nse was first met.  Pr o gressi o n s h o ul d be c o nfir me d b y re peat 
i ma gi ng sca n p erf or me d n ot earlier t ha n 4 wee ks a n d n ot later t ha n 8 wee ks after t he 
criteria f or pr o gressi o n  w as first met.  Deter mi nati o ns of disease pr o gressi o n  will be 
base d u p o n R E CI S T  v 1. 1 ; h o we ver, f or c o nti n uati o n of pe m br oliz u ma b partici pa nts will 
be f oll o we d b y 
.  
R E CI S T v 1. 1 will be use d i n t he assess me nt of disease b ur de n (tar get a n d n o n -tar get 
lesi o ns deter mi nati o n) at Scree ni n g  a n d as t he pri mar y m eas ure of t u m or res p o nse 
e n d poi nts.  
A descri pti o n of t he a d a ptati o ns a n d  
 pr o cess is pr o vi de d i n A p pe n di x 1 0 . 
Di gital c o pies of all ( n o n -l oss y c o m pr esse d, prefera bl y DI C O M f or m atte d) sca ns a n d 
p h ot o gra p hs ( wit h e m be d de d r ulers) m ust be mai nt ai ne d at t he I n v esti gati ve site as 
s o urce d oc u m e nts. All sca ns (sc he d ule d a n d u nsc h e d ule d) are s u b mitte d electr o nicall y t o 
t he ce ntral i ma gi n g ve n d or f or Q C, st ora ge, a n d p ote ntial a nal ysis.  T h e pr ocess f or t u m or 
i ma gi n g a n d tr a ns missi o n t o t he ce ntral i ma gi n g ve n d or are detaile d i n t he I ma gi n g 
Ma n ual.  T u m or i ma gi n g is str o n gl y preferre d t o b e ac q uir e d b y I V/ oral c o ntrast 
e n ha nce d C T.  F or t he a b d o me n a n d pel vis, c o ntrast -e n ha nce d M RI ma y be use d w he n 
C T wit h i o di nate d c o ntrast is c o ntrai n dicate d, or w he n ma n date d b y l o cal practice.  M RI 
is t he preferre d m o dalit y f or i ma gi n g t h e brai n a n d s pi ne.  F D G P E T/ C T will be c ollecte d 
ce ntrall y if perf or me d as part of t he site ’s r o uti ne disease ma na ge ment, at Scree ni n g  a n d 
w hilst o n st u d y , b ut will n ot re place C T s ca ns.   
8. 1. 2.  
L o n g -T er m F oll o w -u p  
All partici pa nt s will be f oll o we d f or s ur vi val a n d f or 1 5 years after T -cell (lete-cel ) 
i nf usi o n f or o bser vati o n of dela ye d A Es i n acc or da nce wit h F D A re q uire m e nts f or ge ne 
t hera p y cli nical trials [F D A , 2 02 0 b; F D A , 2 0 1 0].  Dela ye d A Es, will be c ollecte d i n t he 
I nter ve nti o nal P hase of t he st u d y u ntil disease pr o gressi o n, as defi n e d b y  
 (see 
S ecti o n 1 0. 1 0. 2 ) a n d t hereafter i n t he L T F U pr ot o c ol ( G S K St u d y 2 0 8 7 5 0). If n ot yet 
e nr olle d i n t he L T F U pr ot oc ol, partici pa nts will  be pr o visi o nall y f oll o we d p er L T F U 
sc he d ule u n der t his pr ot oc ol ( Part 5) u ntil e nr olle d i n L T F U pr ot oc ol (s ee S ecti o n 4. 1. 5  
a n d Ta ble 8 ).   
 
C CI
C CI
C CI
C CI


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Delayed AEs are defined as those events that fall into one or more of the 6 categories 
listed below and which occur either after disease progression or the last patient visit, 
whichever occurs first; and are considered related to GSK’s gene modified cell therapy. 
Delayed AEs will be collected until 5 years have elapsed from last T-cell infusion, or 
until patient dies, withdraws consent or is deemed lost to follow-up. Delayed AEs will be 
recorded in the CRF if reported by the patient or investigator between years 6 – 15. 
Specifically, emergence of any of the following new clinical conditions reported or 
observed and the action taken will be reported to the Sponsor as a delayed AE: 
• 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 cell 
therapy 


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8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations 
A complete physical examination will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal, and neurological systems. Neurological 
assessment for encephalopathy syndrome (ES) must be performed as described in the 
SoA (Section 1.3) and Section 10.9.8. Height (Screening only) and weight will also be 
measured and recorded. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2. 
Vital Signs 
• Blood pressure, pulse measurements, respiratory rate, and body temperature 
should be assessed per institutional standards. These will be assessed as per the 
SoA (Section 1.3) and recorded in the eCRF. Methods per institutional standards 
should be consistent throughout the course of the study. Manual techniques will 
be used only if an automated device is not available. 
• Vital signs will be measured more frequently if warranted by clinical condition of 
the participant.  On days where vital signs are measured multiple times, 
temperature does not need to be repeated unless clinically indicated.   
• On lete-cel infusion day, pulse oximetry should be taken according to Table 3.  
On pembrolizumab infusion days, pulse oximetry should be taken pre- and post-
infusion. 
 
8.2.3. 
Cardiac Assessments  
All cardiac assessments will be performed locally.  
The following assessments will be conducted in order to monitor participant safety:  
• An ECHO or MUGA scan will be performed at screening and baseline (Table 2 
and Table 3) 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.  
• Serum troponin and NT-proBNP / BNP as markers for cardiac health will be 
assessed prior to initiation of lymphodepletion. 
Reports of cardiac events in participants with cardiac or pericardial disease following 
treatment with lete-cel will continue to be monitored through normal proactive 
Pharmacovigilance. 
The 12-lead ECGs will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 


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and QTcF intervals.  Refer to Section 7 for QTcF withdrawal criteria and additional 
QTcF readings that may be necessary. 
Participants with clinically significant cardiovascular risk factors such as but not limited 
to: 
- 
prior cardiac insult (ie, prior myocardial infarct and prior coronary 
revascularization)  
- 
significant valvular disease  
- 
low ejection fraction  
- 
cardiomyopathy  
- 
history of heart failure  
- 
significant cardiac arrhythmias  
- 
history of cardiac toxicity from prior therapies 
- 
baseline tumor masses in close proximity to the cardiac muscle 
must: 
• undergo evaluation by a cardiologist prior to lymphodepletion 
• be monitored by inpatient continuous cardiac telemetry for a minimum of 3 days 
post T-cell infusion and as long as deemed necessary by the Investigator.  
 
In these participants with clinically significant cardiovascular risk factors, all reports of 
cardiac events following T-cell infusion will be monitored through proactive 
pharmacovigilance to determine causality.  Supportive treatment for these participants 
will be provided per standard clinical practice guidelines. 
8.2.4. 
Pulmonary Assessments  
Participants should be considered for pulmonary consultation prior to lymphodepletion, 
which may include pulmonary function tests. 
Participants deemed at high risk for pulmonary complications per pulmonologist should 
have closer post-infusion monitoring during the following periods:  
- 
post T-cell infusion, for a minimum of 3 days and as long as deemed necessary by 
the Investigator 
- 
if CRS is suspected, for the first week and until symptoms are improving or an 
alternative diagnosis is confirmed 
and should include:  
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• Close monitoring of fluid balance 


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• Continuous cardiac telemetry monitoring. 
Participants, who have an airway that may be compromised should be assessed prior to 
lymphodepletion, including considerations such as speech and swallow evaluation, 
anaesthesia consultation, or consideration for closer post-infusion monitoring (as above) 
in the event their airway may be compromised due to tumor inflammation, prior 
surgery/radiation, decreased consciousness, infection or other cause. 
8.2.5. 
Clinical Safety Laboratory Assessments 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed 
and to the SoA (Section 1.3) for the timing and frequency.  
• 
The Investigator must review the laboratory report, document this review, 
and record any clinically relevant changes occurring during the study in the 
AE section of the eCRF.  The laboratory reports must be filed with the source 
documents.  Clinically significant abnormal laboratory findings are those 
which are not associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 30 days after the last dose of study 
intervention should be repeated until the values return to normal or baseline 
or are no longer considered significantly abnormal by the Investigator or 
Medical Monitor.  
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified and the 
Sponsor notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2, must 
be conducted in accordance with the Laboratory Manual and the SoA.  
8.3. 
Safety Monitoring 
Safety will be assessed in a continuous manner (See Appendix 9 for general 
considerations on supportive care).   
The Sponsor will review the safety throughout the conduct of the study and share the data 
on a frequent basis with the Investigators (Investigator teleconference) and a Safety 
Review Team (SRT).   
Safety data will be proactively reviewed for each participant and summarized by 
participant and in aggregate across participants by treatment arm.  The toxicities observed 
will be reviewed in the context of the known safety profiles of lete-cel and 
pembrolizumab.   
Most toxicities associated with lymphodepleting chemotherapy and lete-cel occur in the 
first 4 weeks of therapy.  Resolution of these toxicities is generally observed by Week 4 
post T-cell infusion (approximately 6 weeks after the initiation of lymphodepleting 
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When pembrolizumab is administered in combination with lete-cel, it is expected that the 
checkpoint blockade will activate the immune system.  This could lead to enhanced 
antitumor activity as well as toxicity. 
In the absence of a clear alternative etiology (e.g., chemotherapy and concomitant 
medications, disease progression, infections, etc.), AEs should be considered potentially 
immune-related.  Immune-related AEs may include diarrhea/colitis, rash, hepatitis, 
GVHD, CRS, secondary pancytopenia, pneumonitis, endocrinopathies, nephritis, and any 
other manifestations that may indicate an immune-related phenomenon.  Any clinical 
imaging performed to assess AEs may be collected centrally for review. 
Based on review of the safety data, a decision whether to suspend treatment for an 
in-depth evaluation will be made collaboratively with input from the Sponsor, the 
Investigators, and the SRT. 
Additional criteria for possible suspension of treatment/enrollment are also provided in 
Section 8.3.3. 
8.3.1. 
Safety Review Team (SRT) 
The SRT ensures a safety review process for the ongoing evaluation of GSK products 
undergoing clinical development and provides a forum for a proactive, aggregate, and 
holistic evaluation of the safety profile of the investigational product over the 
developmental lifecycle of the product, with systematic, periodic, and documented 
reviews. 
In accordance with routine pharmacovigilance, the SRT, which will include study team 
members will review unblinded safety data, including clinical laboratory parameters and 
AEs, at appropriate intervals during the period of study conduct.  Recommendations on 
study modification, pausing the study and/or pausing enrollment will be provided by the 
SRT.  The roles and accountabilities, and the process for safety review and meeting 
frequency will be specified in the SRT charter. 
8.3.1.1. 
Mandated Study Pause Due to GBS 
The occurrence of any event of GBS will mandate a pause in enrollment and stopping 
lete-cel treatment for all participant within the lete-cel clinical studies. The case must be 
diagnosed by a neurologist as GBS according to diagnostic guidance for GBS [Fokke, 
2014]. 
8.3.2. 
Treatment Limiting Toxicities Definition 
The following toxicities are considered to be treatment limiting toxicities (TLTs): 
• Any ≥ Grade 4 AE (excluding events listed in this section as not considered to be 
TLTs) 
• Grade 3 non-infectious pneumonitis 


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• Any other Grade 3 AE (excluding pneumonitis and events listed in Table 15 and 
in this section as not considered to be TLTs), that does not improve to Grade 2 
within 7 days after onset despite medical management and supportive care 
The following toxicities are NOT considered to be TLTs: 
• Grade 3 or 4 leukopenia, neutropenia, or febrile neutropenia 
• Grade 3 or 4 thrombocytopenia not associated with significant bleeding;  
• Grade 3 anemia that is not aplastic 
• Grade 3 laboratory abnormality determined to be not clinically significant by the 
Investigator 
• Grade 3 or 4 fever and chills 
• Grade 3 or 4 hypoalbuminemia or abnormal electrolytes that are responding to 
supplementation/correction 
• AE related to the cancer or its progression 
Any AE not listed above may be considered a TLT after consultation with the Sponsor, 
the Investigators, and the SRT based on the emerging safety profile. 
In addition, if a participant in Arms B or C could not be administered pembrolizumab on 
Day 22 (Week 4 Day 1) due to an AE and the said AE has not resolved to an acceptable 
level by the next scheduled dosing day (Week 7 Day 1), the participant will be 
discontinued from treatment and the AE will be considered a TLT. 
8.3.3. 
Treatment Limiting Toxicities for Pembrolizumab 
To evaluate the safety of the combination therapy in Arms B or C, TLTs will be assessed 
for the 3-week period as follows: 
• 
from Week 4 to Week 7 for participants who initiated pembrolizumab on 
Week 4 Day 1  
• 
from Week 7 to Week 10 for participants who initiated pembrolizumab on 
Week 7 Day 1  
8.3.4. 
Monitoring and Management of Replication-Competent Lentivirus 
Replication Competent Lentivirus (RCL) is a theoretical risk associated with the use of 
lentiviral vectors; no RCL has ever been reported in vivo and/or in vitro.  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 
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Updated γ retroviral packaging systems have not been associated with RCR.  However, in 
a study with Rhesus monkeys, 3 out of 10 animals 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 participants post infusion with any 
product involving a retrovirus [FDA, 2020a; FDA, 2020b; FDA, 2010]. 
A RCL may be generated during the production phase or subsequently after introduction 
of vector transduced cells into the participant.  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 participant 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 participant’s virus, or could increase the replication rate or pathogenicity of the 
participant’s virus.  Since the development of a strain with increased pathogenicity would 
pose greater risk to both the participant 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 participant [FDA, 2020a; FDA, 
2020b; FDA, 2010].  However, because the probability and characteristics of an RCL are 
unknown, no concrete plans have been put in place.  
The following approaches have been discussed for participant management: 
• Provide targeted antiretroviral therapies based on genotyping of the RCL. 
• Intensive follow-up of participant in consultation with FDA, and other Regulatory 
Authorities, National Institute of Health, gene therapy experts, study 
Investigators, and HIV physicians. 
8.3.4.1. 
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 lentiviral vector, whereby RCL testing will be performed on vector 
supernatant and end of production (EOP) cells by or under the direction of the 
manufacturing facility responsible for manufacturing and releasing the vector. 
• 
The T-cell product, whereby VSV-G qPCR testing will be carried out for release 
and biological RCL testing will also be performed. 


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• 
Participant PBMCs will be collected at time points indicated in the SoA.  Once 
persistence of gene modified cells is below the level of detection for 2 
consecutive assessments, RCL sample collection will discontinue.  
If VSV-G DNA copies are detected at any time point in the first-year post-
infusion, the safety monitoring protocol will be triggered.  Participant samples will 
continue to be tested for VSV-G DNA copies until VSV-G DNA copies are not 
detected for 3 consecutive annual assessments. 
8.3.4.2. 
Safety Monitoring Results 
If a positive VSV-G DNA signal is obtained, the Investigator will be informed and the 
participant 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 GSK’s SRT and Safety 
Governance Board will take place. 
If the second test is positive, infusions for all participants receiving T-cells (lete-cel) 
modified with the same vector lot will be postponed.  Participants 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 lete-cel infusions will be paused.  An action plan will 
be discussed with FDA and other Regulatory Authorities and experts as appropriate.  
Additional participants will not be treated until such time as a plan is agreed upon, 
completed, and reviewed. 
8.3.5. 
Testing for Persistence of Transduced T cells and Insertional 
Oncogenesis 
Peripheral blood mononuclear cell (PBMC) samples will be collected for monitoring 
persistence of gene modified cells.  The samples will be tested using a DNA PCR-based 
method to detect the presence of the Psi gene, which is part of the lentiviral vector used to 
transduce T-cells.  The Sponsor will notify the site once the participants’ transduced T 
cells are below the level of detection for 2 consecutive visit assessments. Following this, 
RCL and persistence sample collection will discontinue.  
At the first instance of >1% of PBMCs testing positive for the WPRE or Psi gene at or 
after 1 year post-infusion, the participant’s PBMCs will be evaluated for integration site 
analysis.  Integration site analysis assesses clonality and the possibility of insertional 
oncogenesis.  While insertional oncogenesis is a potential risk in T cells transduced with 
a lentiviral vector, monitoring for it follows the recommendations set forth in the FDA 
and EMA guidances [FDA, 2020a; FDA, 2020b; EMA, 2009]. 
If there is clonal dominance in the genetically modified T-cell population (either 
monoclonality or oligoclonality), the persistence of gene modified cells and integration 
site assessment will be repeated within 3 months on a new sample.   


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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 GSK’s SRT and Safety Governance Board to develop a 
monitoring plan specific to the health care risk and strategies to inform  participants, 
investigators, FDA, and other regulators of the findings.  
If the integration site analysis indicates polyclonality of the genetically modified T-cell 
population, then study and persistence monitoring will continue as scheduled. Integration 
site assessment will only be repeated if there is a sudden increase in persistence or if there 
is any suspicion/report of potential hematological malignancy. 
In all cases of SAE that occur after T cell infusion, a transgene copy (persistence) sample 
must be obtained if feasible. 
8.3.6. 
Monitoring and Management for Demyelinating Neuropathy and 
Other Neurological Events 
Obtain a neurological consultation for participants with Grade 2 or higher neurologic 
events of ≥ 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 electromyography (EMG), lumbar puncture, 
and/or infectious panel to guide management and follow up. 
8.4. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
The Investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study (see Section 7).  
AEs will be coded using the standard Medical Dictionary for Regulatory Activities 
(MedDRA) and grouped by system organ class (SOC) and will be graded by the 
Investigator according to the NCI-CTCAE (v4.03). 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
Collection of AEs and SAE will be performed as follows: 
• 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 to leukapheresis (Part 1 and 
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. 


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• After leukapheresis until the lymphodepletion, all SAEs assessed as related to study 
participation 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. 
• From lymphodepletion to end of study (Part 3 and Part 4), all AEs and SAEs will be 
collected at the time points specified in the SoA (Section 1.3). 
• All SAEs will be recorded and reported to the Sponsor (or designee) immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 3.  
• The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
it being available. 
• The AESIs  (Section 8.4.4) and will be reported to the Sponsor (or designee) 
immediately and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. 
• All AEs or AESIs (listed in Section 8.4.4) from the time of lymphodepletion through 
30 days following cessation of study treatment or end of study, whichever is later.  
• All SAEs must be collected through 90 days following cessation of study treatment, 
or 30 days following cessation of study treatment if the participant initiates new 
anticancer therapy, whichever is earlier.  
• All pregnancies and exposure during breastfeeding, from the start of chemotherapy 
(lymphodepletion regimen) through the contraception period (see Section 5.3.3) 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. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence.  
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts.  All SAEs, including AESIs (as defined in 
Section 8.4.4), will be followed until the event is resolved, stabilized, otherwise 
explained, or the participant is lost to follow-up (defined in Section 7.3).  Further 
information on follow-up procedures is given in Appendix 3. 


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8.4.4. 
Adverse Events of Special Interest (AESIs) 
AESIs for this trial should be reported to GSK within 24 hours via e-mail to the Medical 
Monitor. The AESIs include:  
• 
CRS, pneumonitis/pneumonia, GVHD, Guillain Barre syndrome (GBS) or acute 
inflammatory demyelinating polyneuropathy (AIDP), pancytopenia/aplastic anemia, 
and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Grade 1 
persisting beyond 24 hours or associated with concurrent CRS; or Grade 2 or higher, 
Treatment-related inflammatory response at tumor site(s), and Grade 4 neutropenia 
lasting ≥28 days (Appendix 9). 
o For pancytopenia/aplastic anemia, this will be treated as an AESI with expedited 
reporting within 24 hours if any of the below events occur: 
• Requiring a transfusion (e.g., platelets or red blood cells [RBC]) 
• Occurs after bone marrow reconstitution following the lymphodepletion 
regimen 
• Any Grade 3 or 4 cytopenia following lymphodepletion lasting more than 
2 weeks with G-CSF support.  
o Any Grade ≥3 CRS or GVHD, and all cases of GBS or acute inflammatory 
demyelinating polyneuropathy must be reported as an SAE within 24 hours. 
• 
An overdose of pembrolizumab, as defined in Section 8.5, that is not associated with 
clinical symptoms or abnormal laboratory results. 
• 
An elevated AST or ALT laboratory value that is greater than or equal to 3X the 
upper limit of normal and an elevated total bilirubin laboratory value that is greater 
than or equal to 2X the upper limit of normal and, at the same time, an alkaline 
phosphatase (ALP) laboratory value that is less than 2X the upper limit of normal, as 
determined by way of protocol-specified laboratory testing or unscheduled 
laboratory testing. 
Note:  These criteria are based upon available regulatory guidance documents.  The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may 
require an additional evaluation for an underlying etiology.  The trial site guidance 
for assessment and follow-up of these criteria can be made available.  It may also be 
appropriate to conduct additional evaluation for an underlying etiology in the setting 
of abnormalities of liver blood tests including AST, ALT, bilirubin, and alkaline 
phosphatase that do not meet the criteria noted above.  In these cases, the decision to 
proceed with additional evaluation will be made through consultation between the 
study investigators and the Sponsor Medical Monitor or designee.  However, 
abnormalities of liver blood tests that do not meet the criteria noted above are not 
AESIs for this trial. 


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8.4.5. 
Reporting Criteria during Long-Term Follow-Up (Years 1 through 
15) 
Delayed Adverse Events: 
 
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 (lete-cel) for observation of 
delayed AEs according to FDA and EMA guidance [FDA, 2020a; FDA, 2020b; EMA, 
2009].  Delayed AEs are defined as those events that fall into one or more of the 6 
categories listed below and which occur either after disease progression or last 
Interventional Phase visit, whichever occurs first, and are considered related to GSK’s 
gene modified cell therapy.  Delayed AEs will be collected as part of the LTFU phase of 
the study or in the LTFU Study 208750, contingent upon formal transfer of participant to 
Study 208750:  
 
Delayed AEs will be collected until 5 years have elapsed from last T-cell infusion, or 
until patient dies, withdraws consent or is deemed lost to follow-up. Delayed AEs will be 
recorded in the CRF if reported by the patient or investigator between years 6 – 15. 
The 6 categories of delayed AEs are: 
• New malignancies 
• New incidence or exacerbation of a preexisting neurological disorder 
• New incidence or exacerbation of a prior rheumatologic or other autoimmune 
disorder 
• New incidence of a hematologic disorder 
• New incidence of an infection (potentially related to gene-modified cell therapy) 
• Unanticipated illness or hospitalization deemed related to gene modified cell 
therapy 
For participants who received pembrolizumab and who have an allogeneic stem cell 
transplant (allo-SCT) within 24 months of last dose of pembrolizumab, specific AEs (all 
grades, and regardless of relationship to study drug) will be collected for 18 months from 
the date of the transplant, to include: 
• Graft-versus-host-disease  
• Veno-occlusive disease  
• Febrile syndrome (a steroid-requiring febrile illness without an infectious cause) 
• Encephalitis  
Additional medically important AEs post-allo-SCT may be reported at the investigator’s 
discretion. 


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If a participant is monitored in this protocol post disease progression, s/he will only be 
monitored for the AEs detailed above. 
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) 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) 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). 
8.4.6. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation.  The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and Sponsor policy and forwarded to investigators as necessary. 
An Investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRB/IEC, if appropriate according to local requirements. 
8.4.7. 
Pregnancy 
Contraception is defined from the start of study intervention and for the period defined 
below, based on the study treatments received:  
Study Intervention Received 
Contraception to continue from start of study intervention through 
longest of all intervals defined below based on all treatments received  
Fludarabine 
6 months after last dose of fludarabine 
Cyclophosphamide 
Time after last dose of cyclophosphamide: 
Females – 12 months 
Males – 6 months 


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NY-ESO-1 specific T cell infusion 
A minimum of 12 months after NY-ESO-1 specific T-cell infusion, or until 
persistence of gene modified cells in the participant’s blood is below the 
level of detection for 2 consecutive assessments, whichever is longer. 
Pembrolizumab 
A minimum of 4 months after the last dose of pembrolizumab, if this time 
frame is longer than the duration of contraception required in the context of 
fludarabine, cyclophosphamide and NY-ESO-1 specific T cells. 
 
The Sponsor will notify the site once the participant’s persistence is below the level of 
detection for 2 consecutive assessments.  
• 
Should female participant or female partner of male participant become pregnant 
during the contraception period, details of pregnancies need to be collected and 
reported as described in Section 10.4.  
• If a pregnancy is reported, the Investigator should inform GSK within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 
4. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
• If appropriate, the investigator should advise fertile male participants to consider 
collecting and storing viable sperm prior to undergoing lymphodepletion, given 
that cyclophosphamide may result in partial (oligospermia) or total (azoospermia) 
sterility 
8.4.8. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Section 10.3.3 (Appendix 3), and all deaths, 
whether or not they are considered SAEs, specific CV and Death sections of the eCRF 
will be required to be completed.  These sections include questions regarding 
cardiovascular (including sudden cardiac death) and non-cardiovascular death.  
The CV eCRFs are presented as queries in response to reporting of certain CV MedDRA 
terms.  The CV information should be recorded in the specific cardiovascular section of 
the eCRF within one week of receipt of a CV Event data query prompting its completion.  
The Death page of the eCRF 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. 
8.4.9. 
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 symptoms cannot be determined 
as exclusively due to the progression of the underlying malignancy or does not fit the 
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If t here is a n y u ncertai nt y a b o ut an A E bei n g d ue o nl y t o t he diseas e u n der st u d y, it 
s h o ul d be re p orte d as a n A E or S A E. 
8. 5.  
Tr e at m e nt  of O v er d o s e  
Let e -cel is a d mi nistere d as a si n gl e d ose b y trai n e d pers o n nel at t he i n vesti gati o nal sites 
i n t his st u d y.  
A n o ver d ose of pe m br oli z u ma b is defi ne d as a n y d ose of ≥1 0 0 0 m g (≥5 ti mes t he 
i n dicate d d ose of 2 0 0 m g ) Q 3 W.  N o s pecific i nf or mati o n is a vaila ble o n t he treat me nt of 
o ver d ose of pe m br oliz u ma b.  I n t h e e ve nt of o ver d ose, t he partici p a nt s h o ul d be o bser ve d 
cl osel y f or si g ns of t o xicit y.  A p pr o priate s u p p orti ve treat me nt s h o ul d be pr o vi de d if 
cli nicall y i n dicat e d.   
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t h e I n vesti gat or 
i n c o ns ultati o n wit h t he S p o ns or’s Me dical M o nit or base d o n t he cli nical e val uati o n of 
the partici pa nt.  
8. 6.  
P h ar m a c o ki n eti c s  
As descri be d i n  Secti o n  8. 9. 3 , t he p har mac o ki n etics ( le vels, e x pa nsi o n, persiste nce) of 
e n gi n eere d T -cells will be meas ur e d a n d will be use d t o deri ve P K para met ers .  T he 
ti mi n g of assess me nt is pr o vi de d i n t he S o A ( Secti o n 1. 3 ).  
•  
W h ole bl o o d sa m ple s will be c ollecte d f or meas ure me nt of lete-cel 
tra ns d uce d cell q ua ntities as s pecifie d i n t he S o A ( Secti o n 1. 3 ). I nstr ucti o ns 
f or t he c ollecti o n a n d ha n dli n g of bi ol o gi cal sa m pl es will be pr o vi de d b y t h e 
S p o ns or .  T he act ual dat e a n d ti me ( 2 4 -h o ur cl o c k ti me) of eac h sa m ple will 
be rec or de d . 
T he f oll o wi n g P K p ara m eters of lete-cel will be c o m p ute d , as data per mit :  
•  
C ma x: ma xi m u m tra ns ge ne e x pa nsi o n 
•  
T ma x, ti me of C ma x  
•  
A U C( 0 -t), area u n d er t he c o nce ntr ati o n/ persiste nce ti me c ur ve fr o m 0 t o ti me 
t. 
Ser u m c o nce ntr ati o ns of pe m br oliz u ma b will be o btai ne d pre a n d p ost i nf usi o n  a n d 
sa m ples f or e v al uati o n of pe m br oliz u ma b 
 will als o be 
c ollecte d as d escri be d i n t he S o A  ( Secti o n 1. 3 ).  
8. 7.  
P h ar m a c o d y n a mi c s  
Researc h c yt o ki ne assess me nts a n d ot her bi o mar kers meas ur e me nts (see Secti o n 8. 9 ) 
ma y b e e val u ate d f or p h ar mac o d y na mic relati o ns hi ps wit h lete-cel a d mi nistrati o n.  
C CI
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8. 9.  
Bi o m ar k er s  
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8. 9. 1.  
C yt o ki n e a n d S ol u bl e F a ct or s A n al y si s  
Ser u m is c ollecte d at Bas eli ne, a n d at eac h visit p ost lete-cel i nf usi o n, at desi g nate d 
ti me p oi nts wit hi n S o A, t o all o w f or meas ure me nt of c yt o ki n es i n t he bl o o d.  Ser u m is 
als o c ollecte d fr o m partici pa nts  wit h s us pecte d C R S, wit h sa m ples bei n g ta ke n e ver y d a y  
f or t he first w ee k a n d a p pr o xi matel y e ver y ot h er da y t h ereafter u ntil s y m pt o ms are 
C CI


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i m pr o vi n g or a n alter nati ve dia g n osis is c o nfir me d ( Secti o n 1 0. 9. 5 ).  Details re gar di n g 
ser u m c ollecti o n are pr o vi de d i n t he SR M  a n d/ or La b orat or y M a n ual . 
8. 9. 2.  
T u m or Bi o p si e s  
T he effi cac y of ca ncer i m m u n ot hera p y is c o n diti o ne d b y t h e i nfiltrati o n of t u m ors b y 
acti vate d t u m or -s pecific T-cells, t he e x pressi o n of tar get a nti ge n, a n d t h e a nti ge n 
pr ocessi n g mac hi ner y t hat e na bles s urface e x pressi o n of t he a nti ge nic e pit o p e o n t he 
t u m or cell s urface.  All of t hese are necessar y f or t he acti vit y of N Y -E S O -1/ L A G E -
1a  s pecific tr a ns d uce d T cells . T he acti vit y of t hes e T -cells will i n t ur n be affect e d b y t he 
prese nce i n t he t u m or of a n i m m u n os u p pressi ve or i m m u ne -p ote ntiati n g e n vir o n me nt  i n 
t he t u m or (e. g., re g ul at or y T-cells or hel p er T cells ).  T heref ore, t h e direct e val uati o n of 
t he prese n ce of N Y -E S O -1/ L A G E -1a  s p ecific tr a ns d uce d T cells, tar get a nti ge n 
e x pressi o n a n d pr ocessi n g ma c hi ner y  (e. g., H L A e x pressi o n, etc.) , a n d t he “i m m u ne 
la n dsca pe” i nsi de t he t u m or are of great val ue f or u n dersta n di n g a n d  o pti mizi n g ca ncer 
i m m u n ot hera p y.  F or t his reas o n, i ncisi o nal, e xcisi o nal, or c ore nee dl e bi o psies are 
re q ueste d. 
Scree ni n g Bi o ps y  
Arc hi val tiss ue  fr o m t he m ost c urre nt setti n g m a y be use d f or t h e Scree ni n g  bi o ps y  if it is 
of g o o d q u alit y . If m ulti ple arc hi val s a m ples are a vaila ble, t he n t he m ost rece nt arc hi val 
sa m ple s h o ul d be use d. If a n arc hi v e d bi o ps y of t he t u m or tiss ue is n ot a vaila ble, t he n a 
fres h t u m or tiss ue bi o ps y is re q uire d f or scree ni n g. T he t u m or bi o ps y will b e scree ne d at 
t he ce ntral refere n ce la b orat or y f or e x pressi o n of t u m or a nti ge ns, N Y-E S O -1 a n d/ or, if 
teste d, L A G E-1 a. I n t he e ve nt t hat t he t u m or tiss ue sa m ples s u b mitte d f or a nti ge n 
e x pressi o n is of i ns ufficie nt q ua ntit y or q ualit y t o c o n d uct t he testi n g a n d d eter mi ne 
t u m or a nti ge n e x pressi o n pr ofile, a d diti o nal tiss ue sa m ples(s) ma y be s u b mitte d t o t he 
ce ntral la b orat or y.  
T u m or sa m ples m ust meet t he f oll o wi n g criteria : 
a. F or mali n -fi x e d paraffi n e m be d de d ( F F P E) t u m or s peci me ns i n paraffi n bl oc ks are 
preferre d. A mi ni m u m of 2 0  ( or m ore) u nst ai ne d sli des ( 5 -micr o n seri al fres h c ut) is  
re q uire d as a n alter nati ve. Patie nts wit h fe wer t ha n 2 0  u nstai ne d sli des ma y still be 
c o nsi dere d f or scree ni n g f oll o wi n g disc ussi o n wit h Me dical M o nit or . T he sites i nter nal 
pat h ol o gist s h o ul d c o nfir m > 2 0 %  t u m or c o nte nt a n d > 1. 0 m m3 t u m or v ol u me pri or t o 
s hi p me nt. 
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b. Acce pt a ble s peci me ns i ncl u de c ore n ee dle bi o psies fr o m dee p t u m or tiss u e ( mi ni m u m 
3 -5 c ores x 1 8 G or lar ger a n d a p pr o xi matel y 1 c m l o n g) or e x cisi o nal, i ncisi o nal p u nc h or 
f orce ps bi o psies f or c uta ne o us, s u bc uta ne o us or m uc osal  lesi o ns. 
c. Fi ne-n ee dle as pirati o n, br us hi n g, cell pellet fr o m pl eural eff usi o n, b o n e metastases, a n d 
la va ges are n ot a cce pta bl e. T u m or tiss ue fr o m b o n e metastasis is n ot a d vise d. 
d. Tiss ue s h o ul d be o btai ne d fr o m 1 year of c o nse nt a n d be of g o o d q ualit y o n t he basis 
of t otal a n d via ble t u m or u nless disc usse d wit h Me dical M o nit or . 
B aseli ne Bi o ps y  
A baseli ne t u m or bi o ps y o btai ne d pri or t o i nitiati n g l y m p h o de pleti n g c h e m ot hera p y will 
be ma n dat or y f or all parti ci pa nts  a n d s h o ul d meet t he f oll o wi n g criteria:  
a. Acce pta ble s peci me ns i ncl u de c ore n ee dle bi o psies fr o m dee p t u m or tiss u e ( mi ni m u m 
3 -5 c ores x 1 8 G or lar ger a n d a p pr o xi matel y 1 c m l o n g) or e x cisi o nal, i ncisi o nal p u nc h or 
f orce ps bi o psies f or c uta ne o us, s u bc uta ne o us or m uc osal lesi o ns 
b. Fi ne -n ee dle as pir ati o n, br us hi n g, cell pellet fr o m ple ural eff usi o n, b o n e metastases, a n d 
la va ges are n ot a cce pta bl e. T u m or tiss ue fr o m b o n e metastasis is n ot a d vise d.  
T h e t u m or sa m ple nee ds t o be eit her a fres hl y c oll ec te d t u m or bi o ps y or a t u m or bi o ps y 
ta ke n after c o m pleti o n of t he partici pa nt’s last li ne of t hera p y.  I n cas es w he n s uc h a 
bi o ps y is cli nicall y u nsafe t o perf or m, arc hi v al ( mea ni n g o btai ne d at earlier ti mes) t u m or 
bi o psies, prefera bl y wit hi n 9 0 da ys pri or t o i nitiati n g l y m p h o de pleti n g c h e m ot hera p y, 
ma y b e acce pte d at t he discreti o n of t he Me di cal M o nit or ( or desi g nee). T u m or tiss ue 
s h o ul d be ta ke n fr o m n o n-tar get lesi o ns.  If t his is n ot feasi ble, t he n a fres h bi o ps y of t he 
tar get lesi o n ma y be c o nsi dere d up o n c o ns ultati o n wit h t he S p o ns or’s Me dical M o nit or 
( or desi g nee).  
P ost -T -Cell I nf usi o n Bi o psies  
A ma n dat or y t u m or bi o ps y i n n o n -tar get lesi o ns will be perf or me d a) 4 wee ks aft er lete-
cel i nf usi o n a n d b) w h e n t he partici pa nt e x perie nces pr o gressi ve dise ase, u nless cli nicall y 
u nsafe t o d o s o. If t his is n ot feasi ble, t he n a fres h bi o ps y of t he tar get lesi o n ma y b e 
c o nsi dere d u p o n c o ns ultati o n wit h t he S p o ns or’s Me dical M o nit or ( or desi g nee).  
W he n p ossi ble, t he sa me lesi o n(s) s h o ul d be bi o psie d at b ot h Scre e ni n g a n d s u bse q ue nt 
ti me p oi nts.  T he a p pare nt cli nical or sca n stat us of t he lesi o n(s) bi o psie d s h o ul d be 
d oc u me nte d at t he ti me (e. g ., d ecreas e d, sta ble, i n creas e d size or acti vit y).  
A d diti o nal details re gar di n g t u m or bi o ps y  c ollecti o n a n d pr ocessi n g are pr o vi de d i n t he 
S R M  a n d/ or La b orat or y Ma n ual . 
Cli nicall y o bt ai ne d ple ural eff usi o n/ascites s a m ples ha ve bee n s h o w n t o be a ric h s o urce 
of t u m or cells, t u m or i nfiltrati n g le u k oc yt es a n d s ol u ble fact ors, c h a n ges i n w hic h ha ve 
bee n re p orte d t o c orrelat e wi t h disease pr o g n osis a n d t hera p y res p o nse.  
 
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 2 4  
 
N ote : If a v aila ble, ple ural eff usi o n or as cites fl ui d s h o ul d be c ollecte d, i n a d diti o n t o, a n d 
n ot, i nstea d of, t he re q u este d t u m or bi o psies.  
8. 9. 3.  
Tr a n s g e n e p er si st e n c e f or P K a s s e s s m e nt  
Let e -cel T -cell p har mac o ki netics i n t he peri p heral bl o o d will be meas ure d i n t he 
partici pa nts  t o esta blis h t he relati o ns hi p bet wee n persiste nce a n d res p o ns e t o lete-cel.  
Persiste nce is als o m o nit ore d as a l o n g -ter m safet y meas ure.   
T he f oll o wi n g m et h o d ol o g y  will be use d t o meas ure t he c ells: Q ua ntitati o n of tra ns d uce d 
cells b y P C R of tra ns ge n e fr o m D N A e xtracte d fr o m fr oze n P B M C s. 
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 2 5  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 2 6  
 
8. 1 0.  
R e q u e st f or A ut o p s y f or D e at h F oll o wi n g A d mi ni str ati o n of 
G e n e Tr a n sf er A g e nt s  
I n acc or da n ce wit h F D A a n d E M A g ui da nce [F D A , 2 02 0 a; E M A , 2 0 0 9 ], all partici pa nts  
e nr olle d i n t his trial are as ke d t o c o nsi der pre -a ut h orizi n g (i n a d va n ce)  a n a ut o ps y i n cas e 
of deat h, a n d a ut o psies will be re q ueste d of t he fa milies f or all partici pa nts  w h o die 
d uri n g partici pati o n i n st u dies after a d mi nistrati o n of ge ne tr a nsfer a ge nts.  T o ass ure 
c o m plia nce, g ui deli nes f or perf or mi n g a n a ut o ps y are pr o vi d e d i n t he S R M  a n d/ or 
La b orat or y M a n ual . 
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 2 7  
 
9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
9. 1.  
St ati sti c al H y p ot h e s e s  
T his is a P hase 1 b/ 2a  st u d y f oc use d o n t he s afet y, t olera bilit y, cli nical acti vit y, a n d 
w het her H L A a n d a nti ge n e x pressi o n bi o mar kers ca n i de ntif y a p o p ulati o n of partici pa nts 
wit h a d va nce d N S C L C t hat c o ul d be nefit fr o m lete-cel a d mi nistere d al o ne or i n 
c o m bi nati o n wit h pe m br oliz u ma b.   
N o f or mal statistical h y p ot heses are b ei n g teste d i n t his st u d y.  
9. 2.  
S a m pl e Si z e D et er mi n ati o n  
T he sa m ple siz e f or eac h ar m was det er mi ne d usi n g a Ba yesia n pre dicti ve a da pti ve 
desi g n t hat all o ws t he st u d y t o be m o nit ore d m or e fre q ue ntl y w hile mai ntai ni n g t he 
desire d T y pe I err or a n d p o wer. T he s a m ple siz e is base d o n testi n g t he h y p ot hesis f or 
eac h ar m se paratel y a n d n ot f or a c o m paris o n bet wee n ar ms. F or all t hree ar ms, cli nical 
res p o nse will be defi ne d as i n vesti gat or-assess e d O R R per R E CI S T v 1. 1. A n i nteri m 
a nal ysis after t h e 1 0 t h partici pa nt bec o mes e v al ua ble will be e m pl o ye d f or Ar ms A, B, 
a n d C, res pecti vel y.   
Partici pa nts wit h N S C L C lac ki n g acti o na ble ge netic a berrati o ns will be assi g ne d  t o 
Ar m  A a n d Ar m B s uc h t hat a p pr o xi matel y 1 5 partici pa nts recei ve T -cell i nf usi o n  wit hi n 
t he tar get d ose ra n ge (let e-cel ) i n Ar m A a n d a p pr o xi matel y 1 5 partici pa nts recei v e T -cell 
i nf usi o n wit hi n t he tar get d ose ra n ge  a n d pe m br oli z u ma b i n Ar m B .  Partici pa nts wit h 
N S C L C wit h acti o na ble ge n etic  a b errati o n s will be assi g n e d t o Ar m C s uc h t hat 
a p pr o xi matel y 1 5 partici pa nts recei ve T -cell i nf usi o n  a n d pe m br oliz u ma b .  Ass u mi n g 
ar o u n d 1 5 % of t h e partici pa nts e nr olle d will disc o nti n ue fr o m t he st u d y pri or  t o lete-cel 
i nf usi o n, a p pr o xi matel y 1 8 s u bjects will be e nr olle d i n eac h ar m t o e ns ure a p pr o xi matel y 
1 5 e val ua ble p artici pa nts will recei ve T -cell i nf usi o n  wit hi n t he tar get d ose ra n ge .  
E nr oll me nt will pr ocee d c o nti n u o usl y wit h n o sc h e d ule d e nr oll me nt pa us e w hile 
C CI


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conducting the interim analysis. Upon completion of the interim analysis, this protocol 
may be amended to allow for expansion. 
Analyses will be conducted for Arms A, B, and C independently. An end of study 
threshold is defined such that meeting this threshold may warrant continuing 
development in the population of interest. For each arm, Bayesian statistics will be 
employed to calculate the predictive probability of meeting the end of study threshold at 
the interim analysis (after the 10th enrolled participant per arm has received T-cell 
infusion (modified Intent-to-Treat [mITT] population) and has completed at least 2 post-
baseline disease assessments since infusion or discontinued earlier) given the responses 
that have already been observed assuming a beta prior for the binomially distributed data. 
A weak prior of beta (0.02, 0.08) is used, which is equivalent to the information present 
in 0.1 participant. 
At the interim analysis for each arm, further enrollment into the arm is recommended to 
be stopped if the predictive probability of meeting the threshold at the final analysis is 
less than 2.8%. Here, this threshold is defined as the posterior probability that the ORR is 
greater than 10% at the end of the arm is larger than 95%. This predictive probability 
aligns with observing at least 2 responders out of 10 evaluable participants, and if not 
met, serves as strong statistical evidence to stop further development of the treatment for 
the target population. 
If 4 responses out of 15 evaluable participants are observed at the final analysis, this will 
serve as evidence in favor of further development in this arm. Operating characteristics 
for a range of true population ORR are given in Table 19. The probability of reaching the 
continuing development criteria at the final analysis, given a true ORR of 30% is 68.1%. 
The inference from the Bayesian predictive probabilities of clinical activity in 
participants in each treatment arm is intended to drive decision making.  Actual decisions 
will depend on the totality of the data including clinical activity, safety, PK, and 
biomarker data. 
Table 19 
Operating Characteristics for Interim and Final Analyses for Arms A, 
B, and C 
True ORR 
Probability of passing futility at 
interim (n=10) 
Probability of reaching end of 
study threshold at final analysis 
(n=15) 
10% 
0.265 
0.054 
20% 
0.625 
0.334 
30% 
0.850 
0.681 
40% 
0.953 
0.896 
50% 
0.988 
0.976 
 


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9.3. 
Populations for Analyses 
For analysis purposes, the following populations are defined: 
Screened Population: All participants who signed an ICF to participate in the study. 
Enrolled Population: All participants who started leukapheresis procedure. 
Intent-to-treat (ITT) Population: All participants who started leukapheresis procedure.  
Modified ITT (mITT) Population: All participants who received lete-cel infusion.  This 
population will be the primary population for the efficacy analysis. 
All Evaluable Population: Defined as the study population used for decision-making at 
the interim analyses.  This population will be the primary population for interim efficacy 
analyses and include participants in the mITT population with at least 2 post-baseline 
radiological disease assessments or have progressed, died, or permanently withdrawn 
from the study if in Arm A or have progressed, died or permanently withdrawn from 
pembrolizumab if in Arm B or C.  Further details are provided in the Reporting and 
Analysis Plan (RAP). 
Safety Population: The ITT Population will be used for all safety analyses. 
Additional analysis populations may be defined in the RAP. 
9.4. 
Statistical Analyses 
9.4.1. 
Efficacy Analyses 
Table 20 
Efficacy Endpoints and Statistical Methods 
Endpoint 
Statistical Analysis Methods 
Primary 
Clinical response: ORR (according to RECIST v1.1) 
Secondary 
PFS 
DCR 
DoR 
TTR 
Exploratory 
Will be reported in the RAP 
Abbreviations: DCR = disease control rate; DoR = duration of response; ORR = overall response rate; 
PFS = progression-free survival; RAP = Reporting and Analysis Plan; TTR = time to response. 
9.4.1.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is the ORR, defined as the percentage of participants 
(mITT Population) with a CR or PR as determined by investigator assessment and 
confirmed by repeat assessment at least 4 weeks after the initial documentationas per 
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Bayesian predictive adaptive design (Lee, 2008) will be used to investigate the clinical 
activity in each treatment arm.   
Participants with unknown or missing response will be treated as non-responders, i.e., 
these participants will be included in the denominator when calculating the percentage.  
The number and types of responses, as outlined in RECIST v1.1, will be listed and 
summarized separately, as appropriate. 
The observed confirmed ORR will be reported at the interim and final analyses for each 
arm.  The estimates along with 95% Clopper-Pearson exact confidence interval (CI) will 
be provided. 
9.4.1.2. 
Secondary Efficacy Analysis 
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable 
disease (SD) for at least 6 months as per RECIST v1.1. 
Participants with unknown or missing response will be treated as non-responders, i.e., 
these participants will be included in the denominator when calculating the percentage.  
The number and types of responses, as outlined in RECIST v1.1, will be listed and 
summarized separately, as appropriate. 
PFS is defined as the time from the date of T-cell (lete-cel) infusion until the earliest date 
of disease progression as assessed by the Investigator per RECIST v1.1, or death due to 
any cause.  For the analysis of PFS, if the participant received subsequent anti-cancer 
therapy prior to the date of documented events, PFS will be censored at the last adequate 
assessment (e.g., assessment when visit level response was CR, PR, or SD) prior to the 
initiation of therapy.  Progressive disease will also be defined per RECIST v1.1 criteria.  
Otherwise, if the participant does not have a documented date of event, PFS will be 
censored at the date of the last adequate assessment.  Further details on rules for 
censoring will be provided in the RAP.  PFS will be summarized by arm using Kaplan-
Meier quantile estimates along with 2-sided 95% CIs estimated using the Brookmeyer-
Crowley method [Brookmeyer, 1982] at the time of final analysis, if data warrant. 
DoR is defined as, in the subset of participants who show a confirmed CR or PR, the time 
from first documented evidence of CR or PR until the first documented sign of disease 
progression or death.  DoR will be summarized descriptively for each arm, if data 
warrant, using Kaplan-Meier medians and quartiles.  Details on rules for censoring will 
be provided in the RAP. 
Time to response (TTR), defined as the time from the date of T-cell (lete-cel) infusion to 
the first documented evidence of response (PR or better) in the subset of participants who 
achieved a confirmed PR or CR as assessed by the Investigator. 
9.4.2. 
Safety Analyses 
All safety analyses will be performed on the ITT Population.  


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All serially collected safety endpoints (e.g., laboratory tests, vital signs, ECGs) will be 
summarized according to the scheduled, nominal visit at which they were collected and 
across all on-treatment time points using a “worst-case” analysis.  Complete details of the 
safety analyses will be provided in the RAP. 
9.4.2.1. 
Adverse Events 
AEs will be coded using the standard Medical Dictionary for Regulatory Activities 
(MedDRA) and grouped by system organ class (SOC) and will be graded by the 
Investigator according to the NCI-CTCAE (v4.03). 
Events will be summarized by frequency and proportion of total participants and by SOC 
and preferred term (PT).  Separate summaries will be given for all AEs, treatment-related 
AEs, SAEs, and AEs leading to discontinuation of study treatment and dose modification.  
In addition, AEs, if listed in the NCI-CTCAE v4.03, will be summarized by the 
maximum grade. AESIs will be further outlined in the RAP. 
The incidence of deaths and the primary cause of death will be summarized. 
9.4.2.2. 
Clinical Laboratory Evaluations 
Hematology and clinical chemistry data will be summarized using frequencies and 
proportions according to NCI-CTCAE v4.03.  Laboratory test results outside the 
reference ranges that do not have an associated NCI-CTCAE criterion will be 
summarized using proportions.  Further details will be provided in the RAP. 
9.4.2.3. 
Other Safety Measures 
Data for vital signs, ECGs, and left ventricular function (ECHO and MUGA) will be 
summarized based on predetermined criteria identified to be of potential clinical concern.  
Further details will be provided in the RAP. 
9.4.3. 
Other Analyses 
Pharmacokinetics (lete-cel persistence and pembrolizumab concentrations), 
pharmacodynamic, and biomarker and other exploratory analyses details will be 
described in the RAP.   
9.5. 
Interim Analyses 
For the primary purpose of informing future lete-cel development, separate interim 
analyses are planned for each arm after at least 10 evaluable participants are available in 
that arm. Evaluable participants are defined as participants who received a T-cell infusion 
and have either progressed, withdrawn from the study treatment, were lost to follow-up, 
or are ongoing and have completed at least two post-treatment disease assessments.  If 
enrollment is still open at the time of the interim analysis, enrollment into a treatment arm 
may be stopped early for toxicity or lack of efficacy (futility) based on the results of an 
interim analysis.  


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Futility interim analysis decision guidelines for each arm, specifying the number of 
participants with a confirmed response needed for continuing enrollment or stopping for 
futility is presented in Table 21.   
Table 21 
Decision-Making Criteria for Futility for Arms A, B, and C at the 
Interim Analysis Conducted with 10 Evaluable Participants/Arm 
Arm (N=10/Arm) 
Stop Enrollment for Futility 
if the Number of Confirmed 
Responses is Less Than or 
Equal to this Number 
Probability of Continuing 
Enrollment under H0 (10%) 
Probability of Continuing 
Enrollment under Ha 
(30%) 
Arm A or B or C 
1 
0.2639 
0.8507 
 
Based on interim analysis results, enrollment for all treatment arms (Arm A, B, or C) may 
be stopped due to futility if ≤1 confirmed response is observed in the first 10 evaluable 
participants within the arm, i.e., the predictive probability that rejecting H0 at end of 
study is small (e.g., less than 2.8% chance to have at least 4 confirmed responders out of 
15 participants who received T-cell infusion in the treatment arm).  The above criteria are 
intended as guidelines. Final decisions with respect to study conduct, including pausing 
enrollment, will be based on a comprehensive review of the totality of the data including 
safety, DCR, DoR, CR rate, and PFS as warranted by the data. 
All planned interim analyses will be described in greater detail in the RAP. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
• Applicable International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC 
by the Investigator and reviewed and approved by the IRB/IEC before the 
study is initiated.  
• 
Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and Sub-Investigators will provide the Sponsor with sufficient, accurate 
financial information as requested to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 


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10.1.3. 
Informed Consent Process 
• 
The Investigator or his/her representative will explain the nature of the study 
to the participant or his/her legally authorized representative and answer all 
questions regarding the study.  
• 
Participants must be informed that their participation is voluntary.  
Participants or their legally authorized representative will be required to sign 
a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the 
IRB/IEC or study center.  
• 
The medical record must include a statement that written informed consent 
was obtained before the participant was enrolled in the study and the date on 
which the written consent was obtained.  The authorized person obtaining the 
informed consent must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study.  
• 
Copies of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative.  
• 
Participants who are rescreened are required to sign a new ICF. 
The ICFs may contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research in accordance with SOP-GSKF-410.  The 
Investigator or authorized designee will explain to each participant the objectives of the 
exploratory research.  Participants will be told that they are free to refuse to participate 
and may withdraw their consent at any time and for any reason during the storage period.  
A separate signature will be required to document a participant’s agreement to allow any 
remaining specimens to be used for exploratory research.  Participants who decline to 
participate will not provide this separate signature. 
10.1.4. 
Data Protection 
• 
Participants will be assigned a unique identifier by the Sponsor.  Any 
participant records or datasets that are transferred to the Sponsor will contain 
the identifier only; participant names or any information which would make 
the participant identifiable will not be transferred.  
• 
The participant must be informed that his/her personal study-related data will 
be used by the Sponsor in accordance with local data protection laws.  The 
level of disclosure must also be explained to the participant.  
• 
The participant must be informed that his/her medical records may be 
examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the Sponsor, by appropriate IRB/IEC members, and 
by inspectors from regulatory authorities. 


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10.1.5. 
Dissemination of Clinical Study Data 
• 
Where required by applicable regulatory requirements, an investigator 
signatory will be identified for the approval of the clinical study report.  The 
Investigator will be provided reasonable access to statistical tables, figures, 
and relevant reports and will have the opportunity to review the complete 
study results at a GSK site or other mutually-agreeable location. 
• 
GSK will also provide the Investigator with the full summary of the study 
results.  The Investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study 
will be in accordance with GSK Policy. 
• 
GSK intends to make anonymized participant-level data from this trial 
available to external researchers for scientific analyses or to conduct further 
research that can help advance medical science or improve patient care.  This 
helps ensure the data provided by trial participants are used to maximum 
effect in the creation of knowledge and understanding. 
• 
A manuscript will be progressed for publication in the scientific literature if 
the results provide important scientific or medical knowledge. 
10.1.6. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on eCRF unless 
transmitted to the Sponsor (or designee) electronically (e.g., laboratory data).  
The Investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the eCRF.  
• 
The Investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF.  
• 
The Investigator must permit study-related monitoring, audits, IRB/IEC 
review, and regulatory agency inspections and provide direct access to source 
data documents.  
• 
The Sponsor (or designee) is responsible for the data management of this 
study including quality checking of the data.  
• 
The Sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
Monitoring details describing strategy (e.g., risk-based initiatives in 
operations and quality such as Risk Management and Mitigation Strategies 
and Analytical Risk-Based Monitoring), methods, responsibilities and 
requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the 
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• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, 
complete, and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the Investigator for 25 years from the issue of 
the final Clinical Study Report (CSR)/ equivalent summary unless local 
regulations or institutional policies require a longer retention period.  No 
records may be destroyed during the retention period without the written 
approval of the Sponsor.  No records may be transferred to another location 
or party without written notification to the Sponsor.  
10.1.7. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected.  Source documents are filed at 
the investigator’s site. 
• 
Data reported/entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies 
must be explained.  The Investigator may need to request previous medical 
records or transfer records, depending on the study.  Also, current medical 
records must be available. 
10.1.8. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include 
but are not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of 
the IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP 
guidelines 
• 
Inadequate recruitment of participants by the Investigator 
• 
Discontinuation of further study intervention development 
10.1.9. 
Publication Policy 
• 
The results of this study may be published or presented at scientific meetings.  
If this is foreseen, the Investigator agrees to submit all manuscripts or 


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abstracts to the Sponsor before submission.  This allows the Sponsor to 
protect proprietary information and to provide comments.  
• 
The Sponsor will comply with the requirements for publication of study 
results.  In accordance with standard editorial and ethical practice, the 
Sponsor will generally support publication of multicenter studies only in their 
entirety and not as individual site data.  In this case, a coordinating 
Investigator will be designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 
 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 22 will be performed by the local laboratory.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
• 
Pregnancy Testing: Refer to Section 1.3 for SoA. 
o Pregnancy testing (urine or serum as required by local regulations) 
should be conducted as indicated in the SoA (Section 1.3). 
o Additional serum or urine pregnancy tests may be performed, as 
determined necessary by the Investigator or required by local 
regulation, to establish the absence of pregnancy at any time during the 
participant’s participation in the study. 
 
 


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Table 22 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
• 
MCV 
• 
MCH 
• 
Reticulocytes 
WBC count with 
Differential: 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Flow Cytometry  
T-Lymphocytes 
CD3/CD4/CD8 
 
 
Clinical Chemistrya 
BUNb 
Potassium 
AST 
Total and direct 
bilirubin 
Creatinine 
Sodium 
ALT 
Total Protein 
Glucose [Indicate if fasting, 
or nonfasting] 
Calcium 
Alkaline 
phosphatase 
Chloride 
Albumin 
Phosphorus 
LDH 
Ureab 
Potassium 
Magnesium 
Bicarbonate 
 
Coagulation 
INR, PT, aPTT and Fibrinogen 
Routine Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte, and 
esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Tests 
• 
CMV IgG and PCR 
• 
TSH with free T4 
• 
CRP 
• 
Uric acid 
• 
GFR or 24-hour urine collection 
• 
Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only) 
• 
Highly sensitive serum or urine hCG pregnancy test (as needed for women of 
childbearing potential)c 
• 
HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochete bacterium). 
• 
Ferritin 
• 
Serum troponin 
• 
NT-proBNP / BNP 
Abbreviations: ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BNP = B-type natriuretic peptide; BUN = blood urea nitrogen; CMV = cytomegalovirus; CRP = 
C-reactive protein; EBV = Epstein- Barr virus; GFR = glomerular filtration rate; HBV = hepatitis B virus; hCG = 
human chorionic gonadotropin; HCV = hepatitis C virus; eCRF = electronic case report form; HIV = human 
immunodeficiency virus; HLA = human leukocyte antigen; HTLV = human T-lymphotropic virus; 
IgG = immunoglobulin G; INR = international normalized ratio; IRB/IEC = Institutional Review Board/Independent 
Ethics Committee; LAGE-1a = cancer testis antigen 2; LDH = lactate dehydrogenase; MCH = mean corpuscular 
hemoglobin; MCV = mean corpuscular volume; NT-proBNP = N-terminal pro B-type natriuretic peptide; NY-ESO-1 
= New York esophageal squamous cell carcinoma 1; PCR = polymerase chain reaction; PT = prothrombin time; 
RBC = red blood cells; SAE = serious adverse event; T4 = thyroxine; TSH = thyroid stimulating hormone; ULN = 
upper limit of normal; WBC = white blood cells.  
a. Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver 
stopping or monitoring event are given in Section 7.1.1 and Table 15.  All events of ALT 3 × ULN and 
bilirubin 2 × ULN (>35% direct bilirubin) or ALT 3 × ULN and INR >1.5, if INR measured, which may 
indicate severe liver injury (possible Hy’s Law), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis). 
a. Either BUN or UREA tests are acceptable 


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b. Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
  
Note: All study-required laboratory assessments will be performed by a local laboratory, with the exception of 
biomarkers HLA –A2:01, A2:05, or A2:06 and NY-ESO-1/LAGE-1a.  The results of each test must be entered 
into the eCRF. 


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition: 
• An adverse event (AE) is any untoward medical occurrence in a clinical study 
participant, temporally associated with the use of a study intervention, whether or 
not considered related to the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention. 
 
Events Meeting the AE Definition: 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from Baseline, considered clinically 
significant in the medical and scientific judgment of the Investigator (i.e., not 
related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• “Lack of efficacy” or “failure of expected pharmacological action” per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfill the definition of an AE 
or SAE.  
 
Events NOT Meeting the AE Definition: 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant’s condition. 


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• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be a serious adverse event 
(SAE) even if serious conditions are met. 
A SAE is defined as any untoward medical occurrence that, at any dose: 
Results in death 
Is life-threatening 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires in-patient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
out-patient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 


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Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
• Grade 3 or higher CRS and all cases of Guillain-Barré syndrome (GBS) or other 
demyelinating neuropathies must be reported within 24 hours as SAEs 
10.3.3. 
Definition of Cardiovascular Events 
Cardiovascular (CV) Events Definition: 
Investigators will be required to fill out the specific CV event page of the eCRF 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 
10.3.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• The Investigator will then record all relevant AE/SAE information in the eCRF. 


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• It is not acceptable for the Investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK AE/SAE eCRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported 
during the study according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE v4.03 as in the SRM) except for the 
following:  
• CRS grading will be based on [Lee, 2019] and include Fever, Hypoxia and 
Hypotension. Organ toxicities associated with CRS will be graded according to 
NCI-CTCAE v5.0 and do not influence CRS grading. 
• ICANS grading will be based on [Lee, 2019].   
 
Assessment of Causality 
• The Investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• The Investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The Investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the Investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the Investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the Investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 


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• The Investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• If a participant dies during participation in the study or during a recognized follow-
up period, the Investigator will provide GSK with a copy of any post-mortem 
findings including histopathology.  
• New or updated information will be recorded in the originally completed eCRF. 
• The Investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
10.3.5. 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to GSK will be the electronic data 
collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to the Medical Monitor/SAE coordinator by telephone. 
• Contacts for SAE reporting can be found in the SRM. 
 


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10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
10.4.1. 
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 
• 
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 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT).  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. 


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10.4.2. 
Contraception Guidance 
Table 23 
Contraceptives Allowed During the Study 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year when used 
consistently and correctly. 
Implantable progestogen-only hormonal 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 90 days. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when used consistently and 
correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
Progestogen-only hormonal 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. 
b. 
Failure rate of <1% per year when used consistently and correctly.  Typical use failure rates differ from 
those when used consistently and correctly. 
c. 
Male condoms must be used in addition to hormonal contraception.  If locally required, in accordance with 
Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those 
which inhibit ovulation as the primary mode of action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception.  Male 
condom and female condom should not be used together (due to risk of failure with friction). 
 
10.4.3. 
Collection of Pregnancy Information: 
Male participants with partners who become pregnant 
• Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is 
participating in this study. This applies only to male participants who receive 
study treatment. 


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• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy.  
• The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to 
GSK. 
• Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of 
fetal status (presence or absence of anomalies) or indication for procedure.  
Female participants who become pregnant 
• Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study.  
• Information will be recorded on the appropriate form and submitted to GSK 
within 24 hours of learning of a participant’s pregnancy.  
• Participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on participant and neonate, which 
will be forwarded to GSK. Generally, follow-up will not be required for longer 
than 6 to 8 weeks beyond the estimated delivery date.   
• Any termination of pregnancy will be reported, regardless of fetal status (presence 
or absence of anomalies) or indication for procedure.  
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.  
• A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  
• Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the Investigator will be reported to 
GSK as described in Appendix 3.  While the Investigator is not obligated to 
actively seek this information in former study participants, he or she may learn of 
an SAE through spontaneous reporting.  
• Any female participant who becomes pregnant while participating will 
discontinue study intervention and be monitored into the LTFU protocol (GSK 
Study 208750) or to Part 5 of this study (if not yet enrolled in the LTFU study).  
 


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10.5. 
Appendix 5: Genetics 
USE/ANALYSIS OF DNA 
• Genetic variation may impact a participant’s response to therapy, susceptibility, 
and severity and progression of disease. Variable response to therapy may be due 
to genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and 
IRB/IEC allow, a blood sample will be collected for DNA analysis. 
• DNA samples will be used for research related to lete-cel or lete-cel in 
combination with pembrolizumab, or advanced/recurrent NSCLC and related 
diseases. They may also be used to develop tests/assays including diagnostic tests 
related to lete-cel alone and/or in combination with pembrolizumab, or study 
treatments of this drug class, and advanced or recurrent NSCLC. Genetic research 
may consist of the analysis of 1 or more candidate genes or the analysis of genetic 
markers throughout the genome or analysis of the entire genome as appropriate. 
• DNA samples will be analyzed if it is hypothesized that this may help further 
understand the clinical data. 
• DNA samples will be analyzed by using appropriate descriptive and/or statistical 
analysis methods. A detailed description of any planned analyses will be 
documented in a RAP prior to initiation of the analysis. 
• The samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to lete-cel alone and/or in combination with 
pembrolizumab or study treatments of this class. The results of genetic analyses 
may be reported in the clinical study report (CSR) or in a separate study 
summary. 
• The Sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• The samples will be retained while research on lete-cel alone and/or in 
combination with pembrolizumab or study treatments of this class or NSCLC and 
related diseases continues but no longer than 15 years after the last participant’s 
last visit or other period as per local requirements. 
10.5.1. 
Screen and Baseline Failures 
If a sample for genetic research has been collected and it is determined that the 
participant does not meet the entry criteria for participation in the study, then the 
Investigator should instruct the participant that their genetic sample will be destroyed.  
No forms are required to complete this process as it will be completed as part of the 
consent and sample reconciliation process.  In this instance, a sample destruction form 
will not be available to include in the site files. 


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10.5.2. 
Germline Control 
United States (US) Food and Drug Administration (FDA) states that an in vitro 
companion diagnostic device (IVD) could be essential for the safe and effective use of a 
corresponding therapeutic product to: 
• Identify participants who are most likely to benefit from a particular therapeutic 
product; 
• Identify participants likely to be at increased risk for serious adverse reactions as 
a result of treatment with a particular therapeutic product; 
• Monitor response to treatment for the purpose of adjusting treatment (e.g., 
schedule, dose, discontinuation) to achieve improved safety or effectiveness; 
• Identify participants in the population for whom the therapeutic product has been 
adequately studied, and found safe and effective, i.e., there is insufficient 
information about the safety and effectiveness of the therapeutic product in any 
other population. 
Global regulatory requirements for IVD companion diagnostic tests are evolving.  If a 
DNA-based IVD companion diagnostic device might be needed to identify participants 
who are appropriate for the GSK medicinal product(s) under investigation in this 
protocol, then GSK should collect and retain DNA samples from participants who carry 
the genetic variant of interest as well as DNA samples from participants who do not carry 
the genetic variants of interest to validate the performance of the companion diagnostic.  
Therefore, where local regulations and IRB/IEC allow, a sample will be collected for 
DNA analysis.  Any IVD companion diagnostic research objectives should be described 
in participant ICFs. 
 
 


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10.6. 
Appendix 6: Liver Safety 
See Table 11 for hepatic parameter requirements for study inclusion. 
See Section 7.1.1.1 for liver event monitoring criteria. 
See Section 7.1.1.1 for study intervention restart and re-challenge criteria 
See Table 16 for pembrolizumab dose modification and treatment guidelines. 
 


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10.7. 
Appendix 7: Country-Specific Requirements 
Not applicable. 
 
 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 5 3  
 
1 0. 8.  
A p p e n di x 8 : A b br e vi ati o n s a n d Tr a d e m ar k s 
Li st of A b br e vi ati o n s  
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
A B W  
A dj uste d b o d y w ei g ht  
A C T  
A d o pti ve T -cell t hera p y 
A E  
A d verse e ve nt  
A E SI  
A d verse e ve nt of s pecial i nterest  
AI D S  
Ac q uire d i m m u ne deficie nc y s y n dr o me  
A L K  
A na plastic l y m p h o ma ki nase 
A L T  
Ala ni ne a mi n otra nsferas e  
A L P  
Al kali ne p h os p hatase  
A N C  
A bs ol ute ne utr o p hil c o u nt  
aP T T  
Acti vate d partial t hr o m b o plasti n ti me  
A S C O  
A merica n S ociet y of Cli nical O nc ol o g y  
A S T  
As partate a mi n otra nsferase  
A T G  
A ntit h y m o c yte gl o b uli n  
A T T A C K  
A d o pti ve e n gi neere d T -cell tar geti n g t o acti vate ca ncer killi n g  
A U C( 0 -t) 
Area u n d er t he c o nce ntr ati o n/ persiste nce ti me c ur ve fr o m 0 t o ti me t  
B C G  
Bacill us Cal mette – G uéri n  
B R A F  
B -R af  
B S A  
B o d y s urface area  
B U N  
Bl o o d urea nitr o ge n  
C A R  
C hi meric a nti ge n rece pt or  
C A R -T  
C hi meric a nti ge n rece pt or T -cell  
C B C  
C o m plete bl o o d c o u nt  
C D C  
Ce nters f or Disease C o ntr ol a n d Pre ve nti o n  
C D 2 8  
Cl uster of differe ntiati o n 2 8  
C D 3  
Cl uster of differe ntiati o n 3  
C D 3ζ  
C D 3 zeta  
C D 4  
Cl uster of differe ntiati o n 4  
C D 8  
Cl uster of differe ntiati o n 8  
cf D N A  
Cell -free D N A 
C F R  
C o de of Fe d eral Re g ul ati o ns ( U S)  
CI O M S  
C o u ncil f or Inter nati o nal O r ga nizati o ns of M e dical S cie nces  
C K D -E PI  
C hr o nic ki d ne y dise ase e pi de mi ol o g y c olla b orati o n  
C LI A  
Cli nical La b orat or y I m pr o ve me nt A me n d me nts  
C ma x  
Ma xi m u m o bser ve d c o nce ntrati o n / persiste nce 
C M V  
C yt o m e gal o vir us  
C N S  
Ce ntral ner v o us s yste m  
C O N S O R T  
C o ns oli date d sta n dar ds of re p orti n g trials  
C P D  
C o nfir me d pr o gressi ve disease (i C P D = C P D base d o n  
)  
C P K  
Creati ne p h os p h o ki nase  
C R  
C o m plete res p o nse  (i C R = C R base d o n i R E CI S T) 
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 5 4  
 
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
Cr Cl  
Calc ulate d creati ni ne cleara nce  
C R E S  
C A R T -cell relate d e nce p hal o pat h y s y n dr o me  
C R F  
Case re p ort f or m  
C R P  
C -reacti ve pr otei n 
C R S  
C yt o ki ne rel ease sy n dr o me  
C S F  
Cere br os pi nal fl ui d  
C S R  
Cli nical st u d y re p ort 
C T  
C o m p ute d t o m o gra p h y  
C T A  
Cli nical Trial Assa y  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
ct D N A  
Circ ulati n g t u m or D N A  
C T F G  
Cli nical Trial Facilitati o n Gr o u p  
C T L A -4  
C yt ot o xic t -l y m p h o c yt e-ass ociate d pr otei n 4  
C V  
Car di o vasc ular  
D C R  
Disease c o ntr ol rate  
 
D L C O  
P ul m o nar y diff usi n g ca p acit y f or car b o n m o n o xi de  
D M S O  
Di met h yls ulf o xi de  
D N A  
De o x yri b o n ucleic aci d  
D o R  
D urati o n of res p o ns e 
 
D R E S S  
Dr u g ras h wit h e osi n o p hilia a n d s yste mic s y m pt o m s 
D S U R  
Dr u g Safet y U p d ate Re p ort  
E B V  
E pstei n -Barr vir us  
E C G  
Electr ocar di o gra m(s)  
E C H O  
Ec h ocar di o gra p h y  
e C O A  
Electr o nic Cli nical O utc o me Assess me nt  
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
e C R F 
Electr o nic Case Re p ort F or m  
E E G  
Electr oe n ce p hal o gra m  
E G F R  
E pi der mal gr o wt h f act or rece pt or  
E M A  
E ur o pea n Me dici nes A ge nc y  
E M G  
Electr o m y o gra p h y   
E O P  
E n d of pr o d ucti o n  
E o T  
E n d of treat me nt  
E S  
E nce p hal o pat h y s y n dr o m e  
E VI 1  
Ec otr o pic viral i nte grati o n site 1  
F A C T -G P 5  
F u ncti o nal  Assess me nt  of Ca ncer T hera p y –  Ge n eral  P o p ulati o n  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F D G P E T  
Fl u or o de o x y gl uc os e p ositr o n e missi o n t o m o gra p h y  
F E V 1  
F orce d e x pirat or y v ol u me  i n 1 sec o n d 
F F P E  
F or mali n -fi x e d paraffi n-e m be d de d  
F S H  
F ollicle sti m ulati n g h or m o ne  
F V C  
F orce d vital ca p acit y  
G B S  
G uillai n -Barré S y n dr o me  
G C L P  
G o o d Cli nical La b orat or y Practice  
G C P  
G o o d Cli nical Practice  
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 5 5  
 
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
G -C S F  
Gra n ul oc yte c ol o n y -sti m ulati n g fact or 
G F R  
Gl o mer ular filtrati o n rate  
GI  
Gastr oi ntesti nal  
G M -C S F  
Gra n ul oc yte -macr o p ha ge c ol o n y sti m ulati n g fact or  
G S K  
Gla x o S mit h K li ne 
G B S  
G uillai n -Barré S y n dr o me  
G V H D  
Graft vers us h ost disease  
G y  
Gra y ( u nit of a bs or be d d ose of ra diati o n)  
H Bc A b  
He patitis B c ore a nti b o d y  
H Bs A g  
He patitis B s urface a nti ge n  
H B V  
He patitis B vir us  
h C G  
H u ma n c h ori o nic g o na d otr o pi n  
H C V  
He patitis C vir us  
H E R 2  
H u ma n e pi der mal gr o wt h fact or rece pt or 2  
HI P A A  
Healt h i ns ura nce p orta bilit y a n d acc o u nta bilit y act  
HI V  
H u ma n i m m u n o deficie nc y vir us  
H L A  
H u ma n le u k oc yte a nti ge n  
H R  
Hazar d rati o 
H R T  
H or m o ne re pl ace m e nt t hera p y  
H T L V  
H u ma n T -l y m p h otr o pi c vir us 
I B 
I n v esti gat or’s br o c h ure 
I B W 
I d eal b o d y wei g ht 
I C E 
I m m u ne Effect or Cell-Ass ociate d E nce p hal o pat h y  
I C A N S 
I m m u ne Effect or Cell-Ass ociate d Ne ur ot o xicit y S y n dr o me  
I C F 
I nf or me d c o ns e nt f or m 
I C H 
I nter nati o nal C o u ncil f or H ar m o ni sati o n  
I C P 
I ntr acra nial press ure 
I E C 
I n d e pe n de nt et hics c o m mittee 
I F N 
I nterfer o n 
I gG  
I m m u n o gl o b uli n G  
I g M 
I m m u n o gl o b uli n M 
I g V 
I m m u n o gl o bul i n varia ble – t y pe 
I L 
I nterle u ki n 
I N D 
I n v esti gati o nal N e w D r u g 
I N L 
I n v esti gat or n otificati o n letter 
I N R 
I nter nati o nal n or malize d rati o 
I P 
I n v esti gati o nal pr o d uct 
I R B 
I nstit uti o nal re vie w b o ar d 
ir A E 
I m m u ne-relat e d a d verse e ve nt 
I R T 
I nteracti ve res p o nse t ec h n ol o g y 
I T T 
I nte nt t o treat 
I U D 
I ntr a uteri ne d e vice 
C CI
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 5 6  
 
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
I U S 
I ntr a uteri ne s yste m 
I V 
I ntr a ve n o us 
I V D 
i n vitr o c o m pa ni o n dia g n ostic de vice  
L A G E -1 a  
C a ncer testis a nti ge n 2  
L A M  
Lactati o nal a me n orr hea met h o d  
L D H  
Lactate d e h y dr o ge n ase  
L F T  
Li ver f u ncti o n test  
L M O 2  
LI M d o m ai n o nl y 2  
L P S  
Li p o p ol ysacc hari d e  
L T F U  
L o n g -t er m f oll o w-u p  
m A b  
M o n ocl o nal a nti b o d y  
M C H  
Mea n c or p us c ular h e m o gl o bi n  
M C V  
Mea n c or p us c ular v ol u m e  
Me d D R A  
Me dical D icti o nar y f or R e g ul at or y A cti vities  
mI T T  
M o difie d i nte nt t o treat  
M RI  
Ma g n etic res o n a nce i ma gi n g  
m R N A  
Messe n ger R N A  
M S D S  
Material Safet y D ata S heet  
M U G A  
M ulti gate d ac q uisiti o n sca n  
N A  
N ot a p plica ble  
N C C N  
Nati o nal C o m pre he nsi ve Ca ncer Net w or k  
N CI  
Nati o nal Ca ncer I nstit ute  
N S AI D  
N o n -ster oi dal a nti-i nfla m mat or y dr u g 
N S C L C  
N o n -s mall cell l u n g ca n cer  
N T R K  
Ne ur otr o p hic tr o p o m y osi n -relate d ki n ase 
N Y -E S O -1  
Ne w Y or k es o p ha geal s q ua m o us cell carci n o ma 1  
N Y H A  
Ne w Y or k Heart Ass ociati o n  
O R R  
O verall res p o nse rate 
 
O S  
O verall sur vi val  
O T C  
O ver -t he-c o u nter  
P B L  
Pe m br oliz u ma b baseli ne  
P B M C  
Peri p heral bl o o d m o n o n u clear cell  
P B P K  
P h ysi ol o gic all y -base d p h ar mac o ki netic (s) 
P C P  
P ne u m oc ystis cari nii p ne u m o nia  
P C R  
P ol y m eras e c hai n r eacti o n  
P D  
Pr o gressi ve disease  
 
P D -1  
Pr o gra m me d deat h pr ot ei n 1  
P D -L 1  
Pr o gra m me d deat h pr ot ei n 1  li ga n d 
P D -L 2  
Pr o gra m me d deat h pr ot ei n 2 li ga n d  
P dc d 1  
Ge ne e n c o di n g P D -1  
P F S  
Pr o gressi o n -free sur vi val  
P F T  
P ul m o nar y f u ncti o n test  
P K  
P har mac o ki netic (s) 
P K C  
Pr otei n ki nase C -t heta 
P M B C  
Peri p heral bl o o d m o n o n u clear cell  
C CI
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 5 7  
 
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
P R  
Partial Res p o nse  
 
P R O  
Patie nt -re p orte d o utc o m es 
P R O -C T C A E  
Patie nt -re p orte d o utc o m e versi o n of t he c o m m o n t er m criteri a f or 
a d verse e ve nts  
P S  
Perf or ma nce stat us  
P T  
Pr ot hr o m bi n ti me  
P V  
P har mac o vi gila nce  
P W  
Pe m br oliz u ma b W ee k  
Q # W  
E ver y #  wee k (s) 
Q L Q  
Q ualit y of lif e q uesti o n naire  
Q o L  
Q ualit y of life 
q P C R  
Q ua ntitati ve p ol y merase c hai n reacti o n  
Q Tc  
C orrecte d Q T i nter val d urati o n  
Q Tc B  
Q T d urati o n c orrect e d f or heart rate b y Bazett’s f or m ula  
Q Tc F  
Q T d urati o n c orrect e d f or heart rate b y F ri deri cia’s f or m ula 
R A M O S  
Re gistrati o n a n d M e dicati o n Or deri n g S yst e m  
R A P  
Re p orti n g a n d a nal ysis pla n  
R B C  
Re d bl o o d cell  
R C L  
Re plicati o n c o m pete nt le nti vir us  
R C R  
Re plicati o n c o m pete nt retr o vir us  
R E CI S T  
Res p o nse E val uati o n C riteria i n S oli d T u m ors  
R O S 1  
c-r os o nc o ge ne 1 
R T  
Re verse tr a nscri ptase  
R T -q P C R  
Re verse tr a nscri pti o n q ua ntitati ve p ol y m eras e c hai n reacti o n  
S A E  
Seri o us a d verse e ve nt  
S CI D -X 1  
X -li n ke d se vere c o m bi ne d i m m u n o deficie nc y 
S D  
Sta ble disease  
 or sta n dar d de vi ati o n 
(c o nte xt de pe n de nt) 
S H P -1  
Src h o m ol o g y 2 c o ntai ni n g p h os p hat ase 1  
S H P -2  
Src h o m ol o g y 2 c o ntai ni n g p h os p hat ase 2  
SJ S  
Ste ve ns -J o h ns o n S y n dr o me 
S o A  
Sc he d ule of acti vities  
S o C  
Sta n dar d of care  
S O P  
Sta n dar d o perati n g pr oce d ure  
S R M  
St u d y R efere nce Ma n ual  
S R T  
Safet y R e vie w Tea m  
S U S A R  
S us pecte d u ne x pecte d seri o us a d verse reacti o ns  
T 1 D M  
T y pe 1 di a betes mellit us  
T 4  
T h yr o xi ne  
T C G A  
T he Ca ncer Ge n o me Atlas  
T C R  
T -cell rece pt or  
T C R Val p ha  
T C R al p ha c hai n vari a ble re gi o n  
T C R V beta  
T C R beta c hai n vari a ble re gi o n  
C CI
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 5 8  
 
A b bre vi ati o n  Defi niti o n or E x pl a n ati o n  
T E A E  
Treat me nt -e mer ge nt a d v erse e v e nt  
T E N  
T o xic E pi der mal Necr ol ysis  
T G F  
Tra nsf or mi n g gr o wt h fact or  
T KI  
T yr osi ne ki nase i n hi bit or  
T L C  
T otal l u n g ca pacit y 
T L T  
Treat me nt li miti n g t o xicit y  
T ma x  
Ti me t o C ma x  
T M D D  
Tar get -me di ate d dr u g dis p ositi o n  
T N F  
T u m or necr osis f act or  
T P S  
T u m or pr o p orti o n sc ore  
T -re gs 
Re g ulat or y T -cells 
T S H  
T h yr oi d  sti m ulati n g h or m o ne 
T T R  
Ti me t o res p o nse  
 
U P D  
U nc o nfir me d pr o gressi ve disease 
 
U L N  
U p per li mit of n or mal  
V 2 0  
Perce nta ge of n or mal l u n g recei vi n g at least 2 0 G y d uri n g ra di ot hera p y  
V S V -G  
Vesic ular St o matitis Vir us G pr otei n  
W B C  
W hite bl o o d cell  
W H O  
W orl d Healt h Or ga nizati o n  
W O C B P  
W o ma n of c hil d beari n g p ote ntial  
W T  
Wil d -t y pe 
X -C G D  
X li n ke d c hr o nic gra n ul o mat o us disease  
Z A P 7 0  
Zet a -c h ai n -ass oci ate d pr otei n ki nase  
 
Tr a de m a r k I nf or m ati o n  
Tr a de m a r ks of t he 
Gl a x o S mit h Kli ne gr o u p of 
c o m p a nies  
 
Tr a de m a r ks n ot o w ne d b y t he 
Gl a x o S mit h Kli ne gr o u p of 
c o m p a nies  
N O N E  
 
K E Y T R U D A  
 
 
C CI
C CI
C CI
C CI
C CI


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10.9. 
Appendix 9: 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 
participants.  During lymphodepletion, supportive care should be provided to participants 
as per local institutional guidelines, based on established standards. 
All participants must be hospitalized on the day of T-cell (lete-cel) infusion (Day 1) and 
may be in the hospital for follow-up care until Day 3 as clinically indicated.  Longer 
hospitalization is allowed if clinically needed.  Staff treating trial participants should be 
experienced in acute post-transplant care and the management of associated toxicities 
(e.g., cytopenias, CRS, autologous GVHD). 
Participants 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. 
10.9.1. 
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 that all participants who 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. 
10.9.2. 
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. For participants with indwelling central lines, consider increased 
surveillance to monitor for catheter-associated infections.  
10.9.2.1. 
Pneumocystis carinii Pneumonia (PCP) 
Participants should receive prophylaxis against PCP with drug, dose and duration 
according to institutional guidelines.  Single strength trimethoprim sulfamethoxazole 


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daily is the recommended first-line agent, starting at Day 28 post T-cell infusion for one 
year.  Other regimens, including atovaquone (1500 mg daily with food) or aerosolized 
pentamidine (300 mg every 4 weeks) are also acceptable (e.g., if sulfonamide allergy). 
10.9.2.2. 
Herpes Simplex and Varicella Zoster 
All participants should receive prophylaxis with acyclovir (800 mg twice daily) or 
valacyclovir (500 mg twice daily) for 1 year, or in accordance with institutional 
guidelines. 
10.9.2.3. 
Cytomegalovirus 
All participants will be screened for CMV IgG seropositivity at study entry and baseline.  
If CMV viremia is detected at baseline, treatment should be initiated with evidence of 
viral clearance prior to lymphodepleting chemotherapy.  All CMV IgG seropositive 
participants will continue to be monitored as shown in Section 1.3 for CMV viremia by 
CMV DNA PCR until 60 days post infusion of lete-cel.  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 absolute neutrophil count (ANC) ≥1000, and foscarnet if 
ANC <1000. 
If a participant 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 10.9.7. 
10.9.2.4. 
Hepatitis B Prophylaxis 
Participants will be screened for hepatitis B virus (HBV) at study entry.  Participants 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 
(300 mg daily), entecavir (0.5 mg daily), or tenofovir (300 mg daily). 
10.9.2.5. 
Syphilis 
Participants will be screened for syphilis at study entry, before leukapheresis, and before 
lymphodepletion.  Participants with positive screening results should be evaluated by an 
infectious diseases consultant.  If before leukapheresis and/or lymphodepletion, the 
participant is determined to have syphilis infection, the participant should be treated as 
needed before the study procedure. 
10.9.2.6. 
Other Anti-Microbial Prophylaxis/Treatment 
Antibacterial and antifungal prophylaxis should follow institutional standards for 
autologous bone marrow transplants. 
If a participant has prolonged leukopenia, consider vigilance for latent viral infections. 


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If a participant presents with severe or gross hematuria, consider checking for BK viruria 
and viremia. 
If a participant requires anti-microbial treatment associated with risk of cardiac toxicity, 
consider close monitoring of cardiac function (Section 8.2.3). 
10.9.3. 
Hematologic and Blood Product Support 
Blood product support should be provided to maintain: 
• platelets >10 x 109/L in the in-patient setting and  
• platelets >20 x 109/L in the out-patient setting;  
• hemoglobin (Hb) >8.0 g/dL  
or as clinically indicated in the judgement of the Investigator, or in accordance with 
institutional practice.   
 
See AABB (formerly American Association of Blood Banks) Guideline on platelet 
transfusion (Kaufman, 2015). 
10.9.3.1. 
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 participant requires systemic 
steroids or immunosuppression for the treatment of toxicity, irradiated blood products 
must be given until recovery of immune function. 
10.9.3.2. 
CMV Screened Blood Products 
Participants will be screened for CMV seropositivity at study entry.  In order to reduce 
the risk of primary CMV infection, all participants (i.e., both CMV-positive and -negative 
participants) should receive leukoreduced blood products where possible (excluding the 
IP infusion).  Where leukoreduced blood is not available, CMV negative participants 
must only receive blood products from CMV-seronegative donors from study entry to 
study completion. 
10.9.4. 
Management of Autoimmunity 
Participants should be monitored throughout the trial for potential autoimmune reactions 
in response to the genetically engineered T-cells (lete-cel); such toxicity 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 lete-cel.  If the participant 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. 


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10.9.5. 
Management of Cytokine Release Syndrome 
Cytokine Release Syndrome (CRS) 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, elevated transaminases, rash, and 
dyspnea.  It is important to evaluate the participant 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, 2019]. CRS grading will include Fever, Hypoxia and Hypotension. Organ toxicities 
associated with CRS will be graded according to NCI-CTCAE v5.0 and do not influence 
CRS grading [Lee, 2019]. 
Table 24 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, in alignment with (the Society 
for Immunotherapy of Cancer SITC) guidelines [Maus, 2020] and should be followed in 
conjunction with any local guidelines, where available.   
If CRS is suspected, a physician with expertise in the management of participants 
following bone marrow transplant should be consulted. 
If CRS is suspected, in addition to assessment for infection, per the Schedule of Activities 
(Section 1.3), the following tests should be conducted every day for the first week and 
approximately every other day thereafter until symptoms are improving or an 
alternative diagnosis is confirmed: 
• Local tests: 
o chemistry, hematology, ferritin and coagulation, as well as C-reactive protein 
(CRP) labs; 
• Central tests: 
o Cytokine-profiling as described in Section 8.9.1. 
If CRS is suspected, participants deemed to have significant cardiovascular risk factors 
(per Section 8.2.3) should be considered for earlier intervention with tocilizumab and/or 
steroids at the onset of CRS.  


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If C R S ≥Gra de 2 is s us pecte d, a n E C H O/ M U G A is re q uire d at o ns et of ≥Gra de 2 C R S. 
A d diti o nal m o nit ori n g m ust be c o n d ucte d f or a mi ni m u m of 3 da ys p ost o nset of 
≥Gra de  2 C R S a n d as l o n g as d ee me d necess ar y b y t he I n v esti gat or:  
•  C o nti n u o us car diac tele m etr y m o nit ori n g  
•  E C H O / M U G A as cli nicall y i n dicate d  
•  L ocal tests:  
o  Dail y tr o p o ni n a n d N -ter mi nal pr o B-t y pe n atri uretic pe pti de ( N T-pr o B N P) or 
B N P tests.  
If i n t he o pi ni o n of t he I n vesti gat or, t h e partici pa nt  de vel o ps  a n y cli nicall y si g nifica nt  
ne w or w ors e ni n g car di o vasc ular s y m pt o ms  or a b n or mal car di ac la bs / i ma gi n g fi n di n gs , 
a car di ol o g y c o ns ult  s h o ul d be c o ns ulte d f or ur ge nt e val uati o n. 
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Partici pa nts  re q uiri n g i m m u n os u p pressi ve i nter ve nti o n ma y recei ve t o ciliz u ma b, ster oi ds, 
or b ot h [Da vila , 2 0 1 4; Lee , 2 0 1 4; Lee , 2 0 1 9].  T ociliz u ma b is a h u ma nize d a nti -I L-6 
rece pt or a nti b o d y t hat has bee n a p pr o ve d f or t h e ma na ge me nt of s e vere or life -
t hreate ni n g C R S i n d uce d b y c hi meric a nti ge n rece pt or ( C A R) T cell t hera p y 
[T ociliz u ma b U S PI , 2 0 2 0; T ociliz u ma b S m P C , 2 0 2 0].  
Per t he pa ka ge i nsert, t he rec o m me n de d d os e of t o ciliz u ma b f or partici pa nts  wit h se vere 
or life -t hreate ni n g C R S is 8 m g/ k g f or t h ose w h o wei g h 3 0 k g or a b o v e, a d mi nistere d 
i ntra ve n o usly o v er 1 h o ur wit h a t otal d ose n ot e x cee di n g 8 0 0  m g per i nf usi o n. If n o 
cli nical i m pr o ve me nt i n t he si g ns a n d s y m pt o ms of C R S occ urs after t he first d ose, u p t o 
3 a d diti o nal d oses of t ociliz u ma b ma y b e a d mi nistere d. T h e i nter val bet wee n c o nsec uti ve 
d oses s h o ul d be at least 8 h o urs. 
Si de effects attri b ute d t o c hr o nic use of t ociliz u ma b i n r he u mat ol o gic dis ease i ncl u de 
ele vate d tra nsa mi nase s, t hr o m b oc yt o p e nia, ele vat e d c h olester ol a n d l o w-d e nsit y 
li p o pr otei ns, a n d ne utr o p e nia a n d i ncreas e d i nfecti o ns ; h o we ver,  ac ute i nf usi o n t o xicities 
ha ve n ot bee n re p ort e d i n C R S use [Lee , 2 0 1 4 ; Lee , 2 0 19 ]. 
Per SI T C 2 0 2 0 g ui deli nes:  
Partici pa nts  u nres p o nsi ve t o t ociliz u ma b or e x perie nci n g s e vere ne ur ol o gi cal s y m pt o ms 
(e. g., c o nf usi o n, d eliri u m, seiz ure, etc.) ma y re q uir e treat me nt wit h ster oi d s.  Lee et al 
[Lee , 2 0 1 4; Lee , 2 0 1 9] rec o m me n d ster oi ds as sec o n d-li ne t hera p y f or C R S as t he 
res p o nse t o t ociliz u ma b ma y b e m ore ra pi d a n d o wi n g t o t he p ote ntial of ster oi ds t o 
atte n uate t he a nti -t u m or effects of t he A C T.  H o we ver, i n partici pa nts  wit h Gra de 3 or 4 
C R S ass ociate d wit h ne ur ol o gic d ysf u ncti o n wit h o ut si g nifica nt he m o d y n a mic i nsta bilit y 
or ot her life -t hr eate ni n g s y m pt o mat ol o g y, c o nsi derati o n ma y b e gi ve n t o t he use of 
c ortic oster oi ds as a preferre d first -li ne i m m un os u p pressi ve t hera p y.  Hi g h d oses (e. g ., 
2  m g/ k g/ da y pre d nis o n e e q ui vale nt) ma y be re q uire d.  
If C R S d oes n ot i m pr o ve after o ne d ose of t ociliz u ma b, t he n ster oi ds s h o ul d be 
a d mi nistere d wit h a sec o n d d ose t ociliz u ma b (e. g. , met h yl pre d nis ol o ne 2  m g/ k g/ da y or 
de x a met has o ne 0. 5  m g/ k g u p t o 1 0  m g/ d ose). If C R S d oes n ot i m pr o ve after 2 d oses of 
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t ociliz u ma b (a n d ster oi ds), t hir d-li ne a ge nts ha v e als o bee n descri b e d pre vi o usl y, 
i ncl u di n g ot her  a nti-I L 6 rece pt or a nti b o dies s uc h as silt u xi ma b wit h or wit h o ut 
c orticoster oi ds [ Lee , 2 0 1 4; C he n , 2 0 1 6], or ot her  a ntic yt o ki ne -direct e d t hera p y [ Fre y , 
2 0 1 5]  s uc h as t he I L-1 rece pt or a g o nist a n a ki nr a. If ster oi ds are use d i n t he ma na ge me nt 
of C R S, a ra pi d ta per s h o ul d be use d o nce s y m pt o ms be gi n t o i m pr o ve  [Ma us , 2 0 2 0]. 
Use of m yel oi d gr o wt h f act ors, partic ul arl y Gra n ul oc yte -Macr o p ha ge C ol o n y Sti m ulati n g 
Fact or ( G M -C S F) is n ot r ec o m me n de d b eca us e G M -C S F ma y t h e oreticall y a g gra vat e 
C R S [ Raje , 2 0 1 9]. 
 
Assess me nt a n d ma na ge me nt of ne ur ol o gical si g ns a n d s y m pt o ms ass ociate d wit h C R S 
s h o ul d i ncl u de c o nsi derati o n of c o nc urre nt occ urre nce of I m m u ne-effect or cell -ass ociate d 
ne ur ot o xicit y s y n dr o m e (I C A N S). See Secti o n  1 0. 9. 8  f or f urt her details. 
1 0. 9. 6.  
M a n a g e m e nt of Gr aft -v er s u s -H o st Di s e a s e ( G V H D)  
A ut ol o g o us G V H D has b ee n descri be d i n ass oci ati o n wit h a d o pti ve tra nsfer of e x -vi v o 
e x pa n de d/c o -sti m ulate d a ut ol o g o us T-cells [Raje , 2 0 1 9; Ra p o p ort , 2 0 0 9] as well as 
i nf usi o n of T-cells wit h e n gi ne ere d s p ecificit y f or N Y -E S O -1 a n d L A G E -1 a [Garfall , 
2 0 1 3] , f oll o wi n g hi g h-d ose c he m ot hera p y a n d a ut ol o g o us ste m cell tra ns pl a nt ( A S C T) i n 
partici pa nts  wit h m ulti ple m yel o m a.  T here  is t he p ote ntial f or partici pa nts  w h o recei ve 
l y m p h o de pleti n g t hera p y f oll o we d b y e n gi neere d a ut ol o g o us T-cell (lete-cel ) i nf usi o n t o 
e x perie nce G V H D a n d/ or a ut oi m m u ne G V H D -li k e s y m pt o mat ol o g y.  A ut ol o g o us 
G V H D is t y pi call y mil der t ha n classic (all o ge neic) G V H D [Kli ne , 2 0 0 8], an d is us uall y 
ma na gea bl e wit h treat me nt.  H o we ver, se vere cases (i ncl u di n g fatalities) ha ve bee n 
re p orte d [Fi dler , 2 0 1 2].  T here are n o p u blis he d g ui deli n es f or t he ma na ge me nt of 
a ut ol o g o us G V H D.  H o we ver, less o ns ca n be dra w n fr o m p u blis he d case re p orts a n d 
g ui deli nes f or t he dia g n osis a n d ma na ge me nt of ac ute G V H D f oll o wi n g all o ge n eic 
tra ns pla nt [Di g na n , 2 0 1 2]. 
1 0. 9. 6. 1.  
Di a g n o si s of G V H D  
T he dia g n osis of G V H D is pre d o mi na ntl y bas e d o n cli nical fi n di n gs a n d is ofte n o ne of 
e x cl usi o n (Ta ble 2 5 ).  Ma n y of t hese s y m pt o ms c a n als o occ ur i n t he setti n g of t he 
pre parati ve re gi me n, hi g h d ose c ycl o p h os p ha mi d e as well as wit h C R S.  A n y of t hes e 
c o n diti o ns i ncl u di n g G V H D ca n b e ass ociat e d wi t h fe ver.  T h e s ki n is t he m ost 
c o m m o nl y i n v ol ve d or ga n, f oll o we d b y t he gastr oi ntesti nal ( GI) tract a n d li ver.  A 
c o nstellati o n of s y m pt o ms i n v ol vi n g t hese or ga n s yste ms ma y be h el pf ul i n esta blis hi n g 
t he dia g n osis of G V H D.  Diarr hea, ras h, fe ver, a n d pa nc yt o pe nia are c o m m o n t o xicities 
i n t he lete-cel pr o gra m.  Mil d ( Gra de 1 or 2) tra nsie nt tra nsa mi nitis wit h o ut c h olestasis 
has bee n o bser ve d.  
T a bl e 2 5  
O v er vi e w of Cli ni c al Fi n di n g s/ S y m pt o m s of G V H D  
Or g a n  
Fi n di n g s/ S y m pt o m s  
Diff er e nti a l Di a g n o si s 
Hi st o p at h ol o g y  
Ski n  
M ac ul o p a p ul ar r as h i nv olvi n g t h e 
n eck a n d s h o ul d ers as w ell as t h e 
Dr u g r e acti o ns, vir al 
ex a nt h e ms, C R S, a n d eff ects 
of c h e m ot h er a py or r a di ati o n  
Ap o pt osis at b as e of e pi d er m al 
r et e p e gs, dysk er at osis, 
ex ocyt osis of ly m p h ocyt es, 
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p al ms a n d s ol es t h at s pr e a ds t o 
i ncl u d e t h e r est of t h e b o dy. 
s at ellit e ly m p h ocyt es a dj ac e nt t o 
dysk er at otic e pi d er m al 
k er ati n ocyt es a n d p eriv asc ul ar 
ly m p h ocytic i nfiltr ati o n i n t h e 
d er mis.  
GI  
S ecr et ory di arr h e a is m ost 
c o m m o n b ut n a us e a, v o miti n g, 
a n or exi a, w ei g ht l oss a n d 
a b d o mi n al p ai n c a n als o occ ur.  
Di arr h e a c a n b e c o pi o us.  
Bl e e di n g m ay r es ult fr o m m uc os al 
ulc er ati o n a n d il e us m ay e ns u e.  
Si d e eff ects of c h e m ot h er a py 
or ot h er dr u gs a n d i nf ecti o n of 
t h e GI tr act 
Patc hy ulc er ati o ns , a p o pt otic 
b o di es at cry pt b as es, cry pt 
ulc er ati o n a n d fl att e ni n g of 
s urf ac e e pit h eli u m 
Liv er  
C h ol est atic p att er n of liv er i nj ury 
i ncl u di n g el ev at e d c o nj u g at e d 
bilir u bi n, alk ali n e p h os p h at as e 
a n d G G T.  P artici p a nts  m ay 
pr es e nt wit h j a u n dic e, wit h pr uriti s 
i n m or e s ev er e c as es. 
Ve n o -occl usiv e dis e as e of t h e 
liv er, vir al i nf ecti o ns, dr u g 
t oxicity a n d s e psis. 
En d ot h eli alitis, ly m p h ocytic 
i nfiltr ati o n of t h e p ort al ar e as, 
p eric h ol a n gitis a n d bil e -d uct 
d estr ucti o n.  
A b br evi ati o ns: C R S = cyt oki n e r el e as e sy n dr o m e; GI = g astr oi nt esti n al; G G T = g a m m a -gl ut a myl tr a nsf er as e ; 
G V H D  =  gr aft vs h ost dis e as e.  
N O T E : B o n e m arr o w s u p pr essi o n a n d r el at e d cyt o p e ni as h av e b e e n d escri b e d i n t h e s etti n g of ac ut e G V H D.  
M a n a g e m e nt of t his c o m plic ati o n is c h all e n gi n g, wit h n o cl e arly est a blis h e d g ui d eli n es r e g ar di n g 
i m m u n os u p pr essi o n.  Tr e at m e nt m ay b e l ar g ely s u p p ortiv e, i ncl u di n g tr a nsf usi o ns a n d tr e at m e nt of i nf ecti o ns. 
 
Ma na ge me nt s h o ul d i ncl u de c o ns ultati o n wit h a p h ysicia n wit h e x pertise i n t he 
ma na ge me nt of p artici pa nts  f oll o wi n g b o ne marr o w tra ns pla nt. 
B o ne marr o w s u p pressi o n is als o a feat ur e of tra nsf usi o n -relate d G V H D.  T o mi ni mize 
t he p ossi bilit y of tra nsf usi o n-relate d G V H D, refer t o Secti o n 1 0. 9. 3. 1  f or g ui da nce o n 
irra diate d bl o o d pr o d u cts.  
1 0. 9. 6. 2.  
Gr a di n g of G V H D  
Gra di n g of ac ute G V H D is base d o n t he sta ge of der mal, gastr oi ntesti nal, a n d he patic 
i n v ol ve me nt as descri be d i n Ta ble 2 7 .  Caref ul meas ure me nt of st o ol v ol u me a n d 
assess me nt of perce nta ge of b o d y area c o v ere d b y ras h are i m p orta nt f or pr o per gra di n g 
a n d treat me nt.  
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Wit h t he a d diti o n of assess me nt of f u ncti o nal i m pair me nt, gra di n g ca n be d eter mi ne d 
usi n g Ta ble 2 7  [Gl uc ks b er g , 1 9 7 4]. 
 
1 0. 9. 6. 3.  
M a n a g e m e nt of G V H D  
Alt h o u g h t he dia g n osis of G V H D is pre d o mi na ntl y bas e d o n cli nical gr o u n ds, bi o ps y of 
affecte d or ga ns ca n b e  hel pf ul i n e x cl u di n g ot her ca uses a n d s u p p orti n g t he dia g n osis of 
G V H D wit h c o nsiste nt hist o pat h ol o gic fi n di n gs.  H o we ver, a waiti n g bi o ps y res ults 
s h o ul d n ot dela y t he i nstit uti o n of a p pr o priate t hera p y. 
If G V H D is s us pecte d: 
•  A p h ysici a n wit h e x pertise i n  t he ma na ge me nt of partici pa nts  f oll o wi n g b o ne 
marr o w tra ns pl a nt s h o ul d be c o ns ulte d . 
•  C o nsi der bi o ps y of t he affecte d or ga n(s) . 
C ortic oster oi ds ha ve bee n use d as t he sta n dar d first -li ne treat me nt f or G V H D f or se v eral 
deca d es.  T heir effect is li kel y beca us e of l y m p h ol ytic effects a n d a nti-i nfla m mat or y 
pr o perties.  I n ge neral, i ntesti nal a n d li ver G V H D re q uire m or e pr ol o n ge d ster oi d t hera p y 
t ha n s ki n disease alt h o u g h res p o nse ti mes var y. 
Diarr hea s h o ul d be ma na ge d wit h v ol u me re place me nt, dietar y restri cti o n , a n d a nti-
diarr heal a ge nts i ncl u di n g t he c o nsi derati o n of s o mat ostati n f or secret or y diarr hea.  
A ge nts t hat sl o w m otilit y s h o ul d be use d ca uti o usl y, e ns uri n g t h at t here is n o e vi de nce of 
ile us or t o xic me gac ol o n, a n d i nfecti o us ca uses of diarr hea s h o ul d be e x cl u de d.  
Ge neral g ui d eli nes f or first -li ne treat me nt base d o n G V H D gra de are pr o vi de d i n Ta ble 
2 8 , a n d s h o ul d be c o nsi d ere d i n c o nj u ncti o n wit h i n p ut fr o m t he c o ns ulti n g p h ysicia n 
wit h b o ne marr o w tra ns pla nt e x pertise.  
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Table 28 
Management Guidelines for GVHD 
GVHD 
Grade 
Management Strategy 
I 
Participants with Grade I disease are not likely to require systemic treatment.  Cutaneous GVHD 
may respond to topical steroid creams.  Antihistamines may be helpful for participants with pruritis.  
Participants should be evaluated frequently for other organ manifestations of GVHD. 
II 
Treat skin symptoms with topical steroids.  For GI symptoms, optimize anti-diarrheal regimen, 
dietary restrictions, and volume replacement as well as consider initiation of non-absorbable 
steroids.  For refractory or progressive symptoms, consider systemic steroids as outlined below 
(text below this table). 
III 
For more severe or progressive symptoms, consider systemic corticosteroids (e.g., 
methylprednisolone one (1) mg/kg per day)1 
IV 
Methylprednisolone two (2) mg/kg per day1 
Abbreviations: GI = gastrointestinal; GVHD = graft vs host disease. 
1. The use of ‘non-absorbable’ 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 participants 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 allogeneic transplant patients concurrently receive 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 Hematology 
and the British Society for Blood and Marrow Transplantation guideline for diagnosis 
and management of acute GVHD [Dignan, 2012]. 


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10.9.7. 
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 lete-cel.  
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 one week. 
Aplastic anemia is a rare hematological disorder characterized by pancytopenia and a 
hypocellular marrow.  Participants are usually symptomatic on presentation but some are 
detected incidentally when unexpected cytopenias are found on a routine blood count.  
The 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 and mortality. 
Management of bone marrow suppression and related cytopenias in aplastic anemia is 
challenging with no clearly established guidelines regarding immunosuppression.  
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 complete blood cell counts (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 SRM and/or Laboratory 
Manual.  
• A matched peripheral blood sample should be collected in parallel with the bone 
marrow sample and provided to the Sponsor. Refer to the Laboratory Manual.  
• Initiate treatment with G-CSF 
• Consult an Infectious Diseases expert 
• Once alternative etiologies have been excluded, strongly consider 
immunosuppression (e.g., methylprednisolone 2 mg/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 


T M F -1 4 1 3 2 1 0 0  
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1 7 0  
 
i nitiate d, c o nti n ue f or a mi ni m u m of 5 da ys a n d t a per gra d uall y wit h a d vice fr o m 
e x pert c o ns ulta nts.  
Refer t o Secti o n  1 0. 9. 6  re gar di n g b o ne marr o w s u p pressi o n as a feat ur e of G V H D. 
1 0. 9. 8.  
M a n a g e m e nt of I m m u n e Eff e ct or C ell-A s s o ci at e d N e ur ot o xi cit y 
S y n dr o m e  (I C A N S) 
E nce p hal o pat h y h as bee n descri be d i n ass o ciati o n wit h c hi meric a nti ge n rece pt or ( C A R) 
T -cell t hera p y, a n d ter m e d C A R T -cell relate d e nce p hal o pat h y s y n dr o me, or C R E S 
[Neela p u , 2 0 1 8].  C R E S t y picall y ma nifests as a t o xic e nce p hal o pat h y w hi c h is ge n erall y 
re versi ble.  Earl y si g ns i ncl u de di mi nis he d atte nti o n, la n g u a ge distur ba n ce a n d i m paire d 
ha n d writi n g.  Ot her si g ns/s y m pt o ms i ncl u de c o nf usi o n, dis orie ntati o n, a gitati o n, a p hasia, 
s o m n ole nce, a n d tr e m ors.  I n s e vere cas es of C R E S ( defi ne d as Gra de  > 2), seiz ures, 
m ot or wea k ness, i nc o nti ne nce, me nt al o bt u n dati o n, i ncreas e d i n tracra nial press ure, 
pa pille de ma, a n d cere bral e de ma ma y als o oc c ur.  
C R E S occ urri n g wit hi n t he first 5 da ys after i m m u n ot hera p y ma y be c o nc urre nt wit h hi g h 
fe ver a n d C R S s y m pt o ms.  T his f or m of C R E S te n ds t o be of s h orter d urati o n, l o wer 
gra de ( G ra d e 1 t o 2), a n d ge n erall y re versi ble wit h a nti -I L-6 t hera p y.  C R E S prese nti n g 
as dela ye d n e ur ot o xicit y wit h seiz ures or e pis o des of c o nf usi o n ca n occ ur t hree or f o ur 
wee ks after C A R  T - cell t hera p y, after t he i nitial fe ver a n d C R S s u bsi de.  
I m m u ne Effect or Cell-Ass o ciate d Ne ur ot o xicit y S y n dr o me  (I C A N S) is a dis or der 
c haracterize d b y a pat h ol o gic pr ocess i n v ol vi n g t he ce ntral ner v o us s yste m f oll o wi n g a n y 
i m m u ne t hera p y t hat res ults i n t he acti vati o n or e n ga ge me nt of e n d o ge n o us or i nf use d T cells 
a n d/ or ot her i m m u ne ef fect or cells. S y m pt o ms or si g ns ca n be pr o gressi ve a n d ma y i ncl u de 
a p hasia, altere d le vel of c o nsci o us ness, i m pair me nt of c o g niti ve s kills, m ot or wea k ness, 
seiz ures, a n d cere bral e de ma. I C A N S ma y o cc ur wit h ot her ca ncer i m m u n ot hera pies, 
i ncl u di n g T C Rs.  Cancer patie nts ma y als o be at ris k f or I C A N S s y m pt o ms d ue t o ot her 
ca uses r a n gi n g fr o m mil d t o m o derate s o m n ole nce a n d c o nf usi o n as a res ult of se dati n g 
me dicati o ns t o seiz ures i n relati o n t o brai n metast ases.  T he p ossi ble c o ntri b uti o n of ot her 
me dicati o ns, u n derl yi n g disease , a n d/ or c o -m or bi dities s h o ul d be e val uate d w he n 
c o nsi deri n g a dia g n osis of I C A N S i n relati o n t o T -cell t hera p y. 
1 0. 9. 8. 1.  
Gr a di n g of I C A N S 
Lee et al [Lee , 2 0 1 9 ] ha v e de vel o pe d a ne w gra di n g s yste m f or I C A N S w hi c h 
i nc or p orates t he us e of a m o difie d versi o n of t he C A R T O X 10 -p oi nt ne ur ol o gical 
assess me nt ( C A R T O X - 1 0) t o ol, ter me d I m m u ne Effect or Cell-Ass ociate d 
E nce p hal o pat h y (I C E) sc ore.   P oi nts a re assi g ne d f or eac h of t he tas ks i n T a ble 2 9 , w hic h 
are perf or m e d c orrectl y.  
 is defi ne d b y a n o verall sc ore of 1 0. 
T he I C E s h o ul d be use d t o m o nit or all partici pa nt s f or I C A N S.  T he I C E s c ore is use d i n 
gra di n g  of I C A N S as pr ese nte d i n Ta ble 3 0 . 
C CI


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C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 7 1  
 
T a bl e 2 9  
I m m u n e Eff e ct or C ell-A s s o ci at e d E n c e p h al o p at h y ( I C E)‑ T o o l 
T a s k  
I C E P oi nt s  
Ori e nt ati o n t o y e ar, m o nt h, city, h os pit al  
T ot al of 4  p oi nts ( o n e p oi nt f or e ac h)  
N a m e t hr e e o bj ects  (f or ex a m pl e, p oi nt t o cl ock, p e n, 
a n d b utt o n ) 
T ot al of 3 p oi nts ( o n e p oi nt f or e ac h)  
F oll o w si m pl e c o m m a n ds (f or ex a m pl e, “ S h o w m e 2 
fi n g ers” or “ Cl os e y o ur ey es a n d stick o ut y o ur t o n g u e”  
1 p oi nt  
Writ e a st a n d ar d s e nt e nc e, e g. ‘ O ur n ati o n al bir d is t h e 
b al d e a gl e .’ 
1 p oi nt  
C o u nt b ack w ar ds fr o m 1 0 0 i n t e ns. 
1 p oi nt  
A b br evi ati o n:  I C E = I m m u n e Eff ect or C ell-Ass oci at e d E nc e p h al o p at hy ; I C A N S = I m m u n e Eff ect or C ell -Ass oci at e d 
N e ur ot oxicity Sy n dr o m e . 
Sc ori n g: 1 0, n o i m p air m e nt; 7 -9; G r a d e 1 I C A N S; 3-6, G r a d e 2 I C A N S; 0-2, G r a d e 3 I C A N S; 0 d u e t o p ati e nt 
u n ar o us a bl e a n d u n a bl e t o p erf or m I C E ass ess m e nt, G r a d e 4 I C A N S 
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 7 2  
 
1 0. 9. 8. 2.  
M o nit ori n g f or I m m u n e Eff e ct or C ell-A s s o ci at e d N e ur ot o xi cit y 
S y n dr o m e  (I C A N S) 
Brai n M RI ( or C T Sca n if M RI n ot f easi ble) m ust be o btai ne d f or all partici pa nt s at t he 
ti me of scree ni n g.  Brai n M RI s h o ul d be o btai ne d wit hi n 4 wee ks pri or t o 
l y m p h o de pleti o n if m ore t ha n 4 m o nt hs ha ve ela ps e d fr o m last brai n M RI. Brai n M RI 
ma y b e perf or me d at ot h er ti me p oi nts, if cli nicall y i n dicat e d . 
I C E s h o ul d be me as ure d o n t he da y of lete-cel i nf usi o n pri or t o recei vi n g tr eat me nt a n d 
t he n at least t hr o u g h Da y 8 acc or di n g t o t he s c he d ule of acti vities.  Partici p a nt s wit h 
k n o w n brai n metastases s h o ul d be m o nit ore d at least t wice per da y f or t he first 5 da ys 
f oll o wi n g lete-cel i nf usi o n.  If a partici pa nt  is f o u n d t o ha ve I C A N S, t he I C E s h o ul d be 
use d at least t wice p er da y u ntil res ol uti o n or sta bl e.  It ca n als o be use d at l ater visits if 
i n dicate d. 
1 0. 9. 8. 3.  
M a n a g e m e nt of I m m u n e Eff e ct or C ell-A s s o ci at e d N e ur ot o xi cit y 
S y n dr o m e  (I C A N S) 
T he rec o m me n de d ma n a ge m e nt of I C A N S s h o ul d be base d o n t o xicit y gra de.  Ta ble 3 1  
pr o vi des g ui d a nce o n t h e ma na ge me nt of I C A N S, a n d s h o ul d be i m ple me nte d i n 
acc or da nce wit h i nstit uti o nal g ui deli nes.     
A ne ur ol o g y c o ns ultati o n s h o ul d be o btai ne d f or all partici pa nt s wit h I C A N S f or 
t h or o u g h n e ur ol o gical e v al uati o n, a n d rec o m me n d ati o ns f or f urt her testi n g s uc h as 
electr oe n ce p h al o g ra m (E E G ) a n d ne ur oi ma gi n g as i n dicate d.  
T he f oll o wi n g t ests s h o ul d be c o n d ucte d e ver y d a y f or t he first wee k  a n d a p pr o xi matel y 
e ver y ot her d a y t here after  u ntil s y m pt o ms are i m pr o vi n g or a n alter nati ve dia g n osis is 
c o nfir me d:  
- 
L ocal tests:  
o  c he mistr y, h e mat ol o g y, ferriti n a n d c o a g ulati o n, as well as C -reati ve 
pr otei n ( C R P) la bs.  
As per SI T C 2 0 2 0 g ui deli nes:  
Acr oss se veral trials, t ociliz u ma b has faile d t o res ol ve s y m pt o ms of I C A N S, des pite 
alle viati n g se v ere C R S. It re mai ns t o be deter mi ne d w het her tar geti n g  I L-6 R i n is olati o n 
d uri n g est a blis he d C R S is i ns ufficie nt t o pre ve nt s u bse q ue nt ne ur ot o xicit y or if t he lac k 
of effic ac y is d ue t o t ociliz u ma b’s i na bilit y t o cr oss t he bl o o d – brai n barri er. It has b ee n 
p ost ulate d t hat t ociliz u ma b ma y w orse n I C A N S a n d t here f ore a n assess me nt of treat me nt 
pri orit y ma y b e re q uir e d bet wee n t he s e verit y of C R S a n d I C A N S. Alter n ati ve I L -6 
bl oc ka de s uc h as silt u xi ma b or t he I L -1 a nta g o nist, a na ki nra, ha v e bee n pr o p ose d as 
p ote ntial alter nati ves, b ut data are lac ki n g o n t heir safet y a n d efficac y.  
C ortic oster oi ds ha ve bee n s uccessf ull y use d f or t h e ma na ge m e nt of I C A N S a n d seiz ure 
pr o p h yla xis has bee n i m ple me nte d i n s o me st u dies, b ut t he i deal d ose a n d d urati o n ha ve 
n ot yet be e n deter mi ne d [ Ma us , 2 0 2 0]. 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 7 3  
 
T a bl e 3 1  
M a n a g e m e nt of I m m u n e Eff e ct or C ell-A s s o ci at e d N e ur ot o xi cit y 
S y n dr o m e  (I C A N S) 
I C A N S 
Gr a d e  
Tre at m e nt  
1  
• Vi gil a nt s u p p ortiv e c ar e; as pir ati o n pr ec a uti o ns; I V hy dr ati o n  
• Wit h h ol d or al i nt ak e of f o o d, m e dici n es, a n d fl ui ds, a n d ass ess s w all o wi n g 
• C o nv ert all or al m e dic ati o ns a n d/ or n utriti o n t o I V or e nt er al t u b e if s w all o wi n g is i m p air e d 
• Av oi d m e dic ati o ns t h at c a us e c e ntr al n erv o us syst e m d e pr essi o n 
• Ev al u at e f or ot h er c o ntri b uti n g c a us es a n d tr e at acc or di n gly 
• N e ur ol o gy c o ns ult ati o n i ncl u di n g f u n d osc o pic ex a m t o ass ess f or p a pill o e d e m a 
• M RI of t h e br ai n wit h a n d wit h o ut c o ntr ast ( C T sc a n of t h e br ai n if M RI is n ot f e asi bl e).  F urt h er t esti n g if 
i n dic at e d a n d a p pr o pri at e s uc h as di a g n ostic l u m b ar p u nct ur e wit h m e as ur e m e nt of o p e ni n g pr ess ur e if 
i ncr e as e d i ntr acr a ni al pr ess ur e is s us p ect e d ( as di a g n os e d by a n e ur ol o gist), or M RI of t h e s pi n e if t h e 
p artici p a nt  h as f oc al p eri p h er al n e ur ol o gic al d eficits  
• C o n si d er l ev etir ac et a m t h er a py a n d E E G if s eiz ur e activity is s us p ect e d 
• C o nsi d er a nti‑I L‑6 t h er a py  if ass oci at e d wit h c o nc urr e nt C R S . T ociliz u m a b 1 m ay w ors e n n e ur ot oxicity. 
M a n a g e m e nt of n e ur ot oxicity m ay t ak e pr ec e d e nc e ov er t h e m a n a g e m e nt of l o w -gr a d e C R S, b ut t his 
d o es n ot a p ply t o hi g h -gr a d e C R S. Alt er n ativ e I L -6 bl ock a d e m ay b e c o nsi d er e d ( e. g. silt uxi m a b) or t h e 
I L-1 a nt a g o nist, a n aki nr a . 
2  
• As d escri b e d f or G ra d e 1 P L U S  
• C o nsi d er I C U tr a nsf er 
• C o nsi d er c ortic ost er oi ds 2 
3  
• A s d escri b e d f or G ra d e 2 P L U S  
• I C U tr a nsf er is r ec o m m e n d e d 
• C ortic ost er oi ds ar e r ec o m m e n d e d  
• C o nsi d er r e p e at n e ur oi m a gi n g ( C T or M RI) ev ery 2 t o 3 d ays if p artici p a nt h as p ersist e nt G r a d e ≥3 
I C A N S 
4  
• As d escri b e d f or Gra d e 3  P L U S  
• C o nsi d er n e ur os ur gic al c o ns ult ati o n f or p artici p a nts wit h evi d e nc e of i ncr e as e d i ntr acr a ni al pr ess ur e  
• I C U m o nit ori n g; c o nsi d er m ec h a nic al v e ntil ati o n f or air w ay pr ot ecti o n 
A b br evi ati o ns: C R S = cyt oki n e r el e as e sy n dr o m e; C S F = c er e br os pi n al fl ui d; C T = c o m p ut e d t o m o gr a p hy; 
E E G  =  el ectr o e nc e p h al o gr a m; I C A N S = I m m u n e Eff ect or C ell-Ass oci at e d N e ur ot oxicity Sy n dr o m e; I C U = i nt e nsiv e 
c ar e u nit; I L-6 = i nt erl e uki n -6; I V =  i ntr av e n o us; M RI = m a g n etic r es o n a nc e i m a gi n g.  
1. Pl e as e r ef er t o S ecti o n 1 0. 9. 5  f or m a n a g e m e nt of c o nc urr e nt C R S. 
2. C o nsi d er d ex a m et h as o n e 1 0 m g I V ev ery 6 h  ( ≤ Gr a d e 3 I C A N S), or m et hyl pr e d nis ol o n e 1 0 0 0 m g I V ev ery 2 4  h f or 
3 d ays ( Gr a d e 4 I C A N S), if r efr act ory t o a nti ‑I L‑6 t h er a py, or f or I C A N S wit h o ut c o nc urr e nt C R S; o nc e i niti at e d 
c o nti n u e c ortic ost er oi ds f or at l e ast t w o d os es u ntil i m pr ov e m e nt t o Gr a d e 1  I C A N S a n d t h e n t a p er. 
 
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 7 4  
 
1 0. 9. 9.  
G uill ai n -B arr é S y n dr o m e  
O btai n a ne ur ol o g y c o ns ultati o n f or all partici pa nts wit h si g ns or s y m pt o ms s u g gesti ve of 
G B S f or a t h or o u g h ne ur ol o gical e val uati o n a n d e x pert rec o m me n dati o ns o n f urt her 
dia g n ostic w or k u p i ncl u di n g ele ctr o m y o gra p h y ( E M G), l u m bar p u nct ur e, a n d i nfecti o us 
pa nel t o g ui d e ma na ge me nt a n d f oll o w u p.  
C CI


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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 4. 
 
10.9.9.1. 
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 lasting days to 4 weeks (often 2 weeks) 
• Relative symmetry of weakness 
• Cranial nerve involvement, especially bilateral weakness of facial muscles 
• Autonomic dysfunction 
• Pain  


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10.9.9.2. 
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 
 
10.9.9.3. 
Erasmus GBS Respiratory Insufficiency Score (EGRIS) 
Probability of acute in the 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 
 
10.9.9.4. 
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 
 
10.9.9.5. 
Summary of diagnosis and treatment for GBS 
Additional information on the diagnosis and management of GBS (Figure 4) can be 
found in a review article on GBS [Willison, 2016]. 


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Figure 4 
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: Willison, 2016 (with permission from Willison H.). 
10.9.10. 
Lymphodepleting 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 6.9.1 for details of prohibited medications. 
The pre-conditioning chemotherapy is intended to cause lymphodepletion.  However, 
neutropenia is also common.  Prophylactic use of G-CSF is recommended for all 
participants.  G-CSF (e.g., filgrastim) should be used for management of neutropenia 


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according to ASCO guidelines [Smith, 2015].  G-CSF should be given starting ~24 hours 
after the administration of lymphodepleting chemotherapy until resolution of neutropenia 
(reaching an ANC of at least 2 × 109/L to 3 × 109/L or as per institutional practice).   
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 at ~24 hours after the final dose of cyclophosphamide.  
 


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10.10. 
Appendix 10: Guidelines for Assessment of Disease, 
Disease Progression, and Response Criteria 
10.10.1. 
RECIST v1.1 Guidelines 
Please note the following: 
• The same diagnostic method, including use of contrast when applicable, must 
be used throughout the study to evaluate a lesion. Contrast agents must be used 
in accordance with the Image Acquisition Guidelines. 
• All measurements must be taken and recorded in whole millimeters (mm). 
• Ultrasound is not a suitable modality of disease assessment. If new lesions are 
identified by ultrasound, confirmation by CT or MRI is required. 
• Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is generally 
not suitable for ongoing assessments of disease. However, FDG-PET can be 
useful in confirming new sites of disease where a positive FDG-PET scans 
correlates with the new site of disease present on CT/MRI or when a baseline 
FDG-PET was previously negative for the site of the new lesion. FDG-PET 
may also be used in lieu of a standard bone scan providing coverage allows 
interrogation of all likely sites of bone disease and FDG-PET is performed at 
all assessments. 
• If PET/CT is performed then the CT component can only be used for standard 
response assessments if performed to diagnostic quality, which includes the 
required anatomical coverage and prescribed use of contrast. The method of 
assessment must be noted as CT on the eCRF. 
Clinical Examination: Clinically detected lesions will only be considered measurable 
when they are superficial (e.g., skin nodules).  In the case of skin lesions, documentation 
by color photography, including a ruler/calipers to measure the size of the lesion, is 
required [Eisenhauer, 2009]. 
CT and MRI: Contrast enhanced CT with 5 mm contiguous slices is recommended.  
Minimum size of a measurable baseline lesion must be twice the slice thickness, with a 
minimum lesion size of 10 mm when the slice thickness is 5 mm.  MRI is acceptable, but 
when used, the technical specification of the scanning sequences must be optimized for 
the evaluation of the type and site of disease and lesions must be measured in the same 
anatomic plane by use of the same imaging examinations.  Whenever possible, the same 
scanner should be used [Eisenhauer, 2009]. 
X-ray: In general, X-ray should not be used for target lesion measurements owing to 
poor lesion definition.  Lesions on chest X-ray may be considered measurable if they are 
clearly defined and surrounded by aerated lung; however, chest CT is preferred over 
chest X-ray [Eisenhauer, 2009]. 
 


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Brain Scan: When brain scans are required, then contrast enhanced MRI is preferable to 
contrast enhanced CT. 
Guidelines for Evaluation of Disease 
Measurable and Non-Measurable Definitions 
Measurable Lesion: 
A non-nodal lesion that can be accurately measured in at least one dimension (longest 
dimension) of 
10 mm with MRI or CT when the scan slice thickness is no greater than 5 mm.  If the 
slice thickness is greater than 5 mm, the minimum size of a measurable lesion must 
be at least double the slice thickness (e.g., if the slice thickness is 10 mm, a 
measurable lesion must be 20 mm). 
10 mm caliper/ruler measurement by clinical exam or medical photography.  
20 mm by chest X-ray. 
Additionally, lymph nodes can be considered pathologically enlarged and measurable if 
15 mm in the short axis when assessed by CT or MRI (slice thickness 
recommended to be no more than 5 mm).  At baseline and follow-up, only the short 
axis will be measured. 
Non-Measurable Lesion: 
All other lesions including lesions too small to be considered measurable (longest 
diameter <10 mm or pathological lymph nodes with ≥10 mm and <15 mm short axis) as 
well as truly non-measurable lesions which include leptomeningeal disease, ascites, 
pleural or pericardial effusions, inflammatory breast disease, lymphangitic involvement 
of the skin or lung, and/or abdominal masses/abdominal organomegaly identified by 
physical exam that is not measurable by reproducible imaging techniques.  
Measurable Disease: The presence of at least one measurable lesion.  Palpable lesions 
that are not measurable by radiologic or photographic evaluations may not be utilized as 
the only measurable lesion. 
Non-Measurable only Disease: The presence of only non-measurable lesions.  
Note: Non-measurable only disease is not allowed per protocol. 
Response Criteria 
Evaluation of Target Lesions: 
Definitions for assessment of response for target lesion(s) are as follows: 
• Complete Response (CR):  Disappearance of all target lesions. Any pathological 
lymph nodes must be <10 mm in the short axis. 


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• Partial Response (PR):  At least a 30% decrease in the sum of the diameters of 
target lesions, taking as a reference, the Baseline sum of the diameters (e.g. 
percent change from Baseline). 
• Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for progressive disease. 
• Progressive Disease (PD): At least a 20% increase in the sum of the diameters of 
target lesions, taking as a reference, the smallest sum of diameters recorded since 
the treatment started (e.g. percent change from nadir, where nadir is defined as the 
smallest sum of diameters recorded since treatment start). In addition, the sum 
must have an absolute increase from nadir of 5 mm. 
• Not Applicable (NA): No target lesions at Baseline. 
• Not Evaluable (NE): Cannot be classified by one of the five preceding definitions. 
Note: 
• If lymph nodes are documented as target lesions the short axis is added into the 
sum of the diameters (e.g., sum of diameters is the sum of the longest diameters 
for non-nodal lesions and the short axis for nodal lesions). When lymph nodes 
decrease to non-pathological size (short axis <10 mm) they should still have a 
measurement reported in order not to overstate progression. 
• If at a given assessment time point all target lesions identified at Baseline are not 
assessed, sum of the diameters cannot be calculated for purposes of assessing CR, 
PR, or SD, or for use as the nadir for future assessments. However, the sum of the 
diameters of the assessed lesions and the percent change from nadir should be 
calculated to ensure that progression has not been documented. If an assessment 
of PD cannot be made, the response assessment should be NE. 
• All lesions (nodal and non-nodal) should have their measurements recorded even 
when very small (e.g., 2 mm). If lesions are present but too small to measure, 
5 mm should be recorded and should contribute to the sum of the diameters, 
unless it is likely that the lesion has disappeared in which case 0 mm should be 
reported. 
• If a lesion disappears and reappears at a subsequent time point it should continue 
to be measured. The response at the time when the lesion reappears will depend 
upon the status of the other lesions. For example, if the disease had reached a CR 
status then PD would be documented at the time of reappearance. However, if the 
response status was PR or SD, the diameter of the reappearing lesion should be 
added to the remaining diameters and response determined based on percent 
change from Baseline and percent change from nadir. 


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Evaluation of Non-target Lesions: 
Definitions for assessment of response for non-target lesions are as follows: 
• Complete Response (CR):  The disappearance of all non-target lesions. All lymph 
nodes identified as a site of disease at Baseline must be non-pathological (e.g., 
<10 mm short axis). 
• Non-CR/Non-PD:  The persistence of 1 or more non-target lesion(s) or lymph 
nodes identified as a site of disease at Baseline ≥10 mm short axis. 
• Progressive Disease (PD): Unequivocal progression of existing non-target lesions.  
• Not Applicable (NA):  No non-target lesions at Baseline. 
• Not Evaluable (NE):  Cannot be classified by one of the four preceding 
definitions. 
Note: 
• In the presence of measurable disease, progression on the basis of solely non-
target disease requires substantial worsening such that even in the presence of SD 
or PR in target disease, the overall tumor burden has increased sufficiently to 
merit discontinuation of therapy. 
• Sites of non-target lesions, which are not assessed at a particular timepoint based 
on the assessment schedule, should be excluded from the response determination 
(e.g., non-target response does not have to be "Not Evaluable").  
New Lesions 
New malignancies denoting disease progression must be unequivocal. Lesions identified 
in follow-up in an anatomical location not scanned at Baseline are considered new 
lesions. 
Any equivocal new lesions should continue to be followed. Treatment can continue at the 
discretion of the Investigator until the next scheduled assessment. If at the next 
assessment the new lesion is considered to be unequivocal, progression should be 
documented. 
Evaluation of Overall Response 
Table 32 presents the overall response at an individual time point for all possible 
combinations of tumor responses in target and non-target lesions with or without the 
appearance of new lesions for participants with measurable disease at Baseline. 


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Table 32 
Evaluation of Overall Response for Participants with Measurable 
Disease at Baseline 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR or NA 
No 
CR 
CR 
Non-CR/Non-PD or NE 
No 
PR 
PR 
Non-PD or NA or NE 
No 
PR 
SD 
Non-PD or NA or NE 
No 
SD 
NE 
Non-PD or NA or NE 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR=complete response, PR=partial response, SD=stable disease, PD=progressive disease, NA=Not applicable, 
and NE=Not Evaluable 
 
Note: Participants with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be 
classified as having "symptomatic deterioration." Objective response status is determined 
by evaluations of disease burden. Every effort should be made to document the objective 
progression even after discontinuation of treatment.  
In some circumstances, it may be difficult to distinguish residual disease from normal 
tissue. When the evaluation of CR depends on this determination, it is recommended that 
the residual lesion be investigated (fine needle aspirate/biopsy) to confirm the CR. 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment 
until disease progression/recurrence and will be determined programmatically by GSK 
based on the Investigators assessment of response at each time point.  
• To be assigned a status of SD, follow-up disease assessment must have met the 
SD criteria at least once after first dose at a minimum interval of 28 days.  
• If the minimum time for SD is not met, best response will depend on the 
subsequent assessments. For example, if an assessment of PD follows the 
assessment of SD and SD does not meet the minimum time requirement the best 
response will be PD. Alternatively, participants lost to follow-up after an SD 
assessment not meeting the minimum time criteria will be considered not 
evaluable. 
Confirmation Criteria: 
• To be assigned a status of PR or CR, a confirmatory disease assessment should be 
performed no less than 4 weeks (28 days) after the criteria for response are first 
met. 
 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 8 4  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 8 5  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 8 6  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 8 7  
 
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 8 8  
 
T a bl e 3 3  
I m a gi n g a n d Tr e at m e nt aft er Fir st R a di ol o gi c E vi d e n c e of 
Pr o gr e s si v e Di s e a s e  
 
Cli ni c all y St a bl e  
Cli ni c all y U n st a bl e  
I m a gi n g 
Tre at m e nt  
I m a gi n g 
Tre at m e nt  
First r a di ol o gic 
evi d e nc e of P D 
b as e d o n  
R E CI S T  v1. 1  
R e p e at i m a gi n g i n 
4 t o 8  w e eks t o 
c o nfir m P D. 
M ay c o nti n u e st u dy 
tr e at m e nt at t h e 
I nv esti g at or’s 
discr eti o n w hil e 
a w aiti n g c o nfir m at ory 
t u m or i m a gi n g. 
R e p e at i m a gi n g i n 
4 t o 8  w e eks t o 
c o nfir m P D p er 
I nv esti g at or’s 
discr eti o n.  
Disc o nti n u e tr e at m e nt  
R e p e at t u m or 
i m a gi n g c o nfir ms 
P D (i C P D) b as e d 
o n
 p er 
I nv esti g at or 
ass ess m e nt  
N o a d diti o n al 
i m a gi n g r e q uir e d. 
Disc o nti n u e tr e at m e nt 
( exc e pti o n p ossi bl e 
u p o n c o ns ult ati o n wit h 
Sp o ns or).  
N o a d diti o n al 
i m a gi n g r e q uir e d. 
N ot a p plic a bl e  
R e p e at t u m or 
i m a gi n g s h o ws 
i U P D b as e d o n  
 p er 
I nv esti g at or 
ass ess m e nt  
R e p e at i m a gi n g i n 
4 t o 8  w e eks t o 
c o nfir m P D.  M ay 
occ ur at n ext 
r e g ul arly 
sc h e d ul e d 
i m a gi n g visit. 
C o nti n u e st u dy 
tr e at m e nt at t h e 
I nv esti g at or’s 
discr eti o n.  
R e p e at i m a gi n g i n 
4 t o 8  w e eks t o 
c o nfir m P D p er 
I nv esti g at or’s 
discr eti o n.  
Disc o nti n u e tr e at m e nt  
R e p e at t u m or 
i m a gi n g s h o ws 
i S D, i P R, or i C R 
b as e d o n
 
p er I nv esti g at or 
ass ess m e nt  
C o nti n u e r e g ul arly 
sc h e d ul e d 
i m a gi n g 
ass ess m e nts.  
C o nti n u e st u dy 
tr e at m e nt at t h e 
I nv esti g at or’s 
discr eti o n.  
C o nti n u e r e g ul arly 
sc h e d ul e d 
i m a gi n g 
ass ess m e nts.  
M ay r est art st u dy 
tr e at m e nt if c o n diti o n 
h as i m pr ov e d a n d/ or 
cli nic ally st a bl e p er 
I nv esti g at or’s discr eti o n.  
N ext t u m or i m a gi n g 
s h o ul d occ ur acc or di n g 
t o t h e r e g ul ar i m a gi n g 
sc h e d ul e. 
A b br evi ati o ns: i C P D =  
 c o nfir m e d pr o gr essiv e dis e as e; i C R =  
 c o m pl et e r es p o ns e; i P R =  
 
p arti al r es p o ns e; 
= m o difi e d R es p o ns e Ev al u ati o n Crit eri a i n S oli d T u m ors 1. 1 f or i m m u n e -b as e d 
t h er a p e utics; i S D =  
 st a bl e dis e as e; i U P D = 
 unc o nfir m e d pr o gr essiv e dis e as e; P D = pr o gr essiv e 
dis e as e; R E CI S T v1. 1 = R es p o ns e Ev al u ati o n Crit eri a i n S oli d T u m ors v ersi o n 1. 1.  
 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 8 9  
 
Fi g ur e 5  
I m a gi n g a n d T r e at m e nt f or C li ni c all y S t a bl e P arti ci p a nt s A ft er t h e 
F ir st R a di ol o gi c E vi d e n c e of  P D a s A s s e s s e d b y t h e In v e sti g at or  
 
A b bre viati o ns:  
 = m o difie d Res p o nse E val uati o n Criteria i n S oli d T u m ors 1. 1 f or i m m u ne -base d 
t hera p e utics; P D = pr o gressi ve disease. 
 
C CI


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10.11. 
Appendix 11: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents. 
Amendment 06: 17-MAY-2021 
Overall Rationale for the Amendment:  
The overall rationale for this amendment is to: 
• Simplify/enhance screening and enrollment efforts 
• Broaden patient eligibility  
• Include additional safety tests and measures. 
 


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Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol  
Made administrative changes and corrected 
clerical errors. 
 
 
Eliminated redundant text. 
 
Replaced GSK3377794 asset number with 
letetresgene autoleucel / lete-cel name. 
 
Eliminated patient reported outcomes. 
 
 
 
Added flexibility in the collection of screening 
and/or baseline assessments. 
 
 
 
 
 
 
Added flexibility in the collection of 
confirmation scan following initial scan 
showing tumor response. Originally: from no 
earlier than 4 and no later than 8 weeks. 
Updated: no earlier than 4 to no later than 
the next scheduled imaging visit. 
Confirmation of progression will maintain 4-8 
week confirmation window.    
 
Updated persistence vs pharmacokinetics 
language 
 
Included an interim provision within the 
study to capture long-term follow-up data for 
patients who have yet to transition into the 
separate LTFU study. This is now 
considered study Part 5. 
 
 
 
 
 
Updated Study Design; Expanded patient 
eligibility to those with all actionable genetic 
aberrations into Arm C; Removed restriction 
on maximum lines of therapy for patients in 
all Arms; Additional safety 
inclusion/exclusion criteria were added for 
fitness of patient population. 
Changes were made 
for clarity and 
consistency 
 
For clarity 
 
For accuracy 
 
 
Decrease patient 
burden in non-
registrational study 
 
Simplify protocol 
procedures; simplify 
screening and 
enrollment efforts and 
add flexibility for patient 
scheduling 
 
 
Decrease patient 
burden 
 
 
 
 
 
 
 
For clarity and 
accuracy 
 
Provide a short 
transition period from 
the interventional 
portion of the study into 
the separate LTFU 
study for the collection 
of delayed AEs, 
persistence/RCL and 
survival information. 
 
Broaden patient 
eligibility 
  


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
1 9 2  
 
S e cti o n # a n d Na me  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
S ecti o n 1 - Pr ot ocol S u m m ary  
S ecti o n 3 - O bj ectiv e a n d 
E n d p oi nts  
 
U p d at e d Obj ectiv es a nd E n d poi nts 
l a n g u a ge; r e mov e d l a n gu a g e rel at e d to 
m e as ures o nly fr o m e nd p oi nts s ectio n; 
ali g n ed l a ng u a g e wit h p ati e nt p o p ul ati o n; 
s e p ar at ed s ec o n d ary o bj ectiv es u n d er 
“ effic acy” or “p h ar m ac oki n etics.” 
 
 
Cl arifi e d th at sec o nd ary efficacy o bj ectiv e 
will eval u ate l et e -c el al o n e a nd i n 
c o m bi n ati on wit h pe m br oliz u ma b. 
  
F or cl arity  
 
 
 
 
 
 
 
F or cl arity a nd t o ali g n 
wit h ot h er prot oc ols 
acr oss t h e l et e -cel 
pr o gr a m  
S ecti o n 1. 3 - Sc he d ule of Activiti es  I ncl u de d ti m e p oi nts for t h e c ollecti o n of a nti-
p e m br oliz u m a b anti b odi es a nd 
p e m br oliz u m a b ph ar m ac oki n etics s a m pl es . 
 
A d d e d clarifyi n g t ext a bo ut t h e c o m pl eti on of 
E o T visit a n d circ u mst a nces un d er w hic h C T 
/ M RI is not r e q uir e d duri n g E o T visit. 
F or cl arity a nd i n 
ali g n m e nt wit h M erck  
 
 
F or cl arity a nd t o 
d ecr e as e p ati e nt 
b ur d e n  
S ecti o n 1. 3 - Sc he d ule of Activiti es  
S ecti o n 8. 3 - S af ety M onit ori ng  
U p d at e d p ersiste nc e (f or s af ety) a n d R C L 
t esti n g r e q uire m e nts.  
Ali g n wit h u p d at ed F D A 
g ui d a nc e  
S ecti o n 1. 3 - Sc he d ule of Activiti es  
S ecti o n 5 - St u dy P o p ul ati o n  
 
Si m plifi e d E C G t esti n g r e quir e m e nts.  
 
 
A d d e d r estrictio ns to eli gi bility crit eri a a n d 
n e w s af ety/ m o nit orin g t ests.  
Si m plify pr otoc ol 
pr oc e d ures  
 
A d diti o nal saf ety 
m o nit ori n g  
S ecti o n 1. 3 - Sc he d ule of Activiti es 
S ecti o n 8. 2. 3 - C ar di ac 
Ass ess m e nts  
A d d e d s er u m tr o po ni n a n d N -ter mi n al pr o B-
ty p e n atri ur etic p epti d e ( NT -pro B N P) / B N P 
t ests 
A d diti o n of c ardi ac 
bi o m ark er t ests as p art 
of r e q uir ed 
scr e e ni n g/ bas eli n e visit 
ass ess me nts  
S ecti o n 1. 3 - Sc he d ule of Activiti es  
S ecti o n 8. 9. 2 - Tu m or Bio psies  
M ov e d ti m ep oi nt f or p ost T -c ell i nf usi o n 
t u m or bio psy a n d li q ui d bio psy fr o m w e ek 7 
t o w e ek 4. 
Ali g n wit h ot h er 
pr ot oc ols acr oss t h e 
l et e-c el pr o gr a m 
S ecti o n 1. 3 Sc he d ul e of Activiti es  
 
S ecti o n 8. 1 1 - P ati e nt I nt ervie ws 
a n d 
 
 
R e pl ac e d t h e t er m “ E n d -of -St udy i nt ervi e w” 
wit h “
,” t er ms 
w er e pr evi ously use d i nt erc h an g e a bly.  
F or cl arity a nd 
c o nsist e ncy withi n t he 
pr ot oc ol  
S ecti o n 1. 3 - Sc he d ule of Activiti es  
S ecti o n 1 0. 9. 8.2 - M onit orin g of 
I m m u n e Eff ect or C ell-Ass oci ate d 
Ne ur ot oxicity Sy n dr o m e (I C A N S)  
A d d e d br ain M RI as  r e q uir e d ass ess me nt 
d uri n g le uk ap h er esis eli gi bility scr e e ni n g; 
a d d e d flexibility in t h e c ollection of br ain 
M RIs d urin g b as elin e ass ess m e nts (if m ore 
t h a n 4 mo nt hs h ave el aps e d fr o m l ast br ain 
M RI).  
Ali g n wit h ot h er 
pr ot oc ols acr oss t h e 
l et e-c el pr o gr a m; ali g n 
wit h st u dy eli gi bility 
crit eri a 
C CI
C CI
C CI


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Section # and Name 
Description of Change 
Brief Rationale 
Section 2.2 - Background 
Updated background information. 
For clarity, in alignment 
with other protocols 
across the lete-cel 
program and in 
alignment with most 
recent Investigator’s 
Brochure for Lete-cel 
Section 2.3 - Benefit/Risk 
Assessment 
Updated Summary of Risks table in 
alignment with B/R profile for lete-cel 
program; Updated the Risk Assessment. 
For clarity, in alignment 
with other protocols 
across the lete-cel 
program and in 
alignment with most 
recent Investigator’s 
Brochure for Lete-cel 
Section 4 - Study Design 
 
Added language about aim to include 
approximately 5 NSCLC participants with 
squamous cell carcinoma (SCC) into Arms 
A/B.  
Improve enrollment of 
SCC patients, if 
possible  
Section 4.1 - Overall Design 
Clarified language about assignment of 
participants into Arms A or B.  
For clarity 
Section 4.1.3 - Part 3: 
Lymphodepletion/Treatment 
 
Section 6.4.1 - Premedication 
Clarified language about the use of 
antihistamines and acetaminophen prior to 
lete-cel infusion, following institutional 
guidance for dosage and specific 
medications. 
For clarity 
Section 4.1 - Overall Design 
 
Section 8.9.2 - Tumor Biopsies 
 
Section 9 - Statistical 
Considerations 
Consolidated details about statistical 
considerations and tumor biopsies from 
Section 4.1 to Sections 9 and 8.9.2, 
respectively; Added further details about 
tumor biopsy collection requirements. 
For clarity 
Section 4.4 - End of Study 
Definition 
Clarified End of Study definition; added 
definition for completion of interventional 
phase.  
For clarity and to align 
with other protocols 
across the lete-cel 
program 
Section 5 - Study Population 
Re-organized layout of eligibility criteria so 
inclusion/exclusion efforts are assessed in 
the appropriate step of the participant’s 
journey  
• Eligibility criteria not required to be met 
prior to target expression screening are 
now to be assessed during leukapheresis 
eligibility screening. 
• Some criteria originally required prior to 
lymphodepletion/treatment are now to be 
assessed during leukapheresis eligibility 
screening.  
• Where possible, eligibility criteria were 
consolidated. 
Simplify protocol 
procedures and to align 
with other protocols 
across the lete-cel 
program 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 5.1 - Inclusion Criteria 
Eliminated restrictions on when 
leukapheresis can be collected. 
 
 
 
Updated disease progression requirements 
from inclusion criteria. Eliminated 
requirement that stated: progression has 
been documented within 12 weeks from the 
last dose of PD-1/PD-L1 checkpoint 
blockade therapy. 
 
Updated predicted life expectancy 
requirements from ≥3 months at screening 
to ≥24 weeks from leukapheresis, per 
relevant IC.  
 
 
Eliminated flexibility for left ventricular 
ejection fraction (LVEF) requirements 
according to institutional standards for 
relevant IC; Updated requirement to ≥45%. 
 
Provided more details for the calculation of 
creatinine clearance, depending on age of 
participants. CKD-EPI formula was moved 
up from appendix. 
For clarity, to align with 
other protocols across 
the lete-cel program  
 
 
Broaden patient 
eligibility  
 
 
 
 
 
Measures to assess 
patient fitness; in 
alignment with other 
protocols across the 
lete-cel program 
 
Consistency across 
sites, in alignment with 
other protocols across 
the lete-cel program 
 
For clarity, to align with 
other protocols across 
the lete-cel program  
 
Section 5.2 - Exclusion Criteria 
Updated exclusion criterion on history of 
prior malignancies. Criterion now lists 
specific malignancies.   
 
Further restricted exclusion criterion for prior 
prior allogeneic/autologous bone marrow or 
solid organ transplantation.  
 
Updated testing requirements for active EBV 
infection in exclusion criteria. 
 
 
Updated exclusion criterion on history of 
allergic reactions to agents used in the 
study, to include dimethylsulfoxide (DMSO).  
 
Updated restricitions to prior radiotherapy 
prior to leukapheresis and 
lymphodepletion/treatment.  
For clarity 
 
 
 
Measures to assess 
patient fitness 
 
 
For clarity and in 
alignment with other 
GSK cell therapy 
studies 
 
In alignment with 
investigator’s brochure 
 
Additional safety 
monitoring and in 
alignment with other 
GSK cell therapy 
studies 
 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2 - Exclusion Criteria 
(Concomitant Treatments and 
Washout Periods) 
Added Tyrosine kinase inhibitors (TKIs) to 
table. 
 
 
 
Corrected washout period for investigational 
treatment, for alignment within the protocol. 
 
Removed gene therapy and allogeneic 
hematopoietic stem cell transplant from table 
for ‘Concomitant Treatments and Washout 
Periods.” 
For clarity, TKIs were 
missing from 
Concomitant 
Treatments and 
Washout Periods  
 
For clarity 
 
 
These treatments are 
not allowed, per 
Section 5, hence no 
washout period needed 
Section 5.3.3 - Contraception 
Section 8.4.7 - Pregnancy 
Included additional contraception 
requirements applicable to the use of 
fludarabine and cyclophosphamide 
chemotherapies. 
 
Added instruction to Investigator to advise 
participants on the conservation of sperm 
prior to initiating treatment.   
 
For participants who have persisting lete-cel 
beyond 12 months post infusion: once 
persistence test results show below level of 
detection for 2 consecutive times, Sponsor 
will notify the site that contraception period 
requirement is over. 
 
Clarification of 
contraception 
requirements 
Section 6.3 - Lymphodepleting 
Chemotherapy 
Added restrictions to the recommended 
lymphodepleting regimen, depending on 
participant’s medical history. Decreased 
fludarabine dose for patients with creatinine 
clearance between 30-50mL/min. 
 
Baseline assessments may be completed 
between Day -17 and Day -8 among 
participants who initiate the lymphodepleting 
regimen on Day -7. 
 
Added information about lymphodepletion 
dose calculation and creatinine clearance 
dose calculation. 
 
Added information for cyclophosphamide 
dose adjustment based on weight.  
Additional safety 
monitoring 
 
 
 
 
Provide flexibility in 
baseline screening 
efforts 
 
 
For clarity 
 
 
 
For clarity 
 
Section 6.4.2 - Lete-cel dose 
Added clarifying language for situations in 
which manufacturing of lete-cel has yielded 
less than the minimum target dose. 
For clarity 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 6.4.3 - Lete-cel 
Administration 
Added language emphasizing that 
leukoreduction filters must not be used for 
the infusion of Lete-cel. 
For clarity 
Section 6.9.1 - Prohibited 
Concomitant Medication and 
Treatment 
Addition of language prohibiting the 
administration of live vaccines during 
lymphodepletion and treatment, and for at 
least three months after. 
In alignment with other 
protocols across the 
lete-cel program 
 
Section 6.9.2 - Permitted 
Concomitant Medication and 
Treatment 
Added request to consult Sponsor before 
immunizing a study participant against SAR-
CoV-2 (COVID-19).  
 
Added “recommendations for participants on 
therapeutic anticoagulants.” 
In alignment with other 
protocols across the 
lete-cel program 
 
Section 6.10.2 - Guidelines for 
Pembrolizumab Withholding and 
Discontinuation 
 
Updated Table 15 - Dose Modification 
Guidelines and Toxicity Management 
Guidelines for Immune-Related Adverse 
Events Associated with Study Treatment, at 
the request of Merck, supplier of 
pembrolizumab. 
At the request of Merck 
Section 7.1.3 - Temporary 
Discontinuation 
Updated language on infusion related 
reactions 
For clarity and to align 
with other protocols 
across the lete-cel 
program 
Section 8.1.1 - Tumor Response 
Assessments 
Included additional details about the 
handling and transfer of tumor images. 
 
Included additional language for non-
contrast enhanced CT if participant is 
contraindicated for contrast scans or if they 
have renal compromise. 
For clarity 
Section 8.3 - Safety Monitoring 
Updated definition of Delayed AEs to align 
with updated FDA guidance [FDA, 2020a]. 
Updated definitions of 
6 categories of delayed 
AEs per FDA 
Section 8.4.4 - Adverse Events of 
Special Interest 
Included AESI of Gr 4 neutropenia lasting > 
28 days 
Additional safety 
monitoring 
 
Section 9 - Statistical 
Considerations 
Updated the statistical considerations for the 
study, in alignment with changes in the 
patient population and changes to standard 
of care. 
 
Amended analysis population definitions. 
For accuracy 
 
 
 
 
Align with other 
protocols across the 
lete-cel program 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 10.2 - Appendix 2 - Clinical 
Laboratory Tests 
Clarified that either BUN or Urea can be 
completed as part of clinical chemistry tests. 
 
Addition of Fibrinogen as part of the 
Coagulation test requirements. 
 
Addition of Ferritin, serum troponin,  
NT-proBNP / BNP as part of the Other 
Tests. 
Align with other 
protocols across the 
lete-cel program 
Section 10.9 - Appendix 9 
Supportive Care Guidance 
Added further details about hospitalization 
for T-cell infusion. 
For clarity and to align 
with other protocols 
across the lete-cel 
program 
Section 10.3.4 - Recording and 
Follow-Up on AE and SAE 
 
Section 10.9.5 - Management of 
Cytokine Release Syndrome 
 
Section 10.9.8 - Management of 
ICANS 
Addition of monitoring requirements and 
management recommendations for 
suspected CRS and/or ICANS.  
 
CRS grading will be based on Lee, 2019 and 
include Fever, Hypoxia and Hypotension. 
Organ toxicities associated with CRS will be 
graded according to NCI-CTCAE v5.0 and 
do not influence CRS grading.  
 
ICANS grading will be based on Lee, 2019. 
Align with SITC 2020 
guidelines on immune 
effector cell-related 
adverse events  
Section 10.3.5 - Reporting of SAE 
to GSK 
Removed 72 hr requirement for the 
Investigator to verify relationship between 
each SAE and IP/study participation. 
Investigator must still document in the 
medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of 
causality. 
For clarity 
Section 10.10.1 - RECIST v1.1 
Guidelines 
Added details about RECIST v1.1 
assessments.  
For clarity 
 
Amendment 05: 21-FEB-2020 
Overall Rationale for the Amendment:  
The overall rationale for this amendment is to add clarification regarding measurable 
lesion, to remove docetaxel as exclusion criterion and add platinum-based combination 
chemotherapy as an inclusion criterion. Docetaxel therapy as supportive therapy between 
leukapheresis and the start of lymphodepletion is removed. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol  
Made administrative changes and corrected 
clerical errors. 
Changes were made 
for clarity and 
consistency 


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Section 1.3-Schedule of 
Assessments  
Section 4.1-Overall Design  
Section 5.1.1-Inclusion Criteria 
Section 8.0 – Study 
assessments and procedures 
Section 8.9.2-Tumor Biopsies 
 
Clarify that fresh biopsy may be considered 
upon consultation with GSK Medical Monitor 
(or designee) at screening for antigen 
expression  
Changes were made 
for clarity and 
consistency 
Section 5.1.3-Lymphodepletion 
/ Treatment (Part 3) 
Add platinum-based combination 
chemotherapy as an inclusion criterion 
Added clarification regarding measurable 
lesion per RECIST 1.1. 
To improve protocol 
clarity 
Section 5.2.1-Screening 
(Part 1) 
Removal of docetaxel therapy as exclusion 
criterion and removal as supportive therapy 
between leukapheresis and the start of 
lymphodepletion.  
Docetaxel could benefit 
patient as Standard of 
Care treatment (SoC) 
Section 6.1- Leukapheresis 
Blood volume collection moved to Apheresis 
Manual 
To improve protocol 
clarity and align with 
Apheresis Manual 
Section 6.2-Supportive 
Therapy and/or SoC Therapy 
Before Lymphodepletion 
Removal of docetaxel therapy as supportive 
therapy between leukapheresis and the start 
of lymphodepletion. 
Introduced as inclusion 
criterion 
Section 8.2.2-Vital Signs 
Added clarification that vital signs should be 
assessed as per the institutional standards 
and the same methods should be used 
throughout the course of the study. 
To improve protocol 
clarity 
 
Amendment 04 29-OCT-2019 
Overall Rationale for the Amendment:  
The overall rationale for this amendment is the addition of fresh biopsy collection in 
order to perform antigen expression screening, in absence of archival tumor tissue. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol  
Made administrative changes and corrected 
clerical errors. 
Changes were made 
for clarity and 
consistency 
Synopsis  
Section 1.3-Schedule of 
Assessments  
Section 4.1-Overall Design  
Section 5.1.1-Inclusion Criteria 
Section 8.0 – Study 
assessments and procedures 
 
Addition of option for fresh biopsy collection 
during screening for antigen expression  
Change was made to 
include fresh biopsy 
collection in case 
archival tumor tissue is 
not available at the 
time of tumor antigen 
screening for 
enrollment. 
Section 8.4.1- Time Period and 
Frequency for Collecting AE 
and SAE Information 
Added clarification to AEs collected during 
the various parts of the study (Parts 1-4) 
To improve protocol 
clarity 


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Amendment 03: 01-OCT-2019 
Overall Rationale for the Amendment:  
The overall rationale for this amendment is the removal of randomization to Arm A and 
Arm B, clarification of aspects related to participant enrollment and clarification 
regarding study stopping and pausing rules.  These additions included modification of 
lymphodepleting regimen for older participants, modification of dose range 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 
 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol  
Made administrative changes and corrected 
clerical errors. 
Changes were made 
for clarity and 
consistency 
Title, Study schema, Participant 
Flow and throughout the 
protocol 
Remove randomization from study design. 
Changes include 
removal of 
randomization to Arm 
A and Arm B. 
Throughout the protocol 
Explicitly stated that NSCLC patients with 
NTRK gene fusion and/or any other 
actionable genetic aberration that can be 
treated with targeted standard of care 
(NCCN recommended) therapy will not be 
included in this study. 
Changes were made 
for clarity. 
Synopsis  
Section 4.1-Overall design  
Section 5.1.1-Sccreening (Part 
1)  
Section 5.1.2-Leukapheresis 
(Part 2) 
Section 5.2.2-Leukapheresis 
(Part 2) 
and throughout the protocol 
 
Added language to allow enrollment to this 
study of participants that have already been 
deemed eligible for HLA alleles and NY-
ESO-1 and/or LAGE-1a tumor antigen in 
other studies. 
Clarify the total number of participants to be 
enrolled 
Provide additional information regarding 
tumor biopsies 
To allow enrollment of 
participants in this 
study. 
 
 
Changes were made 
for clarity. 
Synopsis  
Section 4.3.2- Justification of 
GSK3377794 Dose 
Section  
Section 6.4.2-GSK3377794 
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 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3-Schedule of 
Activities (SoA) 
Made changes to Schedule of Activities.  
Changes were made 
for clarity, to correct 
any incongruencies 
and to reflect all study 
assessments. 
Previously, some 
assessments were in 
the protocol’s main text 
but not in the visit 
schedules. 
Section 2.3.1-Risk assessment 
for GSK3377794 
Section 2.3.2-Benefit for 
GSK3377794 
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 4.3.1-Justification of 
Lymphodepleting 
chemotherapy 
Section 6.3.1- Lymphodepletion 
Dose Modification 
Added lymphodepleting regimen 
adjustments for participants  60 years old 
and participants with severe cytopenia 
To improve 
participants safety 
Section 4.3.2- Justification of 
GSK3377794 Dose 
Section 6.4.2-GSK3377794 
Dose 
Remove dose description for participants 
weighing <40kgr. All adult participants will 
receive a dose range of 1 to 8 × 109 (billion) 
transduced cells 
To align with other 
protocols across the 
GSK3377794 program 
and to improve 
protocol clarity 
Section 5.1.1-Screening (Part 
1)  
Added language to clarify the measurable 
disease is not an indispensable requirement 
for enrollment/leukapheresis 
To improve protocol 
clarity 
Section 5.1.3-
Lymphodepletion/Treatment 
(Part 3) 
Added language to clarify the measurable 
disease per RECIST v1.1 requirement for 
lymphodepletion/treatment 
To improve protocol 
clarity 
Section 5.2.1-Screening (Part 
1) 
Section 6.2-Supportive Therapy 
and/or SoC Therapy Before 
Lymphodepletion 
Added language to Docetaxel therapy as 
supportive therapy between leukapheresis 
and the start of lymphodepletion 
To improve protocol 
clarity 
Section 5.2.1-Screening (Part 
1) 
 
Added language to clarify active infections 
that are part of exclusion criteria 
To improve protocol 
clarity 
Section 6.3.1 Lymphodepletion 
Dose Modification 
Added lymphodepleting regimen 
adjustments for participants ≥60 years old 
and participants with severe cytopenia 
To improve 
participants safety 
Section 7.1- Discontinuation of 
study intervention 
Revised Study stopping and pausing rules 
To align with other 
protocols across the 
GSK3377794 program 
Section 8-Screening 
Assessments 
Clarify that Liquid Biopsy (Blood Sample) is 
an optional assessment 
Total blood volume updated to 500ml 
To improve protocol 
clarity 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.1.2-Long-Term 
Follow-up 
Section 8.4.5- Reporting 
Criteria during Long-Term 
Follow-Up (Years 1 through 15) 
Include definition and reporting of delayed 
adverse events 
 
To improve protocol 
clarity 
Section 8.3.1.1-Mandated 
Study Pause Due to Guillain-
Barré Syndrome (GBS) 
Revised language to utilize diagnostic 
guidance for GBS [Fokke, 2014] 
To align with other 
protocols across the 
GSK3377794 program 
Section 8.4.1- Time Period and 
Frequency for Collecting AE 
and SAE Information 
Added clarification to AEs collected during 
the various parts of the study (Parts 1-4) 
To improve protocol 
clarity 
Section 8.4.4- Adverse Events 
of Special Interest (AESIs) 
Added clarification to AESIs collected during 
the various parts of the study (Parts 1-4) 
To improve protocol 
clarity 
Section 8.4.7-Pregnancy 
Added clarification regarding contraception 
period for participants that received 
pembrolizumab 
To improve protocol 
clarity 
Section 8.9-Biomarkers 
Added mutational analyses at Baseline visit 
as clinical biomarker assessment 
To improve protocol 
clarity 
Section 8.9.9-Stool Collection 
for Microbiome Analysis and  
Section 1.3-Schedule of 
Activities (SoA) 
Included Stool collection for Microbiome 
Analysis 
Evaluate stool 
microbiome 
composition and 
associate with 
response to treatment 
Section 10.9.5 Management of 
Cytokine Release Syndrome 
(CRS) 
Revised guidelines to utilize the American 
Society for Transplantation and Cellular 
Therapy updated grading system 
Changes were based 
on Regulatory Agency 
feedback 
Section 10.9.8-Management of 
Immune Effector Cell-
Associated Neurotoxicity 
Syndrome (ICANS) 
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 10.9.9- Guillain-Barré 
Syndrome (GBS) 
Revised language to utilize diagnostic 
guidance for GBS [Fokke, 2014; Walgaard 
2010; Walgaard, 2011] 
To improve protocol 
clarity and safety 
monitoring 
Abbreviations: AESIs: Adverse Events of Special Interest GBS: Guillain-Barré Syndrome; ICANS: Immune Effector 
Cell-Associated Neurotoxicity Syndrome; NRTK: Neurotrophic Tropomyosin-Related Kinase; 
Amendment 02: 13-FEB-2019 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol 
Made administrative changes and 
corrected clerical errors. 
Changes were made 
for clarity and 
consistency. 
Throughout the protocol 
Participants that receive Pembrolizumab 
Therapy Following Disease Progression 
after GSK3377794 Infusion are 
described as Part 4 Arm A Only. 
Changes were made 
for clarity. 


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Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol 
Explicitly stated that NSCLC patients 
with BRAF, HER2, and/or any other 
actionable genetic aberration that can 
be treated with targeted standard of care 
(NCCN recommended) therapy will not 
be included in this study. 
Changes were made 
for clarity. 
Throughout the protocol 
Described participants as either having 
NSCLC with WT EGFR and WT 
ALK/ROS1 or NSCLC with EGFR or 
ALK/ROS1 aberration. 
Changes were made 
for clarity (to clearly 
contrast the two 
types of participants). 
Throughout the protocol 
Deleted references to KEYTRUDA 
Package Insert 2017 and deleted 
premedication before the first 
pembrolizumab infusion. 
Changes were made 
because they were 
requested by Merck. 
Section 1.1-Synopsis 
Section 1.2-Schema 
Section 2.2-Background 
Section 3.0-Objectives and 
Endpoints 
Section 4.1-Overall Design 
Section 5.0-Study 
Population 
Section 6.7-Measures to 
Minimize bias: 
Randomization and Blinding 
Objectives/Endpoints and Schema were 
updated to specify WT EGFR and WT 
ALK/ROS1 NSCLC in Arms A and B, 
and EGFR or ALK/ROS1 aberration 
NSCLC in Arm C. 
Changes were made 
to study design to 
include patients with 
specific molecular 
characteristics. 
Section 1.1-Synopsis 
Number of Participants changed from 44 
to 45, 15 participants per arm. 
Changes were made 
to accommodate 
changes in study 
design and addition 
of Arm C. 
Section 1.3-Schedule of 
Activities (SoA) 
Made changes to Schedule of Activities.  Changes were made 
for clarity, to correct 
any incongruencies 
and to reflect all 
study assessments. 
Previously, some 
assessments were in 
the protocol’s main 
text but not in the 
visit schedules. 
Section 2.2.3-Rationale for 
the Combination Regimen 
Section 4.1-Overall Design 
Made changes to clarify previous lines 
of treatment. 
Changes were made 
for clarity, to correct 
any incongruencies 
and accommodate 
changes in study 
design. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1-Overall Design 
Text was added to describe in detail: 
• Parts 1-4 of study and Arm C 
• Screening process and steps 
• Leukapheresis/Manufacture 
requirements and timelines 
• Lymphodepletion requirements  
• Need for G-CSF, Mesna, 
antihistamines and 
acetaminophen administration 
• Storage timelines of apheresis 
and/or drug product 
Changes were made 
for clarity and to 
describe changes in 
study design 
regarding Arm A, B 
and C participants. 
Section 4.4.1-Treatment 
Completion 
Text was added to describe completion 
of treatment phase of the study for Arms 
A, B and C. 
Changes were made 
for clarity, to correct 
any incongruencies. 
Section 4.1- Overall Design 
Section 5.1-Inclusion Criteria 
Section 5.2-Exclusion 
Criteria 
Text was added to: 
• clarify the timing and process of 
screening assessments 
• inclusion and exclusion (Part 1, 
Part 2 and Part 3 of study 
conduct) criteria stating the 
intended participant population, 
specified participants should 
have previously received and 
failed appropriate target therapy 
per NCCN guidelines 
• define “intolerant” to chemo-
radiotherapy 
• clarify the number and type of 
prior therapies 
• update Table 10 (Adequate 
Organ Function) 
• exclusion criteria for infectious 
diseases 
Changes were made 
for clarity and/or 
because they were 
requested by the 
Regulatory Agency. 


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Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol 
The word “rescue” in association with 
pembrolizumab given to Arm A 
participants who have progressive 
disease after GSK3377794 infusion was 
removed. 
Where the abbreviation R was used for 
“Rescue” this is now being replaced with 
letter P to denote Pembrolizumab 
administration for Arm A participants 
that receive Pembrolizumab following 
progression after GSK3377794 infusion. 
Change was 
requested by the 
Regulatory Agency. 
Section 4.1 Overall Design 
Text was added to explain the meaning 
of “prior standard of care therapy 
refused” by a participant. 
Change was 
requested by the 
Regulatory Agency. 
Section 4.1 Overall Design  
and  
Section 4.4.1 Treatment 
Completion 
Text was included to explain “on study” 
for participants who receive 
pembrolizumab after disease 
progression after GSK3377794 infusion 
in Arm A. 
Text was added for 
clarity. 
Section 5.1.3-
Lymphodepletion/Treatment 
(Part 3) 
Edited Inclusion Criterion 15. 
Text was edited for 
clarity. 
Section 5.2.3- 
Lymphodepletion/Treatment 
(Part 3) 
Deleted “replacement therapy (e.g., 
thyroxine, insulin, or” from exclusion 
criterion 25b. 
The exclusion 
criterion is meant to 
exclude 
immunosuppressive 
therapy. The deleted 
items are not 
immunosuppressive. 
Section 5.3- Lifestyle 
Considerations 
Text was added to describe additional 
activities. 
Text added for clarity 
Section 6.1-Leukapheresis 
Lymphocyte and CD3 count were 
removed. 
Text removed to 
avoid redundancy 
with counts described 
in Section 5.1.2 
(Leukapheresis). 
Section 6.2- Supportive 
Therapy and/or SoC 
Therapy Before 
Lymphodepletion 
  
and throughout the protocol 
Text was added to describe the 
intermediate SoC line of therapy allowed 
between leukapheresis and treatment. 
Nearly identical sections of text 
elsewhere in the protocol were edited to 
simply refer to Section 6.2. 
Text was edited for 
clarity and to remove 
redundancy. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 6.4.3-GSK3377794 
Administration 
Text referring to drug preparation and 
administration was removed because 
the information can be found in the Drug 
Product and Infusion Manual. 
Redundant text 
(information on drug 
preparation and 
administration is 
described in the Drug 
Product and Infusion 
Manual) was 
removed. 
Section 6.4.4- 
Pembrolizumab Therapy 
Following Disease 
Progression after 
GSK3377794 Infusion (Part 
4, Arm A Only) 
Section 6.5- Pembrolizumab 
Infusion in Arms B and C 
and Part 4 Arm A 
Section 6.5.1- Schedule 
Modification Guidelines for 
Pembrolizumab 
Section 6.10.2- Guidelines 
for Pembrolizumab 
Withholding and 
Discontinuation 
Text was updated to describe 
pembrolizumab administration and 
duration of treatment to Arm A Part 4 
participants. 
Text was added for 
clarity. 
Section 6.6-
Preparation/Handling/ 
Storage/Accountability 
T-cell product storage temperature was 
changed to ≤ -130 °C. 
Text was edited to 
correct any 
incongruency. 
Section 6.9-Concomitant 
Therapy 
Text was added to include replacement 
therapy and an intermediate SoC line of 
therapy between leukapheresis and 
treatment. 
Text was added for 
clarity and 
consistency within 
the protocol.  
Section 6.9.1-Prohibited 
Concomitant Medication and 
Treatment 
 
Text about permitted steroid treatment 
was edited. 
Text was added for 
clarity and 
consistency within 
the protocol. 
Section 7.1-Discontinuation 
of Study Intervention 
Group stopping criteria was updated. 
Changes were based 
on Regulatory 
Agency feedback and 
to provide clarity. 
Section 7.2-Participant 
discontinuation/Withdrawal 
from the study 
Text was changed to include that further 
evaluation be performed at EoT Visit. 
Text edited to provide 
clarity. 


T M F -1 4 1 3 2 1 0 0  
C O N FI D E N TI A L  
 
 
 
2 0 8 4 7 1  
 
2 0 6  
 
S e cti o n # a n d N a me  
D e s cri pti o n of  C h a n g e  
Bri ef R ati o n al e  
S ecti o n 8.0 -St u dy 
ass ess m e nts a nd 
pr oc e dur es  
•  C h a n ge d m axi mu m bl o o d vol u m e 
p er p articip a nt. M axi mu m a m o u nt 
will n ot exc ee d 4 4 0 mL wit hin 
5 6  days, excl u di ng l e uka pher esis.  
•  S p ecifi ed t hat H L A a n d tu mor 
a nti ge n ass ess m e nts o bt ai ne d 
4 2  days prior to l e uka ph er esis 
mi g ht b e acc ept a bl e.  
•  B as eli n e ti meli n e w as a dd ed.  
•  St u dy a nd c o m pl eti o n p hase 
d escrip ti o n w as u p dat e d. 
T ext e dite d t o pr ovi d e 
acc ur acy an d clarity.  
 
S ecti o n 8.3. 1 -Saf ety R evi e w 
T e a m ( S R T)  
S R T d escripti on w as u p date d  
C h a n ges m a d e to 
pr ovi d e acc ur acy a n d 
cl arity. 
S ecti o n 8.3. 3 -T L Ts for 
p e m br oliz u m a b  
T L Ts w er e up d at e d.  
C h a n ges m a d e to 
pr ovi d e acc ur acy a n d 
cl arity. 
S ecti o n 8.4 - A dvers e Eve nts 
a n d S eri o us A dvers e Eve nts  
T ext r e gar di n g M ed D R A a nd t he N CI -
C T C A E w as a d d ed.  
C h a n ges m a d e p er 
r e q u est fr o m M erck. 
S ecti o n 8.4. 1 - Ti me P eri o d 
a n d Fr eq ue ncy for C oll ecti ng 
A E a n d S A E Inf or matio n  
S ecti o n w as u p dat e d wit h full list of 
A E SIs.  
C h a n ges m a d e to 
pr ovi d e acc ur acy a n d 
cl arity. 
S ecti o n 8.4. 9 -Pr ogr essi o n of 
u n derlyi n g m ali g na ncy  
 
S ecti o n w as a d de d.  
S ecti o n a dd ed t o 
cl arify r e p orti n g 
r e q uire m e nts f or 
u n derlyi n g dis eas e 
ev e nts.  
S ecti o n 8.1 1.6 -E n d of St u dy 
I nt ervi e w 
S ecti o n w as u p dat e d.  
C h a n ges w er e m a d e 
f or cl arity a nd 
ali g n m e nt wit h 
S ecti o n 1.3.  
S ecti o n 9 -Statistic al 
C o nsi d er atio ns  
S ecti o n w as u p dat e d.  
C h a n ges w er e ma d e 
t o acco m m o d ate 
c h a ng es i n st u dy 
d esi g n.  
C CI


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Section # and Name 
Description of Change 
Brief Rationale 
Section 10.9.9-Guillain-Barré 
Syndrome 
Section was added. 
Section was added to 
provide guidance for 
management of GBS. 
Amendment 01: 17-OCT-2018 
Overall Rationale for the Amendment: Changes made to the protocol were requested by 
Regulatory Agency 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 # and 
Name 
Description of Change 
Brief Rationale 
2.3.1 Risk 
Assessment 
Updated Table 7. Summary of Risks and 
Risk-Mitigation Strategies Related to 
Study Treatments to include:  
• CRS events ≥ grade 3 will now be 
reported as a SAE and will be 
reported to GSK within 24 hrs.   
• Update to risk assessment to add 
additional risk of Guillain-Barré 
syndrome and other demyelinating 
neuropathies. 
These are Regulatory Agency 
requested changes due to the 
2 reports of Guillain-Barré 
syndrome 
Section 5.2.1 
Screening 
(Exclusion 
Criteria ‘h’) 
Participants with prior or active 
demyelinating disease will now be 
excluded from study participation.   
This is a Regulatory Agency 
requested change due to the 2 
reports of Guillain-Barré 
syndrome   
Added  
Section 8.3.1.1 
Mandated Study 
Pause due to 
GBS 
A mandatory pause in enrollment and 
stopping GSK3377794 treatment for all 
participants within the GSK3377794 
studies has been introduced if an 
occurrence of GBS occurs.   
This is a Regulatory Agency 
requested change due to the 2 
reports of Guillain-Barré 
syndrome.   
Added  
Section 8.3.6 
Monitoring and 
management for 
Demyelinating 
Neuropathy and 
other 
Neurological 
events 
 
Provides guidance on when a 
neurological consultation / evaluation is 
to occur for those participants receiving 
GSK3377794 with a Grade 2 or higher 
neurologic events of a ≥ 7-day duration. 
Further, this section provides guidance 
for those participants who develop signs 
and symptoms consistent with GBS.     
These are Regulatory Agency 
requested changes due to the 
2 reports of Guillain-Barré 
syndrome   


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 8.4.4 
Adverse of 
Special Interest 
(AESIs) 
Added Guillain-Barré syndrome or acute 
demyelinating neuropathy as an AESI.  
Further, added reporting criteria for 
Grade 3 or higher CRS, and for Guillain-
Barré syndrome or other demyelinating 
neuropathies. 
These are Regulatory Agency 
requested changes due to the 
2 reports of Guillain-Barré 
syndrome   
 


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11. 
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TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 6 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 7 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan ............................ 7 
2.2. 
Study Objective(s) and Estimand(s) / Endpoint(s) ......................................... 7 
2.3. 
Study Design ................................................................................................ 9 
2.4. 
Statistical Analyses ..................................................................................... 13 
3. 
PLANNED AND AD HOC ANALYSES ................................................................... 14 
3.1. 
Ad hoc Analyses ......................................................................................... 14 
3.2. 
Interim Analyses ......................................................................................... 14 
3.3. 
Final Analyses ............................................................................................ 16 
4. 
ANALYSIS POPULATIONS ................................................................................... 17 
4.1. 
Protocol Deviations ..................................................................................... 18 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 19 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 19 
5.2. 
Baseline Definitions .................................................................................... 20 
5.3. 
Multicentre Studies ..................................................................................... 21 
5.4. 
Examination of Covariates, Other Strata and Subgroups ............................ 21 
5.4.1. 
Covariates and Other Strata ........................................................ 21 
5.4.2. 
Examination of Subgroups ........................................................... 21 
5.5. 
Multiple Comparisons and Multiplicity ......................................................... 21 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 21 
6. 
STUDY POPULATION ANALYSES ....................................................................... 22 
6.1. 
Overview of Planned Study Population Analyses ........................................ 22 
6.2. 
Disposition of Participants ........................................................................... 22 
6.3. 
Demographic and Baseline Characteristics ................................................. 23 
6.4. 
Concomitant Medications ............................................................................ 23 
6.5. 
Study Treatment Exposure ......................................................................... 24 
6.6. 
Anti-Cancer Therapies and Surgery ............................................................ 25 
6.6.1. 
Prior Anti-Cancer Therapies......................................................... 25 
6.6.2. 
On-study Anti-Cancer Therapies .................................................. 26 
7. 
EFFICACY ANALYSES .......................................................................................... 27 
7.1. 
Final Efficacy Analyses ............................................................................... 27 
7.1.1. 
Endpoint / Variables ..................................................................... 27 
7.1.2. 
Summary Measure ...................................................................... 28 
7.1.3. 
Population of Interest ................................................................... 29 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events ................ 29 
7.1.5. 
Statistical Analyses / Methods ..................................................... 29 
7.2. 
Secondary Efficacy Analyses ...................................................................... 30 
7.2.1. 
Endpoint / Variables ..................................................................... 30 
7.2.2. 
Summary Measure ...................................................................... 33 
7.2.3. 
Population of Interest ................................................................... 34 


 
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7. 2. 4.  
Str at e g y f or I nt er c urr e nt ( P o st -R a n d o mi z ati o n) E v e nt s  ................ 3 4  
7. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 3 5  
8.  
S A F E T Y A N A L Y S E S  ............................................................................................. 4 1  
8. 1.  
A d v er s e E v e nt s A n al y s e s  ........................................................................... 4 1  
8. 2.  
A d v er s e E v e nt s of S p e ci al I nt er e st A n al y s e s  .............................................. 4 5  
8. 3.  
Cli ni c al L a b or at or y A n al y s e s  ....................................................................... 4 7  
8. 3. 1.  
A n al y si s of Li v er F u n cti o n T e st ( L F T)  ........................................... 4 9  
8. 4.  
Ot h er S af et y A n al y s e s  ................................................................................ 5 0  
8. 4. 1.  
D e at h s  ......................................................................................... 5 0  
8. 4. 2.  
P erf or m a n c e St at u s  ..................................................................... 5 1  
8. 4. 3.  
E C G  ............................................................................................. 5 1  
8. 4. 4.  
Vit al Si g n s  .................................................................................... 5 1  
8. 4. 5.  
Pr e g n a n ci e s  ................................................................................. 5 1  
8. 4. 6.  
C ar di o v a s c ul ar E v e nt s  ................................................................. 5 2  
8. 4. 7.  
R e pli c ati o n C o m p et e nt L e nti vir u s a n d I nt e gr ati o n Sit e 
A n al y si s  ....................................................................................... 5 2  
9.  
P H A R M A C O KI N E TI C A N A L Y S E S  ......................................................................... 5 4  
9. 1.  
Pri m ar y P h ar m a c o ki n eti c A n al y s e s  ............................................................. 5 4  
9. 2.  
S e c o n d ar y P h ar m a c o ki n eti c A n al y s e s  ........................................................ 5 4  
9. 2. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 5 4  
9. 2. 2.  
S u m m ar y M e a s ur e  ...................................................................... 5 5  
9. 2. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 5 6  
9. 2. 4.  
S t ati sti c al A n al y s e s / M et h o d s ..................................................... 5 6  
1 0.  BI O M A R K E R A N A L Y S E S  ...................................................................................... 5 7  
1 1.  A D DI TI O N A L A N A L Y S E S D U E T O T H E C O VI D -1 9 P A N D E MI C  ........................... 5 8  
1 1. 1.  St u d y P o p ul ati o n  ......................................................................................... 5 8  
1 1. 1. 1.  
S u bj e ct Di s p o siti o n  ...................................................................... 5 8  
1 1. 1. 2.  
Pr ot o c ol D e vi ati o n s  ...................................................................... 5 8  
1 1. 1. 3.  
A d diti o n al Di s pl a y s f or P arti ci p a nt s wit h a C O VI D -1 9 
I nf e cti o n ....................................................................................... 5 8  
1 1. 2.  Effi c a c y ....................................................................................................... 5 9  
1 1. 3.  S af et y  ......................................................................................................... 5 9  
1 1. 3. 1.  
A s s e s s m e nt of C O VI D -1 9 A E s  .................................................... 5 9  
1 2.  R E F E R E N C E S  ....................................................................................................... 6 0  
1 3.  A P P E N DI C E S  ........................................................................................................ 6 1  
1 3. 1.  A p p e n di x  1: E x cl u si o n s fr o m P er Pr ot o c ol P o p ul ati o n  ................................. 6 1  
1 3. 2.  A p p e n di x 2: S c h e d ul e of A cti viti e s  .............................................................. 6 2  
1 3. 2. 1.  
Pr ot o c ol D efi n e d S c h e d ul e of E v e nt s  ........................................... 6 2  
C CI
C CI
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13.3. 
Appendix 3: Assessment Windows ............................................................. 78 
13.4. 
Appendix 4: Study Phases and Treatment Emergent .................................. 79 
13.4.1. 
Study Phases .............................................................................. 79 
13.4.2. 
Treatment Emergent Flag for Adverse Events ............................. 81 
13.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 83 
13.5.1. 
Reporting Process ....................................................................... 83 
13.5.2. 
Reporting Standards .................................................................... 83 
13.5.3. 
Reporting Standards for Pharmacokinetic .................................... 84 
13.6. 
Appendix 6: Derived and Transformed Data ............................................... 85 
13.6.1. 
General ........................................................................................ 85 
13.6.2. 
Study Population .......................................................................... 86 
13.6.3. 
Efficacy ........................................................................................ 86 
13.6.4. 
Safety .......................................................................................... 87 
13.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 91 
13.7.1. 
Premature Withdrawals ................................................................ 91 
13.7.2. 
Handling of Missing Data ............................................................. 91 
13.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 94 
13.8.1. 
Laboratory Data ........................................................................... 94 
13.8.2. 
ECG Parameters ......................................................................... 94 
13.8.3. 
Vital Signs .................................................................................... 95 
13.9. 
Appendix 11: Abbreviations & Trade Marks ................................................ 97 
13.9.1. 
Abbreviations ............................................................................... 97 
13.9.2. 
Trademarks ................................................................................. 98 
13.10. Appendix 12: List of Data Displays.............................................................. 99 
13.10.1. Data Display Numbering .............................................................. 99 
13.10.2. Mock Example Shell Referencing ................................................ 99 
13.10.3. Deliverables ................................................................................. 99 
13.10.4. Study Population Tables ............................................................ 100 
13.10.5. Study Population Figures ........................................................... 116 
13.10.6. Efficacy Tables .......................................................................... 117 
13.10.7. Efficacy Figures ......................................................................... 121 
13.10.8. Safety Tables ............................................................................. 123 
13.10.9. Safety Figures ........................................................................... 164 
13.10.10. Pharmacokinetic Tables ............................................................. 166 
13.10.11. Pharmacokinetic Figures ........................................................... 167 
13.10.12. ICH Listings ............................................................................... 168 
13.10.13. Non-ICH Listings ........................................................................ 178 
13.11. Appendix 13: Custom Mock-ups ............................................................... 191 
13.11.1. Study Population ........................................................................ 191 
13.11.2. Efficacy ...................................................................................... 192 
13.11.3. Safety ........................................................................................ 200 
13.11.4. Pharmacokinetics (PK) .............................................................. 207 
13.11.5. ICH Listings ............................................................................... 210 
13.11.6. Non-ICH Listings ........................................................................ 211 
 


 
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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 interim (if applicable) and final Clinical Study Report for Protocol: 
Revision Chronology: 
Original/ 
2018N358002_00 
11-JUL-2018 
Original 
Amendment 01/ 
2018N358002_01 
17-OCT-2018 
Changes made to the protocol were requested by 
Regulatory Agency 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 02/ 
2018N358002_02 
13-FEB-2019 
Changes made to the protocol were requested by a 
Regulatory Agency after its review of Amendment 1 
and a third treatment arm was added to the study. 
Amendment 03/ 
2018N358002_05 
01-OCT-2019 
The overall rationale for this amendment is the removal of 
randomization to Arm A and Arm B, clarification of aspects 
related to participant enrollment and clarification regarding 
study stopping and pausing rules. These additions included 
modification of lymphodepleting regimen for older  
articipants, modification of dose range 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. 
Amendment 04/ 
2018N358002_06 
29-OCT-2019 
The overall rationale for this amendment is the addition of 
fresh biopsy collection in order to perform antigen 
expression screening, in absence of archival tumor tissue. 
Amendment 05/ 
2018N358002_08 
21-FEB-2020 
The overall rationale for this amendment is to add 
clarification regarding measurable lesion, to remove 
docetaxel as exclusion criterion and add platinum-based 
combination chemotherapy as an inclusion criterion. 
Docetaxel therapy as supportive therapy between 
leukapheresis and the start of lymphodepletion is removed. 
Amendment 06/ 
2018N358002_09 
17-MAY-2021 
The overall rationale for this amendment is to: 
• 
Simplify/enhance screening and enrolment efforts 
• 
Broaden patient eligibility 
• 
Include additional safety tests and measures 
Amendment 07/ 
TMF-14132100 
04-NOV-2021 
The overall rationale for this amendment is to: 
• 
Implementation of additional safety monitoring 
measures in accordance with a recent Dear Investigator 
Letter and safety events for lete-cel. 
• 
For participants treated as of protocol amendment 7, the 
upper end of the target dose range of transduced T-
cells was increased from 8x109 to 15x109 in order to 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
7 
 
m axi mize t h e deliv ery of  c ells for p artici pa nts w h ose 
m a n uf act ur e yi elds > 8x 1 0 9 tr ans d uce d T-c ells. 
2.  
S U M M A R Y O F K E Y P R O T O C O L I N F O R M A TI O N  
2. 1.   
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n 
At t he ti me of fi nalizati o n of t his d oc u me nt, it is u nli kel y t hat t he st u d y will reac h t h e 
n u m ber of patie nts d ose d necessar y t o perf or m t he pla n ne d i nteri m a nal yses. I n t he cas e 
w here t he i nteri m a nal ysis tri g ger p oi nt is n ot reac he d, n o i nteri m a nal yses will be 
perf or me d a n d t he o nl y pla n ne d a nal ysis will be t h e fi nal a nal ysis. 
2. 2.   
St u d y O bj e cti v e( s) a n d E sti m a n d( s) / E n d p oi nt( s) 
O bj e cti ve s  
E sti m a n d s / E n d p oi nts  
Pri m ar y  
Pri m ar y  
•  
T o ev alu at e th e s afety an d t oler a bility 
of a ut olo g o us g e n etic ally m o difi e d T -
c ells ( G S K 3 3 77 7 9 4) i n h u m a n 
l e uk ocyt e a nti ge n ( H L A) H L A-A* 0 2: 0 1, 
HL A -A* 0 2: 0 5 a n d/ or H L A -A* 02: 0 6 
p ositiv e partici p a nts wit h N Y -E S O -1 
a n d/ or L A G E1 a -p ositiv e a dv anc e d 
N S C L C al o n e [ Ar m A] or l et e-c el i n 
c o m bin ati on wit h pe m br oliz u ma b i n 
p articip a nts wit h N S C L C l ackin g 
acti o na bl e g e n etic a berr ati ons [ Ar m B] 
a n d p artici pa nts with N S C L C wit h a n 
acti o na bl e g e n etic a berr ati on [ Ar m C]  
•  
Fr e q u e ncy a n d s ev erity of A Es , s erio us a dv ers e ev e nts 
( S AEs) a n d A Es of s p eci al i nter est ( A E SI; as d efi ne d i n 
pr ot oc ol) 
•  
A E/ S A Es l e a di n g t o d os e d el ays  a n d/ or wit h dra w als i n 
p articip a nts w h o r eceive d G S K 3 3 7 7 7 9 4 al o n e or i n 
c o m bin ati on wit h pe m br oliz u ma b 
 
•  
T o d et er mi n e t he r esp o ns e t o let e-c el 
al o n e [ Ar m A] or l ete-c el i n 
c o m bin ati on wit h pe m br oliz u ma b i n 
p articip a nts wit h N S C L C l ackin g 
acti o na bl e g e n etic a berr ati ons [ Ar m B] 
a n d p artici pa nts with N S C L C wit h  
acti o na bl e g e n etic a berr ati ons [ Ar m C]  
•  
Ov er all R es po ns e R at e ( O R R) (i nv esti g ator ass ess e d 
acc or di n g t o R E CI S T v1. 1) 
S e c o n d ar y  
S e c o n d ar y  
•  
T o f urt h er inv esti g at e t h e a nti -tu m or 
activity of l et e-c el accor di n g t o 
R E CI S T v 1. 1 crit eri a  
•  
Pr o gr essio n -Fr e e S urviv al ( P F S)  
•  
Dis e as e C o ntr ol R ate ( D C R)  
•  
D ur ati o n of R es p o ns e ( D o R)  
•  
Ti m e t o R es p o ns e ( T T R)  
•  
T o c h ar act eriz e i n viv o cell ul ar P K 
pr ofil e (l ev els, ex p a nsi on, p ersist e nc e) 
of N Y -E S O -1 s p ecific (c 25 9) T c ells  
•  
M axi m u m tra ns ge n e ex p a nsi on ( C m ax) 
•  
T i m e t o C m ax ( T m ax) 
•  
A r e a u n d er t he ti m e c urv e fr o m z er o to ti me t A U C( 0-t), 
as d at a p er mit.  
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
8 
 
A b br evi ati o ns:  
 A E = a dv ers e ev e nt/s; A U C( 0-t) = ar e a u n d er t h e ti m e c urv e fr o m z er o t o ti m e t; C m ax = 
m axi m u m p ersist e nc e; 
; D C R = dis e as e c o ntr ol r at e; D o R = d ur ati o n of r es p o ns e 
(
 E C G = el ectr oc a r di o gr a m; E C O G P S  = East er n C o o p er ativ e O nc ol o gy Gr o u p 
p erf or m a nc e st at us; e C R F = el ectr o nic c as e r e p ort f or m; 
 G-C S F  = gr a n ul ocyt e c ol o ny 
sti m ul ati n g f act or; H L A = h u m a n l e uk ocyt e a nti g e n; I L = i nt erl e uki n; 
 L A G E -1 a  = c a nc er 
t estis a nti g e n 2; N S C L C = n o n -s m all c ell l u n g c a nc er; N Y-E S O -1 = N e w York es o p h a g e al s q u a m o us c ell c arci n o m a 1; 
O R R = ov er all r es p o ns e r at e (
); 
; P D-L 1  = pr o gr a m m e d d e at h 
pr ot ei n 1 li g a n d;  P E T  = p ositr o n e missi o n t o m o gr a p hy; P F S  = pr o gr essi o n -fr e e s urviv al (
 
; P R O-C T C A E  = P ati e nt -R e p ort e d O utc o m es v ersi o n of C o m m o n T er mi n ol o gy Crit eri a f or Adv ers e Ev e nts; 
R E CI S T  = R es p o ns e Ev al u ati o n Crit eri a I n S oli d T u m ors (
); 
 
; S A E = s eri o us a dv ers e ev e nt; 
; 
 T m ax = ti m e t o C max; 
 
 T T R = ti m e t o r es p o ns e; W T = wil d-ty p e. 
 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


CONFIDENTIAL 
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9
 
2.3. 
Study Design 
Overview of Study Design and Key Features 
Abbreviations: EoT = end of treatment; HLA = human leukocyte antigen; LAGE-1a = cancer testis antigen 2; 
NCCN = National Comprehensive Cancer Network; NSCLC = non-small cell lung cancer; NY-ESO-1 = New 
York esophageal squamous cell carcinoma 1; PD-1 = programmed death protein 1; PD-L1 = PD-1 ligand; 
LTFU = long--term follow--up. 
 
1. NSCLC patients with actionable genetic aberrations may receive treatment as part of Arm C only following 
treatment with targeted standard of care therapy (NCCN or equivalent country-guidelines (e.g., ESMO, NICE, 
etc.), as applicable).  
2. Option of pembrolizumab therapy at time of disease progression following lete-cel administration and based on 
benefit-risk evaluation with Sponsor’s Medical Monitor (or designee) approval.  
3. LTFU requires participant enrollment in a dedicated LTFU protocol (GSK Study 208750). If not yet enrolled in the 
LTFU protocol, participants will be followed per LTFU schedule under this protocol (Part 5) until enrolled in the 
separate LTFU protocol. 
Design 
Features 
• 
This is a multi-arm, open-label study of letetresgene autoleucel (lete-cel, 
GSK3377794) in HLA-A*02:01,  HLA-A*02:05 and/or HLA-A*02:06 adults whose 
tumors express NY-ESO-1 and/or LAGE-1a.  
• 
Enrolled participants includes participants who have unresectable Stage IIIb or 
Stage IV NSCLC and also fit criteria outlined in eligibility. 
• 
Up to 54 participants will be enrolled to achieve at least 15 evaluable participants 
per arm. At least 30 participants (15 per each arm) with NSCLC lacking actionable 
genetic aberrations will be assigned to lete-cel alone (Arm A) or in combination with 
pembrolizumab (Arm B). Assignment of participants to Arm A or B will be 
determined upon agreement with the Sponsor. Participants with NSCLC lacking 
actionable genetic aberrations will be assigned to Arm A first and then to Arm B. At 
least 15 evaluable participants with NSCLC with actionable genetic aberrations will 
be assigned to treatment with lete-cel in combination with pembrolizumab (Arm C). 
Note: As enrollment into Arm B was never opened, there are no patients assigned 
to Arm B per study design, thus no analysis of Arm B will be performed.  
• 
This study is divided into five distinct parts: 1) Screening, 2) 
Leukapheresis/manufacture, 3) Lymphodepletion/Treatment (Interventional Phase), 
4) Pembrolizumab Therapy Following Disease Progression after GSK3377794 
Infusion, for Arm A only, 5) Long-Term Follow-Up. 


CONFIDENTIAL 
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10
Participant Flow 
 
Abbreviations: CRS = cytokine release syndrome; EoT = end of treatment; HLA = human 
leukocyte antigen; ICF = informed consent form; I/E = inclusion/exclusion; LAGE-1a = cancer 
testis antigen 2; NSCLC = non-small cell lung cancer; NY-ESO-1 = New York esophageal 
squamous cell carcinoma 1; PD = progressive disease; Q3W = once every 3 weeks; 
RT = radiotherapy; SoC = standard of care. 
1. 
Screening may start at any time after diagnosis of advanced Stage IIIb or IV or 
recurrent NSCLC. 
2. 
Leukapheresis may start once the eligibility criteria are fulfilled.  Wash-out times as 
indicated in Protocol Table 12 may apply. 
3. 
Lymphodepletion starts at clinical and / or radiographic disease progression. Wash-out 
times as indicated in Protocol Table 12 may apply.  
4. 
Participants will receive a single dose of lete-cel five (5) days after completing the 
lymphodepleting chemotherapy (this is considered Day 1). 
5. 
Participants in Arm A who have PD following treatment with lete-cel at or before the 
scheduled Week 25 scan may be offered pembrolizumab therapy (Part 4) following 
assessment of eligibility for pembrolizumab treatment, benefit-risk evaluation, and 
approval by the Sponsor’s Medical Monitor (or designee). (see Section 6.4.4 of 
Protocol).  
6. 
In Arms B and C, the first pembrolizumab administration is on Day 22 (Week 4 Day 1). 
If toxicities that preclude pembrolizumab treatment, including such as CRS Grade ≥2, 
are present at Day 22, infusion of pembrolizumab will start on Week 7 Day 1. In either 
case, pembrolizumab will then be administered Q3W up to 35 cycles or PD as 
described in Section 6.5 of Protocol.  
7. 
LTFU requires participant enrollment in a dedicated LTFU protocol (GSK Study 
208750). If not yet enrolled in the LTFU protocol, participants will be followed per LTFU 
schedule under this protocol (Part 5) until enrolled in the LTFU protocol (see Table 8 of 
Protocol). 
 
 
Note: Dashed boxes and arrows indicate activities that may be performed based on 
clinical need. 
 
• 
Participants will undergo stepwise enrolment on the study followed by treatment 
according to protocol-defined phases within this study which will include: 


 
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Overview of Study Design and Key Features 
o Part 1: Screening 
 
Target expression screening for the presence of HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positivity 
and tumour expression of NY-ESO-1 and, when feasible 
LAGE-1a expression. 
 
Leukapheresis screening phase to determine eligibility 
for undergoing leukapheresis within 42 days prior to the 
day of the scheduled leukapheresis procedure. 
 
Participants screened or enrolled in other GSK studies 
may be considered for enrollment to this study, where it 
is IRB/IEC approved, on a case-by-case scenario 
following risk/benefit evaluation between the 
Investigator and Sponsor Medical Monitor (or designee). 
o Part 2: Leukapheresis/Manufacture 
 
Participants who fulfil the leukapheresis eligibility criteria 
can undergo the leukapheresis procedure. Following 
leukapheresis, lete-cel manufacture can begin. 
o Part 3: Lymphodepletion/Treatment 
 
Following clinical and/or radiographic evidence of 
disease progression, baseline eligibility criteria will be 
reconfirmed and baseline tumor assessments (scan and 
biopsy) obtained prior to initiating the lymphodepleting 
chemotherapy. 
 
The interventional phase includes Lymphodepletion 
from Days -8 to -5, lete-cel infusion on Day 1, 
Pembrolizumab administration beginning on Day 22 
then Q3W up to 35 cycles (Arms B and C only), and 
follow-up until the patient completes the interventional 
phase (per Protocol section 4.4) . 
o Part 4: Pembrolizumab therapy following disease progression 
after GSK3377794 infusion (Arm A only) 
 
Participants in Arm A who have PD following treatment 
with lete-cel at or before the scheduled Week 25 scan, 
may be offered pembrolizumab therapy following 
assessment of eligibility for pembrolizumab treatment, 
benefit-risk evaluation, and approval by the Sponsor’s 
Medical Monitor. 
o Part 5: All participants who are alive and have either ended the 
interventional phase or withdrawn early from the interventional 
phase will be followed for the observation of delayed AEs and 
survival during the 15 years post-infusion in the long-term follow-
up (LTFU) protocol (GSK Study 208750) in accordance with FDA 
regulations [FDA, 2020b] (Section 8.1.2 of Protocol). If not yet 
enrolled in Study 208750, there is a short-term provision (≤6 
months) to follow participants according to the LTFU schedule 
under this protocol (reproduced on Table 8 in Protocol) until 
enrolled in the 208750 study. Participants who fail to consent to 
the 208750 study within this period will be withdrawn from Study 
208471. 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
1 2  
 
O v er vi e w of St u d y D e si g n  a n d K e y F e at ur e s  
•  
P artici pa nts w h o d o n ot r ec eive p e m br olizu m a b will be c o nsid er e d t o hav e 
e n d e d t he i nt erv e nti o n al p h ase of t h e st u dy w h e n o ne of t he f oll o wi ng 
occ urs ( w hic hev er is s o o n er):  
o  P artici pa nt h as b e en o n st u dy u ntil W eek 1 06 p ost G S K 3 37 77 9 4 
i nf usio n 
o  P artici pa nt h as 
 
o  P artici pa nt dies  
•  
P artici pa nts w h o d o r ec eive pe m br oliz u m a b will b e c o nsi d ere d t o h av e 
e n d e d t he i nt erv e nti o n al p h ase w h e n o n e of t h e foll o win g occ urs 
( w hic h ever is s o o ner): 
o  P artici pa nt c o m plet es 3 5 cycles of p e m br oliz u m a b  
o  P artici pa nt h as 
 ( Ar ms B a n d C) or 
f urt h er pr o gressiv e dis eas e ( Ar m A P art 4) 
o  P artici pa nt dies  
•  
All p artici p ants w h o ar e aliv e an d h av e eit her e n d ed t h e i nt erv e nti on al 
p h as e or h ave wit h dr a w n e arly fr o m t h e i nt erv e ntio n al p h as e will b e 
f oll o w e d for t h e obs erv ati on of d el aye d A Es a nd s urvival d urin g t h e 1 5 
y e ars post-inf usi o n in t h e L T F U pr ot oc ol ( G S K St u dy 2 0 8 750). 
•  
T h e pri mary co m pl eti on of t h e st u dy is defi n ed as th e d ate w h e n at le ast 
7 0 % of all p articip a nts w h o r eceiv e d G S K 3 3 7 77 9 4 inf usi o n ( mI T T) h ave 
pr o gr ess e d or di e d or h av e b ee n l ost t o f oll o w-u p. Th e stu dy e n ds w h e n 
all p articip a nts h av e m ov e d t o t h e L T F U pr ot oc ol, d ecli n e d L T F U, h av e 
b e e n l ost t o foll o w -up, wit h dr e w e arly, or di e d.  
N ot e t h at as t h e st u dy is e arly t er mi n ate d, t h e a n alys es d escri b e d h ere ar e  
f or t h e fin al st u dy C S R at th e e n d of t he st udy.  
 
D o si n g  
•  All eligi ble p artici p ants will r eceiv e a si ngl e dos e of l et e-c el by I V i nf usi o n five ( 5) 
d ays aft er co m pleti n g t h e ly m ph o d e pl eti n g c h e mot h er apy (t his is c o nsi d er ed D ay 1).  
A t ar g et d os e r a n ge of 1x 1 0 9  to 1 5x 1 0 9 t otal tr a ns d uc e d T-cells w as c h os e n.  
•  O n D ay 1, I n Ar m A, l et e- c el will b e a d mi nist er e d as a si n gl e i ntr av en o us (I V) 
i nf usio n of 1 t o 1 5 x 1 0 9 tr a ns duc e d cells.  T h ere will b e n o re-tr e at m e nt.  
P artici pa nts w h o s u bs e q u ently pr o gr ess m ay o pti o n ally r ec eiv e t h er apy wit h 
p e m br oliz u m a b 20 0 m g Q 3 W for u p t o 35 cycl es or u ntil dis eas e pr o gressi o n, at 
w hic h p oi nt p articip a nts m ay  ent er t h e L T F U p h as e (f ollo wi ng t h e L T F U sc h e dul e 
u n d er t his pr otoc ol ( P art 5) u ntil e nr oll e d  i nt o a s e p arat e L T F U pr ot oc ol ( G S K St u dy 
2 0 8 7 5 0) ). 
•  I n Ar ms B a nd C, p artici pa nts will als o r ec eive a si n gle I V i nfusi o n of 1 t o 1 5 x 10 9 
l et e-c el tr a ns d uce d c ells o n Day 1 f oll o w e d by p e m br oliz u ma b 2 0 0 m g starti n g o n 
D ay 2 2 ( W e ek 4 D ay 1).  P e mbr oliz u m a b will b e a d mi nist er e d f or u p t o 3 5 cycl es 
Q 3 W or u ntil dis eas e pro gr essi o n, at w hic h poi nt partici p a nts m ay  ent er t h e L T F U 
p h as e (foll o win g t h e L T F U sche d ul e un d er t his pr ot oc ol ( P art 5) u ntil e nr oll e d  i nt o 
t h e L T F U pr ot oc ol ( G S K St u dy 2 0 8 7 5 0). 
Ti m e & 
E v e nt s  
•  
R ef er  t o A pp en dix 2 : Sc h e d ule of Activities  
Tr e at m e nt 
As si g n m e nt  
•  
T his is a m ulti -ar m, op e n -l ab el st u dy wit h 3 ar ms, Ar m A, Ar m B, a n d Ar m C, 
d escrib e d ab ov e u n d er D esi g n F e at ur es  
I nt eri m 
A n al y si s  
•  
S e p ar at e i nt eri m a n alys es m ay b e co n d uct e d w h e n at l east 1 0 p artici p ants b ec o me 
ev al u abl e for Ar ms A, B, a n d C.  
•  
F utility i nteri m a n alysis d ecisi on r ul es f or t h e 1 0 t h ev al u abl e partici pa nts ar e 
d escrib e d bel o w u n der S ecti on  3. 1 
C CI
C CI


 
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2.4. 
Statistical Analyses 
This is a Phase 1b/2a study focused on the safety, tolerability, clinical activity, and 
whether HLA and antigen expression biomarkers can identify a population of participants 
with advanced NSCLC that could benefit from lete-cel administered alone or in 
combination with pembrolizumab.   
No formal statistical hypotheses are being tested in this study. 


 
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3. 
PLANNED AND AD HOC ANALYSES 
3.1. 
Ad hoc Analyses 
An ad hoc analysis was performed using a data cutoff of August 30, 2021 as part of the 
study monitoring and to inform further development of the lete-cel NSCLC program. A 
set of data listings and figures for the first ten dosed patients (5 from Arm A and 5 from 
Arm C) were generated. This analysis is prior to the protocol-specified interim analysis 
detailed below. Based on the analysis of efficacy data from this unplanned interim 
analysis and given active parallel enrolment in NSCLC of a next-gen NYESO-targeting 
TCR-T cell therapy with a CD8a modification which may provide enhanced efficacy over 
lete-cel, the study stopped its further enrolment .  
A second ad hoc analysis was performed using a data cutoff of February 24, 2022 for the 
purpose of internal strategic discussion. An updated set of data listings and figures for the 
first thirteen dosed patients (7 from Arm A and 6 from Arm C) were generated. Based on 
additional cumulative data, the study will allow enrolled patients who are eligible to 
receive the T-cell infusion to be dosed until 18 November 2022.  
More details on each analysis can be found in the filenotes archived in electronic Trial 
Master File (eTMF). 
3.2. 
Interim Analyses 
For the primary purpose of informing future lete-cel development, separate interim 
analyses are planned for each arm after at least 10 evaluable participants are available in 
that arm. Evaluable participants are defined as participants who received a T-cell infusion 
and have either progressed, withdrawn from the study treatment, were lost to follow-up, 
or are ongoing and have completed at least two post-treatment disease assessments.  If 
enrollment is still open at the time of the interim analysis, enrollment into a treatment arm 
may be stopped early for toxicity or lack of efficacy (futility) based on the results of an 
interim analysis.  
The sample size for each arm was determined using a Bayesian predictive adaptive 
design that allows the study to be monitored more frequently while maintaining the 
desired Type I error and power. The sample size is based on testing the hypothesis for 
each arm separately and not for a comparison between arms. For all three arms, clinical 
response will be defined as investigator-assessed ORR per RECIST v1.1. An interim 
analysis after the 10th participant becomes evaluable will be employed for Arms A, B, 
and C, separately.   
Participants with NSCLC lacking actionable genetic aberrations will be assigned to Arm 
A and Arm B such that at least 15 participants receive T-cell infusion within the target 
dose range (lete-cel) in Arm A and at least 15 participants receive T-cell infusion within 
the target dose range and pembrolizumab in Arm B.  Participants with NSCLC with 
actionable genetic aberrations will be assigned to Arm C such that at least 15 participants 
receive T- cell infusion and pembrolizumab.  Assuming around 15% of the participants 
enrolled will discontinue from the study prior to lete-cel infusion, up to approximately 18 


 
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participants will be enrolled in each arm to ensure at least 15 evaluable participants will 
receive T-cell infusion within the target dose range.  Enrollment will proceed 
continuously with no scheduled enrollment pause while conducting the interim analysis. 
Upon completion of the interim analysis, this protocol may be amended to allow for 
expansion beyond 15 participants. 
Analyses will be conducted for Arms A, B, and C independently. An end of study 
threshold is defined such that meeting this threshold may warrant continuing 
development in the population of interest. For each arm, Bayesian statistics will be 
employed to calculate the predictive probability of meeting the end of study threshold at 
the interim analysis (after the 10th enrolled participant per arm has received T-cell 
infusion (modified Intent-to-Treat [mITT] population) and has completed at least 2 post-
baseline disease assessments since infusion or discontinued earlier) given the responses 
that have already been observed assuming a beta prior for the binomially distributed data. 
A weak prior of beta (0.02, 0.08) is used, which is equivalent to the information present 
in 0.1 participant. 
At the interim analysis for each arm, further enrollment into the arm is recommended to 
be stopped due to futility if the predictive probability of meeting the threshold at the final 
analysis is less than 2.8%. Here, this threshold is defined as the posterior probability that 
the ORR is greater than 10% at the end of the arm is larger than 95%. This predictive 
probability aligns with observing at least 2 responders out of 10 participants, and if not 
met, serves as strong statistical evidence to stop further development of the treatment for 
the target population. 
Futility interim analysis decision guidelines for each arm, specifying the number of 
participants with a confirmed response needed for continuing enrollment or stopping for 
futility is presented in Table 1. 
Table 1 
Decision-Making Criteria for Futility for Arms A, B, and C at the 
Interim Analysis Conducted with 10 Evaluable Participants/Arm 
Arm (N=10/Arm) 
Stop Enrollment for Futility 
if the Number of Confirmed 
Responses is Less Than or 
Equal to this Number 
Probability of Continuing 
Enrollment under H0 (10%) 
Probability of Continuing 
Enrollment under Ha 
(30%) 
Arm A or B or C 
1 
0.2639 
0.8507 
 
Based on interim analysis results, enrollment for all treatment arms (Arm A, B, or C) may 
be stopped due to futility if ≤1 confirmed response is observed in the first 10 evaluable 
participants within the arm, i.e., the predictive probability that rejecting H0 at end of 
study is small (e.g., less than 2.8% chance to have at least 4 confirmed responders out of 
15 participants who received T-cell infusion in the treatment arm).  The above criteria are 
intended as guidelines. Final decisions with respect to study conduct, including pausing 
enrollment, will be based on a comprehensive review of the totality of the data including 
safety, DCR, DoR, CR rate, and PFS as warranted by the data. 
 


 
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3.3. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All participants that have received lete-cel infusion (mITT) have moved to the 
separate LTFU protocol, declined LTFU, have been lost to follow-up, withdrew 
early, or died.  
2. All required database cleaning activities have been completed and final database 
release (DBR) and database lock(DBL) have been declared by Data Management. 
 
For Arms A, B, and C, clinical response will be defined as ORR per RECIST v1.1. 
If 4 responses out of 15 are observed at the final analysis, this will serve as evidence in 
favor of further development in this arm. Operating characteristics for a range of true 
population ORR are given in Table 2. The probability of reaching the continuing 
development criteria at the final analysis, given a true ORR of 30% is 68.1%. The 
inference from the Bayesian predictive probabilities of clinical activity in participants in 
each treatment arm is intended to drive decision making.  Actual decisions will depend 
on the totality of the data including clinical activity, safety, PK, and biomarker data. 
Table 2 
Operating Characteristics for Interim and Final Analyses for Arms A, 
B, and C 
True ORR 
Probability of passing futility at 
interim (n=10) 
Probability of reaching end of 
study threshold at final analysis 
(n=15) 
10% 
0.265 
0.054 
20% 
0.625 
0.334 
30% 
0.850 
0.681 
40% 
0.953 
0.896 
50% 
0.988 
0.976 
 


 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened  
• 
All participants who signed an ICF to participate in the 
study. 
• 
Study Population 
Enrolled 
• 
All participants who started the leukapheresis 
procedure. 
• 
Study Population 
Intent-To-Treat 
(ITT) Population 
• 
All participants who started the leukapheresis 
procedure. 
• 
Study Population, 
Safety, Efficacy 
Lymphodepletion 
Population 
• 
All participants who received any dose of 
lymphodepleting chemotherapy. 
• 
Safety 
Modified ITT 
(mITT) 
Population 
• 
All participants who received lete-cel infusion. 
• 
Study Population, 
Safety, Efficacy 
Pembrolizumab 
• 
All participants in the mITT population who received at 
least one infusion of pembrolizumab. 
• 
Study Population, 
Safety, Efficacy 
Evaluable 
Population 
• 
All participants in the mITT population with at least 2 
post-baseline radiological disease assessments or have 
progressed, died, permanently withdrawn from the 
study, or (if relevant) permanently withdrawn from 
pembrolizumab. 
• 
Interim Futility 
Analyses 
Pharmacokinetic 
(PK) Population 
• 
All participants in the mITT population from whom at 
least one persistence sample was obtained, analysed, 
and was measurable. 
• 
PK 
Refer to Appendix 12: List of Data Displays which details the population used for each display. 
 
 


 
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4.1. 
 Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan Version 4 (26 May 2022) . 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 
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 
This is a multi-arm, non-randomized study, in which the participant will receive either 
lete-cel alone (Arm A) or in combination with pembrolizumab (Arms B and C).  Data 
will be listed and summarized according to GSK reporting standards, where applicable.  
Study population summaries will be displayed with separate columns for each arm, as 
well as an “Overall” column, without regard to actual treatment received.  Efficacy 
summaries will be displayed with separate columns for each arm, according to planned 
treatment. An “overall” column will not be produced for the efficacy summaries. Safety 
summaries will be displayed according to actual treatment received within each arm, see 
Section 8 for details of planned safety displays.  
Post-pembrolizumab safety data from patients who received pembrolizumab therapy 
following disease progression after GSK3377794 infusion will be summarized separately, 
as detailed in Sections 8.1 and Section 13.4. Efficacy data after pembrolizumab therapy 
for these patients will be listed separately. 
 


 
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Treatment Group Descriptions 
RandAll NG 
 
Data Displays for Reporting  
Code 
Description 
Tumor Characteristics 
Description 
Order in TLF  
A 
GSK3377794 
monotherapy 1x10^9-
6x10^9 transduced T-
cells 
Patients lacking 
actionable genetic 
aberrations 
Arm A 
1 
B 
GSK3377794 1x10^9 -
6x10^9 transduced T-
cells followed by 200 mg 
of pembrolizumab Q3W 
up to 35 cycles* 
Patients lacking 
actionable genetic 
aberrations 
Arm B 
2 
Patients with actionable 
genetic aberrations 
Arm C 
3 
*Note: The description for Code B shows a target dose of 1x10^9 -6x10^9 transduced T-cells. However, as 
of PA7, the target dose has been expanded to 1x10^9 -15x10^9. The description has not been updated in 
RandAll NG at the study team’s discretion. 
 
5.2. 
Baseline Definitions 
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 
visits, prior to initiating lymphodepletion regardless of how close it is to the 
lymphodepletion date, albeit per protocol, baseline assessments should occur less than 10 
days prior to initiating 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 summaries of laboratory data by CTCAE grade, missing baseline grade will be 
assumed as grade 0. 
For participants who did not receive study treatment during the study, baseline will be 
defined as the latest, non-missing collected value. 
Participants may receive either a single ECG at baseline or a triplicate. For ECG 
analyses, participant level baseline QTc is defined as the mean of triplicate QTc baseline 
assessments, if more than one ECG is present.  If only a single ECG is present, this value 
will be used.  
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
Baseline Assessment: Participants Assigned to Arm A who progress after receiving 
lete-cel and  Receive Anti-PD-1 Rescue with Pembrolizumab  
If the CT/MRI has been obtained at the progressive disease (PD) confirmatory scan 
within 4 weeks (28 days) prior to pembrolizumab rescue therapy initiation, this can be 
considered as baseline measurement for disease assessment during the Pembrolizumab 
Therapy Following Disease Progression Phase (see Section 13.4.1 for phase definitions). 
 


 
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For other endpoints, the same baseline definitions described above for the entire analysis 
population with the exception that the window for baseline being within (<=) 28 days 
prior to the initiation of pembrolizumab rescue therapy will be applied to all assessments 
deemed necessary as the baseline re-evaluation for these participants during the 
pembrolizumab rescue phase 
5.3. 
Multicentre Studies 
• 
Data from all participating centres will be pooled prior to analysis. 
• 
It is anticipated that participant accrual will be spread thinly across centres and 
summaries of data by centre would be unlikely to be informative and will not, 
therefore, be provided.  
5.4. 
Examination of Covariates, Other Strata and Subgroups 
5.4.1. 
Covariates and Other Strata 
No covariates or stratification will be used in any of the analyses. 
5.4.2. 
Examination of Subgroups 
No subgroup analyses will be performed due to small sample size. 
5.5. 
Multiple Comparisons and Multiplicity 
No formal statistical testing for between-treatment comparisons 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: 
Section 
Component 
Section 13.3 
Appendix 3: Assessment Windows 
Section 13.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
Section 13.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section 13.6 
Appendix 6: Derived and Transformed Data 
Section 13.7 
Appendix 7: Reporting Standards for Missing Data 
Section 13.8 
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 modified Intent-to-Treat (mITT) and 
Intent-to-Treat (ITT) population, unless otherwise specified. Some study population 
analyses will be performed using both the mITT and ITT populations. If the mITT and 
ITT populations are identical, then results planned for both populations will only be 
reported for the mITT population. Some study population analyses will be performed on 
the Pembrolizumab Population, where applicable.  
All listings will be based on the ITT population, unless otherwise specified. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
disease characteristics at initial diagnosis and at screening, prior and on study anti-cancer 
therapy, surgical/medical procedures, disease burden at baseline and study treatment  
exposure will be based on GSK Core Data Standards.  Details of the planned displays are 
presented in Appendix 12: List of Data Displays. 
Summaries will present the study population data with separate columns for each arm, as 
well as with an overall column, where applicable. 
6.2. 
Disposition of Participants 
A summary of the number of participants in each of the analysis populations described in 
Section 4 above will be provided. A listing of participants excluded from analysis 
populations will also be provided. 
A summary of screening status and screen failures will be provided using the screened 
population. Per GSK reporting standards, participants who were rescreened will appear 
once in these displays according to their final status. 
A summary of interventional phase status will be produced, with reasons for completion 
and study withdrawal summarized in the order they are displayed in the CRF. Participant 
status will be displayed with the categories and subcategories: Completed study (death, 
progressive disease), ongoing, or did not complete interventional phase (with reasons 
from the CRF). 
Overall study disposition, including long term follow up, will be summarized for the 
mITT population. An additional table will be created to summarize the number of 
participants in the ITT population who did and did not receive lete-cel, as well as the 
reason for not receiving the lete-cel infusion. A supporting listing of reason for study 
withdrawal will be created. 
The number of participants in the Enrolled Population and mITT population will be 
summarized by country and study site ID. 


 
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A summary of study treatment discontinuation for pembrolizumab will be produced for 
the Pembrolizumab Population only, for each arm separately. The number of participants 
ongoing on pembrolizumab, discontinued, and reason for discontinuation will be 
summarized in the order they are displayed in the eCRF. A supporting listing of reasons 
for Pembrolizumab discontinuation will also be provided 
6.3. 
Demographic and Baseline Characteristics 
The demographic characteristics (e.g., race, age, ethnicity, sex, height and body weight at 
leukapheresis eligibility screening visit, the derived body mass index (BMI) according to 
baseline body weight and height at screening visit, and body surface area (BSA) per the 
DuBois & DuBois formula (Dubois & Dubois, 1916)) will be summarized and listed per 
GSK standards. A supportive listing of race and demographic characteristics will be 
produced. 
A summary of disease characteristics at initial diagnosis will be provided, including stage 
of lung cancer at initial diagnosis and enrollment, time from initial diagnosis to 
leukapheresis eligibility screening in months, histology and histology grade at initial 
diagnosis. A supporting listing will be provided, with date of initial diagnosis. Refer to 
Section 13.6.2 for time since initial diagnosis derivation rules. 
A summary of disease characteristics at screening will be provided, as collected in the 
CRF. Example categories may include disease stage at screening, , HLA-A/NY-ESO-
1/LAGE-1a status, status of measurable disease at baseline as assessed by investigator, 
status of visceral/non-visceral disease, non-target lesions and measurable disease, tumor-
node-metastasis (TNM) staging at baseline, time from last progression to leukapheresis 
eligibility screening (if applicable), and time from last recurrence to leukapheresis 
eligibility screening. A supporting listing will be provided. 
A summary of disease burden at baseline will be provided, including number of organs 
involved and location of disease at baseline. Both target and non-target lesions at 
baseline, including both the number of organs, and their locations, will be included.  
Medical conditions present at screening will be listed and summarized by past and 
current categories, separately for the ITT and mITT populations. All medical conditions 
recorded will be summarized, even if they are not pre-specified in the CRF. 
Substance use including smoking history, smokeless tobacco use, betel quid/areca nut 
use, and alcohol use (data collected at onset of liver event only) will be summarized and 
listed.  
6.4. 
Concomitant Medications 
All concomitant medications will be coded using GSK Drug coding dictionary and will 
be summarized using the mITT population. Concomitant medications usage during the 
study 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 


 
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Level 1 (Body System) information based on GSK Drug dictionary 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. 
Refer to Section 13.4.1.1 for prior and concomitant medicine definition. 
Summary of blood products or blood supportive care products ongoing at the time of 
lymphodepletion or initiated on or after lymphodepletion will be produced for the mITT 
population with supportive listings.  
6.5. 
Study Treatment Exposure 
A listing of study treatment will be provided, including overall lete-cel infusion start and 
stop date/time over all bags and for each bag separately, average vector copy number per 
cell in the cell product, total number of transduced cells, transduction efficiency, and 
route of synthesis (i.e. A6, B1, or B2). The listing will also include information 
pertaining to why a bag was partially infused and reason for pausing or discontinuing 
infusion. The total number of transduced T-cells will be summarized for the mITT 
population using mean, standard deviation, median, min and max. The total number of 
transduced T-cells will be categorized into <1, ≥1 to ≤8, and >8 to ≤15, and >15 (x 109 
cells), cumulative cyclophosphamide dose will be categorized into ≤1800, >1800 to 
≤2400, >2400 (mg/m2), and cumulative fludarabine dose will be categorized into ≤60, 
>60 to ≤80, >80 to ≤90, >90 to ≤120, and >120 (mg/m2). Time from leukapheresis to T-
cell infusion will also be summarized. 
All dose administration data for lymphodepletion, including cyclophosphamide and 
fludarabine, for lete-cel infusion will be presented by participant in a data listing. 
Supportive listings to report dose reductions and delay of lymphodepletion 
chemotherapy, as well as reason for dose reduction and delay, will be provided. 
Duration of lymphodepletion dose delays over planned consecutive days is defined as the 
period from the expected start date of dose to actual start date of current dose. The 
calculation of duration of delay is actual start date of current dose – expected start date of 
dose. Expected start date of dose = actual start date of previous dose + 1. 
A summary of exposure to pembrolizumab will be provided for the Pembrolizumab 
Population, including number of doses (n, mean, SD, median, min, max), time on study 
(days) and cumulative actual dose (mg). All exposure to pembrolizumab will also be 
listed by participant. All dose modifications (i.e. delays/interruptions and 
completed/stopped early and not completed) of pembrolizumab will also be summarized 
and listed as collected in the eCRF.  


 
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Total on-study treatment follow-up time will be summarized using descriptive statistics. 
The on-study treatment follow-up time is defined as the last contact date minus T-cell 
infusion date plus 1 and will be expressed in months. 
6.6. 
Anti-Cancer Therapies and Surgery 
Anti-cancer therapies include systemic therapy (coded using the GSK Drug coding 
dictionary), radiotherapy, and cancer-related surgery. 
Anti-cancer systemic therapies will be classified into prior, bridging, and on-study phases 
as described below.  Therapies will be identified using the corresponding CRF pages. 
Type of Systemic 
Therapy 
Definition 
Prior 
Prior therapy is defined as any line of systemic therapy (including 
intermediate therapy after leukapheresis), radiotherapy, and 
cancer-related surgeries given before start of lymphodepletion. 
Bridging 
Bridging therapies (supportive chemotherapy) are defined as 
systemic therapy given between leukapheresis and start of 
lymphodepletion to maintain disease control (not considered a line 
of therapy) 
On-Study/Follow-
up 
On-study and follow-up therapies are defined as systemic therapy, 
radiotherapy, or cancer related surgery given on or after the start of 
T-cell infusion. 
6.6.1. 
Prior Anti-Cancer Therapies 
Systemic anti-cancer therapy regimens initiated between leukapheresis and 
lymphodepletion (as defined in Appendix 4) are categorized as either bridging (regimens 
administered to maintain/stabilize the participant until T-cell infusion) or full lines 
(regimens administered with the intent of disease effect, i.e. intermediate therapy after 
leukapheresis). Full lines of therapy administered after leukapheresis are considered prior 
therapy. 
Anti-cancer therapy will be coded using GSK Drug coding dictionary. The number of 
participants receiving prior anti-cancer therapies will be summarized by ATC Level 1 and 
ingredient. Bridging therapies will be similarly summarized. 
A breakdown of the number of participants who received each category of anti-cancer 
therapy (surgery, radiotherapy, chemotherapy, etc…) in the advanced/metastatic setting 
will be summarized. 
A summary of the number of prior anti-cancer therapy regimens in the 
advanced/metastatic setting will be produced.  
A listing of systemic therapy will be provided and labelled as prior, bridging, or on-study. 
Radiotherapies and cancer-related surgical procedures will be listed separately and 
labelled as prior or on-study. 


 
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6.6.2. 
On-study Anti-Cancer Therapies 
On-study anti-cancer therapies will be summarized using the mITT population. The 
number and percentage of participants that received any on-study systemic anti-cancer 
therapy, radiotherapy, or cancer related surgery will be summarized together with the 
time from T-cell infusion to first post-treatment anti-cancer therapy. For the 
Pembrolizumab population, time from study treatment discontinuation (pembrolizumab) 
to start of subsequent anti-cancer therapy will also be included. On-study systemic 
therapies will be coded using GSK Drug coding dictionary and summarized by 
ingredient. On-study anti-cancer therapy will be listed.  
Palliative radiotherapy is permitted on study and will not be considered an On-study 
Anti-Cancer Therapy for the purpose of censoring. 
 


 
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7. 
EFFICACY ANALYSES 
Tumor assessments for response and progression will be evaluated by the investigator per 
RECIST v1.1 (Eisenhauer, 2009).  
All efficacy summaries will be presented with a separate column for each treatment arm, 
using planned treatment. More specifically, patients from Arm C who received Lete-cel, 
but discontinued treatment before receiving any pembrolizumab will still be pooled with 
all other Arm C patients who received planned pembrolizumab Q3W. Efficacy for Part 4 
participants after treatment with salvage pembrolizumab will be listed separately and 
shall not be included in efficacy tables or figures. An “overall” column will not be 
included for any efficacy summary.  
7.1. 
Final Efficacy Analyses 
The final analysis will be conducted when all participants who received lete-cel infusion 
(mITT) have moved to the separate LTFU protocol, declined LTFU, have been lost to 
follow-up, withdrew from the study, or died. 
7.1.1. 
Endpoint / Variables 
ORR  
Overall Response Rate (ORR), defined as the percentage of participants with a confirmed 
PR or CR relative to the total number of participants within the analysis population, as 
assessed by the investigator per RECIST 1.1 Criteria. 
 
Best Overall Response (BOR) is defined as the best confirmed response (Complete 
Response [CR] > Partial Response [PR] > Stable Disease [SD] [or non-CR/non-PD] > 
Progressive Disease [PD] > Not Evaluable [NE]) from letetresgene autoleucel (lete-cel, 
GSK3377794 infusion date until disease progression or initiation of new anti-cancer 
therapy, whichever is earlier, as assessed by the investigator per RECIST 1.1 Criteria. 
 
RECIST (version 1.1) criteria 
With respect to best overall responses, RECIST will be derived on local investigator 
assessed overall response at each visit: 
• To be assigned a status of PR, or CR, a confirmatory disease assessment should 
be performed no less than 4 weeks (28 days) after the criteria for response are first 
met 
• To be assigned a status of SD, follow-up disease assessment must have met the 
SD criteria at least once after the first dose at a minimum of 4 (28 days) weeks 
(Protocol section 10.10.1) 
• If the minimum of 4 weeks (28 days) for SD is not met, best response will depend 
on the subsequent assessments. For example, if an assessment of PD follows the 
assessment of SD and SD does not meet the minimum 4-week requirement the 
best response will be PD. Alternatively, participants lost to follow-up after an SD 


 
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assessment not meeting the minimum time criteria will be considered not 
evaluable 
• Responses of CR/PR that do not meet the requirements of confirmed CR/PR are 
still eligible to be considered SD if it has met the SD criteria. 
• If PR assessments are separated by more than one SD assessment (e.g. PR-SD-
SD-PR), the PR is not considered confirmed. PR separated by only one SD 
assessment (PR-SD-PR) will be considered a confirmed PR. 
• Assessments that are not done or not evaluable should be disregarded. 
• Disease assessments after new on-study anti-cancer therapy, will not be 
considered when deriving best overall response. On-study anti-cancer therapy is 
defined in Section 6.6.2 No disease assessments after initiation of the rescue 
pembrolizumab will be considered when deriving the best overall responses. 
• The date of disease progression is defined as the date of radiological disease 
progression based on imaging data per RECIST v1.1. For cases where non-
radiological progression is documented by the investigator, the derived overall 
response based on RECIST v1.1 tumor assessment data, not the non-radiological 
progression, will be utilized for investigator assessment. 
• If time is not collected and anti-cancer therapy starts on the same day as the 
disease assessment, it is assumed that the disease assessment occurred first. 
• Inclusion criteria 16 requires participants to have measurable disease according to 
RECIST v1.1 criteria prior to lymphodepletion. If this is violated and a participant 
has no measurable disease at baseline, then the participant will be treated as a 
non-responder and included in the denominator when calculating ORR. 
Participants with no disease assessments on study will be also treated as a non-
responder and included in the denominator when calculating ORR. 
7.1.2. 
Summary Measure 
ORR 
The number and percentage of participants with the BOR in the following response 
categories will be summarized by treatment arm: CR, PR, SD, PD, NE and overall 
response rate (CR+PR). The observed confirmed ORR will be reported along with 95% 
Clopper-Pearson exact confidence interval. Analysis will be based on mITT and ITT 
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 for each treatment arm. 
An overall listing of participant response data will be provided for the ITT population. 
The listing will include all response evaluations, the best confirmed response, whether the 
participant is ongoing in the study (for interim or final analysis), and whether the 
participant is in the mITT population. All supporting lesion data will be listed. 


 
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Details of the planned displays are provided in Appendix 12: List of Data Displays and 
are based on GSK data standards and statistical principles.  
7.1.3. 
Population of Interest  
The efficacy analyses will be based on the modified Intent-To-Treat (mITT) population. 
ORR will be reported in the Evaluable and mITT populations at the time of the interim 
and final analyses, respectively. The Intent-To-Treat (ITT) is the sensitivity analysis 
population for the efficacy endpoint. If the mITT and ITT populations are identical, only 
results associated with the mITT population will be reported. 
7.1.4. 
Strategy for Intercurrent (Post-Randomization) Events 
In the analysis of ORR and BOR in the protocol specified population, there are two types 
of intercurrent events, i.e., missed response assessments and other anticancer therapy. To 
address the missed response assessment as an intercurrent event, a composite strategy 
will be followed for participants who experience death prior to response assessments, or 
have only missing responses or not-evaluable assessments, or have non-measurable 
disease at baseline. These participants will be treated as non-responders (NE) ; i.e. they 
will be included in the denominator when calculating the percentage. 
Start of new anti-cancer therapy as a second type of intercurrent event, is addressed with 
while-on-treatment strategy, as the interest lies in the treatment effect of the 
investigational treatments before start of new anti-cancer therapy. 
7.1.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 12: 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. 
A listing of investigator-assessed target, non-target, and new lesions assessments will be 
provided, as well as a listing of investigator-assessed response at each visit. Assessments 
that occur during pembrolizumab rescue therapy for Arm A, as defined in Section 13.4.1, 
will be flagged. ORR will not be calculated for assessments during pembrolizumab 
rescue therapy. 


 
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7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
Disease Control Rate (DCR) 
DCR, is defined as the percentage of participants with a confirmed CR, PR, or SD with 
minimal 6 months (168 days) duration relative to the total number of participants within 
the analysis population at the time of the analysis (interim or final) as determined by local 
investigators per RECIST v1.1. DCR will be analysed based on mITT population. The 
observed DCR will be reported along with 95% Clopper-Pearson exact confidence 
interval (CI).   
A BOR of SD will be considered to have had a duration of at least 6 months (SD 
durability) if there is at least one follow-up disease assessment that has met the RECIST 
1.1 SD, PR or CR Criteria on or after Week 24 (Day 168), but before disease progression 
or initiation of new anti-cancer therapy. 
Inclusion criteria 16 requires participants to have measurable disease according to 
RECIST v1.1 criteria. If this is violated and a participant has no measurable disease at 
baseline, then the participant will be treated as a non-responder and included in the 
denominator when calculating DCR. Participants with no disease assessments on study 
will be also treated as a non-responder and included in the denominator when calculating 
DCR. 
Progression-Free Survival (PFS) 
PFS is defined as the interval of time (in months) from the date of T-cell infusion to the 
earliest date of radiological progression of disease (PD) as assessed by investigator per 
RECIST v1.1, or death due to any cause. Determination of dates of PFS events and dates 
for censoring are described in Table 3. 
 
The date of disease progression is defined as the date of radiological disease 
progression based on imaging data per RECIST v1.1.  
 
For the analysis of PFS, if the participant received subsequent anti-cancer therapy prior to 
the date of documented events, PFS will be censored at the last adequate disease 
assessment (e.g., assessment when visit level response was CR, PR, or SD) prior to the 
initiation of the new anticancer therapy. If a participant does not have any adequate post-
baseline disease assessments on or beforethe date of initiation of anti-cancer therapy, PFS 
will be censored at the date of the T-cell infusion. 
 
PFS will be censored for participants who have radiological progression or die after 
missing two or more scheduled radiological disease assessments. Specifically, if there are 
two or more consecutive scheduled radiological assessments which are missing followed 
by radiological progression or death, PFS will be censored at the last adequate 
radiological assessment prior to radiological progression or death. If a participant does 
not have an adequate post-baseline disease assessment prior to the date of radiological 
progression or death, PFS will be censored at the date of the T-cell infusion. Refer to the 


 
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section below to identify Extended Loss to Follow-Up at selected time points in the 
study. 
 
 
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. Acceptable imaging 
modalities for this study include: 
• Diagnostic-quality CT scan with oral and/or IV iodinated contrast of the chest and 
abdomen/pelvis (CT is the preferred modality for tumor assessments) 
• MRI of the abdomen/pelvis acquired before and after gadolinium contrast agent 
administration 
• Non-contrast enhanced CT of chest/abdomen/pelvis if a participant is 
contraindicated for both CT and MRI contrast or if they have renal compromise 
• Additional scans (CT/MRI) should be acquired for any other areas of 
suspected/known disease per site SoC, if clinically indicated  
• Digital photographs of skin lesions including a ruler for estimating the size of the 
lesion 
 
If the start date of anticancer therapy is partial, the imputation rules described in 
Appendix 7: Reporting Standards for Missing Data will be applied. If new anti-cancer 
therapy occur on the same day as a radiological disease assessment, assume the disease 
assessment was performed first.  
 
Extended Loss to Follow-up 
 
Since missing scheduled radiological disease assessments prior to radiological 
progression or death increases the uncertainty when the event actually occurs, PFS will 
be censored for participants who have radiological progression or die after missing two or 
more scheduled radiological disease assessments. Specifically, if there are two or more 
scheduled radiological assessments which are missing followed by radiological 
progression or death, PFS will be censored at the last adequate radiological assessment 
prior to radiological progression or death. If a participant does not have an adequate post-
baseline disease assessment prior to the date of radiological progression or death, PFS 
will be censored at the date of the T-cell infusion date. 
As the assessment schedule and windows change through the course of the study (i.e., 
every 6 weeks during the first 24 weeks, an assessment 9 weeks at Wk34D1 , and then 
every 12 weeks thereafter), the following rules will be used for identifying extended loss 
to follow up. 
• If the PFS event is prior to Day 176 (Week 25 + 7 day window), then a participant 
will be identified as extended lost to follow-up without an adequate assessment if 
the participant did not have an adequate disease assessment or T-cell infusion 
during the time period of 98 days (12 weeks + 1 week window + 1 week window) 
prior to PFS event  


 
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• Else if the PFS event is after Day 176 (Week 25 + 7 day window) and on or 
before Day 239 (Week 34 + 7 day window) then a participant will be identified as 
extended lost to follow-up without an adequate assessment if the participant did 
not have an adequate disease assessment during the time period of 119 days (6 
weeks + 9 weeks + 2 week window) 
• Else if the PFS event is after Day 239 (Week 34 + 7 day window) and on or 
before Day 323 (Week 46 + 7 day window) then a participant will be identified as 
extended lost to follow-up without an adequate assessment if the participant did 
not have an adequate disease assessment during the time period of 161 days (9 
weeks + 12 weeks + 2 week window) 
 
• Else if the PFS event is after Day 323 (Week 46 + 7 day window) then a 
participant will be identified as extended lost to follow-up without an adequate 
assessment if the participant did not have an adequate disease assessment during 
the time period of 182 days (12 weeks + 12 weeks + 2 week window) 
The “month” used in these algorithms is 30.4375 days long (365.25/12=30.4375) and 
rounded to the closest integer. 
If the participant has a missing or incomplete baseline assessment and dies before 
missing two scheduled disease assessments, the death will be considered an event. 
A summary of the assignments for progression and censoring dates for PFS are specified 
in  REF _Ref105524333 \h . 
Table 3 
Assignments for Progression and Censoring Dates for PFS Analysis 
Situation 
Date of Event 
(Progression/Death) or 
Censored  
Event 
(Progression/Death) 
Or Censored 
No or incomplete baseline tumor 
assessments or no measurable disease 
at baseline and the participants has not 
died  
Date of T cell infusion 
 
Censored 
No adequate post-baseline disease 
assessments before start of new anti-
cancer therapy and the participant has 
not died  
Date of T cell infusion 
Censored 
Progression documented between 
scheduled visits 
Date of radiological assessment of 
progression[1] 
Event 
With adequate post-baseline 
assessment but no progression (or 
death) 
Date of last adequate radiological 
disease assessment of response[2] 
Censored  
With adequate post-baseline 
assessment and new anticancer 
treatment started (prior to documented 
disease progression) [3] 
Date of last adequate radiological 
disease assessment of response[2] 
(on or prior to starting anti-cancer 
therapy) 
Censored 
Death before first scheduled 
assessment  
Date of death  
Event 


 
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Situation 
Date of Event 
(Progression/Death) or 
Censored  
Event 
(Progression/Death) 
Or Censored 
Death (regardless of having baseline 
assessment) before missing two 
schedule assessments and no 
progression 
Date of death (Use rule above to 
determine missing two scheduled 
assessments) 
Event 
Death (regardless of having baseline 
assessment) or progression after two or 
more consecutive missed adequate 
disease assessment[4] 
Date of last adequate radiological 
disease assessment of response[2] 
(prior to missed assessments) 
Censored 
[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] Refer to Section 7.2.1 for details of extended time without an adequate assessment 
Duration of Response (DOR) 
DOR is defined as the time (in months) from first documented evidence of confirmed PR 
or CR to the date of disease progression, as assessed by RECIST v1.1 or death due to any 
cause in the subset of participants with a confirmed CR or PR as assessed by local 
investigators per RECIST v1.1. Censoring rules and analysis details will follow those for 
PFS as specified in Table 3.  
  
Time to Response (TTR) 
TTR is defined as the time between T cell infusion to initial date of confirmed response 
(PR or CR) as assessed by investigator per RECIST v1.1 in the subset of participants who 
achieved a confirmed PR or CR.  
7.2.2. 
Summary Measure 
DCR 
The number and percentage of participants with the BOR in the following response 
categories will be summarized: CR, PR, SD ≥ 6 months, clinical benefit response 
(CR+PR+SD ≥ 6 months), PD and NE. The corresponding Clopper-Pearson 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 DCR percentages. DCR will be summarized for the ITT and mITT 
population. 
 
PFS 
The distribution of PFS will be estimated using the Kaplan-Meier method if data warrant, 
separately for each study arm. 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 & Crowley, 1982) using the SAS default 
(loglog transformation in PROC LIFETEST). A Kaplan-Meier curve will be produced 


 
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with 95% confidence bands, if data warrant. PFS rate at timepoints every 3 months and 
corresponding 95% CI will also be estimated from the Kaplan-Meier analysis. A 
supporting listing will be provided.  
The follow-up time for PFS will also be estimated based on reverse KM estimate, i.e., 
treating the patients who have had progression or died as censored, and those who 
continue to follow-up as event. The reverse KM estimates suggest the follow-up time for 
patients and provide context for the interpretation of the PFS estimates.  
DOR 
If there is a sufficient number of responses at time of analysis, the distribution of DOR 
will be estimated using the Kaplan-Meier method by study arm. 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 & Crowley, 
1982) using the SAS default (loglog transformation in PROC LIFETEST). A Kaplan-
Meier curve will be produced with 95% confidence bands, if data warrant. DOR will be 
summarized among the participants with confirmed response of PR or CR as the BOR. A 
supporting listing will be provided. 
TTR 
If there is a sufficient number of responses at time of analysis, time to response will be 
summarized descriptively by study arm using median, min, max and quartiles in the 
subset of participants with a confirmed response of PR or CR as the BOR. A supportive 
listing will be provided. 
7.2.3. 
Population of Interest  
The secondary efficacy analyses will be based on the mITT population, unless otherwise 
specified. The ITT is the sensitivity analysis population for DCR. If the mITT and ITT 
populations are identical, only results associated with the mITT population will be 
reported. 
7.2.4. 
Strategy for Intercurrent (Post-Randomization) Events 
For DCR: 
A composite strategy will be followed for participants who experience death prior to 
response assessments, or have only missing responses or not-evaluable assessments, or 
have non-measurable disease at baseline. These participants will be treated as non-
responders (NE) ; i.e. they will be included in the denominator when calculating the 
percentage. 
Start of new anti-cancer therapy is addressed with a while-on-treatment strategy, as the 
interest lies in the treatment effect of the investigational treatments before start of new 
anti-cancer therapy. 
For PFS and DOR: 


 
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New anti-cancer therapy started before documented PD or death is addressed with the 
hypothetical strategy, because the interest lies in the treatment effect attributable to the 
investigational treatments and not confounded by other anti-cancer therapies.  Palliative 
radiotherapy is not considered an anti-cancer therapy since it is permitted per protocol. 
Refer to Table 3 for censoring rules and intercurrent event strategy. 
7.2.5. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 12: 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. 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
3 6  
 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
3 7  
 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
3 8  
 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
3 9  
 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
4 0  
 
C CI


 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the mITT population, unless otherwise specified. 
Additional analyses will be presented using the Intent-to-Treat and Lymphodepletion 
populations. The Pembrolizumab Population will be used as needed to describe the safety 
and tolerability of pembrolizumab after T-cell infusion in the exposed populations. 
Arm C participants are expected to receive lete-cel in combination with pembrolizumab, 
however, since there is a 3 week time period between lete-cel infusion and the first 
scheduled dose of pembrolizumab, it is possible that Arm C participants may not receive 
any dose of pembrolizumab (e.g. if the participant withdraws from the study or dies after 
receiving lete-cel but before receiving any dose of pembrolizumab).  To account for this, 
all safety displays for Arm C in the T-cell infusion phase will be presented in a single 
table with three columns: Arm C (lete-cel monotherapy), Arm C (lete-cel + 
Pembrolizumab), and Arm C (Total). By study design, participants who didn’t receive 
pembrolizumab in Arm C have shorter follow-up times compared to the participants who 
received pembrolizumab, i.e., they are mostly followed shorter than 3 weeks and 
discontinued the study before the first dose of pembrolizumab. The results of the two 
split columns need to be interpreted with caution. Participants will be slotted into these 
columns based on actual treatment received.  Displays in the Pre-Lymphodepletion and 
Lymphodepletion phases will use planned treatment to display data separately by arm. 
Note that within the Arm A Pembrolizumab Population, all safety events (including AEs, 
SAEs, labs, etc) which occur after the first dose of Pembrolizumab therapy following 
disease progression (see phase definition in Appendix 13.4.1) should be excluded from 
the main safety summary tables. Safety data which is collected after the first dose of 
pembrolizumab in Arm A will be listed. The only exception will be summaries of 
Replication Competent Lentivirus and Integration Site Analysis, which will include all 
patient data without excluding data collected after the first dose of pembrolizumab.  
8.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious AEs 
(SAEs), AEs related to study-treatment (lymphodepleting chemotherapy, T-cell infusion, 
pembrolizumab), SAEs related to study treatment (lymphodepleting chemotherapy, T-cell 
infusion, pembrolizumab) and other significant AEs will be based on GSK Core Data 
Standards. AEs leading to dose modifications for Pembrolizumab (dose interruptions, 
dose reduction and dose delays) will also be summarized and listed according to GSK 
Oncology Data Standards for the Pembrolizumab population, as needed. The details of 
the planned displays are provided in Appendix 12: List of Data Displays. 
AEs will be graded according to National Cancer Institute-Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) version 4.03 unless otherwise specified in the protocol. 
For instance, the grading of AE-related Cytokine Release Syndrome (CRS) and ICANS 
will be performed using ASTCT grading criteria (Lee, Santomasso, & Locke, 2019); see 
protocol Section 10.9.5 and 10.9.8.1. For the grading of Graft versus Host Disease 
(GVHD) associated AEs, see protocol Section 10.9.6.2. AEs will be coded to the level of 


 
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Preferred Term (PT) using the latest version of the Medical Dictionary for Regulatory 
Affairs (MedDRA). 
Per GSK standard, Adverse Events that have grade changes over the course of the event 
are entered in the same record, with grade changes indicated within. Other attributes of 
the event (e.g. seriousness, relatedness) are attributed to the full event.  
For specific adverse event displays, Preferred Terms are combined and will be reported 
together as one term. The combined terms for MedDRA Version 24.1 are listed in 
Appendix 6. 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. A 
table showing the relationship between the combined preferred term and contributing 
preferred terms will be produced. Tables that summarize AEs by SOC and PT will use 
MedDRA preferred terms. Most other AE tables will summarize AEs by the combined 
terms in Appendix 6, unless otherwise specified. 
AEs will be summarized in the following phases among participants which have entered 
the phase. 
Phase 
Definition 
Population 
Pre-Lymphodepletion 
Phase 
AEs which start prior to lymphodepletion 
chemotherapy 
Intent-to-Treat 
Population 
Lymphodepletion Phase 
AEs which start or worsen on or after the 
start of lymphodepletion chemotherapy 
until prior to T-cell infusion 
Lymphodepletion 
Population 
T-cell Infusion Phase 
(Treatment-Emergent) 
AEs which start or worsen on or after T-
cell infusion up until Pembrolizumab 
Therapy Following Disease Progression 
after lete-cel Infusion (if applicable) 
mITT Population 
Pembrolizumab 
Therapy Following 
Disease Progression 
after GSK3377794 
Infusion Phase 
AEs which start or worsen on or after 
first dose of Pembrolizumab Rescue 
Therapy (Arm A only) 
Pembrolizumab 
Population (Arm A only) 
These periods are defined in more detail in Section 13.4.2. 
AEs which start within the phase or worsen after initiation of the phase (maximum grade 
after initiation of the phase is larger than the maximum grade before initiation of the 
phase) will qualify to be summarized in the phase. AEs may be summarized in multiple 
phases (ex: A Grade 2 AE after lymphodepletion increases to Grade 3 after T-cell 
infusion and is summarized as a Grade 2 in the lymphodepletion phase and a Grade 3 in 
the T-cell Infusion Phase).  


 
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The primary analysis of adverse events will be performed for AEs which started or 
worsened during the T-cell Infusion Phase i.e. treatment-emergent AEs. However 
additional analyses will be performed in the periods above.  
All AEs collected in the Intent-to-Treat population will be listed and the phase assigned 
to the AE will be indicated in the listing. AEs which led to study treatment withdrawal, 
interruption, delay, or reduction of any study treatment (cyclophosphamide, fludarabine, 
T-cell infusion, or Pembrolizumab) will be flagged in the listing as collected in the CRF. 
Additionally, a listing of participant IDs for each individual AE will be produced.  
SAEs will be included in the listing of all AEs, but also separate supportive listings with 
participant-level details will be generated for: 
• 
Non-fatal SAEs 
• 
Reasons for considering AE as serious 
AEs 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. 
Summaries of number and percentage of participants with adverse events by maximum 
grade will also be produced. AEs will be sorted by combined PT in descending order of 
total incidence. The summary will use the following algorithms for counting the 
participant: 
• 
Combined preferred term row: Participants experiencing the same combined 
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 adverse event will be counted 
only once at the maximum grade no matter how many events they have. 
Summaries will be provided for lymphodepletion-related and T cell-related AEs 
separately. Another separate summary by maximum grade will be provided for AEs 
related to pembrolizumab (Pembrolizumab Population). Study treatment-related AE is 
defined as an AE for which the investigator classifies the relationship to study treatment 
as “Yes”. 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.  
Analyses for AEs in the Pre-Lymphodepletion Phase will include: 
• Summary of AEs by System Organ Class and Preferred Term (using PT term) 
o AEs 
• Summary by maximum grade 
o AEs 
o SAEs 
 


 
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Analyses for AEs in the Lymphodepletion Phase will include: 
• Summary of AEs by System Organ Class and Preferred Term (using PT term) 
o AEs 
• Summary by maximum grade 
o AEs 
o SAEs 
o Lymphodepletion-related AEs 
Analyses for treatment-emergent AEs will include: 
• Summary of AEs by System Organ Class and Preferred Term (using PT term) 
o AEs 
o SAEs 
o T-cell related 
o Pembrolizumab related 
o Common non-serious AEs (number of subjects and occurrences) 
o SAEs (number of subjects and occurrences)  
• Summary by maximum grade  
o AEs 
o SAEs 
o T-cell related AEs 
o Pembrolizumab related AEs 
o Lymphodepletion related AEs 
o T-cell related SAEs 
o Pembrolizumab related SAEs 
o Lymphodepletion related SAEs 
• Descending frequency (using Preferred Term) 
o Non serious T-cell related AEs  
o Serious fatal and non-fatal T-cell related AE  
As displayed above, a summary of common non-serious treatment-emergent AEs that 
occurred in 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 of subjects 
and occurrences of participants with common non-serious adverse events. The summary 
table will be displayed by SOC and PT. A summary of All Treatment-Emergent Serious 
Adverse Events by System Organ Class (SOC) and Preferred Term (PT) will also be 
created to detail the number of participants and occurrences of each event. 
 
Delayed AEs as defined in the FDA 2020 Guidance- Long Term Follow-Up After 
Administration of Human Gene Therapy Products (FDA, 2020) are identified through 
sponsor adjudication as the primary method of reporting. Sponsor adjudication will focus 
on AEs starting 90 days after administration of T-cell therapy that fall into one of 
following categories:  
• New malignancies 


 
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• New incidence or exacerbation of a pre-existing neurological 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 or hospitalization deemed related to gene modified cell 
therapy 
Events that meet the criteria above, are study-treatment related events, and are serious 
and/or Grade ≥ 3 will be the primary focus of sponsor adjudication, although adjudication 
is not limited to these criteria. A listing of delayed AEs as adjudicated by the sponsor by 
delayed AE category will be produced.  
Delayed AEs are also identified by the investigator and captured in the CRF. Delayed 
AEs as adjudicated by the sponsor (provided from external data source) and identified by 
the investigator will be listed separately. 
8.2. 
Adverse Events of Special Interest Analyses 
Adverse events of special interest (AESIs) evaluated in this RAP include: 
• Cytokine release syndrome (CRS) 
• Pneumonitis/pneumonia 
• Graft vs host disease (GvHD) 
• Guillain Barre syndrome (GBS) or acute inflammatory demyelinating 
polyneuropathy (AIDP) 
• Pancytopenia/Aplastic anemia (including analysis of all hematopoietic 
cytopenias) 
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)  
• Treatment-related inflammatory response at tumor site(s) 
 
All analysis of AESIs will be performed in the T-cell Infusion Phase using the mITT 
population, unless otherwise stated.  
A focused list of MedDRA terms based on clinical review will be used to identify each 
type of event. In addition, a comprehensive list of MedDRA terms aligning with 
MedDRA SMQ list will also be used for AESI reporting. 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. The details of the planned displays are provided in Appendix 12: 
List of Data Displays. 
 


 
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The protocol-identified AESI, Treatment-related inflammatory response at tumor site, is 
non-specific and will not be identified using the focused or comprehensive list. 
Investigator identified AEs which may be related to this event will be used to characterize 
this AESI.  
The number and percentage of participants with treatment-emergent AESIs will be 
summarized by categories of AESI, combined preferred term, and grade using both the 
comprehensive list and focused list (if applicable). Hematopoeitic cytopenias will only be 
summarized using the focused list, and presented overall, as well as by cell line. 
 
A summary of AEs linked to the AESI identified by the investigator will be summarized 
by AESI and maximum grade. A summary of the concomitant medications linked to the 
AESI will also be provided by AESI. 
 
A summary of event characteristics for each category of AESI will 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 2 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, e.g. if a participant has an event leading to both study 
treatment discontinuation and dose reduction, the participant will be counted once under 
both actions. This summary will only be created if there are a sufficient number of 
events. 
Cytokine Release Syndrome 
 
The following analyses will be provided: 
• Summary of event characteristics (as detailed above) using the focused list 
• Among participants which experienced CRS, a summary of onset and duration of the 
first occurrence of CRS identified using the focused list will be provided.  
• Time to onset and duration of serious events, if at least 5 events 
• Summary of the procedures and medications associated with CRS from the CRS 
eCRF page 
• Cumulative total doses per patient that received tocilizumab for CRS 
 
 
A supporting CRS listing profile will be provided to detail the CRS adverse event, 
display the procedures and medications received to treat CRS, display symptoms 
associated with the event. 
 
Haematopoetic cytopenias 
 
The following analyses will be provided: 


 
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• Summary of event characteristics of treatment-emergent cytopenias using the focused 
list (as detailed above). 
• Summary of onset and duration of the first occurrence of febrile neutropenia 
 
 
 A supporting Pancytopenia listing profile will be provided to detail these events 
 
Pneumonitis/pneumonia 
The following analyses will be provided: 
• Summary of event characteristics using the focused list (as detailed above).  
• Summary of onset and duration of the first occurrence of pneumonitis/pneumonia 
identified using the focused list   
 
Supporting pneumonitis and pneumonia profile listings will be provided to detail these 
events 
 
Graft versus Host Disease (GvHD)The following analyses will be provided: 
• Summary of event characteristics using the focused list (as detailed above).  
• Summary of onset and duration of the first occurrence of GvHD identified using the 
focused list   
 
A supporting GvHD listing profile will be provided to detail these events 
 
Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS) 
The following analyses will be provided: 
• Summary of event characteristics using the focused list (as detailed above).  
• Summary of onset and duration of the first occurrence of ICANS identified using the 
focused list   
 
A supporting ICANS listing profile will be provided to detail these events 
 
Guillain-Barre Syndrome (GBS) 
A supporting GBS listing profile will be provided to detail these events  
 
The details of the planned displays are provided in Appendix 12: List of Data Displays. 
8.3. 
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 12: List of Data Displays. 
 


 
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Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
• 
MCV 
• 
MCH 
• 
Reticulocytes 
WBC count with 
Differential: 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Flow Cytometry  
T-Lymphocytes 
CD3/CD4/CD8 
 
 
Clinical Chemistry 
BUNb 
Potassium 
AST (SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
ALT (SGPT) 
Total Protein 
Glucose [Indicate if fasting, 
or nonfasting] 
Calcium 
Alkaline 
phosphatase 
Chloride 
Albumin 
Phosphorus 
LDH 
Ureaa 
 
Magnesium 
Bicarbonate 
 
Coagulation 
INR, PT, aPTT and Fibrinogen 
Routine Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte, and 
esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Tests 
• 
CMV IgG and PCR 
• 
TSH with free T4 
• 
CRP 
• 
Uric acid 
• 
GFR or 24-hour urine collection 
• 
Follicle-stimulating hormone and estradiol (as needed in women of non-
childbearing potential only) 
• 
Highly sensitive serum or urine hCG pregnancy test (as needed for women of 
childbearing potential)c 
• 
HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochete bacterium). 
• 
Ferritin 
• 
Serum troponin 
• 
NT-proBNP / BNP 
a. Details of liver chemistry monitoring criteria and required actions and follow-up assessments after liver 
monitoring event are given in Section 7.1.1 and Table 17 of study protocol. All events of ALT ≥ 3 × ULN 
and bilirubin ≥ 2 × ULN (>35% direct bilirubin) or ALT≥ 3 × ULN and INR >1.5, if INR measured, which 
may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE. 
b. Either BUN or UREA tests are acceptable 
c. Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/IEC. 
 
Laboratory grades will be reported using CTCAE v4.03. 
Summary of post-baseline change of laboratory values by visit will be provided. Separate 
summary tables for haematology, chemistry, and urinalysis 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. 
Supporting line graphs of neutrophils, platelets, hemoglobin, and lymphocytes over time 
will also be produced. Plots will be produced by type of lab value. 


 
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Summaries of worst case grade increase from baseline grade will be provided for all the 
laboratory 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, as well as post-baseline increase at all planned visits for 
hematology parameters. 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 laboratory 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. Missing 
baseline grade will be assumed to be normal. 
 
The number of participants with worst case protein or occult blood urinalysis (discrete or 
character) results will be summarized by the combination of specimen, method and test 
and category. 
 
8.3.1. 
Analysis of Liver Function Test (LFT) 
A summary of liver monitoring/stopping event reporting will be provided, with a 
corresponding listing. 
A listing of subjects meeting hepatobiliary laboratory abnormalities aligned with the 
Protocol liver monitoring criteria will be provided. The intent of this listing is to identify 
subjects, in particular possible Hy’s Law subjects, for clinical review. A summary of 
subjects meeting hepatobiliary laboratory abnormalities may be provided if enough 
subjects have events. Details can be found in the IDSL Liver standard document.  
The percentage of participants that met the following criteria will be summarized : ALT 
>3xULN and BIL >2xULN, ALT >3xULN and INR >1.5, ALT >3xULN and BIL 
>2xULN and (ALP <2xULN), Hepatocellular injury, Hepatocellular injury and BIL 
>2xULN, ALT >3xULN, ALT >5xULN, ALT >8xULN, ALT >10xULN, ALT 
>20xULN 
 
• To be counted in the denominator, the participant must have at least one post-baseline 
lab chemistry measurement for the specified lab tests (e.g. in the ‘ALT >3xULN and 
BIL >2xULN’ category, the denominator should include participants who had both a 
post-baseline ALT value AND a post-baseline BIL value that was up to 28 days after 
ALT).   
• Categories are not mutually exclusive.  For example, a participant with ALT 20xULN 
will be included in each of the 3x, 5x, 8x, 10x, and 20x categories. 


 
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• If Direct Bilirubin is available on the same day, then Direct Bilirubin as a portion of 
total bilirubin must be >35% when total Bilirubin is > 2xULN, in order to satisfy the 
criteria.  If all criteria for Hy’s law are satisfied except Direct Bilirubin exists and is < 
35% then the record will not be considered a possible Hy’s Law event.  The total 
Bilirubin elevation must occur on or up to 28 days after the ALT elevation (as this is 
the standard for DILI cases of Hy’s Law).  This was deemed an acceptable window 
through discussion with the GSK Hepatic Safety Panel. 
• Note: In the rare event that total Bilirubin value is not provided within 28 days on or 
after ALT value, Direct Bilirubin cannot be used in place of total Bilirubin in the 
Hy’s law criteria therefore a separate optional category can be included if needed to 
analyse these cases.  
• Hepatocellular injury is defined as ((ALT/ALT ULN)/(ALP/ALP ULN)) >5 and ALT 
>3xULN. ALT and ALP values must occur on the same day. The denominator should 
include participants who had both a post-baseline ALT and ALP on the same day.  In 
addition, the denominator for Hepatocellular injury and BIL >2xULN should include 
participants who had both a post-baseline ALT and ALP on the same day as well as 
BIL on or up to 28 days of that day.   
• For the row ‘ALT >3xULN and BIL >2xULN and (ALP <2xULN)’, the ALP value 
must occur on or up to 28 days after the ALT elevation.  
 
An additional liver stopping event profile will be provided to facilitate medical review of 
participants with liver stopping events. 
A scatter plot of maximum total bilirubin versus maximum ALT will be generated, as 
well as a scatter plot of maximum vs baseline for ALT. 
8.4. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified and these tests are 
gradable by CTCAE v4.03.. The details of the planned displays are presented in 
Appendix 12: List of Data Displays. 
8.4.1. 
Deaths 
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 displayed in the order 
it appears in the CRF.  
An individual participant profile for patients who died will be generated, which will 
report fatal SAEs. 


 
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8.4.2. 
Performance Status 
The frequency and percentage of participant’s ECOG score (0,1,2,3,4-5) at Baseline and 
the Last Assessment Post-Infusion) will be provided in addition to a summary of change 
in ECOG performance score from baseline for each planned assessment time, including 
worst case post-baseline and best case post-baseline. 
8.4.3. 
ECG 
The QTc values based on the Fridericia formula (QTcF) will be categorized into the 
following CTCAE v5.0 grade and ranges: Grade 0 (<450 milliseconds [msec]), Grade 1 
(>=450 to <481 msec), Grade 2 (>=481 to <501 msec), and Grade 3 (≥501 msec) at 
baseline. Summaries of worst-case grade increase will be provided. These summaries will 
display the number and percentage of participants with no change or improvement, any 
grade increase, increase to Grade 1, increase to Grade 2 and increase to Grade 3 for worst 
case post-baseline only. Participants with missing baseline grade will be assumed to be 
Grade 0 at baseline. 
The changes in QTcF values will be categorized into the clinical concern ranges which 
are specific to changes in QTcF from baseline: Increase of <=30 msec, increase of 31 to 
60 msec, and increase of >60 msec. A summary of change in QTc value will display the 
number and percentage of participants with a change within each range for worst case 
post-baseline only. Participants with missing baseline values will be excluded from this 
summary. 
If QTcF is missing, it will be calculated using the formula in Section 13.6.4. QTcB values 
will only be listed. 
QRS Durations will be categorized into the following categories approximately based on 
the limits determined by Ramirez et al. (Ramirez, 2011): Low (<70 msec), Normal (>=70 
msec to <= 105 msec) and High (>105 msec). Additionally these summaries will display 
the number and percentage of participants with no change or improvement to Normal, 
worsening to Low and worsening to High for the worst case (both minimum and 
maximum) post-baseline values only. Participants with missing baseline QRS duration 
will be assumed to be Normal at baseline. 
A listing of Left Ventricular Ejection Fraction results will be provided 
8.4.4. 
Vital Signs 
A summary of change in vital signs (heart rate, diastolic blood pressure, systolic blood 
pressure, pulse oximetry, temperature) from baseline by worst-case change post-baseline 
only will be provided by categories of potential clinical importance.  PCI criteria are 
detailed in Section 13.8.3. 
8.4.5. 
Pregnancies 
The investigator will report all pregnancies immediately to the Sponsor. If participants or 
participants’ partner become pregnant while on the study, the information will be 


 
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included in the narratives. A supportive listing of participants or partners of participants 
who became pregnant during the study will be produced to support the case narratives. 
8.4.6. 
Cardiovascular Events 
As required by the GSK Global Safety Board, profile displays for following ten 
cardiovascular events will be produced if an event occurs and the appropriate CV event 
form has been completed.  
• Arrythmias 
• Congestive Heart Failure 
• Cerebrovascular Events, Stroke and Transient Ischemic Attack 
• Deep Vein Thrombosis/Pulmonary Embolism 
• Unstable Angina / Myocardial Infarction 
• Peripheral Arterial Thromboembolism 
• Pulmonary Hypertension 
• RevascularisationValvulopathy 
8.4.7. 
Replication Competent Lentivirus and Integration Site Analysis 
The results of Replication Competent Lentivirus (RCL) and Integration Site Analysis 
(ISA) will be summarized descriptively.  Note that all available data should be included 
in summaries for RCL and ISA, i.e. for the Arm A cohort patients who received 
Pembrolizumab following progression after lete-cel infusion data will not be excluded 
from summaries, even if after the first dose of pembrolizumab. 
Replication Competent Lentivirus (RCL) 
The proportion of participants who are RCL positive will also be summarized, if data 
warrant. RCL results will also be presented in a data listing. 
The proportion of participants showing >1% gene marked PBMCs one-year post-infusion 
will be summarized. Percentage will be based on the participants with persistence value 
available one-year or later post-infusion. 
For any patient who has greater than 1% gene marked PBMCs at least 1 year or beyond 
post-infusion, integration site analysis will be performed on PBMCs to assess clonality 
and possible insertional oncogenesis.  
Integration Site Analysis 
For participants that undergo Integration Site Analysis, a supportive listing will be 
provided to report the data. Two diversity indices, Shannon diversity index and Gini 
index (GI), will be reported in the data listing. Shannon diversity is a measurement that 
represents the uncertainty about the identity of a single species within a population. 
Therefore, the greater number of unique species within a population, the less certain the 
measure is of the “identity” of any one species, resulting in a higher value of Shannon 
diversity. Likewise, the less complex the population, the lower the value of Shannon 
diversity. When Shannon diversity is calculated it takes into account the number of 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
5 3  
 
disti nct cl o nes (“s peci es”) as well as t he a b u n da nce of eac h cl o ne. A l o w val ue of 
S ha n n o n di versit y has bee n pre vi o usl y re p orte d i n t he literat ure as b ei n g ass ociate d wit h 
cl o nal e x pa nsi o n a n d a re d ucti o n i n o verall cl o nal di versit y Bra u n , 2 0 1 4).  
T he GI is a meas ure f or d etecti n g i ne q uali t y i n t he distri b uti o n of cl o ne sizes. A GI val ue 
of 0 i n dicates c o m plete e q ualit y acr oss t he p o p ulati o n i.e., all cl o nes ha ve t he sa me 
a b u n da nce. A val ue of 1 w o ul d i n dicate c o m plete i ne q ualit y i.e.,  o ne cl o ne is m uc h m ore 
a b u n da nt t ha n t he ot hers. T heref ore, as GI a p pr oac hes 1 t his i n dicates t hat o ne cl o ne is 
hi g hl y a b u n da nt. It h as pre vi o usl y bee n use d f or i nserti o n site a nal ysis (as t he 
oli g ocl o nalit y i n de x ( Gillet , 2 0 1 1)) t o descri be cl o nal p o p ulati o ns w here t h e d o mi na nce 
of a si n gle cl o ne is see n ( e. g., le u kae mia).  
 
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9. 
PHARMACOKINETIC ANALYSES 
9.1. 
Primary Pharmacokinetic Analyses 
There are no primary pharmacokinetic analyses planned for this study. 
9.2. 
Secondary Pharmacokinetic Analyses 
9.2.1. 
Endpoint / Variables 
Evaluation of peak expansion of NY-ESO-1c259T cells over time is a secondary objective. 
All analyses will be performed separately for each treatment arm. 
9.2.1.1. 
Cell Expansion 
Lete-cel T-cell vector copies (expansion/persistence) in the peripheral blood will be 
measured in participants either by quantitation of transduced cells by PCR of transgene 
from DNA extracted from frozen PBMC or quantitation of transduced cells by flow 
cytometry from frozen PBMC. Expansion will be measured to establish the relationships 
with response to lete-cel as well as a long-term safety measure. For all PK analyses, 
expansion of the engineered T-cells will be applied in lieu of “concentration” to derive 
PK parameters. 
Spider plots will be used to graphically summarize persistence over time for each 
participant by responders and non-responders.  
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 13.5.3 
Reporting Standards for Pharmacokinetic) 
9.2.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters will be calculated by the Clinical Pharmacology Modelling 
and Simulation (CPMS) group using standard non-compartmental analysis according to 
current working practices and using appropriate software. All calculations of non-
compartmental parameters will be based on actual sampling times. Pharmacokinetic 
parameters listed will be determined from the expansion-time data, as data permits. 
Peak cell expansion during the study (Cmax), time to peak expansion (Tmax), and as data 
permit, AUC0-28d will be summarized overall and for responders and non-responders 
using descriptive statistics and dot plots. 
The area under the plasma concentration-time curve to day 28 (AUC0-28d) will be 
determined using the linear trapezoidal rule for increasing concentrations and the 
logarithmic trapezoidal rule for decreasing concentrations.  
 


 
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Parameter 
Parameter Description 
AUC0-28d 
Area under the expansion-time curve from time zero to 28 days will be calculated using the 
linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each 
decremental trapezoid. 
Cmax 
Maximum observed persistence, determined directly from the persistence-time data. 
Tmax 
Time to reach Cmax, determined directly from the persistence-time data. 
NOTES: 
• 
Additional parameters may be included as required. 
 
9.2.2. 
Summary Measure 
For each of these parameters, except Tmax, the following summary statistics will be 
calculated: n, median, minimum, maximum, arithmetic mean, 95% confidence interval 
for the arithmetic mean, standard deviation, coefficient of variation (coefficient of 
variation (CV) = 100*(sqrt (exp(SD2) - 1))) [NOTE: SD = SD of log transformed data]), 
geometric mean, 95% confidence interval for the geometric mean and standard deviation 
of logarithmically transformed data. Data will be summarized by treatment arm and 
overall. 
 
For Tmax, calculations will include median, maximum, minimum, arithmetic mean, 95% 
confidence interval, and standard deviation. Data will be summarized by treatment arm 
and overall. 
 
Spider plots will be used to graphically summarize persistence (copies/µg gDNA) over 
time for each participant.  
A listing of persistence will be provided and will include coefficient of variation, number 
of positive replicates, copies/cell, copies/µg DNA, percent gene marked cells of PBMCs 
(%), interpretive result, duration of detectible persistence, time to loss of 25%/50%/75% 
peak expansion, and AUC0-28d.  
Time to loss of 25% of peak expansion will be calculated as the time since T-cell infusion 
corresponding to observing at least 25% loss of peak expansion. If time to 25% loss of 
peak expansion is not observed, the last observed time will be reported with a “+”. The 
same procedure will be followed for 50% and 75%. 
The following calculations will be performed: 
• copies/cell is calculated with the following formula: 
copies/cell=(copies/µg) x (0.0000063 µg gDNA/cell) 
• Percent gene-marked cells of peripheral blood mononuclear cells (PBMCs) = 
(copies/cell) x 100 
 
The final reported result of copies/µg gDNA is calculated as follows: 
copies/µg DNA=copies per well/µg gDNA per well 
 
For persistence value below LLOQ, the following rules will be applied: 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
5 6  
 
Re p orte d C o pies 
per cell Res ult  
Re p orte d C o pies 
per u g g D N A 
Res ult  
Re p orte d Res ult  
Set Val ue f or 
C o pies per cell  
Set Val ue f or 
C o pies per u g 
g D N A  
< 0. 0 0 0 3  
< 5 0. 0  
Ne gati ve  
0  
0  
< 0. 0 0 0 3  
< 5 0. 0  
Detecta ble, 
< L L O Q  
0. 0 0 0 3  
5 0  
 
N ote, s o meti mes val ues f or c o pies per cell a n d c o pies per u g D N A mi g ht b e differe nt 
t ha n a b o ve as it de p e n ds o n t he i n p ut of D N A, b ut r ule w o ul d be t he sa m e: 
- 
If i nter pr eti ve re p orte d res ult is ne gati ve, t he n set val ues t o 0.  
- 
If i nter pr eti ve re p orte d res ult is “ Detecta ble, < L L O Q”, set val u es t o L L O Q (If 
< X X X, set at X X X)  
T he u nit f or persiste n ce will be “ C o pies/ u g of g D N A” 
All P K para meters will be re p ort e d t o at least 3 si g nifica nt di gits, b ut t o n o m ore 
si g nifica nt di gits t ha n t he precisi o n of t he ori gi nal data. 
D urati o n of detecta ble p ersiste nce is defi ne d as ti me fr o m T -cell i nf usi o n u ntil 
persiste nce is n o l o n ger d etecta ble. Persiste nce a b o ve t he assa y li mi t of det ecti o n b ut 
bel o w t he l o wer li mit of q ua ntitati o n is c o nsi dere d f or t he d urati o n det er mi nati o n, i.e. t he 
ti me wi n d o w fr o m i nf usi o n u ntil t he first i nsta nce persiste nce falls bel o w t h e detecti o n 
li mit a n d t he i nter preti ve re p orte d res ult is “ Ne gati ve.” If p ersiste nce f or a gi ve n 
partici pa nt  re mai ns d etecta ble (“ P ositi ve” or “ Det ecta ble, L L O Q”) at t heir last sa m ple 
c ollecti o n ti me p oi nt, t he last o bser ve d ti me is re p orte d a n d c o nsi dere d as ri g ht- ce ns ore d 
wit h a “ +”  a p pe n d e d t o t he n u merical res ult. N ote, tra ns d uce d T-cells fre q u e ntl y persist 
be y o n d t he f oll o w- u p peri o d, a n d he nce, t h e re p orte d d urati o n is directl y i nfl ue nce d b y 
le n gt h of ti me t he partici pa nt is o n-st u d y 
9. 2. 3.  
P o p ul ati o n of I nt er e st  
T he sec o n d ar y  p har mac o ki netic a nal yses will be b ase d o n t he P har mac o ki n etic  
p o p ulati o n, u nless ot her wise s pecifie d. 
9. 2. 4.  
St ati sti c al A n al y s e s / M et h o d s  
Details o f t he pla n ne d dis pla ys are pr o vi d e d i n A p pe n di x 1 2 : List of Data Dis pla ys a n d 
will be base d o n G S K D ata Sta n dar ds a n d statistical pri nci ples.  
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10. 
BIOMARKER ANALYSES 
Details of the exploratory biomarker analyses will be reported under a separate 
Biomarker Clinical Study Plan. 


 
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11. 
ADDITIONAL ANALYSES DUE TO THE COVID-19 
PANDEMIC 
11.1. 
Study Population 
11.1.1. 
Subject Disposition 
A country level listing of the dates of the COVID-19 Pandemic measures will be 
produced. For the definition of the phases of the COVID-19 pandemic measures see 
Section 13.4.1.2. 
The ‘Summary of Subject Status and Subject Disposition for the Study Conclusion 
Record’ will be repeated, with the reason for withdrawal/discontinuation categorised as 
due to versus not due to the COVID-19 pandemic based on information collected on the 
COVID-19 Pandemic Study Impact form. The summary will be based on GSK Core Data 
Standards, and details are provided in Appendix 12: List of Data Displays. Study 
treatment that is discontinued due to the COVID-19 pandemic will be flagged in the 
listing. 
 
11.1.2. 
Protocol Deviations 
In addition to the overall summary of important protocol deviations, separate summaries 
will be produced of important protocol deviations related to COVID-19, and important 
protocol deviations not related to COVID-19. A listing of non-important protocol 
deviations related to COVID-19 will also be produced.  
Visits and assessments missed due to the COVID-19 pandemic, together with visits 
conducted remotely, will be listed by participant. The summaries will be based on GSK 
Core Data Standards, and details are provided in Appendix 12: List of Data Displays. 
11.1.3. 
Additional Displays for Participants with a COVID-19 Infection 
A participant is defined as having a suspected, probable or confirmed COVID-19 
infection during the study if the answer is “Confirmed”, “Probable” or “Suspected” to the 
case diagnosis question from the COVID-19 coronavirus infection assessment eCRF. 
Analysis of participants with a suspected, probable or confirmed COVID-19 infection, 
and of COVID-19 test results will be based on GSK Core Data Standards.  
A summary of COVID-19 assessments for participants with COVID-19 AEs will be 
provided, if the data warrant. A comprehensive profile listing of COVID-19 assessments 
and symptom assessments for participants with COVID-19 adverse events will be 
provided. 
More detailed summaries of additional COVID-19 assessments and symptoms may be 
produced if enough COVID-19 Adverse Events are observed in the ITT population. 
The details of the planned displays are provided in Appendix 12: List of Data Displays. 


 
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11.2. 
Efficacy 
The impact of the COVID-19 pandemic on the efficacy results has been accounted for 
within the estimand definitions and interccurent event strategy, defined in Section 7.  
11.3. 
Safety 
11.3.1. 
Assessment of COVID-19 AEs 
A Standardised MedDRA Query (SMQ) will be used to identify all COVID-19 AEs. 
COVID-19 AEs will either be listed or summarized by overall frequency, depending on 
the number of COVID-19 AEs observed in the ITT population. 
The incidence of AEs and SAEs (Fatal and Non-Fatal) of COVID-19 will be obtained 
from standard AE and SAE summaries. COVID-19 AEs leading to study drug 
discontinuation and study withdrawal can be found in the associated listing. 
Additional analyses of COVID-19 AEs and laboratory results for participants with 
COVID-19 AEs may be provided, if enough COVID-19 AEs are observed. 
All of the above displays will be based on GSK Core Data Standards. The details of the 
planned displays are provided in Appendix 12: List of Data Displays. 
 
 


 
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12. 
REFERENCES 
Braun, C., Boztug, K., Paruzynski, A., Witzel, M., Schwarzer, A., Rothe, M., & ... 
Fronza, R. (2014). Gene therapy for Wiskott-Aldrich Syndrome -- long-term 
efficacy and genotoxicity. . Science translational medicine, 6(227). 
Brookmeyer, R., & Crowley, J. (1982). A confidence interval for the median survival 
time. Biometrics, 38, 29-41. 
Dubois, D., & Dubois, E. (1916). A formula to estimate the approximate surface area if 
height and weight be known. Arch Intern Med, 17, 863-871. 
Eisenhauer, E. A.; Therasse, P.; Bogaerts, J.; Schwartz, L. H.; Sargent, D.; Ford, R. et al. 
(2009): New response evaluation criteria in solid tumours: revised RECIST 
guideline (version 1.1). European journal of cancer, 45 (2), 228–247.  
FDA. (2020, January). Guidance for Industry, Long Term Follow-Up After 
Administration of Human Gene Therapy Products. 
Gillet, N., Malani, N., Melamed, A., Gormley, N., Carter, R., Bentley, D., & ... Bangham, 
C. (2011). The host genomic environment of the provirus determines the 
abundance of HTLV-1-infected T-cell clones. Blood, The Journal of the American 
Society of Hematology, 117(11), 3113-3122. 
Lee, D., Santomasso, B., & Locke, F. (2019). ASTCT Consensus Grading for Cytokine 
Release Syndrome and Neurologic Toxicity Associated with Immune Effector 
Cells. Biology of Blood and Marrow Transplantation, 25, 625-628. 
Ramirez, A., Schildcrout, J., Blakemore, D., Masys, D., Pulley, J., Basford, M., & ... 
Denny, J. (2011). Modulators of normal electrocardiographic intervals identified 
in a large electronic medical record. Heart Rhythm, 8(2), 271-277. 
 


 
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13. 
APPENDICES 
13.1. 
Appendix 1: Exclusions from Per Protocol Population 
This study does not include a Per-Protocol population. 


 
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13.2. 
Appendix 2: Schedule of Activities 
13.2.1. 
Protocol Defined Schedule of Events 
Table 6 
Schedule of Activities - Screening (Part 1) and Leukapheresis (Part 2) 
 
 
Screening Phase1 
Leuka-
pheresis4 
Notes 
Day (D) / 
Week (W)  
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening 
(Within 42 days 
prior to 
Leukapheresis) 3 
 
 
Informed Consent for Screening 
X 
 
 
1. 
Written informed consent must be obtained prior to performing any study 
assessments or procedures, except for those collected as SoC and considered 
acceptable for the study (footnote 11) or as part of other GSK studies (per Protocol 
Section 4.1.1). 
2. 
Target Expression Screening may be performed under a separate protocol, if 
applicable, per Protocol Section 4.1.1. 
3. 
Participants must be HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive and 
have NY-ESO-1/LAGE-1a positive tumor prior to conducting leukapheresis 
eligibility screening procedures. 
4. 
Participants must meet all eligibility requirements prior to leukapheresis, as 
specified in Protocol Section 5. 
5. 
If an archival tumor specimen is not available, then a fresh tumor tissue biopsy 
may be considered at the discretion of the investigator. See Protocol Section 8.9.2. 
6. 
Only collect this sample if optional Liquid Biopsy Consent has been signed by the 
participant as part of the Informed Consent for Screening. Sample may be 
collected any time from signature of optional consent until leukapheresis. 
7. 
Medical history will be recorded in the eCRF at Target Expression Screening and 
at Lymphodepletion Screening/Baseline visits; however, any changes in medical 
history must be recorded in source documents throughout the conduct of the 
study. 
Informed Consent for 
Leukapheresis and Treatment 
 
X 
 
Inclusion/Exclusion for Screening 
X 
 
 
Inclusion/Exclusion for 
Leukapheresis 
 
X 
 
Demographics 
X 
 
 
HLA -A*02:01, A*02:05 and 
A*02:06 genotyping1 
X 
 
 
Tumor expression of NY-ESO-1/ 
LAGE-1a5 
X 
 
 
Liquid Biopsy (blood)6 
X 
 
 
Medical History7 
X 
X 
 
Prior/Concomitant Medications8 
X 
X 
X 
ECOG 
X 
X 
 
Physical Exam10 
 
X 
 
Vital Signs / Height / Weight15  
 
X 
 
12-lead ECG9  
 
X 
 
ECHO/MUGA11 
 
X 
 
CT / MRI11,12 
 
X 
 


 
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Screening Phase1 
Leuka-
pheresis4 
Notes 
Day (D) / 
Week (W)  
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening 
(Within 42 days 
prior to 
Leukapheresis) 3 
 
 
Brain MRI11 
 
X 
 
8. 
Includes all prescriptions, over-the-counter medications, and herbal remedies.  Any 
use of mutagenic agents or investigational agents must also be reported. 
9. 
Collect a single ECG.  If QTc is >480 msec, collect 2 more ECGs 5 minutes apart 
and use the average of those QT values to determine eligibility. If the average QTc 
is >480 msec, obtain a manual overread of the triplicate. 
10. All clinical assessments required at Leukapheresis Eligibility Screening must be 
performed within 42 days prior to leukapheresis, except for vital signs, weight, 
lymphocyte subset (CD3/CD4/CD8), hematology, clinical chemistry, coagulation 
tests, physical exam and urinalysis which must be done within 7 days prior to 
leukapheresis. 
11. ECHO/MUGA, CT/MRI scan, brain MRI 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.  
12. Any FDG PET/CT performed as part of clinical routine within the required time 
period before leukapheresis will also be collected centrally but will not replace CT 
scans. 
13. CD3 count prior to leukapheresis should be preferably performed within 24 hours 
from leukapheresis procedure. 
14. WOCBP must have a negative urine or serum pregnancy test at Screening and 
again prior to leukapheresis. 
15. Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen 
saturation.  Height will be collected at the Screening visit only. FEV1, FVC, TLC, 
and DLCO will be measured to determine eligibility as described in Protocol 
Section 5. 
16. Includes HIV, HBV, HCV, HTLV, EBV, CMV, and syphilis (spirochete bacterium).  
Must be completed within 28 days prior to leukapheresis. Testing is required at 
Screening and needs to be repeated at Baseline (see Table 7) to satisfy eligibility 
criteria. 
Lymphocyte Subset 
(CD3/CD4/CD8)10,11,13 
 
X 
 
Hematology10,11 
 
X 
 
Clinical Chemistry10,11 
 
X 
 
Coagulation Tests10,11 
 
X 
 
Pregnancy Test14 
 
X14 
X14 
Urinalysis10,11 
 
X 
 
PFTs15 
 
X 
 
Infectious Disease Markers11,16 
 
X 
 
Creatinine clearance by GFR or 24-
h Urine Collection 
 
X 
 
Adverse Events17 
X 
X 
X 
Leukapheresis18 
 
 
X 


 
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Screening Phase1 
Leuka-
pheresis4 
Notes 
Day (D) / 
Week (W)  
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening 
(Within 42 days 
prior to 
Leukapheresis) 3 
 
 
17. Adverse events (AEs) should be collected and reported as noted in Protocol 
Section 8.4. 
18. Arm assignment should occur before leukapheresis. 
 
 
Abbreviations: CMV = cytomegalovirus; CT = computed tomography; DLCO =  pulmonary diffusing capacity for carbon monoxide; EBV = Epstein-Barr virus; ECG = electrocardiogram; 
ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; eCRF = electronic case report form; FDG PET = fluorodeoxyglucose positron emission tomography; 
FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; GFR = glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; HLA = human leukocyte antigen; HTLV = human T lymphotropic virus; LAGE-1a = cancer testis antigen 2; MRI = magnetic resonance imaging; 
MUGA = multigated acquisition; NY-ESO-1 = New York esophageal squamous cell carcinoma 1; PFT = pulmonary function test; SoC = standard of care; TLC = total lung capacity; 
WOCBP = women of child-bearing potential. 
 
 


 
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Table 7 
Schedule of Activities - Lymphodepletion/Treatment (Interventional Phase) (Part 3) 
 
Base- 
line 
Lymphodepletion 
Lete-cel 
Infusion1 
Post-T-cell Infusion 
Day (D) / Week (W) 
Day 
-17 to -9 
Day 
Week2 
 
 
-8 
-7 
-6 
-5 
1 
2 
3 
4 
5 
2 
3 
4 
5 
6 
7 
10 to 25 
Q3W 
Arm A: 34-106 Q12W  
Arms B & C: 28-106 Q3W 
Visit Window 
n/a 
 
 
 
 
n/a 
±1 day 
±3 days 
±3 days 
Treatment Fitness 
and 
Lymphodepletion 
Eligibility 
Screening3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med. History4  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Neurological 
assessments5 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ICE5 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Prior/Concomitant 
Medications6 
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 
Vital Signs7,8  
X 
 
 
 
 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECHO/MUGA9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG10 
X 
 
 
 
 
X 
 
 
X 
 
X 
 
 
 
 
 
 
 
Body CT/MRI11,12 
X11,12 
 
 
 
 
See footnotes 11 and 12 
RECIST evaluation 
X11 
 
 
 
 
See footnote 11 
Brain MRI13 
X13 
 
 
 
 
See footnote 13 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ferritin15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Troponin and NT-
proBNP/BNP15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation 
Tests14,15 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
6 6  
 
 
B a s e - 
li ne  
L y m p h o d e pl eti o n  
L et e -c el 
I nf u si o n1 
P o st - T-c ell I nf u si o n  
D a y ( D) / W e e k ( W)  
D a y  
-1 7 t o -9 
D a y  
W e e k 2 
 
 
- 8 
- 7 
- 6 
- 5 
1 
2 
3 
4 
5 
2 
3 
4 
5 
6 
7 
1 0 t o 2 5  
Q 3 W  
Ar m A: 3 4 -1 0 6  Q 1 2 W  
Ar m s B & C: 2 8 -1 0 6  Q 3 W  
Vi sit  Wi n d o w  
n/ a  
 
 
 
 
n/ a  
± 1 d a y  
± 3 d a y s  
± 3 d a y s  
Pr e g n a ncy T est 1 6 
X 1 6 
 
 
 
 
X 1 6  
 
 
 
 
 
 
X  
 
 
X  
X  
X  
Uri n aly sis 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I nf ecti o us Dis e as e 
M ark ers  
( HI V, H B V, H C V, 
H T L V, E B V, a n d 
sy p hilis)   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C M V I g G a n d 
P C R 1 7 
X 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
X 
 
 
T S H wit h Fr e e T 4 1 8 
X  
Se e f o ot n ot e 1 8  
C R P 1 5 
X  
 
 
 
 
X  
 
 
X   
X  
X  
X  
X  
X  
X  
X  
X  
Uric Aci d  
X  
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
G F R or 2 4 -h uri n e 
c oll ecti o n 1 9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A dv ers e Ev e nts 2 0 
X  
X  
X  
X  
X  
X  
X  X  X  X  
X  
X  
X  
X  
X  
X  
X  
X  
V ect or C o pi es 
( P ersist e nc e) f or 
S af ety ( bl o o d) 2 1  
X 
 
 
 
 
 
F or c oll ecti o n, s e e  
f o ot n ot e 2 1 
V S V -G D N A ( R C L) 
f or S af ety ( bl o o d)2 2  
X 
 
 
 
 
 
F or c oll ecti o n, s e e  
f o ot n ot e 2 2 
L y m p h o d e pl eti o n  
Fl u d ar a bi n e  
 
X  
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycl o p h os p h a mi d e  
 
 
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
I n v e sti g ati o n al Pr o d u ct A d mi nistr ati o n 
L et e -c el 
 
 
 
 
 
X 2 3  
 
 
 
 
 
 
 
 
 
 
 
 
P e m br oliz u m a b  
Se e f o ot n ot e 2 4  
S e e T a bl e 1 0  f or P K , I m m u n o g e ni cit y, a n d Bi o m ar k er s Sa m pl es 
G e n etic s a m pl e  
X 2 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
6 7  
 
 
B a s e - 
li ne  
L y m p h o d e pl eti o n  
L et e -c el 
I nf u si o n1 
P o st - T-c ell I nf u si o n  
D a y ( D) / W e e k ( W)  
D a y  
-1 7 t o -9 
D a y  
W e e k 2 
 
 
- 8 
- 7 
- 6 
- 5 
1 
2 
3 
4 
5 
2 
3 
4 
5 
6 
7 
1 0 t o 2 5  
Q 3 W  
Ar m A: 3 4 -1 0 6  Q 1 2 W  
Ar m s B & C: 2 8 -1 0 6  Q 3 W  
Vi sit  Wi n d o w  
n/ a  
 
 
 
 
n/ a  
± 1 d a y  
± 3 d a y s  
± 3 d a y s  
A b br evi ati o ns:  
A E = a dv ers e ev e nt; B N P = B -ty p e n atri ur etic p e pti d e; C M V = cyt o m e g al ovir us; C R P = C-r e activ e pr ot ei n; C R S = cyt oki n e r el e as e sy n dr o m e; C T = c o m p ut e d t o m o gr a p hy; C T C A E = 
C o m m o n T ec h nic al Crit eri a f or A dv ers e Ev e nts; D N A  = d e oxyri b o n ucl eic aci d; E B V = Epst ei n -Barr vir us; E C G = el ectr oc ar di o gr a m; E C H O = ec h oc ar di o gr a m; E C O G = E ast er n C o -
o p er ativ e O nc ol o gy Gr o u p; e C R F = el ectr o nic c as e r e p ort f or m; Eo T = e n d of tr e at m e nt; F D G P E T = fl u or o d e oxy gl uc os e p ositr o n e missi o n t o m o gr a p hy; G F R  = gl o m er ul ar filtr ati o n 
r at e; H B V = h e p atitis B vir us; H C V = h e p atitis C vir us; HI V = h u m a n i m m u n o d efici e ncy vir us; 
; H T L V = h u m a n T ly m p h otr o pic vir us; I C A N S =I m m u n e 
Eff ect or C ell -Ass oci at e d N e ur ot oxicity Sy n dr o m e; I C E = I m m u n e Eff ect or C ell -Ass oci at e d Enc e p h al o p at hy ; I g G = i m m u n o gl o b uli n G; M RI = m a g n etic r es o n a nc e i m a gi n g; M U G A = 
m ulti g at e d ac q uisiti o n; N T -pr o B N P = N -t er mi n al pr o B-ty p e n atri ur etic p e pti d e; P C R = p oly m er as e c h ai n r e acti o n; P D = pr o gr essiv e dis e as e; P K = p h ar m ac oki n etic; P M B C = p eri p h er al 
bl o o d m o n o n ucl e ar c ell; Q 3 W = o nc e ev ery 3  w e eks; Q 6 W = o nc e ev ery six w e eks; Q 9 W = o nc e ev ery 9  w e eks; Q 1 2 W = o nc e ev ery 1 2  w e eks; R C L  = r e plic ati o n c o m p et e nt l e ntivir us; 
R E CI S T = R es p o ns e Ev al u ati o n Crit eri a I n S oli d T u m ors; T 4 = t hyr oxi n e; T S H = t hyr oi d sti m ul ati n g h or m o n e; V S V - G = v esic ul ar st o m atitis vir us G. 
1. O n D ay 1, all s a m pl es will b e c oll ect e d a n d ass ess m e nts p erf or m e d pri or t o L et e -c el i nf usi o n ( wit hi n 2 4 h), u nl ess ot h er wis e s p ecifi e d. 
2. W e ek N visit f or N > 1 is sc h e d ul e d o n 1st d ay of t h e w e ek; D ay = 7 N - 6 
3. Tr e at m e nt fit n ess will b e ev al u at e d acc or di n g t o Pr ot oc ol Secti o n  5 an d d et er mi n e d i n c o ns ult ati o n wit h M e dic al M o nit or.  
4. M e dic al hist ory, i ncl u di n g hist ory of t o b acc o us e, will b e r ec or d e d i n t h e e C R F at Scr e e ni n g a n d B as eli n e visits; h o w ev er,  a ny c h a n g es i n m e dic al hist ory m ust b e r ec or d e d i n s o urc e 
d oc u m e nts t hr o u g h o ut t h e c o n d uct of t h e st u dy  
5. N e ur ol o gic al ass ess m e nts ar e t o b e p erf or m e d f or p ati e nts wit h br ai n m et ast as es a n d p ati e nts wit h n e ur ol o gic al a dv ers e ev e nts u p t o 1 2 w e eks p ost r es ol uti o n of t h e ev e nt. I C E 
s h o ul d b e m e as ur e d o n t h e d ay of L et e-c el i nf usi o n pri or t o tr e at m e nt. F oll o wi n g i nf usi o n, I C E s h o ul d b e m e as ur e d acc or di n g t o i nstr ucti o ns i n Pr ot oc ol S ecti o n  1 0. 9. 8. 2.  
6. I ncl u d es all pr escri pti o ns, ov er -t h e-c o u nt er m e dic ati o ns a n d h er b al r e m e di es.  Any us e of m ut a g e nic a g e nts or i nv esti g ati o n al a g e nts m ust als o b e r e p ort e d.  It als o i ncl u d es us e of  
a nti bi otics a n d pr o bi otics t ak e n 6 0 d ays pri or t o ly m p h o d e pl eti o n a n d u p t o W e ek 7 visit.  
7. I ncl u d es t e m p er at ur e, bl o o d pr ess ur e,  p uls e r at e, r es pir at ory r at e, oxy g e n s at ur ati o n a n d w ei g ht.  H ei g ht will b e c oll ect e d at t h e Scr e e ni n g visit o nly.  
8. Vit al si g ns o n d ay of L et e -c el i nf usi o n s h o ul d b e t ak e n pr e-i nf usi o n, a n d at 5, 1 5, a n d 3 0 mi n ut es, a n d 1, 1. 5, 2, a n d 4 h o urs aft er t h e i nf usi o n h as st art e d. O n p e m br oliz u m a b 
i nf usi o n d ays, vit al si g ns s h o ul d b e t ak e n pr e- a n d p ost -i nf usi o n. 
9. If p artici p a nt's E C H O/ M U G A at l e uk a p h er esis eli gi bility scr e e ni n g m et eli gi bility f or l eft v e ntric ul ar ej ecti o n fr acti o n ≥4 5 % as s p ecifi e d i n Pr ot oc ol S ecti o n  5. 1. 2 , a n d if pri or 
E C H O/ M U G A w as o bt ai n e d wit hi n 9 0 d ays pri or t o t h e first d ay of ly m p h o d e pl eti o n, t h e n a r e p e at E C H O/ M U G A will n ot b e r e q uir e d.  R e p e at E C H O/ M U G A at b as eli n e s h o ul d b e 
o bt ai n e d as cli nic ally i n dic at e d. If s us p ect e d C R S Gr a d e  ≥2, a n E C H O/ M U G A is r e q uir e d at o ns et of Gr a d e ≥2 C R S. Ad diti o n al m o nit ori n g m ust b e c o n d uct e d (i ncl u di n g i n p ati e nt 
c o nti n u o us c ar di ac t el e m etry m o nit ori n g) f or a mi ni m u m of 3 d ays p ost o ns et a n d as l o n g as d e e m e d n ec ess ary by t h e I nv esti g at or  (r ef er t o Pr ot oc ol S ecti o n  1 0. 9. 5) 
C CI
C CI


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
6 8  
 
1 0. C oll ect a si n gl e E C G at b as eli n e.   If Q Tc is > 4 8 0 ms ec, c oll ect 2 m or e E C Gs 5 mi n ut es a p art a n d us e t h e av er a g e of t h os e Q T v al u es t o d et er mi n e eli gi bility. If t h e av er a g e Q Tc is 
> 4 8 0 ms ec, o bt ai n a m a n u al ov err e a d of t h e tri plic at e. Si n gl e E C Gs will b e c oll ect e d at all ot h er ti m e p oi nts t h at r e q uir e E C Gs. E C G c a n als o b e p erf or m e d at ot h er ti m e p oi nts if 
m e dic ally i n dic at e d. P artici p a nts wit h cli nic ally si g nific a nt c ar di ov asc ul ar risk f act ors ( p er Pr ot oc ol S ecti o n  8. 2. 3 ) will u n d er g o ev al u ati o n by a c ar di ol o gist pri or t o ly m p h o d e pl eti o n. 
1 1. Di a g n ostic q u ality C T sc a n of c h est/ a b d o m e n/ p elvis wit h c o ntr ast is r e q uir e d at Bas eli n e ( wit hi n 2 w e eks pri or t o ly m p h o d e pl eti o n),  W e ek 7 ( ± 7 d ays), W e ek 1 3 ( ± 7 d ays), W e ek  1 9 
( ± 7 d ays), W e ek 2 5 ( ± 7 d ays), W e ek 3 4 ( ± 7 d ays), a n d Q 1 2 W ( ± 7 d ays) t h er e aft er, u ntil Eo T.  If a p artici p a nt is f o u n d t o h av e a t u m or r es p o ns e by i m a gi n g, a f oll o w -u p c o nfir m at ory 
sc a n m ust b e d o n e n o e arli er t h a n 4 w e eks a n d n o l at er t h a n t h e n ext sc h e d ul e d i m a gi n g ti m e p oi nt aft er t h e i niti al sc a n s h o wi n g r es p o ns e.  If a p artici p a nt is f o u n d t o h av e pr o gr essiv e 
dis e as e by i m a gi n g, a f oll o w -u p c o nfir m at ory sc a n m ust b e d o n e n o e arli er t h a n 4 w e eks a n d n o l at er th a n 8 w e eks aft er t h e i niti al sc a n s h o wi n g P D.  I nv esti g at or ass ess e d  R E CI S T 
v 1. 1 
 ev al u ati o n m ust b e d o n e f oll o wi n g i nstr ucti o ns i n Ap p e n dix 1 1 .  
1 2 . A ny F D G P E T/ C T p erf or m e d as p art of cli nic al r o uti n e will b e c oll ect e d c e ntr ally b ut will n ot r e pl ac e C T sc a ns. 
1 3. Br ai n M RI ( or C T Sc a n if M RI n ot f e asi bl e) s h o ul d b e p erf or m e d at Bas eli n e ( wit hi n 4 w e eks pri or t o ly m p h o d e pl eti o n) if mor e t h a n 4 m o nt hs  h av e el a ps e d fr o m l ast br ai n M RI. A 
r e p e at br ai n M RI pri or t o ly m p h o d e pl eti o n w o ul d n e e d t o s h o w st a bility or r e d ucti o n of C N S m et ast as es if a ny r a di ot h er a py w as a d mi nist er e d aft er t h e M RI p erf or m e d f or l e uk o p h er esis 
eli gi bility scr e e ni n g. Br ai n M RI s h o ul d b e p erf or m e d as cli nic ally i n dic at e d t h er e aft er (s e e Pr ot oc ol S ecti o n  1 0. 9. 8 ).  
1 4. C o a g ul ati o n t ests i ncl u d e I N R, P T T or a P T T a n d fi bri n o g e n. C o a g ul ati o n t ests s h o ul d b e t ak e n at b as eli n e, D ay 1, 2, 3, 4,  5, 8 a n d 1 5.  
1 5 . If C R S a n d/ or I C A N S  is s us p ect e d, c h e mistry, h e m at ol o gy, f erriti n, c o a g ul ati o n a n d C R P t ests s h o ul d b e p erf or m e d l oc ally ev ery d ay f or t h e first w e ek a n d ev ery  ot h er d ay 
t h er e aft er u ntil sy m pt o ms ar e i m pr ovi n g or a n alt er n ativ e di a g n osis is c o nfir m e d. I n a d diti o n, if C R S is s us p ect e d, cyt oki n e s a m pl es will b e c oll ect e d f or c e ntr al a n alysis f oll o wi n g s a m e 
sc h e d ul e, as d et ail e d i n T a bl e 8 . Tr o p o ni n a n d N T -pr o B N P / B N P t ests s h o ul d b e m o nit or e d f or p artici p a nts wit h C R S Gr a d e ≥2 as cli nic ally i n dic at e d.  
1 6. W O C B P m ust h av e a n e g ativ e uri n e or s er u m pr e g n a ncy t est ( hi g hly s e nsitiv e) at Bas eli n e ( wit hi n 2 4 h o urs pri or t o ly m p h o d e pl eti o n), pri or t o L et e -c el i nf usi o n, a n d t h er e aft er will 
n e e d t o h av e pr e g n a ncy t ests p erf or m e d at all visits i n dic at e d i n t h e t a bl e f or t h e d ur ati o n of t h e c o ntr ac e pti o n p eri o d (s e e  Pr ot oc ol S ecti o n  5. 3. 3. 2  a n d Pr ot oc ol S ecti o n  8. 4. 7 ). 
1 7. O nly p artici p a nts w h o ar e C M V I g G s er o p ositiv e at Bas eli n e will c o nti n u e t o b e m o nit or e d f or C M V vir e mi a by C M V D N A P C R p ost B as eli n e. C M V will als o b e ass es s e d if G B S is 
s us p ect e d. 
1 8. T hyr oi d t ests m ust b e p erf or m e d Q 6 W d uri n g p e m br oliz u m a b a d mi nistr ati o n. Se e f o ot n ot e 2 4 f or first p e m br oliz u m a b a d mi nistr ati o n.  
1 9. S e e  Pr ot oc ol T a bl e 1 1 f or s p ecifics o n r e n al ass ess m e nt.  
2 0. A dv ers e ev e nts s h o ul d b e c oll ect e d a n d r e p ort e d as n ot e d i n Pr ot oc ol Secti o n  8. 4 . 
2 1. P B M Cs f or P ersist e nc e will b e c oll ect e d  at B as eli n e ( D ay -1 7 t o D ay - 9)  a n d at W e ek 1 3, W e ek 2 5, a n d ev ery 6 m o nt hs t h er e aft er ( e. g., 1 2 m o nt hs, 1 8 m o nt hs, 2 4  m o nt hs, et c.) 
u ntil 5  y e ars p ost L et e-c el i nf usi o n, t h e n o nc e a y e ar f or u p t o 1 5 y e ars. Aft er W e ek 2 2, t h e visit wi n d o w f or t his ass ess m e nt will b e ± 3 m o nt hs. S o m e of t h es e s a m pl es m ay b e t ak e n 
aft er t h e p artici p a nt e nt ers t h e L T F U pr ot oc ol ( G S K St u dy 2 0 8 7 5 0) or stu dy Part 5 ( T a bl e 1 2 ). P B M Cs f or Persist e nc e m ay b e c oll ect e d i n a d diti o n al ti m e p oi nts as cli nic ally i n dic at e d. If 
v ect or p ersist e nc e is u n d et ect e d f or t w o c o ns ec utiv e visit ass ess m e nts a n d t h e p artici p a nt is ≥2 y e ars p ost-i nf usi o n, s a m pl es f or p ersist e nc e of g e n e m o difi e d c ells will b e 
disc o nti n u e d.  
2 2. P B M Cs f or R C L will b e c oll ect e d at B as eli n e ( D ay -1 7 t o D ay - 9)  a n d at W e ek 1 3, W e ek 2 5, a n d ev ery 6 m o nt hs t h er e aft er ( e. g., 1 2 m o nt hs, 1 8 m o nt hs, 2 4  m o nt hs, etc.) u ntil 
5 y e ars p ost L et e-c el i nf usi o n, t h e n o nc e a y e ar f or u p t o 1 5 y e ars.  Aft er W e ek 2 2, t h e visit wi n d o w f or t his ass ess m e nt will b e ± 3 m o nt hs. S o m e of t h es e s a m pl es m ay b e t ak e n aft er 
t h e p artici p a nt e nt ers t h e L T F U pr ot oc ol ( G S K St u dy 2 0 8 7 5 0). If v ect or p ersist e nc e is u n d et ect e d f or t w o c o ns ec utiv e visit ass ess m e nts a n d t h e p artici p a nt is ≥2 y e ars p ost-i nf usi o n, 
s a m pl es f or R C L will b e disc o nti n u e d. 
2 3. P artici p a nts will b e h os pit aliz e d o n t h e d ay of T- c ell i nf usi o n ( D ay 1) a n d m ay b e i n t h e h os pit al f or f oll o w-u p c ar e u ntil D ay 3 as cli nic ally i n dic at e d. P artici p a nts will b e i n cl os e 
pr oxi mity t o t h e h os pit al f or at l e ast 7 d ays p ost i nf usi o n. Ad diti o n al h os pit aliz ati o n m ay b e w arr a nt e d b as e d u p o n clinic al n e e d.  
2 4. Ar ms B a n d C o nly. First p e m br oliz u m a b a d mi nistr ati o n o n D ay 2 2 ( W e ek 4 D ay 1), t h e n Q 3 W f or u p t o 3 5 cycl es.  If t oxiciti es t h at pr ecl u d e p e m br oliz u m a b tr e at m e nt, s uc h as C R S 
Gr a d e ≥2, ar e pr es e nt at D ay  2 2, t h e first i nf usi o n of p e m br oliz u m a b will b e o n W e ek 7 D ay 1, i n w hic h c as e, Cycl e 3 5 will occ ur o n W e ek 1 0 9 D ay 1. If A Es d o n ot r es olv e by W e ek 7 
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C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
6 9  
 
D ay 1 t o ≤ Gr a d e 1, p e m br oliz u m a b will n ot b e a d mi nist er e d, a n d t h e p artici p a nt will b e ev al u at e d u ntil dis e as e pr o gr essi o n o r E o T. P e m br oliz u m a b m ay b e a d mi nist er e d u p t o 3 d ays 
b ef or e or aft er t h e sc h e d ul e d D ay 1 of e ac h cycl e d u e t o a d mi nistr ativ e r e as o ns.  
2 5. F or bi o m ark er a n alysis, if g e n etic s a m pl e c oll ecti o n is n ot d o n e at Bas eli n e, it m ay b e d o n e at a ny ot h er s u bs e q u e nt visi t i n t h e I nt erv e nti o n al P h as e. C oll ecti o n of a g e n etic s a m pl e 
is o pti o n al a n d all p artici p a nts m ust pr ovi d e c o ns e nt f or s a m pl e c oll ecti o n a n d a n alysis pri or t o s a m pli n g.  
 
 
C CI


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
7 0  
 
T a bl e 8 
S c h e d ul e of A cti viti e s - P h ar m a c o ki n eti c s, I m m u n o g e ni cit y, a n d Bi o m ar k er s (I nt er v e nti o n a l P h a s e) ( P art 3 c o nt.) 
 
Vi sit  
A s s e s s m e nt  
S a m pl e T y p e  D a y -1 7 t o -9 ( B a s eli n e)  
D 1 ( L et e -c el 
i nf u si o n) 
D 2  
D 3  D 4  D 5  W 2  W 3  W 4  W 7  
W 1 0 t o 
2 5 Q 3 W  
Ar m A: W 3 4 -
W 1 0 6 Q 1 2 W  
Ar m s B & C: 
W 2 8 -W 1 0 6 
Q 3 W  
Vi sit Wi n d o w 1 
 
 
 
± 1 d a y  
± 3 d a y s  
± 3 d a y s  
V ect or C o pi es ( p h ar m ac oki n etics)9 
P B M C  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 2  
C ell P h e n oty p e a n d F u ncti o n al 
Ass ays 9 
P B M C  
X 
 
 
 
X 
 
X 
 
X 
X 
X 
X 2 
Cyt oki n e A n alys es 3,9 
S er u m  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 2  
P e m br oliz u m a b p h ar m ac oki n etics 6 
S er u m  
 
 
 
 
 
 
 
 
X 6  
X 6  
X 6  
X 6  
Li q ui d bi o psy ( bl o o d) 7 
Pl as m a  
X  
 
 
 
 
 
 
 
X 7 
 
X 7  
X 7  
T u m or Bi o psy 8 
Bi o psy  
X  
 
 
 
 
 
 
 
X  
 
 
 
A b br evi ati o ns: cf D N A = c ell -fr e e D N A; C R S = cyt oki n e r el e as e sy n dr o m e; C T = c o m p ut e d t o m o gr a p hy; ct D N A = circ ul ati n g t u m or D N A; D = D ay; M RI = m a g n etic r es o n a nc e i m a gi n g ; 
P B M C = p eri p h er al bl o o d m o n o n ucl e ar c ells; P K = p h ar m ac oki n etics; Q 3 W = o nc e ev ery 3 w e eks; Q 1 2 W = o nc e ev ery 1 2 w e eks; 
; W = W e ek.  
1. W e ek N visit f or N > 1 is sc h e d ul e d o n 1st d ay of t h e w e ek; D ay = 7 N - 6 
2. S a m pl e c oll ecti o n t o m atc h i m a gi n g ( B o dy C T/ M RI) visits as i n dic at e d i n T a bl e 7  
3. If C R S is s us p ect e d, cyt oki n e l ev els s h o ul d b e m e as ur e d ev ery d ay f or t h e first w e ek a n d a p pr oxi m at ely ev ery ot h er d ay t h er e aft er u ntil sy m pt o ms ar e i m pr ovi n g or a n alt er n ativ e 
di a g n osis is c o nfir m e d.  C h e mistry, h e m at ol o gy, f erriti n, c o a g ul ati o n a n d C R P t ests s h o ul d als o b e p erf or m e d l oc ally f oll o wi n g s a m e sc h e d ul e, as d et ail e d i n  T a bl e 7 . Tr o p o ni n a n d  
N T -pr o B N P / B N P t ests s h o ul d b e m o nit or e d f or p artici p a nts wit h C R S Gr a d e ≥2 as cli nic ally i n dic at e d.  
6.  Ar ms B & C o nly. C oll ect bl o o d f or p h ar m ac oki n etics a n alysis at visits W e ek 4 D ay 1 ( b ef or e a n d aft er t h e first p e m br oliz u m a b i nf usi o n), W 7, W 1 0, W 1 3, W 2 2, W 3 4, W 4 6, W 5 8, 
W 8 2, a n d W 1 0 6.  First p e m br oliz u m a b a d mi nistr ati o n s h o ul d b e o n D ay 2 2 ( W e ek 4 D ay 1).  If t oxiciti es t h at pr ecl u d e p e m br oliz u m a b tr e at m e nt, s uc h as C R S Gr a d e ≥2, ar e pr es e nt 
at D ay  2 2, i nf usi o n of p e m br oliz u m a b will st art o n W e ek 7 D ay 1.  F or p artici p a nts w h o st art p e m br oliz u m a b o n W e ek 7 D ay 1, c oll ect bl o o d f or p h ar m ac oki n etics a n alysis at visit 
W e ek 7 D ay 1 ( b ef or e a n d aft er t h e first p e m br oliz u m a b i nf usi o n), W 1 0, W 1 3, W 1 6, W 2 5, W 3 7, W 4 9, W 6 1, W 8 5, a n d W 1 0 9. C oll ect bl o o d b ef or e ( wit hi n 2 4 hrs) a n d aft er ( wit hi n 3 0 
mi ns) t h e first p e m br oliz u m a b i nf usi o n a n d b ef or e ( wit hi n 2 4 hrs) t h e p e m br oliz u m a b i nf usi o n at all ot h er visits t h at i ncl u d e p h ar m ac oki n etics s a m pl e c oll ecti o n.   
C CI
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7. Blood sample from which cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and exosomes may be extracted and should match tumor biopsy visits and imaging (Body CT/MRI) 
visits (Table 7), except for Week 7 where no liquid biopsy sample is needed.  An additional biopsy may be taken at disease progression unless clinically unsafe to do so. 
8. Biopsies for research are taken at Baseline) and Week 4 (with flexibility until Week 6), with the exception of participants for whom there is no safely accessible tumor tissue. In 
addition to the indicated collection times, tumor biopsies can be obtained at any time during the study if clinically indicated.  The baseline biopsy should be collected anytime within 
28 days prior to the start of lymphodepleting chemotherapy, with preference for closer to the time of Lete-cel infusion. An archived FFPE block from a biopsy taken preferably after 
completion of the participant’s last line of therapy and within 90 days prior to initiating lymphodepleting chemotherapy, may be accepted at the discretion of the Medical Monitor (or 
designee).An additional biopsy will be taken at disease progression unless clinically unsafe to do so. 
9. For participants who receive pembrolizumab (Arms B and C), collect samples for these assessments before pembrolizumab infusion. 
 
 


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
7 2  
 
T a bl e 9 
S c h e d ul e of A cti viti e s - P e m br oli z u m a b T h er a p y F oll o wi n g Di s e a s e Pr o gr e s si o n aft er L et e -c el I nf u si o n ( P art 4 - 
Ar m A o nl y)  
P e m br oliz u m a b ( P) W e e k ( W) 
P B L  
P W 1  P W 2  
P W 4  
P W 7  
P W 1 0 
t o 
P W 1 0 3 
( Q3 W) 
N ot e s  
1. W e ek N visit f or N > 1 is sc h e d ul e d o n 1st d ay of t h e w e ek; Day = 7 N -6.  
2. B as eli n e ass ess m e nts r e q uir e d o nly if t h e ass ess m e nts h av e n ot b e e n p erf or m e d wit hi n 2 8 d ays 
pri or t o first p e m br oliz u m a b a d mi nistr ati o n.  
3. S e e Pr ot oc ol S ecti o n  5. 1. 4. 
4. N e ur ol o gic al ass ess m e nt f or p artici p a nts wit h br ai n m et ast as es a n d t h os e wit h n e ur ol o gic al 
a dv ers e ev e nts u p t o 1 2 w e eks p ost r es ol uti o n of t h e ev e nt.  
5. Si n gl e E C G o n t h e d ays of p e m br oliz u m a b a d mi nistr ati o n, pri or t o i nf usio n.  
6. P e m br oliz u m a b B as eli n e C T/ M RI pri or t o p e m br oliz u m a b t h er a py m ust b e o bt ai n e d wit hi n 4 we eks 
pri or t o first p e m br oliz u m a b a d mi nistr ati o n. If t h e C T/ M RI h as b e e n o bt ai n e d at P D wit hi n 4 we eks 
pri or t o p e m br oliz u m a b t h er a py i niti ati o n, t his c a n b e c o nsi d er e d as b as eli n e m e as ur e m e nt. 
Di a g n ostic q u ality C T sc a n of c h est/ a b d o m e n/ p elvis wit h c o ntr ast is r e q uire d ev ery 6 we eks ( ± 7 d ays) 
u ntil P W 2 5, at P W 3 4, a n d t h e n ev ery 1 2 we eks ( ± 7 d ays) t h er e aft er, u ntil E o T f or p e m br oliz u m a b. If 
a p artici p a nt is f o u n d t o h av e a t u m or r es p o ns e by i m a gi n g, a f oll o w -u p c o nfir m at ory sc a n m ust b e 
d o n e n o e arli er t h a n 4 w e eks a n d n o l at er t h a n t h e n ext sc h e d ul e d i m a gi n g ti m e p oi nt aft er t h e i niti al 
sc a n s h o wi n g r es p o ns e.  If a p artici p a nt is f o u n d t o h av e pr o gr essiv e dis e as e by i m a gi n g, a f oll o w - up 
c o nfir m at ory sc a n m ust b e d o n e n o e arli er t h a n 4 we eks a n d n o l at er t h a n 8 we eks aft er t h e i niti al 
sc a n s h o wi n g P D.  I nv esti g at or ass ess e d R E CI S T v 1. 1/
 m ust b e d o n e f oll o wi n g 
i nstr ucti o ns i n A p p e n dix 1 1 . A ny F D G P E T/ C T p erf or m e d as p er cli nic al ro uti n e will b e c oll ect e d 
c e ntr ally b ut will n ot r e pl ac e C T sc a ns. 
7. W O C B P will n e e d t o h av e pr e g n a ncy t ests ( hi g hly s e nsitiv e) p erf or m e d at all visits i n dic at e d i n t h e 
t a bl e f or t h e d ur ati o n of t h e c o ntr ac e pti o n p eri o d (s e e Pr ot oc ol S ecti o n 5. 3. 3. 2  a n d Pr ot oc ol S ecti o n  
8. 4. 7 ). 
8. O nly p artici p a nts w h o ar e C M V I g G s er o p ositiv e at P B L will c o nti n u e t o b e m o nit or e d f or C M V 
vir e mi a by C M V D N A P C R p ost PB L.  
9. T hyr oi d t ests m ust b e p erf or m e d Q 6 W d uri n g p e m br oliz u m a b a d mi nistr ati o n.   
1 0. If C R S a n d/ or I C A N S  is s us p ect e d, c h e mistry, h e m at ol o gy, f erriti n, c o a g ul ati o n a n d C R P t ests 
s h o ul d b e p erf or m e d l oc ally ev ery d ay f or t h e first we ek a n d ev ery ot h er d ay t h er e aft er u ntil 
sy m pt o ms ar e i m pr ovi n g or a n alt er n ativ e di a g n osis is c o nfir m e d. I n a d diti o n, if C R S is s us p ect e d, 
cyt oki n e s a m pl es will b e c oll ect e d f or c e ntr al a n alysis f oll o wi n g s a m e sc h e d ul e, as d et ail e d i n T a bl e 
1 0 . Tr o p o ni n a n d N T -pr o B N P / B N P t ests s h o ul d b e m o nit or e d f or p artici p a nts wit h C R S 
Gr a d e ≥2 as cli nic ally i n dic at e d.  
1 1. P B M Cs f or P ersist e nc e  a n d R C L t esti n g will b e c oll ect e d at P W 1 3, P W 2 5, a n d ev ery 6 m o nt hs 
u ntil E o T f or p e m br oliz u m a b or dis e as e pr o gr essi o n, whic h ev er c o m es first.  Dat a c oll ect e d at 
B as eli n e ( D ay -1 4 t o D ay - 9)  pri or t o l et e -c el will b e us e d as b as eli n e. 
1 2. If v ect or p ersist e nc e is u n d et ect e d f or t wo c o ns ec utiv e visit ass ess m e nts a n d t h e p artici p a nt is ≥2 
y e ars p ost-i nf usi o n, s a m pl es f or R C L a n d p ersist e nc e of g e n e m o difi e d c ells will b e disc o nti n u e d.  
Vi sit Wi n d o w 1 
-2 8  
d a y s 2 
±1 
d a y  
±3  
d a y s  
±3  
d a y s  
P e m br olizu m a b Eligibility 3 
X  
 
 
 
 
 
P hysical Exa m  
X  
X  
X  
X  
X  
X  
N e ur olo gical Exa m 4 a n d I C E  
X  
S e e n ot e 4  
Prior/ C o nco mit a nt M e dicati o ns  
X  
X  
X  
X  
X  
X  
E C O G  
X  
X  
X  
X  
X  
X  
Vit al Sig ns  
X  
X  
X  
X  
X  
X  
E C G 5 
X  
X  
 
X  
 
 
C T/ M RI 6 
X  
 
 
 
X 6  
X  
R E CI S T Evalu atio n 6 
X  
 
 
 
X  
X  
H e m at olo gy 9 
X  
X  
X  
X  
X  
X  
C h e mistry 9 
X  
X  
X  
X  
X  
X  
Pr e g n a ncy T est 7 
X  
S e e n ot e 7  
C M V I g G a n d P C R 8 
S e e n ot e 8  
T S H wit h Fr e e T 4 9 
S e e n ot e 9  
C R P 1 0 
 
X  
X  
X  
X  
X  
F erritin 1 0 
S e e n ot e 1 0  
C o a g ulatio n T ests 1 0 
S e e n ot e 1 0  
Tr o p o nin a n d N T -pr o B N P/ B N P 1 0 
S e e n ot e 1 0  
A dverse Eve nts  
 
X  
X  
X  
X  
X  
V ect or C o pies ( P ersist e nce f or 
S af ety)  [ blo o d] 
S e e n ot es 1 1 a n d 1 2 
V S V -G D N A ( R C L)  [ blo o d] 
S e e n ot es 1 1 a n d 1 2  
P e m br oliz u m a b 
a d mi ni str ati o n 
 
X 
 
X 
X 
X 
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However, if VSV-G DNA copies are detected at any time point during year 1, refer to the safety 
monitoring procedures in Protocol Section 8.3.5. 
See Table 10 for PK, Immunogenicity, and Biomarker Samples 
 
EoT = end of treatment; FDG PET = fluorodeoxyglucose positron emission tomography; IgG = immunoglobulin G; MRI = magnetic resonance imaging; PBL = Pembrolizumab Baseline; 
PCR = polymerase chain reaction; PD = progressive disease; PK = pharmacokinetics; PW = Pembrolizumab Week; Q3W = once every 3 weeks; RCL = replication competent 
lentivirus; RECIST = Response Evaluation Criteria In Solid Tumors; VSV-G = vascular stomatitis virus G.  
Note: Pembrolizumab therapy is only allowed in case of disease progression within the first 25 weeks after lete-cel infusion.  Pembrolizumab therapy will not be allowed if disease 
progression occurs after the Week 25 scan.  Pembrolizumab treatment will be administered for up to 35 cycles Q3W at 200 mg or until subsequent disease progression. 
 
 


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
7 4  
 
T a bl e 1 0  
S c h e d ul e of A cti viti e s ( P K, I m m u n o g e ni cit y, a n d Bi o m ar k er s) – P e m br oli z u m a b T h er a p y F oll o wi n g Di s e a s e 
Pr o gr e s si o n aft er L et e -c el I nf u si o n ( P art 4 -Ar m A o nl y)  
Pe m br oliz u m a b ( P) W e e k ( W)  
Sa m pl e 
T y p e  
P W 1  
P W 2  
P W 4  
P W 7 D 1  
P W 1 0 t o 
P W 1 0 3 Q 3 W  
Vi sit Wi n d o w 1  
± 1 d a y  
± 3 d a y s  
V ect or C o pi es ( p h ar m ac oki n etics) 2  
P B M C  
X  
X  
X  
X  
X 4 
C ell P h e n oty p e a n d F u ncti o n al Ass ays 2 
P B M C  
X  
X  
X  
X  
X 5  
Cyt oki n e A n alys es 2,3 
Ser u m  
X  
X 
X 
X 
X 5 
P e m br oliz u m a b p h ar m ac oki n etics 6 
Ser u m  
X  
  
X  
X  
X  
Li q ui d bi o psy ( bl o o d) 7 
Pl as m a  
X  
  
  
X  
X 7 
T u m or Bi o psy 8 
Bi o psy  
X 9 
  
  
X  
 
A b br evi ati o ns: cf D N A = c ell -fr e e D N A; C T = c o m p ut e d t o m o gr a p hy; ct D N A = circ ul ati n g t u m or D N A; D = D ay; M RI = m a g n etic r es o n a nc e i m a gi n g; P B M C = p eri p h er al bl o o d 
m o n o n ucl e ar c ells; P K  = p h ar m ac oki n etics; Q 3 W = o nc e ev ery 3 w e eks; P W = Pe m br oliz u m a b W e ek.  
1. W e ek N visit f or N > 1 is sc h e d ul e d o n 1st d ay of t h e w e ek; D ay = 7 N - 6 
2. C oll ect s a m pl es f or t h es e ass ess m e nts b ef or e p e m br oliz u m a b i nf usi o n.  
3. If C R S is s us p ect e d, cyt oki n e l ev els s h o ul d b e m e as ur e d ev ery d ay f or t h e first w e ek a n d a p pr oxi m at ely ev ery ot h er d ay t h er e aft er u ntil sy m pt o ms ar e i m pr ovi n g or a n alt er n ativ e 
di a g n osis is c o nfir m e d.  C h e mistry, h e m at ol o gy, f erriti n, c o a g ul ati o n a n d C R P t ests s h o ul d als o b e p erf or m e d l oc ally f oll o wi n g s a m e sc h e d ul e, as d et ail e d i n T a bl e 9 . Tr o p o ni n a n d 
N T -pr o B N P / B N P t ests s h o ul d b e m o nit or e d f or p artici p a nts wit h C R S Gr a d e ≥2 as cli nic ally i n dic at e d.  
  
5. S a m pl e c oll ecti o n t o m atc h i m a gi n g ( B o dy C T/ M RI) visits as i n dic at e d i n T a bl e 9 . 
7 . Bl o o d s a m pl e fr o m w hic h c ell -fr e e D N A (cf D N A), circ ul ati n g t u m or D N A (ct D N A), a n d ex os o m es m ay b e extr act e d s h o ul d m atc h t u m or bi o psy visits a n d i m a gi n g ( B o dy C T/ M RI) 
visits. S e e T a bl e 9  f or t u m or bi o psy b ef or e first p e m br oliz u m a b a d mi nistr ati o n. 
8. I n a d diti o n t o t h e i n dic at e d c oll ecti o n ti m es, t u m or bi o psi es c a n b e o bt ai n e d at a ny ti m e d uri n g t h e st u dy ex ec uti o n if cli nic ally a p pr o pri at e.  
9. T u m or bi o psy t o b e c oll ect e d wit hi n 1 4 d ays b ef or e first p e m br oliz u m a b a d mi nistr ati o n.  
C CI
C CI
C CI


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
7 5  
 
T a bl e 1 1  
S c h e d ul e of A cti viti e s – E n d of Tr e at m e nt / E n d of I nt er v e nti o n al P h a s e 
D a y ( D) /  
W e e k ( W)  
C o m pl eti o n/ 
Wit h dr a w al 1 
N ot e s  
Cli ni c al A s s e s s m e nt s a n d Pr o ce d ur e s 2 
1.  Partici p a nts will c o m pl et e t h e Eo T visit aft er c o m pl eti n g i nt erv e nti o n al p orti o n of t h e st u dy 
( Parts 3 or 4; s e e Pr ot oc ol Secti o n  4. 4. 1 ), disc o nti n u ati o n of p e m br oliz u m a b (if r el ev a nt) or 
e arly wit h dr a w al fr o m t h e i nt erv e nti o n al p h as e. E o T visit is t o b e c o m pl et e d o nly o nc e f or e ac h 
p artici p a nt. All pr oc e d ur es a n d ass ess m e nts, as i n dic at e d, s h o ul d b e p erf or m e d pr ef er a bly 4 
w e eks a n d n o l at er t h a n 6 0  d ays fr o m l ast p e m br oliz u m a b tr e at m e nt or visit, as r el ev a nt. If 
p erf or m e d s o o n er, o nly c o m pl et e ass ess m e nts n ot alr e a dy p erf or m e d as p art of l ast 
p e m br oliz u m a b tr e at m e nt or visit. Eo T visit m ust b e c o m pl et e d pri or t o i niti ati n g n o n -pr ot oc ol 
a nti -c a nc er t h er a py, if r el ev a nt ( S e e Pr ot oc ol S ecti o n 6. 9. 1 ). 
2.  Se e Pr ot oc o l Secti o n 8 f or d et ails. 
3.  I ncl u d es all pr escri pti o ns,  ov er-t h e-c o u nt er m e dic ati o ns, a n d h er b al r e m e di es.  A ny us e of 
m ut a g e nic a g e nts or i nv esti g ati o n al a g e nts m ust als o b e r e p ort e d.  
4.  I ncl u d es t e m p er at ur e, bl o o d pr ess ur e, p uls e r at e, r es pir at ory r at e, a n d oxy g e n s at ur ati o n.   
5.  If cli nic ally n e e d e d.  
6.  If a p artici p a nt is f o u n d t o h av e a t u m or r es p o ns e or pr o gr essiv e dis e as e by i m a gi n g vi a 
R E CI S T v 1. 1, a f oll o w -u p c o nfir m ati o n sc a n m ust b e d o n e n o e arli er t h a n 4 w e eks a n d n o l at er 
t h a n 8 w e eks f oll o wi n g t h e sc a n w h e n r es p o ns e or dis e as e pr o gr essi o n w as first s e e n.  A 
p artici p a nt is n ot c o nsi d er e d t o h av e a r es p o ns e or pr o gr essi o n u ntil a f oll o w -u p sc a n c o nfir ms 
t h e fi n di n g.  Any F D G P E T/ C T p erf or m e d as p er cli nic al r o uti n e will b e c oll ect e d c e ntr ally b ut 
will n ot r e pl ac e C T sc a ns.  
7.  If a C T / M RI ass ess m e nt h as b e e n c o m pl et e d wit hi n t h e l ast 4 w e eks, a d diti o n al C T / M RI 
ass ess m e nts ar e n ot r e q uir e d as p art of E o T visit, u nl ess it is c o nfir m at ory sc a n ( wit hi n t h e 
sc h e d ul e i n N ot e # 6, a b ov e).  
8.  If dis e as e pr o gr essi o n h as b e e n c o nfir m e d pri or t o E o T visit, a d diti o n al C T / M RI 
ass ess m e nts ar e n ot r e q uir e d as p art of E o T visit.  
9.  Adv ers e ev e nts s h o ul d b e r e p ort e d as n ot e d i n Pr ot oc ol S ecti o n  8. 4 . 
Pri or/ C o nc o mit a nt M e dic ati o ns 3 
X  
P hysic al Ex a m  
X  
E C O G  
X  
Vit al Si g ns / H ei g ht / W ei g ht 4  
X  
E C G  
X 5 
C T / M RI 6,7,8 
X  
H e m at ol o gy  
X  
C h e mistry  
X  
A dv ers e Ev e nts 9 
X  
C orr el ati v e St u di e s a n d R e s e arc h A s s e s s m e nt s  
1 1.  Bi o psi es f or r es e arc h ar e t ak e n at B as eli n e, W e ek 7, a n d at c o nfir m ati o n of P D, wit h t h e 
exc e pti o n of p artici p a nts f or w h o m t h er e is n o s af ely acc essi bl e t u m or tiss u e.   
1 2.  Li q ui d Bi o psy s a m pl es s h o ul d m atc h t u m or bi o psy a n d/ or C T/ M RI ass ess m e nt ti m e p oi nts.  
Se e f o ot n ot e 6 f or C T/ M RI ass ess m e nt.  
T u m or bi o psy 1 1 
X  
Li q ui d Bi o psy ( bl o o d) 1 2   
X  
Bl o o d f or C ell P h e n oty p e a n d F u ncti o n al Ass ays  
X  
Cyt oki n e A n alys es  
X  
C CI


 
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Abbreviations: cfDNA = cell-free DNA; CT = computed tomography; CTCAE = Common Technical Criteria for Adverse Events; D = Day; DNA = deoxyribonucleic acid; 
ECG = electrocardiogram; ECOG = Eastern Co-operative Oncology Group; EoT = end of treatment; FDG PET = fluorodeoxyglucose positron emission tomography; MRI = magnetic 
resonance imaging; PD = Progressive Disease;  W = Week. 
 
Table 12 
Schedule of Activities – Long Term Follow-up after Disease Progression or Completion of Interventional Phase 
(Part 5 or Study 208750) 
Allo-SCT = allogeneic stem cell transplant; CBC = complete blood cell (count); RCL = replication competent lentivirus; VSV-G = vesicular stomatitis virus G 
 
1. If a site visit is not feasible, then medical evaluation of participants may take place via telemedicine (e.g., phone call or video conferences) where country and/or local regulations 
allow. Where applicable country and local regulations; and infrastructure for home healthcare allow, upon approval by the sponsor home healthcare may take place at a location 
other than the clinical trial site to perform study assessments, which may include medical history, physical exam, collection of blood samples, measurement of height and weight. 
Remote visits may be performed upon approval by the sponsor at the participant’s home by qualified study personnel or at a local medical facility, unless the Investigator deems 
that a site visit is necessary. 
2. Collect new medical history/medications and chemotherapies and/or radiotherapy.   
Time post-infusion1 
 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Year 6-159 
 
Months 
3 
6 
12 
18 
24 
30 
36 
42 
48 
54 
60 
Annually 
Unscheduled 
Visit7 
Visit Window 
±2 weeks 
±3 months 
±6 months 
 
Medical History2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Subsequent anti-cancer therapies 
or allogeneic stem cell transplant 
(allo-SCT)2,3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Delayed Adverse Events4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X5 
 
CBC with differential and Serum 
Chemistry6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
VSV-G DNA (RCL) and vector 
copies (Persistence) for safety 
(blood)6,7  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Survival Status8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


 
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3. All participants who received pembrolizumab will be followed for 24 months after their last dose to ascertain if they are candidates to receive an allogeneic- stem cell transplant 
(allo-SCT). Participants who receive an allo-SCT within the 24-month follow-up period will be monitored for 18 months for post allo-SCT complications as described in Protocol 
Section 8.4.5. 
4. Delayed adverse event collection is limited to: 
• New malignancies 
• New incidence or exacerbation of pre-existing neurologic disorder 
• New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder 
• New incidence of a hematologic disorder 
• New incidence of infection (potentially related to gene modified cell therapy)  
• Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy 
• Specific events outlined in Protocol Section 8.3 for participants who received pembrolizumab and had allo-SCT  
5. During years 6-15 of annual follow-up period, AEs and SAEs will be entered in the CRF if reported by the patient or investigator.     
6. If a visit for medical evaluation is conducted via telemedicine, a site visit to collect a blood samples should be performed as soon as practicable.  
7. If vector persistence is undetected for two consecutive visit assessments and the participant is ≥2 years post-infusion, samples for RCL and persistence of gene modified cells will 
be discontinued. 
8. If a participant is contacted between the scheduled visits, the date of last contact should be recorded as an unscheduled visit.    
9. Subjects who do not have persistence of gene modified cells may be followed remotely during years 6-15. 
 


 
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13.3. 
Appendix 3: Assessment Windows 
No assessment windows will be applied. 


 
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13.4. 
Appendix 4: Study Phases and Treatment Emergent  
13.4.1. 
Study Phases 
Disposition data will be summarized by the treatment phases defined below. The table 
should also be used to identify any assessments that are part of the Pembrolizumab 
Following Disease Progression Phase, so these data can be removed from the main tables 
as specified in the sections above. Data falling into the Pembrolizumab Following 
Disease Progression after lete-cel Infusion Phase will be flagged in all listings.  
Study Phase 
Definition 
Pre-lymphodepletion Phase 
From the date of treatment informed consent signed (Screening) 
to the date prior to initiating lymphodepletion 
[First leukapheresis ≤ Date < First day of lymphodepletion] 
Interventional Phase – 
Lymphodepletion 
First day of Lymphodepletion ≤ Date < T-cell Infusion 
Interventional Phase – Post T-cell 
Infusion  
 
T-cell infusion ≤ Date ≤ Start of Follow-up Phase (Date of 
confirmed PD / Withdrawal from Interventional Phase) 
Follow-up Phase 
Start of follow-up phase (Date of confirmed PD / Withdrawal from 
Interventional Phase) < Date 
Pembrolizumab Following 
Disease Progression Phase (Arm 
A only) 
 
From the date of initiating pembrolizumab treatment (first dose of 
pembrolizumab) to end of study for participants that received 
pembrolizumab treatment following disease progression in 
treatment Arm A only 
 
13.4.1.1. 
Study Phases for Concomitant Medication and Blood Products 
Study Phase 
Definition 
Prior 
End Date of medication or blood product is not missing and End Date < 
Lymphodepletion Start Date or lymphodepletion start date is missing 
Concomitant 
Any medication or blood product that is not Prior 
NOTES:  
• 
Please refer to Appendix 7: Reporting Standards for Missing Data for handling of missing and partial dates for 
concomitant medication and blood products. Use the rules in this table if concomitant medication or blood product 
date is completely missing. 
 
13.4.1.2. 
Phases of COVID-19 Pandemic Measures 
Pandemic measures began in different countries at different times. A dataset containing 
the date when pandemic measures began, as determined by the GSK country Issue 
Management Teams (IMT), and available within the HARP reporting environment 
(arcomn folder), will be used to determine the start date of pandemic mesures within each 
country. A copy of this dataset will be taken at the time of database lock (DBL). 
Adverse events will be summarised according to whether the onset date was before or 
after the start of the COVID-19 pandemic measures. 


 
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Pandemic 
Measures Phase 
Definition 
Before 
AE onset date < pandemic measures start date 
After 
Pandemic measures start date ≤ AE onset date  
 


 
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13.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
 Treatment Emergent 
(T-cell Phase) 
• 
If the participant is in Arm C or if the participant is in Arm 
A but has not received Pembrolizumab post disease 
progression: 
o  If AE onset date is on or after T-cell infusion start 
date (T-cell Infusion Start Date ≤ AE Start Date) 
OR if AE onset date is before T-cell infusion start 
date, but the AE increases in grade after T-cell 
infusion (with respect to the maximum grade of the 
AE before T-cell infusion) 
• 
If the participant is in Arm A and has received 
Pembrolizumab post disease progression: 
o If AE onset date is on or after T-cell infusion start 
date (T-cell Infusion Start Date ≤ AE Start Date < 
Pembrolizumab Start Date) OR if AE onset date is 
before T-cell infusion start date, but the AE 
increases in grade after T-cell infusion and before 
Pembrolizumab start date (with respect to the 
maximum grade of the AE before T-cell infusion) 
• 
If AE onset date is missing and AE end date is before the T-
cell 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 T-cell start date, 
then the AE will be classified as treatment-emergent.  
o If T-cell infusion date is missing, AE will not 
classified as Treatment Emergent  
Lymphodepletion 
Emergent 
(Lymphodepletion 
Phase) 
• 
If AE onset date is on or after Lymphodepletion start date 
and before T-cell infusion start date ( [Lymphodepletion 
Start Date ≤ AE Start Date < T-cell Infusion Start Date] or 
[Lymphodepletion Start Date ≤ AE Start Date and T-cell 
Infusion Start Date is missing] ) OR if AE onset date is 
before lymphodepletion start date, but the AE increases in 
grade in the lymphodepletion phase (with respect to the 
maximum grade of the AE before lymphodepletion) 
• 
If AE onset date is missing and AE end date is before the 
lymphodepletion start date, then the AE will not be 
classified as Lymphodepletion-Emergent. If AE onset date 
is missing and AE end date is either missing or after 
lymphodepletion start date, then the AE will be classified as 
lymphodepletion-emergent 
o If lymphodepletion date is missing, AE cannot be 
classified as Lymphodepletion-Emergent  
Pre-Lymphodepletion 
Emergent (Pre-
Lymphodepletion 
Phase) 
• 
If AE onset date is before the Lymphodepletion start date 
(AE Start Date ≤ Lymphodepletion Start Date or 
Lymphodepletion Start Date is missing). 
• 
If AE onset date is missing the AE will be classified as Pre-
Lymphodepletion -Emergent.  
 


 
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Pembrolizumab 
Therapy Following 
Disease Progression 
Emergent 
(Pembrolizumab 
Following Disease 
Progression Phase) 
• 
If AE onset date is on or after the first dose of 
pembrolizumab therapy following disease progression after 
lete-cel infusion (AE start date ≥ pembrolizumab start date) 
OR if AE onset date is before the first dose of 
pembrolizumab, but the AE increases in grade after the first 
dose of pembrolizumab (with respect to the maximum grade 
of the AE before start of pembrolizumab) in Arm A 
NOTES:  
• 
Time of study treatment dosing and start[/stop] time of AEs should be considered, if collected. 
 


 
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13.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
13.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: arprod\GSK3377794\mid208471 
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. 
13.5.2. 
Reporting Standards 
General 
• 
The current GSK Statistical Display Standards in the GSK Standards Library (IDSL) will be applied 
for reporting, unless otherwise stated (Library 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 Statistical Display 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 GSK Standard Statistical Display 
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: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• 
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:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to GSK 
Standard Statistical Display Principle 5.05.1). 
• 
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 
worst-case and/or best-case post-baseline or last assessment is calculated. 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to GSK Standard Statistical Display Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to GSK Standard Statistical Display Principals 7.01 to 7.13. 
13.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
PC Windows Non-
Linear (WNL) File 
PC WNL file (CSV format) for the non-compartmental analysis by 
Clinical Pharmacology Modelling and Simulation function will be 
created according to SOP 00000314000: Non-Compartmental Analysis 
of Clinical Pharmacokinetic Data  
Note: Concentration values will be imputed as per GUI_51487 
Descriptive 
Summary Statistics, 
Graphical Displays 
and Listings 
Refer to IDSL PK Display Standards. 
Graphical displays: Refer to Combined Statistical Displays Principles 
section 7. 
Listings: Refer to Combined Statistical Displays Principles section 5. 
Note: Concentration values will be imputed as per GUI_51487 for 
descriptive summary statistics/analysis and summarized graphical 
displays only.  
NONMEM/Pop PK 
File 
Not applicable. 
 
NONMEM/PK/PD 
File 
Not applicable. 
Pharmacokinetic Parameter Derivation 
PK Parameter to be 
Derived by 
Programmer 
None 
Pharmacokinetic Parameter Data 
Is NQ impacted PK 
Parameters Rule 
Being Followed 
Yes, refer to Standards for Handling NQ Impacted PK Parameters  
Descriptive 
Summary Statistics, 
Graphical Displays 
and Listings 
Refer to IDSL PK Display Standards. 
 
 


 
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13.6. 
Appendix 6: Derived and Transformed Data 
13.6.1. 
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 
analysed.  
• 
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 Lete-cel Infusion Date: 
• 
Ref Date = Missing → Study Day = Missing  
• 
Ref Date < Lete-cel Infusion Date → Study Day = Ref Date – Lete-cel Infusion Date 
• 
Ref Data ≥ Lete-cel Infusion Date → Study Day = Ref Date – (Lete-cel 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 or CR) is assigned to the latest 
date of disease assessments; for other response categories (SD [or Non-CR/Non-PD], NE, PD), the 
date of response is assigned to the earliest date of disease assessments based on scan date.    
Date of New Anti-Cancer Therapy 
• 
Derived as the earliest date of new on-study anti-cancer therapy, non-palliative 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 13.7.2.1. 
 


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
8 6  
 
1 3. 6. 2.  
St u d y P o p ul ati o n  
A g e  
•  F or p artici p a nts wit h a L et e -c el I nf usi o n D at e, a g e is d eriv e d usi n g L et e-cel I nfusi on D at e as t h e 
r ef er e nc e d at e. For I T T p articip a nts with o ut a L et e-cel I nfusio n D at e, d ate of eli gibility f or 
l e uk a ph er esis is us e d as t h e ref er e nc e d at e. 
B MI  
•  
( W ei g ht in k g) / ( H ei g ht i n meters)2 
B o d y S urf a c e Ar e a ( B S A) ( m 2) D u B oi s & D u B oi s F or m ul a 
•  
0. 0 0 7 1 8 4 x H ei ght(c m) 0. 7 25 x W ei g ht(kg) 0. 4 25 
Ti m e Si n c e I nitial Di a g n o sis  
•  
Calc ul ate d as t h e nu m b er of M o nt hs fr o m th e D at e of I niti al Di a g n osis:  
o  L e uk a ph er esis Eli gi bility Scr e eni n g Visit D at e = Missin g           → El a ps e Ti m e = Missi n g  
o  D at e of I niti al Dia g n osis = C o m pl et ely/ parti ally Missi n g       → El a pse Ti me = Missi n g  
•  
Ot h er wise       → El a ps e Ti m e = ( L e uk ap h er esis Eli gibility Scr e e ni n g Visit D ate – D at e of I niti al 
Di a g n osis + 1) / 3 0. 43 7 5            
Ti m e Si n c e M et a st atic Di s e as e t o S cr e e ni n g  
•  
Ti m e (in m o nths) si nce m etastatic dis e as e t o scr ee ni n g will be c alc ul ate d as: 
( L e uk a ph er esis Eli gi bility Scr ee ni n g Visit D at e - D at e of Dia gn osis of Met astatic Dis e as e + 1) / 3 0. 4 3 75  
Ti m e Si n c e L ast Pr o gr e s si o n  
•  
Ti m e (in m o nths) si nce l ast pro gr essi o n t o scr ee ni ng will b e c alc ul at e d (if a pplic a bl e) as:  
( L e uk a ph er esis Eli gi bility Scr ee ni n g Visit D at e –  D at e of L ast Pr o gr essi o n + 1) / 3 0. 4 37 5  
Ti m e Si n c e L ast R e c urr e n c e  
•  
Ti m e (in m o nths) si nce l ast pro gr essi o n t o scr ee ni ng will b e c alc ul at e d (if a pplic a bl e) as:  
( L e uk a ph er esis Eli gi bility Scr ee ni n g Visit D at e –  D at e of L ast R ec urr e nce + 1) / 30. 4 3 7 5  
E xt e nt of E x p o s ur e  
•  Ext e nt of ex p os ur e will o nly b e c alcul at ed f or p articip a nts assi g n e d t o c o m bi n ati o n tre at m ent f or 
p e m br oliz u m a b ex p os ur e.  
•  Nu m b er of days of exp os ure to P e m br oliz u m a b  will b e c alc ul at e d b as e d o n t h e for m ul a:   
D ur ati o n of E x p o s ur e i n D a ys = Tr e at m e nt St o p D at e – ( Tr e at m e nt St art D at e) + 2 1 
•  T h e c u m ul ativ e dos e will be bas e d o n t h e f or m ul a:  
C u m ul ati v e D o s e = S u m of D o s e at E a c h Vi sit  
1 3. 6. 3.  
Effi c a c y  
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13.6.4. 
Safety 
Adverse Events 
AEs of Special Interest evaluated in this RAP 
• 
Cytokine release syndrome (CRS) 
• 
Pneumonitis/pneumonia 
• 
Graft vs host disease (GvHD) 
• 
Guillain Barre syndrome (GBS) or acute inflammatory demyelinating polyneuropathy (AIDP) 
• 
Pancytopenia/Aplastic anemia (including analysis of all hematopoietic cytopenias) 
• 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)  
• 
Treatment-related inflammatory response at tumor site(s) 
Duration of AE 
• 
Calculated as the number of days from AE Start Date to AE Stop Date: 
• 
AE Start Date = Missing              → Elapse Time = Missing  
• 
AE Stop Date = Missing              → Elapse Time = Missing 
• 
Otherwise                                    → Elapsed Time = AE Stop Date – AE Start Date + 1     
Imputed dates will not be used to calculate AE duration. 
QTcF Formula (Fridericia Corrected QT Interval) 
• 
 QT / RR1/3 
List of PTs to Be Combined (this list will be reviewed at the time of reporting and may be updated 
with additional terms) 
The following synonyms will be combined under the PT as shown below. The combined term will 
be used when reporting AE data in tables by PT. Synonymous terms will be combined regardless 
of body system. 
Synonym (Combined Term) 
MedDRA Preferred Term Version 23.1 
Anemia/Red blood cell count decreased 
Anemia 
Red blood cell count decreased 
Cytokine Release Syndrome (CRS) 
Cytokine release syndrome 
Cytokine storm 
Acute GVHD – Skin 
Acute graft versus host disease in skin 
Acute GVHD – Gut (Liver and Intestine) 
Acute graft versus host disease in liver 
Acute graft versus host disease in intestine 
Acute GVHD  - Other (Lung, Bone Marrow, not 
specified) 
Acute graft versus host disease 
Chronic GVHD -  Skin 
Chronic graft versus host disease in skin 
Chronic GVHD - Gut (Liver and Intestine) 
  
Chronic graft versus host disease in liver 
Chronic graft versus host disease in intestine 
Chronic GVHD Other -  (Lung, Bone Marrow, not 
specified) 
Chronic graft versus host disease 
Unspecified GVHD - Skin% 
Graft versus host disease in skin 
Unspecified GVHD - Gut (Liver and Intestine)% 
  
Graft versus host disease in liver 
Graft versus host disease in gastrointestinal tract 
Unspecified GVHD - Other (Lung, Bone Marrow, not 
specified)% 
  
  
  
Graft versus host disease 
Graft versus host disease in eye 
Graft versus host disease in lung 
Prophylaxis against graft versus host disease 
Transfusion associated graft versus host disease 


 
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Adverse Events 
  
  
Engraftment syndrome  
 Leukopenia/White blood cell decreased  
  
White blood cell count decreased 
Leukopenia 
Lymphopenia/Lymphocyte count decreased  
  
  
  
Lymphocyte count decreased 
CD4 lymphocytes decreased  
CD8 lymphocytes decreased  
Lymphopenia 
Neutropenia/Neutrophil count decreased  
  
Neutrophil count decreased 
Neutropenia 
Rash/Rash maculo-papular 
  
  
Rash maculo-papular 
Rash 
Rash erythematous 
Thrombocytopenia/Platelet count decreased  
  
Platelet count decreased 
Thrombocytopenia 
Immune effector cell-associated neurotoxicity syndrome 
(ICANS) 
  
Immune effector cell-associated neurotoxicity syndrome 
Encephalopathy 
 
FOCUSED LIST  
(this list will be reviewed at the time of reporting and may be updated with additional terms) 
Guillain-Barre syndrome  
  
  
Demyelinating polyneuropathy 
  
Guillain-Barre syndrome 
  
Peripheral sensorimotor neuropathy 
  
Subacute inflammatory demyelinating polyneuropathy 
  
Zika virus associated Guillain Barre syndrome 
  
  
Graft versus host disease 
  
  
Acute graft versus host disease in skin 
  
Acute graft versus host disease in liver 
  
Acute graft versus host disease in intestine 
  
Acute graft versus host disease 
  
Acute graft versus host disease oral 
  
Chronic graft versus host disease in skin 
  
Chronic graft versus host disease 
  
Chronic graft versus host disease in liver 
  
Chronic graft versus host disease in intestine 
  
Chronic graft versus host disease 
  
Chronic graft versus host disease in eye 
  
Chronic graft versus host disease oral 
  
Graft versus host disease in skin 
  
Graft versus host disease in liver 
  
Graft versus host disease in gastrointestinal tract 
  
Graft versus host disease 


 
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Graft versus host disease in eye 
  
Graft versus host disease in lung 
  
Prophylaxis against graft versus host disease 
  
Transfusion associated graft versus host disease 
  
Engraftment syndrome  
  
  
Cytokine release syndrome 
  
  
Cytokine release syndrome 
  
Cytokine storm 
  
  
Haematopoietic cytopenias 
(including pancytopenia and 
aplastic anaemia) 
  
  
Febrile bone marrow aplasia 
  
Autoimmune aplastic anaemia 
  
Aplastic anaemia 
  
Pancytopenia 
  
Bone marrow failure 
  
Aplastic anaemia 
  
Full blood count abnormal 
  
Full blood count decreased 
  
Cytopenia 
  
Haemoglobin abnormal 
  
Hypoplastic anaemia 
  
Red blood cell count abnormal 
  
Haematocrit decreased 
  
Normochromic anaemia 
  
Normochromic normocytic anaemia 
  
Normocytic anaemia 
  
Reticulocyte count decreased 
  
Reticulocytopenia 
  
Haematocrit abnormal 
  
Haemoglobin decreased 
  
Anaemia macrocytic 
  
Erythropoiesis abnormal 
  
Anaemia 
  
Erythropenia 
  
Microcytic anaemia 
  
Red blood cell count decreased 
  
Neutropenic sepsis 
  
Band neutrophil percentage decreased 
  
Febrile neutropenia 
  
Granulocytopenia 
  
Neutropenia 
  
Neutrophil count abnormal 


 
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Neutrophil percentage decreased 
  
Neutrophil count decreased 
  
Plateletcrit abnormal 
  
Plateletcrit decreased 
  
Acquired amegakaryocytic thrombocytopenia 
  
Megakaryocytes decreased 
  
Platelet production decreased 
  
Platelet count abnormal 
  
Platelet count decreased 
  
Platelet disorder 
  
Thrombocytopenia 
  
White blood cell count decreased 
  
Leukopenia 
  
Lymphocyte count decreased 
  
Lymphopenia 
  
CD4 lymphocytes decreased  
  
CD8 lymphocytes decreased  
  
  
Immune Effector-Cell 
Associated Neurotoxicity 
Syndrome (ICANS) 
  
  
Encephalopathy 
  
Immune effector cell-associated neurotoxicity syndrome 
 
 
 


 
C O N FI D E N TI A L  
 
 
2 0 8 4 7 1  
9 1  
 
1 3. 7.   
A p p e n di x 7: R e p orti n g St a n d ar d s f or Mi s si n g D at a 
1 3. 7. 1.  
Pr e m at ur e Wit h dr a w al s  
El e m e nt  
R e p orti n g D et ail  
G e n er al  
•  
P artici pa nts w h o d o n ot r ec eive p e m br olizu m a b will be c o nsid er e d t o hav e en d e d th e 
i nt erv enti o nal p h as e of t h e st udy aft er b ei n g o n stu dy u ntil We ek 1 0 6 p ost l et e-c el 
i nf usio n ( a ppr oxi m at ely 2 y e ars), 
 
 
, or d e at h ( w hic h ever occ urs first) i n ord er t o all o w for t h e pri m ary a n alysis 
t o occur. P artici p a nts w h o r eceiv e pe m br olizu m a b i n Ar ms B or C, or i n Ar m A 
f oll o wi ng dis e as e pr o gr essio n aft er l et e-c el i nf usi o n ( P art 4), will b e c o nsi d er e d o n 
t h e i nt erv e nti o n al p h ase of t he st u dy u ntil c o m pl eti o n of 3 5 cycl es of pe m br oliz u m a b, 
pr o gr essiv e dise as e ( Ar ms B a n d C), f urt h er pr o gr essiv e dise as e ( Ar m A P ar t 4), or 
d e at h ( w hic h ever occ urs first). P artici pa nt  stu dy c o m pl etio n (i. e. as s p ecifi e d i n t he 
pr ot oc ol) w as d efi n e d as w h en h e/s h e h as P D or has di e d prior t o P D, or 7 0 % of t ot al 
tr e at e d p articip a nts i n this st u dy h av e pr o gr ess e d, di ed or h av e b e e n l ost t o f oll o w-
u p.  
•  
Wit h dr a w n p artici p a nts  will n ot b e r e pl ac e d i n t h e st u dy. 
•  
All av ail a bl e d ata fr o m p artici pa nts w h o w er e wit h dr a w n fr o m t h e st udy will b e liste d 
a n d all av ail a bl e pla n n e d d at a will b e i nclu d e d i n s u m m ary t abl es an d fi gur es, u nl ess 
ot h er wis e s p ecifi ed. 
1 3. 7. 2.  
H a n dli n g of Mi s si n g D at a  
El e m e nt  
R e p orti n g D et ail  
G e n er al  
•  
Missi n g dat a occ urs w h e n a ny r e q u este d d at a is n ot pr ovi d ed, l e a di n g t o bl a nk fi el ds 
o n t h e coll ecti on i nstr u m ent: 
o  T h es e dat a will b e in dic at e d by t h e us e of a “ bl a nk” i n p articip a nt listi ng dis pl ays. 
U nl ess all dat a f or a s p ecific visit ar e missi ng i n w hi c h c as e th e d at a is exclu d e d 
fr o m t h e ta bl e.  
o  A ns w ers s uc h as “ N ot a pplic abl e” a n d “ N ot ev al u a bl e” ar e not c o nsi d er ed t o b e 
missi n g dat a a nd s h oul d be dis pl aye d as s uc h.  
O utliers  
•  
A ny p artici p ants  exclu d e d fro m t h e su m mari es a n d/ or st atistic al a n alys es wil l b e 
d oc u me nt e d al o n g wit h t h e reas o n f or excl usi o n in t h e cli nical st u dy r e port.  
1 3. 7. 2. 1.  
H a n dli n g of Mi s si n g  a n d P arti al D at e s  
I m p ut e d d at e s will n ot b e di s pl a y e d i n li sti n g s. H o w e v er, w h er e n e c e s s ar y, di s pl a y m a cr o s m a y 
i m p ut e d at e s a s t e m p or ar y v ari a bl e s f or t h e p ur p o s e of s orti n g d at a i n li sti n g s o nl y. I n a d diti o n, 
p arti al d at e s m a y b e i m p ut e d f or ‘ sl otti n g’ d at a t o st u d y ti m e p eri o d s or f or s p e cifi c a n al y si s 
p ur p o s e s a s o utli n e d b el o w.  
T h e p arti al d at e i m p ut ati o n will f oll o w A D a M c o n v e nti o n s. T h e A D a M a p pr o a c h i s t o p o p ul at e t h e 
n u m eri c d at e v ari a bl e s wit h t h e i m p ut e d d at e a n d a d d a fl a g v ari a bl e t o t h e d at a s et t h at i n di c at e s 
t h e l e v el of i m p ut ati o n. 
T h e fl a g v ari a bl e c a n c o nt ai n t h e v al u e s: bl a n k, ‘ D’, ‘ M’, ‘ Y’.  
 
Bl a n k: i n di c at e s t h at n o i m p ut ati o n w a s d o n e  
 
D =’ D a y’: i n di c at e s t h at t h e d a y p orti o n of t h e d at e i s i m p ut e d  
 
M =’ M o nt h’: i n di c at e s t h at t h e m o nt h a n d d a y p orti o n s of t h e d at e ar e i m p ut e d  
 
Y =’ Y e ar’: i n di c at e s t h at t h e e ntir e d at e ( y e ar, m o nt h, d a y) i s i m p ut e d  
 
C CI
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Example of date variables: 
 
XYZD_- Character date variable 
 
XYZDT – numeric date variable 
 
XYZDTFL – flag variable 
 
Details on imputing partial dates for specific datasets are outlined below. 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays.  
• 
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 13.4.1) or for specific analysis purposes as outlined below. 
• 
Imputed partial dates will not be used to derive study day, time to onset or duration 
(e.g., time to onset or duration of adverse events), or elapsed time variables (e.g., time 
since diagnosis). In addition, imputed dates are not used for deriving the last contact 
date in overall survival analysis dataset. 
• 
With the exception of new anti-cancer therapy start date in the time to event analysis 
dataset and exposure end date in the exposure analysis dataset, imputed dates will not 
be stored in datasets. 
Concomitant 
Medications/
Blood 
Products 
• 
These imputation rules will be used for classifying a medication as prior or concomitant. 
• 
Completely missing start dates will not be imputed. 
• 
Partial start dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
 
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.       
• 
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 
Earliest of (Dec 31st and date of last contact) will be used. 
Completely missing 
start/end date 
No imputation 
 
• 
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Element 
Reporting Detail 
Surgical 
Procedures/
Radiotherap
y 
• 
No imputation for completely missing dates. 
• 
If partial date contains a year only, set to January 1st. 
• 
If partial date contains a month and a year set to the 1st of the month. 
New Anti-
Cancer 
Therapy/Rad
iotherapy/Su
rical 
Procedures 
for Efficacy 
Evaluation 
Start dates for follow-up on-study anti-cancer therapy, non-palliative radiotherapy (where 
applicable), and surgical procedures (where applicable) will be 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, non-palliative 
radiotherapy, and/or surgical procedures dataset[s]: 
• 
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 date + 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; 
Treatment 
End Date for 
Pembrolizum
ab 
• 
If there is more than one study treatment (e.g. for Pembrolizumab population), 
imputation of missing treatment end date will be applied to all applicable treatments 
following rules below and treatment end date is the latest treatment end date across all 
study treatments.If treatment end date is missing for a cycle, treatment start date for the 
cycle will be used. 
 


 
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13.8. 
Appendix 8: Values of Potential Clinical Importance 
13.8.1. 
Laboratory Data 
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 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).  
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. 
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. For lab tests reported 
descriptively as ‘Normal’, ‘Abnormal, not clinically significant’, or ‘Abnormal, clinically 
significant’ (such as urinalysis), responses of ‘Abnormal, clinically significant’ will be 
considered as of potential clinical concern. 
13.8.2. 
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 eCRF collects either QTcB or QTcF. Note that there 
is a slight inconsistency between NCI-CTCAE v4.03 and ICH E14 (Absolute QTc 


 
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interval prolongation). The clinical concern range for QRS duration is approximately 
based on the limits determined by Ramirez et al. (Ramirez, 2011). 
By default, the definition of PCI is defined based on QTc value (e.g., QTcF Interval, 
Aggregate) where a participant has a QTc value >=450 or a QTc increase of >30msec.  
PCI Flag 
Potential Clinical Importance (PCI) Range 
High (H) 
Grade 1 or Higher (QTc>=450 ms)  
or QTc increase from baseline of >30ms  
or QRS duration >105 msec 
Low (L) 
QRS duration < 70 msec 
 
13.8.3. 
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 ‘Hypothermia’, ‘Fever’, ‘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 
(Absolute) 
Units 
Potential Clinical Importance (PCI) Range 
Lower 
Upper 
Heart Rate 
bpm 
Decrease to <60 
Increase to >100 
Temperature 
Degrees C 
Decrease to ≤35 
Increase to ≥38 
Pulse Oximetry 
% 
Decrease to <88 
N/A 
 
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’. Change 
from baseline to grade 1, 2 or 3 will be presented. Systolic and diastolic blood pressure ≥ 
Grade 1 is flagged as High (H) in the listing. 
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 
 


 
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Values of potential clinical importance for hypotension will be presented as defined 
below 
Vital Sign Parameter 
(Absolute) 
Units 
Potential Clinical Importance (PCI) Range 
Decrease from baseline 
Systolic Blood Pressure 
mmHg 
≥80 to <100 (Low) 
<80 (Very low) 
Decrease from baseline 
Diastolic Blood Pressure 
mmHg 
≥60 to <70 (Low) 
<60 (Very low) 
 
 


 
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13.9. 
Appendix 11: Abbreviations & Trade Marks 
13.9.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AIC 
Akaike’s Information Criteria 
A&R 
Analysis and Reporting  
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Register 
CVb / CVw 
Coefficient of Variation (Between) / Coefficient of Variation (Within) 
DBL 
Database Lock 
DBR 
Database Release 
DOB 
Date of Birth 
DP 
Decimal Places 
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 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee  
IDSL 
Integrated Data Standards Library (GSK Standards Library) 
IMMS 
International Modules Management System 
IP 
Investigational Product 
IMT 
Issue Management Team 
ITT 
Intent-To-Treat 
MMRM 
Mixed Model Repeated Measures 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamic 
PDMP 
Protocol Deviation Management Plan 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PopPK 
Population PK 
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 
RAMOS 
Randomization & Medication Ordering System  
SAC 
Statistical Analysis Complete 


 
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Abbreviation 
Description 
SDSP 
Study Data Standardization Plan 
SDTM 
Study Data Tabulation Model 
SMQ 
Standardised MedDRA Query 
SOP 
Standard Operation Procedure 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
13.9.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
none 
 
WinNonlin 
 
 
SAS 
 
 
NONMEM 
 
 


 
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13.10. 
Appendix 12: List of Data Displays 
All data displays will use the term “subject” rather than “participant” in accordance with 
CDSIC and GSK Statistical Display Standards. 
13.10.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.41 
1.1 to 1.1 
Efficacy 
2.1 to 2.13 
2.1 to 2.8 
Safety 
3.1 to 3.73 
3.1 to 3.6 
Pharmacokinetic 
4.1 to 4.2 
4.1 to 4.1 
gSection 
Listings 
ICH Listings 
1 to 34 
Other Listings 
35 to 71 
 
13.10.2. 
Mock Example Shell Referencing 
Nonstandard specifications will be referenced as indicated and if required example mock-
up displays provided in Appendix 13: Example Mock Shells for Data Displays. 
 
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 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘GSK Statistical Display Standard /  Example Shell’ or ‘Programming 
Notes’ column as ‘[Non-Standard] + Reference.’ 
 
13.10.3. 
Deliverables  
Delivery   
Description 
IA 
Interim Futility Analysis 
SAC  
Final Statistical Analysis Complete 
 
 


 
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13.10.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
GSK Standard  
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
ITT 
ES8 
Summary of Subject Status and Subject Disposition for the 
Study Conclusion Record 
ICH E3, FDAAA, EudraCT 
Participant status will be displayed with 
the categories Completed (Death, 
Transferred to LTFU), Ongoing 
(LEUKAPHERESIS PHASE, 
INTERVENTIONAL PHASE 
(LYMPHODEPLETION), 
INTERNEVTIONAL PHASE (POST T-
CELL INF.), FOLLOW-UP PHASE), 
and Withdrawn (Primary reasons as 
captured in the CRF – add “Death 
before T-cell Infusion” as a sub-
category under Withdrawn). 
Add sub-bullet under FOLLOW-UP 
PHASE: Ongoing on Pembrolizumab 
Therapy Following Disease Progression 
after Lete-cel Infusion 
 
Death after T-cell infusion is considered 
"Completed". 
Death before T-cell infusion is 
considered "withdrawn"  
 
At the end of study reporting, there 
should be no subjects in interventional 
phase. 
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Study Population Tables 
 
Display as: Arm A, Arm C, Overall 
 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
1.2. 
mITT 
ES8 
Summary of Subject Status and Subject Disposition for the 
Study Conclusion Record 
ICH E3, FDAAA, EudraCT 
Participant status will be displayed with 
the categories Completed (death, 
transferred to LTFU), Ongoing (in 
Interventional Phase, in Follow-up 
Phase), Withdrawn (Reasons from 
CRF– add “Death before T-cell 
Infusion” as a sub-category under 
Withdrawn) 
Death after T-cell infusion is considered 
“completed”. Death before t-cell 
infusion is considered "withdrawn" 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Display as: Arm A, Arm C, Overall 
IA, SAC 
1.3. 
ITT 
ES8 
Summary of Subject Status and Subject Disposition for the 
Study Conclusion Record by Relationship to COVID-19 
Pandemic 
Display as: Arm A, Arm C, Overall 
 
SAC 
1.4. 
Lymphodepl
etion 
SD1 
Summary of Interventional Phase Status 
ICH E3 
Footnote: Lymphodepletion population 
includes all participants who received 
any dose of lymphodepletion 
chemotherapy. 
Display as: Arm A, Arm C, Overall 
SAC 


 
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Study Population Tables 
 
1.5. 
Pembrolizu
mab 
SD1 
 
Summary of Treatment Status and Reasons for Discontinuation 
of Pembrolizumab 
ICH E3 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
Only needed for Arm C 
IA, SAC 
1.6. 
Screened 
ES6 
Summary of Screen Status and Reasons for Screen Failures 
Journal Requirements 
Show all categories collected in the 
eCRF. 
Footnote: Screened population includes 
all participants who signed an ICF to 
participate in the study. 
Display as: Arm A, Arm C, Overall 
 
 
SAC 
1.7. 
ITT 
ES10 
Summary of Subject Lete-cel Infusion Status and Reason for 
Failure to Receive Lete-cel Infusion 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure.. 
 
Lete-cel Infusion Status categories: 
Completed, Failed (based on CRF) 
 
Be sure “death prior to lete-cel infusion” 
is a category for reasons for failure 
Display as: Arm A, Arm C, Overall 
 
IA, SAC 
1.8. 
Enrolled 
NS1 
Summary of Number of Participantss by Country and Site ID 
(Enrolled Population) 
EudraCT/Clinical Operations 
SAC 


 
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Study Population Tables 
Footnote: Enrolled population includes 
all participants who started the 
leukapheresis procedure. 
Display as: Arm A, Arm C, Overall 
 
1.9. 
mITT 
NS1 
Summary of Number of Participants by Country and Site ID 
(mITT Population) 
Plain Language Summaries (PLS) 
Display as: Arm A, Arm C, Overall 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 
Protocol Deviation 
1.10. 
ITT 
DV1 
Summary of Important Protocol Deviations 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
Display as: Arm A, Arm C, Overall 
 
IA, SAC 
1.11. 
ITT 
DV1 
Summary of Important COVID-19 Related Protocol Deviations 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
Display as: Arm A, Arm C, Overall 
 
SAC 
1.12. 
ITT 
DV1 
Summary of Important Non COVID-19 Related Protocol 
Deviations 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
Display as: Arm A, Arm C, Overall 
 
SAC 
Population Analysed 
1.13. 
Enrolled 
SP1  
 
Summary of Study Populations  
GSK Statistical Display Standard 
Summarize all populations (except 
Screened) from Section 4 
IA, SAC 


 
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Study Population Tables 
Display as: Arm A, Arm C, Overall 
Footnote: Enrolled population includes 
all participants who started the 
leukapheresis procedure. 
Demographic and Baseline Characteristics 
1.14. 
ITT 
DM1  
Summary of Demographic Characteristics (ITT Population) 
ICH E3, FDAAA, EudraCT 
Report sex, age [years] summary, age 
[years] categories [<=18, 19-64, >=65], 
ethnicity, race, baseline height [cm], 
baseline weight [kg],  BMI, and body 
surface area (BSA). 
Display as: Arm A, Arm C, Overall 
 
Footnote: 
[1] Intent-to-Treat population includes 
all participants who started the 
leukapheresis procedure.  
[2] The reference date for age is lete-
cel infusion date. If the subject did not 
receive lete-cel infusion, 
the reference date for age is the date of 
leukapheresis eligibility. 
Age is imputed when full date of birth is 
not provided. 
 
IA, SAC 
1.15. 
mITT 
DM1 
Summary of Demographic Characteristics (mITT Population) 
ICH E3, FDAAA, EudraCT 
Report sex, age [years] summary, age 
[years] categories [>=18, 19-64, <=65], 
ethnicity, race, baseline height [cm], 
baseline weight [kg], BMI, and body 
surface area (BSA). 
Display as: Arm A, Arm C, Overall 
IA, SAC 


 
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Study Population Tables 
 
Footnote: 
[1] Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion.. 
[2] The reference date for age is lete-
cel infusion date. If the subject did not 
receive lete-cel infusion, 
the reference date for age is the date of 
leukapheresis eligibility. 
Age is imputed when full date of birth is 
not provided. 
 
1.16. 
Enrolled 
DM11 
Summary of Age Ranges 
EudraCT 
Display as: Arm A, Arm C, Overall 
 
Footnote: Enrolled population includes 
all participants who started the 
leukapheresis procedure. 
[1] Age is imputed when full date of 
birth is not provided.  
Note: The reference date for age is 
lete-cel infusion date. If the subject did 
not receive lete-cel infusion, 
the reference date for age is the date of 
leukapheresis eligibility. 
 
SAC 
Prior and Concomitant Medications 
1.17. 
ITT 
MH1 
 
Summary of Past Medical Conditions (ITT Population) 
ICH E3, GSK DS-NPD-101 
Display as: Arm A, Arm C, Overall 
 
SAC 


 
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Study Population Tables 
Footnote: 
[1] Intent-to-Treat population includes 
all participants who started the 
leukapheresis procedure. 
 
1.18. 
mITT 
MH1 
Summary of Past Medical Conditions (mITT Population) 
ICH E3, GSK DS-NPD-101 
Display as: Arm A, Arm C, Overall 
 
Footnote: 
[1] Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
 
SAC 
1.19. 
ITT 
MH1 
Summary of Current Medical Conditions (ITT Population) 
ICH E3, GSK DS-NPD-101 
Display as: Arm A, Arm C, Overall 
 
Footnote: 
[1] Intent-to-Treat population includes 
all participants who started the 
leukapheresis procedure.  
SAC 
1.20. 
mITT 
MH1 
Summary of Current Medical Conditions (mITT Population) 
ICH E3, GSK DS-NPD-101 
Display as: Arm A, Arm C, Overall 
 
Footnote: 
[1] Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
SAC 
1.21. 
mITT 
CM8 
Summary of Concomitant Medications by Ingredient 
ICH E3 
Display as: Arm A, Arm C, Overall 
 
IA, SAC 


 
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Footnote:  
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
Note: Concomitant medications are 
those initiated after or ongoing at 
lymphodepletion. 
 
Exposure and Treatment Compliance 
1.22. 
Lymphodepl
etion 
EX1 
Summary of Exposure to Study Treatment 
n, Mean, SD, Median, Min, Max for 
each: vein to vein time, Cumulative 
Dose of Cyclophosphamide, 
Cumulative Dose of Fludarabine, and 
total number of Transduced T-cells 
Cumulative dose of Cyclophosphamide 
(<=1800, >1800 to <=2400, and >2400 
to <=2700 mg/m2) 
Cumulative Dose of Fludarabine (<=60, 
>60 to <=80, >80 to <=90, >90 to 
<=120, and >120 mg/m2) 
Report total number of transduced T-
cells in 10^9 cells and categorize it into 
<1, >=1 to <=8, and >8 to <=15 and 
>15 (10^9 cells) 
 
Display as: Arm A, Arm C, Overall 
 
Footnote: 
Lymphodepletion population includes 
all participants who received any dose 
of lymphodepletion chemotherapy. 
IA, SAC 


 
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Study Population Tables 
1.23. 
Pembrolizu
mab 
OEX5 
Summary of Exposure to Pembrolizumab (Pembrolizumab 
Population) 
 
ICH E3 
This display will be created for Arms A 
and C with separate tables for each. 
The Arm A table should only contain 
those patients who received pembro 
following PD after lete-cel dosing 
 
Display number of doses and [mean, 
median, SD, min, max] and cumulative 
dose 
 
IA, SAC 
1.24. 
Pembrolizu
mab 
ODMOD3 
Summary of Dose Delays (Pembrolizumab) 
ICH E3 
This display will be created for Arms A 
and C with separate tables for each. 
The Arm A table should only contain 
those patients who received pembro 
following PD after lete-cel dosing 
For this summary, no need to include 
delay duration, please do include the 
dose delays by planned time (can use 
visit, i.e. week 3 day 1, rather than 
cycle)  
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
SAC 
1.25. 
Pembrolizu
mab 
ODMOD9 
Summary of Incomplete Infusions (Pembrolizumab) 
ICH E3 
This display will be created for Arms A 
and C with separate tables for each. 
The Arm A table should only contain 
those patients who received pembro 
following PD after lete-cel dosing 
SAC 


 
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Study Population Tables 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
1.26. 
Pembrolizu
mab 
ODMOD16 
Summary of Infusion Interruptions (Pembrolizumab) 
ICH E3 
(interruption of infusion, but was 
subsequently completed) 
This display will be created for Arms A 
and C with separate tables for each. 
The Arm A table should only contain 
those patients who received pembro 
following PD after lete-cel dosing 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
SAC 
Disease Characteristics 
1.27. 
ITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis (ITT 
Population) 
ICH E3 
Display as: Arm A, Arm C, Overall 
Stage of Lung Cancer at Initial 
Diagnosis 
Disease Stage at Time of Enrolment 
Time from Initial Diagnosis to 
Leukapheresis Eligibility Screening 
(months) 
TNM Staging 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
IA, SAC 
1.28. 
mITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis (mITT 
Population) 
ICH E3 
Display as: Arm A, Arm C, Overall 
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Study Population Tables 
Stage of Lung Cancer at Initial 
Diagnosis 
Disease Stage at Time of Enrolment 
TNM Staging 
Time from Initial Diagnosis to 
Leukapheresis Eligibility Screening 
(months) 
Histology and Histology Grade at Initial 
Diagnosis 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
1.29. 
ITT 
DC2 
Summary of Disease Characteristics at Screening (ITT 
Population) 
ICH E3  
Display as: Arm A, Arm C, Overall 
Stage at Screening 
Number of Prior Systemic Therapy 
Regimens 
Number of Prior Radiotherapy 
Regimens 
LAGE1 status 
HLA status 
NY-ESO-1 status 
Status of visceral/nonvisceral disease 
Measurable Disease at Screening? 
Non-target Lesions? 
Time from last progression to 
leukapheresis eligibility screening 
(months) 
Time from last recurrence to 
leukapheresis eligibility screening 
(months) 
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Study Population Tables 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
1.30. 
mITT 
DC2 
Summary of Disease Characteristics at Screening (mITT 
Population) 
ICH E3  
Display as: Arm A, Arm C, Overall 
Stage at Screening 
Number of Prior Radiotherapy 
Regimens 
LAGE1 status 
HLA status 
NY-ESO-1 status 
Status of visceral/nonvisceral disease 
Measurable Disease at Screening 
Non-target Lesions 
Time from last progression to 
leukapheresis eligibility screening 
(months) 
Time from last recurrence to 
leukapheresis eligibility screening 
(months) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
1.31. 
mITT 
MD1 
Summary of Metastatic Disease at Screening (mITT Population) 
Only include sites present in data (i.e. 
where “yes” on metastatic sites CRF) 
Display as: Arm A, Arm C, Overall 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
1.32. 
mITT 
LA1 
Summary of Disease Burden at Baseline (mITT Population) 
ICH E3 
Display as: Arm A, Arm C, Overall 
IA, SAC 


 
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Study Population Tables 
Include target and non-target lesions at 
baseline 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 


 
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Study Population Tables 
Anti-Cancer Therapy 
1.33. 
ITT 
AC1 
Summary of Prior Anti-Cancer Therapy (ITT Population) 
ICH E3 
Display as: Arm A, Arm C, Overall 
Note: Therapies and procedures prior 
to leukapheresis or full lines of therapy 
given between leukaphersis and 
lymphodepletion are defined as prior. 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
IA, SAC 
1.34. 
mITT 
AC1 
Summary of Prior Anti-Cancer Therapy (mITT Population) 
ICH E3 
Display as: Arm A, Arm C, Overall 
Note: Therapies and procedures prior 
to leukapheresis or full lines of therapy 
given between leukaphersis and 
lymphodepletion are defined as prior. 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
1.35. 
ITT 
CM8 
Summary of Prior Dictionary-Coded Anti-Cancer Therapy (ITT 
Population) 
IDSL 
Display as: Arm A, Arm C, Overall 
Note: Therapies and procedures prior 
to leukapheresis or full lines of therapy 
given between leukaphersis and 
lymphodepletion are defined as prior. 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
SAC 
1.36. 
mITT 
CM8 
Summary of Prior Dictionary-Coded Anti-Cancer Therapy (mITT 
Population) 
IDSL  
Display as: Arm A, Arm C, Overall 
Note: Therapies and procedures prior 
to leukapheresis or full lines of therapy 
SAC 


 
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Study Population Tables 
given between leukaphersis and 
lymphodepletion are defined as prior. 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
1.37. 
ITT 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens in 
the Advanced/Metastatic Setting (ITT Population) 
IDSL 
Display as: Arm A, Arm C, Overall 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure.  
Note: Therapies and procedures that 
begin prior to leukapheresis are defined 
as prior. 
SAC 
1.38. 
mITT 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens in 
the Advanced/Metastatic Setting (mITT Population) 
IDSL 
Display as: Arm A, Arm C, Overall 
Footnote: 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
Note: Therapies and procedures that 
begin prior to leukapheresis are defined 
as prior. 
SAC 
1.39. 
mITT 
CM8 
Summary of Dictionary Coded Bridging Anti-Cancer Therapy 
IDSL 
Display as: Arm A, Arm C, Overall 
Footnote: 
[1] Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
 
Note: Bridging therapy is defined as 
supportive systemic therapy given 
between leukapheresis and 
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Study Population Tables 
lymphodepletion to maintain disease 
control. 
1.40. 
mITT 
FAC1 
Summary of On-Study Anti-Cancer Therapy (mITT Population) 
IDSL 
Display as: Arm A, Arm C, Overall 
Include time from T-cell infusion to first 
post-treatment anti-cancer therapy 
Footnote: 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
On-study and follow-up therapies are 
defined as systemic therapy, 
radiotherapy, or cancer related surgery 
given on or after the start of 
lymphodepletion chemotherapy. 
[1] Time from Study Treatment 
Discontinuation to Start of Subsequent 
Anti-Cancer Therapy align with 
censoring rules for PFS 
SAC 
1.41. 
mITT 
FAC1 
Summary of On-Study Dictionary Coded Anti-Cancer Therapy 
(mITT Population) 
IDSL 
Display as: Arm A, Arm C, Overall 
Include time from T-cell infusion to first 
post-treatment anti-cancer therapy 
Footnote: 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
On-study and follow-up therapies are 
defined as systemic therapy, 
radiotherapy, or cancer related surgery 
given on or after the start of 
lymphodepletion chemotherapy. 
SAC 


 
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Study Population Tables 
[1] Time from Study Treatment 
Discontinuation to Start of Subsequent 
Anti-Cancer Therapy align with 
censoring rules for PFS 
 
13.10.5. 
Study Population Figures 
Study Population Figures 
No. 
Population 
GSK Standard 
 /  Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.1. 
ITT 
PAN6 
Recruitment over time by Country Relative to COVID-19 
Pandemic Measures 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
SAC 
 


 
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13.10.6. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
GSK Standard 
 /  Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response 
2.1.  
mITT 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria)(mITT Population) 
95% CI is based on Clopper-Pearson 
exact confidence interval 
Display as: Arm A, Arm C as two 
columns in the same table 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
2.2.  
ITT 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria)(ITT Population) 
95% CI is based on Clopper-Pearson 
exact confidence interval 
Note: p value not to be reported 
Display as: Arm A, Arm C as two 
columns in the same table 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
SAC 
2.3.  
mITT 
RE1c 
Summary of Investigator-Assessed Disease Control Rate with 
Confirmation (RECIST 1.1 Criteria) (mITT Population) 
95% CI is based on Clopper-Pearson 
exact confidence interval 
 
Note: p value not to be reported 
Display as: Arm A, Arm C as two 
columns in the same table 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 1 8  
 
Effi c a c y: T a bl es  
N o.  
P o p ul ati o n  
G S K St a n d ar d  
 /  E x a m pl e 
S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
2. 4.  
I T T 
R E 1c  
S u m m ary of I nv esti g at or -Ass ess e d Dis e as e C o ntr ol R at e with 
C o nfir m atio n ( R E CI S T 1. 1 Criteri a) (I T T P o p ul atio n)  
9 5 % CI is b as e d o n Cl o p p er -P e ars o n 
ex act c o nfi d e nc e i nt erv al  
 
N ot e: p v al u e n ot t o b e r e p ort e d  
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: I nt e nt -t o-Tr e at p o p ul atio n 
i ncl u d es all p artici p a nts w h o st art e d t h e 
l e uk a p h er esis pr oc e d ur e. 
S A C  
Ti m e -t o-E v e nt E n d p oi nt s  
2. 6.  
mI T T  
E F F _ T 1  
S u m m ary of Ti m e t o R es p o nse B as e d on I nvestig at or 
Ass ess m e nt ( R E CI S T 1. 1 Criteri a)  
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 1 9  
 
Effi c a c y: T a bl es  
N o.  
P o p ul ati o n  
G S K St a n d ar d  
 /  E x a m pl e 
S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
2. 7.  
mI T T  
E F F _ T 2  
S u m m ary of Pr o gr essio n -Fr e e S urviv al B as ed o n Inv esti g ator 
Ass ess m e nt ( R E CI S T 1. 1 Criteri a)  
S u m m ariz e pr o b a bility of ev e nt at 
ti m e p oi nts ev ery 3 m o nt hs 
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
2. 9.  
mI T T  
E F F _ T 3  
S u m m ary of R ev ers e K a pl a n -M ei er Esti m ates f or Pr o gr essio n 
Fr e e S urviv al Foll o w -u p 
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
2. 1 0. 
 
mI T T  
E F F _ T 2  
S u m m ary of D ur atio n of R es po ns e B as e d o n I nv esti gat or 
Ass ess m e nt ( R E CI S T 1. 1 Criteri a)  
S u m m ariz e pr o b a bility of ev e nt at 
ti m e p oi nts ev ery 3 m o nt hs 
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 2 0  
 
Effi c a c y: T a bl es  
N o.  
P o p ul ati o n  
G S K St a n d ar d  
 /  E x a m pl e 
S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
2. 1 2. 
 
mI T T  
T T E 1  
S u m m ary of Ov er all S urviv al  
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
2. 1 3. 
 
mI T T  
E F F _ T 3  
S u m m ary of R ev ers e K a pl a n -M ei er Esti m ates f or Over all 
S urviv al F oll o w -u p 
Dis pl ay as: Ar m A, Ar m C  as t w o 
c ol u m ns i n t h e s a m e t a bl e 
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
 
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Efficacy Figures 
Efficacy: Figures 
No. 
Population 
GSK Standard 
 / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response 
2.1.  
mITT 
EFF_F3 
Plot of Duration on Study 
For Arm C, include marker for pembro 
and final pembro dose (after 
discontinuation) 
Include arrow for ongoing subjects 
Separate figures for Arm A and Arm C 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
2.2.  
mITT 
RE8b 
Investigator-Assessed Maximum Percent Reduction from 
Baseline in Tumour Measurement (RECIST 1.1 Criteria) 
Label with subject ID 
Separate figures for Arm A and Arm C 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
2.3.  
mITT 
EFF_F1 
Spider Plot of Percent Change from Baseline in Target Lesion 
Diameter 
Label with subject ID 
Add symbol to mark new lesions 
Separate figures for Arm A and Arm C 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 
Time-to-Event Endpoints 
2.4.  
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Progression-Free 
Survival with 95% Confidence Bands (RECIST 1.1 Criteria)  
Separate figures for Arm A and Arm C 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 2 2  
 
Effi c a c y: Fi g ur e s  
N o.  
P o p ul ati o n  
G S K St a n d ar d  
 / E x a m pl e 
S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
2. 5.  
mI T T  
T T E 1 0  
Gr a p h of K a pl a n -M eier S urvival C urv es of D ur atio n of R es po ns e 
wit h 9 5 % C o nfi d e nc e B a n ds ( R E CI S T 1. 1 Crit eri a)  
S e p ar at e fi g ur es f or Ar m A a n d Ar m C  
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
2. 6.  
mI T T  
T T E 1 0  
Gr a p h of K a pl a n -M eier S urvival C urv es of Ov er all S urviv al wit h 
9 5 % C o nfi de nc e B an ds  
S e p ar at e fi g ur es f or Ar m A a n d Ar m C  
F o ot n ot e: M o difi e d I nt e nt -t o-Tr e at 
p o p ul ati o n i ncl u d es all p artici p a nts w h o 
r ec eiv e d l et e-c el i nf usi o n. 
S A C  
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Safety Tables 
Safety: Tables 
No. 
Populati
on 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
3.1.  
ITT 
AE1 
Summary of Adverse Events in the Pre-Lymphodepletion Phase by 
System Organ Class and Preferred Term 
ICH E3 
Display as: Arm A, Arm C, Overall 
 
The pre-Lymphodepletion phase 
includes AEs which start before the first 
day of lymphodepletion chemotherapy. 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
IA, SAC 
3.2.  
ITT 
AE5B 
Summary of Adverse Events in the Pre-Lymphodepletion Phase by 
Maximum Grade 
ICH E3 
Display as: Arm A, Arm C, Overall 
 
Include Combined PT Term AEs  
Remove SYSTEM ORGAN CLASS 
row.  
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
IA, SAC 
3.3.  
ITT 
AE1 
Summary of All Adverse Events Grouped by Similarity of 
Preferred Terms 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure.  
 
Only include Combined PT Term AEs 
Remove “Any event” 
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GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
SOC should be Combined PT Term 
Label Column “Synonym/Preferred 
Term”  
If combined AE does not appear, Show 
0 counts 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.4.  
Lymphod
epletion 
AE1 
Summary of Adverse Events in the Lymphodepletion Phase by 
System Organ Class and Preferred Term 
 
ICH E3 
Use Combined PT list 
Lymphodepletion population includes 
all participants who received any dose 
of lymphodepletion chemotherapy. 
The lymphodepletion phase includes 
AEs which start or worsen on or after 
lymphodepletion and before T-cell 
infusion. 
Display as: Arm A, Arm C, Overall 
 
IA, SAC 
3.5.  
Lymphod
epletion 
AE5B 
Summary of Adverse Events in the Lymphodepletion Phase by 
Maximum Grade 
Lymphodepletion population includes 
all participants who received any dose 
of lymphodepletion chemotherapy. 
The lymphodepletion phase includes 
AEs which start or worsen on or after 
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GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
lymphodepletion and before T-cell 
infusion. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms) 
Display as: Arm A, Arm C, Overall 
 
3.6.  
Lymphod
epletion 
AE5B 
Summary of Lymphodepletion Related Adverse Events in the 
Lymphodepletion Phase by Maximum Grade 
ICH E3 
Use combined PT list 
Lymphodepletion population includes 
all participants who received any dose 
of lymphodepletion chemotherapy. 
Lymphodepletion related AEs are 
defined as AEs identified by the 
investigator as related to fludarabine or 
cyclophosphamide. 
The lymphodepletion phase includes 
AEs which start or worsen on or after 
lymphodepletion and before T-cell 
infusion. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms) 
Display as: Arm A, Arm C, Overall 
 
IA, SAC 
3.7.  
mITT 
AE1 
Summary of All Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term 
ICH E3 
Do not use combined PT terms 
IA, SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion.AEs which 
start or worsen on or after T-cell 
infusion are classified as treatment 
emergent. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.8.  
mITT 
AE5B 
Summary of Treatment-Emergent Adverse Events by Maximum 
Grade 
Use combined PT list 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
IA, SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
3.9.  
mITT 
AE1 
Summary of All Treatment-Emergent Adverse Events by System 
Organ Class and Preferred Term (Overall) 
Do not use combined PT terms 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
For this table, columns should be: 
Monotherapy, Combination Therapy, 
Overall (i.e. do not summarize by 
treatment arm) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.10. 
 
mITT 
AE5B 
Summary of All Treatment-Emergent Adverse Events by 
Maximum Grade (Overall) 
Use combined PT list 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms) 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
For this table, columns should be: 
Monotherapy, Combination Therapy, 
Overall (i.e. do not summarize by 
treatment arm) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.11. 
 
mITT 
AE5B 
Summary of Treatment-Emergent Lymphodepletion-Related 
Adverse Events by Maximum Grade 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Lymphodepletion related AEs are 
defined as AEs identified by the 
investigator as related to fludarabine or 
cyclophosphamide. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
IA, SAC 


 
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Deliverable 
[Priority] 
3.12. 
 
mITT 
AE1 
Summary of All Treatment-Emergent T-cell-Related Adverse 
Events by System Organ Class and Preferred Term 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
 T-cell related AEs are defined as AEs 
identified by the investigator as related 
to T-cell infusion. 
Do not use combined PT terms 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
IA, SAC 
3.13. 
 
mITT 
AE5B 
Summary of Treatment-Emergent T-cell-Related Adverse 
Events by Maximum Grade 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after 
lete-cel infusion are classified as 
treatment emergent. 
T-cell related AEs are defined as AEs 
identified by the investigator as related 
to T-cell infusion. 
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GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.14. 
 
Pembroliz
umab 
AE1 
Summary of All Treatment-Emergent Pembrolizumab-Related 
Adverse Events by System Organ Class and Preferred Term 
ICH E3 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
AEs which start or worsen on or after 
lete-cel infusion are classified as 
treatment emergent. 
Pembrolizumab related AEs are defined 
as AEs identified by the investigator as 
related to Pembrolizumab. 
 
Do not use combined PT terms 
This display will be created for Arm C 
only 
 
IA, SAC 
3.15. 
 
Pembroliz
umab 
AE5B 
Summary of Treatment-Emergent Pembrolizumab-Related 
Adverse Events by Maximum Grade 
Use combined PT list 
IA, SAC 


 
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GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
AEs which start or worsen on or after 
lete-cel infusion are classified as 
treatment emergent. 
Pembrolizumab related AEs are defined 
as AEs identified by the investigator as 
related to Pembrolizumab. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
This display will be created for Arm C 
only 
 
3.16. 
 
Pembroliz
umab 
AE1 
Summary of All Adverse Events in the Pembrolizumab Following 
Disease Progression Phase by System Organ Class and 
Preferred Term 
Arm A only 
Footnotes: 
[1] Pembrolizumab population includes 
all participants in the mITT population 
who received at least one infusion of 
pembrolizumab. 
[2] The Pembrolizumab Following 
Disease Progression Phase includes 
AEs which start or worsen on or after 
the first dose of pembrolizumab for 
participants in Arm A who receive 
Pembrolizumab following disease 
progression after Lete-cel infusion. 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
3.17. 
 
Pembroliz
umab 
AE5b 
Summary of Adverse Events in the Pembrolizumab Following Disease 
Progression Phase by Maximum Grade 
Arm A only 
Footnotes: 
[1] Pembrolizumab population includes 
all participants in the mITT population 
who received at least one infusion of 
pembrolizumab. 
[2] The Pembrolizumab Following 
Disease Progression Phase includes 
AEs which start or worsen on or after 
the first dose of pembrolizumab for 
participants in Arm A who receive 
Pembrolizumab following disease 
progression after Lete-cel infusion. 
 
SAC 
3.18. 
 
mITT 
AE15 
Summary of Common (>=5%) Treatment-Emergent Non-Serious 
Adverse Events by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) 
FDAAA, EudraCT 
Do not combine PT terms 
 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
3.19. 
 
mITT 
AE3 
Summary of Treatment-Emergent T-cell Related Non-Serious 
Adverse Events by Overall Frequency 
PLS 
Do not combine PT terms 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
 
T-cell related AEs are defined as AEs 
identified by the investigator as related 
to T-cell infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.20. 
 
Pembroliz
umab 
AE3 
Summary of Treatment-Emergent Pembrolizumab-Related Non-
Serious Adverse Events by Overall Frequency 
Plain Language Summary requirements 
(PLS). 
Do not combine PT Terms 
 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
 
AEs which start or worsen on or after 
lete-cel infusion are classified as 
treatment emergent. 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
Pembrolizumab related AEs are defined 
as AEs identified by the investigator as 
related to Pembrolizumab. 
Arm C only 
Serious and Other Significant Adverse Events 
3.21. 
 
ITT 
AE5B 
Summary of Serious Adverse Events in the Pre-
Lymphodepletion Phase by Maximum Grade 
 
ICH E3 
The pre-Lymphodepletion phase 
includes AEs which start before the first 
day of lymphodepletion chemotherapy. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
 
Display as: Arm A, Arm C, 
OverallFootnote: Intent-to-Treat 
population includes all participants who 
started the leukapheresis procedure. 
IA, SAC 
3.22. 
 
Lymphod
epletion 
AE5B 
Summary of Serious Adverse Events in the Lymphodepletion 
Phase by Maximum Grade 
 
ICH E3 
Lymphodepletion population includes 
all participants who received any dose 
of lymphodepletion chemotherapy. 
The lymphodepletion phase includes 
AEs which start or worsen on or after 
lymphodepletion and before T-cell 
infusion. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Display as: Arm A, Arm C, Overall 
3.23. 
 
mITT 
AE1 
Summary of Treatment-Emergent Serious Adverse Events by 
System Organ Class and Preferred Term 
ICH E3 
Do not use combined PT terms 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
IA, SAC 
3.24. 
 
mITT 
AE1 
Summary of Treatment Emergent Serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) 
ICH E3 
Do not use combined PT terms 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
3.25. 
 
mITT 
AE5B 
Summary of Treatment-Emergent Serious Adverse Events by 
Maximum Grade 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
IA, SAC 
3.26. 
 
mITT 
AE1 
Summary of Treatment-Emergent Serious Adverse Events by 
System Organ Class and Preferred Term (Overall) 
Do not use combined PT terms 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion.AEs which 
start or worsen on or after T-cell 
infusion are classified as treatment 
emergent. 
For this table, columns should be: 
Monotherapy, Combination Therapy, 
Overall (i.e. do not summarize by 
treatment arm) 
Use Actual Treatment received 
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Deliverable 
[Priority] 
3.27. 
 
mITT 
AE5B 
Summary of Treatment-Emergent Serious Adverse Events by 
Maximum Grade (Overall) 
Use combined PT list 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion.AEs which 
start or worsen on or after T-cell 
infusion are classified as treatment 
emergent. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms) 
For this table, columns should be: 
Monotherapy, Combination Therapy, 
Overall (i.e. do not summarize by 
treatment arm) 
Use Actual Treatment received 
SAC 
3.28. 
 
Pembroliz
umab 
AE1 
Summary of Serious Adverse Events in the Pembrolizumab 
Following Disease Progression Phase by System Organ Class 
and Preferred Term 
Arm A only 
Footnotes: 
[1] Pembrolizumab population includes 
all participants in the mITT population 
who received at least one infusion of 
pembrolizumab. 
[2] The Pembrolizumab Following 
Disease Progression Phase includes 
AEs which start or worsen on or after 
the first dose of pembrolizumab for 
participants in Arm A who receive 
Pembrolizumab following disease 
progression after Lete-cel infusion. 
Only create if at least 5 subjects receive 
Pembro in Arm A. 
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Programming Notes 
Deliverable 
[Priority] 
3.29. 
 
Pembroliz
umab 
AE5b 
Summary of Serious Adverse Events in the Pembrolizumab 
Following Disease Progression Phase by Maximum Grade 
Arm A only 
Footnotes: 
[1] Pembrolizumab population includes 
all participants in the mITT population 
who received at least one infusion of 
pembrolizumab. 
[2] The Pembrolizumab Following 
Disease Progression Phase includes 
AEs which start or worsen on or after 
the first dose of pembrolizumab for 
participants in Arm A who receive 
Pembrolizumab following disease 
progression after Lete-cel infusion. 
Only create if at least 5 subjects receive 
Pembro in Arm A. 
SAC 
3.30. 
 
mITT 
AE5B 
Summary of Treatment-Emergent Lymphodepletion-Related 
Serious Adverse Events by Maximum Grade 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Lymphodepletion related AEs are 
defined as AEs identified by the 
investigator as related to fludarabine or 
cyclophosphamide. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
Display as Arm A, Arm C, Overall 
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[Priority] 
3.31. 
 
mITT 
AE5B 
Summary of Treatment-Emergent T-cell-Related Serious 
Adverse Events by Maximum Grade 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
 T-cell related AEs are defined as AEs 
identified by the investigator as related 
to T-cell infusion. 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
IA, SAC 
3.32. 
 
Pembroliz
umab 
AE5B 
Summary of Treatment-Emergent Pembrolizumab-Related 
Serious Adverse Events by Maximum Grade 
Use combined PT list 
Pembrolizumab population includes all 
participants in the mITT population who 
received at least one infusion of 
pembrolizumab. 
AEs which start or worsen on or after 
lete-cel infusion are classified as 
treatment emergent. 
Pembrolizumab related AEs are defined 
as AEs identified by the investigator as 
related to Pembrolizumab. 
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Programming Notes 
Deliverable 
[Priority] 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
Arm C only 
3.33. 
 
mITT 
AE20 
Summary of T-cell Related Serious Fatal and Non-Fatal AEs by 
Overall Frequency 
Plain Language Summary requirements 
(PLS). 
Do not combine PT Terms 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
 T-cell related AEs are defined as AEs 
identified by the investigator as related 
to T-cell infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.34. 
 
Pembroliz
umab 
AE20 
Summary of Pembrolizumab Related Serious Fatal and Non-Fatal AEs 
by Overall Frequency 
Plain Language Summary requirements 
(PLS). 
Do not combine PT Terms 
 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
AEs which start or worsen on or after 
lete-cel infusion are classified as 
treatment emergent. 
Pembrolizumab related AEs are defined 
as AEs identified by the investigator as 
related to Pembrolizumab. 
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[Priority] 
Adverse Events of Special Interest 
3.35. 
 
mITT 
AE5B 
Summary of Treatment Emergent Adverse Events of Special 
Interest by Maximum Grade (Comprehensive List) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.36. 
 
mITT 
AE5B 
Summary of Treatment Emergent Adverse Events of Special 
Interest by Maximum Grade (Focused List) 
Preferred terms are combined as 
shown in table 3.3 (Summary of All 
Adverse Events Grouped by Similarity 
of Preferred Terms). 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.37. 
 
mITT 
AE5B 
Summary of AEs Linked to AESIs Identified by the Investigator 
by Maximum Grade 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
 
Based on new AESI CRF forms (AEs 
marked as related to AESI) 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.38. 
 
mITT 
CM8 
Summary of the Concomitant Medications Linked to AESIs 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Based on new AESI CRF forms (AEs 
marked as related to AESI) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.39. 
 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent Cytokine 
Release Syndrome (CRS) 
Report # of subjects with event & # of 
events 
Report Even charateristics, # of 
occurrences, outcome, and max grade 
based on all subjects and for all 
subjects with event. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
[1] Subjects may be included in more 
than one category for 'Event 
Characteristics'. 
[2] Outcome worst case hierarchy: 
FATAL > NOT RECOVERED/NOT 
RESOLVED > 
RECOVERED/RESOVLED WITH 
SEQUELAE > 
RECOVERING/RESOLVING > 
RECOVERED/RESOLVED 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.40. 
 
mITT 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Treatment Emergent Cytokine Release Syndrome (CRS) 
Time to onset from T-cell infuion (days) 
(<-8, -8-1,1-14,15-30,31-60,>60) 
Duration (days) (1-30, 31-60,61-90,>90, 
Missing) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
Only create if >= 5 subjects 
SAC 


 
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Deliverable 
[Priority] 
3.41. 
 
mITT 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Treatment Emergent Grade 3 and Above Cytokine Release 
Syndrome (CRS) 
Time to onset from T-cell infuion (days) 
(<-8, -8-1,1-14,15-30,31-60,>60) 
Duration (days) (1-30, 31-60,61-90,>90, 
Missing) 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Only create if >= 5 subjects 
SAC 
3.42. 
 
mITT 
EX1 
Summary of Number of Doses per Patient that Received 
Tocilizumab for CRS 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Only create if at least 5 events 
SAC 
3.43. 
 
mITT 
PR1 
Summary of Procedures Associated with Cytokine Release 
Syndrome (CRS) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Include percentage of subjects who 
received both corticosteroids and 
Tocilizumab. 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Only create if at least 5 events 
3.44. 
 
mITT 
ESI2b 
Summary of Onset and Duration of ICU Admission for Subjects 
with Cytokine Release Syndrome (CRS) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Only create if at least 5 events 
SAC 
3.45. 
 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent 
Haematopoietic Cytopenias 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Preferred terms identified in the 
focused list are summarized. 
[1] Subjects may be included in more 
than one category for 'Event 
Characteristics'. 
[2] Outcome worst case hierarchy: 
FATAL > NOT RECOVERED/NOT 
SAC 


 
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[Priority] 
RESOLVED > 
RECOVERED/RESOVLED WITH 
SEQUELAE > 
RECOVERING/RESOLVING > 
RECOVERED/RESOLVED 
 
Report # of subjects with event & # of 
events 
Report Event charateristics, # of 
occurrences, outcome, and max grade 
based on all subjects and for all 
subjects with event. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.46. 
 
mITT 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Treatment Emergent Febrile Neutropenia 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Study Day is relative to the day of first 
T-cell Infusion, which is Study Day 1 
Adverse events with partial or missing 
dates are not used in time of onset and 
duration derivations 
Time to onset from T-cell infuion (days) 
(<-8, -8-1,1-14,15-30,31-60,>60)  
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
Duration (days) (1-30, 31-60,61-90,>90, 
Missing)  
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Create only if >=5 subjects 
3.47. 
 
mITT 
ESI1 
Summary of Characteristics of Pneumonitis/Pneumonia 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Preferred terms identified in the 
focused list are summarized. 
[1] Subjects may be included in more 
than one category for 'Event 
Characteristics'. 
[2] Outcome worst case hierarchy: 
FATAL > NOT RECOVERED/NOT 
RESOLVED > 
RECOVERED/RESOVLED WITH 
SEQUELAE > 
RECOVERING/RESOLVING > 
RECOVERED/RESOLVED 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Report Event characteristics, # of 
occurrences, outcome, and max grade 
based on all subjects and for all 
subjects with event. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.48. 
 
mITT 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Treatment Emergent Pneumonitis/Pneumonia 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Study Day is relative to the day of first 
T-cell Infusion, which is Study Day 1 
Adverse events with partial or missing 
dates are not used in time of onset and 
duration derivations 
Time to onset from T-cell infuion (days) 
(<-8, -8-1,1-14,15-30,31-60,>60)  
Duration (days) (1-30, 31-60,61-90,>90, 
Missing)  
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
Create only if >=5 subjects 
3.49. 
 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent Graft vs 
Host Disease (GvHD) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Preferred terms identified in the 
focused list are summarized. 
[1] Subjects may be included in more 
than one category for 'Event 
Characteristics'. 
[2] Outcome worst case hierarchy: 
FATAL > NOT RECOVERED/NOT 
RESOLVED > 
RECOVERED/RESOVLED WITH 
SEQUELAE > 
RECOVERING/RESOLVING > 
RECOVERED/RESOLVED 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
3.50. 
 
mITT 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Treatment Emergent Graft vs Host Disease (GvHD) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Study Day is relative to the day of first 
T-cell Infusion, which is Study Day 1 
Adverse events with partial or missing 
dates are not used in time of onset and 
duration derivations 
Time to onset from T-cell infuion (days) 
(<-8, -8-1,1-14,15-30,31-60,>60)  
Duration (days) (1-30, 31-60,61-90,>90, 
Missing)  
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Create only if >=5 subjects 
SAC 
3.51. 
 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent Immune 
Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Preferred terms identified in the 
focused list are summarized. 
[1] Subjects may be included in more 
than one category for 'Event 
Characteristics'. 
[2] Outcome worst case hierarchy: 
FATAL > NOT RECOVERED/NOT 
RESOLVED > 
RECOVERED/RESOVLED WITH 
SEQUELAE > 
RECOVERING/RESOLVING > 
RECOVERED/RESOLVED 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.52. 
 
mITT 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Treatment-Emergent Cytokine Release Syndrome (CRS) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
AEs which start or worsen on or after T-
cell infusion are classified as treatment 
emergent. 
Study Day is relative to the day of first 
T-cell Infusion, which is Study Day 1 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse events with partial or missing 
dates are not used in time of onset and 
duration derivations 
Time to onset from T-cell infuion (days) 
(<-8, -8-1,1-14,15-30,31-60,>60)  
Duration (days) (1-30, 31-60,61-90,>90, 
Missing)  
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Create only if at least 5 subjects  
 
COVID-related 
3.53. 
 
ITT 
AE1 
Summary of COVID-19-Related Adverse Events by System 
Organ Class and Preferred Term 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Create only if at least 5 subjects  
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
SAC 


 
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Programming Notes 
Deliverable 
[Priority] 
3.54. 
 
ITT 
PAN1 
Summary of COVID-19 Assessments for Subjects with COVID-
19 Adverse Events 
Sections 1 & 2 of Impact of COVID-19 
on Assessment of Safety in Clinical 
Trials – Points to Consider 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Create only if at least 5 subjects  
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
SAC 
Deaths 
3.55. 
 
mITT 
DD1  
Summary of Deaths 
IDSL 
Time to death from t-cell infusion  is 
reported in days.  
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
 
Laboratory: Chemistry 
3.56. 
 
mITT 
LB1 
Summary of Post-Baseline Change of Chemistry Values by Visit 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 


 
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Deliverable 
[Priority] 
N = Number of subjects per treatment 
group. Calculate n, min, mean, max, 
median, SD by test and visit 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
3.57. 
 
mITT 
LB16A 
 
Summary of Chemistry Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline 
ICH E3 
Includes all labs which are graded by 
CTCAE 
Include worst case post-baseline, and 
at all planned timepoints 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.58. 
 
mITT 
LB15A 
Summary of Worst Case Chemistry Results Relative to Normal 
Range Post-Baseline Relative to Baseline 
ICH E3 
This table will include all labs which are 
NOT graded by CTCAE 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
IA, SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
 
Laboratory: Hematology 
3.59. 
 
mITT 
LB1 
Summary of Post-Baseline Change of Hematology Values by 
Visit 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
N = Number of subjects per treatment 
group. Calculate n, min, mean, max, 
median, SD by test and visit 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.60. 
 
mITT 
LB16A 
 
Summary of Hematology Results by Maximum Grade Increase 
Post-Baseline Relative to Baseline 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
For labs that are gradeable by CTCAE 
Include worst case post-baseline, and 
at all planned timepoints 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
 
3.61. 
 
mITT 
LB15A 
Summary of Worst Case Hematology Results Relative to Normal 
Range Post-Baseline Relative to Baseline 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
This table will include all labs which are 
NOT graded by CTCAE 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
 
IA, SAC 
Laboratory: Urinalysis 
3.62. 
 
mITT 
UR1 
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline 
ICH E3 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Little n does not include Not done or No 
results. 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
 
Laboratory: Hepatobiliary (Liver) 
3.63. 
 
mITT 
LIVER1 
Summary of Liver Monitoring/Stopping Event Reporting 
GSK Statistical Display Standard 
 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Only required if liver stopping event 
form is filled and minimum of 5 subjects 
with event. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.64. 
 
 mITT 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
GSK Statistical Display Standard  
If >=10 events then create both the 
summary table and the listing LIVER13. 
If <10 events, only create listing 
LIVER13. 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
ECG 
3.65. 
 
mITT 
EG10 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category 
GSK Statistical Display Standard 
 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
 
Only QTcF will be reported. If missing, 
then calculate based on derivation 
provided in the RAP. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
 
SAC 
3.66. 
 
mITT 
EG11 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category 
GSK Statistical Display Standard  
 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
Only QTcF will be reported. If missing, 
then calculate based on derivation 
provided in the RAP. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Vital Signs 
3.67. 
 
mITT 
VS7 
Summary of Worst Case Change in Vital Sign Results Relative 
to Potential Clinical Importance (PCI) Criteria Post-Baseline 
Relative to Baseline 
ICH E3 
Heart rate, pulse oximetry, temperature, 
SBP, DBP 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
Cardiovascular Risk Factors 
3.68. 
 
mITT 
SU1 
Summary of Substance Use 
GSK Statistical Display Standard  
 
Smoking History 
Smokeless Tobacco Use 
Betel quid-areca nut use 
Alcohol use  
SAC 


 
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Safety: Tables 
No. 
Populati
on 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Nicotene oral/topical use 
Include Baseline visit only 
Required by GCSP 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Performance Status 
3.69. 
 
mITT 
PS1A 
Summary of ECOG Performance Status 
ICH E3 
All planned assessments (Only 
includeing baseline and last 
assessment post-infusion) 
(not by visit) 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.70. 
 
mITT 
PS3A 
Summary of Change in ECOG Performance Status from 
Baseline 
ICH E3 
SAC 


 
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Safety: Tables 
No. 
Populati
on 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Include all planned visits, best and 
worst case post-baseline, don’t include 
baseline visit 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
Biomarker 
3.71. 
 
mITT 
Custom: 
SAFE_T4 
Summary of Subjects Showing >1% Gene Marked PBMCs 1 
Year Post-Treatment 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
Use actual treatment, separate table for 
each arm. Arm C table has three 
columns: Arm C (lete-cel monotherapy), 
Arm C (lete-cel + Pembrolizumab) and 
Arm C (Total) 
 
SAC 
3.72. 
 
mITT 
Custom: 
SAFE_T4 
Summary of Replication Competent Lentivirus Positive 
n reflects the number of subjects with 
RCL assessed post T-cell infusion. 
Note: for Arm A patients treated with 
pembrolizumab, do not exclude data 
after the first dose of pembrolizumab 
Footnote: Modified Intent-to-Treat 
population includes all participants who 
received lete-cel infusion. 
SAC 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 6 3  
 
S af et y : T a bl e s 
N o.  
P o p ul ati
o n  
G S K St a n d ar d / 
E x a m pl e S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
Us e act u al tr e at m e nt, s e p ar at e t a bl e f or 
e ac h ar m. Ar m C t a bl e h as t hr e e 
c ol u m ns: Ar m C (l et e-c el m o n ot h er a py), 
Ar m C (l et e -c el + P e m br oliz u m a b) a n d 
Ar m C ( T ot al)  
 
 
 
C CI


 
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13.10.9. 
Safety Figures 
Safety: Figures 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Laboratory: Hematology 
3.1.  
mITT 
Custom: 
SAFE_F3 
Hematology Values Over Time (Neutrophils) 
Show each treatment including the 
total on a separate page (actual 
treatment) 
Include Total 
Footnote: Modified Intent-to-Treat 
population includes all participants 
who received lete-cel infusion. 
SAC 
3.2.  
mITT 
Custom: 
SAFE_F3 
Hematology Values Over Time (Hemoglobin) 
Show each treatment including the 
total on a separate page (actual 
treatment) 
Include Total 
Footnote: Modified Intent-to-Treat 
population includes all participants 
who received lete-cel infusion. 
SAC 
3.3.  
mITT 
Custom: 
SAFE_F3 
Hematology Values Over Time (Platelets) 
Show each treatment including the 
total on a separate page (actual 
treatment) 
Include Total 
Footnote: Modified Intent-to-Treat 
population includes all participants 
who received lete-cel infusion. 
SAC 


 
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Safety: Figures 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.4.  
mITT 
Custom: 
SAFE_F3 
Hematology Values Over Time (Lymphocytes) 
Show each treatment including the 
total on a separate page (actual 
treatment) 
Include Total 
Footnote: Modified Intent-to-Treat 
population includes all participants 
who received lete-cel infusion. 
SAC 
Laboratory: Hepatobiliary (Liver) 
3.5.  
mITT 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT 
GSK Statistical Display Standard  
Show each treatment including the 
total on a separate page (actual 
treatment) 
 
Footnote: Modified Intent-to-Treat 
population includes all participants 
who received lete-cel infusion. 
SAC 
3.6.  
mITT 
LIVER9 
Scatter Plot of Maximum Total Bilirubin vs Maximum ALT – 
eDISH Plot 
GSK Statistical Display Standard  
Show each treatment including the 
total on a separate page (actual 
treatment) 
 
Footnote: Modified Intent-to-Treat 
population includes all participants 
who received lete-cel infusion. 
SAC 
 


 
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13.10.10. Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Pharmacokinetic Parameters 
4.1.  
PK 
PK03 
Summary of Derived GSK3377794 Pharmacokinetic 
Parameters 
GSK Statistical Display Standard  
 
The Pharmacokinetic population 
includes all participants in the mITT 
population from whom at least one PK 
sample was obtained, analyzed, and 
was measurable.   
 
Include Cmax, AUC and Tmax 
parameters. Calculate n, min, 
arithmetic mean, 95% CI, max, median 
and SD 
Display as Arm A, Arm C, Overall 
IA, SAC 
4.2.  
PK 
PK05 
Summary of Derived Log-Transformed GSK3377794 
Pharmacokinetic Parameters 
The Pharmacokinetic population 
includes all participants in the mITT 
population from whom at least one PK 
sample was obtained, analyzed, and 
was measurable.   
 
Include Cmax and AUC, Exclude Tmax 
parameter.  Calculate n, geometric 
mean , 95% CI, %CVb and SD (Logs) 
Display as Arm A, Arm C, Overall 
IA, SAC 
 


 
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13.10.11. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
GSK Standard 
/ Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.3
PK 
Custom: 
PK_F1 
GSK3377794 Pharmacokinetic Concentration-Time Plot 
GSK Statistical Display Standard  
The Pharmacokinetic population 
includes all participants in the mITT 
population from whom at least one PK 
sample was obtained, analyzed, and 
was measurable.   
Label x-axis=0 as "Pre T-cell". 
Plot each subject using a different 
coloured line and list all subjects in x-
axis legend. 
Y-axis is log transformed (not the 
values). 
Values <1 are set to 1. 
Display as Arm A, Arm C, Overall 
IA, SAC 
 


 
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13.10.12. ICH Listings 
ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.  
ITT 
ES2  
Listing of Reasons for Study Withdrawal 
ICH E3 
Identify all analysis population for each 
subject in the first column under analysis 
population. 
 
Add a flag variable to indicate withdrawal 
due to COVID 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC 
2.  
Pembrolizumab 
SD2  
Listing of Reasons for Study Treatment Discontinuation 
(Pembrolizumab) 
ICH E3 
Only include study treatment 
discontinuation of pembro 
This display will be created for Arms A 
and C. The Arm A listing should only 
contain those patients who received 
pembro following PD after lete-cel dosing 
 
Flag study treatment that is discontinued 
due to COVID-19 
Footnote: 
IA, SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Pembrolizumab population includes all 
participants in the mITT population who 
received at least one infusion of 
pembrolizumab. 
Protocol Deviation 
3.  
ITT 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
Flag  which PDs are COVID-related 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC 
4.  
ITT 
DV2 
Listing of Non-Important Protocol Deviations due to COVID-19 
Pandemic 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
5.  
ITT 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
Populations Analysed 
6.  
Screened 
SP3 
Listing of Subjects Excluded from Any Population 
ICH E3 
Enrolled, ITT, mITT, PK 
SAC 
Demographic and Baseline Characteristics 
7.  
ITT 
DM2  
Listing of Demographic Characteristics 
ICH E3 
Add BMI, BSA 
SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
8.  
ITT 
DM9 
Listing of Race 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
Exposure and Treatment Compliance 
9.  
ITT 
Custom: 
POP_L1 
Listing of Exposure to T-cell Infusion 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC 
10.  
ITT 
EX3 
Listing of Exposure Data 
Be sure to add Pembro as a treatment 
where applicable 
Cumulative dose column should list 
total number of transduced cell 
dose. 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 7 1  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
G S K 
St a n d ar d  / 
E x a m pl e 
S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
Re s p o n s e  
1 1.   
I T T 
L A 5  
Listi ng of I nv esti g ator -Ass ess ed L esio n Ass ess m e nts 
( R E CI S T 1. 1 Crit eri a) 
I C H E 3 
F or Ar m A , pl e as e a d d a fl a g f or all 
r es p o ns e ass ess m e nts p ost-P D  
F o ot n ot e: I nt e nt -t o-Tr e at p o p ul atio n 
i ncl u d es all p artici p a nts w h o st art e d t h e 
l e uk a p h er esis pr oc e d ur e. 
 
S A C  
1 2.   
I T T 
R E 5  
Listi ng of I nv esti g ator -Ass ess ed R es p o ns es at E ac h Visit with 
C o nfir m atio n ( R E CI S T 1. 1 Criteri a)  
I C H E 3 
F or Ar m A, pl e as e a d d a fl a g f or all 
r es p o ns e ass ess m e nts p ost -P D  
F o ot n ot e: I nt e nt -t o-Tr e at p o p ul atio n 
i ncl u d es all p artici p a nts w h o st art e d t h e 
l e uk a p h er esis pr oc e d ur e. 
 
S A C  
C CI


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
Time to Response 
15.  
mITT 
TTE9 
Listing of Time to Response 
Use T-cell infusion date 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
SAC 
16.  
mITT 
TTE9 
Listing of Progression-Free Survival 
Use T-cell infusion date 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
SAC 
17.  
mITT 
TTE9 
Listing of Duration of Response Based on Investigator-
Assessed Response 
Use T-cell infusion date 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
SAC 
18.  
mITT 
TTE9 
Listing of Overall Survival 
Use T-cell Infusion date 
Modified Intent-to-Treat population 
includes all participants who received 
lete-cel infusion. 
SAC 
Adverse Events 
19.  
ITT 
Custom: 
SAFE_L9  
Listing of All Adverse Events 
ICH E3 
List overall record on 1st line  
(ANL01FL='Y') followed by a row for each 
event segment order by start date, 
segments are linked by AEREFID 
IA, SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Overall record line will contain all phases 
where event started or worsend in 
phase(LEUKEMFL/LYMEMFL/TRTEMFL) 
concatenated in the Overall Phase(s) 
column  
An event can have multiple phases and 
will be determined whether the AE started 
or worsened in a given phase. For 
example, an AE started in Leukapheresis 
phase, continued into but did not worsen 
in the lymphodepletion phase and 
continued in and worsened in the T-cell 
infusion, will have two phases assigned: 
Leukapheresis (LEUKEMFL=1) & T-cell 
Infusion (TRTEMFL=Y). 
This listing shall include outcome of AE 
as well (i.e. dose reduced, etc) 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
 
20.  
ITT 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
All AEs 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Serious and Other Significant Adverse Events 
21.  
ITT 
AE14 
Listing of Reasons for Considering as a Serious Adverse 
Event 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC 
22.  
ITT 
Custom: 
SAFE_L11 
Listing of Non-Fatal Serious Adverse Events 
ICH E3 
List overall record on 1st line  
(ANL01FL='Y') followed by a row for each 
event segment order by start date, 
segments are linked by AEREFID 
Overall record line will contain all phases 
where event started or worsend in 
phase(LEUKEMFL/LYMEMFL/TRTEMFL) 
concatenated in the Overall Phase(s) 
column  
An event can have multiple phases and 
will be determined whether the AE started 
or worsened in a given phase. For 
example, an AE started in Leukapheresis 
phase, continued into but did not worsen 
in the lymphodepletion phase and 
continued in and worsened in the T-cell 
infusion, will have two phases assigned: 
Leukapheresis (LEUKEMFL=1) & T-cell 
Infusion (TRTEMFL=Y). 
IA, SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
 
23.  
ITT 
Custom: 
SAFE_L11 
Listing of Delayed Adverse Events by Delayed Category 
(GSK Adjudicated) 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
Use “Time Since T-cell Infusion” instead 
of Time Since First Dose/Time Since Last 
Dose. 
Report Site ID/unique subject ID/subject 
ID 
 
SAC 
24.  
ITT 
AE8 
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment or Withdrawal from Study 
ICH E3 
Specify if due to T-cell or pembro 
Flag if COVID-19 AE 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
IA, SAC  
Adverse Events of Special Interest 
25.  
ITT 
Custom: 
SAFE_L10 
Cytokine Release Syndrome (CRS) Subject Profile 
See CGT mock up for details 
SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
26.  
ITT 
Custom: 
SAFE_L11 
Pancytopenia/Aplastic Anemia Subject Profile 
See CGT mock up for details 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
27.  
ITT 
Custom: 
SAFE_L12 
Pneumonia Subject Profile 
See CGT mock up for details 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
28.  
ITT 
Custom: 
SAFE_L13 
Pneumonitis Subject Profile 
See CGT mock up for details 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
29.  
ITT 
Custom: 
SAFE_L14 
Graft vs Host Disease (GvHD) Subject Profile 
See CGT mock up for details 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
30.  
ITT 
Custom: 
SAFE_L15 
Immune Effector Cell-Associated Neurotoxicity syndrome 
(ICANS) Subject Profile 
See CGT mock up for details 
SAC 


 
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ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
31.  
ITT 
Custom: 
SAFE_L16 
Guillain-Barre Syndrome (GBS) Subject Profile 
See CGT mock up for details 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
SAC 
All Laboratory 
32.  
ITT 
LB5A 
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance 
ICH E3 
May want to include PCI flag (as seen in 
LB5) 
 
SAC] 
33.  
ITT 
UR2 
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
 
 
SAC 
34.  
ITT 
EG3 
Listing of All ECG Values 
ICH E3 
 
Show all values and indicate potential 
clinical importance QTc, QTcB, and QTcF 
values. 
Footnote: Intent-to-Treat population 
includes all participants who started the 
leukapheresis procedure. 
SAC 


 
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No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
 
 
13.10.13. Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition  
35.  
Screened 
ES7 
Listing of Reasons for Screen Failure 
Footnote: Screened population 
includes all participants who signed 
an ICF to participate in the study. 
SAC 
Protocol Deviation 
36.  
ITT 
PAN5 
Country Level Listing of Start Dates of COVID-19 Pandemic 
Measures 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
37.  
ITT 
PAN7 
Listing of Visits impacted by COVID-19 Pandemic 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Disease Characteristics 
38.  
ITT 
DC3 
Listing of Disease Characteristics at Initial Diagnosis 
Stage of Lung Cancer at Initial 
Diagnosis 
Disease Stage at Time of Enrolment 
Time from Initial Diagnosis to 
Leukapheresis Eligibility Screening 
(months) 
Histology and Histology Grade at 
Initial Diagnosis  
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
39.  
ITT 
DC4 
Listing of Disease Characteristics at Screening 
Stage at Screening 
Number of Prior Systemic Therapy 
Regimens 
Number of Prior Radiotherapy 
Regimens 
LAGE1 status 
HLA status 
NY-ESO-1 status 
Status of visceral/nonvisceral 
disease 
Measurable Disease at Screening? 
Non-target Lesions? 
TNM Staging at Baseline 
Time from last progression to 
leukapheresis eligibility screening 
(months) 
Time from last recurrence to 
leukapheresis eligibility screening 
(months) 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
40.  
ITT 
MD2 
Listing of Metastatic Disease at Screening 
IDSL 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
Anti-Cancer Therapy 
41.  
ITT 
AC6 
Listing of Systemic Anti-Cancer Therapy 
Add a column for Phase [Prior, Prior: 
Bridging, On-study]. 
 
Footnote: Therapies and procedures 
prior to leukapheresis or full lines of 
therapy given between leukaphersis 
and lymphodepletion are defined as 
prior. Bridging therapy is defined as 
supportive systemic therapy given 
between leukapheresis and 
lymphodepletion to maintain disease 
control. 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
42.  
ITT 
AC7 
Listing of Anti-Cancer Radiotherapy 
Add a column for Phase [Prior,  On-
study]. 
 
Footnote: Therapies and procedures 
prior to leukapheresis or full lines of 
therapy given between leukaphersis 
and lymphodepletion are defined as 
prior. 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
Prior and Concomitant Medications 
43.  
ITT 
CM3 
Listing of Concomitant Medications by Ingredient 
Should include blood products/blood 
supportive care products 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
44.  
ITT 
MH2 
Listing of Past and Current Medical Conditions 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Dose Modifications 
45.  
ITT 
ODMOD12A 
Listing of Lymphodepletion Chemotherapy Dose Delays 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
46.  
ITT 
ODMOD10A 
Listing of Lymphodepletion Chemotherapy Dose 
Reductions 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
47.  
Pembrolizumab 
ODMOD12A 
Listing of Dose Delays (Pembrolizumab) 
This listing will be created for Arms 
A and C. The Arm A listing should 
only contain those patients who 
received pembro following PD after 
lete-cel dosing 
Do not include Duration of Delay 
column 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
48.  
Pembrolizumab 
ODMOD14A 
Listing of Incomplete Infusions (Pembrolizumab) 
This listing will be created for Arms 
A and C. The Arm A listing should 
only contain those patients who 
received pembro following PD after 
lete-cel dosing 
Footnote: Pembrolizumab population 
includes all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
SAC 
49.  
Pembrolizumab 
ODMOD17A 
Listing of Infusion Interruptions (Pembrolizumab) 
This listing will be created for Arms 
A and C. The Arm A listing should 
only contain those patients who 
received pembro following PD after 
lete-cel dosing 
Footnote: 
Pembrolizumab population includes 
all participants in the mITT 
population who received at least one 
infusion of pembrolizumab. 
SAC 
Hepatobiliary (Liver) 
50.  
ITT 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting  
GSK Hepatic Safety Panel  
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
51.  
ITT 
LIVER15 
Liver Stopping Event Profile 
GSK Hepatic Safety Panel 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
52.  
ITT 
LIVER13 
Listing of Subjects Meeting Hepatobiliary Laboratory 
Criteria Post-Baseline 
Listing used instead of table if <10 
events 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
Other Safety 
53.  
ITT 
PREG1 
Listing of Subjects or Partners of Subjects Who Became 
Pregnant During the Study  
GSK Statistical Display Standard 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
 
SAC 
54.  
ITT 
LVEF2 
Listing of Left Ventricular Ejection Fraction Results 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
55.  
ITT 
PAN12 
Listing of COVID-19 Assessments and Symptom 
Assessments for Subjects with COVID-19 Adverse Events 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
56.  
ITT 
ARR1 
Patient Profile for Arrythmias 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
57.  
ITT 
CHF1 
Patient Profile for Congestive Heart Failure 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
58.  
ITT 
CVATIA1 
Patient Profile for Cerebrovascular Events, Stroke and 
Transient Ischemic Attack 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
59.  
ITT 
DVT1 
Patient Profile for Deep Vein Thrombosis/Pulmonary 
Embolism 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
60.  
ITT 
MI1 
Patient Profile for Myocardial Infarction  
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
61.  
ITT 
PATE1 
Patient Profile for Peripheral Arterial Thromboembolism 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
62.  
ITT 
PUL1 
Patient Profile for Pulmonary Hypertension 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
63.  
ITT 
REV1 
Patient Profile for Revascularisation 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
64.  
ITT 
VAL1 
Patient Profile for Valvulopathy 
GSK Statistical Display Standard 
Only produce if a subject 
experiences this CV event 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
65.  
ITT 
DD3 
Subject Profile for Death 
ICH E3 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
GSK 
Standard / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Substance Use 
66.  
ITT 
SU2 
Listing of Substance Use 
List smoking history, smokeless 
tobacco use, betel quid/areca nut 
use, cigarettes per day, years 
smoked, and current nicotine use 
 
Replace Study day with ”Time from 
lete-cel infusion” 
Footnote: Intent-to-Treat population 
includes all participants who started 
the leukapheresis procedure. 
 
SAC 
Biomarker 
67.  
mITT 
Custom: 
SAFE_L7 
Listing of Subjects with Integration Site Analysis Data 
Produce a null report if there is no 
data to report 
Modified Intent-to-Treat population 
includes all participants who 
received lete-cel infusion. 
SAC 
68.  
mITT 
Custom: 
SAFE_L8 
Listing of Replication Competent Lentivirus Data 
For “Analysis Pop” in first column, 
include only the non-default 
populations (i.e. Evaluable, Pembro, 
PK) 
Modified Intent-to-Treat population 
includes all participants who 
received lete-cel infusion. 
SAC 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 9 0  
 
N o n -I C H: Li sti n g s 
N o.  
P o p ul ati o n  
G S K 
St a n d ar d  / 
E x a m pl e 
S h ell  
Titl e   
Pr o gr a m mi n g N ot e s  
D eli v er a bl e 
[ Pri orit y] 
P K E n d p oi nt s  
7 0.   
P K  
P K 0 7  
Listi ng of G S K 3 3 7 7 79 4 P h ar mac okin etic C o nc entr atio n -
Ti m e D at a  
 
S A C   
7 1.   
P K  
P K 1 3  
Listi ng of D eriv e d G S K 3 3 7 7 794 P h ar m acokin etic 
P ar a m et ers  
 
S A C  
 
C CI


 
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13.11. 
Appendix 13: Custom Mock-ups 
13.11.1. 
Study Population 
13.11.1.1. Tables 
N/A 
13.11.1.2. Figures 
N/A 
 
 


 
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13.11.2. 
Efficacy 
13.11.2.1. Tables 
13.11.2.1.1. 
EFF_T1: Summary of Time to Response Based on Investigator Assessment (RECIST 1.1 Criteria) 
Protocol: ABC123456 
Page 1 of x 
Population: study specific 
(Data as of: DDMMMYYYY) 
Table X.XX 
 
 
Arm A 
Arm C 
  
(N=xxx) 
(N=xxx) 
 
Number of  responders 
 xx (yy%) 
 xx (yy%) 
 
 
 
Time to Response (months) 
 
 
  Min 
x 
x 
  1st Quartile 
x.x 
x.x 
  Median 
x.x 
x.x 
  3rd Quartile 
x.xx 
x.xx 
  Max. 
x 
x 
 
 
 
 
/Directory/program.sas  DDMMMYYYY HH:MM  
  
 
 


 
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13.11.2.1.2. 
EFF_T2: Summary of [Time-to-Event Endpoint] 
Protocol: ABC123456 
Page 1 of 1 
Population: Intent-to-Treat/Safety/Other study specific 
 
(Data as of: 
30MAY2011) 
Table X 
  
Summary of [Time-to-
Event Endpoint] 
  
  
Arm A 
Arm C 
  
  
(N = 300) 
(N = 100) 
  
  
  
Number of Subjects 
  
  
n 
200 
150 
  
  Endpoint (event) 
 255 (85%) 
 175 (88%) 
  
Event sub-category 
  
 100 (50%) 
  
Event sub-category 
  
  75 (38%) 
  
Censored 
  45 (15%) 
  25 (13%) 
  


 
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Follow-up ended 
  25  (8%) 
  10  (5%) 
  
Follow-up ongoing 
  20  (7%) 
  15  (8%) 
  
  
  
Estimates for Time Variable 
(TimeUnit)[1] 
  
  1st Quartile 
12.3 
13.2 
  
    95% CI 
(10.1,14.5) 
(10.8,15.1) 
  
  Median 
12.3 
13.2 
  
    95% CI 
(10.1,14.5) 
(10.8,15.1) 
  
  3rd Quartile 
12.3 
13.2 
  
    95% CI 
(10.1,14.5) 
(10.8,15.1) 
  
  
Probability of [Time-to-Event] at 
[timepoint 1] [1]  
  
  Number of subjects at Risk 
xx 
xx 
  
  Estimate 
12.3 
12.3 
  
  95% CI 
(10.1,14.5) 
(10.1,14.5) 
  


 
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Probability of [Time-to-Event] at 
[timepoint 2] [1]  
 
 
  
  Number of subjects at Risk 
xx 
xx 
  
  Estimate 
13.2 
13.2 
  
  95% CI 
(10.8,15.1) 
(10.8,15.1) 
  
  
Probability of [Time-to-Event] at 
[timepoint 2] [1]  
  
  Number of subjects at Risk 
xx 
xx 
  
  Estimate 
13.2 
13.2 
  
  95% CI 
(10.8,15.1) 
(10.8,15.1) 
  
[1] Confidence Intervals estimated using the Brookmeyer Crowley method 
 
 
 
 


 
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13.11.2.1.3. EFF_T3: Summary of Reverse Kaplan-Meier Estimates for [Progression Free/Overall] Survival Follow-up (RECIST 
1.1 Criteria) 
 
Protocol: ABC123456 
Page 1 of 
1 
Population: Intent-to-Treat/Safety/Other study specific 
(Data as 
of: 
30MAY2011) 
Table X 
  
Summary of Reverse Kaplan-Meier 
Estimates for Progression Free 
Survival Follow-up 
  
  
Arm A 
Arm C 
  
  
(N = 300) 
(N = 200) 
  
  
  
Number of Subjects 
  
  
  Progressed or Died 
xx 
xx 
  
  Follow-up ongoing 
xx 
xx 
  
  Follow-up ended 
xx 
xx 
  
  
  
  
  
Estimates for PFS Follow-up 
(Months)[1][2]  
 
  
  
  1st Quartile 
12.3 
13.2 
  
    95% CI 
(10.1,14.5) 
(10.8,15.1) 
  
  Median 
12.3 
13.2 
  
    95% CI 
(10.1,14.5) 
(10.8,15.1) 
  
  3rd Quartile 
12.3 
13.2 
  
    95% CI 
(10.1,14.5) 
(10.8,15.1) 
  
  
  
  
  


 
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[1] Estimated using the reverse Kaplan-Meier method from investigator-assessed progression 
free survival values. 
[2] Confidence Intervals estimated using the Brookmeyer Crowley method. 
  
 
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 9 8  
 
 
1 3. 1 1. 2. 2.  Fi g ur e s  
1 3. 1 1. 2. 2. 1.  E F F _ F 1: S pi d er Pl ot of <I n v e sti g at or -A s s e s s e d > <I n d e p e n d e nt -R e vi e w er A s s e s s e d > P er c e nt C h a n g e fr o m B a s eli n e 
i n T ar g et L e si o n Di a m et er 
 
<f o ot n ot es as d efi n e d i n t h e pr o gr a m mi n g d oc u m e nt >  
/ Dir ect ory/ pr o gr a m.s as  D D M M M Y Y Y Y  H H :M M  
T h e i m a g e is us e d as t h e m ock ex a m pl e f or t his fi g ur e. All c o nt e nt m ust b e u p d at e d b as e d o n 2 0 8 4 7 1.  
 
 
 
 
 
 
 
 
 
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
1 9 9  
 
1 3. 1 1. 2. 2. 2.  
E F F _ F 3: Pl ot of D ur ati o n o n I nt er v e nti o n al P h a s e  
 
<f o ot n ot es as d efi n e d i n t h e pr o gr a m mi n g d oc u m e nt >  
/ Dir ect ory/ pr o gr a m.s as  D D M M M Y Y Y Y  H H :M M  
T h e i m a g e is us e d as t h e m ock ex a m pl e f or t his fi g ur e. All c o nt e nt m ust b e u p d at e d b as e d o n 2 0 8 4 7 1  n e e ds  
 
 
 
Pr ot oc ol: 2 0 8 4 7 1  
 
 
 
P a g e 1 of x  
Po p ul ati o n: St u dy S p ecific  
 
 
( D at a as of: D D M M M Y Y Y Y) 
Fi g ur e X  
Pl ot of D ur ati o n o n I nt erv e nti o n al Ph as e 
Tr e at m e nt: Ar m A / Ar m C  
 
P P D
P P D


 
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13.11.3. 
Safety 
13.11.3.1. Tables 
13.11.3.1.1. 
SAFE_T1: Summary of Time to Resolution of Persistent Clinically Significant <AESI> 
Protocol: ABC123456                              
 
 
Page 1 of 1 
Population: Intent-to-Treat/ Study specified 
 
 
(Data as of: 
DDMMMYY) 
 
 
 
 
Table x 
Summary of Time to Resolution of Persistent Clinically Significant <AESI> 
 
 
 
 
 
Arm C – 
Lete-cel 
Monotherapy 
Arm C – Lete-cel + 
Pembrolizumab 
Arm C -- Total 
Parameter 
(N=10) 
(N=10) 
(N=20) 
 
 
 
 
Subjects with Grade 3 or 4 [1] 
8 (80%) 
8 (80%) 
16 (80%) 
 
 
 
 
Subjects with Persistent Grade 3 or 4 at Month 1 [2] 
 
 
 
    n  
4 
4 
4 
Recovered [3] 
  2 (50%) 
  2 (50%) 
  2 (50%) 
Not recovered 
  2 (50%) 
  2 (50%) 
  2 (50%) 
Death  
  1 (25%) 
  1 (25%) 
  1 (25%) 
Ongoing  
0 
0 
0 
Lost to follow-up 
  1 (25%) 
  1 (25%) 
  1 (25%) 
 
 
 
 
Estimates of Time to Recovery (Days) [4] 
 
 
 
  1st Quartile 
12.3 
12.3 
12.3 
    95% CI 
(10.1,14.5) 
(10.1,14.5) 
(10.1,14.5) 
  Median 
12.3 
12.3 
12.3 


 
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    95% CI 
(10.1,14.5) 
(10.1,14.5) 
(10.1,14.5) 
  3rd Quartile 
12.3 
12.3 
12.3 
    95% CI 
(10.1,14.5) 
(10.1,14.5) 
(10.1,14.5) 
 
 
 
 
Recovery Probability  
 
 
 
  Recovery at Study Day 90 
0.82 
0.82 
0.82 
    95% CI 
(0.70,0.95) 
(0.70,0.95) 
(0.70,0.95) 
 
 
 
 
<analysis population definition as provided in the RAP/SAP.> 
NA = Not applicable. 
[1] Events occurring within 31 days post T-cell infusion 
[2] Events at last value within 31 days of T-cell infusion 
[3] Recovery defined as first time resolve to Grade 2 or below 
[4] Confidence Intervals estimated using the Brookmeyer Crowley method 
/Directory/program.sas  01JAN2002 12:01 
 
  
  
  
 
 
 
 
Note: this mock shell shows the column layout for Arm C, please refer to programming notes for details of how to display different arms in different treatment phases. 
 
 


 
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13.11.3.1.2. 
SAFE_T4: Multiple titles as defined in section 13.10.5 
Protocol: ABC123456                              
Page 1 of 1 
Population: Intent-to-Treat/ Study specified 
 
(Data as of: 
24APR2018) 
 
 
 
 
Table x.xx 
Multiple titles as defined in section 13.10.5 
 
 
 
 
 
Arm A 
Arm C 
Overall 
  
(N=10) 
(N=10) 
(N=20) 
<Replication Competent Lentivirus Positive> 
<>1% Gene Marked PBMCs 1 Year Post-treatment> 
n 
xx 
xx 
xx 
Count 
xx (yy%) 
xx (yy%) 
xx (yy%) 
<footnotes as defined in the programming document> 
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This is a mock example for this display. All content must be updated based on 208471 needs (please refer to Section 8 and programming notes for more details) 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 0 3  
 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 0 4  
 
 
 
C CI


 
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13.11.3.2. Figures 
13.11.3.2.1. SAFE_F3: <Lab Category> Values Over Time <Among Subjects With <Condition> on or After <Timepoint>> - <Lab 
Parameter> 
Protocol: ABC123456 
 
 
Page 1 of 1 
Population: Intent-to-Treat/Safety/Other study 
specific 
 
 
(Data as of: 30MAY2011) 
Figure x.xx 
Multiple titles as defined in section 13.12.9 
 
<footnotes as defined in the programming document> 
PPD


 
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13.11.4. 
Pharmacokinetics (PK) 
13.11.4.1. Tables 
N/A 
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 0 8  
 
1 3. 1 1. 4. 2.  Fi g ur e s  
1 3. 1 1. 4. 2. 1.  
P K _ F 1: G S K 3 3 7 7 7 9 4 P h ar m a c o ki n eti c C o n c e ntr ati o n -Ti m e Pl ot  
Pr ot oc ol: A B C 1 2 3 4 5 6  
 
 
P a g e 1 of 1  
P o p ul ati o n: As d efi n e d i n t h e R A P  
 
 
( D at a as of: 3 0 M A Y 2 0 1 1) 
Fi g ur e x.xx  
G S K 3 3 7 7 7 9 4 Ph ar m ac oki n etic C o nc e ntr ati o n -Ti m e Pl ot  
Tr e at m e nt: Ar m A / Ar m C  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o pi es p er micr o gr a m of g D N A  
Ti m e si nc e T -c ell I nf usi o n ( D a ys) 
Pr e T -
c ell 
P P D


 
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<footnotes as defined in the programming document> 
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C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 0  
 
1 3. 1 1. 5.  
I C H Li sti n g s 
1 3. 1 1. 5. 1.  P O P _ L 1: Li sti n g of E x p o s ur e t o T- c ell I nf u si o n  
P r o t o c o l :  A B C 1 2 3 4 5 6                               
 
 
 
P a g e  1  o f  x  
P o p u l a t i o n :  < a n a l y s i s  p o p u l a t i o n >  
 
( D a t a  a s  o f :  D D M M M Y Y Y Y )  
 
L i s t i n g   X  
 
L i s t i n g  o f  E x p o s u r e  t o  T - c e l l  I n f u s i o n  
 
 
 
 
 
 
 
 
 
  
 
T r e a t m e n t :  A r m  A  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
S i t e  I d . /  
U n i q u e  S u b j e c t  
I d . /   
S u b j e c t  I d .  /  
A n a l y s i s  P o p .  
S t a r t  D a t e /  
S t a r t  T i m e /  
S t a r t  D a y  
E n d  D a t e /  
E n d  T i m e /  
E n d  D a y  
T o t a l  C e l l  
D o s e  ( u n i t )  
T o t a l  N u m b e r  
o f  
T r a n s d u c e d  
C e l l s  
I n f u s e d  
( u n i t )  
P e r c e n t a g e  
o f  
M a n u f a c t u r e d  
C e l l s  
T r a n s d u c e d  
( % )  
A v e r a g e  
V e c t o r  
C o p y  
L o t  N u m b e r  
1  
L o t  
N u m b e r  
2  
 
 
 
 
 
 
 
 
 
 
 
S C R ,  E N R L ,  I T T ,  
S A F ,  m I T T  
0 0 8 /  
1 4 : 3 0 /  
1  
0 0 8 /  
1 4 : 3 0 /  
1  
x x . x x  
x x . x x  
x x . x x  
x x . x x  
A D 0 3 - 1 7 - P 2 -
0 4 3  
A D 0 3 -
1 7 - P 2 -
0 4 4  
 
 
 
 
 
 
 
 
 
 
 
S C R ,  E N R L ,  I T T ,  
2 0 0 8 /  
1 4 : 3 0 /  
1  
2 0 0 8 /  
1 4 : 3 0 /  
1  
x x . x x  
x x . x x  
x x . x x  
x x . x x  
A D 0 3 - 1 7 - P 2 -
0 4 3  
A D 0 3 -
1 7 - P 2 -
0 4 4  
 
 
 
 
 
 
 
 
 
  
 
 
P P D
P P D
P P D
P P D
P P D
P P D


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 1  
 
1 3. 1 1. 6.  
N o n -I C H Li sti n g s 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 2  
 
C CI


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 3  
 
1 3. 1 1. 6. 2.  S A F E _ L 7 : Li sti n g of I nt e gr ati o n Sit e A n al y si s R e s ult s 
 
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
 
 
 
 
P o p u l a t i o n :  I n t e n t - t o - T r e a t / S a f e t y / O t h e r  s t u d y  s p e c i f i c  
 
 
 
L i s t i n g  X  
L i s t i n g  o f  I n t e g r a t i o n  S i t e  A n a l y s i s  R e s u l t s  
 
 
 
 
 
 
 
[ A D x x . T R T A ]  
 
 
 
 
 
 
T r e a t m e n t :  A r m  A /  A r m  C  
 
 
 
 
[ A D x x . S I T E I D ]  
 
 
 
 
 
 
 
S i t e  I d . :  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A D x x . U S U B J I D /  
A D x x . S U B J I D /  
A D x x . A N A L P O P  
A D x x . A G E /  
A D x x . S E X /  
A D x x . R A C E  
A D x x . A V I S I T  
A D ? ? . ? ? D T C /  
A D ? ? . ? ? D Y  
? ? ?  
? ? ?  
? ? ?  
U n i q u e  S u b j e c t  
I d . /  
S u b j e c t  I d . /  
A n a l y s i s  P o p .  
A g e  ( Y E A R S ) /  
S e x /  
R a c e  D e t a i l  
[ V i s i t ]  o r  [ P l a n n e d  
T i m e ]  
D a t e /  
S t u d y  D a y  
S h a n n o n  
I n d e x  
( N o r m a l  
R a n g e )  
G i n i  I n d e x  
D N A  A m o u n t  
( n g )  
 
 
 
 
 
 
 
/ D i r e c t o r y / p r o g r a m . s a s   0 1 J A N 2 0 0 2  1 2 : 0 1  
  
  
  
  
 
 
P P D


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 4  
 
1 3. 1 1. 6. 3.  S A F E _ L 8 : Li sti n g of R e pli c ati o n C o m p et e nt L e nti vir u s D at a  
Pr ot oc ol: A B C 1 2 3 4 5 6  
 
 
 
P a g e 1 of 1  
P o p ul ati o n: St u d y s p ecific  
( D at a as of: D D M M M Y Y Y Y)  
Listi n g X 
Listi n g of R e plic ati o n C o m p et e nt L e nti vir us D at a 
 
 
 
 
 
Tr e at m e nt: Ar m A / Ar m C  
 
 
Sit e I d./  
U ni q u e S u bj ect I d./  
S u bj ect I d./  
A n al ysis P o p.  
A g e ( Y E A R S)/  
S ex/  
R ac e D et ail  
Visit  
D at e/  
St u d y D a y  
R CL I nt er pr eti v e R es ult  
S C R,  E N RL, I T T 
B as eli n e _ Pr e _L y m p h o  
Y Y Y Y - M M-D D/  
1 5  
N E G A TI V E  
 
 
D A Y x  
Y Y Y Y -M M -D D/  
1 5  
N E G A TI V E  
 
 
W E E K x  
Y Y Y Y - M M-D D/  
4 4  
N E G A TI V E  
 
 
M O N T H x  
Y Y Y Y -M M -D D/  
1 8 0  
N E G A TI V E  
 
 
C O M PL E TI O N / 
WI T H D R A W N  
Y Y Y Y - M M-D D/  
1 8 0  
N E G A TI V E  
 
 
 
 
 
 
 
 
 
 
/ Dir ect or y/ pr o gr a m.s as  0 1J A N 2 0 0 2 1 2: 0 1 
 
 
 
 
P P D
P P D


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 5  
 
1 3. 1 1. 6. 4.  S A F E _ L 9: Li sti n g of All A d v er s e E v e nt s; Li sti n g of N o n -F at al S eri o u s A d v er s e E v e nt s; Li sti n g of D el a y e d A d v er s e 
E v e nt s b y D el a y e d C at e g or y ( G S K A dj u di c at e d)   
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
 
 
 
 
 
 
P a g e  1  o f  x  
P o p u l a t i o n :  s t u d y  s p e c i f i c  
 
 
 
 
 
( D a t a  a s  o f :  D D M M M Y Y Y Y )  
L i s t i n g  X  
< T i t l e >  
< B y  D e l a y e d  A E  C a t e g o r y  ( o n l y  f o r  G S K  a d j u d i c a t e d  l i s t i n g ) >  
 
 
 
 
 
  
S i t e  I d . :  
 
 
 
 
 
 
 
  
T r e a t m e n t :  A r m  A  /  A r m  C  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
U n i q u e  S u b j e c t  I d . /  
S u b j e c t  I d . /  
A n a l y s i s  P o p .  
A g e  ( Y E A R S ) /  
S e x /  
R a c e  D e t a i l /  
W e i g h t  ( k g )   
P r e f e r r e d  T e r m /  
V e r b a t i m  T e x t   
O n s e t  D a t e /  
D a t e  o f  
R e s o l u t i o n /  
D u r a t i o n  ( D A Y S )  
T i m e  S i n c e  
T - C e l l  
I n f u s i o n  
M a x i m u m  G r a d e /  
O v e r a l l  
P h a s e ( s ) /  
S e r i o u s /  
S e g m e n t  
G r a d e /  
S e g m e n t  
P h a s e  
A c t i o n ( s )  T a k e n /  
O u t c o m e /  
R e l a t i o n  t o  S t u d y  
T r e a t m e n t  
I n v e s t i g a t o r  
A s s e s s e d  D e l a y e d  
A E  [ 1 ]  
 
 
 
 
 
 
 
 
S C R ,  I T T ,  m I T T  
N a s a l  c o n g e s t i o n  
a n d  b l o c k a g e /  
Y Y Y Y - M M - D D /  
Y Y Y Y - M M - D D /  
x x  
1 9 d  
1 /  
T - c e l l /  
Y  
 
D O S E  R E D U C E D /  
R E C O V E R E D / R E S O L V E
D /  
N  
Y e s :  < D e l a y e d  A E  
C a t e g o r y >  
 
 
 
 
 
 
 
  
S C R ,  I T T ,  m I T T ,  E V A L  
C a n d i d i a s i s  m o u t h  
1 9 9 9 - 0 5 - 0 4 /  
/  
3 6 d  
4 /  
L e u k ,  L y m p h ,  T -
c e l l /  
Y  
 
D R U G  W I T H D R A W N ,  
D O S E  R E D U C E D /  
N O T  R E C O V E R E D / N O T  
R E S O L V E D /   
N /  
Y :  T R T  A ,  T R T  B ,  
T R T  C  
N o  
 
 
 
Y Y Y Y - M M - D D /  
Y Y Y Y - M M - D D /  
x x  
 
 
2 /  
L e u k  
 
  
 
 
 
Y Y Y Y - M M - D D /  
Y Y Y Y - M M - D D /  
x x  
 
 
3 /  
L y m p h  
 
  
 
 
 
Y Y Y Y - M M - D D /  
Y Y Y Y - M M - D D /  
x x  
 
 
3 /  
T - c e l l   
 
  
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
CONFIDENTIAL 
 
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216 
 
 
 
 
YYYY-MM-DD/ 
YYYY-MM-DD/ 
xx 
 
 
4/ 
T-cell 
Infusion 
 
  
 
 
 
 
 
 
 
 
  
/Directory/program.sas  01JAN2002 12:01 
  
  
  
  
  
  
  
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 1 7  
 
1 3. 1 1. 6. 5.  S A F E _ L 1 0: C yt o ki n e R el e a s e S y n dr o m e ( C R S)  S u bj e ct Pr ofil e  
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
 
( D a t a  a s  o f :  
D D M M M Y Y Y Y )  
L i s t i n g  X  
 
C y t o k i n e  R e l e a s e  S y n d r o m e  ( C R S )  S u b j e c t  P r o f i l e  
 
 
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
 
S i t e  I d . :
 
 
U n i q u e  S u b j e c t  I d :
 
 
 
 
 
S u b j e c t  I d :
 
A g e  ( Y E A R S ) :
 
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
 
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :
 
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
  
 
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
 
R e f e r e n c e  I D  
x x x  
 
P r e f e r r e d  t e r m  
< t e x t >  
 
V e r b a t i m  t e r m  
< t e x t >  
 
P P D
P P D
P P D
P P D
P P D
P P D


 
CONFIDENTIAL 
 
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218 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ 
Serious 
4/ Leuk, Lymph, T-cell/ Y 
 


 
CONFIDENTIAL 
 
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219 
 
Seriousness Criteria 
Y: Results in Death, Is Life Threatening 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
DOSE INTERRUPTED/DELAYED 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
INFUSION INTERRUPTED BUT COMPLETED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
Signs and symptoms experienced by the 
subject 
Rash; Decreased Cardiac Output; Dyspnea 
  
Tests performed 
C-reactive Protein; Aspartate Amino Transferase 
  


 
CONFIDENTIAL 
 
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220 
 
Indication of Procedure/ Start Date/ 
Stop Date 
Supplemental Oxygen/ YYYY-MM-DD/ YYYY-MM-DD 
  
 
 
 
Reference ID 
xxx 
 
Preferred term 
<text> 
 
Verbatim term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ 
Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
NOT APPLICABLE 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
DOSE NOT CHANGED 
 
Related to study treatment(s) 
No 
 
Signs and symptoms experienced by the 
subject 
Rash, Decreased Cardiac Output, Dyspnea 
  
Tests performed 
C-reactive Protein, Aspartate Amino Transferase 
  


 
CONFIDENTIAL 
 
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221 
 
Indication of Procedure/ Onset Date/ 
Date Of Resolution 
Mechanical Ventilation Assisstance (e.g. C-PAP, 
Ventilator)/ 2020-11-10/ 2020-11-17 
  
 
 
 
All Adverse Events Suspected to be Linked 
to CRS 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ 
Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ 
Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
No 
 
 
 
 


 
CONFIDENTIAL 
 
208471 
 
222 
 
Concomitant Medication Information 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
Indication of Medication 
Vasopression; Intravenous fluids; Other Medication 
  
 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
Indication of Medication 
Vasopression; Intravenous fluids; Other Medication 
  
 
 
 


 
CONFIDENTIAL 
 
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223 
 
For definition of analysis populations refer to table x.xxx: Summary of Study Populations. 
 
AESI specific details. 
 
 
 
 
 
/Directory/program.sas  01JAN2002 12:01 
  
  
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 2 4  
 
1 3. 1 1. 6. 6.  S A F E _ L 1 1 : P a n c yt o p e ni a / A pl a sti c A n e mi a S u bj e ct Pr ofil e   
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
 
( D a t a  a s  o f :  
D D M M M Y Y Y Y )  
L i s t i n g  X  
 
P a n c y t o p e n i a  /  A p l a s t i c  A n e m i a  S u b j e c t  P r o f i l e  
 
 
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
 
S i t e  I d . :  
 
 
 
U n i q u e  S u b j e c t  I d :  
 
 
 
 
 
 
S u b j e c t  I d :
A g e  ( Y E A R S ) :
 
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
 
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :
 
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
  
 
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
 
R e f e r e n c e  I D  
x x x  
 
P r e f e r r e d  t e r m  
C o n f u s i o n a l  s t a t e  
 
V e r b a t i m  t e r m  
O n s e t  D a t e /  D a t e  o f  r e s o l u t i o n  
Y Y Y Y - M M - D D /  Y Y Y Y - M M - D D  
 
D u r a t i o n  ( D A Y S )  
x x x  
 
T i m e  S i n c e  T - C e l l  I n f u s i o n  ( D A Y S )  
x x x  
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
CONFIDENTIAL 
 
208471 
 
225 
 
Maximum Grade/ Overall Phase(s)/ Serious 
4/ Leuk, Lymph, T-cell/ Y 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
DOSE INTERRUPTED/DELAYED 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
INFUSION INTERRUPTED BUT COMPLETED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
Was treatment with G-CSF initiated? 
Yes or No 
 
Was immunosuppresive agent given? 
Yes or No 
 
Other Immunosuppression methods provided 
aggressive regimens 
 
 
 
 
Reference ID 
xxx 
 
Preferred term 
<text> 
 
Verbatim term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 


 
CONFIDENTIAL 
 
208471 
 
226 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
NOT APPLICABLE 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
DOSE NOT CHANGED 
 
Related to study treatment(s) 
No 
 
Was treatment with G-CSF initiated? 
Yes or No 
 
Was immunosuppresive agent given? 
Yes or No 
 
Other Immunosuppression methods provided 
aggressive regimens 
 
 
 
 
All Adverse Events Suspected to be Linked to P-AA 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 


 
CONFIDENTIAL 
 
208471 
 
227 
 
Related to study treatment(s) 
No 
 
 
 
 
Concomitant Medication Information 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date [time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
For definition of analysis populations refer to table x.xxx: Summary of Study Populations. 
 
AESI specific details. 
 
 
 
 
 
/Directory/program.sas  01JAN2002 12:01 
  
  
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 2 8  
 
1 3. 1 1. 6. 7.  S A F E _ L 1 2: P n e u m o ni a S u bj e ct Pr ofil e  
P r o t o c o l :  A B C 1 2 3 4 5 6  
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
( D a t a  a s  o f :  D D M M M Y Y Y Y )  
L i s t i n g  X  
P n e u m o n i a  S u b j e c t  P r o f i l e  
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
S i t e  I d . :  
 
U n i q u e  S u b j e c t  I d :  
 
 
 
S u b j e c t  I d :  
A g e  ( Y E A R S ) :
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
R e f e r e n c e  I D  
x x x  
P r e f e r r e d  t e r m  
< t e x t >  
V e r b a t i m  t e r m  
< t e x t >  
O n s e t  D a t e /  D a t e  o f  r e s o l u t i o n  
Y Y Y Y - M M - D D /  Y Y Y Y - M M - D D  
D u r a t i o n  ( D a y s )  
x x x  
T i m e  S i n c e  T - C e l l  I n f u s i o n  ( D A Y S )  
x x x  
M a x i m u m  G r a d e /  O v e r a l l  P h a s e ( s ) /  S e r i o u s  
4 /  L e u k ,  L y m p h ,  T - c e l l /  Y  
O u t c o m e  
N O T  R E C O V E R E D / R E S O L V E D  
A c t i o n  t a k e n :  C y c l o p h o s p h a m i d e  
D O S E  I N T E R R U P T E D / D E L A Y E D  
A c t i o n  t a k e n :  F l u d a r a b i n e  
N O T  A P P L I C A B L E  
A c t i o n  t a k e n :  G S K 3 3 7 7 7 9 4  
I N F U S I O N  I N T E R R U P T E D  B U T  C O M P L E T E D  
R e l a t e d  t o  s t u d y  t r e a t m e n t ( s )  
Y e s :  C y c l o p h o s p h a m i d e ;  G S K 3 3 7 7 7 9 4  
L e v e l  o f  c o u g h  
U s u a l  l e v e l  o f  c o u g h  
I n c r e a s e d  c o u g h  
P P D
P P D
P P D
P P D
P P D
P P D


 
CONFIDENTIAL 
 
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229 
 
Increased sputum purulence 
Yes 
No 
Unknown 
Did the chest auscultation show evidence of crackles/rales 
and/or bronchial or bronchovesicular breath sounds? 
Yes 
No 
Unknown 
Worsening dyspnea? 
Yes <Grade 1 or 2 or 3 or 4> 
No 
Temperature 
xxx 
Respiration rate 
xxx 
Was an x-ray performed? 
Yes 
No 
Was a culture/swab taken? 
Yes 
No 
Unknown 
Does subject have pleural effusion? 
Yes <specify location> 
No 
Unknown 
Does subject have hypoxemia? 
Yes 
No 
Unknown 
Does subject have WBC count performed at time of event? 
Yes <High WBC, Normal WBC, Low WBC> 
No 
Unknown 
Was BUN >19mg/dL (7mmol/L)? 
Yes 
No 
Unknown 
Was there evidence that the subject was confused? 
Yes 
No 
Unknown 


 
CONFIDENTIAL 
 
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230 
 
Was this subject in a health care setting (inpatient) when the 
pneumonia developed? 
Yes 
No 
Unknown 
 
 
Bacteria Culture 
 
Observation date 
YYYY-MM-DD 
Sample source for bacteria culture 
Blood 
Respiratory secretion 
Other 
Pathogen from pneumonia culture 
<list all pathogens> 
 
 
<Footnote 1> 
 
<Footnote …> 
 
<Footnote 9> 
 
/Directory/program.sas  DDMMMYYYY HH:MM 
 
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 3 1  
 
1 3. 1 1. 6. 8.  S A F E _ L 1 3: P n e u m o niti s S u bj e ct Pr ofil e  
P r o t o c o l :  A B C 1 2 3 4 5 6  
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
( D a t a  a s  o f :  D D M M M Y Y Y Y )  
L i s t i n g  X  
P n e u m o n i t i s  S u b j e c t  P r o f i l e  
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
S i t e  I d . :
 
U n i q u e  S u b j e c t  I d :  
 
 
 
 
S u b j e c t  I d :
A g e  ( Y E A R S ) :
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :  
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
R e f e r e n c e  I D  
x x x  
P r e f e r r e d  t e r m  
< t e x t >  
V e r b a t i m  t e r m  
< t e x t >  
O n s e t  D a t e /  D a t e  o f  r e s o l u t i o n  
Y Y Y Y - M M - D D /  Y Y Y Y - M M - D D  
D u r a t i o n  ( D a y s )  
x x x  
T i m e  S i n c e  T - C e l l  I n f u s i o n  ( D A Y S )  
x x x  
M a x i m u m  G r a d e /  O v e r a l l  P h a s e ( s ) /  S e r i o u s  
4 /  L e u k ,  L y m p h ,  T - c e l l /  Y  
O u t c o m e  
N O T  R E C O V E R E D / R E S O L V E D  
A c t i o n  t a k e n :  C y c l o p h o s p h a m i d e  
D O S E  I N T E R R U P T E D / D E L A Y E D  
A c t i o n  t a k e n :  F l u d a r a b i n e  
N O T  A P P L I C A B L E  
A c t i o n  t a k e n :  G S K 3 3 7 7 7 9 4  
I N F U S I O N  I N T E R R U P T E D  B U T  C O M P L E T E D  
R e l a t e d  t o  s t u d y  t r e a t m e n t ( s )  
Y e s :  C y c l o p h o s p h a m i d e ;  G S K 3 3 7 7 7 9 4  
C o u g h ?   
Y e s :  < m i l d ,  m o d e r a t e ,  s e v e r e >  
N o  
P P D
P P D
P P D
P P D
P P D
P P D


 
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Increased sputum purulence 
Yes: <is there blood in cough or sputum? Yes/no> 
No 
Did the chest auscultation show evidence of 
crackles/rales and/or bronchial or bronchovesicular breath 
sounds? 
Yes 
No 
Unknown 
Worsening dyspnea? 
Yes <Grade 1 or 2 or 3 or 4> 
No 
Temperature 
xxx 
Respiration rate 
xxx 
Was an x-ray performed? 
Yes 
No 
Was a blood test taken to check for other infections? 
Yes 
No 
Unknown 
Does subject have pleural effusion? 
Yes <specify location> 
No 
Unknown 
Does subject have hypoxemia? 
Yes 
No 
Unknown 
Does subject have WBC count performed at time of event? 
Yes <High WBC, Normal WBC, Low WBC> 
No 
Unknown 
Was this subject in a health care setting (inpatient) 
when the pneumonitis developed? 
Yes 
No 
Unknown 
 
 
Bacteria Culture 
 
Observation date 
YYYY-MM-DD 
Sample source for bacteria culture 
Blood 
Respiratory secretion 
Other <text> 


 
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233 
 
 
 
<Footnote 1> 
 
<Footnote …> 
 
<Footnote 9> 
 
/Directory/program.sas  DDMMMYYYY HH:MM 
 
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 3 4  
 
1 3. 1 1. 6. 9.  S A F E _ L 1 4 : Gr aft v s H o st Di s e a s e ( G v H D) S u bj e ct Pr ofil e 
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
 
( D a t a  a s  o f :  
D D M M M Y Y Y Y )  
L i s t i n g  X  
 
G r a f t - V e r s u s - H o s t  D i s e a s e  ( G V H D )  S u b j e c t  P r o f i l e  
 
 
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
 
S i t e  I d . :
 
 
U n i q u e  S u b j e c t  I d :  
 
 
 
 
 
 
S u b j e c t  I d :
A g e  ( Y E A R S ) :
 
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
 
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :
 
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
  
 
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
 
R e f e r e n c e  I D  
x x x  
 
P r e f e r r e d  t e r m  
C o n f u s i o n a l  s t a t e  
 
V e r b a t i m  t e r m  
O n s e t  D a t e /  D a t e  o f  r e s o l u t i o n  
Y Y Y Y - M M - D D /  Y Y Y Y - M M - D D  
 
D u r a t i o n  ( D A Y S )  
x x x  
 
T i m e  S i n c e  T - C e l l  I n f u s i o n  ( D A Y S )  
x x x  
 
M a x i m u m  G r a d e /  O v e r a l l  P h a s e ( s )  
4 /  L e u k ,  L y m p h ,  T - c e l l  
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
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Serious[: Criteria for determining 
seriousness] 
Y: Results in Death, Is life threatening, … 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
DOSE INTERRUPTED/DELAYED 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
INFUSION INTERRUPTED BUT COMPLETED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
Symptoms Experienced 
Fever, Rash, Nausea, … 
 
Tests Performed 
Alanine Amino Transferase, Bilirubin, … 
 
Biopsy Site 
<site> 
 
Medication Administered 
Corticosteroids - Prophylactic, Sirolimus, … 
 
 
 
 
Reference ID 
xxx 
 
Preferred term 
<text> 
 
Verbatim term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s) 
1/ T-cell 
 
Serious[: Criteria for determining 
seriousness] 
Y: Results in Death, Is life threatening, … 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
NOT APPLICABLE 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
DOSE NOT CHANGED 
 
Related to study treatment(s) 
No 
 
Symptoms Experienced 
Fever, Rash, Nausea, … 
 


 
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236 
 
Tests Performed 
Alanine Amino Transferase, Bilirubin, … 
 
Biopsy Site 
<site> 
 
Medication Administered 
Corticosteroids - Prophylactic, Sirolimus, … 
 
 
 
 
All Adverse Events Suspected to be Linked to GVHD 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s) 
1/ T-cell 
 
Serious[: Criteria for determining 
seriousness] 
Y: Results in Death, Is life threatening, … 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s) 
1/ T-cell 
 
Serious[: Criteria for determining 
seriousness] 
N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
No 
 
 
 
 
Concomitant Medication Information 
 
 


 
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237 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
For definition of analysis populations refer to table x.xxx: Summary of Study Populations. 
 
AESI specific details. 
 
 
 
 
 
/Directory/program.sas  01JAN2002 12:01 
  
  
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 3 8  
 
1 3. 1 1. 6. 1 0.  S A F E _ L 1 5 : I m m u n e Eff e ct or-C ell A s s o ci at e d N e ur ot o xi cit y S y n dr o m e (I C A N S) S u bj e ct Pr ofil e  
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
 
( D a t a  a s  o f :  
D D M M M Y Y Y Y )  
L i s t i n g  X  
 
I m m u n e  E f f e c t o r - C e l l  A s s o c i a t e d  N e u r o t o x i c i t y  S y n d r o m e  ( I C A N S )  S u b j e c t  P r o f i l e  
 
 
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
 
S i t e  I d . :
 
 
U n i q u e  S u b j e c t  I d :  
 
 
 
 
 
S u b j e c t  I d :
A g e  ( Y E A R S )
 
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
 
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :  
 
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
  
 
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
 
R e f e r e n c e  I D  
x x x  
 
P r e f e r r e d  t e r m  
C o n f u s i o n a l  s t a t e  
 
V e r b a t i m  t e r m  
O n s e t  D a t e /  D a t e  o f  r e s o l u t i o n  
Y Y Y Y - M M - D D /  Y Y Y Y - M M - D D  
 
D u r a t i o n  ( D A Y S )  
x x x  
 
T i m e  S i n c e  T - C e l l  I n f u s i o n  ( D A Y S )  
x x x  
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
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Maximum Grade/ Overall Phase(s)/ Serious 
4/ Leuk, Lymph, T-cell/ Y 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
DOSE INTERRUPTED/DELAYED 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
INFUSION INTERRUPTED BUT COMPLETED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
Participant received anti-seizure prophylaxis 
Yes: <treatment name> 
No 
 
ICANS panel completed for the participant 
Yes: <value from predefined drop down options> 
No: <reason> 
 
 
 
 
Reference ID 
xxx 
 
Preferred term 
<text> 
 
Verbatim term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
NOT APPLICABLE 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
DOSE NOT CHANGED 
 


 
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240 
 
Related to study treatment(s) 
No 
 
Participant received anti-seizure prophylaxis 
Yes: <treatment name> 
No 
 
ICANS panel completed for the participant 
Yes: <value from predefined drop down options> 
No: <reason> 
 
 
 
 
All Adverse Events Suspected to be Linked to ICANS 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
No 
 
 
 
 


 
CONFIDENTIAL 
 
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241 
 
Concomitant Medication Information 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
For definition of analysis populations refer to table x.xxx: Summary of Study Populations. 
 
AESI specific details. 
 
 
 
 
 
/Directory/program.sas  01JAN2002 12:01 
  
  
 
 


 
C O N FI D E N TI A L  
 
2 0 8 4 7 1  
 
2 4 2  
 
1 3. 1 1. 6. 1 1.  S A F E _ L 1 6 : G uill ai n-B arr e S y n dr o m e ( G B S) S u bj e ct Pr ofil e  
P r o t o c o l :  A B C 1 2 3 4 5 6  
 
P a g e  1  o f  x  
P o p u l a t i o n :  < s t u d y  s p e c i f i e d >  
 
( D a t a  a s  o f :  
D D M M M Y Y Y Y )  
L i s t i n g  X  
 
G u i l l i a n - B a r r e  S y n d r o m e  ( G B S )  S u b j e c t  P r o f i l e  
 
 
 
 
T r e a t m e n t :  G S K  T r e a t m e n t  
 
 
S i t e  I d . :
 
 
U n i q u e  S u b j e c t  I d :  
 
 
 
 
 
 
S u b j e c t  I d :
A g e  ( Y E A R S ) :
 
 
A n a l y s i s  P o p u l a t i o n :  S C R ,  I T T ,  S A F ,  m I T T  
S e x :
 
S t a r t  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
R a c e  D e t a i l s :  
 
 
E n d  D a t e / [ T i m e ]  o f  T r e a t m e n t :  Y Y Y Y - M M - D D  
W e i g h t  ( k g )  :  x x  
  
 
 
 
A d v e r s e  E v e n t  I n f o r m a t i o n  
 
 
R e f e r e n c e  I D  
x x x  
 
P r e f e r r e d  t e r m  
< t e x t >  
 
V e r b a t i m  t e r m  
< t e x t >  
 
O n s e t  D a t e /  D a t e  o f  r e s o l u t i o n  
Y Y Y Y - M M - D D /  Y Y Y Y - M M - D D  
 
D u r a t i o n  ( D a y s )  
x x x  
 
T i m e  S i n c e  T - C e l l  I n f u s i o n  ( D A Y S )  
x x x  
 
M a x i m u m  G r a d e /  O v e r a l l  P h a s e ( s ) /  S e r i o u s  
4 /  L e u k ,  L y m p h ,  T - c e l l /  Y  
 
O u t c o m e  
N O T  R E C O V E R E D / R E S O L V E D  
 
A c t i o n  t a k e n :  C y c l o p h o s p h a m i d e  
D O S E  I N T E R R U P T E D / D E L A Y E D  
 
A c t i o n  t a k e n :  F l u d a r a b i n e  
N O T  A P P L I C A B L E  
 
P P D
P P D
P P D
P P D
P P D
P P D


 
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Action taken: GSK3377794 
INFUSION INTERRUPTED BUT COMPLETED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
Any vaccination received within 4 weeks 
prior to onset of symptoms 
Yes: <treatment name> 
No 
 
Was Brighton Criteria Assessed at 
hospital admission? 
Yes: <treatment name> 
No 
 
Brighton Criteria Score at GBS hospital 
admission 
Grade 1 or 2 or 3 or 4  
 
Brighton Criteria Score 7 days after GBS 
hospital admission 
Grade 1 or 2 or 3 or 4  
 
Symptoms Experienced 
Preceding symptoms of respiratory or gastrointestinal 
tract, Pain, Cranial Nerve…. 
 
Did the patient experience Hypokalaemia, 
Phosphataemia, Magnesaemia, Hypoglycaemia? 
Yes: Magnesaemia, Hypoglycaemia 
 
Was Patient Diabetic? 
Yes 
No 
 
Did Patient develop CNS metastasis? 
Yes 
No 
 
Early initiation of intravenous or plasma 
exchange 
Yes 
No 
 
Did Patient receive Supplemental Oxygen 
or Mechanical Ventilation assisitance? 
Supplemental Oxygen (Start Date/End Date) 
Mechanical Ventilation assisitance (Start Date/End Date) 
 
Was Patient admitted to ICU? 
Yes 
No 
 
MRC score at hospital admission 
31-40 
 
MRC score at 7 days from hospital 
admission 
51-60 
 
EGRS score at hospital admission 
High Risk (EGRIS 5-7) 
 
EGRS score at 7 days from hospital 
admission 
Low Risk (EGRIS 0-2) 
 
mEGOS score at hospital admission 
Value from drop down menu 
 
mEGOS score at 7 days from hospital 
admission 
Value from drop down menu 
 
Test performed 
CSF , Electropysiological & pathologicval studies or Other (Specify) 
 
 
 


 
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Reference ID 
xxx 
 
Preferred term 
<text> 
 
Verbatim term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Action taken: Cyclophosphamide 
NOT APPLICABLE 
 
Action taken: Fludarabine 
NOT APPLICABLE 
 
Action taken: GSK3377794 
DOSE NOT CHANGED 
 
Related to study treatment(s) 
No 
 
Brighton Criteria Score at GBS hospital 
admission 
Grade 1 or 2 or 3 or 4  
 
Brighton Criteria Score 7 days after GBS 
hospital admission 
Grade 1 or 2 or 3 or 4  
 
Symptoms Experienced 
Preceding symptoms of respiratory or gastrointestinal 
tract, Pain, Cranial Nerve…. 
 
Was Brighton Criteria Assessed at 
hospital admission? 
Yes: <treatment name> 
No 
 
Any vaccination received within 4 weeks 
prior to onset of symptoms 
Yes: <treatment name> 
No 
 
Did Patient Experience any? 
Hypokalaemia, Phosphataemia, Magnesaemia, Hypoglycaemia 
 
Was Patient Diabetic? 
Yes 
No 
 
Did Patient develop CNS metastasis? 
Yes 
No 
 
Early initiation of intravenous or plasma 
exchnage 
Yes 
No 
 
Did Patient receive Supplemental Oxygen 
or Mechanical Ventilation assisitance? 
Supplemental Oxygen (Start Date/End Date) 
Mechanical Ventilation assisitance (Start Date/End Date) 
 


 
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245 
 
Was Patient admitted to ICU? 
Yes 
No 
 
MRC score at hospital admission 
31-40 
 
MRC score at 7 days from hospital 
admission 
51-60 
 
EGRS score at hospital admission 
High Risk (EGRIS 5-7) 
 
EGRS score at 7 days from hospital 
admission 
Low Risk (EGRIS 0-2) 
 
mEGOS score at hospital admission 
Value from drop down menu 
 
mEGOS score at 7 days from hospital 
admission 
Value from drop down menu 
 
Test performed 
CSF , Electropysiological & pathologicval studies or Other (Specify) 
 
 
 
All Adverse Events Suspected to be Linked to 
GBS 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 
Related to study treatment(s) 
Yes: Cyclophosphamide; GSK3377794 
 
 
 
 
Preferred term 
<text> 
 
Onset Date/ Date of resolution 
YYYY-MM-DD/ YYYY-MM-DD 
 
Duration (DAYS) 
xxx 
 
Time Since T-Cell Infusion (DAYS) 
xxx 
 
Maximum Grade/ Overall Phase(s)/ Serious 
1/ T-cell/ N 
 
Outcome 
NOT RECOVERED/RESOLVED 
 


 
CONFIDENTIAL 
 
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246 
 
Related to study treatment(s) 
No 
 
 
 
 
Concomitant Medication Information 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
Ingredient 
<text> 
 
Verbatim text 
<text> 
 
Start date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
End date[/time]/ Study day 
YYYY-MM-DD/ xxx 
 
Dose/ Dose unit/ Frequency/ Route 
240/ mg/ Q12H/ ORAL 
 
 
 
 
For definition of analysis populations refer to table x.xxx: Summary of Study Populations. 
 
AESI specific details. 
 
 
 
 
 
/Directory/program.sas  01JAN2002 12:01