Evaluation of Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
Phase: PHASE2
Conditions: Neoplasms
Sponsor: USWM, LLC (dba US WorldMeds)

Protocol Amendment 6
Study ID:  208467
Main Study Title: Master Protocol to Assess the Safety and Antitumor 
Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, 
Alone or in Combination With Other Agents, in HLA-A2+ Participants With 
NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO)
Sub-study 1 Title:  Evaluation of Safety and Antitumor Activity of Lete-Cel 
(GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive 
Previously Untreated Advanced (Metastatic or Unresectable) Synovial 
Sarcoma and Myxoid/Round Cell Liposarcoma
NCT ID for Sub-study 1: NCT05993299
Date of Document: 04-NOV-2021

TMF-14132897 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
208467 
 
 
1 
Core 
 
TITLE PAGE 
Protocol Title: Master Protocol to Assess the Safety and Antitumor Activity of 
Genetically Engineered NY-ESO-1-Specific (c259) T Cells, alone or in combination with 
other agents, in HLA-A2+ Participants with NY-ESO-1 and/or LAGE-1a Positive Solid 
Tumors (IGNYTE-ESO) 
Protocol Number: 208467/Amendment 6 
Compound Number: GSK3377794 (letetresgene autoleucel, lete-cel) 
Short Title: Master Protocol to Assess the Safety and Antitumor Activity of Genetically 
Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors 
 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline LLC 
5 Crescent Drive 
Philadelphia, PA 19112 
US 
 
Regulatory Agency Identifying Number(s):  
IND Number: 18944 
EudraCT Number: 2019-000415-87 
Approval Date: 04-NOV-2021 
 
 
 
 
 
Copyright 2021 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited. 
 

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SPONSOR SIGNATORY: 
Protocol Title: Master Protocol to Assess the Safety and Antitumor Activity of 
Genetically Engineered NY-ESO-1-Specific (c259) T Cells, alone or in combination with 
other agents, in HLA-A2+ Participants with NY-ESO-1 and/or LAGE-1a Positive Solid 
Tumors (IGNYTE-ESO) 
Protocol Number: 208467/Amendment 6 
Compound Number 
or Name: 
GSK3377794 (letetresgene autoleucel, lete-cel) 
 
 
 
 
 
 
 
The signed page is a separate document. 
 
 
 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual 
 
 
 
Carsten Goessl, MD 
Vice President, Clinical Development,  
Synthetic Lethality and Cell and Gene Therapies 
Oncology 
GlaxoSmithKline 
 
 
 
Date 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
List dates of original protocol and all amendments in reverse chronological order. 
Document 
Date 
DNG Number 
Amendment 6 
04-NOV-2021 
TMF-14132897 
Amendment 5 
19-MAY-2021 
TMF-13778474 
Amendment 4 
03-DEC-2020 
2018N385677_07 
Amendment 3 
06-APR-2020 
2018N385677_05 
Amendment 2 
05-FEB-2020 
2018N385677_03 
Amendment 1 
21-JUN-2019 
2018N385677_01 
Original Protocol 
05-Apr-2019 
2018N385677_00 
 
Amendment 6 -  Date 04-NOV-2021 
Overall Rationale for Amendment 6: 
The primary rationale for protocol Amendment 6 is: 
1. Implementation of additional safety monitoring measures in accordance with a 
recent Dear Investigator Letter and safety events. 
2. An increase in the number of participants in Substudy 2 from 70 planned to 87 
participants (with 72 expected to receive the intended commercial drug product 
supply) was made to ensure greater statistical power for the purpose of 
registration. 
3. For participants treated as of protocol amendment 6, the cyclophosphamide dose 
in the lymphodepleting chemotherapy was reduced on Day -7 thru Day -4 to 
further optimize and reduce potential for acute and prolonged cytopenias while 
also minimizing impact on efficacy.  
4. For participants treated as of protocol amendments 6, 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. 
 

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Section # and Name 
Description of Change 
Brief Rationale 
Core protocol 
Synopsis 
Number of participants was updated as per 
Core Section 5.2 
This revision was made for 
consistency across sections 
Synopsis 
‘Key decisions’ was changed to ‘key 
recommendations’ of IDMC as per Core 
Section 5.4.1 
This revision was made for 
consistency across sections 
5.1 Overall Design 
The note under Part 1: Screening was 
updated to align with changes made to the 
text in Section 6.3. 
This revision was made for 
consistency across sections in the 
core and substudy sections of the 
protocol. 
5.1 Overall Design 
The window for pre-treatment tumor biopsy 
prior to initiating lymphodepletion was 
removed from the Core section 
Part 3: Lymphodepletion/Treatment, as it may 
be different for each substudy. 
This revision was made to correct a 
discrepancy between window 
requirements for biopsy in the Core 
section (originally 28 days) and in 
substudy 1 (allowed to be 90 days 
for the 1L indication). 
5.1 Overall Design 
A window of “no sooner than 90 days post 
T-cell infusion” was added for patients 
entering a separate long-term follow-up 
protocol. 
This window will allow the capture 
of adequate safety information after 
the T-cell infusion. 
5.2 Number of Participants 
The total planned participant numbers were 
changed from 80 to 97: 
Planned participant numbers in Substudy 2 
changed from 70 to 87 
Planned participant number to receive 
intended commercial drug product supply 
changed from 55 to 72 
The planned participant number to ensure 
receive letetresgene changed from 45 to 60 
A sentence was added stating that an 
additional 20% enrollment is factored in 
between leukapheresis and dosing. 
The substudy 2 sample size was 
increased to ensure greater 
statistical power.   
5.4.1 Data Monitoring 
Committee 
‘Key decisions’ was changed to ‘key 
recommendations’ of IDMC 
This revision was to align with 
IDMC charter wording. 
6.1 Screen Failures 
Collection of data may include disease 
characteristics, prior lines of anti cancer 
treatment, performance status and any 
serious adverse events (SAEs). 
This revision was made to clarify 
collection of data on screenfailed 
participants 
6.3 Screening Under Other 
GSK Studies (new section) 
This section was added to indicate that 
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. 
This revision was to allow for target 
expression eligibility of participants 
screened under other GSK studies 
under identical testing conditions 

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Section # and Name 
Description of Change 
Brief Rationale 
9.3.6 Cardiac 
Assessments 
This section was revised to include a definition 
of participants with increased burden of 
cardiovascular risk, and for those identified 
patients to mandate a cardiologist consult 
prior to lymphodepletion and continuous 
cardiac telemetry for a minimum of 3 days 
post T-cell infusion.  
This revision was made to mitigate 
cardiac complications in 
participants with high risk factors 
9.3.7 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) 
9.3.12 Testing for 
Persistence of Transduced 
T cells and Insertional 
Oncogenesis 
Participants with a persistence of transduced 
T cells >1% PBMCs and who have already 
been tested for Integration Site Analysis with a 
result of ‘polyclonal’, will only be retested if: 
persistence of transduced T cells has 
suddently increased; OR 
in case of suspected/reported hematological 
maligancy    
This revision was to clarify 
conditions for monitoring and 
retesting of participants who have 
already been tested for Integration 
Site Analysis with a result of 
‘polyclonal’ 
9.9 Biomarkers 
A sentence was added concerning immune 
cell phenotyping to be assessed in the 
apheresis material, manufactured product, 
and post infusion blood samples. 
This revision was to clarify the 
testing and to align with an addition 
in Section 9.9.4 
9.9.1 Tumor biopsy 
List of planned research studies to be 
performed with tumor biopsies was 
rearranged for better clarity on intent. 
This revision was made to clarify 
the list of planned research studies 
9.9.2 Liquid Biopsies (from 
circulating blood) 
Removal of circulating cell-free RNA (cf-RNA) 
from list of biological entities to be extracted 
from liquid biopsies 
Assay deprioritized to reduce 
amounts of blood collected.  
9.9.4 Cell Phenotype and 
Functional Activity 
Text was added to include the apheresis 
(starting material) in the planned testing.  
This revision was to clarify of the 
materials to be tested. 
Previous 9.9.8 Stool 
Collection for Microbiome 
analysis 
(Section deleted) 
Removal of plan to collect stool sample to 
assess gut microbial community 
Assay deprioritized. 

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Section # and Name 
Description of Change 
Brief Rationale 
9.9.8 Genetic Blood 
Sample 
(formerly 9.9.9) 
The association of candidate or genome-wide 
genetic variants may be explored with 
efficiacy (ORR) and safety such as but not 
limited to cytokine release syndrome 
frequency/severity/duration. 
Harmonized language to central 
wording on genetic analyses. 
12.7.2 Infection 
For participants with indwelling central lines, 
consider increased surveillance to monitor for 
catheter-associated infections. 
This revision was made to add 
recommendation to monitor for 
catheter-associated infections  
12.7.2.6 Other Anti-
Microbial 
Prophylaxis/Treatment 
If a participant requires anti-microbial 
treatment associated with risk of cardiac 
toxicity, consider close monitoring of cardiac 
function (Section 9.3.6). 
This revision was made to add 
recommendation to monitor for 
cardio toxicity associated with any 
anti-microbial treatment.  
12.7.3 Hematologic and 
Blood Product Support. 
Blood product support should be provided to 
maintain platelets >20 x 109/L in the out-
patient setting. 
This revision was made to clarify 
recommendation for blood product 
on participants in out-patient setting  
12.7.5 Management of 
Cytokine Release 
Syndrome 
Participants with increased cardiovascular risk 
factors (per Section 9.3.6)  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 
• Daily troponin and N-terminal pro B-type 
natriuretic peptide (NT-proBNP) or BNP 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 
Substudy 1 
2 Schedule of Activities 
Table 2 
Footnote 11 was added for additional 
monitoring requirement if suspected CRS 
Grade ≥2.   
Footnote 14 was amended to indicate that 
participants with an increased burden of 
cardiovascular risk factors (as per Section 
9.3.6) will undergo evaluation by a cardiologist 
prior to lymphodepletion. 
Footnote 29 was added to ensure collection of 
a Transgene Copies (Persistence for Safety) 
in case of any SAE that occurs after T‑cell 
infusion. 
Footnote 30 was updated to align with recent 
revisions made in related protocols 
A cyclophosphamide infusion timepoint was 
added on Day -6. 
 
Removal of requirement for Creatinine 
Clearance (CrCl) assessment originally 
scheduled at months 18 and 30.  
Serum creatinine test maintained at these 
timepoints as part of chemistry panel and  
can still provide an estimaetion of CrCl. 
These revisions were made to align 
with additional safety cardiac 
monitoring requirements 
 
 
 
 
These revisions were made to 
maintain consistency among 
studies for this investigative 
therapy. 
 
 
 
The revision was made to 
implement the optimized 
cyclophosphamide regimen 
schedule over 3 days. 
 
Optimization of the schedule of 
assessments and reduction of 
burden to participants. 
2 Schedule of Activities 
Table 3 
Removal of Microbiome Stool sample row and 
footnote 10. 
Removal of Microbiome Stool 
sample collection as assay is 
deprioritized. 
3.2.1 Risk assessment 
Added potential risk of cardiac arrest. 
Added identified risk of haemorrhage 
secondary to thrombocytopenia 
Updated risk assessment table to 
align with Dear Investigator Letter 
and recent safety events 
5.1 Overall Design 
The note under Part 1: Screening was 
updated to align with text in Section 6.3 of the 
Core Protocol. 
This revision was made for 
consistency across sections in the 
core and substudy sections of the 
protocol. 
5.5.1 Justification of 
Lymphodepleting Regimen 
Text was updated to revise the 
cyclophosphamide dose from 
1800 mg/m2 x 2 days to 900 mg/m2 x 3 days.  
In addition, justification for this change was 
added. 
The lymphodepleting chemotherapy 
regimen was updated in order to 
mitigate risk of acute and prolonged 
toxicities while not compromising 
efficacy.  
5.5.2 Justification of lete-
cel (GSK3377794) Dose 
The dose range maximum was expanded 
from 8×109 transduced T cells to 15×109 
transduced T cells for participants treated 
under protocol amendments 6 and beyond. 
The dose range maximum was 
updated in order to maximize the 
use of cells in participants whose 
manufacture yields >8×109 
transduced T cells.   

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Section # and Name 
Description of Change 
Brief Rationale 
6.1.1 Target Expression 
Screening 
 
 
Inclusion #3 
Inclusion was simplified at this stage  
by postponing requirement for evidence of 
disease-specifc translocation to 
Leukapheresis Eligibility Screening (Inclusion 
#9) 
This revision was made to allow 
target expression screening to 
proceed while evidence of disease-
specifc translocation is being 
obtained. 
6.1.2 Leukaperesis 
Eligibility Screening 
 
 
Inclusion #9 
(newly added) 
Requirement for evidence of disease-specifc 
translocation is being added at Leukapheresis 
Eligibility Screening stage with clarification on 
the requirement of gene involvements and  
update to the methods typically used for 
translocation identification. 
This revision was made for 
optimization of the inclusion 
language on disease-specifc 
translocations. 
Inclusion #11 
The note under inclusion #11 was updated to 
align with text in Section 6.3 of the Core 
Protocol. 
This revision was made for 
consistency across sections in the 
core and substudy sections of the 
protocol. 
Inclusion #15 
The alternative threshold for hemoglobin 
under Table 5 was corrected from 5.6 to 5.0 
mmol/L to match with the original threshold of 
8 g/dL. 
This correction was made to align 
the 2 thresholds for haemoglobin 
expressed in different units.. 
6.2.2 Leukaperesis 
Eligibility Screening 
Table 6 Washout periods 
for Substudy 1 
 
 
Exclusion #10 
 
 
Washout period for radiotherapy only applies 
prior to lymphodepletion. 
 
 
Ongoing or active infection (including, but not 
limited to systemic fungal infection) are 
excluded 
 
 
This revison was made to clarify 
that the radiotherapy washout 
period requirement only applies 
prior to lymphodepletion and not 
prior to leukapheresis. 
This revison was made to clarify 
that any systemic fungal infection is 
excluded 
6.2.3 Treatment Eligibility 
Screening 
Exclusion #22 
The text was amended to exclude participants 
with all measurable lesions irradiated within  
3 months prior to lymphodepletion, exhausting 
the possibility of picking a target lesion for 
RECIST v1.1 assessment.. 
This revison was made to allow 
irradiation to measurable lesions as 
long as there are measurable 
lesions spared to be used as target 
lesions . 
7.1.3 Lymphodepleting 
Chemotherapy  
Text was added that refers to Table 7 for dose 
adjustment of participants ≥60 years of age.  
In addition, the cyclophosphamide doses were 
revised in Table 7. 
In the Mesna subsection, the 
cyclophosphamide dose was updated. 
The revisions were made to clarify 
the dose adjustments and provide 
consistency with Section 5.5.1. 

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Section # and Name 
Description of Change 
Brief Rationale 
7.5.1 Prohibited 
Concomitant Medications 
and Treatments 
Text was added to specifiy that the listed 
prohibited therapies during the Interventional 
Phase of the study are those that are 
anti-cancer therapies. 
Revisions were made to clarify the 
language on prohibited 
Concomitant Medications and 
Treatments. 
10.3.1 Efficacy Analyses 
In subsection “Final Efficacy Analysis” the 
ORR reporting was redefined by removing the 
phrase:  (participants) “who have had at least 
two post-baseline disease assessments or 
have died or progressed or have withdrawn 
from the study.” 
This revision was made to align 
with the Statistical Analysis Plan. 
10.3.2 Safety Analysis 
Text was clarified that listings may be 
provided in lieu of summaries in case of low-
event counts. 
“Left ventricular function (ECHO and MUGA)” 
were removed from the clinical laboratory 
evaluations. 
These revisions were made to align 
with the Statistical Analysis Plan. 

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Section # and Name 
Description of Change 
Brief Rationale 
Substudy 2 
2 Schedule of Activities 
Table 2 
Footnote 11 was added for additional 
monitoring requirement if suspected CRS 
Grade ≥2.   
Footnote 14 was amended to indicate that 
participants with an increased burden of 
cardiovascular risk factors (as per Section 
9.3.6) will undergo evaluation by a cardiologist 
prior to lymphodepletion. 
Footnote 29 was added to ensure collection of 
a Transgene Copies (Persistence for Safety) 
in case of any SAE that occurs after T‑cell 
infusion. 
Footnote 30 was updated to align with recent 
revisions made in related protocols. 
Footnote 33 was updated to add instructions 
for completing the Healthcare Utilization 
Worksheet. 
A cyclophosphamide infusion timepoint was 
added on Day -6. 
 
Removal of requirement for Creatinine 
Clearance (CrCl) assessment originally 
scheduled at months 18 and 30.  
Serum creatinine test maintained at these 
timepoints as part of chemistry panel and  
can still provide an estimaetion of CrCl. 
These revisions were made to align 
with additional safety cardiac 
monitoring requirements 
 
 
 
 
These revisions were made to 
maintain consistency among 
studies for this investigative 
therapy. 
 
 
 
The revision was made to improve 
collection of Healthcare Utilization. 
 
The revision was made to 
implement the optimized 
cyclophosphamide regimen 
schedule over 3 days. 
 
Optimization of the schedule of 
assessments and reduction of 
burden to participants. 
2 Schedule of Activities 
Table 3 
Removal of Microbiome Stool sample row and 
footnote 10. 
Removal of Microbiome Stool 
sample collection as the assay was 
deprioritized. 
3.2.1 Risk assessment 
Added potential risk of cardiac arrest. 
Added identified risk of haemorrhage 
secondary to thrombocytopenia 
Updated risk assessment table to 
align with Dear Investigator Letter 
and recent safety events 
4 Objectives and 
Endpoints 
The endpoint for the treatment-related 
healthcare resource utilization objective was 
revised (i.e., “treatment-related” changed to 
“oncology-related” and an example added). 
To clarify the healthcare objective. 
5.1 Overall Design 
5.2 Number of Participants 
5.4 Scientific Rationale for 
Substudy Design 
The planned participant numbers were 
changed from 55 to 72.   
The intended number of participants who 
ultimately receive therapy and completed a 
minimum of 6-month follow-up or have died or 
have withdrawn early following lete-cel 
treatment was changed from 45 to 60. 
Substudy 2 sample size increase to 
ensure greater statistical power and 
to align with the Core Protocol. 

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Core 
 
Section # and Name 
Description of Change 
Brief Rationale 
5.1 Overall Design 
The note under Part 1: Screening was 
updated to align with changes made to the 
text in Section 6.3 of the Core Protocol. 
This revision was made for 
consistency across sections in the 
core and substudy sections of the 
protocol. 
5.5.1 Justification of 
Lymphodepleting Regimen 
Text was updated to revise the 
cyclophosphamide dose from 
1800 mg/m2 x 2 days to 900 mg/m2 x 3 days.  
In addition, justification for this change was 
added. 
The lymphodepleting chemotherapy 
regimen was updated in order to 
further optimize and reduce 
potential for acutre and prolonged 
toxicities while also minimizing the 
impact on efficacy.  
5.5.2 Justification of lete-
cel (GSK3377794) dose 
The upper end of the target dose range was 
increased from 8×109 transduced T cells to 
15×109 transduced T cells for participants 
treated as of protocol amendment 6  
Revisions were made in order to 
maximize the delivery of cells for 
participants whose manufacture 
yields >8×109 transduced cells.   
6.1.1 Target Expression 
Screening 
 
 
Inclusion #3 
Inclusion was simplified at this stage  
by postponing requirement for evidence of 
disease-specifc translocation to 
Leukapheresis Eligibility Screening (Inclusion 
#8) 
This revision was made to allow 
target expression screening to 
proceed while evidence of disease-
specifc translocation is being 
obtained. 
Inclusion #5 was moved to 
Section 6.1.2 
(Leukapheresis Eligibility 
Screening) to become 
Inclusion #9 
Requirement for participant to be either 
currently treated with or have completed at 
least one standard of care treatment including 
anthracycline-containing regimens was moved 
to Leukapheresis Eligibility screening.  
A note was added to indicate that participants 
with advanced (metastatic or unresectable) 
disease can also still undergo leukapheresis 
prior to initiating first line or standard therapy. 
Removal of “within 12 weeks” restriction on 
eligibility requirement of progression post 
completion of anthracycline-based therapy in 
neoadjuvant/adjuvant setting. 
Revisions were made to clarify the 
timing of eligibility in regards to 
prior line of standard of care 
treatment. 
Harmonization of language with 
Inclusion #17 to ensure that 
participants who have received 
anthracycline-based therapy as 
neoadjuvant, would still be eligible 
even if they were not able to 
receive anthracycline as 1L 
metastatic treatment.  
6.1.2 Leukapheresis 
Eligibility Screening 
 
 
Inclusion #8 
(newly added) 
Requirement for evidence of disease-specifc 
translocation is being added at Leukapheresis 
Eligibility Screening stage with clarification on 
the requirement of gene involvements and  
update to the methods typically used for 
translocation identification. 
This revision was made for 
optimization of the inclusion 
language on disease-specifc 
translocations. 

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Core 
 
Section # and Name 
Description of Change 
Brief Rationale 
Inclusion #9 
(moved from prior 
 Inclusion #5) 
Requirement for participant to be either 
currently treated with or have completed at 
least one standard of care treatment including 
anthracycline-containing regimens was moved 
to Leukapheresis Eligibility screening.  
Revisions were made to clarify the 
timing of eligibility in regards to 
prior line of standard of care 
treatment. 
 
Inclusion #10 
The note under inclusion #10 was updated to 
align with text in Section 6.3 of the Core 
Protocol. 
This revision was made for 
consistency across sections in the 
core and substudy sections of the 
protocol. 
Inclusion #14 
The alternative threshold for hemoglobin 
under Table 5 was corrected from 5.6 to 5.0 
mmol/L to match with the original threshold of  
8 g/dL. 
This correction was made to align 
the 2 thresholds for haemoglobin 
expressed in different units. 
6.1.3 Treatment Eligibility 
Screening 
Inclusion #20 
The requirement that radiographic evidence of 
disease progression adhere to “RECIST v1.1 
from prior line of therapy” was removed 
This revision was made to allow for 
greater flexibility in patient 
treatment. 
6.2.2 Leukaperesis 
Eligibility Screening 
Table 6 Washout periods 
for Substudy 2 
 
 
 
Exclusion #9 
 
 
Washout period for radiotherapy only applies 
prior to lymphodepletion. 
 
 
 
 
Ongoing or active infection (including, but not 
limited to systemic fungal infection) are 
excluded 
 
 
This revison was made to clarify 
that the radiotherapy washout 
period requirement only applies 
prior to lymphodepletion and not 
prior to leukapheresis. 
 
This revison was made to clarify 
that any systemic fungal infection is 
excluded 
6.2.3 Treatment Eligibility 
Screening 
Exclusion #21 
The text was amended to exclude participants 
with all measurable lesions irradiated within  
3 months prior to lymphodepletion, exhausting 
the possibility of picking a target lesion for 
RECIST v1.1 assessment.. 
This revison was made to allow 
irradiation to measurable lesions as 
long as there are measurable 
lesions spared to be used as target 
lesions . 
7.1.3 Lymphodepleting 
Chemotherapy 
Text was added that refers to Table 6 for dose 
adjustment of participants ≥60 years of age.   
In the Mesna subsection, the 
cyclophosphamide dose was updated. 
Revisons were made to clarify the 
dose adjustments and revision of 
doses for consistency with 
Section 5.5.1. 
7.5.1 Prohibited 
Concomitant Medications 
and Treatments 
Text was added to specifiy that the listed 
prohibited therapies during the Interventional 
Phase of the study are those that are 
anti-cancer therapies. 
Clarification of language on 
prohibited Concomitant Medications 
and Treatments. 

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Core 
 
Section # and Name 
Description of Change 
Brief Rationale 
9.3 Healthcare Resource 
Utilization 
The title was changed from “Medical and 
Health Economics Resource Utilization” to 
“Healthcare Resource Utilization.”  The text 
was replaced to clarify the healthcare 
resource data collection process and to 
remove patient paper form. 
The text was replaced to clarify the  
data collection process and the 
information collected. 
10.1 Statistical Hypotheses 
A hierarchical testing strategy is being 
implemented: 
• Interim Analysis 1: After approximately 20 
patients infused with intended commercial 
drug product supply and followed for 
approximately 3 months.  No early claim for 
efficacy nor alpha adjustment are planned for 
this analysis. 
• Interim Analysis 2: After 45 patients infused 
with intended commercial drug product supply 
and followed for approximately 6 months, 
efficacy will be evaluated for the overall 
population (SS+MRCLS).   
• Primary Efficacy Analysis:  After 60 patients 
infused with intended commercial drug 
product supply and followed for approximately 
6 months, efficacy will be evaluated for the 
overall population (SS+MRCLS). Observing 
an ORR of 16 of 60 responders would provide 
a successful outcome for the study. 
• Primary Efficacy Analysis (SS sub-
population):  After 60 patients (SS+MRCLS) 
infused with intended commercial drug 
product supply and followed for approximately 
6 months, the SS sub-population will be 
evaluated.  
This section was updated to reflect 
the increase in sample size and 
clarify the hierarchical testing 
strategy 
10.2 Sample Size 
Justification 
The sample size was changed from 45 to 60.  
Thus, the ORR needed to claim success at 
the time of primary analysis was changed 
from “(12/45)” to “(16/60).” 
A hierarchical testing strategy for an interim 
analysis and primary efficacy analysis was 
added. 
The sample size was updated to 
align with revisions in previous 
sections. 
10.3 Populations for 
analyses 
Participants who received drug product supply 
that was released as a “non conforming batch” 
will not be included in mITT, mITTc, PEAP 
and PEAPi populations  
The definition of the populations for 
analyses was updated to specify 
how participants treated under a 
“non-conforming batch” release will 
be analysed. 
10.5.2 Safety Analyses 
Text was clarified that listings may be 
provided in lieu of summaries in case of low-
event counts. 
The text was revised to clarify the 
processing of listings. 

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Section # and Name 
Description of Change 
Brief Rationale 
10.5.5 Interim Analyses 
A second interim analysis was added, and 
changes were made to clarify the plans for the 
first interim analysis.  
The revisions were made to clarify 
the interim analysis plans for this 
study. 
Throughout Core and rest of document 
 
‘GSK3377794’ was replaced by ‘lete-cel’ 
throughout document only leaving reference 
to GSK3377794 when relevant. 
To generalize use of shortname 
‘lete-cel’ deived from the 
GSK3377794’s  generic drugname 
“Letetresgene Autoleucel”  
 
Accrual numbers as well as lete-cel safety 
profile have been updated based on the most 
current Lete-cel Investigator’s Brochure as of 
27 January 2021. 
 
 
 
 

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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY: ............................................................................................... 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1 
SYNOPSIS ............................................................................................................. 23 
2 
SCHEDULE OF ACTIVITIES (SOA) ....................................................................... 28 
3 
INTRODUCTION .................................................................................................... 28 
3.1 
Study Rationale .......................................................................................... 29 
3.2 
Background ................................................................................................ 29 
3.3 
GSK3377794 (letetresgene autoleucel, lete-cel) ......................................... 30 
4 
OBJECTIVES AND ENDPOINTS ........................................................................... 32 
5 
STUDY DESIGN .................................................................................................... 33 
5.1 
Overall Design ............................................................................................ 33 
5.2 
Number of Participants ............................................................................... 38 
5.3 
End of Master Protocol Definition ................................................................ 38 
5.3.1 
End of Study for Individual Participants ........................................ 38 
5.3.2 
End of Master Protocol ................................................................ 38 
5.4 
Scientific Rationale for Protocol Design ...................................................... 39 
5.4.1 
Data Monitoring Committee ......................................................... 39 
6 
PROTOCOL POPULATION ................................................................................... 39 
6.1 
Screen Failures........................................................................................... 40 
6.2 
Rescreening ............................................................................................... 40 
6.3 
Screening Under Other GSK Studies .......................................................... 40 
7 
STUDY INTERVENTION ........................................................................................ 41 
8 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 41 
8.1 
Discontinuation of Study Intervention .......................................................... 41 
8.2 
Liver Chemistry Increased Monitoring Criteria ............................................ 41 
8.2.1 
Temporary Discontinuation .......................................................... 43 
8.3 
Participant Discontinuation/Withdrawal from the Study ............................... 44 
8.4 
Lost to Follow Up ........................................................................................ 44 
8.5 
Study Stopping and Pausing Rules ............................................................. 45 
9 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 45 
9.1 
Efficacy Assessments ................................................................................. 46 
9.1.2 
Long-Term Follow-up ................................................................... 47 
9.2 
Patient Reported Outcomes ........................................................................ 47 
9.3 
Safety Assessments ................................................................................... 47 
9.3.1 
Safety Review Team .................................................................... 47 
9.3.2 
Physical Examinations and Developmental Examinations ........... 47 

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9.3.3 
Additional Assessments for Pediatric Participants ........................ 48 
9.3.4 
Lansky, Karnofsky, or ECOG Performance Status ....................... 48 
9.3.5 
Vital Signs .................................................................................... 48 
9.3.6 
Cardiac Assessments .................................................................. 49 
9.3.7 
Pulmonary Assessments ............................................................. 50 
9.3.8 
Monitoring for Immune Effector Cell-Associated 
Neurotoxicity  Syndrome .............................................................. 50 
9.3.9 
Monitoring for Demyelinating Neuropathy and Other 
Neurological Events ..................................................................... 51 
9.3.10 
Clinical Safety Laboratory Assessments ...................................... 51 
9.3.11 
Monitoring and Management of Replication-Competent 
Lentivirus (RCL) using Vesicular Stomatitis Virus G protein 
(VSV-G) ....................................................................................... 51 
9.3.11.1 
Testing for RCL in Clinical Studies ............................. 52 
9.3.11.2 
Safety Monitoring Protocol .......................................... 52 
9.3.12 
Testing for Persistence of Transduced T cells and 
Insertional Oncogenesis .............................................................. 53 
9.4 
Adverse Events and Serious Adverse Events ............................................. 54 
9.4.1 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 55 
9.4.2 
Method of Detecting AEs and SAEs ............................................. 56 
9.4.3 
Follow-up of AEs and SAEs ......................................................... 56 
9.4.4 
Regulatory Reporting Requirements for SAEs ............................. 57 
9.4.5 
Pregnancy ................................................................................... 57 
9.4.6 
Cardiovascular Events and Death ................................................ 58 
9.4.7 
Adverse Events of Special Interest (AESIs) ................................. 58 
9.5 
Treatment of Overdose ............................................................................... 59 
9.6 
Pharmacokinetics ....................................................................................... 59 
9.7 
Pharmacodynamics .................................................................................... 60 
9.8 
Genetics ..................................................................................................... 60 
9.9 
Biomarkers ................................................................................................. 60 
9.9.1 
Tumor Biopsy .............................................................................. 61 
9.9.2 
Liquid Biopsies (from circulating blood) ........................................ 62 
9.9.3 
Cytokine Analyses ....................................................................... 62 
9.9.4 
Cell Phenotype and Functional Activity ........................................ 63 
9.9.5 
Immunogenicity Assessments ...................................................... 63 
9.9.6 
RNA Transcriptome Research ..................................................... 63 
9.9.7 
RNA Expression Research of a Subset of RNA Species .............. 64 
9.9.8 
Genetic Blood Sample ................................................................. 64 
9.9.9 
Request for Autopsy in case of Death Following 
Administration of Gene Transfer Agents ...................................... 64 
10 STATISTICAL CONSIDERATIONS ........................................................................ 65 
11 REFERENCES ....................................................................................................... 66 
12 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 75 
12.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 75 
12.1.1 
Regulatory and Ethical Considerations ........................................ 75 
12.1.2 
Financial Disclosure ..................................................................... 75 

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12.1.3 
Informed Consent Process .......................................................... 76 
12.1.4 
Data Protection ............................................................................ 76 
12.1.5 
Publication Policy ......................................................................... 77 
12.1.6 
Dissemination of Clinical Study Data ........................................... 77 
12.1.7 
Data Quality Assurance ............................................................... 78 
12.1.8 
Source Documents ...................................................................... 78 
12.1.9 
Study and Site Closure ................................................................ 79 
12.1.10 Remote Monitoring and Source Data Verification ......................... 79 
12.2 
Appendix 2: Clinical Laboratory Tests ......................................................... 80 
12.3 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 82 
12.3.1 
Definition of AE ............................................................................ 82 
12.3.2 
Definition of SAE .......................................................................... 83 
12.3.3 
Definition of Cardiovascular Events ............................................. 84 
12.3.4 
Recording and Follow-Up of AE and SAE .................................... 85 
12.3.5 
Reporting of SAE to GSK ............................................................. 87 
12.4 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 88 
12.4.1 
Definitions .................................................................................... 88 
12.4.2 
Contraception Guidance .............................................................. 88 
12.4.3 
Collection of Pregnancy Information: ........................................... 90 
12.5 
Appendix 5: Genetics .................................................................................. 92 
12.5.1 
Germline Control .......................................................................... 92 
12.6 
Appendix 6: Guidelines for Assessment of Disease, Disease 
Progression and Response Criteria ............................................................ 94 
12.6.1 
RECIST v1.1 Assessment Guidelines .......................................... 94 
12.6.2 
iRECIST Guidelines ..................................................................... 99 
12.7 
Appendix 7: Supportive Care Guidance .................................................... 105 
12.7.1 
T cell Infusion Symptom Management ....................................... 105 
12.7.2 
Infection ..................................................................................... 105 
12.7.2.1 
Pneumocystis carinii Pneumonia (PCP) ................... 106 
12.7.2.2 
Herpes Simplex,Varicella Zoster and Epstein-
Barr Virus ................................................................. 106 
12.7.2.3 
Cytomegalovirus ....................................................... 106 
12.7.2.4 
Hepatitis B Prophylaxis ............................................. 106 
12.7.2.5 
Syphilis ..................................................................... 106 
12.7.2.6 
Other Anti-Microbial Prophylaxis ............................... 107 
12.7.3 
Hematologic and Blood Product Support ................................... 107 
12.7.3.1 
Irradiated Blood Product ........................................... 107 
12.7.3.2 
CMV Screened Blood Products ................................ 107 
12.7.4 
Management of Autoimmunity ................................................... 107 
12.7.5 
Management of Cytokine Release Syndrome ............................ 108 
12.7.6 
Management of Graft-versus-Host Disease (GvHD) .................. 111 
12.7.6.1 
Diagnosis of GvHD ................................................... 111 
12.7.6.2 
Grading of GvHD ...................................................... 112 
12.7.6.3 
Management of GvHD .............................................. 113 
12.7.7 
Management of Pancytopenia with Bone Marrow 
Failure/Aplastic Anemia ............................................................. 114 
12.7.8 
Management of Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) ............................................... 115 
12.7.8.1 
Grading of ICANS ..................................................... 116 

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12.7.8.2 
Monitoring for Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) .............................. 119 
12.7.8.3 
Management of ICANS ............................................. 119 
12.7.9 
Chemotherapy Symptom Management ...................................... 122 
12.7.9.1 
Management of Neutropenia .................................... 122 
12.7.10 Management of Guillain-Barré Syndrome (GBS) ....................... 122 
12.7.10.1 Neurological symptoms ............................................ 123 
12.7.10.2 Brighton key diagnostic criteria ................................. 124 
12.7.10.3 Erasmus GBS Respiratory Insufficiency Score 
(EGRIS) .................................................................... 124 
12.7.10.4 Modified Erasmus GBS Outcomes Score 
(mEGOS) ................................................................. 124 
12.7.10.5 Summary of diagnosis and treatment for GBS .......... 124 
12.8 
Appendix 8: Neurology Consultation – Further Guidelines for Signs 
and Symptoms Suggestive of Guillain-Barré Syndrome ............................ 126 
12.8.1 
Additional Assessments for Suspected GBS at Hospital 
Admission .................................................................................. 126 
12.8.1.1 
Risk of Respiratory Insufficiency Assessment ........... 126 
12.8.1.2 
Prognostic Tool for Assessment of GBS 
Outcome at Hospital Admission ................................ 127 
12.8.2 
Assessments Post Hospital Admission for GBS ......................... 128 
12.8.2.1 
Brighton Criteria ....................................................... 128 
12.8.2.2 
Prognostic Tool for Assessment of GBS 
Outcome at Day 7 Post Hospital Admission ............. 128 
12.9 
Appendix 9: Eastern Cooperative Oncology Group Performance 
Scale ........................................................................................................ 129 
12.10 Appendix 10: Abbreviations and Trademarks ............................................ 130 
13 SUBSTUDIES ...................................................................................................... 136 
SUBSTUDY 1: LETETRESGENE AUTOLEUCEL (LETE-CEL, GSK3377794) IN 
NY-ESO-1 POSITIVE PREVIOUSLY UNTREATED ADVANCED 
(METASTATIC OR UNRESECTABLE) SYNOVIAL SARCOMA AND 
MYXOID/ROUND CELL LIPOSARCOMA ............................................................ 136 
1 
SYNOPSIS ........................................................................................................... 139 
2 
SCHEDULE OF ACTIVITIES (SOA) ..................................................................... 139 
3 
INTRODUCTION .................................................................................................. 152 
3.1 
Background and Rationale for First Line Therapy with Lete-cel 
(GSK3377794) .......................................................................................... 152 
3.2 
Benefit/Risk Assessment .......................................................................... 155 
3.2.1 
Risk Assessment ....................................................................... 156 
3.2.2 
Benefit Assessment ................................................................... 161 
3.2.3 
Overall Benefit/Risk Conclusion ................................................. 162 
4 
OBJECTIVES AND ENDPOINTS ......................................................................... 163 
5 
SUBSTUDY DESIGN ........................................................................................... 165 
5.1 
Overall Design .......................................................................................... 165 
5.2 
Number of Participants ............................................................................. 169 
5.3 
End of Study Definition ............................................................................. 169 

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5.3.1 
End of Substudy for Individual Participants ................................ 169 
5.3.2 
End of Substudy ........................................................................ 169 
5.4 
Scientific Rationale for Substudy Design .................................................. 170 
5.5 
Justification for Dose ................................................................................ 171 
5.5.1 
Justification of Lymphodepleting Regimen ................................. 171 
5.5.2 
Justification of lete-cel (GSK3377794) Dose .............................. 171 
6 
STUDY POPULATION ......................................................................................... 173 
6.1 
INCLUSION CRITERIA ............................................................................. 173 
6.1.1 
Target Expression Screening ............................................................. 173 
6.1.2 
Leukapheresis Eligibility Screening...................................................... 174 
6.1.3 
Treatment Eligibility Screening ........................................................... 177 
6.1.3.1 
Treatment Fitness (for Safety) .......................................... 178 
6.2 
EXCLUSION CRITERIA ........................................................................... 178 
6.2.1 
Target Expression Screening ............................................................. 178 
6.2.2 
Leukapheresis Eligibility Screening...................................................... 179 
6.2.3 
Treatment Eligibility Screening ........................................................... 180 
6.2.3.1 
Treatment Fitness (for Safety) .......................................... 182 
6.3 
Lifestyle Considerations ............................................................................ 182 
6.3.1 
Meals and Dietary Restrictions .................................................. 182 
6.3.2 
Activity ....................................................................................... 182 
6.3.3 
Screen Failures.......................................................................... 182 
6.3.4 
Rescreening .............................................................................. 182 
7 
STUDY INTERVENTION ...................................................................................... 183 
7.1 
Study Intervention(s) Administered ........................................................... 183 
7.1.1 
Leukapheresis ........................................................................... 183 
7.1.2 
Bridging Therapy and/or Standard of Care Intermediate 
Anti-Cancer Therapy before Lymphodepletion ........................... 183 
7.1.3 
Lymphodepleting Chemotherapy ............................................... 183 
7.1.4 
Lete-cel (GSK3377794) Infusion ................................................ 187 
7.2 
Preparation / Handling / Storage / Accountability ...................................... 188 
7.3 
Measures to Minimize Bias: Randomization and Blinding ......................... 189 
7.4 
Study Intervention Compliance ................................................................. 189 
7.5 
Concomitant Therapy................................................................................ 189 
7.5.1 
Prohibited Concomitant Medication and Treatment .................... 190 
7.5.2 
Permitted Concomitant Medication and Treatment .................... 191 
7.5.3 
Rescue Medicine ....................................................................... 192 
7.6 
Dose Modification ..................................................................................... 192 
7.7 
Intervention after the End of the Study ...................................................... 192 
8 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION / WITHDRAWAL ................................................................. 192 
9 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 192 
9.1 
Interviews ................................................................................................. 193 
9.1.1 
Post T cell Infusion Interview ..................................................... 193 
9.1.2 
End of Treatment Interview ........................................................ 193 
9.2 
Patient Reported Outcomes ...................................................................... 193 
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9.3 
Safety Assessments ................................................................................. 195 
10 STATISTICAL CONSIDERATIONS ...................................................................... 195 
10.1 
Statistical hypotheses ............................................................................... 195 
10.2 
Sample size justification ............................................................................ 195 
10.3 
Statistical Analyses ................................................................................... 196 
10.3.1 
Efficacy Analyses ....................................................................... 196 
10.3.2 
Safety Analyses ......................................................................... 198 
10.3.3 
Other Analyses .......................................................................... 199 
10.3.4 
Interim Analyses ........................................................................ 199 
SUBSTUDY 2: LETETRESGENE AUTOLEUCEL (LETE-CEL, GSK3377794) IN 
NY-ESO-1 POSITIVE PREVIOUSLY TREATED ADVANCED 
(METASTATIC OR UNRESECTABLE) SYNOVIAL SARCOMA OR 
MYXOID/ROUND CELL LIPOSARCOMA ............................................................ 200 
1 
SYNOPSIS ........................................................................................................... 203 
2 
SCHEDULE OF ACTIVITIES (SOA) ..................................................................... 204 
3 
INTRODUCTION .................................................................................................. 218 
3.1 
Substudy 2 Background and Rationale ..................................................... 218 
3.2 
Benefit/Risk Assessment .......................................................................... 221 
3.2.1 
Risk Assessment ....................................................................... 222 
3.2.2 
Benefit Assessment ................................................................... 227 
3.2.3 
Overall Benefit/Risk Conclusion ................................................. 228 
4 
OBJECTIVES AND ENDPOINTS ......................................................................... 228 
5 
STUDY DESIGN .................................................................................................. 231 
5.1 
Overall Design .......................................................................................... 231 
5.2 
Number of Participants ............................................................................. 235 
5.3 
End of Study Definition ............................................................................. 235 
5.3.1 
End of Substudy for Individual Participants ................................ 235 
5.3.2 
End of Substudy ........................................................................ 236 
5.4 
Scientific Rationale for Substudy Design .................................................. 237 
5.5 
Justification for Dose ................................................................................ 237 
5.5.1 
Justification of Lymphodepleting Regimen ................................. 237 
5.5.2 
Justification of lete-cel (GSK3377794) Dose .............................. 238 
6 
STUDY POPULATION ......................................................................................... 239 
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6.1 
INCLUSION CRITERIA ............................................................................. 239 
6.1.1 
Target Expression Screening ............................................................. 239 
6.1.2 
Leukapheresis Eligibility Screening...................................................... 240 
6.1.3 
Treatment Eligibility Screening ........................................................... 244 
6.1.3.1 
Treatment fitness (for safety) ............................................ 245 
6.2 
EXCLUSION CRITERIA ........................................................................... 245 
6.2.1 
Target Expression Screening ............................................................. 245 
6.2.2 
Leukapheresis Eligibility Screening...................................................... 246 
6.2.3 
Treatment Eligibility Screening ........................................................... 247 
6.2.3.1 
Treatment fitness (for safety) ............................................ 249 
6.3 
Lifestyle Considerations ............................................................................ 249 
6.3.1 
Meals and Dietary Restrictions .................................................. 249 
6.3.2 
Activity ....................................................................................... 249 
6.3.3 
Screen Failures.......................................................................... 249 
6.3.4 
Rescreening .............................................................................. 249 
7 
STUDY INTERVENTION ...................................................................................... 250 
7.1 
Study Intervention(s) Administered ........................................................... 250 
7.1.1 
Leukapheresis ........................................................................... 250 
7.1.2 
Bridging Therapy and/or Standard of Care Intermediate 
Anti-Cancer Therapy before Lymphodepletion ........................... 250 
7.1.3 
Lymphodepleting Chemotherapy ............................................... 251 
7.1.4 
Lete-cel (GSK3377794) Infusion ................................................ 254 
7.2 
Preparation / Handling / Storage / Accountability ...................................... 256 
7.3 
Measures to Minimize Bias: Randomization and Blinding ......................... 256 
7.4 
Study Intervention Compliance ................................................................. 257 
7.5 
Concomitant Therapy................................................................................ 257 
7.5.1 
Prohibited Concomitant Medication and Treatment .................... 257 
7.5.2 
Permitted Concomitant Medication and Treatment .................... 258 
7.5.3 
Rescue Medicine ....................................................................... 259 
7.6 
Dose Modification ..................................................................................... 259 
7.7 
Intervention after the End of the Study ...................................................... 260 
8 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION / WITHDRAWAL ................................................................. 260 
9 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 260 
9.1 
Interviews ................................................................................................. 260 
9.1.1 
Post T-cell Infusion Interview ..................................................... 260 
9.1.2 
End of Treatment Interview ........................................................ 260 
9.2 
Patient Reported Outcomes ...................................................................... 260 
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9.3 
Healthcare Resource Utilization ................................................................ 263 
10 STATISTICAL CONSIDERATIONS ...................................................................... 263 
10.1 
Statistical Hypotheses............................................................................... 263 
10.2 
Sample Size Justification .......................................................................... 264 
10.3 
Populations for Analyses .......................................................................... 265 
10.4 
Study Population Analyses ....................................................................... 266 
10.5 
Statistical Analyses ................................................................................... 268 
10.5.1 
Efficacy Analyses ....................................................................... 268 
10.5.2 
Safety Analyses ......................................................................... 272 
10.5.3 
Immunogenicity.......................................................................... 275 
10.5.4 
Other Analyses .......................................................................... 275 
10.5.5 
Interim Analyses ........................................................................ 275 
14 PROTOCOL AMENDMENT HISTORY ................................................................. 277 
 
 
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1 SYNOPSIS 
Protocol Title: Master Protocol to Assess the Safety and Antitumor Activity of 
Genetically Engineered NY-ESO-1 specific (c259) T Cells, alone or in combination with 
other agents, in HLA-A2+ Participants with NY-ESO-1 and/or LAGE-1a Positive Solid 
Tumors (IGNYTE-ESO) 
Short Title: Master Protocol to Assess the Safety and Antitumor Activity of Genetically 
Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors  
Rationale:  
In this master protocol we will investigate T cells that have been genetically engineered 
to recognize NY-ESO-1 and LAGE-1a tumor antigens.  Adoptive T-cell therapy (ACT) is 
a therapeutic approach that uses a cancer patient’s own T lymphocytes obtained by 
leukapheresis, genetically engineered to express a tumor-targeting receptor, such as a 
T-cell receptor (TCR) or a chimeric antigen receptor (CAR), expanded ex vivo and 
re-infused into the participant, with the aim of generating and propagating an anti-tumor 
T-cell immune response.   
NY-ESO-1 and LAGE-1a are members of the cancer-testis family of tumor antigens 
(CTAs).  NY-ESO-1 is a cytoplasmic protein that is detectable in multiple cancer types 
including non-small cell lung cancer (NSCLC), bladder cancer, melanoma, liver cancer, 
synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), and many others. Specific 
peptide epitopes of the NY-ESO-1 or LAGE-1a protein are processed and presented on 
the surface of the tumor cell in complex with an HLA molecule, which can be recognized 
by T cells.  An HLA-A*02 binding peptide (SLLMWITQCaa 157-165) that is common to 
both NY-ESO-1 and LAGE-1a antigens has been identified that can be recognized by 
NY-ESO-1 reactive T cells.  The T cells for therapy have been genetically engineered to 
express an affinity-enhanced TCR toward the SLLMWITQC peptide bound to HLA-
A*02. The retained optimized TCR clone was called NY-ESO-1c259 or c259.  The T-cell 
product consists of autologous T cells transduced with a self-inactivating lentiviral vector 
encoding the affinity enhanced NY-ESO-1 specific TCR (c259).   
In previous clinical trials using adoptively transferred T cells directed against 
NY-ESO-1/LAGE-1a, objective responses have been observed in 40 to 60% of treated 
participants who are HLA-A*02+, bearing NY-ESO-1+ synovial sarcoma.  Similar or 
higher response rates have been observed with this treatment in metastatic melanoma, 
and multiple myeloma post autologous stem cell transplant (ASCT).  Letetresgene 
autoleucel (lete-cel, GSK3377794) is the first generation product consisting of 
autologous T cells expressing the affinity enhanced TCR (c259), and this is currently 
being investigated in ongoing GSK-sponsored pilot clinical trials in HLA-A*02+ 
participants with NY-ESO-1+ metastatic synovial sarcoma (208466 [ADP-04511]), 
advanced MRCLS (study 208469 [ADP-0011-007]), NSCLC (GSK study 208749 
[ADP-0011-004] and GSK study 208471), and relapsed refractory multiple myeloma 
(study 208470 [ADP-0011-008]).  A summary of the clinical data obtained to date with 
these TCR engineered NY-ESO-1/LAGE-1a targeting T cells is presented in the most 
current Lete-cel Investigator’s Brochure.   

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This is a master protocol (208467) consisting of a core protocol with multiple 
independent substudies.  The protocol will initially include a substudy to investigate 
letetresgene autoleucel (lete-cel, GSK3377794) treatment in previously untreated (1L) 
HLA-A*02+ participants with NY-ESO1+ advanced (metastatic or unresectable) synovial 
sarcoma or myxoid/round cell liposarcoma (Substudy 1).  A separate substudy will 
investigate letetresgene autoleucel (lete-cel, GSK3377794) infusion as second line or 
higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced 
(metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma, who 
have progressed following treatment with anthracycline based chemotherapy for the 
purpose of registration (Substudy 2).  
The protocol may be amended at a later time to add additional substudies to investigate 
other NY-ESO-1 or LAGE-1a positive tumor types and other NY-ESO-1 specific (c259) 
T cells (potentially in combination with other agents). 
Objectives and Endpoints: 
Objectives and endpoints are outlined in the substudies.  
In general, the objectives and endpoints below will apply to all substudies unless 
otherwise specified.  Discrepancies between those stated here and those in the substudies 
will not require amendment and those stated in the substudies will apply. 
Exploratory objectives and endpoints, if any, will be provided in the substudies.  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of NY-ESO-1 specific 
(c259) T cells, alone or in combination with 
other anti-cancer agents, in HLA-A*02:01, 
HLA-A*02:05 and/or HLA-A*02:06 participants 
with NY-ESO-1 and/or LAGE-1a positive solid 
tumors 
Overall Response Rate (ORR) per RECIST 
v1.11 
Secondary - Efficacy 
To further evaluate the efficacy of NY-ESO-1 
specific (c259) T cells alone or in combination 
with other anti-cancer agents in HLA-A*02:01, 
HLA-A*02:05 and/or HLA-A*02:06 participants 
with NY-ESO-1 and/or LAGE-1a positive solid 
tumors 
• Time to Response (TTR) 
• Duration of Response (DoR) 
• Disease Control Rate (DCR) 
• Progression Free Survival (PFS) 
Secondary - Safety 
To evaluate the safety and tolerability of 
NY-ESO-1 specific (c259) T cells alone or in 
combination with other anti-cancer agents in 
HLA-A*02:01, HLA-A*02:05 and/or 
• Frequency and severity of Adverse events 
(AEs), serious adverse events (SAEs) and 
AEs of special interest (AESI; as defined in 
protocol) 
• Laboratory parameters 
• Replication Competent Lentivirus (RCL) 

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Objectives 
Endpoints 
HLA-A*02:06 participants with NY-ESO-1 
and/or LAGE-1a positive solid tumors 
• Instances of Insertional oncogenesis (IO) 
Secondary - Pharmacokinetics 
To characterize in vivo cellular PK profile  
(levels, expansion, persistence) of  
NY-ESO-1 specific (c259) T cells 
• Maximum transgene expansion (Cmax) 
• Time to Cmax (Tmax) 
• Area under the time curve from zero to time t  
AUC(0-t), as data permit 
 
AE/s = adverse events; AESI/s = adverse event/s of special interest; AUC(0-t)  = area under the time curve 
from zero to time t; Cmax = maximum concentration; DCR = disease control rate; DoR = duration of 
response; HLA = human leukocyte antigen; IO = insertional oncogenesis; ORR = overall response rate; 
OS = overall survival; PFS = progression-free survival; RCL = replication competent lentivirus; 
RECIST = Response Evaluation Criteria In Solid Tumors; SAE/s = serious AE/s; Tmax = Time to Cmax; 
TTR = Time to Response 
 
1 Independent central review where applicable will be specified in the specific substudies.  
Overall Design:  
This is a master protocol to investigate the safety and antitumor activity of TCR 
engineered NY-ESO-1 specific (c259) T cells alone or in combination with other agents 
in HLA-A*02+ participants with NY-ESO-1 and/or LAGE-1a positive solid tumors. 
The protocol will initially evaluate a first generation of NY-ESO-1 specific TCR (c259) 
engineered T cells, letetresgene autoleucel (lete-cel, GSK3377794), in HLA-A*02+ 
participants with NY-ESO-1+ advanced metastatic or unresectable synovial sarcoma. 
The protocol may be amended later to investigate the activity of TCR engineered 
NY-ESO-1 specific (c259) T cells in other NY-ESO-1+ or LAGE-1a+ tumor types or in 
combination with other agents (see the Study Design schematic below). Details of 
treatment will be provided in the specific substudies. 
Unless otherwise specified in a substudy, participants will receive a single dose of 
NY-ESO-1 specific (c259) T cells after completing lymphodepleting chemotherapy. 

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Disclosure Statement: This is an open-label treatment master protocol with no masking.  
Number of Participants: 
As this is a master protocol consisting of multiple substudies, the overall sample size is 
not fixed. The initial number of participants is expected to be approximately 97 in 
Substudies 1 and 2 combined.  Substudy 1 will enrol 10 participants with previously 
untreated advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell 
liposarcoma, that is either newly diagnosed or relapsed after surgery and radiotherapy 
and/or adjuvant therapy.  Substudy 2 will enrol approximately 87 participants previously 
treated with anthracycline-based regimen for advanced (metastatic or unresectable) 
synovial sarcoma or myxoid/round cell liposarcoma, including : 
• Approximately 15 participants expected to receive the clinical drug product 
supply; 
• Approximately 72 participants will be enrolled to ensure that at least 60 
participants will receive letetresgene autoleucel (letecel, GSK3377794) using 
commercial vector supply and manufacturing process. An additional 20% 
enrollment is factored in between leukapheresis and dosing to account for: early 
withdrawal, manufacturing issues, and extended waiting-time for progression.  
 
Any additional substudies will be added via protocol amendments with specification of 
number of participants for each substudy.  
Methodology and Study Duration: 
Participants identified by the Investigator as possible candidates for a substudy must have 
completed preliminary target expression screening for HLA-typing and NY-ESO-1 or 

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LAGE-1a antigen expression (Note: target expression screening may also be performed 
under a separate GSK-sponsored screening protocol or under another GSK-sponsored 
NY-ESO-1 and/or LAGE-1a targeting T-cell protocol or substudy).  Participants with the 
HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 alleles and whose tumor expresses 
the NY-ESO-1 or LAGE-1a antigen (as specified in each substudy) by validated testing 
at a designated central laboratory are eligible to undergo further screening under this 
protocol.   
Following screening, participants who meet substudy entry criteria will be eligible to the 
study. Eligible participants will undergo leukapheresis to collect autologous T cells to 
manufacture TCR engineered NY-ESO-1 specific (c259) T cells; the Investigational 
Product. The successful initiation of leukapheresis procedure constitutes enrollment in 
the study. 
Once the TCR engineered NY-ESO-1 specific autologous (c259) T cells have been 
successfully manufactured, released, and are available for infusion at the site, and once 
participants’ fitness for lymphodepletion has been assessed and additional eligibility 
criteria for treatment are met, participants will then receive lymphodepleting 
chemotherapy  as specified within each substudy.  Lymphodepleting chemotherapy may 
be given as outpatient treatment per institutional guidelines. 
The investigational product, TCR engineered NY-ESO-1 specific (c259) T cells , will be 
administered as a single intravenous (IV) infusion on Day 1, unless otherwise indicated in 
a specific substudy. Participants will be hospitalized on the day of T-cell infusion (Day 1) 
and may be in the hospital for follow-up care until Day 3 as clinically indicated. Through 
Day 14, participants must be closely monitored by the Investigator. Additional close 
monitoring or hospitalization may be warranted based upon clinical need and is at 
Investigator’s discretion. Participants will receive growth factor support with 
Granulocyte-Colony Stimulating Factor (G-CSF) from ~24 hours following 
lymphodepleting chemotherapy (i.e. on Day -3) until neutrophil count recovery in 
accordance with ASCO guidelines [Smith, 2015] or institutional practice.   
After NY-ESO-1 specific (c259) T-cell infusion, participants are followed in the 
interventional portion of a given substudy until confirmed disease progression at which 
time the participants enter the follow up phase.  All participants will be followed for the 
period defined in each specific substudy, and subsequently entered into a separate 
long-term follow-up (LTFU) protocol (GSK study 208750) for up to 15 years after T-cell 
infusion for gene therapy related adverse events per health authority guidance.   
In order to maximize patient benefit, participants who have failed screening or withdrawn 
before T-cell infusion, may rescreen in the same substudy or be screened for another 
substudy.  

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Participant Journey Schema  
 
 
Data Monitoring Committee: 
An Independent Data Monitoring Committee (IDMC) consisting of external experts has 
been established for ongoing review of safety events and efficacy to enable benefit/risk 
determination for all substudies of this master protocol, independent of the study team. 
Additional details is provided in an IDMC Charter.  
Key recommendations of the IDMC will be documented and reported to regulatory 
agencies if requested, all participating Principle Investigators (PIs) and if required, 
Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs) as 
appropriate with impactful decisions communicated as priority. 
2 SCHEDULE OF ACTIVITIES (SOA) 
Schedule of activities will be documented in each substudy. 
3 INTRODUCTION 
This is a master protocol investigating the safety and antitumor activity of genetically 
engineered autologous NY-ESO-1 specific (c259) T-cells alone or in combination with 
other agents in HLA-A*02+ participants with NY-ESO-1 and/or LAGE-1a positive solid 
tumors.   
This master protocol consists of a core protocol with multiple independent substudies.  
The protocol will initially include a substudy to investigate letetresgene autoleucel (lete-
cel, GSK3377794) treatment in previously untreated (1L) HLA-A*02+ participants with 
NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma or myxoid/round 
cell liposarcoma (Substudy 1).  A separate substudy will investigate letetresgene 
autoleucel (lete-cel, GSK3377794) infusion as second line or higher (2L+) treatment in 
HLA-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) 
synovial sarcoma or myxoid/round cell liposarcoma, who have progressed following 
treatment with anthracycline based chemotherapy for the purpose of registration 
(Substudy 2). 

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The protocol may be amended at a later time to add additional substudies to investigate 
other NY-ESO-1 or LAGE-1a positive tumor types and other NY-ESO-1 specific (c259) 
T cells (potentially in combination with other agents). 
3.1 
Study Rationale 
In this protocol we will investigate T cells that have been genetically engineered to 
recognize NY-ESO-1 and LAGE-1a tumor antigens.  Adoptive T-cell therapy (ACT) is a 
therapeutic approach that uses a cancer patient’s own T lymphocytes obtained by 
leukapheresis, genetically engineered to express a tumor-targeting receptor, such as a 
T-cell receptor (TCR) or a chimeric antigen receptor, expanded ex vivo and re-infused 
into the participant, with the aim of generating and propagating an anti-tumor T-cell 
immune response.     
NY-ESO-1 and LAGE-1a are members of the cancer-testis family of tumor antigens 
(CTAs).  NY-ESO-1 is a cytoplasmic protein that is detectable in multiple cancer types 
including non-small cell lung cancer (NSCLC), bladder cancer, malignant melanoma, 
liver cancer, synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), and many 
others.  Specific peptide epitopes of the NY-ESO-1 or LAGE-1a protein are processed 
and presented on the surface of the tumor cell in complex with an HLA molecule, which 
can be recognized by T cells.  An HLA-A2 binding peptide (SLLMWITQCaa 157-165) that 
is common to both NY-ESO-1 and LAGE-1a antigens has been identified that can be 
recognized by NY-ESO-1 reactive T-cells.  The T cells for therapy have been genetically 
engineered to express an affinity enhanced T-cell receptor toward the SLLMWITQC 
peptide bound to HLA-A*02. The retained optimized TCR clone was called 
NY-ESO-1c259 or c259. The T-cell product consists of autologous T cells transduced with 
a self-inactivating lentiviral vector encoding the affinity enhanced NY-ESO-1 specific 
TCR (c259).   
In previous clinical trials using adoptively transferred T cells directed against 
NY-ESO-1/LAGE-1a, objective responses have been observed in 40 to 60% of treated 
participants who are HLA-A*02+ bearing NY-ESO-1+ synovial sarcoma [Robbins, 2011; 
Robbins, 2015; D’Angelo, 2018b].  Similar or higher response rates have been observed 
with this treatment in metastatic melanoma [Robbins, 2011] and multiple myeloma post 
autologous stem cell transplant (ASCT) [Rapoport, 2015]. 
3.2 
Background 
Genetic modification of autologous T cells targeting specific tumor antigens has been 
developed to overcome immune tolerance and to empower the immune system of the 
cancer patient with lasting anti-tumor immunity permitting long term remission of 
disease.  TCRs can recognize not only cell surface proteins (as is the case with CAR T 
cells) but also any intracellular proteins, since TCRs recognize peptide fragments of these 
intracellular proteins that are processed and presented on the cell surface in the context of 
HLA. The TCR-modified T-cell approach is also particularly suited for solid tumors due 
to their ability to recognize low concentrations of these intracellular cognate antigens.  In 
addition, the TCR approach mimics the natural function of the T cell by recruiting the 
endogenous signalling molecules and adhering to correct spatial orientation between the 

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T cell and its target. These aspects may contribute to enhanced safety, anti-tumor activity 
of TCR engineered cells, as well as enhanced persistence of the infused TCR engineered 
T cells compared to CAR-T cells, providing ongoing anti-cancer protection.  
Morgan et al. first demonstrated tumor regression in 2 of 17 patients after adoptive 
transfer of genetically engineered T cells expressing a TCR specific for a 
melanocyte-differentiating antigen (MART-1) [Morgan, 2006]. 
Responding patients demonstrated long term persistence of infused T cells. Identification 
and sequencing of TCRs able to recognize epitopes expressed by human tumors together 
with improvements in TCR gene transfer technology has allowed for rapid redirection of 
T cells and targeting of a variety of tumor antigens, including gp100, carcinoembryonic 
antigen (CEA) [Johnson, 2009], p53 [Kuball, 2005], cancer testis antigen (CTA) family 
members such as NY-ESO-1 [Robbins, 2011] as well as melanoma associated antigens 
(MAGE)-A3 [Morgan, 2013], MAGE-A4 [Kageyama, 2015] and MAGE-A10 [Border, 
2018].  
Most clinical protocols with TCR gene therapy have incorporated preconditioning of the 
patient with a lymphodepleting chemotherapy regimen prior to T-cell infusion [Rohaan, 
2019].  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. 
Studies conducted by the NCI Surgery Branch have demonstrated that adoptive 
immunotherapy using T cells genetically engineered to recognize NY-ESO-1 following 
lymphodepletion led to objective antitumor responses in 4 of 6 patients (67%) [Robbins, 
2011] and 11 of 18 patients (61%) [Robbins, 2015] with synovial sarcoma. The estimated 
overall three and five-year survival rates for patients with synovial sarcoma were 38% 
and 14%, respectively [Robbins, 2015]. No toxicity attributed to the infused cells was 
reported in these studies.  
This protocol 208467 initially includes letetresgene autoleucel (lete-cel,  GSK3377794), 
for which background information is provided below.  Should other NY-ESO-1 specific 
(c259) T cells or combination agents be added in future, any applicable background 
information will be added via amendment.  
3.3 
GSK3377794 (letetresgene autoleucel, lete-cel)   
Lete-cel is the first generation product consisting of autologous T cells transduced with 
lentiviral vectors to express the affinity enhanced TCR (c259) and is currently being 
investigated in ongoing GSK sponsored pilot clinical trials in HLA-A*02+ participants 
with NY-ESO-1 and/or LAGE-1a positive metastatic synovial sarcoma (SS) (208466 
[ADP-04511]), advanced myxoid/ round cell liposarcoma (MRCLS) (study 208469 

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[ADP-0011-007]), non-small cell lung cancer (NSCLC) (GSK study 208749 [ADP-0011-
004] and GSK study 208471), and relapsed refractory multiple myeloma (MM) (study 
208470 [ADP-0011-008]).  
The most recent summary of the ongoing studies and clinical data obtained to date with 
these TCR engineered NY-ESO-1/LAGE-1a targeting T cells is presented in the most 
current Lete-cel Investigator’s Brochure.   
Lete-cel in combination with other anti-cancer agents such as PD-1/PD-L1 blocking 
agents like pembrolizumab is also being evaluated in MM (208470/ADP-0011-008) and 
in NSCLC (208471). In addition, an observational long-term follow-up study (Study 
208750) is being conducted in participants exposed to lete-cel in previous clinical trials 
as required for gene therapy products [EMA, 2009; FDA, 2020a; FDA, 2020b].  
As of 27 January 2021, 125 participants have received lete-cel across tumour types 
including SS, MM, MRCLS and NSCLC, investigated in our ongoing clinical 
programmes.  The efficacy and safety of lete-cel is described in the most current version 
of Lete-cel Investigator’s Brochure and summarized in the benefit/risk assessment in the 
relevant specific substudies.  

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4 OBJECTIVES AND ENDPOINTS 
Objectives and endpoints are outlined in the substudies.  
In general, the objectives and endpoints below will apply to all substudies unless 
otherwise specified. Discrepancies between those stated here and those in the substudies 
will not require amendment and those stated in the substudies will apply. 
Exploratory objectives and endpoints, if any, will be provided in the substudies.  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of 
NY-ESO-1 specific (c259) T cells, alone or 
in combination with other anti-cancer 
agents, in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 participants with 
NY-ESO-1 and/or LAGE-1a positive solid 
tumors 
Overall Response Rate (ORR) per RECIST v1.11 
Secondary - Efficacy 
To further evaluate the efficacy of 
NY-ESO-1 specific (c259) T cells alone or 
in combination with other anti-cancer 
agents in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 participants with NY-
ESO-1 and/or LAGE-1a positive solid 
tumors 
• Time to Response (TTR) 
• Duration of Response (DoR) 
• Disease Control Rate (DCR) 
• Progression Free Survival (PFS) 
Secondary - Safety  
To evaluate the safety and tolerability of 
NY-ESO-1 specific (c259) T cells alone or 
in combination with other anti-cancer 
agents in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 participants with 
NY-ESO-1 and/or LAGE-1a positive solid 
tumors 
• Frequency and severity of Adverse events 
(AEs), serious adverse events (SAEs) and 
AEs of special interest (AESI; as defined in 
protocol) 
• Laboratory parameters 
• Replication Competent Lentivirus (RCL) 
• Instances of Insertional oncogenesis (IO) 
Secondary - Pharmacokinetics 
To characterize in vivo cellular PK profile 
(levels, expansion, persistence) of 
NY-ESO-1 specific (c259) T cells 
• Maximum transgene expansion (Cmax) 
• Time to Cmax (Tmax) 
• Area under the time curve from zero to time t 
AUC(0-t), as data permit 
 
AE/s = adverse event/s; AESI/s = adverse event/s of special interest; AUC(0-t)  = area under the time curve 
from zero to time t; Cmax = maximum concentration; DCR = disease control rate; DoR = duration of 
response; HLA = human leukocyte antigen; IO = insertional oncogenesis; ORR = overall response rate; 
OS = overall survival; PFS = progression-free survival; RCL = replication competent lentivirus; 
RECIST = Response Evaluation Criteria In Solid Tumors; SAE/s = serious AE/s; Tmax = Time to Cmax; 
TTR = Time to Response 
1 Independent central review where applicable will be specified in the specific substudies.  

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5 STUDY DESIGN 
5.1 
Overall Design 
This is a master protocol investigating the safety and antitumor activity of TCR 
engineered NY-ESO-1 specific (c259) T-cells alone or in combination with other agents 
in HLA-A*02 + participants with NY-ESO-1 and/or LAGE-1a positive advanced solid 
tumors. 
The protocol will initially evaluate a first generation of NY-ESO-1 specific TCR (c259) 
engineered T-cells, letetresgene autoleucel (lete-cel, GSK3377794), in HLA-A*02+ 
participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma. 
The protocol may be amended later to investigate the activity of other TCR engineered 
NY-ESO-1 specific (c259) T-cells in other NY-ESO-1+ or LAGE-1a + tumor types and/or 
in combination with other agents (see Figure 1 Study Design schematic below).  Details 
of treatment are provided in the substudies. 
Figure 1 
Study Design 
 
If additional treatments are combined with T-cell treatment in future substudies, the 
details of treatment will be given in the specific substudies. 
Participant Journey 
Unless otherwise specified in a given substudy, participants will undergo stepwise 
enrollment followed by treatment according to defined phases within each substudy (See 
Figure 2 Participant Journey Schema below) which will include the following: 

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Part 1: Screening 
1) Target expression screening for the presence of HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 positivity and tumor expression of NY ESO-1 and/or 
LAGE-1a, 
(Note: If a participant was previously tested for HLA and NY-ESO-1/LAGE-1a expression under 
a different GSK-sponsored protocol, testing of HLA and/or NY-ESO-1 for 208467 may not be 
required dependent on the test platform(s) used and whether they meet the 208467 protocol 
requirements [see Section 6.3]) 
2) Leukapheresis eligibility screening phase to determine eligibility for undergoing 
leukapheresis beginning up to 28 days prior to leukapheresis,  
Part 2: Leukapheresis/Manufacture 
3) Leukapheresis procedure, 
(Note: leukapheresis may have been performed under another GSK-sponsored protocol or 
substudy of this protocol)   
Part 3: Lymphodepletion/Treatment 
4)  Treatment fitness assessment for safety and final Treatment eligibility screening,  
5)  Interventional phase including Lymphodepletion from Days-7 to -4, TCR 
engineered T-cell infusion on Day 1 and follow-up as defined in each specific 
substudy, 
(Note: TCR engineered T-cell may have been manufactured under another GSK-sponsored 
protocol or substudy of this protocol)   
Part 4: Long-Term Follow-Up (LTFU) 
6) Long-term follow-up phase for up to 15 years from the date of TCR engineered 
T-cell infusion.   
Figure 2 
Participant Journey Schema 
 
Part 1: Screening 
Screening will consist of two phases: target expression screening and leukapheresis 
eligibility screening. 
Target expression screening (i.e. HLA type and tumor NY-ESO-1/LAGE-1a antigen 
expression) may start at any time after diagnosis of high-risk locally advanced disease 

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(i.e. deeply seated, high grade, positive margins, large [≥5 cm], or locally recurrent) for 
Substudy 1, or advanced (metastatic or unresectable) disease for Substudy 2, subject to 
any substudy specific requirements.  Disease recurrence or progression may be present 
but is not mandatory for screening.  
For target expression screening, once informed consent has been obtained, 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/or LAGE-1a expression will also 
be evaluated on representative tumor tissue from a formalin-fixed and paraffin-embedded 
(FFPE) archival (most recent preferred) or fresh biopsy. HLA-typing and tumor antigen 
expression testing should be performed sequentially (considering the expected >50% 
attrition with HLA) but may also be performed in parallel at the discretion of the 
Investigator. In the future, if a tumor type is known to express NY-ESO-1 and/or 
LAGE-1a in a high percentage of cases, testing for the antigen expression may be 
omitted. 
Once participants are deemed positive for HLA and tumor antigen expression, they will 
sign the main study informed consent to undergo screening for leukapheresis eligibility 
within 28 days prior to the day of the scheduled leukapheresis procedure. 
Part 2: Leukapheresis/Manufacture 
Leukapheresis can be initiated following confirmation of eligibility for leukapheresis, 
which includes a series of lab assessments required to be completed within 7 days from 
the day of 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.  
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.  Manufacture 
of autologous T cells (lete-cel, GSK3377794) requires an average of 35-42 days.  
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, 
thereby improving chances of a treatment effect.   
• 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.   
The cryopreserved T-cell product from leukapheresis is stable for 2 years.  The 
cryopreserved drug product (NY-ESO-1 specific (c259) T cells) is also stable for 2 years. 

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It is expected that early leukapheresis can be safely performed in a participant receiving 
either chemotherapy and / or targeted agents, as long as the protocol specified 
leukapheresis eligibility requirements are satisfied.   In general, leukapheresis is well 
tolerated.  Side effects during the procedure may include numbness and/or tingling in the 
extremities or muscle twitching due to the anticoagulant used in the machine.  Low blood 
pressure with light-headedness, chest discomfort, and/or shortness of breath may occur at 
the beginning of the procedure.  Uncommon events include fainting, pain, nausea, 
vomiting, blood clotting difficulties, fatigue, and/or bruising at the needle injection sites.  
Extremely rare events may include air embolism, blood loss from accidental leakage 
from tubing, infection, difficulty breathing, transient arrhythmias, shock, or heart failure.  
Both the Investigators and potentially eligible participants will be fully informed and 
aware of these potential risks.  Also, sites are chosen based on expertise for managing 
any potential risks associated with NY-ESO-1 specific (c259) T cells and/or procedural 
risks.  Adverse events will be monitored as described in Section 9.4.1. 
Following leukapheresis, T-cell manufacture will be undertaken.  
Unless otherwise specified in a specific substudy, bridging or standard of care 
intermediate anti-cancer therapies [e.g. chemotherapy, local therapy (e.g. radiotherapy, 
cryoablation, surgical resection, etc.)] may be administered between leukapheresis and 
the start of lymphodepletion, if a participant cannot be treatment-free. The following 
conditions must be met: 
1. Mandatory washout periods prior to start of T-cell infusion must be respected (See 
specific substudies) 
AND 
2. Indicated based on benefit/risk assessment and/or local regulatory requirements and 
following agreement with Sponsor’s Medical Monitor (or designee) 
AND 
3. Treatments, AEs and other clinical observations are reported into the current study 
database 
A baseline scan is performed prior to lymphodepletion to confirm the presence of 
measurable disease and then the participant will receive T-cell infusion and be followed 
as per RECIST v1.1 for efficacy analysis and per iRECIST for treatment decisions.  
Participants who have failed screening or withdrawn before T-cell infusion, may rescreen 
in the same substudy or consider entering screening for another substudy (see Section 6.2 
for further details).  
Part 3: Lymphodepletion/Treatment 
The following conditions need to be satisfied prior to initiating lymphodepletion and 
T cell treatment. 
1. Treatment fitness assessment and confirmation of additional inclusion/exclusion 
criteria for treatment must be completed within 10 days prior to initiating 
lymphodepleting chemotherapy. 

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2. Baseline radiological tumor assessment is obtained within 10 days prior to 
lymphodepletion.  
3. T-cell product availability verified by site for each criterion below:  
a. Confirmation of successful manufacture of T-cell product 
b. T-cell product satisfies all release criteria as stated on Certificate of Analysis 
c. T-cell product available for infusion at the site per criteria specified in the Drug 
Product and Infusion Manual 
4. Pre-treatment tumor biopsy collected prior to initiating lymphodepletion is required. 
This biopsy will be used as baseline for biomarker analyses. If it is not feasible to 
obtain a fresh biopsy, archival tumor biopsy (FFPE block) taken preferably after 
completion of the participant’s last line of therapy, preferably within 90 days prior to 
initiating lymphodepleting chemotherapy, may be accepted at the discretion of the 
Medical Monitor (or designee).  For participants who already provided a fresh biopsy 
for antigen expression and did not receive any bridging or standard of care 
intermediate anti-cancer therapy, the screening biopsy will be used for baseline.  
Following lymphodepletion, after ~24 hours of completing lymphodepleting 
chemotherapy (i.e., on Day -3), participants must receive Granulocyte-Colony 
Stimulating Factor (G-CSF) support in accordance with ASCO guidelines [Smith, 2015] 
or institutional practice.  The formulation of G-CSF to be used can be decided by the 
Investigator based on the institutional practice. 
Participants will be hospitalized on the day of T‑cell infusion (Day 1) and may be in the 
hospital for follow-up care until Day 3 as clinically indicated. Through Day 14, 
participants must be closely monitored by the Investigator. Additional close monitoring 
or hospitalization may be warranted based upon clinical need and is at Investigator’s 
discretion (please refer to Section 9.3 for safety assessments and monitoring; Section 9.4 
for reporting of adverse events; and Section 12.7 for supportive care guidance on T-cell 
infusion, CRS and other potential risks). 
Participants will be frequently monitored for any unexpected Grade ≥3 AE and any 
SAEs, according to the SoA in the specific substudies. 
Participants who are not eligible for study intervention by the time NY-ESO-1 specific 
(c259) T cells expire, will be withdrawn from the study and will not undergo 
lymphodepletion within this study.   
Any remaining manufactured T cells from each participant (whether or not eligible for 
study intervention) will be stored by the Sponsor for the current shelf life of the cells after 
manufacture is completed.  After expiry of the shelf life, the stored T cells can be 
destroyed or, if consented, used for scientific research at the Sponsor’s discretion for a 
period of up to 15 years depending on local regulations.  
Part 4:  Long-Term Follow-Up (LTFU) 
At the end of the study for each participant (as defined in Section 5.3.1), and no sooner 
than 90 days post T-cell infusion (in order to capture minimal safety information), 

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participant will be entered into a separate LTFU protocol (GSK study 208750) and will 
be monitored for up to 15 years post T-cell infusion.  
5.2 
Number of Participants 
As this is a master protocol consisting of multiple substudies, the overall sample size is 
not fixed. The initial number of participants is expected to be approximately 97 in 
Substudies 1 and 2 combined.  Substudy 1 will enroll 10 participants with previously 
untreated advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell 
liposarcoma, that is either newly diagnosed or relapsed after surgery and radiotherapy 
and /or adjuvant therapy.  Substudy 2 will enroll approximately 87 participants 
previously treated with anthracycline-based regimen for advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma, including : 
• Approximately 15 participants expected to receive the clinical drug product 
supply; 
• Approximately 72 participants will be enrolled to ensure that at least 60 
participants will receive letetresgene autoleucel (lete-cel, GSK3377794) using 
commercial vector supply and manufacturing process.  An additional 20% 
enrollment is factored in between leukapheresis and dosing to account for: early 
withdrawal, manufacturing issues, and extended waiting-time for progression. 
Any additional substudies will be added via protocol amendments with specification of 
number of participants for each substudy.  
Refer to the substudies for additional details on sample size determinations. 
5.3 
End of Master Protocol Definition 
5.3.1 End of Study for Individual Participants 
Refer to the substudies (including Substudy 1-Section 5.3 and Substudy 2-Section 5.3) 
for end of substudy definitions for Individual Participants. 
5.3.2 End of Master Protocol 
This Master Protocol will end as of the last visit of the last participant in the last 
sub-study, or when all participants have met their respective substudy end criteria 
including those who have died, withdrawn consent or are lost to follow-up. 
Subject to specific criteria outlined in each substudy, in general any participant who has 
not reached progressive disease by end of substudy or is still being followed in long-term 
follow-up phase by end of substudy will be transferred to a separate long-term follow up 
protocol (GSK study 208750) for observation of delayed AEs and survival for a duration 
of up to 15 years post-T cell infusion in accordance with FDA [FDA, 2020a] and EMA 
guidance [EMA, 2009]. 

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5.4 
Scientific Rationale for Protocol Design 
This is a master protocol design to evaluate TCR engineered NY-ESO-1 specific (c259) 
T cells alone or in combination with other agents in HLA-A*02+ participants with 
NY-ESO-1 and/or LAGE-1a Positive Solid Tumors via independent substudies.  
The scientific rationale for each substudy is provided in each specific substudy.  
5.4.1 Data Monitoring Committee  
An Independent Data Monitoring Committee (IDMC) consisting of external experts will 
be established for ongoing review of safety events and efficacy to enable benefit/risk 
determination, for all substudies of this master protocol, independent of the study team. 
Additional details will be provided in an IDMC Charter. 
Key recommendations of the IDMC will be documented and reported to regulatory 
agencies if requested, all participating Principle Investigators (PIs) and if required, 
Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs) as 
appropriate with impactful decisions communicated as priority.  
6 PROTOCOL POPULATION 
Prospective approval of protocol deviations relating to enrollment criteria for the purpose 
of recruiting participants, also known as protocol waivers or exemptions, is not permitted. 
The protocol will enroll participants with solid tumors to independent substudies. 
Initially, the protocol will enroll participants with advanced (metastatic or unresectable) 
synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS) (Substudies1 and 2).  
Substudy 2 will be a registration substudy and will enroll participants with advanced 
metastatic or unresectable sarcomas or MRCLS who have progressed following 
anthracycline based chemotherapy.   
Due to differences in entry criteria for the specific participant populations, all inclusion 
and exclusion criteria and lifestyle considerations are presented in the specific substudies.   
Eligibility Screening will take place in the following 3 steps: 
• Target Expression Screening: A set of criteria permitting participants’ blood to be 
screened for HLA status and archival (most recent preferred) or fresh tumor 
biopsy samples to be screened for the expression of NY-ESO-1 and/or LAGE-1a.   
• Leukapheresis Screening:  Eligibility must be fulfilled prior to performing 
leukapheresis procedure. 
• Lymphodepletion and Treatment Eligibility Screening: To be fulfilled prior to 
commencing lymphodepleting chemotherapy and administration of T cells. 

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6.1 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical 
protocol but are not subsequently enrolled into a substudy. 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 may also 
include disease characteristics, prior lines of anti cancer treatment, performance status 
and any serious adverse events (SAEs). 
6.2 
Rescreening 
Individuals who do not meet the criteria for participation in a given substudy at any stage 
(screen failure or withdrawal) may be rescreened for any applicable substudy upon 
Sponsor agreement.  Participants rescreened will be assigned a new participant number. 
For each rescreened participant, the Sponsor will confirm the following on evaluation for 
an applicable substudy: 
• Participant has previously tested positive for protocol-specified HLA typing by a 
validated test in a designated central laboratory; 
• Participant’s tumor has previously been pathologically reviewed by a Sponsor 
designated central laboratory with confirmed positive NY-ESO-1 and/or LAGE-
1a antigen expression;  
• Participant has previously completed Sponsor protocol-specified leukapheresis, 
and cryopreserved T cells or manufactured product are available and within shelf-
life specifications. 
6.3 
Screening Under Other GSK Studies 
Participants screened or enrolled in other GSK studies may be considered for enrollment 
into this study, where it is IRB/IEC approved, on a case-by-case scenario following a 
risk/benefit evaluation between the Investigator and Sponsor Medical Monitor (or 
designee).  
Where a participant was previously tested for HLA and/or antigen expression under a 
different GSK-sponsored protocol, testing of HLA and/or antigen expression for 208467 
may not be required dependent on the test platform(s) used and whether they meet the 
208467 protocol requirements. If the Study 208467 testing requirements are not met, 
repeat test(s) may be 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 accepted, in consultation 
with the Sponsor. Additionally, if the NY-ESO-1 specific TCR engineered T cells are 
already manufactured for these participants, leukapheresis and/or re-manufacture process 
may not be necessary, in consultation with the Sponsor. 

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7 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. 
Details of study interventions and guidelines, including dose, administration, and 
concomitant medications are specified in each substudy.  
In general, however, study intervention will follow the steps outlined in Section 5.1 and 
in the intervention schema included there.   
8 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
The guidelines and criteria below apply to all protocol participants except where 
otherwise indicated in specific substudies.  
8.1 
Discontinuation of Study Intervention 
As the T-cell intervention is administered as a single dose, there is no possibility of 
discontinuation of study intervention.  In the event of severe reactions 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 9.3 for safety 
assessments and monitoring; Section 9.4 for reporting of adverse events; and Section 12.7 
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 Co-ordinator 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. The bag of cells that was being infused prior to reaction, cannot be 
used beyond 45 min after thawing. When restarting infusion, new previously unthawed 
bag of cells needs to be used following Drug Product and Infusion Manual.  
Should other agents be added in future either as monotherapy or combination therapy, 
any additional details will be added via amendment to this core or via additional 
substudies, as applicable. 
8.2 
Liver Chemistry Increased Monitoring Criteria 
Liver chemistry increased monitoring criteria have been designed to assure participant 
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The following Level 1 and Level 2 monitoring are required for all participants.  
Level 1 Monitoring 
In the event that a participant develops elevations in liver function test (LFT) parameter 
values as defined below, an increase to liver chemistry monitoring i.e., at weekly 
intervals, will apply. 
Liver Chemistry Monitoring Criteria Level 1 
Criteria 
Actions 
ALT ≥3x ULN 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, stabilise 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. 
ALT = alanine aminotransferase; ULN = upper limit of normal; AST = aspartate aminotransferase. 
Level 2 Monitoring 
In the event that the participant develops elevations in LFT parameters as defined below, 
an increase to liver chemistry monitoring at more frequent intervals i.e. twice weekly, 
will apply.  
Liver Chemistry Monitoring Criteria Level 2 
ALT Absolute 
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 CRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• 
Perform liver event follow-up assessments  
• Viral hepatitis serology4 
• Obtain INR and recheck with each liver chemistry 
assessment until the transaminases values show 
downward trend 
• Serum creatine phosphokinase (CPK) and lactate 
dehydrogenase (LDH). 

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• 
Monitor the participant until liver chemistries 
resolve, stabilize, or return to within baseline 
(pre-gene therapy) 
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 participants 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 24-72 hrs  
• 
Monitor participants at least weekly until liver 
chemistries resolve, stabilize or return to 
within baseline (pre-Gene Therapy) 
• Fractionate bilirubin, if total bilirubin 2xULN 
• If possible, obtain peripheral blood for persistence of 
genetically modified cells. 
• Obtain complete blood count 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, other over the counter 
medications. 
• Record alcohol use on the liver event alcohol intake 
case report form 
For bilirubin or INR criteria: 
• Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 
quantitative total immunoglobulin G (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 CRFs. 
1. 
Serum bilirubin fractionation should be performed if testing is available. Additionally, if serum bilirubin fractionation 
testing is unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin 
elevations and suggesting liver injury.  
2. 
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR >1.5, which may 
indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis); The INR threshold value stated will not apply to participants receiving anticoagulants. 
3. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia).  
4. 
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen (HbsAg) and Hepatitis B Core Antibody (IgM); 
Hepatitis C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
obtain heterophile antibody or monospot testing); Hepatitis E IgM antibody. 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase; CRF = Case 
Report Form; LDH = lactate dehydrogenase; INR = International normalized ratio; ULN = upper limit of normal. 
 
8.2.1 Temporary Discontinuation 
NY-ESO-1 specific (c259) T-cell intervention is administered as a single dose via IV 
infusion.  In the event of severe reactions associated with liver toxicities during infusion, 
the infusion may be interrupted.  Please refer to Section 8.1 for guidance on 
discontinuation of intervention and restarting of infusion.  
Should other agents be added in future either as monotherapy or combination therapy, 
any additional details will be added via amendment to this core or via additional 
substudies, as applicable. 

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8.3 
Participant Discontinuation/Withdrawal from the Study 
• A participant may withdraw from the substudy to which he/she is enrolled at any 
time at his/her own request or at the discretion of the Investigator for safety, 
behavioral, compliance or administrative reasons. No further assessments will be 
required, and the Investigator must document this in the site study records.  
• At the time of study withdrawal, if possible, participant will be asked to consent 
to LTFU study.   
• If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• If a participant withdraws from the substudy to which he/she is enrolled after 
providing study samples, GSK will retain those samples and any results generated 
from testing prior to participant withdrawal, as described in the informed consent.  
If the participant specifically requested destruction of their samples at the time of 
withdrawal, the Investigator should notify GSK, and document this in the site 
study records. Once notified, GSK will not perform any further testing, and will 
destroy the sample.  
• A participant will be considered to have withdrawn from the substudy to which 
he/she is enrolled if the participant has not died and is lost to follow-up 
(Section 8.4).  
• Refer to the SoA in each substudy for data to be collected at the time of study 
discontinuation and for any further evaluations that need to be completed.  
8.4 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the substudy to which he/she is enrolled. 
• Before a participant is deemed lost to follow up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the substudy to which he/she is enrolled.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Section 12.1. 

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8.5 Study Stopping and Pausing Rules  
The 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 
IDMC, IRBs/ECs, and the Sponsor: 
• Any event of Guillain-Barré 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 and IDMC. 
 
Premature study termination may occur if: 
• Sponsor, in consultation with IDMC, decides for any reason that participant safety 
may be compromised by continuing the study. 
• The Sponsor decides to discontinue the development of the intervention to be 
used in this study.  
 
It is expected that AEs will occur frequently in these patient populations based on  
underlying advanced malignancies in the initial and future substudies and these AEs can 
be SAEs.  A review of individual significant safety events across all substudies in 
conjunction with the cumulative review of safety data by the sponsor, IDMC, and 
Investigators, will inform decisions for premature termination of individual substudies or 
the entire study.  SAEs that are related to the direct effects of T cell therapy may be 
considered as stopping criteria, upon consultation with IDMC. Premature termination of 
individual substudies or the entire clinical study may occur because of a regulatory 
authority decision.  
9 STUDY ASSESSMENTS AND PROCEDURES 
Study assessments and procedures and their timings are summarized in the SoA tables 
within each substudy.  
Unless otherwise stated in a substudy and its SoA, the descriptions and guidelines in this 
section and subsections will apply.  Where there is a discrepancy between this core 
protocol and the relevant substudy, the substudy should be followed.  
Adherence to the substudy design requirements, including those specified in the SoA, is 
essential and required for study conduct. Protocol waivers or exemptions are not allowed 
except for immediate safety concerns.  
Immediate safety concerns should be discussed with the Sponsor upon occurrence or 
awareness to determine if the participant should continue or discontinue study treatment.  

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All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
Informed consent must be signed by a participant before any study required procedures 
are performed. However, procedures conducted as part of the routine clinical 
management (e.g., imaging studies) and conducted prior to signing of the study informed 
consent may be used for screening/baseline assessments provided the procedure fulfills 
the protocol defined specifications and has been performed within the protocol indicated 
timeframe.  
If assessments are scheduled for the same nominal time, then the assessments should 
occur in the following order:  
1. 12-lead ECG  
2. Vital signs  
3. Blood draws  
 
9.1 
Efficacy Assessments 
See individual substudies for any additional assessments.  
9.1.1 Evaluation of Anti-Cancer Activity 
Tumor assessments for response and progression will be evaluated according to 
RECIST v1.1 [Eisenhauer, 2009] and iRECIST (see Section 12.6):   
• RECIST v1.1 will be used in the assessment of disease burden (target and non-
target lesions determination) at baseline and as the primary measure of tumor 
response endpoints.   
• iRECIST will be used to aid in clinical decision making and for exploratory 
evaluations. 
 
See the SoA within each specific substudy for the schedule of assessments of anti-cancer 
activity. Acceptable imaging modalities for this study include: 
• Diagnostic-quality computed tomography (CT) scan with oral and/or IV iodinated 
contrast of the chest and abdomen/pelvis (CT is the preferred modality for tumor 
assessments).  Extremities and/or skin lesions will be assessed if required. 
• In cases where contrast enhanced CT is contraindicated, a Magnetic resonance 
imaging (MRI) of the abdomen/pelvis (with and without gadolinium contrast), 
and an MRI (with and without gadolinium contrast) or a non-contrast enhanced 
CT of the chest is acceptable.  The same imaging modality should be followed for 
each subsequent assessment.   
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• Digital photographs of skin lesions including a ruler for estimating the size of the 
lesion. 
 
Tumor measurements for each participant should be performed by the same Investigator 
or radiologist (to the extent that this is feasible). 
To allow time for the immune response to become apparent and for potential transient 
inflammatory reaction of the disease to the treatment (‘tumor flare’), response will not be 
assessed before 4 weeks post infusion of NY-ESO-1-specific (c259) T-cells unless there 
is unequivocal clinical evidence of deterioration.  Response or progression is to be 
confirmed by repeat imaging scan performed not earlier than 4 weeks and not later than 8 
weeks after the criteria for response or progression was first met.  For post-baseline 
assessments, a window is permitted to allow for flexible scheduling as defined in the SoA 
within each specific substudy.  
Tumor images will be obtained and transmitted to a central imaging vendor for potential 
central review. The process for tumor imaging and transmission to the central imaging 
vendor are detailed in the Imaging Manual. 
9.1.2 Long-Term Follow-up 
Upon the end of the applicable substudy for each participant, participant will be entered 
into a separate LTFU protocol (GSK study 208750) and will be monitored for up to 
15 years post T-cell infusion. 
9.2 
Patient Reported Outcomes 
Patient reported outcomes will be assessed as part of this protocol.  Specifics regarding 
which measures will be employed are outlined in the substudies. 
9.3 
Safety Assessments 
9.3.1 Safety Review Team 
An internal Safety Review Team (SRT) is in place, consisting of a cross functional team 
of the appropriate disciplines required to ensure holistic evaluation of the safety profile of 
the NY-ESO-1 specific (c259) T-cell product under evaluation.  The Safety review team 
conducts systematic, periodic and documented reviews of available safety data from all 
studies in the program and addresses the safety issues pertinent to the medicine.   
9.3.2 Physical Examinations and Developmental Examinations 
A complete physical examination will include, at a minimum, weight, and assessments of 
the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height 
will be assessed at timepoints indicated in the SoA for each substudy. 
A dedicated physical examination will include assessments based on specific concerns of 
the Investigator. 

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Investigators should pay special attention to clinical signs related to previous serious 
illnesses or tumor sites.  
9.3.3 Additional Assessments for Pediatric Participants 
For pediatric participants, height and weight will also be evaluated as a percentile vs 
national growth charts (based on sex and age) and vs genetic height target (expected 
height based on parental heights) and evaluation will be performed on whether growth is 
normal or abnormal. 
For pediatric participants, puberty assessments will be undertaken once a year until 
puberty is completed.  Puberty will be assessed by means of genital examination in the 
physical examination, completion of the Tanner scale, general questioning of the 
participant about their sexual activity, sexual potency (males) and menstrual cycles 
(females). 
Developmental examinations will also be performed once a year. 
9.3.4 Lansky, Karnofsky, or ECOG Performance Status 
The performance status will be assessed per Table 1 below: 
Table 1 
Performance status scale 
Participant age  
(years) 
Performance status scale to be used  
(Section 12.9)  
<16 
Lansky 
≥16 and < 18 
Karnofsky 
≥18 
ECOG 
 
using Lansky (for participants <16 years of age) or Karnofsky (for participants 16 and 
<18 years of age) or ECOG (for participants 18 years of age) scale (Section 12.9) at the 
time points specified in the SoA in each substudy.  Participants who become 16 or 18 
years of age during the study should switch to the age-appropriate index at that time. 
9.3.5 Vital Signs 
Blood pressure, pulse measurements (rate and oximetry), respiratory rate, and body 
temperature should be assessed per institutional standards. These will be assessed as per 
the SOA Tables in Section 2 of each substudy and recorded in the eCRF. The same 
methods should be used throughout the course of the substudy. Manual techniques will be 
used only if an automated device is not available. 
Where vital signs and blood collection for laboratory tests are performed on the same 
day, vitals signs should be taken before blood collection. 
On the day of T-cell infusion (Day 1), vital signs must be assessed pre-infusion, at 
approximately 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has 
started. On the day of T-cell infusion (Day 1), pulse oximetry should be taken pre-

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infusion, and at approximately 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the 
infusion has started. 
9.3.6 Cardiac Assessments 
All cardiac assessments will be performed locally at the site. 
The following assessments will be conducted in order to monitor participant safety: 
An ECHO or MUGA scan is required to determine eligibility. Additional scans may be 
performed as clinically indicated.  NOTE: the same method of cardiac evaluation should 
be used consistently for all follow-up scans. 
Single or triplicate 12-lead ECG will be obtained using an ECG machine that 
automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.  
The replicate ECG tracings should be obtained as closely as possible in succession.  The 
full set of triplicates should be completed in less than 4 minutes.   
Serum troponin and NT-proBNP / BNP as markers for cardiac health will be assessed 
prior to initiation of lymphodepletion. 
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.  

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9.3.7 Pulmonary Assessments 
Participants with known lung metastases (active or previously treated with surgical 
resection or radiotherapy) should be considered for pulmonary consultation prior to 
lymphodepletion, which may include pulmonary function tests. 
Participants deemed at high risk for pulmonary complications per the 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:  
• Close monitoring of chest imaging, as clinically indicated 
• Close monitoring of fluid balance 
• 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. 
9.3.8 Monitoring for Immune Effector Cell-Associated Neurotoxicity  
Syndrome 
Brain MRI (or CT Scan if MRI is not feasible) must be obtained for all participants as 
part of leukapheresis eligibility screening.  This should be repeated at baseline prior to 
lymphodepletion if more than 4 months have elapsed since leukapheresis screening. 
Brain MRI may be performed as clinically indicated thereafter. 
Immune Effector Cell-Associated Encephalopathy (ICE) ICE (see Section 12.7.8 for 
definition) must be measured immediately prior to T-cell infusion on the day of infusion, 
and then according to each substudy SoA. Participants with known brain metastases (if 
not excluded in the substudy) must be monitored at least twice per day for the first 5 days 
following T-cell infusion. If a participant is found to have Immune Effector Cell-
Associated Neurotoxicity Syndrome (ICANS), the ICE neurological assessment tool 
should be used at least twice per day until ICANS is resolved or stable and may be 
measured at follow up visits if indicated. 
For management of ICANS, refer to Section 12.7.8. 

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9.3.9 Monitoring for Demyelinating Neuropathy and Other Neurological 
Events 
Obtain a neurological consultation for participants with Grade 2 or higher neurologic 
events of a ≥ 7 day duration.  Participants who develop signs and symptoms consistent 
with GBS must be evaluated by a neurologist according to diagnostic guidance for GBS 
[Fokke, 2014] to provide expert recommendations to guide appropriate diagnostic 
workup such as electromyography (EMG), lumbar puncture, infectious panel to guide 
management and follow up (See Section 12.7.10). 
Any additional monitoring requirements or modifications to these requirements as well as 
any management guidelines will be addressed in the substudies. 
9.3.10 Clinical Safety Laboratory Assessments 
Refer to Section 12.2 for the list of clinical laboratory tests to be performed.  
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 CRF. 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 abnormal laboratory values considered clinically significant occurring during 
participation in the study or within 30 days after the last dose of study treatment should 
be repeated until the values return to normal or baseline. 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 Section 12.2 must be 
conducted in accordance with the laboratory manual and the SoA in each 
substudy. Reference ranges for all safety parameters must be provided to the site by the 
laboratory responsible for the assessments.  
9.3.11 Monitoring and Management of Replication-Competent Lentivirus 
(RCL) using Vesicular Stomatitis Virus G protein (VSV-G) 
Replication Competent Lentivirus (RCL) is a potential risk associated with the use of 
lentiviral vectors; no RCL has ever been detected ex vivo or in vivo. The risk is derived 
from the detection of Replication Competent Retrovirus (RCR) during the use of early γ 
retroviral vector packaging systems which were inadequately designed to avoid 
recombination events between the vector and packaging components [Miller, 1990]. 
Updated γ retroviral packaging systems have not been associated with RCR. However, 
RCR/L must continue to be rigorously evaluated in vector and cell lots, and in 
participants post infusion [FDA, 2020a; FDA, 2020b; FDA, 2010]. 
Regulatory Agencies and the gene therapy community have previously discussed 
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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. 
9.3.11.1 
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.  
Participant’s PBMCs will be collected at timepoints indicated in the SoA within each 
substudy. If no gene modified cells are detected for 2 consecutive assessments 
post-infusion, and the participant is 2 years post infusion, RCL sample collection will 
discontinue. 
If VSV-G deoxyribonucleic acid (DNA) copies are detected at any time point in the first 
year post-infusion, the safety monitoring protocol in Section 9.3.11.2 will be triggered. 
Participant’s samples will continue to be tested for VSV-G DNA copies until VSV-G 
DNA copies are not detected for 2 consecutive annual assessments. 
NOTE: The participant will continue to be followed by the Investigator by phone call or 
survey for up to 15 years post-infusion. If contact with the Investigator becomes no 
longer feasible, follow up can be transitioned to a local physician, preferably an 
oncologist.  
9.3.11.2 
Safety Monitoring Protocol 
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 will take 
place. 
If the second test is positive, infusions for all participants receiving cells modified with 
the same vector lot will be postponed. The participant with the confirmed positive 

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VSV-G signal will be scheduled for leukapheresis and a biological RCL test will be 
performed on the leukapheresis product. The biological RCL test assesses whether there 
is active production of infectious viral particles from the leukapheresis product [Manilla, 
2005]. 
If the biological RCL is positive, all NY-ESO-1 specific (c259) T-cell infusions will be 
halted. 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. 
9.3.12 Testing for Persistence of Transduced T cells and Insertional 
Oncogenesis 
Peripheral blood mononuclear cells (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.  
If no gene modified cells are detected for two consecutive assessments post infusion, and 
the participant is ≥2 years post infusion (for example, negative persistence assessments at 
year 4 and 4.5), monitoring will end including for other laboratory assessments such as 
hematology and chemistry. The participant will continue to be followed by the 
Investigator by phone call or survey for up to 15 years post-infusion. If contact with the 
Investigator becomes no longer feasible, follow up can be transitioned to a local 
physician, preferably an oncologist.  
At the first instance of >1% of PBMCs testing positive for the 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), persistence and integration site assessment will 
be repeated within 3 months on a new sample. If the repeated analysis 
demonstrates: 1) persistent monoclonality, 2) evidence of insertional oncogenesis; 
OR 3) clonal expansion (an increase in percent predominance of a clone), there 
will be a review by 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 any suspicion/report of potential hematological 
malignancy. 
 

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In all cases of SAE that occur after T cell infusion, a transgene copy (persistence) sample 
must be obtained if feasible. 
9.4 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 12.3. 
The Investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE.  The Investigator or 
designee is 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 
intervention or the study (see substudies).  
In the absence of a clear alternative etiology (e.g., chemotherapy, concomitant 
medications, disease progression, infections, etc.), AEs should be considered potentially 
immune-related. Immune-related AEs may include diarrhea/colitis, rash, hepatitis, Graft 
versus host disease (GVHD), cytokine release syndrome (CRS), secondary pancytopenia, 
pneumonitis, endocrinopathies, nephritis, and any other manifestations that may indicate 
an immune-related phenomenon. 
Adverse events of special interest (AESIs) in this study are defined in Section 9.4.7. 
AESIs will be reported to Sponsor (Medical Monitor or designee) within 24 hours via 
e-mail (see SRM for further instructions).  
Due to the nature of the treatment, participants are required to be followed for up to 
15 years after treatment with genetically modified T cells according to FDA and EMA 
guidances [FDA, 2020a; FDA, 2020b; EMA, 2009].  Certain events in this protocol are 
identified as delayed AEs and should be marked as delayed AEs in the eCRF. 
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.  Delayed AEs will be collected as part of the LTFU phase of 
the substudy 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. Any 
AE collected on-study may also be indicated as a delayed AE by the Investigator at their 
discretion.  
The 6 categories for delayed AEs are: 
• New malignancies 
• 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 a hematologic disorder 

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• New incidence of an infection (potentially related to gene modified cell therapy) 
• Unanticipated illness or hospitalization deemed related to gene modified cell 
therapy 
 
If a participant is monitored in this protocol post disease progression (for example, in 
Substudy 2), s/he will only be monitored for delayed AEs. 
9.4.1 Time Period and Frequency for Collecting AE and SAE Information 
Collection of AEs and SAE starts from time of signing the ICF for target expression 
screening, and will be performed as follows: 
• All SAEs will be collected from the start of leukapheresis until the end of study, 
or through 90 days following T-cell infusion if the participant does NOT initiate 
new anticancer therapy, or through 30 days following T-cell infusion if the 
participant initiates new anticancer therapy, whichever is later. 
• All AEs will be collected from the start of leukapheresis until 30 days following 
cessation of interventional phase OR the end of study, whichever is later, at the 
time points specified in the SoA in each substudy.  
• Additionally, any 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 for 
target expression screening.  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. 
 
Figure 3 displays the AE/SAE collection time periods in relationship to the 4 phases of a 
substudy intervention. 

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Figure 3 
Time Period for Collecting AE and SAE Information 
 
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 Section 12.3. The 
Investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
• Events of special interest (AESIs) (Section 9.4.7) will be reported to the Sponsor 
(Medical Monitor or designee) within 24 hours via e-mail (see SRM for further 
instructions) AESIs should be communicated as soon as suspected, and any 
confirmed diagnosis must be reported immediately. 
• Events occurring after the participant enrolls onto the LTFU will be collected and 
reported in the LTFU protocol database. 
• Any SAE, including death, 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. 
 
9.4.2 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 Section 12.3. 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
9.4.3 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, and non-serious AEs of special 
interest (as defined in Section 9.4.7), will be followed until the event is resolved, 

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stabilized, otherwise explained, or the participant is lost to follow-up (as defined in the 
substudies). Further information on follow-up procedures is given in Section 12.3. 
9.4.4 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 suspected unexpected serious adverse 
reactions (SUSAR) 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. 
9.4.5 Pregnancy 
Should female participant or female partner of male participant become pregnant, collect 
details of pregnancy and report per guidelines in Section 12.4.  Contraception period is 
mandated from the start of study intervention and defined as followed in Table 2, based 
on the study treatments received. 
Table 2 
Time Periods for Contraception Usage 
Treatment 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 
Lete-cel (GSK3377794) 
A minimum of 12 months after lete-cel T-cell infusion. 
In the event that there is still evidence of persistence/gene modified cells in 
the participant’s blood beyond 12 months, contraception to continue until 
notification by Sponsor that lete-cel T cells are not detected in blood for 2 
consecutive times. 
 
The Sponsor will notify the site once the participants’ persistence is below the level of 
detection for 2 consecutive times. 

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Should female participant or female partner of male participant become pregnant, collect 
details of pregnancy and report per guidelines in Section 12.4. Should a female partner of 
a male participant be pregnant or become pregnant, collect details of pregnancy and 
report per guidelines in Section 12.4. 
The Investigator should inform GSK within 24 hours of learning of any pregnancy and 
should follow the procedures outlined in Section 12.4. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAE. 
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. 
9.4.6 Cardiovascular Events and Death 
For any cardiovascular events detailed in Section 12.3.3 and all deaths including those 
attributed to progression of malignant disease, whether or not they are considered SAEs, 
specific Cardiovascular (CV) and Death sections of the CRF will be required to be 
completed. These sections include questions regarding cardiovascular (including sudden 
cardiac death) and non-cardiovascular death.  
The CV CRFs are presented as queries in response to reporting of certain CV Medical 
dictionary for regulatory activities (MedDRA) terms. The CV information should be 
recorded in the specific cardiovascular section of the CRF within one week of receipt of a 
CV Event data query prompting its completion.  
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
9.4.7 Adverse Events of Special Interest (AESIs) 
Adverse events of special interest for this trial will be reported to Sponsor (Medical 
Monitor or designee) within 24 hours via email (see SRM for further instructions). The 
AESIs include but are not limited to:  
• Cytokine release syndrome (CRS) [Note: Grade 3 or higher should be reported as 
SAE within 24 hours] 
• Graft vs host disease (GvHD) [Note: Grade 3 or higher should be reported as SAE 
within 24 hours] 
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Grade 1 
persisting beyond 24 hrs or associated with concurrent CRS; or Grade 2 or higher 
• Guillain Barré syndrome (GBS) including acute inflammatory demyelinating 
polyneuropathy (AIDP) [Note: all cases must be reported as SAEs within 24 
hours] 

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• Pancytopenia/aplastic anemia if any of the below events occur: 
– Occurs after the bone marrow reconstitution following the lymphodepletion 
regimen 
– Any Grade 3 or 4 cytopenia following lymphodepletion lasting more than 
2 weeks with G-CSF support.  
– Requiring transfusion support (e.g. platelets or RBC) lasting more than 2 weeks 
following lymphodepletion 
• Treatment-related inflammatory response at tumor site(s) 
• Neutropenia Grade 4 lasting ≥28 days 
 
9.5 
Treatment of Overdose 
NY-ESO-1 specific (c259) T cells must be administered as a single-dose by trained 
personnel at the investigational sites in this study.  Infusion guidelines provided in the 
Drug Product and Infusion Manual must be strictly followed, including premedication, 
duration of infusion, and vital sign monitoring. In the event of an allergic reaction, the 
infusion must be immediately stopped, and anti-histamine treatment initiated.  Please 
refer to Section 12.7 for further supportive care guidance.  Acute mild respiratory distress 
developing during or immediately after (within 48 hours) T-cell infusion can be managed 
with supportive care, as detailed in Section 12.7.   
Should any substudy of the protocol include agents other than NY-ESO-1 specific (c259) 
T cells, any additional overdose considerations will be provided in the applicable 
substudy. 
9.6 
Pharmacokinetics 
Pharmacokinetics of T cells (also known as T-cell  expansion or persistence) in the 
peripheral blood will be measured in treated participants to evaluate the relationship 
between T-cell expansion and response to IP.  Persistence of T cells is also monitored as 
a long-term safety measure.   
Whole blood samples will be collected for measurement of transduced cell quantities; 
samples will be processed to PBMC. DNA will be isolated from these PBMCs to 
quantify the transduced cells using PCR of the Psi transgene as described in Section 
9.3.12. Samples may be collected at additional time points during a substudy if warranted 
and agreed upon between the Investigator and the Sponsor. Instructions for the collection 
and handling of biological samples will be provided by the sponsor. The actual date and 
time (24-hour clock time) of each sample will be recorded. 
The following PK parameters will be computed, as data permit:  
• Cmax: maximum concentration/T-cell expansion 
• Tmax, time of Cmax 

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• AUC(0-t), area under the concentration/T-cell expansion time curve from 0 to 
time t. 
 
Samples collected for analyses of transduced T cells in blood may also be used to 
evaluate safety or efficacy aspects related to concerns arising during or after the study. 
T-cell pharmacokinetics in the peripheral blood will be measured in the participants to 
establish the relationship between persistence and response to NY-ESO-1 specific (c259) 
T cells.  Persistence is also monitored as a long-term safety measure.  The following 
methodology will be used to measure the cells: 
• Quantitation of transduced cells by PCR of transgene from DNA extracted from 
PBMC 
 
9.7 
Pharmacodynamics 
Serum cytokine levels and other biomarkers measured for research purposes (see 
Section 9.9) may be evaluated for pharmacodynamic relationships with 
NY-ESO-1 specific (c259) T-cell administration.  
9.8 
Genetics 
Genetics research will be conducted on a genetics blood sample, plasma and tumor 
samples collected in the study as indicated in Section 9.9. Consent for Leukapheresis and 
Treatment encompasses consent for genetics research. See Section 12.5 for additional 
information regarding genetic research. Details on processes for collection and shipment 
and destruction of these samples can be found in the Study reference manual (SRM) or 
Laboratory Manual. 
9.9 
Biomarkers 
Collection of samples for biomarker research is also part of this study. Peripheral blood, 
serum, plasma, and tumor are required for biomarker research and will be collected as 
specified in the SoA within each substudy. These samples will be tested by the Sponsor 
or Sponsor's designee. 
Biomarkers will be assessed to monitor biological parameters that may influence 
treatment outcome, including, but not limited to, immune cell phenotype, function, and 
expansion of the engineered infused T cells, as well as evaluation of candidate predictive 
biomarkers and their association with clinical response to treatment. Immune cell 
phenotyping will be assessed in the apheresis material, manufactured product, and 
post-infusion blood samples. Data from such studies will be correlated with clinical 
outcome.  
As new technologies and data emerge, other novel biomarker tests involving DNA, RNA, 
or protein analysis relevant to the study objectives may be performed on consented blood, 
serum, plasma, and tumor samples. 

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If a participant has an AE, an additional biopsy (for example skin, GI tract, bone marrow, 
tumor) or blood (serum, plasma and PBMC) samples may be requested with the objective 
of gaining an understanding of the underlying etiology of the AE. For this purpose, the 
biomarker research tests applied on blood, plasma, tumor biopsy, and serum may also be 
performed on these samples. 
Any consented samples collected may be used for research to develop methods, assays, 
prognostics and/or companion diagnostics related to NY-ESO-1 specific (c259) T cells. 
In addition, if consent for future research is obtained, leukapheresis product not utilized 
for cell manufacture may be used for research to improve manufacturing processes and 
analytical testing of adoptive T cell therapies. 
With the participant’s consent, samples may be stored for a maximum of 15 years (or 
according to local regulations) following the last participant’s last visit for the study to 
enable further analysis of biomarkers in response to NY-ESO-1 specific (c259) T cells. 
9.9.1 Tumor Biopsy 
The efficacy of cancer immunotherapy is conditioned by the infiltration of tumors by 
activated tumor-specific T cells, the expression of target antigen, and the antigen 
processing machinery that enables surface expression of the antigenic epitope on the 
tumor cell surface.  All of these are necessary for the activity of NY-ESO-1 specific 
(c259) T cells. The activity of these T cells will in turn be affected by an 
immunosuppressive or immune-potentiating environment in the tumor (e.g., regulatory 
T cells or helper T cells). Therefore, the direct evaluation of the presence of NY-ESO-1 
specific (c259) T cells transduced cells, target antigen expression and processing 
machinery, and the “immune landscape” inside the tumor is of great value for 
understanding and optimizing cancer immunotherapy.  
For this purpose, incisional, excisional, or core needle tumor biopsies are required. As 
listed in the inclusion criteria for lymphodepetion and treatment under each substudy, a 
biopsy collected prior to initiating lymphodepleting chemotherapy is mandatory. A newly 
obtained tumor biopsy is highly desirable and preferred, but if it is not feasible to obtain a 
fresh biopsy, archival tumor biopsy (FFPE block) taken after completion of the 
participant’s last line of therapy may also be accepted. For participants who already 
provided a fresh biopsy for antigen expression and did not receive any bridging or 
standard of care intermediate anti-cancer therapy, the screening biopsy will be used for 
baseline. In addition, tumor biopsies at Week 4 (at the expected time of an active 
anti-tumor response by infused T cells) and at disease progression are also required.   
Baseline and on-treatment tumor biopsies must be taken from non-target lesions.  When 
possible, the same lesion(s) should be biopsied at both baseline and subsequent time 
points. The radiographic and/or clinical status of the biopsied lesion(s) should be 
documented at each time (e.g. decreased, stable, increased size or activity).  
Tumor biopsy research studies may include but are not limited to: 
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• Infiltration of TCR engineered NY-ESO-1 specific (c259) T cells  
• PD-L1 status  
• Presence of immune suppressive or potentiating cells (including Treg, Myeloid 
Derived Suppressor Cells, M2 macrophages) and immune suppressive or 
potentiating environment (including TGFβ expression and signature) 
• Protein analysis including immunohistochemistry  or similar technologies to 
measure immune cell infiltrate and functional biomarkers 
• RNA analysis including RNAseq, Nanostring, or similar technologies to measure 
immune cell infiltrate and signalling pathway biomarkers via gene expression 
profile (genetic analysis) 
• Deep gene sequencing to assess T cell clonality through TCR Vbeta and/or 
Valpha sequencing (genetic analysis) 
• Tissue analysis to determine the tumor mutational burden, evolution of tumor 
mutation profile over the course of therapy, microsatellite instability and genetic 
alterations by DNA sequencing (genetic analysis) 
 
Additional details regarding tumor biopsy collection are provided in the SRM. 
9.9.2 Liquid Biopsies (from circulating blood)  
With an understanding on the limitations of collecting tumor biopsies which cannot 
always be obtained safely, liquid biopsies (peripheral blood plasma) are commonly used 
as surrogates to assess disease burden and response to the therapy. In addition to tumor 
biopsies, liquid biopsies will be collected (see SoA Table 3 of each individual substudy).  
These liquid biopsies may be used to extract circulating cell-free DNA (cfDNA), 
circulating tumor DNA (ctDNA) and exosomes. Analyses may include but are not limited 
to the following genetic research: 
• Evaluation of expression of cancer testis antigens, including NY-ESO-1 and/or 
LAGE-1a. 
• Evaluation of the global tumor mutational burden and genetic profiling of tumor 
specific genes (including NY-ESO-1 and/or LAGE-1a). 
• Assessment and phenotyping of exosomes. 
 
9.9.3 Cytokine Analyses 
Serum is collected as specified in the SoA within each substudy.  If cytokine release 
syndrome (CRS) is suspected, serum for cytokine analysis should be collected every day 
for the first week and approximately every other day thereafter until symptoms improve 
or an alternative diagnosis is confirmed (See Section 12.7). Details regarding serum 
collection are provided in the SRM. 

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Cytokines, growth factors and soluble receptors including but not limited to IL-6, IFNγ, 
TNFα, IL-2Rα, IL-10, IL-13, IL-1β, IL-1Ra, IL-8, IL-12, IL-15, IL-2, and GM-CSF, may 
be measured utilizing a multiplexed immuno-assay. 
Measurement of the cytokine subset IL-1β, IL-10, IL-6, TNFα, and IFNγ is performed 
under Good Clinical Laboratory Practice (GCLP) conditions. All other measurements are 
exploratory. 
9.9.4 Cell Phenotype and Functional Activity 
A range of assays will be performed to elucidate the phenotype and activity of the cells 
collected from the apheresis (starting material), and of the gene-modified T cells 
(manufactured product) before and after infusion in the blood. The assays performed will 
depend upon availability of sample and clinical/scientific significance. The following 
assays may be included but are not limited to: 
• Phenotype analysis for determination of T cell lineages by flow cytometry 
• Quantitation of the activation status of immune subsets from PBMC by flow 
cytometry 
• Analysis of gene expression profile to reflect activity of the cells 
• Histologic evaluation of tumor-immune cell environment by single or multiplexed 
probe binding and microscopy. 
 
NOTE: Analysis may not be limited to these assays; additional assays may be added as 
they become available. 
9.9.5 Immunogenicity Assessments 
Serum samples for determination of anti- NY-ESO-1 specific (c259) T-cell antibodies 
will be taken from all participants for anti-drug antibody (ADA) testing.   
Serum samples will be tested for anti-NY-ESO-1 specific (c259) T-cell antibodies using a 
validated assay and a tiered-testing scheme (e.g., screening, confirmation, and titer 
assays). Briefly, all samples will be tested in a screening assay to identify potential 
positives. Next, all potentially positive samples will be tested in a confirmation assay to 
determine the specificity of the response. Finally, titer values will be determined of all 
confirmed positive samples. For each participant, immunogenicity results (e.g., positive 
or negative) and titer values will be reported. Other analyses (e.g., neutralizing antibody 
assay) may be performed to further characterize anti-NY-ESO-1 specific (c259) T-cell 
antibodies, if necessary.  
All samples collected for detection of antibodies to study intervention(s) may also be 
evaluated to enable interpretation of the antibody data. 
9.9.6 RNA Transcriptome Research 
Transcriptome studies may be conducted using RNA-seq, and/or alternative equivalent 
technologies, which facilitates the simultaneous measurement of the relative abundances 

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of thousands of ribonucleic acid (RNA) species resulting in a transcriptome profile for 
each tumor biopsy sample. This will enable the evaluation of changes in transcriptome 
profiles that may correlate with biological response relating to the action of the 
NY-ESO-1 specific (c259) T cells. 
The same samples may also be used to confirm findings by application of alternative 
technologies. 
9.9.7 RNA Expression Research of a Subset of RNA Species 
RNA expression studies may be conducted using quantitative reverse transcriptase 
polymerase chain reaction (RT-qPCR), Nanostring, or other methods, which can facilitate 
the simultaneous measurement of the relative abundances of RNA species resulting in an 
RNA expression profile for each blood and tumor biopsy sample. The RNAs assayed 
may be those involved with the pathogenesis of synovial sarcoma or myxoid/round cell 
liposarcoma; or the action of NY-ESO-1 specific (c259) T cells. In addition, continuing 
research may identify other proteins or regulatory RNAs that may be involved in the 
response to NY-ESO-1 specific (c259) T cells. The RNAs that code for these proteins 
and/or regulatory RNAs may also be studied. This will enable the evaluation of changes 
in RNA expression profiles that may correlate with biological response relating to the 
action of NY-ESO-1 specific (c259) T cells. 
9.9.8 Genetic Blood Sample 
A blood sample for DNA isolation will be collected from participants as specified in the 
SoA within each substudy. Genetic analysis may be conducted on this sample to 
investigate the relationship between genetic variants in the host and disease under study. 
The association of candidate or genome-wide genetic variants may be explored with 
efficiacy (ORR) and safety such as but not limited to cytokine release syndrome 
frequency/severity/duration.   
9.9.9 Request for Autopsy in case of Death Following Administration of 
Gene Transfer Agents 
In accordance with the FDA guidance [FDA, 2020a], all participants enrolled in this trial 
are asked to consider an autopsy and autopsies will be requested of the families for all 
participants who die during participation in studies after administration of gene transfer 
agents. To assure compliance, guidelines for performing an autopsy are provided in the 
SRM. 

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10 STATISTICAL CONSIDERATIONS 
For each substudy, the objective (unless otherwise stated in substudy) is to evaluate 
whether NY-ESO-1 specific (c259) T cells, alone or in combination with other agents, 
improve the Overall Response Rate (ORR) over the standard of care for the specific 
tumor type and the target population.  Response assessment for most solid tumors will be 
evaluated by RECIST v1.1 while all other tumors will use the appropriate established 
response criteria. 
The sample size for each substudy of the protocol is chosen to adequately characterize the 
efficacy and safety data according to the objective of each substudy. 
Definitions of populations for analyses and the statistical analyses for the 
primary/secondary endpoint are found in the substudies. 

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Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen MJ,  et al. 
Prediction of Respiratory Insufficiency in Guillain-Barré Syndrome. Ann Neurol. 
2010;67(6):781–7. 
Walgaard C, Lingsma HF, Ruts L, van Doorn PA, Steyerberg EW, Jacobs BC. Early 
recognition of poor prognosis in Guillain-Barré syndrome. Neurology.  
2011;76(11):968–75. 
Wang SJ, O’Neill RT, Hung HM. Approaches to evaluation of treatment effect in 
randomized clinical trials with genomic subset. Pharm Stat. 2007;6:227–44. 
Wang S, Song R, Sun T, Hou B, Hong G, Mallampati S, et al. Survival changes in 
Patients with Synovial Sarcoma, 1983–2012. J Cancer. 2017;8(10):1759–68. 
WHO Cancer Fact Sheet, February 2018. 
http://www.who.int/mediacentre/factsheets/fs297/en/ (last accessed: 23 March 2018) 
WHO Classification of Tumours of Soft Tissue and Bone. Fourth Edition, 2013. Fletcher, 
C. D.M., Bridge, J.A., Hogendoorn, P., Mertens, F. WHO Classification of Tumours, 
Volume 5; IARC WHO Classification of Tumours, No 5; ISBN-13 9789283224341. 
Willison HJ, Jacobs BC, van Doom PA. Guillain-Barré Syndrome. Lancet. 
2016;388(10045):717–27. 
Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of 
regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 
2003;9(2):606–12. 
World Health Organization (WHO) Classification of Tumours. Pathology and 
genetics of tumours of soft tissue and bone. 2002. C.D.M.Fletcher, K.K.Unni, and 
F.Mertens, editors. IARC Press, Lyon. 360–2. 
Yondelis SmPC.  August 2012 https://www.ema.europa.eu/documents/product-
information/yondelis-epar-product-information_en.pdf 
Yondelis USPI. October 2015. 
 
 

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12 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
12.1 Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
12.1.1 
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 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 IEC/IRB 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/EC 
– Notifying the IRB/IEC of SAE 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 
– Reporting cases of suspected child abuse and/or neglect according to local 
medical association (e.g., AAP) or health department guidelines. 
 
12.1.2 
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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12.1.3 
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 the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• For pediatric participants, the medical record must include a statement that legally 
authorized representative (parent/guardian) consent and child/adolescent assent (if 
deemed appropriate by local ethics review) was obtained before the participant 
was enrolled in the study and the date the written consent was obtained. The 
medical record should also describe how the clinical Investigator determined that 
the person signing the ICF was the participant’s legally authorized representative 
(parent/guardian). The authorized person obtaining the informed consent must 
also sign the ICF. 
• Participants and, if applicable, their legally authorized representative 
(parent/guardian) must be re-consented to the most current version of the ICF(s) 
during their participation in the study.  
• Minor participants must be re-consented if they reach the age of majority during 
the course of the study, in order to continue participating. 
• A copy 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 ICF 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. 
12.1.4 
Data Protection 
• Participants will be assigned a unique identifier by the sponsor. Any participant 
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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 law. 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. 
12.1.5 
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 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. 
12.1.6 
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. 
 

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12.1.7 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or electronic 
CRF 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 CRF.  
• The Investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 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 Monitoring Plan. 
• 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). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF 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.  
12.1.8 
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 on the CRF or 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. 

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• Definition of what constitutes source data can be found in the Monitoring plan. 
 
12.1.9 
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. 
 
12.1.10 
Remote Monitoring and Source Data Verification 
208467 study requires close, ongoing monitoring of patient data to ensure treatments are 
safe and tolerated by study participants. When onsite monitoring is not permissible due to 
site/local restrictions (such as with epidemic and/or pandemic), remote monitoring may 
be employed that ensures all of the following requirements are met: 
• Monitoring plan and execution details [(remote source data monitoring (rSDV) 
method and scope of activities]) are outlined in the Study  Monitoring Plan 
• Remote monitoring method to be employed ias permitted by local regulations, 
agreed upon by study site and approved by IRB/IEC 
• Appropriate security systems/provisions are in place to ensure protection of 
patient data and shared information 
• Participants sign ICF including disclosure of remote monitoring for 
(redacted/anonymized) patient data with security provisions in place 
 

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12.2 Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 3 will be performed by the local laboratory. 
• Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in the substudies. 
• 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 substudies for screening pregnancy criteria. 
– Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at all times indicated in the SoA in each substudy. 
– 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. 
 
Table 3 
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 
CD3/CD4/CD8 
 
 
 
Clinical Chemistry a 
BUN b 
Potassium 
AST (SGOT) 
Total and direct 
bilirubin 
Creatinine 
Sodium 
ALT (SGPT) 
Total Protein 
Glucose [nonfasting] 
Calcium 
Alkaline 
phosphatase 
Chloride 
Albumin 
Phosphorus 
LDH 
Ureaa 
 
Magnesium 
Bicarbonate 
 
Coagulation 
INR, PT, and aPTT, 
Fibrinogen 
 
 
 
Routine Urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 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 
• Follicle-stimulating hormone and estradiol (as needed in women of non-childbearing 
potential only) 

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Laboratory 
Assessments 
Parameters 
• Highly sensitive serum or urine human chorionic gonadotropin (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 8.2. 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. 
 
Note: All study-required laboratory safety assessments will be performed by a local laboratory, with the exception of 
biomarkers HLA-A*02:01, A*02:05, or A*02:06 and NY-ESO-1. The results of each test must be entered into the eCRF. 
 
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; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; HTLV = human T-lymphotropic virus; INR = international normalized ratio; LDH = lactate 
dehydrogenase; MCH = mean corpuscular hemoglobin; MCV = mean corpuscular volume; NT-proBNP = N-terminal 
pro-BNP; PCR = polymerase chain reaction; PT = prothrombin time; RBC = red blood cells; T4 = thyroxine; TSH = 
thyroid stimulating hormone; WBC = white blood cells. 
 

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12.3 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
12.3.1 
Definition of AE 
AE Definition 
• An 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 fulfil 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. 
 
12.3.2 Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met. 
1. 
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. 
2. Requires inpatient 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 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfils 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. 
3. 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, 

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influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
4. Is a congenital anomaly/birth defect 
5. 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 GBS or other demyelinating neuropathies 
must be reported within 24 hours as SAEs. 
 
12.3.3 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following Aes and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
 

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12.3.4 
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 CRF. 
• 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 CRF 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 and will assign a grade according to the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0), 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]. Organ toxicities associated with 
ICANS will be graded according to NCI-CTCAE v5.0 and do not influence ICANS 
grading. 
 
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. 

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• 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. 
• 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 CRF. 
• 
The Investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 

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12.3.5 
Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• The primary mechanism for reporting 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. 
SAE Reporting to GSK via Paper CRF 
• Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the medical monitor/SAE coordinator. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• Initial notification via telephone does not replace the need for the Investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in the SRM. 
 

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12.4 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information 
12.4.1 
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: 
• Premenarchal 
• 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. 
• Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
A high follicle stimulating hormone (FSH) level in the postmenopausal range 
(as per laboratory parameters for postmenopausal range) may be used to 
confirm a postmenopausal state in women not using hormonal contraception 
or hormonal replacement therapy (HRT) when postmenopausal status is in 
doubt. However, in the absence of 12 months of amenorrhea, confirmation 
with more than one FSH measurement is required. 
Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 
 
12.4.2 
Contraception Guidance 
Participants should be informed that treatment with fludarabine, cyclophosphamide 
and/or genetically engineered T cells (including lete-cel) may have adverse effects on a 

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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.  
Participants who are WOCBP must use a barrier method (male condom) and should 
comply with one of the following: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methods That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb 
Intrauterine device (IUD) 
Intrauterine hormone-releasing system (IUS)b 
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 Methods 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 ovulationb 
oral 
intravaginal 
transdermal 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationb 
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. Periodic abstinence (calendar, sympto-thermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhoea method (LAM) are not acceptable methods of contraception. 
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. 
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: Male condom and female condom should not be used together (due to risk of failure with friction). 

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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.  
The IB and Informed consent also contain language describing the risks and 
contraceptive guidelines described above. 
12.4.3 
Collection of Pregnancy Information: 
Male participants with partners who are or become pregnant 
• Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who is or becomes pregnant while the male 
participant is participating in this study. This applies only to male participants 
who receive study intervention. 
• 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 

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GSK as described in Section 12.3. 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 or be withdrawn from the study. 
 

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12.5 Appendix 5: Genetics 
USE/ANALYSIS OF DNA 
• Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention 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, DNA 
analysis will be conducted on blood, plasma, stool and tumor biopsy per local 
regulations and IRB/IEC. 
• DNA samples will be used for research related to NY-ESO-1 specific TCR (c259) 
engineered T-cells or cancer indication(s) under study and related diseases. They 
may also be used to develop tests/assays including diagnostic tests related to NY-
ESO-1 specific TCR (c259) engineered T-cells and cancer indications under 
study. Genetic research may consist of the analysis of one or more candidate 
genes or the analysis of genetic markers throughout the genome or analysis of the 
entire genome, as appropriate. 
• The samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to NY-ESO-1 specific TCR (c259) engineered T 
cells. The results of genetic analyses may be reported in the clinical study report 
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 NY-ESO-1 specific TCR (c259) 
engineered T cells (or study interventions of this class) or indications under study 
continues but no longer than 15 years after the last participant last visit or other 
period as per local requirements. 
 
12.5.1 
Germline Control 
US Food and Drug Administration 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. 

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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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12.6 
Appendix 6: Guidelines for Assessment of Disease, Disease 
Progression and Response Criteria  
12.6.1 
RECIST v1.1 Assessment 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 should be taken and recorded in millimeters (mm), using a 
ruler or calipers. 
• 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)-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 should be noted as CT on the CRF. 
 
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 should 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 should 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]. 
Brain Scan:  If brain scans are required, then contrast-enhanced MRI is preferable to 
contrast enhanced CT. 

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Bone Scan (typically bone scintigraphy):  If a bone scan is performed and a new 
lesion(s) is equivocal, then correlative imaging (i.e., X-ray, CT, or MRI) is required to 
demonstrate malignant characteristics of the lesion(s).  
Note:  PET [FDG or fluoride] may be used in lieu of a standard bone scan providing 
coverage allows interrogation of all likely sites of bone disease and PET is performed at 
all assessments. 
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 5mm. If 
the slice thickness is greater than 5mm, 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 
• 15mm 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 [Eisenhauer, 2009]. 
 
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, abdominal masses/abdominal organomegaly identified by physical 
exam that is not measurable by reproducible imaging techniques [Eisenhauer, 2009]. 
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. 

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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. 
• 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 4 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 4 
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. 
 

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12.6.2 
iRECIST Guidelines 
iRECIST is based on RECIST v1.1 but adapted to account for the unique tumor response 
seen with immunotherapeutic drugs. iRECIST will be used to assess tumor response and 
progression and make treatment decisions. When clinically stable, participants should not 
be discontinued until progression is confirmed according to the rules described below. 
This allowance to continue treatment despite initial radiologic PD takes into account the 
observation that some participants can have a transient tumor flare in the first few months 
after the start of immunotherapy, and then experience subsequent disease response. These 
data will be captured in the clinical database. 
Clinical stability is defined as meeting all of the following:  
• Absence of symptoms and signs indicating clinically significant progression of 
disease 
• No decline in Lansky, Karnofsky, or ECOG performance status  
• No requirements for intensified management, including increased analgesia, 
radiation, or other palliative care 
 
Any participant deemed clinically unstable may be discontinued from study intervention 
at site-assessed first radiologic evidence of PD. It is strongly preferred to obtain the 
repeat tumor imaging, when feasible, for confirmation of PD by iRECIST.  
In a clinically unstable participant, if the Investigator decides to continue treatment, 
following consultation with the Sponsor medical monitor, the participant may continue to 
receive study intervention. The tumor assessment should be repeated at least 4 weeks and 
up to 12 weeks later to confirm PD by iRECIST. Images should continue to be sent in to 
the central imaging vendor for potential central review.  
If repeat imaging does not confirm PD per iRECIST and the participant continues to be 
clinically stable, study intervention may continue and follow the regular imaging 
schedule. If PD is confirmed, participants will be discontinued from study intervention. 
If a participant has confirmed radiographic progression (iCPD) as defined below, study 
intervention should be discontinued; however, if the participant is achieving a clinically 
meaningful benefit, continuation of study intervention may be considered following 
consultation with the Sponsor. In this case, if study intervention is continued, tumor 
imaging should continue to be performed following the intervals as outlined in the SoA in 
each substudy and submitted to the central imaging vendor.  
Description of the iRECIST Process for Assessment of Disease Progression 
Assessment at Screening and Prior to RECIST v1.1 Progression 
Until radiographic disease progression based on RECIST v1.1, there is no distinct 
iRECIST assessment. 
Assessment and Decision at RECIST v1.1 Progression 

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For participants who show evidence of radiological PD by RECIST v1.1, the Investigator 
will decide whether to continue a participant on study intervention until repeat imaging is 
obtained (using iRECIST for participant management [see Table 5]). This decision 
should be based on the participant’s overall clinical condition. (See discussion of clinical 
stability above).  
Tumor flare may manifest as any factor causing radiographic progression per RECIST 
v1.1, including: 
• Increase in the sum of diameters of target lesion(s) identified at baseline to ≥20% 
and ≥5 mm from nadir 
Note: the iRECIST publication uses the terminology “sum of measurements”, but 
“sum of diameters” will be used in this protocol, consistent with the original 
RECIST v1.1 terminology. 
• Unequivocal progression of non-target lesion(s) identified at baseline 
• Development of new lesion(s) 
 
iRECIST defines response categories, including iUPD (unconfirmed progressive disease) 
and iCPD (confirmed progressive disease). For purposes of iRECIST assessment, the first 
visit showing progression according to RECIST v1.1 will be assigned a visit (overall) 
response of iUPD, regardless of which factors caused the progression. 
At this visit, target and non-target lesions identified at baseline by RECIST v1.1 will be 
assessed as usual. 
New lesions will be classified as measurable or non-measurable, using the same size 
thresholds and rules as for baseline lesion assessment in RECIST v1.1. From measurable 
new lesions, up to 5 lesions total (up to 2 per organ), may be selected as New Lesions – 
Target. The sum of diameters of these lesions will be calculated and kept distinct from 
the sum of diameters for target lesions at baseline. All other new lesions will be followed 
qualitatively as New Lesions – Non-target. 
Assessment at the Confirmatory Imaging 
At the confirmatory imaging visit assessment, the participant will be classified as 
progression confirmed (with an overall response of iCPD), or as showing persistent 
unconfirmed progression (with an overall response of iUPD), or as showing disease 
stability or response (iSD/iPR/iCR).  
Confirmation of Progression 
Progression is considered confirmed, and the overall response will be iCPD, if ANY of 
the following occurs: 
• Any of the factors that were the basis for the initial iUPD show worsening 
– For target lesions, worsening is a further increase in the sum of diameters of 
≥5 mm, compared to any prior iUPD time point 

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– For non-target lesions, worsening is any significant growth in lesions overall, 
compared to a prior iUPD time point; this does not have to meet the 
“unequivocal” standard of RECIST v1.1 
– For new lesions, worsening is any of these: 
o An increase in the new lesion sum of diameters by ≥5 mm from a prior iUPD 
time point  
o Visible growth of new non-target lesions  
o The appearance of additional new lesions 
• Any new factor appears that would have triggered PD by RECIST v1.1 
 
Persistent iUPD 
Progression is considered not confirmed, and the overall response remains iUPD, if: 
• None of the progression-confirming factors identified above occurs AND 
• The target lesion sum of diameters (initial target lesions) remains above the initial 
PD threshold (by RECIST v1.1) 
 
Additional imaging for confirmation should be scheduled 4 to 8 weeks from the imaging 
on which iUPD is seen. This may correspond to the next visit in the original visit 
schedule. The assessment of the subsequent confirmation imaging proceeds in an 
identical manner, with possible outcomes of iCPD, iUPD, and iSD/iPR/iCR. 
Resolution of iUPD 
Progression is considered not confirmed, and the overall response becomes iSD/iPR/iCR, 
if: 
• None of the progression-confirming factors identified above occurs, AND 
• The target lesion sum of diameters (initial target lesions) is not above the initial 
PD threshold.  
 
The response is classified as iSD or iPR (depending on the sum of diameters of the target 
lesions), or iCR if all lesions resolve. 
In this case, the initial iUPD is considered to be pseudo-progression, and the level of 
suspicion for progression is “reset”. This means that the next visit that shows 
radiographic progression, whenever it occurs, is again classified as iUPD by iRECIST, 
and the confirmation process is repeated before a response of iCPD can be assigned. 
Management Following the Confirmatory Imaging 
If repeat imaging does not confirm PD per iRECIST, as assessed by the Investigator, and 
the participant continues to be clinically stable, study intervention may continue and 
follow the regular imaging schedule. If PD is confirmed, participants will be discontinued 
from study intervention. 

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NOTE: If a participant has confirmed radiographic progression (iCPD) as defined above, 
but the participant is achieving a clinically meaningful benefit, continuation of study 
intervention may be considered following consultation with the Sponsor. In this case, if 
study intervention is continued, tumor imaging should continue to be performed 
following the intervals as outlined in the SoA in each substudy and submitted to the 
central imaging vendor. 
Detection of Progression at Visits after Pseudo-Progression Resolves 
After resolution of pseudo-progression (i.e., achievement of iSD/iPR/iCR), iUPD is 
indicated by any of the following events: 
• Target lesions 
– Sum of diameters reaches the PD threshold (≥20% and ≥5 mm increase from 
nadir) either for the first time, or after resolution of previous pseudo-progression. 
The nadir is always the smallest sum of diameters seen during the entire trial, 
either before or after an instance of pseudo-progression. 
 
• Non-target lesions 
– If non-target lesions have never shown unequivocal progression, doing so for the 
first-time results in iUPD. 
– If non-target lesions have shown previous unequivocal progression, and this 
progression has not resolved, iUPD results from any significant further growth of 
non-target lesions. 
 
• New lesions 
– New lesions appear for the first time 
– Additional new lesions appear 
– Previously identified new target lesions show an increase of ≥5 mm in the new 
lesion sum of diameters, from the nadir value of that sum 
– Previously identified non-target lesions show any significant growth 
 
If any of the events above occur, the overall response for that visit is iUPD, and the iUPD 
evaluation process (see Assessment at the Confirmatory Imaging above) is repeated. 
Progression must be confirmed before iCPD can occur. 
The decision process is identical to the iUPD confirmation process for the initial PD, with 
one exception: if new lesions occurred at a prior instance of iUPD, and at the 
confirmatory imaging the burden of new lesions has increased from its smallest value (for 
new target lesions, the sum of diameters is ≥5 mm increased from its nadir), then iUPD 
cannot resolve to iSD or iPR. It will remain iUPD until either a decrease in the new lesion 
burden allows resolution to iSD or iPR, or until a confirmatory factor causes iCPD. 
Additional details about iRECIST are provided in the iRECIST publication [Eisenhauer, 
2009].  

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Table 5 
Imaging and Treatment after First Radiologic Evidence of 
Progressive Disease 
 
Clinically Stable 
Clinically Unstable 
Imaging 
Treatment 
Imaging 
Treatment 
First radiologic 
evidence of PD by 
RECIST v1.1  
Repeat imaging at 
4 to 8 weeks to 
confirm PD. 
May continue study 
intervention at the 
Investigator’s 
discretion while 
awaiting confirmatory 
tumor imaging by site 
by iRECIST. 
Repeat imaging at 
4 to 8 weeks to 
confirm PD per 
Investigator’s 
discretion only. 
Discontinue treatment 
Repeat tumor 
imaging confirms 
PD (iCPD) by 
iRECIST per 
Investigator 
assessment 
No additional 
imaging required. 
Discontinue treatment 
(exception is possible 
upon consultation with 
Sponsor). 
No additional 
imaging required. 
Not applicable 
Repeat tumor 
imaging shows 
iUPD by iRECIST 
per Investigator 
assessment 
Repeat imaging at 
4 to 8 weeks to 
confirm PD. May 
occur at next 
regularly 
scheduled 
imaging visit. 
Continue study 
intervention at the 
Investigator’s 
discretion. 
Repeat imaging at 
4 to 8 weeks to 
confirm PD per 
Investigator’s 
discretion only. 
Discontinue treatment 
Repeat tumor 
imaging shows 
iSD, iPR, or iCR by 
iRECIST per 
Investigator 
assessment. 
Continue regularly 
scheduled 
imaging 
assessments. 
Continue study 
intervention at the 
Investigator’s 
discretion. 
Continue regularly 
scheduled 
imaging 
assessments. 
May restart study 
intervention if condition 
has improved and/or 
clinically stable per 
Investigator’s discretion. 
Next tumor imaging 
should occur according 
to the regular imaging 
schedule. 
iCPD = iRECIST confirmed progressive disease; iCR = iRECIST complete response; iRECIST = modified Response 
Evaluation Criteria in Solid Tumors 1.1 for immune-based therapeutics; iSD = iRECIST stable disease; iUPD = 
iRECIST unconfirmed progressive disease; PD = progressive disease; RECIST v1.1 = Response Evaluation Criteria in 
Solid Tumors v1.1. 
 

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Figure 4 
Imaging and Treatment for Clinically Stable Participants after First 
Radiologic Evidence of PD Assessed by the Investigator 
 
 

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12.7 Appendix 7: 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 oncology practice guidelines for 
chemotherapy administration and supportive care. 
All participants should be hospitalized for the T-cell infusion. Staff treating trial 
participants should be experienced in acute post-transplant care and the management of 
associated toxicities (e.g., cytopenias, cytokine release syndrome (CRS), autologous graft 
versus host disease). 
Participants are at risk for the development of certain adverse effects for which 
recommended management strategies have been developed. Adverse events 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. 
12.7.1 
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 or an alternative per institutional practice. It is recommended all 
participants that develop fever or chills have a blood culture drawn. 
• Nausea and vomiting may be treated with a non-steroidal anti-emetic of choice. 
• Hypotension will initially be managed by intravenous fluid administration and 
further measures as dictated by standard medical practice. 
• Hypoxemia will initially be managed with supplemental oxygen and further 
measures as dictated by standard medical practice. 
 
In participants with infusion-related reaction Grade ≤2, infusion may be restarted once 
resolved to Grade <1. The bag of cells that was being infused prior to reaction, cannot be 
used beyond 45 min after thawing. Infusion-related reactions Grade 3 or higher during 
infusion should be reported to Sponsor promptly. 
12.7.2 
Infection 
Additional measures to treat and prevent infection are outlined below. In particular, fever 
and neutropenia should be aggressively managed as well as pre-emptive 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. 

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12.7.2.1 
Pneumocystis carinii Pneumonia (PCP) 
Participants should receive prophylaxis against PCP with drug, dose and duration 
according to institutional guidelines. Single strength trimethoprim sulfamethoxazole daily 
is the recommended first-line agent, starting at Day 28 post T-cell infusion for one year. 
Other regimens include atovaquone (1500 mg daily with food in adults) or aerosolized 
pentamidine (300 mg every four weeks in adults for example, if sulfonamide allergy), or 
in accordance with institutional guidelines and labels. 
12.7.2.2 
Herpes Simplex,Varicella Zoster and Epstein-Barr Virus 
All participants should receive prophylaxis with acyclovir (800 mg twice daily in adults) 
or valacyclovir (500 mg twice daily in adults) for one year initiated prior to 
lymphodepletion, or in accordance with institutional guidelines and labels. 
12.7.2.3 
Cytomegalovirus 
All participants will be screened for cytomegalovirus (CMV) IgG seropositivity at study 
entry. If CMV viremia is detected at Baseline, treatment should be initiated with evidence 
of viral clearance prior to lymphodepleting chemotherapy. All CMV IgG seropositive 
participants will continue to be monitored for CMV viremia by CMV DNA PCR until 60 
days post infusion of cell therapy. In the event CMV viremia is observed, an infectious 
diseases specialist should be consulted and treatment initiated if necessary according to 
institutional practice. Recommended regimens include ganciclovir-based therapy if ANC 
≥1000, and foscarnet if ANC <1000. 
If a 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 12.7.7. 
12.7.2.4 
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 for adults include 
lamivudine (300 mg daily), entecavir (0.5 mg daily), or tenofovir (300 mg daily). 
Additional considerations will be left to Investigator’s discretion in accordance with label 
recommendations and institutional guidelines. 
12.7.2.5 
Syphilis 
Participants will be screened for syphilis at study entry. Participants with positive 
screening results should be evaluated by an infectious diseases consultant. If determined 
to have syphilis infection, the participant should be treated before leukapheresis. 

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12.7.2.6 
Other Anti-Microbial Prophylaxis 
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. 
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 9.3.6). 
12.7.3 
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; 
• Hb >8.0 g/dL  
or as clinically indicated in the judgement of the Investigator, or in accordance with 
institutional practice.  
See AABB Guideline on platelet transfusion [Kaufman, 2015]. 
12.7.3.1 
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. 
12.7.3.2 
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. 
12.7.4 
Management of Autoimmunity 
Participants should be monitored throughout the trial for potential autoimmune reactions 
in response to the genetically engineered T cells that could include skin toxicity, liver 

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toxicity, colitis, eye toxicity etc. If autoimmunity is suspected, the Investigator should be 
contacted, and every attempt should be made to biopsy the affected organ to clarify 
whether the symptoms are related to the administered T-cell therapy. If the participant 
sustains persistent Grade 2, or Grade 3 or 4 autoimmunity, consideration should be given 
to administration of corticosteroid therapy, either locally (e.g., skin, eyes) or systemically 
as clinically indicated. 
12.7.5 
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, transaminitis, 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 causes 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 6 provides the recommended management of CRS according to grade, which has 
been further adapted from CTCAE for use with immunotherapy and should be 
implemented in accordance with institutional guidelines. Symptoms can mimic those 
seen with infection. The diagnosis of CRS is clinical and is supported by the exclusion of 
infection as well as the presence of increased cytokine levels and other biomarkers. 
Assessment and treatment guidelines are provided below 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, 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: 
– Chemistry, hematology, ferritin and coagulation, as well as C-reactive protein 
(CRP) labs; 
• Central tests: 
– Cytokine-profiling as described in Section 9.9.3. 

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If CRS is suspected, participants deemed to be with an increased burden of 
cardiovascular risk factors (per Section 9.3.6)  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 of ≥ Grade 2 CRS. 
Additional monitoring should be conducted for a minimum of 3 days post onset of 
≥ Grade 2 CRS and as long as deemed necessary by the Investigator: 
• Continuous cardiac telemetry monitoring 
• ECHO/MUGA as clinically indicated 
• Local tests: 
– Daily troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) or 
BNP tests. 
If, in the opinion of the Investigator, a participant develops any clinically significant new 
or worsening cardiovascular symptoms or abnormal cardiac labs / imaging finding, a 
cardiology consult should be conducted for urgent evaluation. 
Table 6 
Management Guidelines for Cytokine Release Syndrome 
Grade 
Clinical Presentation for Grading Assessment 1,2 
Management Guidelines 
1 
Temperature 38.0°C 
Vigilant supportive care 4 
Assess for infection and treat 5 
2 
Temperature 38.0°C with hypotension not requiring 
vasopressors and/or hypoxia requiring the use of 
oxygen delivered by low-flow nasal cannula 
(≤6 L/minute) or blow-by. 
Monitor cardiac and other organ function 
Vigilant supportive care 4 
Assess for infection and treat 5 
Treat hypotension with fluid and pressors 
Administer O2 for hypoxia6 
Consider administering tocilizumab  
corticosteroids 7  
3 
Temperature 38.0°C with hypotension requiring a 
vasopressor with or without vasopressin and/or 
hypoxia requiring high-flow nasal cannula 
(>6 L/minute), facemask, non-rebreather mask, or 
venturi mask not attributable to any other cause 3 
Monitor participant very closely for cardiac and 
other organ dysfunction. Most likely will require 
monitoring in an intensive care unit (ICU). 
Vigilant supportive care 4 
Assess for infection and treat 5 
Treat hypotension with fluid and pressors 6  
Administer O2 for hypoxia. 
Administer tocilizumab  corticosteroids 7 
4 
Temperature 38.0°C with hypotension requiring 
multiple vasopressors (excluding vasopressin) 
and/or hypoxia requiring positive pressure 
(e.g., CPAP, BiPAP, intubation and mechanical 
ventilation) 8 
Manage participant in ICU 
Intensive supportive care including mechanical 
ventilation, fluids, pressors, antibiotics and 
other measures as required 6 
Administer tocilizumab  corticosteroids 7 
5 
Death 9 
 
1. 
Fever is defined as temperature 38°C not attributable to any other cause. The constitutional symptoms of CRS, 
such as myalgia, arthralgia, and malaise, are by themselves nonspecific; however, when coincident with fever in 
the expected timeframe, the etiology of CRS is more likely. In patients who have CRS then receive antipyretic or 
anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS 
severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 

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2. 
CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. 
For example, a patient with temperature of 39.5°C, hypotension requiring 1 vasopressor, and hypoxia requiring 
low-flow nasal cannula is classified as Grade 3 CRS. 
3. 
Low-flow nasal cannula is defined as oxygen delivered at 6 L/minute. Low flow also includes blow-by oxygen 
delivery, sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at >6 L/minute. 
4. 
Supportive care includes:  monitor fluid balance, maintain adequate hydration and blood pressure  
5. 
Assessment and treatment to include history and physical, blood and urine cultures, imaging studies, 
administration of antimicrobial agents for concurrent bacterial infections, and for treatment of fever and 
neutropenia as per institutional practice; and antipyretics, analgesics as needed.  
6. 
Given that prolonged fluid resuscitation without pressor use is associated with worse outcome and because early 
and aggressive supportive care, early use of vasopressors, and timely anti-cytokine therapy are paramount to 
mitigating life-threatening CRS. 
7. 
Other immunosuppressor agents may be used, including TNFα and IL-1R inhibitors.  
8. 
Intubation a patient without hypoxia for the possible neurologic compromise of a patient airway alone or for a 
procedure is not, by definition, Grade 4 CRS. By extension, a patient experiencing seizures in which a 
compromised airway affects oxygenation and intubation reverses such deficits is not considered to have Grade 4 
CRS, because the seizure rather than CRS is the cause of the hypoxia. Furthermore, a patient who remains 
intubated for a neurologic cause is not considered to be CRS when the other signs of CRS have resolved. 
9. 
Grade 5 CRS is defined as death due to CRS in which another cause is not the principle factor leading to this 
outcome. 
Source: [Lee, 2019] 
 
Participants requiring immunosuppressive intervention may receive tocilizumab, steroids, 
or both [Davila, 2014; Lee, 2014; Lee, 2019]. Tocilizumab is a humanized anti-IL-6 
receptor antibody that has been approved for the management of severe or 
life-threatening CRS induced by chimeric antigen receptor (CAR) T cell therapy 
[Tocilizumab USPI, 2020; Tocilizumab SmPC, 2020].  
Per the package insert, the recommended dose of tocilizumab for patients with severe or 
life-threatening CRS who weigh 30kg or above is 8mg/kg, administered intravenously 
over 1 hour with a total dose not exceeding 800mg per infusion. If no clinical 
improvement in the signs and symptoms of CRS occurs after the first dose, up to 
3 additional doses of tocilizumab may be administered. The interval between consecutive 
doses should be at least 8 hours.  
Side effects attributed to chronic use of tocilizumab in rheumatologic disease include 
transaminitis, thrombocytopenia, elevated cholesterol and low-density lipoproteins, 
neutropenia and increased infections but acute infusional toxicities have not been 
reported in CRS use [Lee, 2014; Lee, 2019]. 
Per SITC 2020 guidelines: 
If CRS does not improve after one dose of tocilizumab, then steroids should be 
administered with a second dose tocilizumab (e.g. methylprednisolone 2 mg/kg/day or 
dexamethasone 0.5 mg/kg up to 10 mg/dose). If CRS does not improve after 2 doses of 
tocilizumab (and steroids), third-line agents, including anakinra, siltuximab, and 
high-dose methylprednisolone have been considered. If steroids are used in the 
management of CRS, a rapid taper should be used once symptoms begin to improve 
[Maus, 2020].  

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Use of myeloid growth factors, particularly Granulocyte-Macrophage Colony Stimulating 
Factor (GM-CSF) is not recommended because GM-CSF may theoretically aggravate 
CRS [Raje, 2019]. Consider holding G-CSF during CRS [Maus, 2020].  
Assessment and management of neurological signs and symptoms associated with CRS 
should include consideration of concurrent occurrence of Immune-effector cell-associated 
neurotoxicity syndrome (ICANS). See Section 12.7.8 for further details. 
12.7.6 
Management of Graft-versus-Host Disease (GvHD) 
Autologous GvHD has been described in association with adoptive transfer of ex-vivo 
expanded/co-stimulated autologous T cells [Rapoport, 2009], as well as infusion of 
T cells with engineered specificity for NY-ESO-1 and LAGE-1a [Garfall, 2013], 
following high-dose chemotherapy and ASCT in participants with multiple myeloma. 
There is the potential for participants who receive lymphodepleting therapy followed by 
engineered autologous T-cell infusion to experience GvHD and/or autoimmune 
GvHD-like symptomatology. Autologous GvHD is typically milder than classic 
(allogeneic) GvHD [Kline, 2008], and is usually manageable with treatment. However, 
severe cases (including fatalities) have been reported [Fidler, 2012].  There are no 
published guidelines for the management of autologous GvHD. However, lessons can be 
drawn from published case reports and guidelines for the diagnosis and management of 
acute GvHD following allogeneic transplant [Dignan, 2012]. 
12.7.6.1 
Diagnosis of GvHD 
The diagnosis of GvHD is predominantly based on clinical findings and is often one of 
exclusion (Table 7). Many of these symptoms can also occur in the setting of the 
preparative regimen, high dose cyclophosphamide, as well as with CRS. Any of these 
conditions including GvHD can be associated with fever. The skin is the most commonly 
involved organ, followed by the gastrointestinal (GI) tract and liver. A constellation of 
symptoms involving these organ systems may be helpful in establishing the diagnosis of 
GvHD.  Diarrhea, rash, fever, and pancytopenia are common toxicities in the lete-cel 
program where we have the most clinical experience. Mild (Grade 1 or 2) transient 
transaminitis without cholestasis has been observed. 
Table 7 
Overview of Clinical Findings/Symptoms of GvHD 
Organ 
Findings/Symptoms 
Differential Diagnosis 
Histopathology 
Skin 
Maculopapular rash involving the 
neck and shoulders as well as the 
palms and soles that spreads to 
include the rest of the body. 
Drug reactions, viral 
exanthems, CRS, and effects 
of chemotherapy or radiation 
Apoptosis at base of epidermal 
rete pegs, dyskeratosis, 
exocytosis of lymphocytes, 
satellite lymphocytes adjacent to 
dyskeratotic epidermal 
keratinocytes and perivascular 
lymphocytic infiltration in the 
dermis. 

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Organ 
Findings/Symptoms 
Differential Diagnosis 
Histopathology 
GI 
Secretory diarrhea is most 
common but nausea, vomiting, 
anorexia, weight loss and 
abdominal pain can also occur. 
Diarrhea can be copious. 
Bleeding may result from mucosal 
ulceration and ileus may ensue. 
Side effects of chemotherapy 
or other drugs and infection of 
the GI tract 
Patchy ulcerations, apoptotic 
bodies at crypt bases, crypt 
ulceration and flattening of 
surface epithelium 
Liver 
Cholestatic pattern of liver injury 
including elevated conjugated 
bilirubin, alkaline phosphatase 
and GGTP. Participants may 
present with jaundice, with pruritis 
in more severe cases. 
Veno-occlusive disease of the 
liver, viral infections, drug 
toxicity and sepsis. 
Endothelialitis, lymphocytic 
infiltration of the portal areas, 
pericholangitis and bile-duct 
destruction. 
 
NOTE:  Bone marrow suppression and related cytopenias have been described in the 
setting of acute GvHD. Management of this complication is challenging, with no clearly 
established guidelines regarding immunosuppression. Treatment may be largely 
supportive, including transfusions and treatment of infections. 
Management should include consultation with a physician with expertise in the 
management of participants following bone marrow transplant. 
Bone marrow suppression is also a feature of transfusion-related GvHD. To minimize the 
possibility of transfusion-related GvHD, refer to Section 12.7.3.1 for guidance on 
irradiated blood products.  
12.7.6.2 
Grading of GvHD 
Grading of acute GvHD is based on the stage of dermal, gastrointestinal, and hepatic 
involvement as described in Table 8. Careful measurement of stool volume and 
assessment of percentage of body area covered by rash are important for proper grading 
and treatment. 
Table 8 
Staging of Dermal, Gastrointestinal and Hepatic Involvement with 
Acute GvHD 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

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With the addition of assessment of functional impairment, grading can be determined 
using Table 9 [Glucksberg, 1974]. 
Table 9 
Grading of Acute GvHD 
12.7.6.3 
Management of GvHD 
Although the diagnosis of GvHD is predominantly based on clinical grounds, biopsy of 
affected organs can be helpful in excluding other causes and supporting the diagnosis of 
GvHD with consistent histopathologic findings. However, awaiting biopsy results should 
not delay the start of appropriate therapy. 
If GvHD is suspected: 
• A physician with expertise in the management of participants following bone marrow 
transplant should be consulted 
• Biopsy of the affected organ(s) should be considered 
 
Corticosteroids have been used as the standard first-line treatment for GvHD for several 
decades. Their effect is likely to be due to lympholytic effects and anti-inflammatory 
properties. In general, intestinal and liver GvHD require more prolonged steroid therapy 
than skin disease although response times vary. 
Diarrhea should be managed with volume replacement, dietary restriction, and anti-
diarrheal agents including the consideration of somatostatin for secretory diarrhea. 
Agents that slow motility should be used cautiously, ensuring that there is no evidence of 
ileus or toxic megacolon, and infectious causes of diarrhea should be excluded. 
General guidelines for first-line treatment based on grade are provided in Table 10 and 
should be considered in conjunction with input from the consulting physician with bone 
marrow transplant expertise. 
Table 10 
Management Guidelines for 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 in participants with pruritis. 
Participants should be reviewed frequently for other organ manifestations of GvHD. 
II 
Treat skin symptoms with topical steroids. For GI symptoms – optimize anti-diarrheal regimen, 
dietary restrictions, volume replacement and consider initiation of non-absorbable steroids. For 
refractory or progressive symptoms consider systemic steroids as outlined below. 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

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Grade 
Management Strategy 
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 day 1 
1. 
The use of ‘nonabsorbable’ steroids (budesonide and beclomethasone) can be considered for acute intestinal 
GvHD in order to reduce the dose of systemic steroids. 
 
If high-dose corticosteroids are required, treatment should generally be continued for at 
least 5 days followed by tapering doses over several weeks. A physician with expertise in 
infectious diseases in immunocompromised hosts should be consulted, and prophylactic 
antimicrobials should be considered. 
Second-line treatment can be considered for 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 of the allogeneic transplant participants are concurrently receiving calcineurin 
inhibitors in part as prophylaxis against GvHD. Therefore, for Grade II-IV disease 
refractory to high dose steroids, the addition of a calcineurin inhibitor can be considered. 
Otherwise, there are several additional second-line treatment options for which there is 
currently limited and/or evolving supporting data. Treating physicians can refer to the 
Haemato-oncology Task Force of the British Committee for Standards in Hematology 
and the British Society for Blood and Marrow Transplantation guideline for diagnosis 
and management of acute graft-versus-host disease [Dignan, 2012]. 
12.7.7 Management of Pancytopenia with Bone Marrow Failure/Aplastic 
Anemia 
Pancytopenia with bone marrow failure / aplastic anemia has been reported after initial 
bone marrow recovery from high-dose chemotherapy followed by infusion of NY-ESO-1 
specific TCR (c259) engineered T cells. Bone marrow recovery following 
lymphodepletion will be defined as: 
• ANC ≥1,000/μL for 2 consecutive measurements approximately seven days apart, 
and 
• Platelet count ≥20,000/μL without transfusion support for 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 

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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 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.  
• A matched peripheral blood sample should be collected in parallel with the bone 
marrow sample and provided to the Sponsor.  
• Initiate treatment with G-CSF 
• Consult an Infectious Diseases expert 
• Once alternative etiologies have been excluded, strongly consider 
immunosuppression (e.g. methylprednisolone 2mg/kg initial dose) or more 
aggressive regimens (e.g. antithymocyte globulin (ATG), cyclosporine, 
eltrombopag) as well as antimicrobial prophylaxis/therapy with the advice of your 
hematology/Infectious Diseases consultant(s). If high dose corticosteroids are 
initiated, continue for a minimum of 5 days and taper gradually with advice from 
expert consultants. 
 
Refer to Section 12.7.6 regarding bone marrow suppression as a feature of GvHD. 
12.7.8 Management of Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) 
Encephalopathy has been described in association with chimeric antigen receptor (CAR) 
T therapy and termed CAR T cell related encephalopathy syndrome, or CRES [Neelapu, 
2018]. CRES typically manifests as a toxic encephalopathy which is generally reversible. 
Early signs include diminished attention, language disturbance and impaired handwriting. 
Other signs/symptoms include confusion, disorientation, agitation, aphasia, somnolence, 
and tremors. In severe cases of CRES (defined as Grade >2), seizures, motor weakness, 
incontinence, mental obtundation, increased intracranial pressure, papilledema, and 
cerebral edema may also occur. 

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CRES occurring within the first 5 days after immunotherapy may be concurrent with high 
fever and CRS symptoms. This form of CRES tends to be of shorter duration, lower 
grade (Grade 1–2), and the CRS is generally reversible with anti-IL-6 therapy. CRES 
presenting as delayed neurotoxicity with seizures or episodes of confusion can occur 
three or four weeks after CAR T cell therapy, after the initial fever and CRS subside. 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) is a disorder 
characterized by a pathologic process involving the central nervous system following any 
immune therapy that results in the activation or engagement of endogenous or infused 
T cells and/or other immune effector cells. Symptoms or signs can be progressive and 
may include aphasia, altered level of consciousness, impairment of cognitive skills, motor 
weakness, seizures, and cerebral edema. ICANS may occur with other cancer 
immunotherapies, including ACT. Cancer patients may also be at risk for ICANS 
symptoms due to other causes ranging from mild to moderate somnolence and confusion 
as a result of sedating medications, to seizures in relation to CNS tumors. The possible 
contribution of other medications, underlying disease and/or co-morbidities should be 
evaluated when considering a diagnosis of ICANS in relation to T-cell therapy. 
12.7.8.1 
Grading of ICANS 
Lee et al. [Lee, 2019] have developed a new grading system for ICANS which 
incorporates the use of a modified version of the CARTOX 10-point neurological 
assessment tool termed Immune Effector Cell-Associated Encephalopathy (ICE) (Table 
11). Points are assigned for each of the tasks in Table 11, which are performed correctly. 
Normal cognitive function is defined by an overall score of 10.  The ICE should be used 
to monitor all participants 12 years old for ICANS. 
Table 11 
Immune Effector Cell-Associated Encephalopathy (ICE) Assessment 
Tool 
While the 10-point ICE assessment is useful for screening adults for encephalopathy, its 
use in children may be limited to those who are 12 years with sufficient level of 
cognitive abilities to perform the ICE assessment. For children <12 years, the Cornell 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

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Assessment of Pediatric Delirium (CAPD) (Table 12) is recommended to assist in the 
overall grading of ICANS. A CAPD score of 9 is suggestive of delirium and should be 
considered as Grade 3 ICANS. The CAPD score may also be used in patients >12 years 
with baseline developmental delay as it has been validated up to age 21. Other domains 
evaluated to grade ICANS in children are similar to those used in adults and include level 
of consciousness, motor symptoms, seizures, and signs of raised ICP. 
Table 12 
Encephalopathy Assessment for Children Age <12 Years Using the 
CAPD 
Abbreviations: CAPD= Cornell Assessment of Pediatric Delirium 
 
The ICE score is used in grading of ICANS in adults as presented in Table 13.  For 
children either ICE (12 years old) or CAPD (< 12 years old) scores are used as 
presented in Table 14. 
Table 13 
Grading of Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

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Abbreviations:  ICANS= Immune Effector Cell-Associated Neurotoxicity Syndrome; ICE = Immune Effector Cell-
Associated Encephalopathy; CSF = cerebrospinal fluid; ICP = Intracranial Pressure; N/A = not applicable. 
 
1. See Table 11 for ICE. A patient with an ICE score of 0 may be classified as Grade 3 ICANS if awake with global 
aphasia, but a patient with an ICE score of 0 may be classified as Grade 4 ICANS if unarousable. 
2. Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication) 
3. Papilloedema grading is performed according to the modified Frisén scale. 
4. Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded 
from ICANS grading.  
5. Tremors and myoclonus associated with immune effector cell therapies do not influence ICANS grading 
This table is based on Lee, 2019. 
 
Table 14 
ICANS Grading for Children (Based on Lee, 2019) 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.

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ICANS grade is determined by the most severe event (ICE or CAPD score, level of consciousness, seizure, motor 
findings, raised ICP/cerebral edema) not attributable to any other cause. Baseline CAPD score should be considered 
before attributing to ICANS. 
 
1. 
A patient with an ICE score of 0 may be classified as Grade 3 ICANS if awake with global aphasia, but a patient 
with an ICE score of 0 may be classified as Grade 4 ICANS if unarousable. 
2. 
Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication). 
3. 
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0, 
but they do not influence ICANS grading. 
4. 
Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is 
excluded from ICANS grading. It may be graded according to CTCAE v5.0. 
12.7.8.2 
Monitoring for Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) 
Brain MRI (or CT Scan if MRI not feasible) should be obtained for all participants at the 
time of screening:  Baseline brain MRI must be obtained within 4 weeks prior to 
leukapheresis and should be repeated at Baseline visit prior to lymphodepletion only if 
more than 4 months have elapsed between last MRI and Baseline. Brain MRI may be 
performed at other time points, if clinically indicated. 
ICE should be measured on the day of lete-cel infusion prior to receiving treatment and 
then at least through Day 8 according to the schedule of procedures in individual 
substudies.  If a participant is found to have ICANS, the ICE should be used at least twice 
per day until resolution or stable.  It can also be used at later visits if indicated. 
12.7.8.3 
Management of ICANS 
The recommended management of ICANS should be based on toxicity grade. Table 15 
provides guidance on the management of ICANS and should be implemented in 
accordance with institutional guidelines.  
A neurology consultation should be obtained for all participants with ICANS for 
thorough neurological evaluation, and recommendations for further testing such as 
electroencephalogram (EEG) and neuroimaging as indicated.  
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: 
– Chemistry, hematology, ferritin and coagulation, as well as C-reactive protein 
(CRP) labs. 
 
Per SITC 2020 guidelines: 
Across several trials, tocilizumab has failed to resolve symptoms of ICANS, despite 
alleviating severe CRS [Maus, 2020]. It remains to be determined whether targeting 
IL-6R in isolation during established CRS is insufficient to prevent subsequent 
neurotoxicity or if the lack of efficacy is due to tocilizumab’s inability to cross the blood–
brain barrier. It has been postulated that tocilizumab may worsen ICANS and therefore an 

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assessment of treatment priority may be required between the severity of CRS and 
ICANS. Alternative IL-6 blockade such as siltuximab or the IL-1 antagonist, anakinra, 
have been proposed as potential alternatives, but data are lacking on their safety and 
efficacy. 
Corticosteroids have been successfully used for the management of ICANS and seizure 
prophylaxis has been implemented in some studies, but the ideal dose and duration have 
not yet been determined [Maus, 2020].  
Table 15 
Management of ICANS 
ICANS 
Grade 
Treatment 
1 
• Vigilant supportive care; aspiration precautions; IV hydration 
• Withhold oral intake of food, medicines, and fluids, and assess swallowing 
• Convert all oral medications and/or nutrition to IV or enteral tube if swallowing is impaired 
• Avoid medications that cause central nervous system depression 
• Evaluate for other contributing causes and treat accordingly 
• Neurology consultation including fundoscopic exam to assess for papilloedema 
• MRI of the brain with and without contrast (CT scan of the brain if MRI is not feasible).  Further testing 
if indicated and appropriate such as diagnostic lumbar puncture with measurement of opening 
pressure if increased intracranial pressure is suspected, or MRI of the spine if the participant has focal 
peripheral neurological deficits 
• Consider levetiracetam therapy and EEG if seizure activity is suspected 
• Consider anti‑IL‑6 therapy. Tocilizumab1 IV may worsen neurotoxicity. Management of neurotoxicity 
may take precedence over the management of low-grade CRS, but this does not apply to high-grade 
CRS. Alternative IL-6 blockade may be considered (e.g. siltuximab) or the IL-1 antagonist, anakinra. 
2 
• As described for Grade 1 PLUS 
• Consider ICU transfer 
• Consider corticosteroids2 
3 
• As described for Grades 1 & 2 PLUS 
• Corticosteroids are recommended. 
• Stage 1 or 2 papilloedema with CSF opening pressure <20 mmHg should be treated corticosteroid 
regimen as per Grade 4 below. 
• Consider repeat neuroimaging (CT or MRI) every 2 to 3 days if participant has persistent Grade ≥3 
ICANS 
4 
• As described for Grades 1, 2 & 3 PLUS 
• Consider neurosurgical consultation for participants with evidence of increased intracranial pressure 
• ICU monitoring; consider mechanical ventilation for airway protection 
Abbreviations: CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed tomography; 
EEG = electroencephalogram; h = hour(s); ICANS= Immune Effector Cell-Associated Neurotoxicity Syndrome; 
ICU = intensive care unit; IL-6 = interleukin-6; IV = intravenous; MRI = magnetic resonance imaging. 
1. Tocilizumab: 8mg/kg IV for patients weighing 30kg or above, administered over 1hr, max dose 800mg, doses at 
least 8hrs apart. 
2. Consider dexamethasone 10 mg IV every 6 h (Grade ≤3 ICANS), or methylprednisolone 1 mg/kg IV every 24 h for 
3days (Grade 4 ICANS), if refractory to anti‑IL‑6 therapy, or for ICANS without concurrent CRS; once initiated 
continue corticosteroids for at least two doses until improvement to Grade 1 ICANS and then taper. 
Source: [Maus, 2020] 
 
Grade 1 ICANS. Grade 1 ICANS is defined as a score of 7-9 on the ICE assessment for 
patients ≥12 years (Table 13) or a score of 1-8 on the CAPD assessment for patients 

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<12 years (Table 14).  A patient with grade 1 ICANS may have a delay in responses or 
disorientation to time or place, mild inattention with difficulty in counting numbers 
backwards, or impairment of handwriting. There may be drowsiness but patients awaken 
spontaneously, and when prompted, the patientshould be able to complete most of the 
ICE assessment. Grade 1 ICANS may be seen during CRS waxing and waning with 
febrile episodes. 
Grade 2 ICANS. Grade 2 ICANS is defined as a score of 3-6 on the ICE assessment for 
patients ≥12 years (Table 13) or a score of 1-8 on the CAPD assessment for patients 
<12 years (Table 14).  Expressive aphasia is the most specific first sign of severe 
neurotoxicity and early signs during Grade 2 include paraphasic errors (the production of 
unintended syllables and words during attempts to speak) and verbal perseveration with 
patients repeating the same words over and over. Patients with Grade 2 ICANS are able 
to communicate their needs but it is effortful. Patients may have depressed level of 
consciousness but are arousable to voice and the responses may be slowed. 
Grade 3 ICANS. Grade 3 ICANS is defined as a score of 0-2 on the ICE assessment for 
patients ≥12 years (Table 13) or a score of  ≥9 on the CAPD assessment for patients 
<12 years (Table 14).  Patients with Grade 3 ICANS have severe global aphasia and are 
not speaking or following commands even when wide awake and therefore may be 
unable to complete any of the ICE questions. Alternatively, they may have excessive 
drowsiness and need tactile stimulus to attend to examiner. Any clinical seizure whether 
simple partial, complex partial or generalized, and any electrographic seizures would also 
meet criteria for Grade 3 ICANS (Table 13, Table 14). If neuroimaging shows new focal 
or local edema this would also be categorized as Grade 3 ICANS (Table 13, Table 14). 
However, intracranial hemorrhage due to coagulopathy or other causes with or without 
associated edema is not considered a neurotoxicity feature and is excluded from ICANS 
grading. 
Grade 4 ICANS.  Grade 4 ICANS is defined as patients who have a score of 0 on the 
ICE assessment due to being unarousable and unable to perform the ICE assessment.  For 
patients <12 years, Grade 4 ICANS is defined as patients unable to perform CAPD.  
Stupor and coma may be seen; the stuporous patient only responds by grimacing or 
drawing away from vigorous or repetitive tactile stimuli and the comatose patient is 
unarousable and/or unresponsive (Table 13, Table 14). This depressed level of 
consciousness should be attributable to no other cause (e.g. no sedating medication), 
which is often a complicating factor in sick patients with CRS. Some patients may 
require intubation for airway protection. In addition, any patient having prolonged or 
repetitive clinical or subclinical electrographic seizures without return to baseline in 
between, or deep focal motor weakness such as hemiparesis or paraparesis would be 
considered to have Grade 4 ICANS (Table 13, Table 14). Patients with symptoms and 
signs of elevated ICP such as projectile vomiting with headache, depressed 
consciousness, cranial nerve VI palsies, papilledema, Cushing’s triad of bradycardia, 
hypertension and respiratory depression, decerebrate or decorticate posturing, or diffuse 
cerebral edema on head imaging would also be considered to have Grade 4 ICANS 
(Table 13, Table 14).  

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Grade 5 ICANS. By convention, Grade 5 ICANS is defined as death due to ICANS 
where another cause is not the principle factor leading to this outcome. 
12.7.9 
Chemotherapy Symptom Management 
Cyclophosphamide and fludarabine are used as conditioning chemotherapy in this study 
to cause lymphodepletion and facilitate expansion of the infused T-cells. Symptoms 
associated with the use of cyclophosphamide and fludarabine are included in the product 
labels. Refer to the most current product labels, and Section 7.5.1 for details of prohibited 
medications. 
12.7.9.1 
Management of Neutropenia 
The conditioning chemotherapy is intended to cause lymphodepletion. However, 
neutropenia is also common. Prophylactic use of G-CSF is recommended in all 
participants. G-CSF (e.g., filgrastim) should be used for management of neutropenia 
according to ASCO guidelines [Smith, 2015]. G-CSF must be given starting ~24 hours 
after the administration of chemotherapy (i.e. on Day -3) 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 ~24 hours post the final dose of cyclophosphamide(i.e. on Day -3). 
12.7.10 
Management of Guillain-Barré Syndrome (GBS) 
Please obtain a neurology consultation for all participants with signs or symptoms 
suggestive of GBS for thorough neurological evaluation, and for expert recommendations 
on further diagnostic workup including EMG, lumbar puncture, infectious panel to guide 
management and follow up. 

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Case assessment for possible Guillain Barré Syndrome using diagnostic and 
prognostic tools supported by medical diagnosis and/or medical treatment 
 
*Please refer to algorithm for treatment described in Figure 5. 
Additional details specific to the neurology consultation are included in Appendix 8 
(Section 12.8). 
12.7.10.1 Neurological symptoms 
The following features should be considered as suggestive of a GBS diagnosis in clinical 
practice and the use of the Brighton criteria [Fokke, 2014] together with further 
neurological evaluation will be the basis for confirmation of diagnosis: 
 
Progressive weakness in legs and arms (sometimes initially only in legs). 
• Areflexia (or decreased tendon reflexes) in weak limbs. 
 
Additional symptoms 
• Progressive weakness phase lasts 2 to 4 weeks (often 2 weeks). 
• Relative symmetry of weakness. 
• Cranial nerve involvement, especially bilateral weakness of facial muscles. 
• Autonomic dysfunction. 
• Pain  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Peripheral 
neuropathy 
Symptoms 
suggestive of 
GBS/AIDP 
Treatment according 
to guidelines/clinical 
practice 
GBS Diagnostic tool: 
Brighton Criteria 
At hospital admission 
Indicator of prognosis 
EGRIS tool 
At hospital 
admission* 
mEGOS tool 
At hospital admission and Day 7 
Yes 
Confirmatory assessment 
targeted within 7 days from 
hospital admission 
Suspected 
GBS 
Strength of diagnosis includes 
clinical assessment and CSF and 
NCV measures. Some tests may not 
be available until several days after 
hospital admission. 
• 
Confirmed GBS required to 
implement mEGOS.  
• 
At hospital admission (data 
that supports Brighton level 1 
or 2) may not be available.  
• 
Level 1 or 2 assessment 
required before mEGOS 
assessment i.e. Day 7 
Neurology 
consultation 

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12.7.10.2 
Brighton key diagnostic criteria  
At admission and confirmation within 7 days of admission 
• Bilateral and flaccid weakness of limbs 
• Decreased or absent deep tendon reflexes in weak limbs 
• Monophasic course and time between onset – nadir 12 hours to 28 days 
• CSF cell count < 50/µl 
• CSF protein concentration > normal value 
• Nerve conduction studies findings consistent with one of the subtypes of GBS 
• Absence of alternative diagnosis for weakness 
 
12.7.10.3 
Erasmus GBS Respiratory Insufficiency Score (EGRIS) 
Probability of acute risk first week following hospital admission of respiratory 
insufficiency [Walgaard, 2010].  
Parameters required at hospital admission: 
• Days of onset of weakness and admission 
• Facial and/or bulbar weakness at admission 
• Medical Research Council sum score 
 
12.7.10.4 
Modified Erasmus GBS Outcomes Score (mEGOS) 
Parameters required at hospital admission and 7 days later [Walgaard, 2011]:  
• Age at onset 
• Preceding diarrhoea (in 4 weeks preceding onset of weakness) 
• Medical Research Council sum score 
 
12.7.10.5 
Summary of diagnosis and treatment for GBS 
Additional information on the diagnosis and management of GBS (Figure 5) can be 
found in a review article on GBS [Willison, 2016].  

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Figure 5 
Diagnosis and Treatment of Guillain-Barré Syndrome (GBS)  
 
Abbreviations: EGRIS = Erasmus GBS Respiratory Insufficiency Score; GBS = Guillain-Barré Syndrome; 
ICU = intensive care unit; IVIg = intravenous immunoglobulin; TRF = treatment related fluctuation. 
Source with permission: Willison, 2016. . 

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12.8 
Appendix 8: Neurology Consultation – Further Guidelines for 
Signs and Symptoms Suggestive of Guillain-Barré Syndrome 
For patients presenting with neurological events, a confirmed diagnosis of peripheral 
neuropathy should be treated according to local guidelines and/or clinical practice.  
However, any patient with presenting signs and symptoms suggestive of GBS (see 
protocol, Section 12.7.10.1), must be further evaluated by a neurologist according to 
diagnostic guidance for GBS using the Brighton diagnostic criteria [Fokke, 2014] see 
Table 16 below). The initial assessment at hospital admission should be further verified 
within 7 days of initial assessment, following availability of all test results as listed: 
Table 16 
Brighton diagnostic criteria 
Brighton diagnostic criteria include assessment of the following: 
Criteria 
Level of diagnostic certainty 
 
1 
2 
3 
4 
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 
+ 
+1 
- 
 
CSF protein concentration > normal value 
+ 
1 
- 
 
Nerve conduction study findings consistent with 
one of the subtypes of GBS 
+ 
 
- 
 
Absence of alternative diagnosis for weakness 
+ 
+ 
+ 
+ 
1. 
If CSF not collected or results not available, nerve conduction studies must be consistent with diagnosis of 
GBS (modified from Fokke et al,2014). 
 
12.8.1 
Additional Assessments for Suspected GBS at Hospital 
Admission 
12.8.1.1 
Risk of Respiratory Insufficiency Assessment 
An assessment of the probability of risk of respiratory insufficiency during the first week 
following admission of suspected GBS is required using the Erasmus GBS Respiratory 
Insufficiency Score (EGRIS) tool (total score 0 to 7) [Walgaard, 2010]. 

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Please access link to assessment tool and record total score in eCRF. 
https://qxmd.com/calculate/calculator_527/erasmus-gbs-respiratory-insufficiency-score-
egris 
Assessment at hospital admission to include: 
• 
Days of onset of weakness and admission  
• 
Facial and/or bulbar weakness at admission  
• 
Medical Research Council score  
 
The Medical Research Council score includes assessment for 6 muscle groups, 
including shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, 
and foot dorsiflexors on both sides. The MRC score of an individual muscle group range 
from 0 to 5: 
Taken from: [Van Koningsveld, 2007] 
The MRC total scores range from 60 (
) to 0 (
). The total score should 
be included in the eCRF assessment for EGRIS. 
12.8.1.2 
Prognostic Tool for Assessment of GBS Outcome at Hospital 
Admission 
An assessment of prognosis using the modified Erasmus GBS Outcomes Score 
(mEGOS) (total score 0 to 9) for diagnosed cases of GBS [Walgaard, 2011] should also 
be performed. Early assessment following hospital admission includes assessment of the 
following: 
• 
Age (years) at onset:  ≤ 40, 41 – 60, > 60 
• 
Preceding diarrhoea (in 4 weeks preceding onset of weakness): absent/present 
• 
MRC sum score (see above): 0 – 30, 31 – 40, 41 – 50, 51 – 60 
 
Please access link to assessment tool and record total score in eCRF. 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.
CCI
CCI

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https://qxmd.com/calculate/calculator_529/modified-erasmus-gbs-outcome-score-egos-
at-day-7-of-admission 
12.8.2 
Assessments Post Hospital Admission for GBS 
12.8.2.1 
Brighton Criteria 
The initial assessment at hospital admission should be further verified within 7 days of 
initial assessment, following availability of all test results. 
12.8.2.2 
Prognostic Tool for Assessment of GBS Outcome at Day 7 Post 
Hospital Admission 
An assessment of prognosis using the modified Erasmus GBS Outcomes Score 
(mEGOS) (total score 0 to 9) for diagnosed case of GBS [Walgaard, 2011]. Assessment 
following Day 7 hospital admission includes assessment of the following: 
• 
Age (years) at onset:  ≤ 40, 41 – 60, > 60 
• 
Preceding diarrhoea (in 4 weeks preceding onset of weakness): absent/present 
• 
MRC sum score (see above): 0 – 30, 31 – 40, 41 – 50, 51 – 60 
 
Please access link to assessment tool and record total score in eCRF. 
https://qxmd.com/calculate/calculator_529/modified-erasmus-gbs-outcome-score-egos-
at-day-7-of-admission 
• 
Brighton criteria – the initial assessment at hospital admission should be further 
verified within 7 days of initial assessment, following availability of all test results. 
 

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12.9 
Appendix 9: Eastern Cooperative Oncology Group 
Performance Scale 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.

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12.10 Appendix 10: Abbreviations and Trademarks 
1L 
First line 
2L 
Second line 
AABB 
American Association of Blood Banks 
ABW 
Adjusted body weight 
ACT 
Adoptive T cell therapy 
AE 
Adverse event 
AESI 
Adverse events of special interest 
AIDP 
Acute inflammatory demyelinating polyneuropathy 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
aPTT 
Activated Partial Thromboplastin Time 
ASCO 
American Society of Clinical Oncology 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
ATG 
Antithymocyte globulin 
AUC(0-t) 
Area under the concentration-time curve over the dosing 
interval 
BUN 
Blood urea nitrogen 
CA 
Competent Authority 
CAR 
Chimeric antigen receptor 
CBC 
Complete blood count 
CD3/CD4/CD8 
Cluster of differentiation 3/ cluster of differentiation 4/ cluster 
of differentiation 8 
CDC 
Center for Disease Control 
CFR 
Code of federal regulations 
CI 
Confidence Interval 
CIOMS 
Council for international organizations of medical sciences 
CKD-EPI 
Chronic kidney disease epidemiology collaboration 
cm 
Centimetres 
Cmax 
Maximum observed concentration 
Cmin 
Minimum observed concentration; 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
CONSORT 
Consolidated standards of reporting trials 
CPD 
Confirmed progression 
CPK 
Creatine phosphokinase 
CR 
Complete response 
CRF 
Case report form 
CRP 
C-reactive protein 
CRS 
Cytokine release syndrome 

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CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common terminology criteria for adverse events 
ctDNA 
Circulating tumor DNA 
CTFG 
Clinical Trial Facilitation Group 
CV 
Cardiovascular 
CYP2D6 
Cytochrome P450 2D6 
CYP3A4 
Cytochrome P450 3A4 
D 
Day 
dL 
Decilitre 
DCR 
Disease control rate 
DLCO 
Diffusing capacity of the lung for carbon monoxide 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
EBV 
Epstein-Barr virus 
ECG 
Electrocardiogram(s) 
ECHO 
Echocardiography 
eCOA 
electronic Clinical Outcome Assessment 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EDTA 
Ethylenediaminetetraacetic acid 
EMA 
European Medicines Agency 
EMG 
Electromyography 
EOT 
End of treatment 
FACT 
Functional assessment of cancer therapy 
FACT-G 
Functional assessment of cancer therapy – general 
FDA 
Food and Drug Administration 
FDG-PET 
Fluorodeoxyglucose positron emission tomography 
FEV1 
Forced expiratory volume in 1 second 
FFPE 
Formalin-fixed paraffin-embedded 
FPCP 
Female participants of child bearing potential 
FSH 
Follicle stimulating hormone 
FVC 
Forced vital capacity 
GBS 
Guillain-Barré Syndrome 
GCLP 
Good clinical laboratory practice 
GCP 
Good clinical practice 
CCI
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G-CSF 
Granulocyte colony-stimulating factor 
GFR 
Glomerular filtration rate 
GI 
Gastrointestinal 
GSK 
Glaxosmithkline 
GvHD 
Graft versus host disease 
Hb 
Haemoglobin 
HBV 
Hepatitis B virus 
HbsAg 
Hepatitis B surface antigen 
HbcAb 
Hepatitis B core antibody 
hCG 
human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HIPAA 
Health insurance portability and accountability act 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HPLC 
High performance liquid chromatography 
hr 
Hour 
HRT 
Hormone replacement therapy 
HTLV 
Human T-lymphotropic virus 
IB 
Investigator’s brochure 
IBW 
Ideal Body Weight 
ICANS 
Immune Effector Cell-Associated Neurotoxicity Syndrome 
ICE 
Immune Effector Cell-Associated Encephalopathy 
ICF 
Informed consent form 
ICH 
International council on harmonization of technical 
requirements for registration of pharmaceuticals for human use 
iCPD 
iRECIST confirmed progressive disease 
iCR 
iRECIST complete response 
IEC 
Independent ethics committees 
IFN 
Interferon 
IFN 
Interferon, gamma 
IgG 
Immunoglobulin G 
IL 
Interleukin 
IL-1R 
Interleukin-1 Receptor 
IND 
Investigational new drug 
INR 
International normalized ratio 
IO 
Insertional oncogenesis 
iPR 
iRECIST progressive disease 
irAEs 
Immune-related Aes 
IRB 
Institutional review board 
iRECIST 
Modified recist 1.1 for immune-based therapeutics 
iSD 
iRECIST stable disease 
ITT 
Intent to treat 

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IUD 
Intrauterine device  
iUPD 
iRECIST unconfirmed progressive disease 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
IVD 
In vitro companion diagnostic device 
IVRS 
Interactive voice response system 
IWRS 
Interactive web response system 
kg 
Kilograms 
LAM 
Lactational amenorrhoea method 
LDH 
Lactate dehydrogenase 
Lete-cel 
Letetresgene autoleucel (GSK3377794) 
LTFU 
Long-term follow-up 
m2 
Meters squared 
mAb 
Monoclonal antibody 
MCH 
Mean corpuscular haemoglobin 
MCV 
Mixed cell volume 
MedDRA 
Medical dictionary for regulatory activities 
mg 
Milligram 
mITT 
Modified Intent to treat 
mL 
Millilitre 
L 
Microliter 
mm 
Millimetres 
MRI 
Magnetic resonance imaging 
MSDS 
Material Safety Data Sheet 
MUGA 
Multigated acquisition scan 
NA 
Not applicable 
NCI 
National Cancer Institute 
NE 
Not evaluable 
NIH 
National Institutes for Health 
NSAIDs 
Nonsteroidal anti-inflammatory drugs 
NSCLC 
Non-small-cell lung cancer 
NSCLC-SAC 
Non-small-cell lung cancer Symptom Assessment 
Questionnaire 
NY-ESO-1 
New York esophageal antigen-1 
NYHA 
New York Heart Association 
ORR 
Overall response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PCI 
Potential clinical importance 
PCP 
Pneumocystis carinii Pneumonia 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 

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PD-1 
Programmed death receptor-1 
PD-L1 
Programmed cell death ligand 1 
PD-L2 
Programmed cell death ligand 2 
PEAP 
Primary Efficacy Analysis Population 
PFS 
Progression-free survival 
PFT 
Pulmonary function test 
P-gp 
P-glycoprotein 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
PR 
Partial response 
PRO 
Patient-reported outcome 
PS 
Performance status 
PT 
Preffered term 
PT 
Prothrombin time 
Q2W 
Every 2 weeks 
Q3W 
Every 3 weeks 
Q12W 
Every 12 weeks 
QLQ 
Quality of life questionnaire 
QoL 
Quality of life 
QTc 
Corrected QT interval duration 
QTcB 
QT duration corrected for heart rate by Bazzetts’s formula 
QTcF 
QT duration corrected for heart rate by Fridericia’s formula 
RAP 
Reporting and analysis plan 
RBC 
Red blood cell 
RCL 
Replication competent lentivirus 
RECIST 
Response evaluation criteria in solid tumors 
RT-qPCR 
Reverse transcriptase polymerase chain reaction 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SCT 
Stem cell transplant 
SD 
Stable disease 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 
SoA 
Schedule of assessments 
SoC 
Standard of care 
SRM 
Study reference manual 
SRT 
Safety Review Team 
SUSAR 
Suspected unexpected serious adverse reactions 
T4 
Thyroxine 4 
TCR 
T cell receptor 
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TGF 
Transforming growth factor 
TLC 
Total lung capacity 
TLTs 
Treatment Limiting Toxicities 
Tmax 
Time to maximum concentration 
TMB  
Tumor mutational burden 
TMDD 
Target-mediated drug disposition 
TNF 
Tumor necrosis factor 
TSH 
Thyroid stimulating hormone 
TTR 
Time to response 
ULN 
Upper limit of normal 
UPD 
Unconfirmed progression 
UPENN 
University of Pennsylvania 
VSV-G 
Vesicular stomatitis virus G protein 
W 
Week 
WBC 
White blood cell 
WHO 
World health organization 
WOCBP 
Woman of childbearing potential 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
Lartruvo 
 
 
WinNonlin 
 
 
 
 
 

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13 SUBSTUDIES 
SUBSTUDY 1: LETETRESGENE AUTOLEUCEL (LETE-CEL, 
GSK3377794) IN NY-ESO-1 POSITIVE PREVIOUSLY UNTREATED 
ADVANCED (METASTATIC OR UNRESECTABLE) SYNOVIAL 
SARCOMA AND MYXOID/ROUND CELL LIPOSARCOMA 
Substudy Title: Evaluation of Safety and Antitumor Activity of Lete-Cel (GSK3377794) 
in HLA-A2+ Participants with NY-ESO-1 Positive Previously Untreated Advanced 
(Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma 
 

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TABLE OF CONTENTS 
1 
SYNOPSIS ........................................................................................................... 139 
2 
SCHEDULE OF ACTIVITIES (SOA) ..................................................................... 139 
3 
INTRODUCTION .................................................................................................. 152 
3.1 
Background and Rationale for First Line Therapy with Lete-cel 
(GSK3377794) .......................................................................................... 152 
3.2 
Benefit/Risk Assessment .......................................................................... 155 
3.2.1 
Risk Assessment ....................................................................... 156 
3.2.2 
Benefit Assessment ................................................................... 161 
3.2.3 
Overall Benefit/Risk Conclusion ................................................. 162 
4 
OBJECTIVES AND ENDPOINTS ......................................................................... 163 
5 
SUBSTUDY DESIGN ........................................................................................... 165 
5.1 
Overall Design .......................................................................................... 165 
5.2 
Number of Participants ............................................................................. 169 
5.3 
End of Study Definition ............................................................................. 169 
5.3.1 
End of Substudy for Individual Participants ................................ 169 
5.3.2 
End of Substudy ........................................................................ 169 
5.4 
Scientific Rationale for Substudy Design .................................................. 170 
5.5 
Justification for Dose ................................................................................ 171 
5.5.1 
Justification of Lymphodepleting Regimen ................................. 171 
5.5.2 
Justification of lete-cel (GSK3377794) Dose .............................. 171 
6 
STUDY POPULATION ......................................................................................... 173 
6.1 
INCLUSION CRITERIA ............................................................................. 173 
6.1.1 
Target Expression Screening ............................................................. 173 
6.1.2 
Leukapheresis Eligibility Screening...................................................... 174 
6.1.3 
Treatment Eligibility Screening ........................................................... 177 
6.1.3.1 
Treatment Fitness (for Safety) .......................................... 178 
6.2 
EXCLUSION CRITERIA ........................................................................... 178 
6.2.1 
Target Expression Screening ............................................................. 178 
6.2.2 
Leukapheresis Eligibility Screening...................................................... 179 
6.2.3 
Treatment Eligibility Screening ........................................................... 180 
6.2.3.1 
Treatment Fitness (for Safety) .......................................... 182 
6.3 
Lifestyle Considerations ............................................................................ 182 
6.3.1 
Meals and Dietary Restrictions .................................................. 182 
6.3.2 
Activity ....................................................................................... 182 
6.3.3 
Screen Failures.......................................................................... 182 
6.3.4 
Rescreening .............................................................................. 182 
7 
STUDY INTERVENTION ...................................................................................... 183 
7.1 
Study Intervention(s) Administered ........................................................... 183 
7.1.1 
Leukapheresis ........................................................................... 183 
7.1.2 
Bridging Therapy and/or Standard of Care Intermediate 
Anti-Cancer Therapy before Lymphodepletion ........................... 183 
7.1.3 
Lymphodepleting Chemotherapy ............................................... 183 
7.1.4 
Lete-cel (GSK3377794) Infusion ................................................ 187 
7.2 
Preparation / Handling / Storage / Accountability ...................................... 188 

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7.3 
Measures to Minimize Bias: Randomization and Blinding ......................... 189 
7.4 
Study Intervention Compliance ................................................................. 189 
7.5 
Concomitant Therapy................................................................................ 189 
7.5.1 
Prohibited Concomitant Medication and Treatment .................... 190 
7.5.2 
Permitted Concomitant Medication and Treatment .................... 191 
7.5.3 
Rescue Medicine ....................................................................... 192 
7.6 
Dose Modification ..................................................................................... 192 
7.7 
Intervention after the End of the Study ...................................................... 192 
8 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION / WITHDRAWAL ................................................................. 192 
9 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 192 
9.1 
Interviews ................................................................................................. 193 
9.1.1 
Post T cell Infusion Interview ..................................................... 193 
9.1.2 
End of Treatment Interview ........................................................ 193 
9.2 
Patient Reported Outcomes ...................................................................... 193 
9.3 
Safety Assessments ................................................................................. 195 
10 STATISTICAL CONSIDERATIONS ...................................................................... 195 
10.1 
Statistical hypotheses ............................................................................... 195 
10.2 
Sample size justification ............................................................................ 195 
10.3 
Statistical Analyses ................................................................................... 196 
10.3.1 
Efficacy Analyses ....................................................................... 196 
10.3.2 
Safety Analyses ......................................................................... 198 
10.3.3 
Other Analyses .......................................................................... 199 
10.3.4 
Interim Analyses ........................................................................ 199 
 
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Substudy 1 
 
SUBSTUDY 1: LETETRESGENE AUTOLEUCEL (LETE-CEL, 
GSK3377794) IN NY-ESO-1 POSITIVE PREVIOUSLY UNTREATED 
ADVANCED (METASTATIC OR UNRESECTABLE) SYNOVIAL 
SARCOMA AND MYXOID/ROUND CELL LIPOSARCOMA  
This previously untreated (first line, 1L) advanced (metastatic or unresectable) 
translocation-related sarcoma Substudy 1 contains substudy specific details. Refer to the 
body of the Core Protocol for all other information.  
1 SYNOPSIS 
This is a non-randomized substudy to investigate letetresgene autoleucel (lete-cel, 
GSK3377794) in previously untreated participants with advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma as defined in the 
inclusion criteria.  In this substudy, we will not be evaluating tumors for LAGE-1a 
expression since the Immunohistochemistry assay used for the antigen detection 
recognizes NY-ESO-1 only and not LAGE-1a.  LAGE-1a is rarely expressed in synovial 
sarcoma or myxoid/round cell liposarcoma. 
Substudy 1 Design 
 
* The lymphodepleting regimen is to be adjusted as described in Section 7.1.3 of this Substudy. 
 
See Section 1 Synopsis in the core protocol for overall study summary. 
2 SCHEDULE OF ACTIVITIES (SOA) 
The timing and number of planned study assessments, including safety, pharmacokinetic, 
pharmacodynamic/biomarker or other assessments may be altered during the course of 
this substudy based on newly available data to ensure appropriate monitoring.  

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Table 1: 
Substudy 1 Schedule of Activities– Screening and Leukapheresis 
 
Screening Phase1 
Leukapheresis 
Notes 
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening,  within 
28 days prior to 
leukapheresis3 
Informed Consent for Screening 
X 
 
 
1. Written informed consent must be obtained prior to performing any study 
assessments or procedures, except as stated in footnote 12.  Informed 
Consent for Leukapheresis and Treatment must be repeated if given more 
than 90 days prior to leukapheresis procedure. 
2. This visit may be performed under a separate protocol when it is introduced. 
3. Participants must be HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 
positive and have NY-ESO-1 positive tumor prior to conducting leukapheresis 
eligibility screening procedures.  
4. Only collect this sample if optional Genetics Research Consent has been 
signed by the participant. Sample may be collected any time from signature of 
optional consent until leukapheresis.  Liquid biopsy is a blood sample from 
which circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and 
exosomes may be extracted. 
5. 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. 
6. Includes all prescription, over-the-counter medications, and herbal remedies. 
Any use of mutagenic agents or investigational agents must also be reported. 
7. In pediatric participants height and weight will also be evaluated as a 
percentile vs national growth charts (based on sex and age) and vs genetic 
height target (expected height based on parental heights) and evaluation will 
be performed on whether growth is normal or abnormal. 
8. To be performed within 7 days prior to the day of leukapheresis. 
9. CD3 count prior to leukapheresis should be preferably performed within 
24 hours from leukapheresis procedure. 
10. Lansky will be used for participants <16 years of age; Karnofsky will be used 
for participants 16 and <18 years of age; and ECOG will be used for 
participants 18 years of age. 
Informed Consent for Leukapheresis 
and Treatment1 
 
X 
 
Inclusion/Exclusion for Screening 
X 
 
 
Inclusion/Exclusion for Leukapheresis 
 
X 
 
Demographics 
X 
 
 
Central Lab HLA -A genotyping3 
X 
 
 
Tumor expression of NY-ESO- 13 
X 
 
 
Liquid biopsy (blood)4 
X 
 
 
Medical History5  
X 
X 
 
Prior/Concomitant Medications6 
X 
X 
X 
Height and Weight7 
 
X 
 
Physical Exam (complete) 
 
X 
X8 
ECOG or Lansky or Karnofsky10 
X 
X 
 
Vital Signs11 
 
X 
X8 
12-lead ECG (in triplicate) 
 
XXX 
XXX8 
ECHO/MUGA 
 
X12 
 
CT / MRI 
 
X13 
 
Brain MRI14 
 
X13 
 
Hematology 
 
X12 
X8 
Clinical Chemistry 
 
X12 
X8 
Coagulation Tests 
 
X12 
X8 
Lymphocyte Subset (CD3/CD4/CD8) 
 
X8 
X8,9 
Estradiol and FSH, if needed to 
determine CBP 
 
X 
 
Pregnancy Test15 
 
X15 
X15 
Urinalysis 
 
X12 
X8 
Infectious disease markers16 
 
X12 
 

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Screening Phase1 
Leukapheresis 
Notes 
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening,  within 
28 days prior to 
leukapheresis3 
Creatinine clearance by GFR or 24h 
urine17  
 
X 
 
11. Includes temperature, blood pressure, pulse rate, respiratory rate, and oxygen 
saturation. 
12. ECHO/MUGA  and laboratory assessments performed as standard of care 
prior to study consent will be acceptable as long as assessment is done within 
28 days before leukapheresis.  
13. CT/MRI scan performed as standard of care prior to study consent will be 
acceptable as long as assessment is done within 90 days before 
leukapheresis. Any FDG PET/CT performed as part of clinical routine within  
90 days before leukapheresis, will also be collected. 
14. In addition to the Brain MRI, MRI of the spine will be performed when clinically 
indicated. 
15. WOCBP must have a highly sensitive negative urine or serum pregnancy test 
at screening for leukapharesis and within 24 h prior to leukapheresis.  
16. Includes HIV, HBV, HCV, HTLV, EBV, CMV, and syphilis (spirochaete 
bacterium). 
17. See Section 6.1 Table 5 for specifics on renal assessment. 
18. SAEs and Aes assessed as related to study participation (e.g., study 
intervention, protocol-mandated procedures, invasive tests, or change in 
existing therapy) or leading to study withdrawal will be collected from signing 
informed consent for target expression screening.  All SAEs and Aes will be 
collected starting at leukapheresis (See Section 9.4.1 in the Core Protocol). 
Adverse Events and Serious Adverse 
Events 
X18 
X18 
X 
Leukapheresis 
 
 
X 
 
AE=adverse event; CBP=child-bearing potential; CT = computerized tomography; EBV = Epstein Barr virus; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern 
Cooperative Oncology Group; FDG = Fluorodeoxyglucose; FSH=follicle-stimulating hormone; GFR = glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; 
HIV = human immunodeficiency virus; HTLV = human T-lymphotropic virus; MRI = magnetic resonance imaging; MUGA = multigated acquisition; SAE=serious adverse event; 
WOCBP = Women of childbearing potential. 

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Table 2 
Substudy 1 Schedule of Activities – Interventional Phase (Lymphodepletion and Treatment)  
 
Treatment 
Fitness & 
Eligibility / 
Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week  
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 or 
until confirmed 
PD, whichever 
is sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
Treatment Fitness and 
Inclusion/Exclusion for 
Treatment Eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Request lete-cel 
shipment 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med. History3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
(complete) 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
Physical Exam 
(dedicated) 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
 
 
Prior/Con Meds4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG, Karnofsky or 
Lansky5 
X 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
X 
Developmental exam, 
height, and puberty 
assessment6,7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X8 
Vital Signs9 and 
weight7 
X 
X 
X 
X 
X 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECHO/MUGA11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulse oximetry 
 
 
 
 
 
X12 
X 
X 
X 
X 
X 
X13 
X 
X13 
 
X 
X 
X 
 
12-lead ECG14 
XXX 
 
 
 
 
X 
 
 
X 
 
X 
 
 
 
 
 
 
 
 

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Treatment 
Fitness & 
Eligibility / 
Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week  
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 or 
until confirmed 
PD, whichever 
is sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
CT/MRI15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X16 
X16 
Brain MRI17 
X17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ICE or CAPD18 
 
 
 
 
 
X19 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology20 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Chemistry20 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Uric acid 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Creatinine clearance by 
GFR or 24 h urine21 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation Tests20, 22 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Ferritin20 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Troponin and  
NT-proBNP / BNP 
test23 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
X 
 
 
 
 
X24 
 
 
 
 
 
 
X 
 
 
 
X 
X25 
X25 
Urinalysis26 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious disease 
markers27 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CMV IgG and PCR28 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
 
 
Thyroid function tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CRP20 
X 
 
 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Treatment 
Fitness & 
Eligibility / 
Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week  
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 or 
until confirmed 
PD, whichever 
is sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
Adverse Events and 
Serious Adverse 
Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Transgene Copies 
(Persistence for Safety) 
and VSV-G DNA 
(RCL)29 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 and 
24 
Month 12 
and Q6M30 
Genetic sample 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Survival follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Lymphodepletion 
Fludarabine 
 
X31 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamide 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigational Product Administration 
Lete-cel (GSK3377794) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient-Reported Outcomes32 
Post-lete-cel infusion 
interview  
(adult participants only) 
 
 
 
 
 
 
 
 
 
 
X33 
 
 
 
 
 
 
 
 
EOT interview 
(adult participants only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X34 
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Treatment 
Fitness & 
Eligibility / 
Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week  
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 or 
until confirmed 
PD, whichever 
is sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
1. 
On Day 1, all samples will be collected and assessments performed prior to T-cell infusion (within 24 h), unless otherwise specified.  
2. 
As lete-cel needs to be on site prior to lymphodepletion, request lete-cel no later than 4 working days prior to the day of lymphodepletion.  The mechanism of request will be 
provided in and the Drug Product and Infusion Manual. 
3. 
Medical history will be recorded in the eCRF at Treatment Eligibility Screening / Baseline visit; however, any changes in medical history must be recorded in source documents 
throughout the conduct of the study. 
4. 
Includes all prescription, over-the-counter medications, and herbal remedies. Any use of mutagenic agents or investigational agents must also be reported. 
5. 
Lansky will be used for participants <16 years of age; Karnofsky will be used for participants 16 and <18 years of age; and ECOG will be used for participants 18 years of age. 
6. 
To be assessed in pediatric participants only. 
7. 
In pediatric participants height and weight will also be evaluated as a percentile vs national growth charts (based on sex and age) and vs genetic height target (expected height 
based on parental heights) and evaluation will be performed on whether growth is normal or abnormal. 
8. 
To be assessed once a year. 
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9. 
Vital signs include temperature, blood pressure, pulse rate, and respiratory rate. 
10. Vital signs on day of T-cell infusion should be taken pre-infusion, and approximately at 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started.  
11. If suspected CRS Grade ≥2, an ECHO/MUGA is required at onset of Grade ≥2 CRS. Additional monitoring must be conducted (including inpatient continuous cardiac telemetry 
monitoring) for a minimum of 3 days post onset and as long as deemed necessary by the Investigator (refer to Section 12.7.5).   
12. On T-cell infusion day, pulse oximetry should be taken pre-infusion, and at approximately 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started.  
13. Pulse oximetry at these visits will be performed if medically indicated.  
14. ECG can also be performed at other time points if medically indicated.  Triplicate ECG will be collected at Treatment Eligibility Screening / Baseline visit and single ECGs at other 
timepoints. Participants with an increased burden of cardiovascular risk factors (as per Section 9.3.6) will undergo evaluation by a cardiologist prior to lymphodepletion. 
15. See Section 9.1.1 in the core protocol for scan description and areas to scan.  If a participant is found to have a tumor response or PD by imaging and considered to be clinically 
stable by iRECIST criteria (see Section 12.6.2), a follow-up confirmation scan must be done no earlier than 4 weeks and no later than 8 weeks following the scan when 
response or PD first seen. A participant is not considered to have a response or PD until follow-up scan confirms the finding. 
16. CT/MRI will not be performed at Week 10.  CT/MRI assessments only need to continue until confirmed PD.  
17. Brain MRI should be performed at baseline if more than 4 months have elapsed from last MRI. Brain MRI will be performed at other time points, if clinically indicated. MRI of the 
spine will be performed, if clinically indicated. 
18. All participants will be monitored as shown in the SoA. If a participant is found to have Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), the ICE neurological 
assessment tool should be used at least twice per day until ICANS is resolved or stable. It can also be used at later visits if indicated.  In participants < 12 years of age, CAPD 
should be used in place of ICE. 
19. To be administered prior to T-cell infusion. 
20. If CRS and/or ICANS is suspected, chemistry, hematology, ferritin, coagulation and CRP tests should be performed locally every day for the first week and approximately every 
other day thereafter until symptoms are improving or an alternative diagnosis is confirmed. In addition, if CRS is suspected, cytokine samples will be collected for central analysis 
following same schedule (as per SOA Table 3 footnote 4).  
21. See Section 6.1 Table 5 for specifics on renal assessment. 
22. Coagulation tests include INR, PTT or aPTT and fibrinogen. Coagulation tests should be taken at baseline, Day 1, 2, 3, 4, 6, 8 and 15.  
23. Troponin and NT-proBNP / BNP tests should be monitored for participants with CRS Grade ≥2 as clinically indicated.  
24. WOCBP must have a negative urine or serum pregnancy test prior to lete-cel infusion.   
25. WOCBP will need to have pregnancy tests performed at all visits indicated in the table for the duration of the contraception period (Section 6.1 of this Substudy). 
26. In addition to the specified time points, urinalysis will be done at other timepoints if warranted by the symptoms. 
27. Includes HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochaete bacterium). 
28. Only participants who are CMV positive at Baseline will continue to be monitored for CMV viremia.  CMV will also be assessed if GBS is suspected. 
29. If possible, this sample also needs to be obtained in case of any SAE that occurs after T‑cell infusion, unless the sample has been collected recently due to a scheduled visit 
assessment. 
30. If no gene modified cells are detected for two consecutive assessments post-infusion, and the participant is 2 years after T-cell infusion, samples for VSV-G DNA (RCL) and 
persistence of gene modified cells will be discontinued (Section 9.3.11.1 of the Core Protocol).  
31. On Day -7 fludarabine will not be administered to participants 60 years old. 
32. Patient-Reported Outcomes instruments are only for adult participants. 

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33. Contact participant about one week after T-cell infusion to schedule the phone interview to be conducted by Day 21 of the study.  If phone interview cannot be scheduled at this 
time, contact participant every two weeks until successful or the 60-day limit is reached from T-cell infusion.  Beyond 60 days from T-cell infusion, no need to conduct the 
participant interview as recall may not be reliable. 
34. To be conducted within approximately 21 days following the last study visit. 
35. To be administered prior to infusion. 
 
BNP = B-type natriuretic peptide; CAPD = Cornell Assessment of Pediatric Delirium; CMV = Cytomegalovirus; Con Meds = concomitant medications; CRS=cytokine release syndrome; 
CT = computerized tomography; EBV = Epstein Barr virus; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EDC = electronic data 
capture; 
 
 
EOT = end of treatment; 
 
; GFR = glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; HTLV = 
human T-lymphotropic virus; ICANS = Immune Effector Cell-Associated Neurotoxicity Syndrome; ICE=Immune Effector Cell-Associated Encephalopathy; Med history=medical history; 
MRI = magnetic resonance imaging; MUGA = multigated acquisition; NT-proBNP = N-terminal pro-BNP; PCR = Polymerase chain reaction; PD=progressive disease; 
 
; 
 
Q3M = every 3 months; RCL=replication competent lentivirus; TSH = Thyroid stimulating hormone; VSV-G =vesicular stomatitis virus G protein; WOCBP = Women of childbearing 
potential 
 
CCI
CCI
CCI
CCI

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Table 3 
Substudy 1 Schedule of Activities – PK, Immunogenicity and Biomarkers (Interventional Phase) 
 
Sample 
Type 
Baseline 
Lymphodepletion 
T-cell infusion 
Post T-cell infusion 
Month 
(1 month = 4 
weeks) 
 
-1 
1 
2 
3-6  
Q3M from 
month 9 until 
confirmed PD1 
Week 
 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
8 
(10) 2, 12, 
18, 24 or 
until 
confirmed 
PD, 
whichever 
is sooner1,2 
 
Day 
 
-17 to -8 
-7 
-6 
-5 
-4 
13 
2 
3 
4 
6 
8 
15 
22 
29 
36 
50 
(64) 2, 78, 
120, 162  
 
Visit Window 
 
N/A 
±1 day 
±3 days 
±7 days 
±3 months 
Cell phenotype 
and Functional 
Assays 
PBMC 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
Transgene 
Copies 
(Persistence)  
PBMC 
X 
 
 
 
 
X 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
Cytokine 
Analyses4 
Serum 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
TGF-β analyses 
Plasma 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
 
X 
 
X 
X 
Anti-lete-cel 
Antibodies 
Serum 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
Week 12, 
24 
Month 9, 12, 
18, 24, 30, 
36 
Liquid biopsy 
(blood)5 
Plasma 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Tumor Biopsy6 
Biopsy 
X7 
 
 
 
 
 
 
 
 
 
 
 
X8 
 
 
 
X9 
 
1. 
All assessments need to be performed at all visits specified in the Table, up to the visit establishing confirmed PD or study withdrawal or discontinuation. 
2. 
Assessments should match imaging (Body CT/MRI) visits; consequently PK, immunogenicity and Biomarker samples will not be collected at Week 10.  
3. 
All assessments to be performed prior to T-cell infusions 

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4. 
If CRS is suspected, serum for cytokine analysis  should be collected for research every day for the first week and approximately every other day thereafter until symptoms 
are improving or an alternative diagnosis is confirmed.  
Notes:   
- For scheduled visits where a cytokine sample collection is already requested, there is no need to collect an additional sample from the CRS collection kit that day. 
- Chemistry, hematology, ferritin, coagulation and CRP tests should also be performed locally following same schedule (as per SOA Table 2 footnote 20).  
5. 
Blood sample from which circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and exosomes may be extracted. 
6. 
Biopsies for research are at Baseline, at Week 4, and at disease progression 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 execution.   
7. 
The Baseline biopsy should be collected anytime within 90 days prior to the start of lymphodepleting chemotherapy An archived FFPE block from a biopsy preferably taken 
after completion of the participant’s last line of therapy, preferably within 90 days prior to initiating lymphodepleting chemotherapy, may be accepted at the discretion of the 
Medical Monitor (or designee).  
8. 
Week 4 biopsy must be taken preferably from D21 if medically feasible, but window for collection is extended until Week 6 visit (D39). 
9. 
Must be taken once at disease progression if medically feasible. 
 
PBMC=peripheral blood mononuclear cell; PD=progressive disease; Q3M = every 3 months 

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Table 4 
Substudy 1 Schedule of Activities – Follow-up post Completion of Interventional Phase and before 
transition to Long-Term Follow-up protocol (208750) 
Substudy 1:  Completion of Interventional Phase Follow-up1  
Time post lete-cel infusion 
Year 1 2 
Year 2  
Year 3  
Year 4  
Year 5  
Years 6-15 3  
Months (1 month = 4 weeks) 
3 
6 
12 
18 
24 
30 
36 
42 
48 
54 
60 
Annually 
Visit window 
± 2 weeks 
± 3 months 
± 6 months 
Safety Assessments 
Medical History, Tobacco Use, and Physical Exam 4 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mutagenic agents, other investigational agents or 
anti-cancer therapies  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events and Serious Adverse Events 5 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 6 
Pregnancy test for WOCBP 7 
<===========================X 7===========================> 
Haematology 8 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Serum chemistry 8 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Laboratory Assessments 
Transgene Copies (Persistence) for safety association 
VSV-G DNA (RCL) for safety 8,9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 9 
Other Assessments 
Survival Status 10 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
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. 
Assessments for the Year 1 will be conducted per Table 2 and Table 3 until disease progression. 
3. 
Participants who do not have persistence of gene modified cells may be followed remotely during years 6-15. 
4. 
New medical history/medications/chemotherapies. 

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5. 
Adverse Event and Serious Adverse Event collection is limited to: 
a. 
New malignancies 
b. 
New incidence or exacerbation of a pre-existing neurologic disorder 
c. 
New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder 
d. 
New incidence of a hematologic disorder 
e. 
New incidence of infection (potentially related to gene-modified cell therapy) 
f. 
Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy 
6. 
During years 6-15 of annual follow-up period, AEs and SAEs will be entered in the CRF if reported by the participants or investigator. 
7. 
For Women of child bearing potential (WOCBP), pregnancy testing should be conducted during contraception period only.  When pregnancy testing is performed at visits 
where haematology sample is collected, blood pregnancy testing will be done.  At visits where haematology sample is not collected, urine pregnancy test is acceptable unless 
serum testing is required by local regulation or IRB/IEC. 
8. 
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. 
9. 
If no gene modified cells are detected for 2 consecutive assessments post infusion and the participant is ≥2 years post T-cell infusion, all laboratory assessments including 
persistence and RCL may be discontinued (Section 9.3.12 of the Core Protocol). 
10. If a participant is contacted between the scheduled visits, the date of last contact should be recorded as an unscheduled visit.    
 
Abbreviations:  RCL=replication competent lentivirus; VSV-G =vesicular stomatitis virus G protein 
 

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3 INTRODUCTION 
3.1 
Background and Rationale for First Line Therapy with Lete-cel 
(GSK3377794) 
Background 
See Core Protocol Section 3.2 for background information on TCR approach, NY-ESO-1, 
and letetresgene autoleucel (lete-cel, GSK3377794).  
For evaluation of lete-cel in translocation-related sarcomas of synovial sarcoma (SS) and 
myxoid/round cell liposarcoma (MRCLS), this substudy will enroll 10 first line  
participants with advanced (metastatic or unresectable) SS or MRCLS. This substudy will 
start with the clinical drug product supply and may use the intended commercial drug 
product supply once it is available and the regulatory document has been amended to 
support this supply.  The change from clinical to intended commercial drug product 
supply will include a different manufacturing platform for T cell selection and activation 
and other appropriate changes in line with the phase of development. 
This Substudy has been designed to generate safety and efficacy data for lete-cel in 
participants ≥10 years of age who have previously untreated advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma expressing the 
NY-ESO-1 antigen, who are HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06 allele 
positive.  
Rationale 
Soft Tissue Sarcomas (STS) are a heterogeneous group of connective tissue cancers 
originating from mesenchymal cells and their precursors [Blay, 2014] representing ~1% 
of all cancers in adults worldwide each year and accounting for ~2% of cancer related 
mortality [Singer, 2000; Amankwah, 2013].  STS consists of approximately 50 
histological subtypes [Amankwah, 2013], each with distinct specific characteristics, 
including differential chemo-sensitivity.  
Synovial Sarcoma: 
Synovial sarcoma is a rare malignancy accounting for approximately 5–10% of all STS 
[Riedel, 2018; Noone, 2018; Brennan, 2016; Honoré, 2015].  The estimated incidence of 
synovial sarcoma is 0.15 per 100,000 in the US and 0.14 per 100,000 in the UK [Wang, 
2017; Stacchiotti, 2018; Brennan, 2016].  Approximately one-third of synovial sarcoma 
occurs in childhood, with a peak incidence in the third decade of life [Ferrari, 2008].  The 
European Paediatric Soft Tissue Sarcoma Study Group conducted a prospective trial 
exploring the incidence and outcome of synovial sarcoma in European patients [Ferrari, 
2015].  From August 2005 to August 2012, 138 patients <21 years old with synovial 
sarcoma were registered from 60 centers in 9 European countries.  The median age at 
diagnosis was 13.7 years.  Of the 138 participants included in this study, 29 (21%) were 
<10 years of age and 109 (79%) were ≥10 years of age.   
Synovial sarcoma is a life-threatening disease.  Although 5-year overall and 
cancer-specific survival of adult patients diagnosed with synovial sarcoma is about 

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50-60%, the outcome of patients who develop metastatic disease is dismal [Spillane, 
2000; Lewis, 2000; Singer, 2000].  Approximately 50% of patients with synovial sarcoma 
will develop metastatic disease [Ten Heuvel, 2009; Krieg, 2011], and the survival for 
patients developing metastatic disease is approximately 12-15 months with current 
treatment options.   
Current standard treatments for patients with metastatic synovial sarcoma are suboptimal 
and provide no survival benefit.   
Standard first-line (1L) treatment for patients with advanced unresectable, or metastatic 
synovial sarcoma consists of anthracycline chemotherapy as single agent or as a 
combination regimen with alkylators (e.g., doxorubicin with ifosfamide).  These 
chemotherapy regimens have response rates ranging between 18-30% in the reported 
series [Spurrell, 2005; Sleijfer, 2010; Vlenterie, 2016], with an average durability of 
response less than 6 months.  
Two years ago, Lartruvo (olaratumab) received accelerated FDA approval as 1L 
treatment in combination with doxorubicin for metastatic soft tissue sarcoma (STS) 
[Lartruvo USPI, 2016].  However, recently the confirmatory trial (ANNOUNCE study) 
did not demonstrate any survival benefit nor any improvement in response rates (18%) 
over standard chemotherapy, and therefore, the study failed to meet its primary endpoint 
[Tap, 2019]. Accordingly, the approval for this agent has been recended in the US and 
EU. A review of the medicine has now been initiated by the regulators (US/EU) and its 
approval status has been rescinded.  Other targeted agents such as pazopanib and 
trabectedin in the second line setting have also not demonstrated an improvement in 
survival and responses with these agents remain low (6-13%).  These data highlight the 
ongoing unmet medical need in metastatic soft tissue sarcomas.  Novel therapies are 
needed that are sarcoma subtype-specific, and biomarker driven studies are needed to 
improve survival in this disease. 
From the immunological perspective, synovial sarcomas are considered “cold tumors”, 
and have not demonstrated any responses to checkpoint inhibitor therapies in studies 
evaluating these as single agents or in combination approaches with vaccines or other 
agents [Maki, 2013; Patnaik, 2015; NCT02609984; NCT01643278; NCT02304458; 
NCT02428192; NCT02301039; NCT02500797; NCT02636725; NCT02331251].   
Myxoid/Round Cell Liposarcoma (MRCLS): 
Myxoid/round cell liposarcoma is a subtype of liposarcoma which is associated with 
specific translocations, t (12;16)(q13;p11) or t (12;22)(q13;q12) and represents about 
30-35% of liposarcomas and 5-10% of all adult STS [WHO, 2002]. In the 2013 edition 
of the WHO classification, the term “round-cell liposarcoma” was removed as the 
prognosis and the frequency of metastasis in patients with myxoid liposarcoma is related 
to the degree of cellularity of the tumor rather than the presence of round cells vs spindle 
cells. In addition, the same molecular abnormalities are found in both round-cell and 
spindle-cell morphologies of high-grade myxoid liposarcoma [Doyle, 2014]. Therefore, 
patient diagnoses of “high grade myxoid liposarcoma” and “myxoid/ round cell 
liposarcoma” are equivalent when assessing patients for eligibility for this study, in 

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accordance with the WHO 2013 classification [IARC WHO Classification of Tumours, 
No 5, Fletcher 2013]. 
MRCLS commonly presents at an age ranging from 35-55 years. The prognosis varies 
depending on the site of origin, the type of cancer cell, the tumor size, the depth and 
proximity to lymph nodes. MRCLS is prone to recur locally and, dependent on the 
histological grade, one-third of MRCLS cases will become metastatic with multifocal 
synchronous tumor spread to unusual bone and soft tissue locations and lung. 
Myxoid tumor types have relatively favorable prognoses, with an ~80-90% 5-year 
survival rate but tumors with a round-cell component >5% have a poor prognosis with a 
5-year survival rate of ~50-75% because they recur locally and tend to metastasize 
quickly and widely [Smith, 1996]. The median time from diagnosis to metastases is 
35 months. 
Treatment involves the wide surgical excision of the tumor and surrounding tissue ; 
high-grade round cell liposarcoma may be treated with pre-operative chemotherapy 
and/or pre-operative or post-operative radiotherapy [NCCN, 2012]. Radiotherapy 
decreases the incidence of local relapse but chemotherapy may not prevent metastatic 
occurrence nor improve survival [Moreau, 2012; Hoffman, 2013]. 
Doxorubicin and ifosfamide are usually first line treatment options for metastatic disease. 
Retrospective analyses in previously untreated patients demonstrated response rates of 
~38-45% [Jones  2005; Katz, 2012].  In a recent retrospective study in the United States 
on 350 patients, median OS and median PFS from start of first-line therapy for MRCLS 
was 29.9 months (95% CI, 27-44.6) and 8.9 months (95% CI 4.5-12.0) [Pollack, 2020]. 
It has been recognized that a proportion of patients with soft tissue sarcomas, and up to 
76% of synovial sarcomas, express high levels of the cancer testis antigen NY-ESO-1 
[Lai, 2012] which is known to be immunogenic [Stockert 1998, Jäger, 2000].  Based on 
these data, a pilot study in patients with metastatic STS evaluated the activity of a 
dendritic cell based NY-ESO-1 vaccine as 2L or 3L therapy, wherein biomarker analysis 
revealed incremental T cell responses against NY-ESO-1 peptides in vaccinated patients, 
which correlated with improved survival [Pollack, 2017].  This vaccine was subsequently 
evaluated in a recent phase 3 trial in previously untreated (1L) NY-ESO-1+ metastatic 
STS and HLA-A*02:01+ patients, wherein patients completed anthracycline based 
chemotherapy and were then randomized to either receive the NY-ESO-1 vaccine as 
maintenance or placebo [NCT03520959].  This study was terminated early due to lack of 
clinical benefit.   
Nevertheless, these data are indicative of the potential for these tumors to respond to 
immunotherapy, and of the relevance of NY-ESO-1 targeting.  Indeed, adoptive transfer 
of lete-cel has demonstrated clinical responses in patients with metastatic synovial 
sarcoma who have failed prior treatment with standard chemotherapy and pazopanib 
(study 208466) and in patients with advanced myxoid/round cell liposarcoma (study 
208469).  The efficacy and safety of lete-cel in study 208466 and 208469 is described in 
the Lete-cel Investigator’s Brochure and summarized in the Benefit/Risk section below.   

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In previous studies with lete-cel (see Section 3.2.2 below), objective responses have been 
observed with a response rate of 50%, a durability of response of 30.9 weeks, and median 
survival of approximately 24 months which represents a marked improvement over a 
median survival of 12 months in relapsed metastatic synovial sarcoma with current 
standard of care treatments.  It is expected that treatment in first line setting for synovial 
sarcoma and myxoid/round cell liposarcoma should have similar outcomes. 
In the frontline setting, adoptive immunotherapy with lete-cel may also facilitate a 
favorable alteration of the tumor immune microenvironment, that may further enhance 
activity of subsequent chemotherapy in this disease and the activity of other 
immunomodulating agents; thereby providing a mechanism for life extending treatment 
options to these patients.    
These and other results (See Section 3.2.2 of this Substudy) demonstrating encouraging 
clinical activity of lete-cel across multiple NY-ESO-1 expressing tumor types,  provide a 
reasonable rationale for testing lete-cel in a small pilot study for previously untreated 
patient population with advanced (metastatic or unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma, expressing NY-ESO-1. 
3.2 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks as well as 
reasonably expected adverse events of lete-cel (GSK3377794) may be found in the 
Lete-cel Investigator’s Brochure. 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. This 
section outlines the potential benefits, risks and the mitigation strategy for this study. 

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3.2.1 Risk Assessment  
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 
• 
Hyponatraemia 
• 
Neurotoxicity 
Cases were reported with both drugs. 
Please refer to the prescribing information of fludarabine 
and cyclophosphamide and Section 12.7. 
• 
Autoimmune haemolytic anaemia 
• 
Autoimmune thrombocytopenia 
• 
Decreased vision 
• 
Peripheral neuropathy 
Cases were reported with fludarabine 
Please refer to the prescribing information of fludarabine. 
Lete-cel (GSK3377794) 
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 
(Core Section 9.3.6 and Section 12.7.5).   
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 (Core Section 
9.3.7).  
Central lines should be closely monitored for infection 
(Core Section 12.7.2).  
Systemic fungal infections are excluded (Substudy 1 
Exclusion 10)  
Monitoring of risk of increased cardiac toxicity with the 
use of anti-microbials (Core Section 12.7.2.6) 
Cytokine release syndrome (CRS) 
Identified risk due to TCR T-cell infusion considered 
adverse event of special interest (AESI) 
Participants with pre-existing autoimmune disorders are 
excluded (Section 6.2 of this Substudy). Management for 

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Risks of Clinical Significance (Identified or Potential) 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
CRS is described in Section 12.7.5.  Events Grade ≥3 
must be reported as SAEs and submitted to GSK within 
24 hours. 
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 6.2 of this Substudy). Management for 
GVHD is described in Section 12.7.6. 
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 (Section 6.2 of 
this Substudy). Management for pancytopenia is 
described in Section 12.7.7.  
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 12.7.3. 
Hypersensitivity  
Identified risk due to TCR-T cell infusion. Hypersensitivity 
reactions (including anaphylaxis) may be due to the 5% 
(v/v) DMSO inTCR-T formulation. 
Participants with history of allergic reactions to any 
agents used in the study are excluded. See Section 6.2 
for details. 
Participants will be premedicated against potential 
infusion reactions with antihistamines on the day of 
TCR-T cell infusion. See Section 7.1.4 for details. 
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 6.2 for details. 
Lymphodepletion dose will be modified in participants 
with potentially reduced bone marrow reserve. See 
Section 7.1.3 for details. 
Participants with active infection are excluded. 
Participants with CMV seropositivity will be monitored 
regularly for viral reactivation. For HSV/VZV prophylaxis, 
participants will receive acyclovir or valacyclovir for one 
year from LD.  Prophylaxis will be given to those with 

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Risks of Clinical Significance (Identified or Potential) 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
HBV seropositivity. See Section 6.2 and Core Section 
12.7.2 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 6.1.2). Investigator must discuss with 
Medical Monitor or designee to determine the need for 
dose modification of the lymphodepletion regimen in 
participants at risk (Section 7.1.3). 
G-CSF to be administered in accordance with ASCO 
guidelines or institutional practice (Section 7.1.3).  
Dose modifications are included for fludarabine and 
cyclophosphamide (Section 7.1.3) 
Grade 4 Neutropenia events lasting ≥28 days must be 
submitted to GSK within 24 hours (Core Section 9.4.7). 
Decreased Vision 
Potential risk: There was a report of decreased vision in a 
patient who received lete-cel infusion following 
lymphodepletion with fludarabine and cyclophosphamide. 
Dose reductions for fludarabine for renal impairment are 
included (Section 7.1.3). Investigator must discuss with 
Medical Monitor or designee to determine the need for 
dose modification of the lymphodepletion regimen in 
patients at risk (Section 7.1.3) 
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 6.2 of this Substudy).  
Neurologic consultation is required for participants 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) 
Identified 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 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 6.2 of this Substudy). Monitoring criteria for 
ICANS are described in Section 12.7.8.  
Insertional oncogenesis 
Potential risk in T cells transduced with lentiviral vector 
Routine PV. To be monitored in the LTFU Protocol 
(208750) or LTFU portion of this study. Monitoring to 

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Risks of Clinical Significance (Identified or Potential) 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
follow the recommendations set forth in the FDA 
guidance, 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. 
Samples will be tested for the presence of VSV-G DNA 
copies (Section 9.3.11 in the Core Protocol). 
On/Off-Target Off-Tumor Risks 
Potential risk associated with use of TCR T-cell therapy 
To be monitored in this protocol and in the LTFU 
Protocol. Protocol includes eligibility criteria (Section 6.1 
and Section 6.2 of this Substudy), routine PV, and 
management strategies as appropriate to limit, diagnose, 
characterize and treat toxicities related to potential risks 
(Section 12.7). 
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. 
Non Standard of Care Treatment in Frontline 
Delayed frontline chemotherapy 
Potential risk that participant will not respond to lete-cel 
and will have delayed start of frontline chemotherapy 
While participants are deferring standard of care 
chemotherapy, the protocol does allow for administration 
of 2 cycles of doxorubicin as bridging therapy prior to 
infusion with lete-cel. 
Time from end of bridging chemotherapy until the start of 
lymphodepletion is estimated to be approximately 
3 weeks (due to washout). Participants will be monitored 
thereafter closely for progression / lack of response to 
lete-cel and will be treated subsequently at investigator 
discretion.  
Only those participants expressing NY-ESO-1 are 
eligible and therefore only those participants who are 
most likely to benefit from lete-cel will be treated. 

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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. 
The known safety profile of lete-cel is based on 166 enrolled and 125 treated participants 
as of 27 January 2021 as decribed in the Lete-cel Investigator’s Brochure. The most 
commonly reported treatment-emergent adverse events which occurred in 50% of 
participants following lete-cel infusion were leukopenia/WBC decreased (81%), 
neutropenia/neutrophil count decreased (80%), nausea (78%), anemia/RBC decreased (78%), 
thrombocytopenia/platelet count decreased (77%), fatigue (70%), pyrexia (66%), diarrhea 
(57%), and lymphopenia/lymphocyte count decreased (54%).  The most common Grade 3 
and 4 AEs which occurred in 20% of participants following lymphodepleting 
chemotherapy and lete-cel infusion were leukopenia/WBC decreased (78%), 
neutropenia/neutrophil count decreased (74%), thrombocytopenia/platelet count decreased 
(62%), anemia/RBC decreased (58%), lymphopenia/lymphocyte count decreased (52%), 
febrile neutropenia (36%), and hypophosphatemia (27%). These AEs are consistent with 
expected immediate adverse events after lymphodepletion chemotherapy.  
Across all studies, 47 (38%) participants had SAEs considered by the Investigator to be 
related to study treatment.  Treatment-related SAEs occurring in more than 2 subjects 
following lete-cel infusion were: cytokine release syndrome (CRS) (15%), pyrexia (6%), 
neutropenia/neutrophil count decreased (5%), rash/rash maculo-papular (4%), 
thrombocytopenia/platelet count decreased (4%) and febrile neutropenia (3%). For the 16 
participants who received a second infusion, five treatment related SAEs were reported 
after second T-cell infusion, which included 1 (6%) case each of CRS, cytomegalovirus 
infection, embolism, febrile neutropenia, and rash/rash maculo-papular. 
Among the adverse events of special interest,  
1. CRS was reported in 52 (42%) cases (of 125) as of 27 January 2021 across all lete-
cel clinical trials.  Of these, there was 1 participant with Grade 4, 9 with Grade 3, 
21 with Grade 2, and 19 with Grade 1.  There were a total of 19 cases of CRS that 
were reported as SAEs. All 19 SAEs resolved in 2 weeks or less. Five of the 19 
reported SAEs were treated with tocilizumab.  Median duration of the CRS events 
was 8-9 days (range 1-28 days).  
2. A total of 7 cases (of 125) of GvHD have been reported of which 3 cases were 
reported as an SAE.  All cases were Grade 1-3, occurred in patients with multiple 
myeloma, and completely recovered with supportive treatment.  Six (6) out of 7 
participants with reported GvHD were from Study 209393 (formerly ADP-01411) 
which required an allogeneic stem cell transplant prior to the T-cell infusion.   
3. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), originally 
named as ‘encephalopathy’ was reported in 1 case with multiple brain metastasis, 
that was transient, and resolved in 2 days with supportive care. 
4. Five (5%) participants had reported treatment-emergent AE of pancytopenia (3 
participants: 2 with Grade 3, and 1 with Grade 1) or bone marrow failure (2 
participants: 1 with Grade 5 fatal, and 1 with Grade 2) (refer to Lete-cel 
Investigator’s Brochure for details). 

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5. GBS has been reported in 2 participants, both of which completely recovered with 
standard gamma globulin treatment. 
 
To date, none of the analyses for insertional oncogenesis and replication competent 
lentivirus have been positive. 
Pediatric Participants 
This substudy allows pediatric participants 10 years of age or older.  Previously, 2 
pediatric participants have been treated in Study 208466 (ADP-04511).  The first was a 
15-year-old caucasian hispanic female treated in Cohort 3 of the study in which a milder, 
cyclophosphamide-only containing lymphodepletion regimen was used prior to T-cell 
infusion; and this participant achieved PR after the first infusion, progressed 9 months 
following treatment, and received a second infusion and achieved stable disease, and she 
died in September 2018, nearly 2 years after initial treatment with GSK3377793.  The 
second participant was a 12-year-old caucasian female enrolled into Cohort 2; which 
included participants with tumors that have low NY-ESO-1 expression levels and 
received a high dose cyclophosphamide and fludarabine containing lymohodepletion 
regimen prior to lete-cel infusion.  This participant achieved SD as her best response, 
subsequently progressed 8 months following lete-cel treatment, and died 11 months after 
lete-cel treatment. 
As of 24 February 2019, a total of 29 AEs were reported for both pediatric participants as 
definitely or probably related to lete-cel.  A total of 14 Grade 4 AEs (5%) were reported, 
none of which were reported as being related to lete-cel.  The first participant 
experienced 2 SAEs:  acute cholecystitis and CMV infection.  Neither event was reported 
as related to study drug, and both events resolved.  There were no SAEs reported by the 
second participant.  There were 5 events of cytokine release syndrome reported.  All 
events were Grade 1 or 2, and all resolved.  Overall, the observed AEs are similar to 
those observed in adult participants treated with lete-cel, with the vast majority consistent 
with events observed as a result of the lymphodepletion regimen. 
3.2.2 Benefit Assessment 
As of 27 January 2021, 125 participants have been treated with lete-cel. Objective 
responses have been observed in the ongoing synovial sarcoma study (208466/ADP-
04511) and in multiple myeloma post-autologous transplant study (209393/ADP-01411) 
[Lete-cel Investigator’s Brochure].   
In Cohort 1 of study 208466 (which is similar to the treatment regimen proposed for this 
protocol), a single infusion of lete-cel demonstrated an encouraging response rate of 50% 
(6/12 participants, 95% CI: 0.21-0.79), with an encouraging durability of response of 30.9 
weeks (95% CI: 14-72) and one participant demonstrating a complete response.  
Importantly, the responses induced after T-cell infusion were associated with a median 
survival of approximately 24 months, which represents a marked improvement over a 
median survival of 12 months in relapsed metastatic synovial sarcoma.   

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Objective responses have been observed in 21 (84%) out of 25 of participants in multiple 
myeloma after autologous transplant (study 209393/ADP-01411) [Lete-cel Investigator’s 
Brochure]. 
Additionally, studies conducted by the NCI Surgery Branch have demonstrated that 
adoptive immunotherapy using T cells genetically engineered to recognize NY-ESO-1 
following lymphodepletion led to objective antitumor responses in 4 of 6 patients (67%) 
[Robbins, 2011] and 11 of 18 patients (61%) [Robbins, 2015] with synovial sarcoma. The 
estimated overall three and five-year survival rates for these patients with synovial 
sarcoma were 38% and 14%, respectively [Robbins, 2015]. 
More recently, responses have also been observed in patients with myxoid round cell 
liposarcoma (MRCLS , study 208469) [D’Angelo, 2018a], thereby demonstrating 
encouraging clinical activity of lete-cel across multiple NY-ESO-1 and LAGE-1a 
expressing tumor types.   
3.2.3 Overall Benefit/Risk Conclusion 
Treatment with letetresgene autoleucel (lete-cel, GSK3377794) has been well tolerated in 
103 participants with different tumor types [Lete-cel Investigator’s Brochure].  Toxicities 
associated with engineered T-cell infusion, specifically CRS, have been observed in less 
than one third of the treated participants, were of low grade, and managed with 
supportive care in the majority of cases.  To date, lete-cel has demonstrated an AE profile 
that has generally been manageable and acceptable in the context of benefit/risk 
assessment.   
As described in this section, other agents, including frontline agents, have failed to 
demonstrate survival benefit or improvement in response rates over approved standard 
chemotherapy.  In pilot studies, treatment with lete-cel has demonstrated objective 
responses in participants with relapsed metastatic disease that were durable and that 
extended survival in treated participants, therefore representing a meaningful clinical 
benefit and a marked improvement over current standard of care treatments in relapsed 
metastatic synovial sarcoma and myxoid/round cell liposarcoma.  It is expected that 
treatment in first line setting should have similar outcomes.  In the frontline setting, 
adoptive immunotherapy with lete-cel may also facilitate a favorable alteration of the 
tumor immune microenvironment, which may further enhance activity of subsequent 
chemotherapy in this disease, and the activity of other immunomodulating agents; 
thereby providing a mechanism for life extending treatment options to these participants.    
This substudy is enrolling a previously untreated participant population for whom an 
approved standard of care exists. While there is a potential risk that participants will not 
respond to lete-cel and will have delayed start of frontline chemotherapy, participants can 
receive 2 cycles of approved standard chemotherapy (doxorubicin) while awaiting 
lymphodepleting chemotherapy and the time from end of bridging chemotherapy to start 
of lymphodepletion is estimated to be approximately 3 weeks (due to washout).  
Participants will be monitored thereafter closely for progression / lack of response to lete-
cel and will be treated subsequently at investigator discretion.  

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In view of the clinical responses observed in relapsed, refractory participants, and results 
demonstrating encouraging clinical activity of lete-cel across multiple NY-ESO-1 
expressing tumor types, and as per the risk assesment presented above, the benefit/risk 
ratio provides a reasonable rationale and acceptable risk for testing lete-cel in NY-ESO-
1-positive synovial sarcoma and myxoid/round cell liposarcoma in this small pilot study 
for previously untreated participant population. 
4 OBJECTIVES AND ENDPOINTS  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of lete-cel in HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 
participants with NY-ESO-1 positive advanced 
synovial sarcoma or myxoid/round cell 
liposarcoma 
Overall Response Rate (ORR) per RECIST 
v1.1 assessed by Investigators 
Secondary - Efficacy 
To further evaluate the efficacy of lete-cel in 
HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 participants with NY-ESO-1 
positive advanced synovial sarcoma or 
myxoid/round cell liposarcoma 
 
• Time to Response (TTR) 
• Duration of Response (DoR) 
• Disease Control Rate (DCR) 
• Progression Free Survival (PFS) 
Secondary - Safety 
To evaluate the safety and tolerability of 
lete-cel in HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 participants with NY-ESO-1 
positive advanced synovial sarcoma or 
myxoid/round cell liposarcoma 
• Frequency and severity of Adverse events 
(AEs), serious adverse events (SAEs) and 
AEs of special interest (AESI; as defined 
in protocol) 
• Replication Competent Lentivirus (RCL) 
• Instances of Insertional oncogenesis (IO) 
Secondary - Pharmacokinetics 
To characterize in vivo cellular PK profile 
(levels, expansion, persistence) of 
NY-ESO-1 specific (c259) T cells 
• Maximum transgene expansion (Cmax) 
• Time to Cmax (Tmax) 
• Area under the time curve from zero to 
time t AUC(0-t), as data permit 
Exploratory / Other 
CCI

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Objectives 
Endpoints 
 
AE/s = adverse event/s; AESI/s: adverse event/s of special interest; AUC (0-t) = area under the time curve 
from zero to time t; Cmax = maximum concentration; DOR = duration of response; HLA = human 
leukocyte antigen; ORR = overall response rate; OS = overall survival; PFS = progression-free survival; 
RECIST = Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; Tmax = Time to 
Cmax; TTR = Time to Response 
 
CCI

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5 SUBSTUDY DESIGN 
5.1 
Overall Design  
Study 208467 Substudy 1 is a multicenter, open-label study evaluation of the safety and 
efficacy of letetresgene autoleucel (lete-cel, GSK3377794) in participants with synovial 
sarcoma or myxoid/round cell liposarcoma. 
For evaluation of lete-cel in synovial sarcoma and myxoid/round cell liposarcoma, this 
Substudy will enroll 10 previously untreated participants with advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma (Figure 1).  
Participants identified by the Investigator as possible candidates for the study must have 
completed target expression screening for HLA-typing and NY- ESO-1 antigen 
expression; participants with the HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 
alleles and whose tumor expresses the NY-ESO-1 antigen above the cut-off according to 
the applied immunohistochemistry assay are eligible to undergo further screening for this 
study.  
This substudy will start with the clinical drug product supply and may use intended 
commercial drug product supply once it is available and the regulatory document has 
been amended to support this supply.  Drug product supply type (‘clinical’ vs 
‘commercial’) will be recorded in the CRF as part of the route of synthesis. 
Figure 1 
Substudy 1 Design 
 
* The lymphodepleting regimen is to be adjusted as described in Section 7.1.3 of this Substudy. 
Participants will undergo stepwise enrollment on the study followed by treatment 
according to defined phases within this substudy (See Figure 2 Participant Journey 
Schema below) which will include: 

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Part 1: Screening 
1) Target expression screening for the presence of HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 type and tumor expression of NY ESO-1, 
(Note: If a participant was previously tested for HLA and/or NY-ESO-1/LAGE-1a expression 
under a different GSK-sponsored protocol, testing of HLA and/or NY-ESO-1 for 208467 may not 
be required dependent on the test platform(s) used and whether they meet the 208467 protocol 
requirements [see Section 6.3 of the Core Protocol]) 
2) Leukapheresis screening phase to determine eligibility for undergoing leukapheresis 
beginning up to 28 days prior to the day of leukapheresis,  
Part 2: Leukapheresis/Manufacture 
3) Leukapheresis procedure,  
(Note: leukapheresis may have been performed under another GSK-sponsored protocol or 
substudy of this protocol)   
Part 3: Lymphodepletion/Treatment 
4) Treatment fitness assessment and eligibility confirmation,  
5) Interventional phase including Lymphodepletion from Days -7 to -4, lete-cel infusion 
on Day 1 and follow-up until the end of study (as defined in Section 5.3 of this 
Substudy), 
(Note: TCR engineered T-cell may have been manufactured under another GSK-sponsored 
protocol or substudy of this protocol)   
Part 4: Long-Term Follow-Up (LTFU) 
6) Long-term follow-up phase for up to 15 years from the date of lete-cel infusion.   
 
Figure 2 
Participant Journey Schema 
 
* The lymphodepleting regimen is to be adjusted as described in Section 7.1.3 of this Substudy. 
Part 1: Screening  
See Core Protocol Section 5 of this Substudy for complete details of screening approach. 
Inclusion / exclusion criteria are listed in Section 6. 
This substudy will enroll previously untreated (first line) participants with advanced 
(metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma.  

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Participant screening may start at any time after diagnosis of high-risk locally advanced 
(i.e. deeply seated, high grade, positive margins, large [≥5 cm], or locally recurrent) 
synovial sarcoma or myxoid/round cell liposarcoma disease.   
Disease progression may be present but is not mandatory for screening. Screening will 
consist of two phases: target expression screening and leukapheresis eligibility screening. 
For target expression screening, once informed consent has been obtained, 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 expression will also be evaluated on 
tumor tissue from a formalin-fixed and paraffin-embedded (FFPE) archival (most recent 
preferred) or fresh biopsy (see Tumor biopsies section below for more details). HLA-
typing and tumor antigen expression testing should be performed sequentially 
(considering the expected >50% attrition with HLA) but may also be performed in 
parallel at the discretion of the Investigator. 
Note: target expression Screening may also be performed under a separate Screening 
protocol such as athe GSK molecular disease characterization initiative (MDCI) study 
(213299), or under other NY-ESO-1/LAGE-1a T-cell protocols. 
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 
28 days prior to the day of the scheduled leukapheresis procedure. 
Part 2: Leukapheresis/Manufacture 
In this first line population, participants may receive up to 2 cycles of doxorubicin 
between leukapheresis and lymphodepletion as outlined in Section 7.1.2 of this Substudy. 
The initiation of leukapheresis procedure constitutes enrollment in the study. The 
collected T  cells will be sent for manufacturing. 
See Core Protocol Section 5 for complete details of leukapheresis and manufacture 
approach. 

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Part 3: Lymphodepletion/Treatment 
See Core Protocol Section 5 for complete details of lymphodepletion and treatment 
approach. 
Part 4:  LTFU 
See Core Protocol Section 5 for complete details of the long term follow up study. See 
end of substudy definition in Section 5.3 of this Substudy for details of participant 
transition to LTFU.  
Tumor Biopsies 
Archival tumor FFPE or fresh biopsy from a representative tissue is required from all 
participants to be used for antigen expression (NY-ESO-1) eligibility screening.  If 
multiple archival samples are available, then the most recent archival sample should be 
used. If fresh biopsy is performed, then this tissue should be used: 
a. Formalin-fixed paraffin embedded (FFPE) tumor specimens in paraffin blocks are 
preferred. A minimum of 20 unstained slides (5-micron serial fresh cut) is required 
as an alternative. Patients with fewer than 20 unstained slides may still be 
considered for screening following discussion with Medical Monitor 
b. Acceptable specimens include core needle biopsies from deep tumor tissue 
(minimum 3-5 cores x 18G or larger and approximately 1 cm long) or excisional, 
incisional punch or forceps biopsies for cutaneous, subcutaneous or mucosal lesions 
c. Fine-needle aspiration, brushing, cell pellet from pelural effusion, bone metastases, 
and lavages are not acceptable 
d. Tissue should be obtained from 1 year of consent and be of good quality on the 
basis of total and viable tumor unless discussed with Medical Monitor 
 
A pre-treatment tumor sample collected within 90 days prior to initiating 
lymphodepletion is required for Substudy 1.  This biopsy will be used as baseline for 
biomarker analyses.  If it is not feasible to obtain a fresh biopsy, an archival tumor biopsy 
(FFPE block) preferably taken after completion of the participant’s last line of therapy, 
preferably within 90 days prior to initiating lymphodepleting chemotherapy, may be 
accepted at the discretion of the Medical Monitor (or designee).  For participants who 
already provided a fresh biopsy for antigen expression and did not receive any bridging 
or standard of care intermediate anti-cancer therapy, the screening biopsy will be used for 
baseline. 
Additional biopsies will also be collected at Week 4, and at disease progression.  In 
exceptional cases, where such biopsies cannot be collected, these may be deferred in 
consultation with the sponsor.  These cases include participants for whom there is no 
safely accessible tumor tissue; or if conducting such a biopsy would compromise the 
medical condition of the participant; or if other clinical considerations preclude conduct 
of the biopsy procedure.  In addition to the indicated collection times, tumor biopsies can 
be obtained at any time during the study execution. 

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See Core Protocol Section 9.9.1 for other biopsy considerations. 
5.2 
Number of Participants 
It is anticipated that Substudy 1 will enroll 10 participants with previously untreated 
advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell 
liposarcoma, that is either newly diagnosed or relapsed after surgery and radiotherapy 
and /or adjuvant therapy.   
5.3 
End of Study Definition 
5.3.1 End of Substudy for Individual Participants 
a) End of Interventional phase for individual participants 
A participant is considered to have completed the Interventional phase of the Substudy 
when one of the following occurs (whichever is sooner): 
• 
Participant has confirmed disease progression (also need to ensure that participant is 
followed for SAEs through 90 days following T-cell infusion, or 30 days following 
T-cell infusion if the participant initiates new anticancer therapy, whichever is 
earlier);  
• 
Participant dies; 
• 
Interventional phase ends for the Substudy (See Section 5.3.2 of this Substudy).   
 
If participant withdraws consent or is withdrawn for other reasons prior to end of their 
Interventional phase, they will be considered early withdrawal. 
All participants alive after confirmed disease progression will be followed in a separate 
long term follow up (LTFU) protocol (GSK study 208750) for observation of delayed 
AEs and survival for a duration of 15 years post-T-cell infusion in accordance with FDA 
[FDA, 2020a] and EMA guidance [EMA, 2009].  If LTFU protocol is not yet available at 
the particular clinical site, participants may be temporarily followed per LTFU schedule 
under this protocol (Section 2 Table 5 of this Substudy) until LTFU protocol becomes 
available. The transfer of any individual participant to the LTFU protocol 208750 should 
not exceed 6 months.   
b) End of Substudy for individual participants 
The substudy ends for an enrolled participant when they have transferred to the separate 
LTFU protocol (GSK study 208750), declined consenting to the separate LTFU protocol, 
completed LTFU requirement in this study, have been lost to follow-up, or withdrawn, or 
died. 
5.3.2 End of Substudy  
a) End of Interventional phase: 
The interventional phase ends when all enrolled participants have withdrawn early or 
have been dosed and confirmed disease progression, died or have been lost to follow-up. 

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All participants alive after the end of the Interventional Phase of the substudy, will be 
followed in a separate long term follow up (LTFU) protocol (GSK study 208750) for 
observation of delayed AEs and survival for a duration of 15 years post-T-cell infusion in 
accordance with FDA [FDA, 2020a] and EMA guidance [EMA, 2009].  If LTFU 
protocol is not yet available at the particular clinical site, participants may be temporarily 
followed per LTFU schedule under this protocol (Section 2 of this Substudy) until LTFU 
protocol becomes available. The transfer of any individual participant to the LTFU 
protocol 208750 should not exceed 6 months.   
b) End of Substudy: 
The substudy ends when all treated participants have transferred to the separate LTFU 
protocol (GSK study 208750), declined consenting to the LTFU protocol, completed 
LTFU requirement in this study, have been lost to follow-up, or withdrawn early, or died. 
5.4 
Scientific Rationale for Substudy Design 
There is lack of effective treatments for metastatic synovial sarcoma and myxoid/round 
cell liposarcoma.  The currently approved chemotherapy regimens provide limited 
durability of clinical efficacy with response rates in 18-28% range lasting 4-6 months in 
STS.  NY-ESO-1 (c259) specific T cells (lete-cel, GSK3377794) have demonstrated 
response rates of ~50% in 2L+ metastatic synovial sarcoma with survival benefit.  To 
improve survival and treatment options for participants, in this substudy we will explore 
the efficacy, including survival benefit, and safety as well as feasibility of this treatment 
in participants with newly diagnosed advanced (metastatic or unresectable) synovial 
sarcoma or  myxoid/round cell liposarcoma disease.   

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5.5 
Justification for Dose  
5.5.1 Justification of Lymphodepleting Regimen 
Based on prior experience with lete-cel in participants with synovial sarcoma and 
melanoma, where similar lymphodepletion regimen was associated with optimal 
responses [Merchant, 2015; D’Angelo, 2018b], the  lymphodepleting regimen for 
participants treated under protocol amendments 1-5 has been to administer fludarabine, 
30 mg/m2/day × 4 days (Day -7 to -4) and cyclophosphamide, 1800 mg/m2/day × 2 days 
(Day -5 to -4), with lete-cel infusion on Day 1.  
Based on additional safety data (prolonged neutropenia; fatal neutropenia [see IB, 
GlaxoSmithKline Document Number RPS-CLIN-015027, 2021]) and modelling data, to 
further optimize lymphodeletion and reduce potential for acute and prolonged cytopenias 
while also minimizing impact on efficacy, the cyclophosphamide cumulative dose is 
modified from 3600 to 2700 mg/m2. The fludarabine dose remains unchanged.  
This regimen was previously used in Study 208469 (Cohort 2) in MRCLS, and the dosing 
is currently in use for NSCLC participants in Study 208471 (slightly different schedule).  
The refined lymphodepleting regimen for participants treated as of protocol amendment 6 
is as follows: 
• 
Fludarabine, 30 mg/m2/day × 4 days (Day -7 to -4) and  
Cyclophosphamide, 900 mg/m2/day × 3 days (Day-6 to -4),  
with lete-cel infusion on Day 1.  
Rules for further dose reductions on cyclophosphamide are also adapted by applying the 
same 33% reduction as previously used (in protocol amendments 1-5) as follows: 
• 
As of protocol amendment 6, a standard reduction for cyclophosphamide dose  
(in mg/m2) of 2700 = 900 × 3 days is to use 1800 = 600 × 3 days. 
 
5.5.2 Justification of lete-cel (GSK3377794) Dose 
A dose range of 1×109 to 8×109 total  transduced T cells had initially been chosen as it 
was within the cell dose in which clinical responses were observed without significant 
toxicity in previous clinical trials and which was logistically feasible to manufacture 
(based on initial assumptions related to yield).   
At this target dose, lete-cel has resulted in objective responses 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 protocol amendments 1 through 5. 
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. 

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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 two 
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: the genetically 
engineered T cells with a TCR targeting human papilloma virus-associated epithelial 
cancer HPV-16 E7 (E7 TCR) were reported in a first-in-human, phase 1 clinical trial of 
12 participants, to not show any dose limited by toxicity with a maximum dose of 
100 × 109 engineered T cells administered [Nagarsheth, 2021]. 
Since no dose-toxicity relationship has been established todate on 125 patients dosed with 
lete-cel (see Lete-cel Investigator’s Brochure), 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 amendments 6, 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 SRT.  

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6 STUDY POPULATION 
Inclusion/Exclusion criteria are grouped into 3 parts and eligibility screening will take 
place in the following 3 steps: 
• 
Target expression screening: A set of criteria permitting participants’ blood to be 
screened for HLA-type and an archival or fresh  tumor sample to be screened for the 
expression of NY-ESO-1. 
• 
Leukapheresis eligibility screening:  To be fulfilled prior to performing 
leukapheresis procedure. 
• 
Treatment eligibility screening:  To be fulfilled prior to starting lymphodepletion 
procedure. 
– Treatment fitness (for safety): To be evaluated prior to commencing 
lymphodepleting chemotherapy and administration of lete-cel (GSK3377794). 
 
6.1 
INCLUSION CRITERIA 
6.1.1 
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) only if all of the following criteria apply: 
1. Capable of giving signed informed consent including compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in the 
protocol. For participants <18 years of age (or the legal minimum age in the relevant 
country) their legal guardian must give informed consent. Pediatric participants will 
be included in age-appropriate discussion in order to obtain assent. 
2. Participant must be ≥10 years of age at the time of signing the informed consent. 
Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg. 
For participant scheduled to receive intended commercial drug product supply and 
weighing <40kg, the Investigator must also consult with the Medical Monitor prior to 
inclusion. 
3. Participant has a diagnosis of synovial sarcoma or myxoid/round cell liposarcoma, 
confirmed by local histopathology with evidence of disease-specific translocation. 
Note: Evidence of a relevant disease-specific translocation is required at latest prior to 
leukapheresis (Inclusion 9). 
4. Participant has at minimum high-risk locally advanced (i.e. deeply seated, high grade, 
positive margins, large [≥5 cm], or locally recurrent) or advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma.   
5. Participant with synovial sarcoma or myxoid/round cell liposarcoma who is 
a) Newly diagnosed, previously untreated OR 
b) Relapsed after surgery or radiotherapy for localized disease OR 
c) Relapsed 1 year after adjuvant/neoadjuvant therapy for localized disease  

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6. Male or female. Contraception requirements will apply at the time of leukapharesis 
and treatment. 
7. A representative tumor tissue specimen (archived or fresh biopsy) with associated 
pathology report should be available to perform NY-ESO-1 antigen expression 
analysis, unless a recent NY-ESO-1 expression test result from the same designated 
central laboratory, following the same procedures, has already been performed under 
a separate GSK-sponsored protocol or under another substudy.  For guidance on 
acceptable specimen material see Tumor Biopsies under Section 5.1. 
 
6.1.2 
Leukapheresis Eligibility Screening 
Prior to finalizing participant treatment plan, please note that bridging/standard of care 
anti-cancer therapy is allowed under Section 7.1.2 conditions but that there are washout 
requirements prior to leukapheresis and prior to lymphodepletion. Additional 
considerations should be given to accumulated radiotherapy prior to lymphodepletion.  
All the Inclusion Criteria from Section 6.1.1 must apply again prior to leukapheresis.  In 
addition, the following criteria must also apply: 
8. Life expectancy ≥24 weeks  
9. Participant has confirmed evidence of a relevant disease-specific translocation per 
below: 
• For synovial sarcoma, presence of a translocation involving chromosome 18 
(SYT gene) and/or chromosome X (SSX1, SSX2 or SSX4 genes); 
• For myxoid/round cell liposarcoma, presence of a translocation involving 
chromosome 12 (DDIT3 gene) and/or chromosome 16 (FUS gene) and/or 
chromosome 22 (EWSR1 gene). 
Note: Methods, such as, but not limited to, fluorescence in situ hybridization (FISH) 
assay or Next Generation Sequencing (NGS) or Immuno HistoChemistry (IHC) using 
fusion-specific antibody are commonly used to detect translocations. 
10. Participant has advanced (metastatic or unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma.  Unresectable refers to a tumor lesion in which clear 
surgical excision margins cannot be obtained without leading to significant functional 
compromise. 
11. Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 
alleles by a validated test in a designated central lab prior to leukapheresis. 
NOTE: If a participant was previously tested for HLA type under a different GSK-sponsored 
protocol, testing of HLA type for 208467 may not be required dependent on the test platform(s) 
used and whether they meet the 208467 protocol requirements [see Section 6.3 of the Core 
Protocol]. 
12. Participant’s tumor has been pathologically reviewed by a designated central 
laboratory with confirmed positive NY-ESO-1 expression defined as 30% of cells 
that are 2+ or 3+ by immunohistochemistry.   
NOTE: If a participant was previously tested for NY-ESO-1 expression under a different GSK-
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on the test platform(s) used and whether they meet the 208467 protocol requirements [see Section 
6.3 of the Core Protocol]. 
13. Left ventricular ejection fraction ≥45% with no evidence of clinically significant 
pericardial effusion. 
14. Performance status: for participants <16 years of age, Lansky >60, or for participants 
16 and <18 years of age, Karnofsky >60, or for participants 18 years of age, 
Eastern Cooperative Oncology Group (ECOG) of 0-1.  
15. Participant must have adequate organ function and blood cell counts, within 7 days 
prior to the day of leukapheresis procedure, as indicated by the following laboratory 
values in Table 5. 
Table 5 
Definitions of Adequate Organ Function 
System 
Laboratory Value 
Hematologicala,b,c 
Absolute Neutrophil count (ANC) 
≥1.5 x109/L (without granulocute colony-stimulating support) 
Absolute Lymphocyte count (ALC) 
≥0.5 x 109/L 
Hemoglobin 
8 g/dL or ≥5.0 mmol/L (without transfusion support) 
Platelets 
≥100 x109/L (without transfusion support) 
Renal 
Creatinine clearance ≥40 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 (CrCl) calculated as outlined 
below by using the CKD-EPI equation and adjusting the result by multiplying with (BSA/1.73) to obtain 
CrCl in mL/min:  
Step 1: estimated glomerular filtration rate (GFR) to be obtained from the Chronic kidney disease 
Epidemiology Collaboration (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 (ABW) 
may be required for cyclophosphamide, see below 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. 
• 
Participants <18 years of age must have renal function measured either by 24-hour urine creatinine collection 
or by nuclear medicine EDTA GFR measurement or by serum creatinine collection, according to standard 
practice at the treating institution. 

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System 
Laboratory Value 
Participants <18 years of age must have GFR≥ 70mL/min/1.73m2 OR have a serum creatinine based on 
age/gender as follows: 
Age 
Maximum serum creatinine 
(mg/dL) 
 
Male 
Female 
10 to < 13 years 
1.2 
13 to <16 years 
1.5 
1.4 
16 to <18 years 
1.7 
1.4 
Hepatic 
Total bilirubin 
Participants with Gilbert’s Syndrome (only if 
direct bilirubin 35%) 
1.5 x ULN (isolated bilirubin ≤1.5 x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
ALT 
2.5 x ULN (or 5 x ULN if documented history of liver metastases)  
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 
Nutritional status 
Albumin 
≥3.5 g/dL 
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 7.5.2  for guideline on use of anticoagulant medications.  
 
16. Participant is fit for leukapheresis and has adequate venous access for the cell 
collection.   
17. Male or female. Contraceptive use by men or women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies.  
a. 
Male Participants: 
Male participants are eligible to participate if they agree to the following during the 
intervention period starting at the first dose of chemotherapy for at least 12 months 
after receiving the T-cell infusion, or until persistence of gene modified cells in the 
participant’s blood is below the level of detection for 2 consecutive assessments, 
whichever is longer.     
Refrain from donating sperm 
Plus, either:  
• 
Be abstinent from heterosexual or homosexual intercourse as their preferred 
and usual lifestyle (abstinent on a long term and persistent basis) and agree to 
remain abstinent  
OR 
• 
Must agree to use contraception/barrier as detailed below 

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– 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 
described in Section 12.4 when having sexual intercourse with a woman 
of childbearing potential (WOCBP) who is not currently pregnant (as a 
condom may break or leak) 
– Agree to use male condom when engaging in any activity that allows for 
passage of ejaculate to another person  
b. 
Female Participants:  
A female participant is eligible to participate if she is not pregnant or 
breastfeeding, and at least one of the following conditions applies: 
• 
Is not a WOCBP as defined in Section 12.4 
OR 
• 
Is a WOCBP (as defined in Section 12.4) 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 12.4 
during the intervention period and 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.  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. 
• 
A WOCBP must have a negative highly sensitive pregnancy test (urine or 
serum as required by local regulations) within 24 hours before any 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. 
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.  
18. Female participants of childbearing potential (FCBP) must have a negative urine or 
serum pregnancy test. 
 
6.1.3 
Treatment Eligibility Screening 
In addition to confirming Treatment fitness per Section 6.1.3.1, the following criteria 
must also apply prior to lymphodepletion: 
19. Participant has measurable disease according to RECIST v1.1.  
20. A biopsy (excisional, incisional, or core) of non-target tumor tissue obtained within 
90 days prior to initiating lymphodepleting chemotherapy is mandatory if clinically 
feasible. This biopsy will be used as baseline for biomarker analyses. If it is not 
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taken after completion of the participant’s last line of therapy, preferably within 
90 days prior to initiating lymphodepleting chemotherapy, may be accepted at the 
discretion of the Medical Monitor (or designee).  For participants who already 
provided a fresh biopsy for antigen expression and did not receive any bridging or 
standard of care intermediate anti-cancer therapy, the screening biopsy will be used 
for baseline. 
21. A hematologist has been consulted prior to lymphodepletion in participants who have 
had a serious/significant bleeding/thrombosis history. 
6.1.3.1 Treatment Fitness (for Safety) 
Given potential changes in clinical status between screening/enrollment and the start of 
lymphodepleting chemotherapy, safety assessments from Section 6.1.1 and Section 6.1.2 
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. 
6.2 
EXCLUSION CRITERIA 
6.2.1 
Target Expression Screening 
Participants are not eligible to be screened for target expression (HLA-A*02:01, 
A*02:05, or A*02:06 and NY-ESO-1) if any of the following criteria apply: 
1. Participant has been previously treated for advanced (metastatic or unresectable) 
synovial sarcoma or myxoid/round cell liposarcoma. 
2. Central nervous system (CNS) metastases.  
3. Any other prior malignancy that is not in complete remission.  
Exceptions include: 
a. completely resected non-melanoma skin cancer, or successfully treated in situ 
carcinoma (e.g. melanoma in situ, basal cell carcinoma, prostate cancer in-situ, 
periosteal osteosarcoma) 
b. previous malignancies that have been definitively treated, and have been in 
remission for 5 years may be enrolled upon consultation with sponsor Medical 
Monitor or designee 
4. Previous treatment with genetically engineered NY-ESO-1 specific T cells.  
5. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. 
6. Prior gene therapy using an integrating vector. 
7. Previous allogeneic hematopoietic stem cell transplant. 
8. Clinically significant systemic illness: 
c. Serious active infections or significant cardiac, pulmonary, hepatic or other organ 
dysfunction, that in the judgment of the Investigator would compromise the 
participant’s ability to tolerate protocol therapy or significantly increase the risk 
of complications  
OR 

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d. Prior or active demyelinating disease 
 
6.2.2 
Leukapheresis Eligibility Screening 
Participants are not eligible for leukapharesis if any of the Exclusion criteria from 
Section 6.2.1 apply. Please note in particular that mandatory washout period restrictions 
must be respected (Table 6) before starting leukapheresis. In addition, participants are 
not eligible for leukapharesis if any of the following criteria apply: 
9. Participant has history of chronic or recurrent (within the last year prior to 
leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn’s disease, 
systemic lupus) requiring steroids or other immunosuppressive treatments.  
10. Uncontrolled intercurrent illness including, but not limited to: 
a. Ongoing or active infection (including, but not limited to systemic fungal 
infection) 
b. Clinically significant cardiac disease defined by congestive heart failure New 
York Heart Association (NYHA) Class 3 or Class 4 
c. Uncontrolled clinically significant arrhythmia  
d. Acute coronary syndrome (angina or myocardial infarction) in last 6 months 
e. Interstitial lung disease (participants with existing pneumonitis as a result of 
radiation are not excluded; however, participants cannot be oxygen dependent)  
11. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or 
asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per 
Investigator assessment). 
NOTE: Stable chronic liver disease should generally be defined by the absence of 
ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric 
varices, persistent jaundice or cirrhosis. 
12. QTc >480 msec  
NOTES:  
The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or 
manually over-read. 
The specific formula that will be used to determine eligibility 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. 
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). 
13. Participant has a history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to cyclophosphamide, fludarabine, other agents 
used in the study.  

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14. Pregnant or breastfeeding females (due to risk to fetus or newborn). 
15. Prior/Concomitant Therapy: 
a. Any prior treatment-related toxicities must be CTCAE (Version 5.0) Grade ≤1 at 
the time of initiating study intervention (except for non-clinically significant 
toxicities e.g., alopecia, vitiligo).  Participants with Grade 2 toxicities that are 
deemed stable or irreversible (e.g. chemotherapy related arthritis or tendinitis, 
skin discoloration or erythema) can be enrolled. 
b. Other standard of care lines of therapy are allowed only if guidelines and washout 
periods are followed as described in Table 6. 
16. Investigational treatment within 30 days or 5 half-lives (whichever is shorter) prior to 
leukapheresis. Investigational vaccines (other than NY-ESO-1 vaccines that are not 
allowed) must follow the washout period specified in Table 6. Exceptions to this rule 
must be evaluated by the Investigator in agreement with the Sponsor’s Medical 
Monitor (or designee). 
17. Participant has active infection with HIV, HBV, HCV, EBV, CMV, syphilis, or 
HTLV as defined below: 
• 
Positive serology for HIV; 
• 
Active hepatitis B infection as demonstrated by test for hepatitis B surface 
antigen. Participants who are hepatitis B surface antigen negative but are 
hepatitis B core antibody positive must have undetectable hepatitis B DNA and 
receive prophylaxis against viral reactivation; 
• 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; 
• 
Active EBV infection. Participants with positive EBV serology need to undergo 
additional tests/assessments in order to rule out active infection; 
• 
Active CMV infection. Participants with positive CMV serology need to undergo 
additional tests/assessments in order to rule out active infection; 
• 
Positive test for syphilis (spirochete bacterium);  
• 
Positive serology for HTLV 1 or 2.   
18. Has known psychiatric or substance abuse disorders that would interfere with 
cooperating with the requirements of the study. 
 
6.2.3 
Treatment Eligibility Screening 
Please note that mandatory washout period restrictions must be respected (Table 6) 
before starting lymphodepletion. In addition to confirming Treatment fitness per Section 
6.2.3.1, participants cannot proceed with lymphodepletion or treatment if any of the 
following criteria apply: 
19. Participant has received cytotoxic therapy within 3 weeks prior to lymphodepleting 
chemotherapy. 

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20. Systemic corticosteroids or any other immunosuppressive therapy within 2 weeks 
prior to lymphodepleting chemotherapy.  
NOTE: Isolated doses of systemic corticosteroids are permitted to manage acute 
allergic reactions.  Use of inhaled or topical steroids is not exclusionary  
21. Participant has received ≥50 Gy to a significant volume of the pelvis, long bones or 
spine, or a cumulative dose of radiation that, in the Investigator’s opinion would 
predispose patients to prolonged cytopenia after lymphodepletion. 
22. All of the participant’s measurable lesions have been irradiated within 3 months prior 
to lymphodepletion. An irradiated measurable lesion with unequivocal progression 
following irradiation may be considered a target lesion regardless of time from last 
radiotherapy dose.  
NOTE: There is no washout period for palliative radiation to non-target lesions 
23. Participant has received an anti-cancer vaccine within 2 months in the absence of 
tumor response. The participant should be excluded if their disease is responding to 
an experimental vaccine given within 6 months. 
24. Participant has received live vaccine within 4 weeks prior to lymphodepletion or 
intends to receive live vaccine during the 3 month period following administration of 
lete-cel. 
25. Participant has received immune therapy (monoclonal antibody therapy, checkpoint 
inhibitors) within 4 weeks of lymphodepletion. 
26. Participant had major surgery 28 days of first dose of study intervention. 
 
Table 6 
Washout Periods for Substudy 1 
Treatment/Therapya 
Required Washout  
Prior to Leukapheresis 
Required Washout 
Prior to Lymphodepletionb 
Cytotoxic chemotherapy (including bridging 
chemotherapy) 
3 weeks 
Live-virus vaccination (there is no required 
washout for seasonal flu vaccines that do not 
contain live virus). 
4 weeks 
Systemic corticosteroids or any other 
immunosuppressive therapy (there is no washout 
required for inhaled or topical steroids as they are 
allowed during the study) 
2 weeks 
Investigational treatment  
4 weeks  
2 weeks 
Radiotherapy 
To the target lesions within 3 months prior to 
lymphodepletion.c  
NOTE: There is no washout period for palliative radiation to 
non-target lesions 
a. 
Permission and washout for any other anticancer therapies must be discussed with the Sponsor’s Medical 
Monitor (or designee). 
b. 
Bridging therapy allowed on Substudy 1 between leukapheresis and lymphodepletion includes doxorubicin 
60-75 mg/m2 IV every 3 weeks for up to two cycles (see Section 7.1.2). 
c. 
A lesion with unequivocal progression may be considered a target lesion regardless of time from last 
radiotherapy dose. 

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6.2.3.1 Treatment Fitness (for Safety) 
Given potential changes in clinical status between screening/enrollment and the start of 
lymphodepleting chemotherapy, safety assessments from Section 6.2.1 and Section 6.2.2 
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. 
6.3 
Lifestyle Considerations 
6.3.1 Meals and Dietary Restrictions 
Participants should maintain the current/regular diet unless modifications are required to 
manage an AE such as diarrhea, nausea, or vomiting. 
6.3.2 Activity 
Participants should abstain from extraordinarily strenuous athletic activity for 24 h before 
each blood collection for clinical laboratory tests. Participants may participate in light 
recreational activities during studies (e.g., watching television, reading). 
6.3.3 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, disease characteristics, 
prior lines of anti-cancer treatments and any serious adverse events (SAEs). 
6.3.4 Rescreening 
Individuals who do not meet the criteria for participation in this study (screen failure or 
withdrawal) may be rescreened upon Sponsor agreement.  
Rescreened participants will be assigned a new participant number. 
For each rescreened participant, the Sponsor will review the following on evaluation of 
eligibility to Substudy 1 and before initiating leukapheresis or manufacturing of the 
T cells: 
• 
Participant will be considered HLA positive if already tested positive for  
HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a 
designated central lab under this substudy or under another GSK-sponsored study or 
substudy of this protocol;  
• 
Participant’s tumor antigen expression will be considered positive if previously 
pathologically reviewed by a designated central laboratory under this substudy or 
under another GSK-sponsored study or substudy of this protocol, with confirmed 
positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+  
by immunohistochemistry;   

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• 
If participant has previously completed Sponsor protocol-specified leukapheresis:  
– Already banked cryopreserved T cells under an applicable process may be used 
in the manufacturing of lete-cel if within shelf-life specifications;  
– Already stored manufactured lete-cel (GSK3377794) product under an applicable 
process may be used for the T-cell infusion if within shelf-life specifications. 
7 STUDY INTERVENTION 
7.1 
Study Intervention(s) Administered 
7.1.1 Leukapheresis 
Participants will undergo leukapheresis to obtain starting material for the manufacture of 
autologous letetresgene autoleucel (lete-cel, GSK3377794).  
Investigators will follow institutional guidelines and the minimum requirements as 
outlined in the Apheresis Manual. 
A CD3 count of ≥200/L prior to leukaheresis is recommended to ensure an adequate 
T-cell collection for manufacture of lete-cel. If the lab test returns a value lower than 200, 
there is the potential that more than one collection will be needed to reach the T-cell 
target. The lab test should be repeated, and the Sponsor alerted as soon as possible.    
7.1.2 Bridging Therapy and/or Standard of Care Intermediate Anti-Cancer 
Therapy before Lymphodepletion 
In this first line population, participants may receive doxorubicin 60-75 mg/m2 IV every 
three weeks for up to two cycles between leukapheresis and the start of lymphodepletion. 
Use of doxorubicin is at Investigator’s discretion in accordance with the label and local 
institutional guidelines. Clinically significant interactions have been reported for 
doxorubicin with inhibitors of CYP3A4, CYP2D6, and/or P-glycoprotein (P-gp) 
(e.g., verapamil) and also with inducers of CYP3A4 (e.g, phenobarbital, phenytoin, 
St. John’s Wort), which may affect the concentration of doxorubicin, and therefore 
should be used with caution. 
Mandatory washout periods (Table 6 Section 6.2 of this Substudy) must be respected. For 
therapies not already described in this protocol, washout periods must be around 
5 half-lives, except for biologic agents for which a Sponsor consultation is required. 
7.1.3 Lymphodepleting Chemotherapy 
Prior to the administration of lymphodepleting chemotherapy, participant’s fitness for 
lymphodepletion will be assessed, treatment eligibility criteria will be confirmed and 
baseline tumor assessment CT/MRI obtained per Section 9.1.1 of the Core Protocol and 
the SoA in this Substudy.  
When lete-cel has been manufactured, has fulfilled release criteria, and is available for 
infusion at the site, lymphodepleting fludarabine and cyclophosphamide can be 

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administered as described in Table 7. Cyclophosphamide and fludarabine will be supplied 
by the pharmacy of the participating Institution. 
Dose and regimen for lymphodepleting chemotherapy is adjusted for participants 
60 years of age, as specified in Table 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 
the bone marrow reserve, 
• 
Participants with documented low albumin (≤3.5 g/dL). 
 
A default dose adjustment for participants meeting one of the listed conditions above 
should be aligned to the standard dose modification otherwise applied for participants 
60 years of age, as specified in Table 7.  
For any conditions that are more complex, further discussion to determine the need for 
dose modification with the Sponsor’s Medical Monitor or designee will be warranted. 
For investigators with patients approaching lymphodepletion, Sponsor requires that site 
review creatinine clearance (CrCl) and lymphodepleting chemotherapy 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 
(estimated or measured).  Any significant discrepancy that would lead to a change in dose 
will be discussed with Medical monitor prior to commencing lymphodepletion. 
• 
Calculations methods are provided in Section 6.1 Table 5 Definitions of Adequate 
Organ Function, Renal for CKD-EPI using 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 
estimation of creatinine clearance. 
 
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. 
Supportive therapy guidelines are provided in Section 12.7. 

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Table 7 
Lymphodepleting Chemotherapy 
 
Lymphodepleting chemotherapy 
Recommended prophylaxis 
and supportive medication 
Day 
Drug 
Dose, 
mg/m2 
Dose for 
participants 
 60 years 
old, mg/m2 
Route Administrationc 
Infection:  On admission for 
lymphodepleting 
chemotherapy, commence 
anti-microbial and anti-fungal 
prophylaxis as recommended 
in Section 12.7 or in line with 
institutional standard 
practice. 
 
Hydration:  Ensure adequate 
hydration and antiemetic 
provision prior to 
commencing 
cyclophosphamide infusions 
 
Mesna:  May be given to 
prevent urotoxicity per 
institutional guidelines or as 
recommended in this Section 
below. 
 
G-CSF:  Must start ~24 hours 
after the last 
cyclophosphamide infusion 
(i.e., on Day -3). G-CSF 
support to continue until 
resolution of neutropenia in 
accordance with ASCO 
guidelines [Smith, 2015] or 
institutional practice. 
-7 
Fludarabine1 
30 
none 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
-6 
Fludarabine1 
30 
30 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
Cyclophosphamide3 
900 
600 
IV 
in 200 – 500 mL 
0.9% NaCl over 
1 hour2 
-5 
Fludarabine1 
30 
30 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
Cyclophosphamide3 
900 
600 
IV 
in 200 – 500 mL 
0.9% NaCl over 
1 hour2 
-4 
Fludarabine1 
30 
30 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
Cyclophosphamide3 
900 
600 
IV 
in 200 – 500 mL 
0.9% NaCl over 
1 hour2 
-3 
Start G-CSF4 
+1 
Lete-cel (GSK3377794) 
1. 
Fludarabine dose will be adjusted in renal impairment as described in this section.  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 actual body weight 
[Bubalo, 2014], unless required otherwise by institutional guidelines. 
2. 
Or per institutional guidelines. 
3. 
Cyclophosphamide dose will be adjusted in obese participants and in pediatric participants as described in this 
section. This adjustment needs to be applied to all doses, on top of the age-related modification. 
4. 
Long-acting (pegylated) G-CSF may be given instead of short acting G-CSF according to institutional standard 
practice. If pegylated G-CSF is administered, give one dose ~24 hours after the last chemotherapy administered. 
 
ASCO = American Society of Clinical Oncology; ASBMT = American Society for Blood and Marrow Transplantation 
practice; IV = intravenous; NaCl = sodium chloride; G-CSF = granulocyte-colony stimulating factor 
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 
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Creatinine clearance (CrCl) 
Fludarabine dose 
>80 mL/min 
30 mg/m2 
>50 – 80 mL/min 
20 mg/m2 
30 – 50 mL/min 
15 mg/m2 
Note: to estimate CrCl (in mL/min) please use Section 6.1 Table 5 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 for this BSA calculation, use actual body weight.   
Creatinine clearance must be reassessed prior to lymphodepletion for use in these calculations. 
Cyclophosphamide Dose Adjustments 
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 Adjusted Body Weight (ABW). 
Calculating Ideal Body Weight 
 
Estimated ideal body weight (IBW) in kg 
Males 
 
Females 
 
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:  
 
Estimation of Adujsted 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 (BSA). 
Cyclophosphamide Dose Adjustment for Pediatric Participants 
For pediatric participants, where participant weight is >175% of the calculated ideal body 
weight (IBW) use the following formula to calculate cyclophosphamide dose: 
 
Estimation of Adujsted Body Weight may be performed per local institutional guidelines 
instead. 

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Use ABW in the calculation for body surface area (BSA). 
Mesna 
Mesna should be administered per institutional guidelines or as recommended below:  
• 
50% of cyclophosphamide daily dose (450 or 300 mg/m2) divided into 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. 
 
7.1.4 Lete-cel (GSK3377794) Infusion 
Refer to the most current version of Lete-cel Investigator’s Brochure regarding lete-cel 
and related clinical experience. Refer to the Drup Product and Infusion Manual for details 
and instruction on storage and administration of lete-cel. 
Participants will receive a single dose of lete-cel four days after completing the 
lymphodepleting chemotherapy. This is considered Day 1 and all procedures and 
assessments to be performed are listed in the SoA. Supportive care guidelines are 
provided in Section 12.7. 
Tocilizumab availability in institution’s local pharmacy 
A minimum of 2 doses of tocilizumab available for each participant will be required for 
administration within 2 hours after T-cell infusion, if needed for treatment of Cytokine 
Release Syndrome (CRS). 
Premedication 
Thirty to sixty (30 to 60) minutes prior to T-cell infusion, participants will be 
premedicated against potential infusion reactions with antihistamines and acetaminophen 
(paracetamol). Follow institutional practice for dosage and specific medications. Steroids 
should not be administered as premedication for T-cell infusion because they are 
lymphotoxic and inhibitory to the T-cell product. 
Lete-cel (GSK3377794) Dose 
The dose of lete-cel will be within the range of 1×109 – 15×109 transduced T cells, which 
will be administered by a single intravenous infusion on Day 1.  The minimum 
transduced cell dose for meeting release criteria is 1×109. 
If the transduced cell dose is less than the minimum dose required, 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.  
Dosing of participants weighing less than 40 kg (including pediatric participants): 
For participants weighing less than 40 kg, lete-cel will be dosed per body weight with a 
range of 0.025×109 transduced cells/kg to 0.2×109 transduced cells/kg. The per body 

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weight adjusted dosing can only be manufactured from the intended commercial cell 
manufacturing process and participants weighing less than 40 kg will only be treated with 
intended commercial drug product supply, as soon as it becomes available.  Screening of 
such participants may however begin before intended commercial drug product supply 
becomes available.   
Pediatric participants weighing greater than or equal to 40 kg will be dosed per adult 
dosing. 
Lete-cel (GSK3377794) Administration 
On Day 1, the participant will receive thawed T cells by intravenous infusion. Prior to 
infusion, two clinical personnel in the presence of the participant, will independently 
verify and confirm that the information on the infusion bag is correctly matched to the 
participant, as per the sponsor’s and clinical site’s procedures. 
The specific instructions for preparation and administration are found in the Drug Product 
and  Infusion Manual.  
Any deviation from the procedures detailed in the Drug Product and Infusion Manual 
should be recorded and reported accordingly. 
In the event of adverse reaction to the cell infusion, the infusion rate should be reduced, 
and the reaction managed according to institutional standard procedures (Section 12.7). 
Steroid treatment should be avoided unless medically required. In the event a participant 
develops a febrile episode following the infusion, appropriate cultures and medical 
management should be initiated, with attention to the initiation of empirical antibiotic 
treatment in the case of febrile neutropenia. 
The day of T-cell infusion may be delayed in participants with significant complications 
of lymphodepleting chemotherapy if according to the Investigator it is in the best interest 
of the participant. The timing of all assessments post-infusion will be calculated with 
reference to the T-cell infusion date. Participants who have undergone leukapheresis but 
do not receive the T-cell infusion will be replaced. Cytopenias alone should not be a 
reason to delay T-cell infusion unless complications are present (see Section 12.7 for 
guidance).  
Vital signs will be recorded prior to the infusion (see SoA). 
7.2 
Preparation / Handling / Storage / Accountability 
1. Deliveries of the investigational product 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 study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
3. Only participants enrolled in the study may receive study intervention and only 
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interventions 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. 
4. The participant’s T-cell product received at the site from the manufacturer will be 
stored below -130°C until ordered by the Investigator (or designee) to be infused. 
5. The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
6. Further guidance and information for the final disposition of unused study 
intervention will be provided in the Study Reference Manual or Drug Product and 
Infusion Manual.  
 
Precaution will be taken to avoid direct contact with the investigational product. A 
Material Safety Data Sheet (MSDS) describing occupational hazards and recommended 
handling precautions will be provided to the Investigator. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or GSK study contact. 
7.3 
Measures to Minimize Bias: Randomization and Blinding 
Not applicable to this open-label substudy. 
7.4 
Study Intervention Compliance 
Lete-cel will be intravenously administered to participants at the site per guidelines 
specified in the Drug Product and Infusion Manual.  Administration will be documented 
in the source documents and reported in the eCRF. 
7.5 
Concomitant Therapy 
Only chemotherapy (doxorubicin) and, if medically necessary for symptom management, 
palliative radiotherapy are allowed in the period between leukapheresis and 
lymphodepletion.   
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving starting at the time 
of screening for leukapheresis or receives during the study must be recorded along with: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 
 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
All concomitant medications including all prescription, over-the-counter medications, 
and herbal remedies, will be recorded, including dose and frequency. The following will 
be recorded on the appropriate eCRF pages: 

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1. All prescription and non-prescription medication, vitamins, herbal and nutritional 
supplements taken by the participant during the 30 days prior to Screening for 
leukapheresis will be recorded at the Screening Phase visit. 
2. All prior anti-cancer treatments taken by the participant must be recorded regardless 
of time. 
3. All concomitant medications taken by the participant while in the Interventional 
Phase.  
4. Use of any mutagenic agents or investigational agents must be reported. 
5. Concomitant medications administered after the Interventional phase of the study will 
be recorded for SAEs and adverse events of special interest (AESIs). 
 
Any changes to concomitant medication regimens must be recorded throughout the study 
in the eCRF. 
7.5.1 Prohibited Concomitant Medication and Treatment 
The following anti-cancer treatments are prohibited during the Interventional Phase of the 
study until PD is confirmed:  non-protocol chemotherapy, immune therapy, biological  
therapy (including targeted therapies with tyrosine kinase inhibitors or monoclonal 
antibodies), or investigational anti-cancer therapy.  Once PD has been confirmed 
following T-cell infusion, participants can receive therapy at the discretion of their 
healthcare provider while they remain in this study.  This includes participation in other 
interventional clinical studies as needed. 
During the Interventional Phase of the study until PD is confirmed participants should 
also not undergo other anticancer locoregional therapies, such as surgical resection, 
excisional biopsies or non-palliative radiation. Procedures intended for palliative care or 
symptomatic relieve on non-target lesions are permitted.   
Systemic steroids may abrogate the effects of the T-cell therapy and therefore; are 
discouraged unless required to manage CRS (refer to Section 12.7 for CRS management) 
or other significant immune-mediated AEs. According to local standard of care or 
American Society of Clinical Oncology (ASCO) guidelines [Basch, 2010], steroids may 
be used as anti-emetics before cyclophosphamide but must be discontinued no later than 
3 days prior to infusion of the investigational product. Topical steroids for cutaneous 
application and inhaled steroidal treatments are permitted. 
Systemic glucocorticoids are prohibited for any purpose other than to treat an event of 
suspected immunologic etiology (see Section 12.7). The use of physiologic doses of 
corticosteroids may be approved after consultation with the Sponsor.  
Participants may receive other medications that the Investigator deems to be medically 
necessary in agreement with the Sponsor’s Medical Monitor (or designee). 
Medications or vaccinations specifically prohibited in the exclusion criteria are not 
allowed during the ongoing trial. Administration of live vaccine during the period of 
infusion of fludarabine, cyclophosphamide or lete-cel, and for at least 3 months after last 

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dose of any of these agents is prohibited. If there is a clinical indication for any 
medication or vaccination specifically prohibited during the trial, discontinuation from 
trial therapy may be required. The Investigator should discuss any questions regarding 
this 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 intervention requires the mutual agreement of the 
Investigator, the Sponsor and the participant. 
7.5.2 Permitted Concomitant Medication and Treatment 
Participants should receive full supportive care during the study, including transfusion of 
blood and blood products, and treatment with antibiotics, antiemetics, antidiarrheals, and 
analgesics, as appropriate. 
Lesions that previously required radiotherapy should be recorded prior to 
lymphodepleting chemotherapy. Radiotherapy is not permitted after T-cell infusion until 
disease progression.  However, in emergent clinical situations, palliative radiation for 
pain relief to non-measurable lesions or non-target lesions present at baseline may be 
permitted upon approval of Sponsor’s Medical Monitor. However, lesions requiring 
radiotherapy after the T-cell infusion should be evaluated as to whether that indicates 
disease progression. These lesions are not suitable to be biopsied for biomarker analysis. 
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 a 
guidance such as the CDC Clinical Practice Guideline for Vaccination of the 
Immunocompromised Host. 
Permitted concomitant medications with required washout periods are listed Section 6.2, 
Table 6 of this Substudy.  For therapies not already described in this protocol, washout 
periods must be around 5 half-lives, except for biologic agents for which a Sponsor 
consultation is required. 
Once PD has been confirmed following T-cell infusion, participants can receive further 
therapy at the discretion of their healthcare provider while they continue to be followed in 
this study.  
Recommendations for participants on therapeutic anticoagulants: [Maus, 2020] 
• 
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. 

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• 
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. 
 
7.5.3 Rescue Medicine 
Anti IL-6 drugs such as Tocilizumab may be administered to participants experiencing 
cytokine release syndrome (see Section 12.7.5 for details).  Steroids may be used for 
emergent medical conditions.  For all non-emergent conditions, consult with the 
Sponsor’s Medical Monitor.  Guidelines for management of complications are provided 
separately in the appendices. 
See Section 12.7 for details on general supportive care that can be given during the study. 
7.6 
Dose Modification 
Dose modification is not applicable to T cells.  The entire dose of T cells that has been 
received by the site for the participant needs to be administered as a single dose.  If a 
reaction occurs that does not allow safe administration of the full dose, the dose 
administered needs to be recorded. 
If the transduced cell dose is less than the minimum dose required, 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.   
7.7 
Intervention after the End of the Study 
No therapeutic intervention will be provided after the end of the study.  Participant may 
receive any necessary treatment interventions from their oncologist. 
8 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION / WITHDRAWAL 
Definitions and procedures for discontinuation of study intervention and participant 
discontinuation / withdrawal should follow the SoA in this Substudy and details outlined 
in Core Protocol Section 8. 
9 STUDY ASSESSMENTS AND PROCEDURES 
Study assessments and procedures should be performed per the SoA and as defined in the 
Core Protocol Section 9.   
The following additional Substudy specific assessments should be performed per the 
SoA. 

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9.1 
Interviews 
9.1.1 Post T cell Infusion Interview 
To evaluate T-cell infusion related experiences, symptoms and associated impacts, adult 
participants will be asked to participate in an optional telephone interview.  Adult 
participants will be contacted about one week after infusion to set up a phone 
interview.  The informed consent for this phone interview will be part of the clinical trial 
informed consent process. All of the interviews will be conducted by a trained 
interviewer will be audio recorded for transcription and analysis.  Failure to complete the 
interviews will not constitute a protocol deviation. 
9.1.2 End of Treatment Interview  
To further evaluate disease and treatment related symptoms and associated impacts on 
function and health-related quality-of-life, adult participants will complete an optional 
Exit Interview conducted via telephone within approximately 21 days following 
completion of the last Interventional Phase visit and will focus on symptoms and 
impacts following discontinuation of study intervention.  Failure to complete the 
interviews will not constitute a protocol deviation. 
9.2 
Patient Reported Outcomes 
Patient reported outcomes will be assessed in adult participants as part of this protocol. 
The instruments in use in this section are only suitable for adult populations. 
CCI

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CCI

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9.3 
Safety Assessments 
Study assessments and procedures should be performed per the SoA and as defined in the 
Core Protocol Section 9.   
10 STATISTICAL CONSIDERATIONS  
10.1 Statistical hypotheses  
No formal statistical hypotheses are being tested in this substudy. 
10.2 Sample size justification 
Bayesian statistics will be employed to calculate the predictive probability [Lee, 2008] 
that the pooled overall response rate (ORR) will be ≥20% at the primary analysis (after 
the 10th treated participant across synovial sarcoma and myxoid/round cell liposarcoma 
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 beta (0.02, 0.08) is used, which is equivalent to 
the information present in 0.1 participant. If the predictive probability of 20 participants 
CCI

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treated in total that the response rate of ≥20% is less than 1% (i.e., 1 or less responders 
out of 10 participants at the primary analysis) is observed during the primary analysis, 
strong statistical evidence has been provided for no further development of the treatment 
for the target population. If the predictive probability of 20 participants treated in total 
that the response rate of ≥20% is greater than 90% (i.e., 6 or more responders out of 
10 participants at the primary analysis) is observed during the primary analysis, strong 
statistical evidence has been provided in favor of further development of the treatment for 
the population. If the observed number of responders is between 2 and 5 at the primary 
analysis, this substudy may further enroll to treat 10 additional participants.  The defined 
efficacy/futility thresholds are equivalent to the hypothetical study design: Bayesian 
predictive adaptive design [Lee, 2008] based on a historical response rate of 
approximately 20% versus a response rate of interest of 50% assuming 0.1 type I error 
and 80% power. Actual decisions will depend on the totality of the data including clinical 
activity, safety, PK, and biomarker data. 
Populations for Analyses. 
For purposes of analysis, the following populations are defined, the details of additional 
analysis populations will be defined in RAP: 
Population 
Description 
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. 
Safety Population 
All participants who received any dose of lete-cel (GSK3377794).  
Modified ITT (mITT) 
Population 
All participants who received any dose of lete-cel.  
10.3 
Statistical Analyses 
10.3.1 Efficacy Analyses 
Endpoint 
Statistical Analysis Methods 
Primary 
ORR, which includes confirmed complete or partial response as determined by 
Investigator assessment will be reported along with Clopper-Pearson exact 
95% CI. 
Secondary 
PFS, DOR and TTR will be summarized using Kaplan-Meier quantile estimates 
along with 2-sided 95% CIs at the time of final analysis, if data warrant. DCR will 
be reported along with Clopper-Pearson exact 95% CI. 

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Endpoint 
Statistical Analysis Methods 
Exploratory 
Will be described in the reporting and analysis plan. 
 
Primary Efficacy Analysis 
The primary analysis will be performed after all the enrolled participants have received 
T-cell infusion (mITT population) or withdrawn earlier and have completed at least 
2 post-baseline disease assessments since infusion or discontinued earlier (due to death, 
loss to follow-up, or permanent study withdrawal).   
Final Efficacy Analysis 
The final analysis will be performed after all the treated participants have progressed or 
died or withdrew from the study.  
ORR: Overall Response Rate (ORR) is defined as the percentage of participants with a 
confirmed CR or a PR relative to the total number of participants within the analysis 
population per RECIST v1.1 as determined by the local Investigators.  At the primary 
analysis, ORR will be analysed based on mITT population.  
ORR will also be reported in the ITT and mITT populations at the time of primary 
analysis for all participants.  
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 defined by RECIST v1.1, will be listed and 
summarized separately, as appropriate. 
The observed confirmed ORR will be reported at the primary analysis along with 95% 
Clopper-Pearson exact confidence interval (CI). 
Secondary Efficacy Analysis 
DCR: DCR, is defined as the percentage of participants within mITT population with a 
confirmed CR, PR, or SD with minimal 12 weeks duration relative to the total number of 
mITT participants at the time of  primary analysis as determined by local Investigators 
per RECIST v1.1. The observed DCR will be reported along with 95% Clopper-Pearson 
exact CI. 
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: PFS, is defined as the time from the date of T-cell infusion until the earliest date of 
radiological PD as assessed by local Investigators per RECIST v1.1, or death due to any 
cause. For the analysis of PFS, if the participant received subsequent anticancer therapy 
prior to the date of documented events, PFS will be censored at the last adequate 

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assessment (e.g., assessment when visit level response was CR, PR, or SD) prior to the 
initiation of the new anticancer therapy. Progressive disease will also be defined per 
RECIST v1.1 criteria. Further details on rules for censoring will be provided in the RAP. 
PFS will be summarized using Kaplan-Meier quartile estimates along with 2-sided 95% 
CIs at the time of final analysis, if data warrant. 
DOR: DOR is defined as, in the subset of participants who show a confirmed CR or PR 
as assessed by local Investigators, the time from first documented evidence of CR or PR 
until the first documented sign of disease progression or death. Duration of response will 
be summarized descriptively, if data warrant, using Kaplan-Meier medians and quartiles. 
Details on rules for censoring will be provided in the RAP (Report analysis Plan). 
TTR: TTR is defined as the time from the date of T-cell infusion to initial date of 
confirmed response (PR or CR) as assessed by local Investigators per RECIST v1.1 in the 
subset of participants who achieved a confirmed PR or CR. 
TTR will be listed and summarized descriptively using median and quartiles in the subset 
of participants with a confirmed response of PR or CR.  
Efficacy listings such as  best overall response (BOR), DOR, PFS and OS will be 
reported for the mITT population (all participants who received lete-cel infusion at 
primary and final analysis data cut if data warrant). 
Sensitivity Analysis 
The analysis of primary endpoint, ORR, will also be performed among all participants in 
the ITT population. 
10.3.2 Safety Analyses 
All safety analyses will be performed on the ITT  and Safety Populations.  
Endpoint 
Statistical Analysis Methods 
Primary 
AEs will be summarized using frequencies and proportions. 
Secondary 
AEs/SAEs/AESIs will be summarized using frequencies and proportions. RCL 
and instances of (IO will be summarized descriptively. 
Exploratory 
Will be described in the reporting and analysis plan  
 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively. 
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, if 
warranted, and across all on-treatment time points using a “worst-case” analysis. 
Complete details of the safety analyses will be provided in the RAP. 

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Adverse Events 
AEs will be coded using the standard MedDRA and grouped by system organ class and 
will be graded by the Investigator according to the NCI-CTCAE v5.0. In addition CRS 
and ICANS will be graded according to [Lee, 2019]. 
Events will be summarized by frequency and proportion of total participants and by 
system organ class and preferred term. Separate summaries will be given for all AEs, 
treatment-related AEs, SAEs, AESIs, and AEs leading to discontinuation of study 
intervention and dose modification. In addition, AEs, if listed in the NCI-CTCAE v5.0, 
will be summarized by the maximum grade.  In the case of low-event count, listings may 
be provided in lieu of summaries. 
AEs of special interest will be further outlined in the RAP. 
The incidence of deaths and the primary cause of death will be summarized. 
Clinical Laboratory Evaluations 
Data for vital signs and ECGs will be summarized based on predetermined criteria 
identified to be of potential clinical concern. Further details will be provided in the RAP. 
Replication Competent Lentivirus (RCL) and instances of insertional oncogenesis 
(IO) 
RCL and instances of IO will be summarized descriptively. 
10.3.3 
Other Analyses 
PK (T-cell persistence), pharmacodynamic, and biomarker analyses will be described in 
the RAP. PK data from this study may be combined with PK data from other studies and 
analysed using population PK approaches. If performed, the population PK analysis and 
pharmacodynamic analyses will be presented separately from the main clinical study 
report (CSR).  
10.3.4 
Interim Analyses  
Detailed interim safety and efficacy reports will be provided to the IDMC (see 
Section 5.4.1 of the Core Protocol) on a regular basis and the intervals will be specified in 
the IDMC charter. 

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SUBSTUDY 2: LETETRESGENE AUTOLEUCEL (LETE-CEL, 
GSK3377794) IN NY-ESO-1 POSITIVE PREVIOUSLY TREATED 
ADVANCED (METASTATIC OR UNRESECTABLE) SYNOVIAL 
SARCOMA OR MYXOID/ROUND CELL LIPOSARCOMA 
 
Substudy Title: Evaluation of Safety and Antitumor Activity of Lete-Cel (GSK3377794) 
in HLA-A2+ Participants with NY-ESO-1 Positive Previously Treated Advanced 
(Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma 
 
 

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TABLE OF CONTENTS 
1 
SYNOPSIS ........................................................................................................... 203 
2 
SCHEDULE OF ACTIVITIES (SOA) ..................................................................... 204 
3 
INTRODUCTION .................................................................................................. 218 
3.1 
Substudy 2 Background and Rationale ..................................................... 218 
3.2 
Benefit/Risk Assessment .......................................................................... 221 
3.2.1 
Risk Assessment ....................................................................... 222 
3.2.2 
Benefit Assessment ................................................................... 227 
3.2.3 
Overall Benefit/Risk Conclusion ................................................. 228 
4 
OBJECTIVES AND ENDPOINTS ......................................................................... 228 
5 
STUDY DESIGN .................................................................................................. 231 
5.1 
Overall Design .......................................................................................... 231 
5.2 
Number of Participants ............................................................................. 235 
5.3 
End of Study Definition ............................................................................. 235 
5.3.1 
End of Substudy for Individual Participants ................................ 235 
5.3.2 
End of Substudy ........................................................................ 236 
5.4 
Scientific Rationale for Substudy Design .................................................. 237 
5.5 
Justification for Dose ................................................................................ 237 
5.5.1 
Justification of Lymphodepleting Regimen ................................. 237 
5.5.2 
Justification of lete-cel (GSK3377794) Dose .............................. 238 
6 
STUDY POPULATION ......................................................................................... 239 
6.1 
INCLUSION CRITERIA ............................................................................. 239 
6.1.1 
Target Expression Screening ............................................................. 239 
6.1.2 
Leukapheresis Eligibility Screening...................................................... 240 
6.1.3 
Treatment Eligibility Screening ........................................................... 244 
6.1.3.1 
Treatment fitness (for safety) ............................................ 245 
6.2 
EXCLUSION CRITERIA ........................................................................... 245 
6.2.1 
Target Expression Screening ............................................................. 245 
6.2.2 
Leukapheresis Eligibility Screening...................................................... 246 
6.2.3 
Treatment Eligibility Screening ........................................................... 247 
6.2.3.1 
Treatment fitness (for safety) ............................................ 249 
6.3 
Lifestyle Considerations ............................................................................ 249 
6.3.1 
Meals and Dietary Restrictions .................................................. 249 
6.3.2 
Activity ....................................................................................... 249 
6.3.3 
Screen Failures.......................................................................... 249 
6.3.4 
Rescreening .............................................................................. 249 
7 
STUDY INTERVENTION ...................................................................................... 250 
7.1 
Study Intervention(s) Administered ........................................................... 250 
7.1.1 
Leukapheresis ........................................................................... 250 
7.1.2 
Bridging Therapy and/or Standard of Care Intermediate 
Anti-Cancer Therapy before Lymphodepletion ........................... 250 
7.1.3 
Lymphodepleting Chemotherapy ............................................... 251 
7.1.4 
Lete-cel (GSK3377794) Infusion ................................................ 254 
7.2 
Preparation / Handling / Storage / Accountability ...................................... 256 
7.3 
Measures to Minimize Bias: Randomization and Blinding ......................... 256 

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7.4 
Study Intervention Compliance ................................................................. 257 
7.5 
Concomitant Therapy................................................................................ 257 
7.5.1 
Prohibited Concomitant Medication and Treatment .................... 257 
7.5.2 
Permitted Concomitant Medication and Treatment .................... 258 
7.5.3 
Rescue Medicine ....................................................................... 259 
7.6 
Dose Modification ..................................................................................... 259 
7.7 
Intervention after the End of the Study ...................................................... 260 
8 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION / WITHDRAWAL ................................................................. 260 
9 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 260 
9.1 
Interviews ................................................................................................. 260 
9.1.1 
Post T-cell Infusion Interview ..................................................... 260 
9.1.2 
End of Treatment Interview ........................................................ 260 
9.2 
Patient Reported Outcomes ...................................................................... 260 
9.3 
Healthcare Resource Utilization ................................................................ 263 
10 STATISTICAL CONSIDERATIONS ...................................................................... 263 
10.1 
Statistical Hypotheses............................................................................... 263 
10.2 
Sample Size Justification .......................................................................... 264 
10.3 
Populations for Analyses .......................................................................... 265 
10.4 
Study Population Analyses ....................................................................... 266 
10.5 
Statistical Analyses ................................................................................... 268 
10.5.1 
Efficacy Analyses ....................................................................... 268 
10.5.2 
Safety Analyses ......................................................................... 272 
10.5.3 
Immunogenicity.......................................................................... 275 
10.5.4 
Other Analyses .......................................................................... 275 
10.5.5 
Interim Analyses ........................................................................ 275 
 
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SUBSTUDY 2: LETETRESGENE AUTOLEUCEL (LETE-CEL, 
GSK3377794) IN NY-ESO-1 POSITIVE PREVIOUSLY TREATED 
ADVANCED (METASTATIC OR UNRESECTABLE) SYNOVIAL 
SARCOMA OR MYXOID/ROUND CELL LIPOSARCOMA 
This previously treated (2L+) advanced (metastatic or unresectable) translocation-related 
sarcoma substudy contains substudy specific details. Refer to the body of the Core 
Protocol for all other information.  
1 SYNOPSIS 
This is a single-arm, non-randomized substudy to investigate the proposed commercial 
drug product supply process of letetresgene autoleucel (lete-cel, GSK3377794) in 
participants with advanced (metastatic or unresectable) NY-ESO-1 positive synovial 
sarcoma or myxoid/round cell liposarcoma, who have progressed following treatment 
with anthracycline-based chemotherapy, for the purpose of registration, as defined in the 
inclusion criteria (Section 6.1 of this Substudy).  In this Substudy, we will not be 
evaluating tumors for LAGE-1a expression since the Immunohistochemistry assay used 
for the antigen detection recognizes NY-ESO-1 only and not LAGE-1a.  LAGE-1a is 
rarely expressed in synovial sarcoma or myxoid/round cell liposarcoma. 
Confirmation of disease progression from prior line of therapy will be required before 
lymphodepletion. 
Substudy 2 Design 
 
 
* The lymphodepleting regimen is to be adjusted as described in Section 7.1.3 of this Substudy. 
See Section 1 Synopsis in the core protocol for overall study summary. 

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2 SCHEDULE OF ACTIVITIES (SOA) 
The timing and number of planned study assessments, including safety, pharmacokinetic, 
pharmacodynamic/biomarker or other assessments may be altered during the course of 
the study based on newly available data to ensure appropriate monitoring.  

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Table 1 
Substudy 2 Schedule of Activities – Screening and Leukapheresis 
 
Screening 
Phase1 
Leukapheresis 
Notes 
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening,  
within 28 days 
prior to 
leukapheresis3 
Informed Consent for Screening 
X 
 
 
1. 
Written informed consent must be obtained prior to performing any study 
assessments or procedures, except as stated in footnote 12.  Informed 
Consent for Leukapheresis and Treatment must be repeated if given more 
than 90 days prior to leukapheresis procedure. 
2. This visit may be performed under a separate protocol when it is introduced. 
3. Participants must be HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 
positive and have NY-ESO-1 positive tumor prior to conducting 
leukapheresis eligibility screening procedures.  
4. Only collect this sample if optional Genetics Research Consent has been 
signed by the participant.  Sample may be collected any time from signature 
of optional consent until leukapheresis.  Liquid biopsy is a blood sample 
from which circulating cell-free DNA (cfDNA), circulating tumor DNA 
(ctDNA), and exosomes may be extracted. 
5. 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. 
6. Includes all prescription, over-the-counter medications, and herbal 
remedies. Any use of mutagenic agents or investigational agents must also 
be reported. 
7. In pediatric participants height and weight will also be evaluated as a 
percentile vs national growth charts (based on sex and age) and vs genetic 
height target (expected height based on parental heights) and evaluation 
will be performed on whether growth is normal or abnormal. 
8. To be performed within 7 days prior to the day of leukapheresis. 
9. CD3 count prior to leukapheresis should be preferably performed within 
24 hours from leukapheresis procedure.  
Informed Consent for Leukapheresis 
and Treatment1 
 
X 
 
Inclusion/Exclusion for Screening 
X 
 
 
Inclusion/Exclusion for Leukapheresis 
 
X 
 
Demographics 
X 
 
 
Central Lab HLA -A genotyping3 
X 
 
 
Tumor expression of NY-ESO- 13 
X 
 
 
Liquid biopsy (blood)4 
X 
 
 
Medical History5  
X 
X 
 
Prior/Concomitant Medications6 
X 
X 
X 
Height and Weight7 
 
X 
 
Physical Exam (complete) 
 
X 
X8 
ECOG or Lansky or Karnofsky10 
X 
X 
 
Vital Signs11 
 
X 
X8 
12-lead ECG (in triplicate) 
 
XXX 
XXX8 
ECHO/MUGA 
 
X12 
 
CT / MRI 
 
X13 
 
Brain MRI14 
 
X13 
 
Hematology 
 
X12 
X8 
Clinical Chemistry 
 
X12 
X8 
Coagulation Tests 
 
X12 
X8 
Lymphocyte Subset (CD3/CD4/CD8) 
 
X8 
X8,9 
Estradiol and FSH, if needed to 
determine CBP 
 
X 
 
Pregnancy Test15 
 
X15 
X15 

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Screening 
Phase1 
Leukapheresis 
Notes 
Target 
Expression 
Screening2 
Leukapheresis 
Eligibility 
Screening,  
within 28 days 
prior to 
leukapheresis3 
Urinalysis 
 
X12 
X8 
10. Lansky will be used for participants <16 years of age; Karnofsky will be used 
for participants 16 and <18 years of age; and ECOG will be used for 
participants 18 years of age. 
11. Includes temperature, blood pressure, pulse rate, respiratory rate, and 
oxygen saturation. 
12. ECHO/MUGAand laboratory assessments performed as standard of care 
prior to study consent will be acceptable as long as assessment is done 
within  
28 days before leukapheresis.  
13. CT/MRI scan performed as standard of care prior to study consent will be 
acceptable as long as assessment is done within 90 days before 
leukapheresis. Any FDG PET/CT performed as part of clinical routine within  
90 days before leukapheresis, will also be collected. 
14. In addition to the Brain MRI, MRI of the spine will be performed when 
clinically indicated. 
15. WOCBP must have a highly sensitive negative urine or serum pregnancy 
test at screening for leukapharesis and within 24 h prior to leukapheresis.  
16. Includes HIV, HBV, HCV, HTLV, EBV, CMV, and syphilis (spirochaete 
bacterium). 
17. See Section 6.1 Table 5 for specifics on renal assessment. 
18. SAEs and AEs assessed as related to study participation (e.g., study 
intervention, protocol-mandated procedures, invasive tests, or change in 
existing therapy) or leading to study withdrawal will be collected from 
signing informed consent for target expression screening.  All SAEs and 
AEs will be collected starting at leukapheresis (See Section 9.4.1 in the 
Core Protocol). 
Infectious disease markers16 
 
X12 
 
Creatinine clearance by GFR or 24h 
urine17 
 
X 
 
Adverse Events and Serious Adverse 
Events 
X18 
X18 
X 
Leukapheresis 
 
 
X 
 
AE=adverse event; CBP=child-bearing potential; CT = computerized tomography; EBV = Epstein Barr virus; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern 
Cooperative Oncology Group; FDG = Fluorodeoxyglucose; FSH=follicle-stimulating hormone; GFR = glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = 

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human immunodeficiency virus; HTLV = human T-lymphotropic virus; MRI = magnetic resonance imaging; MUGA = multigated acquisition; SAE=serious adverse event; WOCBP = 
Women of childbearing potential 

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Table 2 
Substudy 2 Schedule of Activities – Interventional Phase (Lymphodepletion and Treatment)  
 
Treatment 
Fitness & 
Eligibility 
/ Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week 
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 
or until 
confirmed PD, 
whichever is 
sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
Treatment Fitness and 
Inclusion/Exclusion for 
Treatment Eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Request lete-cel 
shipment 
X2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Med. History3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
(complete) 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
X 
Physical Exam 
(dedicated) 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
 
 
Prior/Con Meds4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG, Lansky, or 
Karnofsky5 
X 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
X 
Developmental exam 
and puberty 
assessment6,7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X8 
Vital Signs9 and 
weight7 
X 
X 
X 
X 
X 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECHO/MUGA11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulse oximetry 
 
 
 
 
 
X12 
X 
X 
X 
X 
X 
X13 
X 
X13 
 
X 
X 
X 
 

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Treatment 
Fitness & 
Eligibility 
/ Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week 
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 
or until 
confirmed PD, 
whichever is 
sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
12-lead ECG14 
XXX 
 
 
 
 
X 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
CT/MRI15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X16 
X16 
Brain MRI17 
X17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ICE or CAPD18 
 
 
 
 
 
X19 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Chest X-Ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology20 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Chemistry20 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Uric acid 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Creatinine clearance by 
GFR or 24 h urine21 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation Tests20, 22 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Ferritin20 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Troponin and  
NT-proBNP / BNP20,23 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
X 
 
 
 
 
X24 
 
 
 
 
 
 
X 
 
 
 
X 
X25 
X25 
Urinalysis26 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious disease 
markers27 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CMV IgG and PCR28 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
 
 
Thyroid function tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CRP20 
X 
 
 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Treatment 
Fitness & 
Eligibility 
/ Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week 
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 
or until 
confirmed PD, 
whichever is 
sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
Adverse Events and 
Serious Adverse 
Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Transgene Copies 
(Persistence for Safety) 
and VSV-G DNA 
(RCL)29 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
weeks 12 and 
24 
Month 12 
and Q6M30  
Genetic sample 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Survival follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Lymphodepletion 
Fludarabine 
 
X31 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamide 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigational Product Administration 
Lete-cel (GSK3377794) 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient-Reported Outcomes32 
Healthcare Resource 
Utilization33 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Post-lete-cel infusion 
interview  
(adult participants only) 
 
 
 
 
 
 
 
 
 
 
X34 
 
 
 
 
 
 
 
 
EOT interview 
(adult participants only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X35 

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Treatment 
Fitness & 
Eligibility 
/ Baseline 
Lymphodepletion 
T-cell 
Infusion1 
Post T-cell Infusion 
Month 
(1 month = 4 weeks) 
-1 
1 
2 
3-6 
Q3M from 
month 9 until 
confirmed PD 
Week 
(Week N visit for N≥1  
is scheduled on 1st day  
of the week = Day 7N-6) 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
10, 12, 18, 24 
or until 
confirmed PD, 
whichever is 
sooner 
 
Day 
-17 to -8 
-7 
-6 
-5 
-4 
1 
2 
3 
4 
6 
8 
15 
22 
29 
36 
43 
50 64, 78, 120, 162 
 
Visit Window 
N/A 
±1 day 
±3 days 
±7 days   
±1 month  
 
1. 
On Day 1, all samples will be collected and assessments performed prior to T-cell infusion (within 24 h), unless otherwise specified.  
2. 
As lete-cel needs to be on site prior to lymphodepletion, request lete-cel no later than 4 working days prior to the day of lymphodepletion.  The mechanism of request will be 
provided in Apheresis and Drug Product and Infusion Manual. 
3. 
Medical history will be recorded in the eCRF at Treatment Eligibility Screening / Baseline visit; however, any changes in medical history must be recorded in source 
documents throughout the conduct of the study. 
4. 
Includes all prescription, over-the-counter medications, and herbal remedies. Any use of mutagenic agents or investigational agents must also be reported. 
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5. 
Lansky will be used for participants <16 years of age; Karnofsky will be used for participants 16 and <18 years of age; and ECOG will be used for participants 18 years of 
age. 
6. 
To be assessed in pediatric participants only. 
7. 
In pediatric participants height and weight will also be evaluated as a percentile vs national growth charts (based on sex and age) and vs genetic height target (expected 
height based on parental heights) and evaluation will be performed on whether growth is normal or abnormal. 
8. 
To be assessed once a year. 
9. 
Vital signs include temperature, blood pressure, pulse rate, and respiratory rate. 
10. Vital signs on day of T-cell infusion should be taken pre-infusion, and approximately at 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started. 
11. If suspected CRS Grade ≥2, an ECHO/MUGA is required at onset of Grade ≥2 CRS. Additional monitoring must be conducted (including inpatient continuous cardiac 
telemetry monitoring) for a minimum of 3 days post onset and as long as deemed necessary by the Investigator (refer to Section 12.7.5).  
12. On T-cell infusion day, pulse oximetry should be taken pre-infusion, and approximately at 5, 15 and 30 minutes, and 1, 1.5, 2, and 4 hours after the infusion has started.  
13. Pulse oximetry at these visits will be performed if medically indicated.  
14. ECG can also be performed at other time points if medically indicated.  Triplicate ECG will be collected at Treatment Eligibility Screening / Baseline visit and single ECGs at 
other timepoints. Participants with an increased burden of cardiovascular risk factors (as per Section 9.3.6) will undergo evaluation by a cardiologist prior to lymphodepletion. 
15. See Section 9.1.1 of the core protocol for scan description and areas to scan.  If a participant is found to have a tumor response or PD by imaging and considered to be 
clinically stable by iRECIST criteria (see Section 12.6.2), a follow-up confirmation scan must be done no earlier than 4 weeks and no later than 8 weeks following the scan 
when response or PD first seen. A participant is not considered to have a response or PD until follow-up scan confirms the finding. 
16. CT/MRI will not be performed at Week 10.  CT/MRI assessments only need to continue until confirmed PD.   
17. Brain MRI should be performed at baseline if more than 4 months have elapsed from last MRI. Brain MRI will be performed at other time points, if clinically indicated. MRI of 
the spine will be performed, if clinically indicated. 
18. All participants will be monitored as shown in the SoA. If a participant is found to have Immune effector cell-associated neurotoxicity syndrome (ICANS), the ICE neurological 
assessment tool should be used at least twice per day until ICANS is resolved or stable. It can also be used at later visits if indicated.  In participants < 12 years of age, 
CAPD should be used in place of ICE. 
19. To be administered prior to T-cell infusion. 
20. If CRS and/or ICANS is suspected, chemistry, hematology, ferritin, coagulation and CRP tests should be performed locally every day for the first week and approximately 
every other day thereafter until symptoms are improving or an alternative diagnosis is confirmed. In addition, if CRS is suspected, cytokine samples will be collected for 
central analysis following same schedule (as per SOA Table 3 footnote 4). 
21. See Section 6.1 Table 5 for specifics on renal assessment. 
22. Coagulation tests include INR, PTT or aPTT and fibrinogen. Coagulation tests should be taken at baseline, and on Days 1, 2, 3, 4, 6, 8 and 15.  
23. Troponin and NT-proBNP / BNP tests should be monitored for participants with CRS Grade ≥2 as clinically indicated. 
24. WOCBP must have a negative urine or serum pregnancy test prior to lete-cel infusion.   
25. WOCBP will need to have pregnancy tests performed at all visits indicated in the table for the duration of the contraception period (Section 6.1 of this Substudy). 
26. In addition to the specified time points, urinalysis will be done at other timepoints if warranted by the symptoms. 
27. Includes HIV, HBV, HCV, HTLV, EBV, and syphilis (spirochaete bacterium). 
28. Only participants who are CMV IgG seropositive at Baseline will continue to be monitored for CMV viremia by CMV DNA PCR post Baseline.  CMV will also be assessed if 
GBS is suspected. 
29. If possible, this sample also needs to be obtained in case of any SAE that occurs after T‑cell infusion. 

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30. If no gene modified cells are detected for two consecutive assessments post-infusion, and the participant is  years post T-cell infusion,  samples for VSV-G DNA (RCL) 
and persistence of gene modified cells will be discontinued (Section 9.3.9.1 of the Core Protocol). 
31. On Day -7. fludarabine will not be administered to participants 60 years old. 
32. Patient-Reported Outcomes instruments are only for adult participants. 
33. Only perform until PD is confirmed. Site staff will complete the paper Healthcare Utilization Worksheet and enter data in the eCRF.   
34. Contact participant about one week after T-cell infusion to schedule the phone interview to be conducted by Day 21 of the study.  If phone interview cannot be scheduled at 
this time, contact participant every two weeks until successful or the 60-day limit is reached from T-cell infusion.  Beyond 60 days from T-cell infusion, no need to conduct the 
participant interview as recall may not be reliable. 
35. To be conducted within approximately 21 days following the last visit in the Interventional Phase. 
36. To be administered prior to infusion. 
 
BNP = B-type natriuretic peptide; CAPD= Cornell Assessment of Pediatric Delirium; CMV = Cytomegalovirus; Con Meds = concomitant medications; CRS=cytokine release syndrome; 
CT = computerized tomography; EBV = Epstein Barr virus; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EDC = electronic data 
capture; 
 
 
 
 = glomerular filtration rate; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; HTLV = human T-lymphotropic 
virus; ICANS = Immune Effector Cell-Associated Neurotoxicity Syndrome; ICE=Immune Effector Cell-Associated Encephalopathy; Med history=medical history; MRI = magnetic 
resonance imaging; MUGA = multigated acquisition; NT-proBNP = N-terminal pro-BNP; PCR = Polymerase chain reaction; PD=progressive disease; 
 
 
 Q3M = every 
3 months; RCL=replication competent lentivirus; TSH = Thyroid stimulating hormone; VSV-G =vesicular stomatitis virus G protein; WOCBP = Women of childbearing potential. 
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Table 3 
Substudy 2 Schedule of Activities – Immunogenicity and Biomarkers (Interventional Phase) 
 
Sample 
Type 
Baseline 
Lymphodepletion 
T-cell infusion 
Post T-cell infusion 
Month 
(1 month = 4 weeks) 
 
-1 
1 
2 
3-6  
Q3M from month 9 
until confirmed PD1 
Week 
 
-3 to -2 
-1 
1 
2 
3 
4 
5 
6 
8 
(10) 2, 12, 18, 24 
or until 
confirmed PD, 
whichever is 
sooner1,2  
 
Day 
 
-17 to -8 
-7 
-6 
-5 
-4 
13 
2 
3 
4 
6 
8 
15 
22 
29 
36 
50 
(64) 2, 78, 120, 
162  
 
Visit Window 
 
N/A 
±1 day 
±3 days 
±7 days 
±3 months 
Cell phenotype and 
Functional Assays 
PBMC 
X 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
Transgene Copies 
(Persistence)  
PBMC 
X 
 
 
 
 
X 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
Cytokine Analyses4 
Serum 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
TGF-β analyses 
Plasma 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
 
X 
 
X 
X 
Anti-lete-cel 
Antibodies 
Serum 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
Week 12, 24 
Month 9, 12, 18, 24, 
30, 36 
Liquid biopsy 
(blood)5 
Plasma 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Tumor Biopsy6 
Biopsy 
X7 
 
 
 
 
 
 
 
 
 
 
 
X8 
 
 
 
X9 
 
1. 
All assessments need to be performed at all visits specified in the Table, up to the visit establishing confirmed PD or study withdrawal or discontinuation. 
2. 
Assessments should match imaging (Body CT/MRI) visits; consequently PK, immunogenicity and Biomarker samples will not be collected at Week 10.  
3. 
All assessments to be performed prior to T-cell infusions 
4. 
If CRS is suspected, serum for cytokine analysis should be collected for research every day for the first week and approximately every other day thereafter until symptoms 
are improving or an alternative diagnosis is confirmed.  
Notes:   
- For scheduled visits where a cytokine sample collection is already requested, there is no need to collect an additional sample from the CRS collection kit that day.  
- Chemistry, hematology, ferritin, coagulation and CRP tests should also be performed locally following same schedule (as per SOA Table 2 footnote 20). 
5. 
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6. 
Biopsies for research are at Baseline, at Week 4, and at disease progression, 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 execution.  
7. 
The Baseline biopsy should be collected anytime within 28 days prior to the start of lymphodepleting chemotherapy. An archived FFPE block from a biopsy taken preferably 
after completion of the participant’s last line of therapy, preferably within 90 days prior to initiating lymphodepleting chemotherapy, may be accepted at the discretion of the 
Medical Monitor (or designee). 
8. 
Week 4 biopsy must be taken preferably between D21-23 if medically visibile, but window for collection is extended until Week 6 visit (D39). 
9. 
Must be taken once at confirmed disease progression if medically feasible. 
 
PBMC=peripheral blood mononuclear cell; PD=progressive disease; Q3M = every 3 months. 

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Table 4 
Substudy 2 Schedule of Activities – Follow-up after Disease Progression 
Substudy 2:  Completion of Interventional Phase Follow-up1 
Time post lete-cel infusion 
Year 1 2  
Year 2  
Year 3  
Year 4  
Year 5  
Years 6-15 3  
Months (1 month = 4 weeks) 
3 
6 
12 
18 
24 
30 
36 
42 
48 
54 
60 
Annually 
Visit window 
± 2 weeks 
± 3 month 
± 6 months 
Safety Assessments 
Medical History and Physical Exam including Weight 4  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mutagenic agents, other investigational agents or anti-
cancer therapies  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events and Serious Adverse Events 5  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 6 
Pregnancy test for WOCBP 7 
<===========================X7===========================> 
Hematology 8 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Serum chemistry 8 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Developmental exam, height4 and puberty assessment in 
pediatric participants 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Laboratory Assessments 
Transgene Copies (Persistence) for safety 
VSV-G DNA (RCL) for safety 8,9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 9 
Other Assessments 
Survival Status 10 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
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. 
Assessments for the Year 1 will be conducted per Table 2 and Table 3 until disease progression. 
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3. Participants who do not have persistence of gene modified cells may be followed remotely during years 6-15. 
4. 
New medical history/medications/chemotherapies.  In pediatric participants height and weight will also be evaluated as a percentile vs national growth charts (based on sex 
and age) and vs genetic height target (expected height based on parental heights) and evaluation will be performed on whether growth is normal or abnormal. 
5. 
Adverse Event and Serious Adverse Event collection is limited to: 
a. 
New malignancies 
b. 
New incidence or exacerbation of a pre-existing neurologic disorder 
c. 
New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder 
d. 
New incidence of a hematologic disorder 
g. 
New incidence of infections (potentially related to gene-modified cell therapy) 
e. 
Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy 
6. 
During years 6-15 of annual follow-up period, AEs and SAEs will be entered in the CRF if reported by the participants or investigator. 
7. 
For Women of child bearing potential (WOCBP), pregnancy testing should be conducted during contraception period only as defined in Section 5.1 of this substudy.  When 
pregnancy testing is performed at visits where hematology sample is collected, blood pregnancy testing will be done.  At visits where hematology sample is not collected, 
urine pregnancy test is acceptable unless serum testing is required by local regulation or IRB/IEC. 
8. 
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. 
9. 
If no gene modified cells are detected for 2 consecutive assessments post infusion, and the participant is 2 years post T-cell infusion, all laboratory assessments including 
persistence and RCL may be discontinued  (Section 9.3.12 of the Core Protocol).  
10. If a participant is contacted between the scheduled visits, the date of last contact should be recorded as an unscheduled visit. 
 
Abbreviations:  
;  EOT=end of treatment; 
 
;  RCL=replication competent lentivirus; VSV-G =vesicular stomatitis virus G protein. 
 
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3 INTRODUCTION 
3.1 
Substudy 2 Background and Rationale 
See Core Protocol Section 3.2 for background information on TCR approach, NY-ESO-1, 
and letetresgene autoleucel (lete-cel, GSK3377794).  
For evaluation of the proposed commercial cell manufacturing process of lete-cel in 
translocation-related sarcomas of synovial sarcoma (SS) and myxoid/round cell 
liposarcoma (MRCLS), this substudy will enroll participants with advanced (metastatic 
or unresectable) SS or MRCLS, who have progressed following treatment with 
anthracycline-based chemotherapy.   
This substudy is intended for registration purposes and will enroll and treat the defined 
number of participants using proposed commercial vector/cell manufacturing process.  
This substudy will use the intended commercial drug product supply once it is available 
and the regulatory document has been amended accordingly to support this supply. 
This substudy has been designed to generate efficacy and safety data for lete-cel in 
participants ≥10 years of age who have previously treated, advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma expressing the 
NY-ESO-1 antigen, who are HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06 allele 
positive.  
Soft Tissue Sarcomas (STS) are a heterogeneous group of connective tissue cancers 
originating from mesenchymal cells and their precursors [Blay, 2014] representing ~1% 
of all cancers in adults worldwide each year and accounting for ~2% of cancer related 
mortality [Singer, 2000; Amankwah, 2013].  STS consists of approximately 50 
histological subtypes [Amankwah, 2013], each with distinct specific characteristics, 
including differential chemo-sensitivity.  
Synovial Sarcoma: 
Synovial sarcoma is a rare malignancy  accounting for approximately 5–10% of all STS 
[Riedel, 2018; Noone, 2018; Brennan, 2016; Honoré, 2015].  The estimated incidence of 
synovial sarcoma is 0.15 per 100,000 in the US and 0.14 per 100,000 in the UK [Wang, 
2017; Stacchiotti, 2018; Brennan, 2016].  Approximately one-third of synovial sarcoma 
occurs in childhood, with a peak incidence in the third decade of life [Ferrari, 2008].  The 
European Paediatric Soft Tissue Sarcoma Study Group conducted a prospective trial 
exploring the incidence and outcome of synovial sarcoma in European patients [Ferrari, 
2015]. From August 2005 to August 2012, 138 patients <21 years old with synovial 
sarcoma were registered from 60 centers in 9 European countries.  The median age at 
diagnosis was 13.7 years.  Of the 138 participants included in this study, 29 (21%) were 
<10 years of age and 109 (79%) were ≥10 years of age.  
Synovial sarcoma is a life-threatening disease with a 5-year overall and cancer-specific 
survival of 50-60% in adult patients [Spillane, 2000; Lewis, 2000; Singer, 2000].  For 
patients presenting with localised disease, standard treatment consists of  a wide surgical 
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for intermediate-high grade tumors and deep tumors >5 cm in diameter. There is no clear 
role of neoadjuvant and adjuvant chemotherapy in high risk patients.   Approximately 
50% of patients with synovial sarcoma will develop metastatic disease [Ten Heuvel, 
2009; Krieg, 2011], and the survival for patients developing metastatic disease is 
12-15 months.  These rates have not improved over the last 2 decades.  
Myxoid/Round Cell Liposarcoma (MRCLS): 
Myxoid/round cell liposarcoma is a subtype of liposarcoma which is associated with 
specific translocations, t (12;16)(q13;p11) or t (12;22)(q13;q12) and represents about 
30-35% of liposarcomas and 5-10% of all adult STS [WHO, 2002]. In the 2013 edition 
of the WHO classification, the term “round-cell liposarcoma” was removed as the 
prognosis and the frequency of metastasis in patients with myxoid liposarcoma is related 
to the degree of cellularity of the tumor rather than the presence of round cells vs spindle 
cells. In addition, the same molecular abnormalities are found in both round-cell and 
spindle-cell morphologies of high-grade myxoid liposarcoma [Doyle, 2014]. Therefore, 
patient diagnoses of “high grade myxoid liposarcoma” and “myxoid/ round cell 
liposarcoma” are equivalent when assessing patients for eligibility for this study, in 
accordance with the WHO 2013 classification [IARC WHO Classification of Tumours, 
No 5, Fletcher 2013]. 
MRCLS commonly presents at an age ranging from 35-55 years. The prognosis varies 
depending on the site of origin, the type of cancer cell, the tumor size, the depth and 
proximity to lymph nodes. MRCLS is prone to recur locally and, dependent on the 
histological grade, one-third of MRCLS cases will become metastatic with multifocal 
synchronous tumor spread to unusual bone and soft tissue locations and lung. 
Myxoid tumor types have relatively favorable prognoses, with an ~80-90% 5-year 
survival rate but tumors with a round-cell component >5% have a poor prognosis with a 
5-year survival rate of ~50-75% because they recur locally and tend to metastasize 
quickly and widely [Smith, 1996]. The median time from diagnosis to metastases is 
35 months. 
Treatment involves the wide surgical excision of the tumor and surrounding tissue; 
high-grade round cell liposarcoma may be treated with pre-operative chemotherapy 
and/or pre- operative or post-operative radiotherapy [NCCN, 2012]. Radiotherapy 
decreases the incidence of local relapse but chemotherapy may not prevent metastatic 
occurrence nor improve survival [Moreau, 2012; Hoffman, 2013]. 
Treatment options for patients with advanced MRCLS have been evaluated. In a 
retrospective analysis of trabectedin in advanced pre-treated MRCLS (in which 46 of the 
51 patients had received anthracycline and ifosfamide either in combination or in 
sequence), a response rate of 51% was reported [Grosso, 2007]. A randomized, 
open-label, active-controlled trial comparing trabectedin (n=345) treatment with 
dacarbazine (n=173) in patients with unresectable, locally advanced or metastatic 
leiomyosarcoma (73%) or liposarcoma (27%) (dedifferentiated, myxoid round cell, or 
pleomorphic) and previous treatment with an anthracycline-containing regimen and one 
additional cytotoxic chemotherapy regimen demonstrated an overall response rate (ORR 
of 7% (CI 4.3, 9.8) with trabectedin, an improvement of median progression-free survival 

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(PFS) of 4.2 (CI 3.0, 4.8) vs 1.5 (CI 1.5, 2.6) months on dacarbazine but no difference in 
overall survival [Yondelis prescribing information 2015]. Eribulin demonstrated an 
improvement in survival (median OS 13.5 vs 11.5 months; HR= 0.768; 95% CI, 0.618; 
0.954) compared with darcarbazine in subjects with liposarcoma and leiomyosarcoma 
who received 2 or more prior lines of therapy. There was no difference in PFS and ORR 
was 3.9% with Eribulin and 4.9% with darcarbazine [Schöffski, 2015]. 
GSK pilot study 208469 is an ongoing open label, Phase I/II pilot study of lete-cel in ≥2L 
myxoid/round cell liposarcoma with NY-ESO-1 positive tumors expressing the antigen in 
≥30% cells at 2+/3+ by immunohistochemistry in subjects with HLA-A*02:01, HLA-
A*02:05 and/or HLA-A*02:06 allele [D’Angelo, 2017]. 
The 208469 protocol completed accrual of the first cohort of 10 treated subjects, treated 
under the initial lymphodepletion regimen.  Treatment with NY-ESO-1c259T-cells in 
MRCLS appears to have an acceptable safety profile consistent with other NY-ESO-
1c259T-cell studies [D’Angelo, 2018a; D’Angelo, 2018c].  Biomarker analyses including 
peak persistence, expression of serum cytokines and of activation markers post infusion 
were reported [Van Tine, 2019a; Van Tine, 2019b]. Final analysis is on-going. 
Standard first-line treatment in patients with advanced, unresectable, or metastatic 
synovial sarcoma consists of anthracycline chemotherapy as single agent or as part of 
combination regimens (e.g., doxorubicin with ifosfamide), which induces responses in 
20-30% [Spurrell, 2005; Sleijfer, 2010; Vlenterie, 2016].  Two years ago, Lartruvo 
(olaratumab) received accelerated FDA approval as 1L treatment in combination with 
doxorubicin for metastatic soft tissue sarcoma (STS) [Lartruvo USPI, 2016].  However, 
recently the confirmatory trial (ANNOUNCE study) did not demonstrate any survival 
benefit nor any improvement in response rates (18%) over standard chemotherapy, and 
therefore, the study failed to meet its primary endpoint [Tap, 2019]. Accordingly, the 
approval for this agent has been recended in the US and EU. A review of the medicine 
has now been initiated by the regulators (US/EU) and its approval status has been 
rescinded.   
Dacarbazine is also authorised in some countries in the EU for the advanced soft tissue 
sarcoma as a part of combination chemotherapy and dacarbazine monotherapy response 
rates range from 4% to 6% in prospective studies [Dacarbazine SmPC, 2015].   
After failure of anthracycline-based chemotherapy, few options exist for patients to be 
treated in second-line setting.  These patients have poor clinical outcomes with currently 
available treatments.    
Pazopanib (Votrient) is authorised by EMA and by FDA for treatment of patients with 
metastatic STS who have failed prior chemotherapy.  However, response rates in synovial 
sarcoma are low, ranging from 4% to 13%, and this offers no improvement in overall 
survival [Votrient SmPC, 2018; Votrient USPI, 2017]. Trabectedin (Yondelis) is 
approved in the EU for patients with advanced soft tissue sarcoma, after failure of 
anthracyclines and ifosfamide, or who are unsuited to receive these agents. Trabectedin 
(Yondelis) is also approved in the US for select histological subtypes of STS 
(liposarcoma and leiomyosarcoma).  Efficacy data are based mainly on liposarcoma and 
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[Yondelis SmPC, 2012; Yondelis USPI, 2015].  While the registration studies with 
trabectedin did not include synovial sarcoma patients, in a Phase 2 study, synovial 
sarcoma patients treated with trabectedin demonstrated an ORR of about 10% 
[Sanfilippoa, 2015].  Trabectedin has also not been shown to improve survival in any 
sarcoma population.  
Thus clear unmet medical need exists for treatment options in this population. 
3.2 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks as well as 
reasonably expected adverse events of lete-cel (GSK3377794) may be found in the 
Lete-cel Investigator’s Brochure. 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. This 
section outlines the potential benefits, risks and the mitigation strategy for this study. 

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3.2.1 Risk Assessment  
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 
• 
Hyponatraemia 
• 
Neurotoxicity 
Cases were reported with both drugs. 
Please refer to the prescribing information of fludarabine 
and cyclophosphamide and Section 12.7. 
• 
Autoimmune haemolytic anaemia 
• 
Autoimmune thrombocytopenia 
• 
Decreased vision 
• 
Peripheral neuropathy 
Cases were reported with fludarabine 
Please refer to the prescribing information of fludarabine. 
Lete-cel (GSK3377794) 
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 
(Core Section 9.3.6 and Section 12.7.5).   
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 (Core Section 
9.3.7).  
Central lines should be closely monitored for infection 
(Core Section 12.7.2).  
Systemic fungal infections are excluded (Substudy 2 
Exclusion 9)  
Monitoring of risk of increased cardiac toxicity with the 
use of anti-microbials (Core Section 12.7.2.6) 
Cytokine release syndrome (CRS) 
Identified risk due to TCR T-cell infusion considered 
adverse event of special interest (AESI) 
Participants with pre-existing autoimmune disorders are 
excluded (Section 6.2 of this Substudy). Management for 

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Risks of Clinical Significance (Identified or Potential) 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
CRS is described in Section 12.7.5.  Events  Grade ≥3 
must be reported as SAEs and submitted to GSK within 
24 hours. 
 
 
 
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 6.2). Management for GVHD is 
described in Section 12.7.6. 
Haematopoietic cytopenias (including 
Pancytopenia/aplastic with bone marrow failure/anemia) 
Identified risk associated with lymphodepletion 
chemotherapy and TCR-T cell infusion considered an 
AESI 
Participants with cytopenias are excluded (Section 6.2 of 
this Substudy). Management for pancytopenia is 
described in Section 12.7.7.  
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 and 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 12.7.3. 
Hypersensitivity  
Identified risk due to TCR-T cell infusion. Hypersensitivity 
reactions (including anaphylaxis) may be due to the 5% 
(v/v) DMSO inTCR-T formulation. 
Participants with history of allergic reactions to any 
agents used in the study are excluded. See Section 6.2 
for details. 
Participants will be premedicated against potential 
infusion reactions with antihistamines on the day of 
TCR-T cell infusion. See Section 7.1.4 for details. 
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 6.2 for details. 
Lymphodepletion dose will be modified in participants 
with potentially reduced bone marrow reserve. See 
Section 7.1.3 for details. 
Participants with active infection are excluded. 
Participants with CMV seropositivity will be monitored 
regularly for viral reactivation. For HSV/VZV prophylaxis, 
participants will receive acyclovir or valacyclovir for one 
year from LD.  Prophylaxis will be given to those with 
HBV seropositivity. See Section 6.2 and Core Section 
12.7.2 for details. 

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Risks of Clinical Significance (Identified or Potential) 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Neutropenia (including fatal neutropenia) 
Identified risk associated with lymphodepletion 
chemotherapy and TCR T-cell infusion 
Patients are excluded based on absolute neutrophil 
counts (Section 6.1.1). Investigator must discuss with 
Medical Monitor or designee to determine the need for 
dose modification of the lymphodepletion regimen in 
participants at risk (Section 7.1.3). 
G-CSF to be administered in accordance with ASCO 
guidelines or institutional practice (Section 7.1.3).  
Dose modifications are included for fludarabine and 
cyclophosphamide (Section 7.1.3) 
Grade 4 Neutropenia events lasting ≥28 days must be 
submitted to GSK within 24 hours (Core Section 9.4.7). 
Decreased Vision 
Potential risk: There was a report of decreased vision in a 
patient who received lete-cel infusion following 
lymphodepletion with fludarabine and cyclophosphamide. 
Dose reductions for fludarabine for renal impairment are 
included (Section 7.1.3). Investigator must discuss with 
Medical Monitor or designee to determine the need for 
dose modification of the lymphodepletion regimen in 
patients at risk (Section 7.1.3) 
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 6.2 of this Substudy).  
Neurologic consultation is required for participants 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) 
Identified risk associated with TCR T-cell infusion 
Routine monitoring and testing as clinically required. 

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Risks of Clinical Significance (Identified or Potential) 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Immune Effector Cell-Associated Neurotoxicity Syndrome 
(ICANS) 
Potential risk associated with inflammation in the brain 
following TCR 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 6.2 of this Substudy). Monitoringcriteria for 
ICANS are described in Section 12.7.8. 
Insertional oncogenesis 
Potential risk in T cells transduced with lentiviral vector
 
 
Routine PV. To be monitored in the LTFU 
Protocol.(208750) or LTFU portion of this study. 
Monitoring to follow the recommendations set forth in the 
FDA guidance, 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. 
Samples will be tested for the presence of VSV-G DNA 
copies (Section 9.3.11 of the Core Protocol). 
On/Off-Target Off-Tumor Risks 
Potential risk associated with use of lentivirus  
To be monitored in this protocol and in the LTFU 
Protocol. Protocol includes eligibility criteria (Section 6.1 
and Section 6.2 of this Substudy), routine PV, and 
management strategies as appropriate to limit, diagnose, 
characterize and treat toxicities related to potential risks 
(Section 12.7). 
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. 
 

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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. 
The known safety profile of lete-cel is based on 166 enrolled and 125 treated participants 
as of 27 January 2021 as decribed in Lete-cel Investigator’s Brochure.  The most 
commonly reported treatment-emergent adverse events which occurred in 50% of 
participants following lete-cel infusion were leukopenia/WBC decreased (81%), 
neutropenia/neutrophil count decreased (80%), nausea (78%), anemia/RBC decreased (78%), 
thrombocytopenia/platelet count decreased (77%), fatigue (70%), pyrexia (66%), diarrhea 
(57%), and lymphopenia/lymphocyte count decreased (54%). The most common Grade 3 
and 4 AEs which occurred in 20% of participants following lete-cel infusion were 
leukopenia/WBC decreased (78%), neutropenia/neutrophil count decreased (74%), 
thrombocytopenia/platelet count decreased (62%), anemia/RBC decreased (58%), 
lymphopenia/lymphocyte count decreased (52%), febrile neutropenia (36%), and 
hypophosphatemia (27%). These AEs are consistent with expected immediate adverse 
events after lymphodepletion chemotherapy.  
Across all studies, 47 (38%) participants had SAEs considered by the Investigator to be 
related to study treatment.  Treatment-related SAEs occurring in more than 2 subjects 
following lete-cel infusion were: cytokine release syndrome (CRS) (15%), pyrexia (6%), 
neutropenia/neutrophil count decreased (5%), rash/rash maculo-papular (4%), 
thrombocytopenia/platelet count decreased (4%) and febrile neutropenia (3%).  For the 
16 participants who received a second infusion, five treatment related SAEs were 
reported after second T-cell infusion, which included 1 (6%) case each of CRS, 
cytomegalovirus infection, embolism, febrile neutropenia, and rash/rash maculo-papular. 
Among the adverse events of special interest, 
1. CRS was reported in 52 (42%) cases (of 125) as of 27 January 2021 across all lete-cel 
clinical trials.  Of these, there was 1 participant with Grade 4, 9 with Grade 3, 21 with 
Grade 2, and 19 with Grade 1.  There were a total of 19 cases of CRS that were 
reported as SAEs. All 19 SAEs resolved in 2 weeks or less. Five cases of the 19 
reported SAEs were treated with tocilizumab.  Median duration of the CRS events 
was 8-9 days (range 1-28 days).  
2. A total of 7 cases  (of 125) of GvHD have been reported of which 3 cases were  
reported as an SAE.  All cases were Grade 1-3, occurred in patients with multiple 
myeloma, and completely recovered with supportive treatment.  Six (6) out of 7 
participants with reported GvHD were from Study 209393 (formerly ADP-01411) 
which required an allogeneic stem cell transplant prior to the T-cell infusion. 
3. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), originally 
named as ‘encephalopathy’ was reported in 1 case with multiple brain metastasis, that 
was transient, and resolved in 2 days with supportive care. 
4. Five (5%) participants had reported treatment-emergent AE of pancytopenia (3 
participants: 2 with Grade 3, and 1 with Grade 1) or bone marrow failure (2 
participants: 1 with Grade 5 fatal, and 1 with Grade 2) (refer to Lete-cel Investigator’s 
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5. GBS has been reported in 2 participants, both of which completely recovered with 
standard gamma globulin treatment. 
 
To date, none of the analyses for insertional oncogenesis and replication competent 
lentivirus have been positive. 
Pediatric Participants 
This substudy allows pediatric participants 10 years of age or older.  Previously, 2 
pediatric participants have been treated in Study 208466 (ADP-04511).  The first was a 
15-year-old white hispanic female treated in Cohort 3 of the study in which  a milder, 
cyclophosphamide only containing lymphodepletion regimen was used prior to T-cell 
infusion; and this participant achieved PR after the first infusion, progressed 9 months 
following treatment, and received a second infusion and achieved stable disease, and she 
died in September 2018, nearly 2 years after initial treatment with GSK3377793.  The 
second participant was a 12-year-old white female enrolled into Cohort 2; which included 
participants with tumors that have low NY-ESO-1 expression levels and received a high 
dose cyclophosphamide and fludarabine containing lymohodepletion regimen prior to 
lete-cel infusion.  This participant achieved SD as her best response, subsequently 
progressed 8 months following lete-cel treatment, and  died 11 months after lete-cel 
treatment. 
As of 24 February 2019, a total of 29 AEs were reported for both pediatric participants as 
definitely or probably related to lete-cel.  A total of 14 Grade 4 AEs (5%) were reported, 
none of which were reported as being related to lete-cel.  The first participant 
experienced 2 SAEs:  acute cholecystitis and CMV infection.  Neither event was reported 
as related to study drug, and both events resolved.  There were no SAEs reported by the 
second participant.  There were 5 events of cytokine release syndrome reported.  All 
events were Grade 1 or 2, and all have resolved.  Overall, the observed AEs are similar to 
those observed in adult participants treated with lete-cel, with the vast majority consistent 
with events observed as a result of the lymphodepletion regimen. 
3.2.2 Benefit Assessment 
As of 27 January 2021, 125 participants have been treated with lete-cel.  Objective 
responses have been observed in the ongoing synovial sarcoma study 
(208466/ADP-04511) and in multiple myeloma post-autologous transplant study 
(209393/ADP-01411)  [Lete-cel Investigator’s Brochure].  
In Cohort 1 of study 208466 (which is similar to the treatment regimen and participant 
population proposed for this protocol), a single infusion of GSK3377794 demonstrated an 
encouraging response rate of 50% (6/12 participants, 95% CI: 0.21-0.79), with an 
encouraging durability of response of 30.9 weeks (95% CI: 14-72) and one participant 
demonstrating a complete response.  Importantly, the responses induced after T-cell 
infusion were associated with a median survival of approximately 24 months, which 
represents a marked improvement over a median survival of 12 months in relapsed 
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Objective responses have been observed in 21 (84%) out of 25 of participants in multiple 
myeloma after autologous transplant (study 209393/ADP-01411) [Lete-cel Investigator’s 
Brochure]. 
Additionally, studies conducted by the NCI Surgery Branch have demonstrated that 
adoptive immunotherapy using T cells genetically engineered to recognize NY-ESO-1 
following lymphodepletion led to objective antitumor responses in 4 of 6 patients (67%) 
[Robbins, 2011] and 11 of 18 patients (61%) [Robbins, 2015] with synovial sarcoma. The 
estimated overall three and five-year survival rates for patients with synovial sarcoma 
were 38% and 14%, respectively [Robbins, 2015]. 
More recently, responses have also been observed in patients with myxoid round cell 
liposarcoma (MRCLS , study 208469) [D’Angelo, 2018a], thereby demonstrating 
encouraging clinical activity of lete-cel across multiple NY-ESO-1 and LAGE-1a 
expressing tumor types.   
3.2.3 Overall Benefit/Risk Conclusion 
Treatment with letetresgene autoleucel (lete-cel, GSK3377794) has been well tolerated in 
103 participants with different tumor types [Lete-cel Investigator’s Brochure].  Toxicities 
associated with engineered T-cell infusion, specifically CRS, have been observed in less 
than one-third of the treated participants, were of low grade, and managed with 
supportive care in the majority of cases.  To date, lete-cel has demonstrated an AE profile 
that has generally been manageable and acceptable in the context of benefit/risk 
assessment.   
In view of the clinical responses observed in relapsed, refractory patients, and as per the 
risk asseement presented above, the benefit/risk ratio supports continued development of 
lete-cel in NY-ESO-1-positive synovial sarcoma, myxoid/round cell liposarcoma and 
other solid tumors of high unmet medical need. 
4 OBJECTIVES AND ENDPOINTS  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of lete-cel in HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 
participants with NY-ESO-1 positive advanced 
synovial sarcoma or myxoid/round cell 
liposarcoma 
Overall Response Rate (ORR) per RECIST 
v1.1 by central independent review in the full 
analysis set of participants treated with 
commercial vector supply and cell 
manufacturing processes 
Secondary - Efficacy 
To further evaluate the efficacy of lete-cel in 
HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 participants with NY-ESO-1 
positive advanced synovial sarcoma or 
myxoid/round cell liposarcoma 
• Overall Response Rate (ORR) per  
RECIST v1.1 assessed by Investigators  
• Time to Response (TTR) 
• Duration of Response (DoR) 
• Disease Control Rate (DCR) 

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Objectives 
Endpoints 
 
• Progression Free Survival (PFS) 
• Overall Survival (OS) 
Secondary - Safety 
To evaluate the safety and tolerability of 
lete-cel in HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 participants with NY-ESO-1 
positive advanced synovial sarcoma or 
myxoid/round cell liposarcoma 
• Frequency and severity of Adverse events 
(AEs), serious adverse events (SAEs) and 
AEs of special interest (AESI; as defined 
in protocol) 
• Laboratory parameters 
• Replication Competent Lentivirus (RCL) 
• Instances of Insertional oncogenesis (IO) 
To evaluate potential immune response to 
lete-cel.  
• Presence and titers of anti-GSK3377794 
antibodies over time 
Secondary - Pharmacokinetics 
To characterize in vivo cellular PK profile 
(levels, expansion, persistence) of 
NY-ESO-1 specific (c259) T cells 
• Maximum transgene expansion (Cmax) 
• Time to Cmax (Tmax) 
• Area under the time curve from zero to 
time t AUC(0-t), as data permit 
Exploratory / Other 
CCI

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Objectives 
Endpoints 
 
AE/s = adverse event/s; AESI/s: adverse event/s of special interest; AUC (0-t) = area under the time curve from zero to 
time t; Cmax = maximum concentration; DOR = duration of response; HLA = human leukocyte antigen; ORR = overall 
response rate; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria In Solid 
Tumors; SAE = serious adverse event; Tmax = Time to Cmax; TTR = Time to Response. 
 
CCI

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5 STUDY DESIGN 
5.1 
Overall Design  
Study 208467 Substudy 2 is a multicenter, open-label study evaluation of the safety and 
efficacy of letetresgene autoleucel (lete-cel, GSK3377794) in participants with synovial 
sarcoma or myxoid/round cell liposarcoma. 
For evaluation of lete-cel proposed commercial cell manufacturing process in synovial 
sarcoma and myxoid/round cell liposarcoma, this substudy will enroll participants with 
advanced (metastatic or unresectable) NY-ESO-1+ synovial sarcoma or myxoid/round 
cell liposarcoma who have progressed following treatment with anthracycline-based 
chemotherapy.  This substudy will consist of at least 60 participants dosed with the 
intended commercial vector supply and manufacturing processes who have completed a 
minimum of 6-month follow-up or have died or have withdrawn early following lete-cel 
treatment. This substudy will enroll the number of participants needed to obtain 60 
treated with intended commercial vector supply and manufacturing process for the 
primary analysis population (approximately 72). 
Participants identified by the Investigator as possible candidates for the substudy must 
have completed HLA-typing and preliminary target expression screening for NY- ESO-1 
antigen expression; participants with the HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 alleles whose tumor expresses the NY-ESO-1 antigen above the cut-off 
according to the applied immunohistochemistry assay are eligible to undergo further 
screening for this study.  
It is intended that the data from Substudy 2 will be used to support registration of lete-cel 
in synovial sarcoma and myxoid/round cell liposarcoma.  T cells infused to participants 
within Substudy 2 to support this registration will be generated using the intended 
commercial vector supply and cell manufacturing processes (application supplement to 
be submitted).   Substudy 2 may initiate screening prior to the availability of the intended 
commercial vector supply and cell manufacturing process.   
This study allows that participants weighing greater than or equal to 40 kg and identified 
as eligible for treatment prior to availability of the intended commercial vector supply 
and cell manufacturing processes may receive treatment with the clinical drug product 
supply.  Any such participants will be counted separately to ensure that at least 60 
participants are treated with intended commercial drug product supply for the intended 
analysis population PEAP. Drug product supply type (‘clinical’ vs ‘commercial’) will be 
recorded in the CRF as part of the route of synthesis. 

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Figure 1 
Substudy 2 Design 
 
* Approximately 72 out of 87 will be enrolled on intended commercial drug product supply in 
order to ensure that at least 60 participants will receive lete-cel using intended commercial 
vector supply and manufacturing process. 
** The lymphodepleting regimen is to be adjusted as described in Section 7.1.3 of this Substudy. 
Participants will undergo stepwise enrollment on the study followed by treatment 
according to defined phases within the study (See Figure 2 Participant Journey Schema 
below) which will include: 
Part 1: Screening 
1) Target expression screening for the presence of HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 type and tumor expression of NY ESO-1, 
(Note: If a participant was previously tested for HLA and/or NY-ESO-1 expression under a different 
GSK-sponsored protocol, testing of HLA and/or NY-ESO-1 for 208467 may not be required 
dependent on the test platform(s) used and whether they meet the 208467 protocol requirements [see 
Section 6.3 of the Core Protocol]) 
2) Leukapheresis screening phase to determine eligibility for undergoing leukapheresis 
beginning up to 28 days prior to the day of leukapheresis,  
Part 2: Leukapheresis/Manufacture 
3)  Leukapheresis procedure,  
(Note: leukapheresis may have been performed under another GSK-sponsore protocol or substudy 
of this protocol)   
Part 3: Lymphodepletion/Treatment 
4) Treatment fitness assessment and eligibility confirmation including confirmation of 
disease progression from last line of treatment, per RECIST v1.1,  
5) Interventional phase including Lymphodepletion from Days -7 to -4, lete-cel infusion 
on Day 1 and follow-up until the end of study (as defined in Section 5.3 of this 
Substudy),  

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(Note: TCR engineered T-cell may have been manufactured under another GSK-sponsored protocol 
or substudy of this protocol)   
Part 4: Long-Term Follow-Up (LTFU) 
6) Long-term follow-up phase for up to 15 years from the date of lete-cel infusion.   
 
Figure 2 
Participant journey Schema 
 
* The lymphodepleting regimen is to be adjusted as described in Section 7.1.3 of this Substudy. 
Part 1: Screening  
See Core Protocol Section 5 of this Substudy for complete details of screening approach. 
Inclusion / exclusion criteria are listed in Section 6. 
In this substudy enrolling participants with advanced (metastatic or unresectable) 
synovial sarcoma or myxoid/round cell liposarcoma, participant screening may start at 
any time after diagnosis of advanced disease.  Participants may also be screened upon 
relapse of metastatic disease.   
Disease progression may be present but is not mandatory for screening. Screening will 
consist of two phases: target expression screening and leukapheresis eligibility screening. 
For target expression screening, once informed consent has been obtained, 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 expression will also be evaluated on 
tumor tissue from a formalin-fixed and paraffin-embedded (FFPE) archival (most recent 
preferred) or fresh biopsy (see Tumor biopsies section below for more details). 
HLA-typing and tumor antigen expression testing should be performed sequentially 
(considering the expected >50% attrition with HLA) but may also be performed in 
parallel at the discretion of the Investigator. 
Note: target expression Screening may also be performed under a separate Screening 
protocol such as athe GSK molecular disease characterization initiative (MDCI) study 
(213299), or under other NY-ESO-1/LAGE-1a T-cell protocols. 
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 
28 days prior to the day of the scheduled leukapheresis procedure.   

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Supportive chemo- or radio-therapy may be administered between leukapheresis and 
lymphodepletion if a participant cannot be treatment-free.  Mandatory washout periods 
prior to start of NY-ESO-1-Specific (c259) T-cell infusion must be respected (See 
Section 6.2 of this Substudy). 
Part 2: Leukapheresis/Manufacture 
The initiation of leukapheresis procedure constitutes enrollment in the study. The 
collected T  cells will be sent for manufacturing. 
See Core Protocol Section 5 for complete details of leukapheresis and manufacture 
approach, including use of supportive chemo- or radio-therapy between leukapheresis 
and the start of lymphodepletion. 
Part 3: Lymphodepletion/Treatment 
See Core Protocol Section 5 for complete details of lymphodepletion and treatment 
approach.  For this substudy, confirmation of disease progression per RECIST v1.1 is 
required prior to lymphodepletion. 
Part 4:  LTFU 
See Core Protocol Section 5 for complete details of the long term follow up study. See 
end of substudy definition in Section 5.3 of this Substudy for details of participant 
transition to LTFU.  
Tumor Biopsies 
Archival tumor FFPE or fresh biopsy from a representative tissue is required from all 
participants to be used for antigen expression (NY-ESO-1) eligibility screening.  If 
multiple archival samples are available, then the most recent archival sample should be 
used. If fresh biopsy is performed, then this tissue should be used: 
a. Formalin-fixed paraffin embedded (FFPE) tumor specimens in paraffin blocks are 
preferred. A minimum of 20 unstained slides (5-micron serial fresh cut) is required 
as an alternative. Patients with fewer than 20 unstained slides may still be considered 
for screening following discussion with Medical Monitor 
b. Acceptable specimens include core needle biopsies from deep tumor tissue 
(minimum three cores x 18G or larger and approximately 1 cm long) or excisional, 
incisional punch or forceps biopsies for cutaneous, subcutaneous or mucosal lesions 
c. Fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, 
and lavages are not acceptable 
d. Tissue should have been obtained from 1 year of consent and be of good quality on 
the basis of total and viable tumor unless discussed with Medical Monitor 
 
A pre-treatment tumor sample collected within 28 days prior to initiating 
lymphodepletion is required for Substudy 2.  This biopsy will be used as baseline for 
biomarker analyses.  If it is not feasible to obtain a fresh biopsy, an archival tumor biopsy 
(FFPE block) taken preferably after completion of the participant’s last line of therapy, 

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preferably within 90 days prior to initiating lymphodepleting chemotherapy, may be 
accepted at the discretion of the Medical Monitor (or designee).  For participants who 
already provided a fresh biopsy for antigen expression and did not receive any bridging 
or standard of care intermediate anti-cancer therapy, the screening biopsy will be used for 
baseline.   
Additional biopsies will also be collected at Week 4 and at disease progression.  In 
exceptional cases, where such biopsies cannot be collected, these may be deferred in 
consultation with the sponsor.  These cases include participants for whom there is no 
safely accessible tumor tissue; or if conducting such a biopsy would compromise the 
medical condition of the participant; or if other clinical considerations preclude conduct 
of the biopsy procedure.  In addition to the indicated collection times, tumor biopsies can 
be obtained at any time during the study execution. 
See Core Protocol Section 9.9.1 for other biopsy considerations. 
5.2 
Number of Participants 
Substudy 2 will enroll approximately 87 participants previously treated with 
anthracycline-based regimen for advanced (metastatic or unresectable) synovial sarcoma 
or myxoid/round cell liposarcoma, including : 
• 
Approximately 15 participants expected to receive the clinical drug product supply; 
• 
Approximately 72 participants planned to receive intended commercial drug product 
supply in order to ensure that at least 60 participants will receive letetresgene 
autoleucel (lete-cel, GSK3377794) using commercial vector supply and 
manufacturing process and who have completed a minimum of 6-month follow-up or 
have died or have withdrawn early following treatment.  
 
This study allows pediatric participants 10 years of age or older.   
5.3 
End of Study Definition 
5.3.1 End of Substudy for Individual Participants 
a) End of Interventional phase for individual participants 
A participant is considered to have completed the Interventional phase of the Substudy 
when one of the following occurs (whichever is sooner): 
• 
Participant has confirmed disease progression (also need to ensure that participant is 
followed for SAEs through 90 days following T-cell infusion, or 30 days following 
T-cell infusion if the participant initiates new anticancer therapy, whichever is 
earlier); 
• 
Participant dies; 
• 
Interventional phase ends for the Substudy (See Section 5.3.2 of this Substudy). 
 
If participant withdraws consent or is withdrawn for other reasons prior to end of their 
Interventional phase, they will be considered early withdrawal. 

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b) End of Follow-up phase for individual participants 
All participants who are alive at the end of the Interventional phase will enter a follow-up 
phase and will remain in the Follow-up phase until one of the following occurs 
(whichever is sooner):   
• 
Participant dies; 
• 
Substudy ends (See Section 5.3.2 of this Substudy). 
 
If participant withdraws consent or is withdrawn for other reasons prior to end of their 
Follow-up phase, they will be considered early withdrawal. 
All participants alive after the end of the Follow-up phase, will be followed in a separate 
long term follow up (LTFU) protocol (GSK study 208750) for observation of delayed 
AEs and survival for a duration of 15 years post-T-cell infusion in accordance with FDA 
[FDA, 2020a] and EMA guidance [EMA, 2009].  If LTFU protocol is not yet available at 
the particular clinical site, participants may be temporarily followed per LTFU schedule 
under this protocol (Section 2 Table 4 of this Substudy) until LTFU protocol becomes 
available. The transfer of any individual participant to the LTFU protocol 208750 should 
not exceed 6 months.       
5.3.2 End of Substudy 
a) End of Interventional phase: 
The interventional phase ends when the total number of participants dosed will have 
confirmed disease progression or died or have been lost to follow-up or withdrawn early. 
b) End of Follow-up phase: 
The Follow-up phase ends when 70% of the total number of participants who received at 
least the minimum target dose of lete-cel (mITT) have died or have been lost to follow-
up, to allow for mature data on overall survival (OS). 
All participants alive after the end of the Follow-up phase of the Substudy, will be 
followed in a separate long term follow up (LTFU) protocol (GSK study 208750) for 
observation of delayed AEs and survival for a duration of 15 years post-T-cell infusion in 
accordance with FDA [FDA, 2020a] and EMA guidance [EMA, 2009].  If LTFU 
protocol is not yet available at the particular clinical site, participants may be temporarily 
followed per LTFU schedule under this protocol (Section 2 Table 4 of this Substudy) 
until LTFU protocol becomes available. The transfer of any individual participant to the 
LTFU protocol 208750 should not exceed 6 months.   
c) End of Substudy: 
The substudy ends when all treated participants have transferred to the separate LTFU 
protocol (GSK study 208750), declined consenting to the LTFU protocol, completed 
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5.4 
Scientific Rationale for Substudy Design 
This substudy has been designed to generate efficacy and safety data for lete-cel in 
participants ≥10 years of age who have previously treated, advanced (metastatic or 
unresectable) synovial sarcoma or myxoid/round cell liposarcoma, whose tumor 
expresses the NY-ESO-1 antigen and who are HLA-A*02:01, HLA-A*02:05, or 
HLA-A*02:06 allele positive. The single arm design has taken into consideration that:  
1. Synovial sarcoma and myxoid/round cell liposarcoma are rare, life-threatening 
diseases of which the target population for lete-cel is a small subset.  
2. After failure of anthracycline-based chemotherapy, currently available therapies to 
treat synovial sarcoma or myxoid/round cell liposarcoma do not provide adequate 
disease control and no approved products for this targeted population exist.  
3. Compelling data from pilot Studies 208466 (for synovial sarcoma) and 208469 (for 
myxoid/round cell liposarcoma) indicate that lete-cel may offer a meaningful 
advantage over available 2L therapies.  
 
This substudy will enroll approximately 72 participants to support the primary analysis 
consisting of at least 60 participants treated with intended commercial drug product 
supply who have completed a minimum of 6-months follow-up or have died or have 
withdrawn early following lete-cel treatment. The over-enrollment takes into account an 
estimated 5-10% dropout to achieve 60 participants for the PEAP population.  
5.5 
Justification for Dose  
5.5.1 Justification of Lymphodepleting Regimen 
Based on prior experience with lete-cel in participants with synovial sarcoma and 
melanoma, where similar lymphodepletion regimen was associated with optimal 
responses [Merchant, 2015; D’Angelo, 2018b], the lymphodepleting regimen for 
participants treated under protocol amendments 1-5 has been to administer fludarabine, 
30 mg/m2/day × 4 days (Day -7 to -4) and cyclophosphamide, 1800 mg/m2/day × 2 days 
(Day -5 to -4), with lete-cel infusion on Day 1.  
Based on additional safety data (prolonged neutropenia; fatal neutropenia [see Lete-cel 
Investigator’s Brochure] and modelling data, to further optimize lymphodeletion and 
reduce potential for acute and prolonged cytopenias while also minimizing impact on 
efficacy, the cyclophosphamide cumulative dose is modified from 3600 to 2700 mg/m2. 
The fludarabine dose remains unchanged.  
This regimen was previously used in Study 208469 (Cohort 2) in MRCLS, and the dosing 
is currently in use for NSCLC participants in Study 208471 (slightly different schedule).  
The refined lymphodepleting regimen for participants treated as of protocol amendment 6 
is as follows: 
• 
Fludarabine, 30 mg/m2/day × 4 days (Day -7 to -4) and cyclophosphamide, 
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Rules for further dose reductions on cyclophosphamide are also adapted by applying the 
same 33% reduction as previously used (in protocol amendments 1-5) as follows: 
• 
As of protocol amendment 6, a standard reduction for cyclophosphamide dose  
(in mg/m2) of 2700 = 900 × 3 days is to use 1800 = 600 × 3 days. 
 
5.5.2 Justification of lete-cel (GSK3377794) Dose 
A dose range of 1×109 to 8×109 total  transduced T cells had initially been chosen as it 
was within the cell dose in which clinical responses were observed without significant 
toxicity in previous clinical trials and which was logistically feasible to manufacture 
(based on initial assumptions related to yield).   
At this target dose, lete-cel has resulted in objective responses 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 protocol amendments 1 through 5. 
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 two 
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: the genetically 
engineered T cells with a TCR targeting human papilloma virus-associated epithelial 
cancer HPV-16 E7 (E7 TCR) were reported in a first-in-human, phase 1 clinical trial of 
12 participants, to not show any dose limited by toxicity with a maximum dose of 
100 × 109 engineered T cells administered [Nagarsheth, 2021]. 
Since no dose-toxicity relationship has been established todate on 125 patients dosed with 
lete-cel (see Lete-cel Investigator’s Brochure), 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 amendments 6, 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 SRT.  

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6 STUDY POPULATION 
Inclusion/Exclusion criteria for the registration substudy are grouped into 3 parts and 
eligibility screening will take place in the following 3 steps: 
• 
Target Expression Screening: A set of criteria permitting participants’ blood to be 
screened for HLA-type and an archival or fresh tumor sample to be screened for the 
expression of NY-ESO-1. 
• 
Leukapheresis Eligibility Screening:  To be fulfilled prior to performing 
leukapheresis procedure. 
• 
Treatment eligibility screening:  To be fulfilled prior to starting lymphodepletion. 
– Treatment fitness (for safety): To be evaluated prior to commencing 
lymphodepleting chemotherapy and administration of lete-cel (GSK3377794). 
 
6.1 
INCLUSION CRITERIA 
6.1.1 
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) only if all of the following criteria apply: 
1. Capable of giving signed informed consent including compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in the 
protocol. For participants <18 years of age (or the legal minimum age in the relevant 
country) their legal guardian must give informed consent. Pediatric participants will 
be included in age-appropriate discussion in order to obtain assent. 
2. Participant must be ≥10 years of age at the time of signing the informed consent. 
Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg.  
For participant scheduled to receive intended commercial drug product supply and 
weighing <40kg, the Investigator must also consult with the Medical Monitor prior to 
inclusion. 
3. Participant has a diagnosis of synovial sarcoma or myxoid/round cell liposarcoma, 
confirmed by local histopathology with evidence of disease-specific translocation. 
Note: Evidence of a relevant disease-specific translocation is required at latest prior to 
leukapheresis (Inclusion 8). 
4. Participant has advanced (metastatic or unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma.  Unresectable refers to a tumor lesion in which clear 
surgical excision margins cannot be obtained without leading to significant functional 
compromise. 
5. Male or female. Contraception requirements will apply at the time of leukapharesis 
and treatment. 
6. A representative tumor tissue specimen (archived or fresh biopsy) with associated 
pathology reportshould be available to perform NY-ESO-1 antigen expression 
analysis, unless a recent NY-ESO-1 expression test result from the same designated 

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central laboratory, following the same procedures, has already been performed under 
a separate GSK-sponsored protocol or under another substudy.  For guidance on 
acceptable specimen material see Tumor Biopsies under Section 5.1. 
 
6.1.2 
Leukapheresis Eligibility Screening 
Prior to finalizing participant treatment plan, please note that bridging/standard of care 
anti-cancer therapy is allowed under Section 7.1.2 conditions but that there are washout 
requirements prior to leukapheresis and prior to lymphodepletion. Additional 
considerations should be given to accumulated radiotherapy prior to lymphodepletion.  
All the Inclusion Criteria in Section 6.1.1 must apply again prior to leukapheresis.  In 
addition, the following criteria must also apply: 
7. Life expectancy ≥24 weeks 
8. Participant has confirmed evidence of a relevant disease-specific translocation per 
below: 
• 
For synovial sarcoma, presence of a translocation involving chromosome 18 
(SYT gene) and/or chromosome X (SSX1, SSX2 or SSX4 genes); 
• 
For myxoid/round cell liposarcoma, presence of a translocation involving 
chromosome 12 (DDIT3 gene) and/or chromosome 16 (FUS gene) and/or 
chromosome 22 (EWSR1 gene). 
Note: Methods, such as, but not limited to, fluorescence in situ hybridization (FISH) 
assay or Next Generation Sequencing (NGS) or Immuno HistoChemistry (IHC) 
using fusion-specific antibody are commonly used to detect translocations. 
9. Participant is either currently being treated with or has completed at least one 
standard-of-care treatment including anthracycline-containing regimens 
(e.g., doxorubicin alone, doxorubicin with ifosfamide) for advanced (metastatic or 
inoperable) disease. Participants who are intolerant to anthracycline may receive 
ifosfamide alone unless intolerant to or ineligible to receive ifosfamide. Participants 
who received anthracycline-based therapy in the neoadjuvant/adjuvant setting and 
progressed will be eligible.  
NOTE:  Participants "intolerant" to a chemo-radiotherapy are those who EITHER are ineligible to 
receive chemotherapy due to poor functional status OR have developed a Grade ≥3 toxicity 
necessitating discontinuation of chemotherapy or dose modification, and/or unplanned 
hospitalization to alleviate effects of toxicity [Van Abbema, 2019]. 
NOTE:  Participants with advanced (metastatic or unresectable) disease can also undergo 
leukapheresis prior to initiating first line or standard therapy.   
10. Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 
alleles by a validated test in a designated central lab prior to leukapheresis. 
 
NOTE: If a participant was previously tested for HLA type under a different GSK-sponsored 
protocol, testing of HLA type for 208467 may not be required dependent on the test platform(s) used 
and whether they meet the 208467 protocol requirements [see Section 6.3 of the Core Protocol]). 

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11. Participant’s tumor has been pathologically reviewed by a designated central 
laboratory with confirmed positive NY-ESO-1 expression defined as 30% of cells 
that are 2+ or 3+ by immunohistochemistry.   
NOTE: If a participant was previously tested for NY-ESO-1 expression under a different GSK-
sponsored protocol, testing of NY-ESO-1 expression for 208467 may not be required dependent on 
the test platform(s) used and whether they meet the 208467 protocol requirements [see Section 6.3 
of the Core Protocol]). 
12. Left ventricular ejection fraction ≥45% with no evidence of clinically significant 
pericardial effusion. 
13. Performance status: for participants <16 years of age, Lansky >60, or for participants 
16 and <18 years of age, Karnofsky >60, or for participants 18 years of age, 
Eastern Cooperative Oncology Group (ECOG) of 0-1.  
14. Participant must have adequate organ function and blood cell counts, within 7 days 
prior to the day of the leukapheresis procedure, as indicated by the following 
laboratory values in Table 5.  

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Table 5 
Definitions of Adequate Organ Function 
System 
Laboratory Value 
Hematologicala,b,c 
Absolute Neutrophil count (ANC) 
≥1.5 x109/L (without granulocyte colony-stimulating support) 
Absolute Lymphocyte count (ALC) 
≥0.5 x 109/L 
Hemoglobin 
8 g/dL or ≥5.0 mmol/L (without transfusion support) 
Platelets 
≥ 100 x109/L (without transfusion support) 
Renal 
Creatinine clearance ≥40 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 (CrCl) calculated as outlined 
below by using the CKD-EPI equation and adjusting the result by multiplying with (BSA/1.73) to 
obtain CrCl in mL/min:  
Step 1: estimated glomerular filtration rate (GFR) to be obtained from the Chronic kidney disease 
Epidemiology Collaboration (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 
(ABW) may be required for cyclophosphamide, see below 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. 
• 
Participants <18 years of age must have renal function measured either by 24-hour urine creatinine collection 
or by nuclear medicine EDTA GFR measurement or by serum creatinine collection, according to standard 
practice at the treating institution. 
Participants <18 years of age must have GFR ≥70mL/min/1.73m2 OR have a serum creatinine based on 
age/gender as follows: 
Age 
Maximum serum creatinine (mg/dL) 
 
Male 
Female 
10 to < 13 years 
1.2 
13 to <16 years 
1.5 
1.4 
16 to <18 years 
1.7 
1.4 
Hepatic 
Total bilirubin 
Participants with Gilbert’s Syndrome (only if 
direct bilirubin 35%) 
1.5 x ULN (isolated bilirubin ≤1.5 x ULN is acceptable if bilirubin is 
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System 
Laboratory Value 
ALT 
2.5 x ULN (or 5 x ULN if documented history of liver metastases)  
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 
Nutritional status 
Albumin 
≥3.5 g/dL 
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 7.5.2  for guideline on use of anticoagulant medications. 
15. Participant is fit for leukapheresis and has adequate venous access for the cell 
collection.  
16. Male or female.  Contraceptive use by men or women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies.  
a. Male Participants: 
Male participants are eligible to participate if they agree to the following during the 
intervention period starting at the first dose of chemotherapy for at least 12 months 
after receiving the T-cell infusion, or until persistence of gene modified cells in the 
participant’s blood is below the level of detection for 2 consecutive assessments, 
whichever is longer.   
Refrain from donating sperm 
Plus, either:  
Be abstinent from heterosexual or homosexual intercourse as their preferred and 
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent  
OR 
Must agree to use contraception/barrier as detailed below 
• 
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 described in 
Section 12.4 when having sexual intercourse with a woman of childbearing 
potential (WOCBP) who is not currently pregnant (as a condom may break or 
leak) 
• 
Agree to use male condom when engaging in any activity that allows for 
passage of ejaculate to another person  
b. Female Participants:  
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 

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• 
Is not a WOCBP as defined in Section 12.4 
OR 
• 
Is a WOCBP (as defined in Section 12.4) 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 12.4 
during the intervention period and 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.  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. 
• 
A WOCBP must have a negative highly sensitive pregnancy test (urine or 
serum as required by local regulations) within 24 hours before any 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. 
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.  
17. Female participants of childbearing potential (FCBP) must have a negative urine or 
serum pregnancy test. 
6.1.3 
Treatment Eligibility Screening 
In addition to confirming Treatment fitness per Section 6.1.3.1, the following criteria 
must also apply prior to lymphodepletion: 
18. Participant has received/completed treatment with an anthracycline-containing 
regimen for advanced (metastatic or inoperable) disease and progressed. Participants 
who received neoadjuvant/adjuvant anthracycline or ifosfamide based therapy and 
progressed will be eligible.  Participants who are intolerant to anthracycline and 
received ifosfamide alone unless intolerant to or ineligible to receive ifosfamide will 
be eligible.  
19. Participant has measurable disease according to RECIST v1.1.  
20. Participant has documented radiographic evidence of disease progression from prior 
line of therapy. 
21. A biopsy (excisional, incisional, or core) of non-target tumor tissue obtained within 
28 days prior to initiating lymphodepleting chemotherapy is mandatory if clinically 
feasible. This biopsy will be used as baseline for biomarker analyses.  If it is not 
feasible to obtain a fresh biopsy, an archival tumor tissue (FFPE block) taken 
preferably after completion of the participant’s last line of therapy, preferably within 
90 days prior to initiating lymphodepleting chemotherapy, may be accepted at the 
discretion of the Medical Monitor (or designee).  For participants who already 
provided a fresh biopsy for antigen expression and did not receive any bridging or 

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standard of care intermediate anti-cancer therapy, the screening biopsy will be used 
for baseline. 
22. A hematologist has been consulted prior to lymphodepletion in participants who have 
had a serious/significant bleeding/thrombosis history. 
 
6.1.3.1 Treatment fitness (for safety) 
Given potential changes in clinical status between screening/enrollment and the start of 
lymphodepleting chemotherapy, safety assessments from Section 6.1.1 and Section 6.1.2 
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. 
6.2 
EXCLUSION CRITERIA 
6.2.1 
Target Expression Screening 
Participants are not eligible to be screened for target expression (HLA-A*02:01, 
A*02:05, or A*02:06 and NY-ESO-1) if any of the following criteria apply: 
1. Central nervous system (CNS) metastases.  
2. Any other prior malignancy that is not in complete remission.  
Exceptions include: 
a. Completely resected non-melanoma skin cancer, or successfully treated in situ 
carcinoma (e.g., melanoma in situ, basal cell carcinoma, prostate cancer in-situ, 
periosteal osteosarcoma) 
b. Previous malignancies that have been definitively treated, and have been in 
remission for 5 years may be enrolled upon consultation with sponsor Medical 
Monitor or designee 
3. Previous treatment with genetically engineered NY-ESO-1-specific T-cells.  
4. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. 
5. Prior gene therapy using an integrating vector. 
6. Previous allogeneic hematopoietic stem cell transplant. 
7. Clinically significant systemic illness: 
a. serious active infections or significant cardiac, pulmonary, hepatic or other organ 
dysfunction, that in the judgment of the Investigator would compromise the 
participant’s ability to tolerate protocol therapy or significantly increase the risk 
of complications  
OR 
b.  prior or active demyelinating disease 
 

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6.2.2 
Leukapheresis Eligibility Screening 
Participants are not eligible for leukapharesis if any of the Exclusion criteria from 
Section 6.2.1 apply. Please note in particular that mandatory washout period restrictions 
must be respected (see Table 6) before starting leukapheresis. In addition, participants 
are not eligible for leukapharesis if any of the following criteria apply: 
8. Participant has history of chronic or recurrent (within the last year prior to 
leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn’s disease, 
systemic lupus) requiring steroids or other immunosuppressive treatments.  
9. Uncontrolled intercurrent illness including, but not limited to: 
a. Ongoing or active infection (including, but not limited to systemic fungal 
infection)  
b. Clinically significant cardiac disease defined by congestive heart failure New 
York Heart Association (NYHA) Class 3 or Class 4 
c. Uncontrolled clinically significant arrhythmia  
d. Acute coronary syndrome (angina or myocardial infarction) in last 6 months 
e. Interstitial lung disease (participants with existing pneumonitis as a result of 
radiation are not excluded; however, participants cannot be oxygen dependent)  
10. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or 
asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per 
Investigator assessment). 
NOTE: Stable chronic liver disease should generally be defined by the absence of 
ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric 
varices, persistent jaundice or cirrhosis. 
11. QTc >480 msec  
NOTES:  
The QTc is the QT interval corrected for heart rate according to Bazett’s formula 
(QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or 
manually over-read. 
The specific formula that will be used to determine eligibility 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. 
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). 
12. Participant has a history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to cyclophosphamide, fludarabine, other agents 
used in the study.  
13. Pregnant or breastfeeding females (due to risk to fetus or newborn). 

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14. Prior/Concomitant Therapy: 
a. Any prior treatment-related toxicities must be CTCAE (Version 5.0) Grade ≤1 at 
the time of initiating study intervention (except for non-clinically significant 
toxicities e.g., alopecia, vitiligo).  Participants with Grade 2 toxicities that are 
deemed stable or irreversible (e.g. chemotherapy related arthritis or tendinitis, 
skin discoloration or erythema) can be enrolled. 
b. Other standard of care lines of therapy are allowed only if guidelines and washout 
periods are followed as described in Table 6. 
15. Investigational treatment within 30 days or 5 half-lives (whichever is shorter) prior to 
leukapheresis. Investigational vaccines (other than NY-ESO-1 vaccines that are not 
allowed) must follow the washout period specified in Table 6. Exceptions to this rule 
must be evaluated by the Investigator in agreement with the Sponsor’s Medical 
Monitor (or designee). 
16. Participant has active infection with HIV, HBV, HCV, EBV, CMV, syphilis, or 
HTLV as defined below: 
• 
Positive serology for HIV; 
• 
Active hepatitis B infection as demonstrated by test for hepatitis B surface 
antigen. Participants who are hepatitis B surface antigen negative but are hepatitis 
B core antibody positive must have undetectable hepatitis B DNA and receive 
prophylaxis against viral reactivation; 
• 
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; 
• 
Active EBV infection. Participants with positive EBV serology need to undergo 
additional tests/assessments in order to rule out active infection; 
• 
Active CMV infection. Participants with positive CMV serology need to undergo 
additional tests/assessments in order to rule out active infection; 
• 
Positive test for syphilis (spirochete bacterium) 
• 
Positive serology for HTLV 1 or 2.   
17. Has known psychiatric or substance abuse disorders that would interfere with 
cooperating with the requirements of the study. 
 
6.2.3 
Treatment Eligibility Screening 
Please note that mandatory washout period restrictions must be respected (see Table 6) 
before starting lymphodepletion. In addition to confirming Treatment fitness per Section 
6.2.3.1, participants cannot proceed with lymphodepletion or treatment if any of the 
following criteria apply: 
18. Participant has received cytotoxic therapy within 3 weeks prior to lymphodepleting 
chemotherapy. 

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19. Systemic corticosteroids or any other immunosuppressive therapy within 2 weeks 
prior to lymphodepleting chemotherapy.  
NOTE: Isolated doses of systemic corticosteroids are permitted to manage acute 
allergic reactions.  Use of inhaled or topical steroids is not exclusionary  
20. Participant has received ≥50 Gy to a significant volume of the pelvis, long bones or 
spine, or a cumulative dose of radiation that, in the Investigator’s opinion would 
predispose patients to prolonged cytopenia after lymphodepletion. 
21. All of the participant’s measurable lesions have been irradiated within 3 months prior 
to lymphodepletion. An irradiated measurable lesion with unequivocal progression 
following irradiation may be considered a target lesion regardless of time from last 
radiotherapy dose.  
NOTE: There is no washout period for palliative radiation to non-target lesions 
22. Participant has received an anti-cancer vaccine within 2 months in the absence of 
tumor response. The participant should be excluded if their disease is responding to 
an experimental vaccine given within 6 months. 
23. Participant has received live vaccine within 4 weeks prior to lymphodepletion or 
intends to receive live vaccine during the 3 month period following administration of 
lete-cel. 
24. Participant has received immune therapy (monoclonal antibody therapy, checkpoint 
inhibitors) within 4 weeks of lymphodepletion. 
25. Participant had major surgery 28 days of first dose of study intervention. 
 
Table 6 
Washout Periods for Substudy 2 
Treatment/Therapya 
Required Washout  
Prior to Leukapheresis 
Required Washout 
Prior to Lymphodepletion 
Cytotoxic chemotherapy 
3 weeks 
Immune therapy (including monoclonal antibody 
therapy) 
4 weeks 
Anticancer Vaccine 
• 2 months in the absence of tumor response 
• The participant should be excluded if the Investigator 
considers their disease is responding to an experimental 
vaccine given within 6 months 
Live-virus vaccination (there is no required 
washout for seasonal flu vaccines that do not 
contain live virus). 
4 weeks 
Systemic corticosteroids or any other 
immunosuppressive therapy (there is no washout 
required for inhaled or topical steroids as they are 
allowed during the study) 
2 weeks 
Investigational treatment  
4 weeks 
2 weeks 
Radiotherapy 
To the target lesions within 3 months prior to 
lymphodepletion.b  
NOTE: There is no washout period for palliative radiation to 
non-target lesions 
Tyrosine kinase inhibitors 
1 week 

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a. Permission and washout for any other anticancer therapies must be discussed with the Sponsor’s Medical Monitor 
(or designee). 
b. A lesion with unequivocal progression may be considered a target lesion regardless of time from last radiotherapy 
dose. 
6.2.3.1 
Treatment fitness (for safety) 
Given potential changes in clinical status between screening/enrollment and the start of 
lymphodepleting chemotherapy, safety assessments from Section 6.2.1 and Section 6.2.2 
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.  
6.3 
Lifestyle Considerations 
6.3.1 Meals and Dietary Restrictions 
Participants should maintain the current/regular diet unless modifications are required to 
manage an AE such as diarrhea, nausea, or vomiting. 
6.3.2 Activity 
Participants should abstain from extraordinarily strenuous athletic activity for 24 h before 
each blood collection for clinical laboratory tests. Participants may engage in light 
recreational activities during studies (e.g., watching television, reading). 
6.3.3 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, disease characteristics, 
prior lines of anti-cancer treatments, performance status and any serious adverse events 
(SAEs). 
6.3.4 Rescreening 
Individuals who do not meet the criteria for participation in this study (screen failure or 
withdrawal) may be rescreened upon Sponsor agreement.  
Rescreened participants will be assigned a new participant number. 
For each rescreened participant, the Sponsor will review the following on evaluation of 
eligibility to Substudy 2 and before initiating leukapheresis or manufacturing of the 
T cells: 
• 
Participant will be considered HLA positive if already tested positive for 
HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a 
designated central lab under this substudy or under another GSK-sponsored study or 
substudy of this protocol;  

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• 
Participant’s tumor antigen expression will be considered positive if previously 
pathologically reviewed by a designated central laboratory under this substudy or 
under another GSK-sponsored study or substudy of this protocol, with confirmed 
positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by 
immunohistochemistry;   
• 
If participant has previously completed Sponsor protocol-specified leukapheresis 
under this substudy or under another GSK-sponsored study or substudy of this 
protocol:  
– Already banked cryopreserved T cells under an applicable process may be used 
in the manufacturing of lete-cel if within shelf-life specifications;  
– Already stored manufactured lete-cel (GSK3377794) product under an applicable 
process may be used for the T-cell infusion if within shelf-life specifications. 
 
7 STUDY INTERVENTION 
7.1 
Study Intervention(s) Administered 
7.1.1 Leukapheresis 
Participants will undergo leukapheresis to obtain starting material for the manufacture of 
autologous letetresgene autoleucel (lete-cel, GSK3377794).  
Investigators will follow institutional guidelines and the minimum requirements as 
outlined in the Apheresis Manual. 
A CD3 count of ≥200/L prior to leukaheresis is recommended to ensure an adequate 
T-cell collection for manufacture of lete-cel. If the lab test returns a value lower than 200, 
there is the potential that more than one collection will be needed to reach the T-cell 
target. The lab test should be repeated and the Sponsor alerted as soon as possible. 
7.1.2 Bridging Therapy and/or Standard of Care Intermediate Anti-Cancer 
Therapy before Lymphodepletion 
Since HLA-typing and NY-ESO-1 expression testing are required prior to treatment, 
standard of care systemic chemotherapy, experimental therapy and/or local therapy 
(e.g., radio-therapy, cryoablation, surgical resection) may be administered between target 
expression screening and leukapheresis. Mandatory washout periods prior to 
leukapheresis (see Section 6.2 Table 6) must be respected when planning treatment or 
procedure. 
Additionaly, because this substudy allows leukapheresis to occur in earlier lines of 
therapy, systemic chemotherapy may be administered between leukapheresis and the start 
of lymphodepletion (bridging therapy), if a participant has progressive disease and cannot 
be treatment-free. Mandatory washout periods prior to lymphodepletion (see Table 6) 
must be respected when planning treatment or procedure. For therapies not already 
described in this protocol, washout periods must be around 5 half-lives, except for 
biologic agents for which a Sponsor consultation is required. 

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At the discretion of the Investigator and after discussion with the Medical Monitor, 
bridging or standard of care intermediate anti-cancer therapy may be considered for any 
participant, particularly those with high disease burden or disease-related symptoms at 
screening. 
Clinically significant interactions have been reported for doxorubicin with inhibitors of 
CYP3A4, CYP2D6, and/or P-gp (e.g. verapamil) and also with inducers of CYP3A4 
(e.g., phenobarbital, phenytoin, St. John's Wort), which may affect the concentration of 
doxorubicin, and therefore should be used with caution. 
A line of standard of care therapy may be administered to participants before 
lymphodepletion based on Investigator’s evaluation of benefit/risk, in accordance with 
local regulatory requirements and standards, and in agreement with the Sponsor’s 
Medical Monitor (or designee). 
7.1.3 Lymphodepleting Chemotherapy 
Prior to the administration of lymphodepleting chemotherapy, participant’s fitness for 
lymphodepletion will be assessed, treatment eligibility criteria will be confirmed and 
baseline tumor assessment CT/MRI obtained per Section 9.1.1 of the Core Protocol and 
the SoA in this Substudy.  Disease progression after prior line of treatment per RECIST 
v1.1 needs to be documented prior to performing lymphodepletion.   
When lete-cel has been manufactured, has fulfilled release criteria, and is available for 
infusion at the site, lymphodepleting fludarabine and cyclophosphamide can be 
administered as described in Table 7. Cyclophosphamide and fludarabine will be supplied 
by the pharmacy of the participating Institution. 
Dose and regimen for lymphodepleting chemotherapy is adjusted for participants 
60 years of age, as specified in Table 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 
the bone marrow reserve, 
• 
Participants with documented low albumin (≤3.5 g/dL). 
 
A default dose adjustment for participants meeting one of the listed conditions should be 
aligned to the standard dose modification otherwise applied for participants 60 years of 
age, as specified in Table 7.  
For any more complex conditions further discussion to determine the need for dose 
modification with the Sponsor’s Medical Monitor or designee will be warranted.   

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For Investigators with patients approaching lymphodepletion, the Sponsor requires that 
the site reviews creatinine clearance (CrCl) and lymphodepleting chemotherapy 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 (estimated or measured).  Any significant discrepancy that would lead to a 
change in dose will be discussed with Medical monitor prior to commencing 
lymphodepletion. 
• 
Calculations methods are provided in Section 6.1 Table 5 Definitions of Adequate 
Organ Function, Renal for CKD-EPI using 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 
estimation of creatinine clearance. 
 
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. 
Supportive therapy guidelines are provided in Section 12.7. 
Table 7 
Lymphodepleting Chemotherapy 
 
Lymphodepleting chemotherapy 
Recommended prophylaxis 
and supportive medication 
Day 
Drug 
Dose, 
mg/m2 
Dose for 
participants 
 60 years 
old, mg/m2 
Route 
Administrationc 
Infection:  On admission for 
lymphodepleting 
chemotherapy, commence anti-
microbial and anti-fungal 
prophylaxis as recommended in 
Section 12.7 or in line with 
institutional standard practice. 
 
Hydration:  Ensure adequate 
hydration and antiemetic 
provision prior to commencing 
cyclophosphamide infusions 
 
Mesna:  May be given to 
prevent urotoxicity per 
institutional guidelines or as 
recommended in this Section 
below. 
 
G-CSF:  Must start ~24 hours 
after the last cyclophosphamide 
infusion (i.e., on Day-3). G-CSF 
support to continue until 
-7 
Fludarabine1 
30 
none 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
-6 
Fludarabine1 
30 
30 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
Cyclophosphamideh3 
900 
600 
IV 
in 200 – 500 mL 
0.9% NaCl over 
1 hour2 
-5 
Fludarabine1 
30 
30 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 
Cyclophosphamide3 
900 
600 
IV 
in 200 – 500 mL 
0.9% NaCl over 
1 hour2 
-4 
Fludarabine1 
30 
30 
IV 
in 50 – 100 mL 
0.9% NaCl over 
30 mins2 

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Lymphodepleting chemotherapy 
Recommended prophylaxis 
and supportive medication 
Cyclophosphamide3 
900 
600 
IV 
in 200 – 500 mL 
0.9% NaCl over 
1 hour2 
resolution of neutropenia in 
accordance with ASCO 
guidelines [Smith, 2015] or 
institutional practice. 
-3 
Start G-CSF4 
+1 
Lete-cel (GSK3377794) 
1. 
Fludarabine dose will be adjusted in renal impairment as described in this section.  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 actual body weight 
[Bubalo, 2014], unless required otherwise by institutional guidelines. 
2. 
Or per institutional guidelines. 
3. 
Cyclophosphamide dose will be adjusted in obese participants and in pediatric participants as described in this 
section. This adjustment needs to be applied to all doses, on top of the age-related modification. 
4. 
Long-acting (pegylated) G-CSF may be given instead of short acting G-CSF according to institutional standard 
practice. If pegylated G-CSF is administered, give one dose ~24 hours after the last chemotherapy administered. 
 
ASCO = American Society of Clinical Oncology; ASBMT = American Society for Blood and Marrow Transplantation 
practice; IV = intravenous; NaCl = sodium chloride; G-CSF = granulocyte-colony stimulating factor 
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 (CrCl) 
Fludarabine dose 
>80 mL/min 
30 mg/m2 
>50 – 80 mL/min 
20 mg/m2 
30 – 50 mL/min 
15 mg/m2 
Note: to estimate CrCl (in mL/min) please use Section 6.1 Table 5 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 for this BSA calculation, use actual body weight.   
Creatinine clearance must be reassessed prior to lymphodepletion for use in these calculations. 
Cyclophosphamide Dose Adjustments 
This adjustment needs to be applied to all doses, on top of the age-related a modification.  
If the participant’s weight is greater than 175% Ideal Body Weight (IBW), then calculate 
cyclophosphamide dose based on Adjusted Body Weight (ABW). 
Calculating Ideal Body Weight 
 
Estimated ideal body weight (IBW) in kg 
Males 
 
Females 
 
Estimation of Ideal Body Weight may be performed per local institutional guidelines 
instead. 

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Calculating Adjusted Body Weight 
If the actual body weight is greater than 175% of the calculated IBW, calculate the ABW:  
 
Estimation of Adujsted 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 (BSA). 
Cyclophosphamide Dose Adjustment for Pediatric Participants 
This adjustment needs to be applied to all doses, on top of the renal impairment 
modification.  For pediatric participants, where participant weight is >175% of the 
calculated IBW use the following formula to calculate cyclophosphamide dose: 
 
Estimation of Adujsted Body Weight may be performed per local institutional guidelines 
instead. 
Use ABW in the calculation for body surface area (BSA). 
Mesna 
Mesna should be administered per institutional guidelines or as recommended below:  
• 
50% of cyclophosphamide daily dose (450 or 300 mg/m2) divided into 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. 
 
7.1.4 Lete-cel (GSK3377794) Infusion 
Refer to the current version of the Lete-cel Investigator’s Brochure regarding lete-cel and 
related clinical experience. Refer to the Drug Product and Infusion Manual for details and 
instruction on storage and administration of lete-cel. 
Participants will receive a single dose of lete-cel four days after completing the 
lymphodepleting chemotherapy. This is considered Day 1 and all procedures and 
assessments to be performed are listed in the SoA. Supportive care guidelines are 
provided in Section 12.7. 
Tocilizumab availability in institution’s local pharmacy 
A minimum of 2 doses of tocilizumab available for each participant will be required for 
administration within 2 hours after T-cell infusion, if needed for treatment of Cytokine 
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Premedication 
Thirty to sixty (30 to 60) minutes prior to T-cell infusion, participants will be 
premedicated against potential infusion reactions with antihistamines and acetaminophen 
(paracetamol). Follow institutional practice for dosage and specific medications. Steroids 
should not be administered as premedication for T-cell infusion because they are 
lymphotoxic and inhibitory to the T-cell product. 
GSK3377794 Dose 
The dose of GSK3377794 will be within the range of 1×109 – 15×109 transduced T cells, 
which will be administered by a single intravenous infusion on Day 1. The minimum 
transduced cell dose for meeting release criteria is 1×109. 
If the transduced cell dose is less than the minimum dose required, 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. 
Dosing of participants weighing less than 40 kg (including pediatric participants): 
For participants weighing less than 40 kg, lete-cel will be dosed per body weight with a 
range of 0.025×109 transduced cells/kg to 0.2×109 transduced cells/kg. The per body 
weight adjusted dosing can only be manufactured from the intended commercial cell 
manufacturing process and participants weighing less than 40 kg will only be treated with 
intended commercial drug product supply, as soon as it becomes available.  Screening of 
such participants may, however, begin before intended commercial drug product supply 
availability.   
Pediatric participants weighing greater than or equal to 40 kg will be dosed per adult 
dosing.  
Lete-cel (GSK3377794) Administration 
On Day 1, the participant will receive thawed T cells by intravenous infusion. Prior to 
infusion, two clinical personnel in the presence of the participant, will independently 
verify and confirm that the information on the infusion bag is correctly matched to the 
participant, as per the sponsor’s and clinical site’s procedures. 
The specific instructions for preparation and administration are found in Drug Product 
and  Infusion Manual.  
Any deviation from the procedures detailed in the Drug Product and Infusion Manual 
should be recorded and reported accordingly. 
In the event of adverse reaction to the cell infusion, the infusion rate should be reduced, 
and the reaction managed according to institutional standard procedures (Section 12.7). 
Steroid treatment should be avoided unless medically required. In the event a participant 
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management should be initiated, with attention to the initiation of empirical antibiotic 
treatment in the case of febrile neutropenia. 
The day of T-cell infusion may be delayed in participants with significant complications 
of lymphodepleting chemotherapy if according to the Investigator it is in the best interest 
of the participant. The timing of all assessments post-infusion will be calculated with 
reference to the T-cell infusion date. Participants who have undergone leukapheresis but 
do not receive the T-cell infusion will be replaced. Cytopenias alone should not be a 
reason to delay T-cell infusion unless complications are present (see Section 12.7 for 
guidance).  
Vital signs will be recorded prior to the infusion (see SoA). 
7.2 
Preparation / Handling / Storage / Accountability 
1. Deliveries of the investigational product 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 study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
3. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions 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. 
4. The participant’s T-cell product received at the site from the manufacturer will be 
stored below -130°C until ordered by the Investigator (or designee) to be infused. 
5. The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
6. Further guidance and information for the final disposition of unused study 
intervention will be provided in the Study Reference Manual or Drug Product and 
Infusion Manual.  
 
Precaution will be taken to avoid direct contact with the investigational product. A 
Material Safety Data Sheet (MSDS) describing occupational hazards and recommended 
handling precautions will be provided to the Investigator. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or GSK study contact. 
7.3 
Measures to Minimize Bias: Randomization and Blinding 
Not applicable to this open-label substudy. 

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7.4 
Study Intervention Compliance 
Lete-cel will be intravenously administered to participants at the site per guidelines 
specified in the Drug Product and Infusion Manual.  
Administration will be documented in the source documents and reported in the eCRF. 
7.5 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving starting at the time 
of screening for leukapheresis or receives during the study must be recorded along with: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 
 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
All concomitant medications including all prescription, over-the-counter medications, 
and herbal remedies, will be recorded, including dose and frequency. The following will 
be recorded on the appropriate eCRF pages: 
1. All prescription and non-prescription medication, vitamins, herbal and nutritional 
supplements taken by the participant during the 30 days prior to Screening for 
leukapheresis will be recorded at the Screening Phase visit. 
2. All prior anti-cancer treatments taken by the participant must be recorded regardless 
of time. 
3. All concomitant medications taken by the participant while in the Interventional 
Phase.  
4. Use of any mutagenic agents or investigational agents must be reported. 
5. Concomitant medications administered after the Interventional phase of the study will 
be recorded for SAEs and adverse events of special interest (AESIs). 
 
Any changes to concomitant medication regimens must be recorded throughout the study 
in the eCRF. 
7.5.1 Prohibited Concomitant Medication and Treatment 
The following anti-cancer treatments are prohibited during the Interventional Phase of the 
study until PD is confirmed:  non-protocol chemotherapy, immune therapy, biological 
therapy (including targeted therapies with tyrosine kinase inhibitors or monoclonal 
antibodies), or investigational anti-cancer therapy.  Once PD has been confirmed 
following T-cell infusion, participants can receive therapy at the discretion of their 
healthcare provider while they remain in this study.  This includes participation in other 
interventional clinical studies as needed. 

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During the Interventional Phase of the study until PD is confirmed participants should 
also not undergo other anticancer locoregional therapies, such as surgical resection, 
excisional biopsies or non-palliative radiation. Procedures intended for palliative care or 
symptomatic relieve on non-target lesions are permitted.   
Systemic steroids may abrogate the effects of the T cell therapy and therefore are 
discouraged unless required to manage CRS (refer to Section 12.7 for CRS management) 
or other significant immune-mediated AEs. According to local standard of care or 
American Society of Clinical Oncology (ASCO) guidelines [Basch, 2010], steroids may 
be used as anti-emetics before cyclophosphamide but must be discontinued no later than 
3 days prior to infusion of the investigational product. Topical steroids for cutaneous 
application and inhaled steroidal treatments are permitted. 
Systemic glucocorticoids are prohibited for any purpose other than to treat an event of 
suspected immunologic etiology (see Section 12.7). The use of physiologic doses of 
corticosteroids may be approved after consultation with the Sponsor.  
Participants may receive other medications that the Investigator deems to be medically 
necessary in agreement with the Sponsor’s Medical Monitor (or designee). 
Medications or vaccinations specifically prohibited in the exclusion criteria are not 
allowed during the ongoing trial. Administration of live vaccine during the period of 
infusion of fludarabine, cyclophosphamide or lete-cel, and for at least 3 months after last 
dose of any of these agents is prohibited. If there is a clinical indication for any 
medication or vaccination specifically prohibited during the trial, discontinuation from 
trial therapy may be required. The Investigator should discuss any questions regarding 
this 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 intervention requires the mutual agreement of the 
Investigator, the Sponsor and the participant. 
7.5.2 Permitted Concomitant Medication and Treatment 
Participants should receive full supportive care during the study, including transfusion of 
blood and blood products, and treatment with antibiotics, antiemetics, antidiarrheals, and 
analgesics, as appropriate. 
Lesions that previously required radiotherapy should be recorded prior to 
lymphodepleting chemotherapy. Radiotherapy is not permitted after T-cell infusion until 
disease progression.  However, in emergent clinical situations, palliative radiation for 
pain relief to non-measurable lesions or non-target lesions present at baseline may be 
permitted upon approval of Sponsor’s Medical Monitor. However, lesions requiring 
radiotherapy after the T-cell infusion should be evaluated as to whether that indicates 
disease progression. These lesions are not suitable to be biopsied for biomarker analysis. 
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 
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(or member of the participant’s household), consult an Infectious Disease specialist or a 
guidance such as the CDC Clinical Practice Guideline for Vaccination of the 
Immunocompromised Host. 
Permitted concomitant medications with required washout periods are listed in Section 
6.2, Table 6 of this Substudy. 
Once PD has been confirmed following T-cell infusion, participants can receive further 
therapy at the discretion of their healthcare provider while they continue to be followed in 
this study.  
Recommendations for participants on therapeutic anticoagulants: [Maus, 2020] 
• 
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. 
 
7.5.3 Rescue Medicine 
Anti IL-6 drugs such as Tocilizumab may be administered to participants experiencing 
cytokine release syndrome (see Section 12.7.5 for details).  Steroids may be used for 
emergent medical conditions.  For all non-emergent conditions, consult with the 
Sponsor’s Medical Monitor.  Guidelines for management of complications are provided 
separately in the appendices. 
See Section 12.7 for details on general supportive care that can be given during the study. 
7.6 
Dose Modification 
Dose modification is not applicable to T cells.  The entire dose of T cells that has been 
received by the site for the participant needs to be administered as a single dose.  If a 
reaction occurs that does not allow safe administration of the full dose, the dose 
administered needs to be recorded. 
If the transduced cell dose is less than the minimum dose required, 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.   

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7.7 
Intervention after the End of the Study 
No therapeutic intervention will be provided after the end of the study.  Participant may 
receive any necessary treatment interventions from their oncologist. 
8 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION / WITHDRAWAL 
Definitions and procedures for discontinuation of study intervention and participant 
discontinuation / withdrawal should follow the SoA in this substudy and details outlined 
in Core Protocol Section 8. 
9 STUDY ASSESSMENTS AND PROCEDURES 
Study assessments and procedures should be performed per the SoA in this substudy and 
as defined in the Core Protocol Section 9.   
The following additional Substudy specific assessments should be performed per the 
SoA. 
9.1 
Interviews 
9.1.1 Post T-cell Infusion Interview 
To evaluate T-cell infusion related experiences, symptoms and associated impacts, adult 
participants will be asked to participate in an optional telephone interview. Adult 
participants will be contacted about one week after infusion to set up a phone 
interview.  The informed consent for this phone interview will be part of the clinical trial 
informed consent process. All of the interviews will be conducted by a trained 
interviewer will be audio recorded for transcription and analysis.  Failure to complete the 
interviews will not constitute a protocol deviation. 
9.1.2 End of Treatment Interview  
To further evaluate disease and treatment related symptoms and associated impacts on 
function and health-related quality-of-life, adult participants will complete an optional 
Exit Interview conducted via telephone within approximately 21 days following 
completion of the last Interventional Phase visit and will focus on symptoms and 
impacts following discontinuation of study intervention.  Failure to complete the 
interviews will not constitute a protocol deviation. 
9.2 
Patient Reported Outcomes 
Patient reported outcomes will be assessed in adult participants as part of this protocol. 
The instruments in use in this section are only suitable for adult populations. 

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9.3 
Healthcare Resource Utilization  
Healthcare resource utilization (HRU) is to be collected per the Schedule of Activities 
(SoA). The site staff will complete the paper Healthcare Utilization Worksheet using 
information available from the electronic medical records (EMR) and participant 
interview. The site staff will enter the data from the Healthcare Utilization Worksheet 
into the eCRF.  
All oncology related HRU since the last visit will be collected, including the current visit.  
10 STATISTICAL CONSIDERATIONS  
10.1 Statistical Hypotheses  
This substudy is designed to evaluate the benefit/risk of lete-cel relative to historical 
controls. The ORR for pazopanib and other available second line (2L) treatments ranges 
between 4-13% based on available data. To account for the potential variability in 
historical control efficacy, the upper range of the historical ORR of 13% is considered.  It 
is expected that treatment with lete-cel will result in a 40% ORR or higher. 
The primary efficacy analysis will be performed by testing whether the ORR is less than 
or equal to 13% against the alternative hypothesis that ORR is greater than 13% at overall 
2.5% level of significance (one-sided), that is H0: p ≤0.13 vs. H1: p >0.13. The ORR will 
be summarized along with the two-sided exact Clopper-Pearson 95% confidence interval 
(CI). The study will be considered successful if the lower bound of the two-sided exact 
confidence interval for ORR exceeds 13%.  The primary analysis will be based on the 
combined data from both SS and MRCLS.  Additional subgroup analyses by indication 
may be prepared as appropriate. 
A hierarchical testing strategy is being implemented which will maintain an overall 
alpha-level of 0.025 for assessing ORR across the study as described below - further 
details included in the Analysis Plan: 
• 
Interim Analysis 1: After approximately 20 patients have been infused with 
intended commercial drug product supply lete-cel and followed for approximately 3 
months, an interim analysis will be conducted to facilitate planning and discussion 
with relevant health authorities regarding further development and registration 
strategy for lete-cel.  No early claim for efficacy is planned and no alpha adjustment 
is planned for this analysis. 
• 
Interim Analysis 2: After 45 patients have been infused with intended commercial 
drug product supply lete-cel and followed for approximately 6 months, efficacy will 
be evaluated for the overall population (SS+MRCLS).  Observing an ORR of 14 of 
45 responders would provide a successful outcome for the study. 
• 
Primary Efficacy Analysis:  After 60 patients have been infused with intended 
commercial drug product supply lete-cel and followed for approximately 6 months, 
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efficacy will be evaluated for the overall population (SS+MRCLS). Observing an 
ORR of 16 of 60 responders would provide a successful outcome for the study. 
o Primary Efficacy Analysis (SS sub-population):  After 60 patients 
(SS+MRCLS) have been infused with intended commercial drug product 
supply lete-cel and followed for approximately 6 months, the SS sub-
population will be evaluated. Observing an ORR of 12 of 45 responders 
would provide a successful outcome for the study. 
 
 
 
 
 
10.2 Sample Size Justification 
Based on the exact binomial distribution and the null hypothesis of ORR ≤13% and 
alternative hypothesis of ORR >13%, a sample size of 60 participants in the PEAP 
population will provide over 98% power to demonstrate statistical significance at 
one-sided 0.025 type 1 error rate, if the underlying ORR is 40%. In this setting, an ORR 
of 26.6% (16/60) will be needed to claim success at the time of primary analysis with the 
two-sided exact Clopper-Pearson 95% confidence interval (CI). The study will be 
considered successful if the lower bound of the two-sided exact confidence interval for 
ORR exceeds 13%.  

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Though a smaller sample size could be utilized for the efficacy assessment with adequate 
power >90%, the larger sample size has been implemented to allow for a more robust 
evaluation of safety. 
The primary analysis will be performed after the first 60 participants have received T-cell 
infusion (PEAP population) and have completed at least 6-months of follow-up since 
infusion or progressed or discontinued earlier (due to death, loss to follow-up, or 
permanent study withdrawal). The final analysis will be performed when 70% of the total 
number of participants who received at least the minimum target dose of lete-cel (mITT) 
have died or have been lost to follow-up. 
The PEAP sample size proposed for Study 208467 (N=60) is sufficient to demonstrate 
the risk / benefit in this highly selected and rare patient population. It is assumed that 
approximately 5%-10% of enrolled participants will not receive lete-cel infusion due to 
consent withdrawal, product manufacturing issues, death occurring before progression on 
prior lines of treatments, being ineligible to receive lete-cel after progression, or other 
issues.  Approximately 72 participants will be enrolled to ensure that at least 
60 participants are treated with intended commercial drug product supply. 
 
At the time of the primary analysis (n=60 participants), it is anticipated approximately 45 
SS participants and 15 MRCLS participants will be treated.  The distribution between SS 
and MRCLS participants treated may naturally vary from the projections. A summary of 
the sample size sensitivity for the SS subgroup analysis is also provided to show the 
power under different scenarios if the sample size for the SS subgroup is less than the 
planned n=45 SS patients. 
N for SS/pooled 
Alpha for SS analysis 
Power for SS analysis 
45/60 
0.02285 
98% 
43/60 
0.0223 
98% 
40/60 
0.0219 
97% 
35/60 
0.0211 
94% 
 
10.3 Populations for Analyses 
For purposes of analysis, the following populations are defined, the details of additional 
analysis populations will be defined in RAP: 
Population 
Description 
Screened Population 
All participants who signed an ICF to participate in the study. 
Enrolled Population 
All participants who started leukapheresis procedure. 
ITT Population  
All participants who started leukapheresis procedure. 

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Population 
Description 
Safety Population  
All participants who received any dose of lete-cel (GSK3377794).  
Modified ITT (mITT) 
Population 
All participants who received at least the minimum target dose1 and 
meeting the product specifications2 of lete-cel. 
Primary Efficacy Analysis 
Population (PEAP) 
The first 60 participants who received at least the minimum target dose1 
and meeting the product specifications2 of lete-cel from intended 
commercial drug product supply. This population will be the primary 
population for the primary/secondary efficacy analysis.  
Primary Efficacy Analysis 
Population for Interim 
(PEAPi) 
The first 45 participants who received at least the minimum target dose1 
and meeting the product specifications2 of lete-cel from intended 
commercial drug product supply. This population will be the primary 
population for the primary/secondary efficacy interim analysis. 
1. Minimum target dose = 1x109 transduced cells of lete-cel. 
Note: while all manufactured products are to be released with a dose greater than the minimum target dose, it may 
be possible that a participant does not receive the intented minimum target dose, due to an AE requiring infusion 
discontinuation, or due to a bag being quarantined.  
2. Participants who received drug product supply released as “non-conforming batch” will be excluded from mITT, 
PEAP and PEAPi populations.  
 
The primary efficacy analysis population (PEAP) will be used for the primary analysis 
(n=60). The PEAPi will be used in place of the PEAP at the time of the interim analysis 
(n=45) for the planned analyses. 
A summary of the number of participants in each of the analysis populations will be 
provided. A listing of participants excluded from analysis populations (if any) will also 
be provided. 
A summary and listing of screening status and screen failures will be provided using the 
screened population. 
10.4 Study Population Analyses 
The study population analyses will be based on the ITT, mITT and PEAP population, 
unless otherwise specified. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
exposure and treatment compliance will be based on GSK Core and Oncology Data 
Standards.  
Disposition of Participants 
The number of participants receiving lymphodepleting chemotherapy and the number of 
participants infused with the minimum target dose of 1×109 transduced cells of lete-cel 
will be summarized. A summary of participant status, reason for study withdrawal and 

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study treatment status will be provided. This display will show the number and 
percentage of participants who completed the study, those withdrew from the study, those 
ongoing for study.  
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, participant management or participant assessment) will be 
summarised and listed. 
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. 
Demographic and Baseline Characteristics 
The demographic characteristics (e.g., race, age, ethnicity, sex, height, and baseline body 
weight) will be summarized and listed. Age, height, weight will be summarized using the 
mean, standard deviation, minimum, median and maximum. In addition, age will also be 
categorized and summarized by GSK IDSL standard as ≤18, 19-64, ≥65. The count and 
percentage will be computed for sex and ethnicity. 
Race and racial combinations will be summarized and listed. 
Concomitant Medication 
All concomitant medications will be summarized.  
Concomitant medications will be coded using WHO Drug coding dictionary, summarized 
and listed. The summary of concomitant medications will show the number and 
percentage of participants taking concomitant medication by Ingredient. Multi-ingredient 
products will be summarized by their separate ingredients rather than as a combination of 
ingredients. Anatomical Therapeutic Chemical (ATC) classification Level 1 (Body 
System) information will be included in the dataset created but will not appear on the 
listing or summary. 
In the summary of concomitant medications, each participant is counted once within each 
unique ingredient. For example, if a participant takes Amoxycillin on two separate 
occasions, the participant is counted only once under the ingredient ‘Amoxycillin’. In the 
summary of concomitant medications, the ingredients will be summarized by the base 
only. 
Blood products will be summarized. Supporting listing will also be provided. 
Study Treatment Exposure 
A listing of study treatment will be provided, including participant number, total cells, 
transduction efficiency, derived total transduced dose, and lot number / T-cell 
manufacturer. The total number of transduced T cells will be summarized using mean, 
standard deviation, median and range. 

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All dose administration data for lymphodepletion, including cyclophosphamide and 
fludarabine, for T-cell infusion will be presented by participant in a data listing. 
Subsequent Anti-Cancer Therapies 
The number and percentage of participants that received any anti-cancer medication, 
radiotherapy or cancer-specific surgery as post study treatment anti-cancer therapy will 
be summarized. Time from T-cell infusion to the first post study treatment anti-cancer 
therapy will also be included in this summary table. 
Follow-up anti-cancer therapy will be coded using WHO Drug coding dictionary, then 
summarized by ingredient. Participant level details of the anti-cancer therapy will be 
provided in the listings. On-study surgeries and radiotherapy will be listed. 
10.5 Statistical Analyses 
10.5.1 
Efficacy Analyses 
Endpoint 
Statistical Analysis Methods 
Primary 
ORR, which includes confirmed complete or partial response as determined by independent 
review assessment will be reported along with Clopper-Pearson exact 95% CI. 
Secondary 
PFS, OS, DOR, and TTR will be summarized using Kaplan-Meier quantile estimates along with 
2-sided 95% CIs at the time of final analysis, if data warrant. DCR will be reported along with 
Clopper-Pearson exact 95% CI. 
Exploratory 
Will be described in the reporting and analysis plan. 
 
Primary Efficacy Analysis 
ORR: Overall response rate is defined as the percentage of participants with a confirmed 
CR or a PR relative to the total number of participants within the analysis population per 
RECIST v1.1 as determined by central independent review.  At the primary analysis, 
ORR will be analysed based on the PEAP population.  
ORR will also be reported in the ITT and mITT populations at the time of primary 
analysis for all participants who have had at least two post-baseline disease assessments 
or have died or progressed or have withdrawn from the study. Additional sensitivity 
analysis will be performed using the ORR as assessed by local Investigators at final 
analysis. 
The overall response is the overall response recorded from the start of T-cell infusion 
until disease progression or start of new anti-cancer therapy, whichever earlier, and will 
be determined programmatically based on disease assessment at each time point. 
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. 

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The number and types of responses, as defined by RECIST v1.1, will be listed and 
summarized separately, as appropriate. 
The observed confirmed ORR will be reported at the primary analysis along with 95% 
Clopper-Pearson exact CI. 
An overall listing of participant response data will be provided for the ITT population. 
This listing will be sorted by the first T-cell infusion date and will display all the central 
independent review response evaluations, the best confirmed response, whether the 
participant is ongoing in the study, whether the participant is evaluable for the PEAP 
population. All supporting lesion data will be listed. 
Secondary Efficacy Analysis 
DCR: DCR, is defined as the percentage of participants with a confirmed CR, PR, or SD 
with minimal 12 weeks duration relative to the total number of participants within the 
analysis population at the time of  primary analysis as determined by independent central 
review per RECIST v1.1. The observed DCR will be reported along with 95% 
Clopper-Pearson exact confidence interval (CI).  DCR will be analysed based on PEAP 
and mITT populations. 
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: PFS, is defined as the time from the date of T-cell infusion until the earliest date of 
radiological PD as assessed by independent central review per RECIST v1.1, or death 
due to any cause. For the analysis of PFS, if the participant received subsequent 
anticancer 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 
an adequate post-baseline disease assessment that is no later than the date of initiation of 
anti-cancer therapy, PFS will be censored at the date of the T-cell infusion date.  
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 more 
than two scheduled radiological disease assessments. Specifically, if there are more than 
two 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. 
If a participant has neither progressed, died, nor started new anti-cancer therapy, PFS will 
be censored at the date of the last adequate disease assessment. 

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For participants who receive subsequent anti-cancer therapy the following rules will 
apply: 
• 
If anti-cancer therapy is started without documented disease progression or is started 
prior to documented disease progression, PFS will be censored at the date of the last 
adequate disease assessment that is no later than the date of initiation of anti-cancer 
therapy (i.e., if an assessment occurs on the same day as the start of new anti-cancer 
therapy the assessment will be used, as it will be assumed the assessment occurred 
prior to the administration of new anti-cancer therapy).  
• 
If a participant has only a baseline visit or does not have an adequate disease 
assessment that is no later than the date of initiation of subsequent anti-cancer 
therapy, PFS will be censored at the date of T-cell infusion. 
 
A summary of the assignments for progression and censoring dates for PFS are specified 
in table below. 
Situation 
Date of Event (Progression/Death) 
or Censored  
Event 
(Progression/Death) 
Or Censored 
No (or inadequate) baseline tumor 
assessments and the participant has 
not died (if the participant has died 
follow the rules for death indicted at the 
bottom of the table) 
Date of T-cell infusion 
Censored 
No post-baseline adequate disease 
assessments and the participant has 
not died (if the participant has died 
follow the rules for death indicted at the 
bottom of the table) 
Date of T-cell infusion 
Censored 
Progression documented between 
scheduled visits 
Date of assessment of progression 1,3 
Event 
No progression (or death)  
Date of last adequate disease 
assessment of response 2 
Censored 
New anticancer treatment started (prior 
to documented disease progression) 3 
Date of last adequate disease 
assessment of response 2 (on or prior 
to starting anti-cancer therapy)  
Censored 
Death before first PD assessment (or 
Death at baseline or prior to any 
adequate assessments) 
Date of death 
Event 
Death between adequate assessment 
visits  
Date of death 
Event 
Death or progression after more than 
two missed adequate disease 
assessment 
Date of last adequate 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 disease assessment is defined as an assessment where the response is CR, 
PR, or SD. For purposes of defining adequate assessment, PD is not considered 
adequate. 

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3. If PD and new anti-cancer therapy (including systemic ctx, radiotherapy and cancer-related procedures) 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). If anti-cancer therapy is started prior to any adequate assessments, censoring 
date should be the date of T-cell infusion.  
 
PFS will be listed and summarized using Kaplan-Meier quartile estimates along with 
2-sided 95% CIs. 
OS: OS, is defined as the interval of time between the date of T-cell infusion and the date 
of death due to any cause. For participants who do not die, time of death will be censored 
at the date of last contact. The date of death should be taken from that recorded on the 
Record of Death page. Death on study due to any cause will be included. Survival will be 
listed and summarized using Kaplan-Meier quartile estimates along with 2-sided 95% CI. 
DOR: DOR is defined as, in the subset of participants who show a confirmed CR or PR 
as assessed by independent central review per RECIST v1.1, the time from first 
documented evidence of CR or PR until the first documented sign of disease progression 
or death. Duration of response will be summarized descriptively, if data warrant, using 
Kaplan-Meier medians and quartiles. Censoring: same as PFS censorship table. 
TTR: TTR is defined as the time from the date of T-cell infusion to initial date of 
confirmed response (PR or CR) as assessed by independent central review per RECIST 
v1.1 in the subset of participants who achieved a confirmed PR or CR. 
TTR will be listed and summarized descriptively using median and quartiles in the subset 
of participants with a confirmed response of PR or CR.  
Efficacy listings such as BOR , DOR, PFS and OS will be reported for the PEAP and 
mITT populations. 
Sensitivity Analysis 
The analysis of primary endpoint, ORR, will also be performed among all participants in 
the ITT population.  
Additional sensitivity analysis will be performed for the ORR, PFS and DOR as assessed 
by local Investigators.  
Specifically, the ORR based on local Investigators assessed response will be determined 
programmatically and summarized in the same way as the ORR based on independent 
central review. An assessment of the concordance between the Investigator-assessed 
response and independent central review assessed response will be performed. An overall 
listing of participants response data based on Investigator assessed response will be 
provided alongside the independent central review assessed responses for the mITT 
population. This listing will be sorted by by the first T-cell infusion date and will display 
both independent reviewer-assessed and Investigator assessed response evaluations, the 
best confirmed responses, whether the participant is ongoing in the study, and whether 
the participant is evaluable for the PEAP. 

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The sensitivity analysis of PFS and DOR will be based on radiological response from the 
local Investigator assessment. The date of disease progression is defined as the date of 
radiological disease progression based on imaging data per RECIST v1.1. Participants 
who do not meet the RECIST v1.1 criteria for progression and are still alive will be 
censored. Clinical progression, defined as Investigator assessed clinical progression in the 
absence of radiological confirmation, is not considered a progression event in this 
analysis. Specifically, in the event of clinical progression leading to discontinuation of 
study treatment and radiological assessment, if radiological assessments do not indicate 
radiological progression, then the participant will be censored at the time of last 
radiological assessment. If a participant has not progressed, not died, and not started new 
anti-cancer therapy, PFS and DOR will be censored at the date of the last adequate 
assessment. Censoring rule for the sensitivity analysis of PFS and DOR will be the same 
as the censoring rule for the secondary efficacy analysis for PFS as described above. 
As a sensitivity analysis, PFS and DOR based on local Investigator assessment will be 
summarized and listed similarly as that of PFS and DOR based on independent reviewer 
assessment. 
10.5.2 
Safety Analyses 
All safety analyses will be performed on the ITT and Safety Populations.  
Endpoint 
Statistical Analysis Methods 
Primary 
AEs will be summarized using frequencies and proportions. 
Secondary 
AEs/SAEs/AESIs will be summarized using frequencies and proportions; RCL and 
instances of insertional oncogenesis (IO) will be summarized descriptively. 
Exploratory 
Will be described in the reporting and analysis plan  
 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively. In the case of low-event count, listings may be provided in lieu of 
summaries. 
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, if 
warranted, and across all on-treatment time points using a “worst-case” analysis. 
Complete details of the safety analyses will be provided in the RAP. 
Adverse Events 
AEs will be coded using the standard MedDRA and grouped by system organ class 
(SOC) and preferred term (PT). The severity of AEs will be graded by the Investigator 
according to the NCI-CTCAE v5.0. In addition CRS and ICANS will be graded 
according to [Lee, 2019]. 
PT may be combined and reported together as one term. The combined terms for 
MedDRA will be included/updated in the RAP. For all tables that summarize AEs by just 
PT, the combined version of the terms will be used. Tables that summarize AEs by SOC 
and PT will use the explicit MedDRA preferred terms. 

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Events will be summarized by frequency and proportion of total participants and by SOC 
and PT. Separate summaries will be given for all AEs, treatment-related AEs, 
treatment-related SAEs, SAEs, AESIs, and AEs leading to discontinuation of study 
intervention. In addition, AEs, if listed in the NCI-CTCAE v5.0, will be summarized by 
the maximum grade. AEs will be sorted by PT in descending order of total incidence. 
A summary of non-serious 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 and percentage of participants with common non-serious adverse 
events. The summary table will be displayed by SOC and PT. 
Summaries will be provided for lymphodepletion-related and T-cell infusion-related 
adverse events separately by overall frequency and maximum grade. A worst-case 
scenario approach will be taken to handle missing relatedness data, i.e. the summary table 
will include events with the relationship to study treatment as ‘Yes’ or missing. The 
summary tables by maximum grade will be displayed in descending order of total 
incidence by PT only. 
All AEs will be listed. The relationship between MedDRA SOC, PT, and Verbatim Text 
will be displayed in a listing.  Additionally, a listing of participant IDs for each individual 
AE will be produced.  
Adverse Events of Special Interest 
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. 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. 
According to Section 9.4.7 of protocol, AESIs for this trial include, but are not limited to: 
• 
Cytokine release syndrome (CRS) 
• 
Graft vs host disease (GvHD)  
• 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Grade 1 
persisting beyond 24 hrs or associated with concurrent CRS; or Grade 2 or higher 
• 
Guillain Barré syndrome (GBS) including acute inflammatory demyelinating 
polyneuropathy (AIDP) 
• 
Pancytopenia/aplastic anemia  
• Treatment-related inflammatory response at tumor site(s) 
 
For each AESI category, time from T-cell infusion to first onset (in days) and duration of 
first occurrence will be summarized.  
The number and percentage of participants with these events will be summarized by 
categories of AESI and maximum grade in one table. 

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Listing for participants experiencing AE of GvHD will be provided, which will include 
leukapheresis date, chemo start date, T-cell infusion date, AE start date, time since 
infusion (days), AE end date, severity, relationship to the lymphodepleting 
chemotherapy, relationship to T cell infusion outcome of event.  
Listing for participants experiencing AESI of CRS will also include time from infusion to 
first CRS (days) and time from infusion to max CRS (days).  
AEs of special interest will be further outlined in the RAP. 
Deaths and Serious Adverse Events 
In the event that a participant has withdrawn consent, no data after the withdrawal of 
consent date from this participant (except publically available information such as date of 
death) is supposed to appear in the database, which should be part of the data cleaning 
process. All deaths will be summarized based on the number and percentage of 
participants. This summary will classify participants by time of death relative to the date 
of T-cell infusion (>30 days or 30 days) and primary cause of death. A supportive 
listing will be generated to provide participant-specific details on participants who died.  
All SAEs will be tabulated based on the number and percentage of participants who 
experienced the event. One summary will be displayed by SOC and PT. Another table 
will summarize the frequency and percentage of SAEs in descending order of total 
incidence by PT only.  
Summaries will be provided for lymphodepletion-related and T-cell infusion-related 
SAEs separately by overall frequency and maximum grade.  A summary will also be 
provided for fatal adverse events, as well as separate summaries for study 
treatment-related fatal SAEs, as described above. 
SAEs are included in the listing of all adverse events. Separate supportive listings with 
participant-level details will be generated for 
• 
Fatal SAEs  
• 
Non-fatal SAEs. 
 
Clinical Laboratory Evaluations 
Summary of post-baseline change of laboratory values by visit will be provided.  
Summaries of worst case grade increase from baseline grade will be provided for all the 
laboratory tests that are gradable by CTCAE. These summaries will display the number 
and percentage of participants with a maximum post-baseline grade increasing from their 
baseline grade. Missing baseline grade will be assumed as Grade 0. For laboratory tests 
that are graded for both low and high values, summaries will be done separately and 
labeled by direction, e.g. sodium will be summarized as hyponatremia and 
hypernatremia. 
For laboratory tests that are not gradable by CTCAE, summaries of worst case changes 
from baseline with respect to normal range will be generated. The worst case will be 

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chosen from all available tests, including scheduled and unscheduled visits. Decreases to 
low, changes to normal or no changes from baseline, and increases to high will be 
summarized for the worst case post-baseline. If a participant has a decrease to low and an 
increase to high during the same time interval, then the participant is counted in both the 
“Decrease to Low” categories and the “Increase to High” categories.  
Separate summary tables for haematology, chemistry, urinalysis and laboratory tests will 
be produced. 
A supporting listing of laboratory data for participants with any value outside normal 
range will be provided, as well as laboratory values and urinalysis values. 
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. 
Further details on the analysis of exploratory endpoints and the list of statistical analysis 
displays will be provided in the RAP. 
Replication Competent Lentivirus (RCL) and instances of insertional oncogenesis (IO) 
RCL and instances of IO will be summarized descriptively. 
10.5.3 
Immunogenicity 
Presence and titres of anti-lete-cel antibodies over time will be summarized based on 
Safety population. 
10.5.4 
Other Analyses 
PK, pharmacodynamic, and biomarker analyses will be described in the RAP.  
10.5.5 
Interim Analyses  
Interim Analysis 1:  An interim analysis is included to facilitate planning and discussion 
with relevant health authorities regarding further development and registration strategy 
for lete-cel.  The interim analysis will occur after approximately 20 participants have 
been treated with intended commercial drug product supply and followed up for 
approximately 3 months.  No early claim of efficacy is planned at the Interim Analysis 1, 
and no alpha adjustment is planned for this analysis. Data from approximately 10 
additional patients treated with clinical supply will also be provided for review. This 
interim analysis will use efficacy data based on Investigators’ assessments instead of the 
independent central review assessments. 
Interim Analysis 2:  A formal interim analysis is planned when 45 patients have been 
treated with intended commercial drug product supply and followed up for approximately 
6 months.  The primary endpoint of ORR based on independent central review data will 
be assessed for the combined group (SS+MRCLS). 

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Interim safety data will be provided to the IDMC on a regular basis.  Interim efficacy 
data will be provided at the pre-specified interim efficacy analyses. Details will be 
specified in the IDMC charter.  

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14 
PROTOCOL AMENDMENT HISTORY 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). Below is history of prior protocol 
amendments. 
14.1 Amendment 1 (21-JUN-2019) 
Overall Rationale for Amendment 1: 
The overall rationale for this amendment is addition or clarification of aspects related to 
participant safety and rationale for Substudy 1 patient population. These additions 
included modification of lymphodepleting regimen for older participants, and changes 
related to FDA requests including addition of study stopping rules, and update 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 
Core protocol 
8 
Discontinuation 
of study 
intervention 
Section added: 8.5 Study stopping and 
pausing rules 
FDA request 
9.3.2 Physical 
examinations 
Added developmental assessments for 
pediatric participants 
To monitor long-term effects of study treatment on 
participant development 
9.3.3 ECOG and 
Appendix 8 
ECOG 
Added Lansky and Karnofsky 
assessment scales for pediatric 
participants 
To align with other protocols across the 
GSK3377794 program 
9.4 Adverse 
events and 
serious adverse 
events 
Added delayed AE definition. Modified 
AE and SAE collection times for the 
study; added clarification to AEs collected 
during follow-up post disease progression 
to match SoA 
To align with other protocols across the 
GSK3377794 program and to improve protocol 
clarity 
12.7.5 
Management of 
CRS 
Revised guidelines to utilize the 
American Society for Transplantation and 
Cellular Therapy updated grading system 
FDA request 
12.7.8 
Management of 
encephalopathy 
Revised guidelines to utilize the 
American Society for Transplantation and 
Cellular Therapy updated grading system 
[Lee, 2019] 
FDA request 
Substudy 1 
1  Synopsis and 
5  Study design 
Study schemas modified to include 
adjustments for lymphodepletion regimen 
To improve participant safety 

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Section # 
and Name 
Description of Change 
Brief Rationale 
2. Schedule of 
activities 
Added developmental assessments for 
pediatric participants; added Lansky and 
Karnofsky assessments; modified AE and 
SAE collection times; added ePRO 
collection at Week 3 
To monitor long-term effects of study treatment 
on participant development: ePRO changes to 
evaluate short-term impacts of treatment and 
adverse events on quality of life between Week 1 
and Week 6. 
3.1 Background 
and rationale 
and 3.2 
Benefit/risk 
assessment 
Revised rationale and benefit/risk 
conclusions for inclusion of 
participants with previously untreated 
advanced synovial sarcoma 
FDA request 
6.1 Inclusion 
criteria 
Added Lansky and Karnofsky scales to 
assessing performance status in pediatric 
participants 
To align with other protocols across the 
GSK3377794 program 
7.1.3 
Lymphodepleting 
chemotherapy 
Added lymphodepleting regimen 
adjustments for participants  60 years 
old and participants with severe 
cytopenia 
To improve participants safety 
Substudy 2 
1  Synopsis and 
5  Study design 
Study schemas modified to include 
adjustments for lymphodepletion regimen 
To improve participant safety 
2 Schedule of 
activities 
Added developmental assessments for 
pediatric participants; added Lansky and 
Karnofsky assessments; modified AE and 
SAE collection times; added ePRO 
collection at Week 3 
To monitor long-term effects of study treatment on 
participant development: ePRO changes to 
evaluate short-term impacts of treatment and 
adverse events on quality of life between week 1 
and week 6. 
5 Study design 
Allow Substudy 2 screening to begin prior 
to the availability of the commercial 
vector supply and cell manufacturing 
process 
To align with the original intent to allow participant 
screening on Substudy 2 prior to availability of the 
commercial vector supply and cell manufacturing 
process 
6.1 Inclusion 
criteria 
Added Lansky and Karnofsky scales to 
assessing performance status in pediatric 
participants 
To align with other protocols across the 
GSK3377794 program 
7.1.3 
Lymphodepleting 
chemotherapy 
Added lymphodepleting regimen 
adjustments for participants  60 years 
old and participants with severe 
cytopenia 
To improve participants safety 
10.5.1 Efficacy 
Analyses 
Corrected the inconsistency in ORR 
analysis language to align with primary 
analysis language in Section 10.2. 
FDA request 
Throughout 
Corrected inconsistencies and typos 
To improve quality of the protocol 
 

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14.2 Amendment 2 (05-FEB-2020) 
Overall Rationale for Amendment 2: 
The primary rationale for protocol Amendment 2 is clarification of aspects related to drug 
product supply used for treatment on Substudy 2.  
Per protocol Amendment 1, for Substudy 2, at least 45 participants will be treated using 
the intended commercial vector supply and cell manufacturing processes (application 
supplement to be submitted).  In the event participants eligible for Substudy 2 require 
treatment before commercial drug product supply is available, protocol Amendment 2 
allows for treatment to begin with the currently registered drug product supply. Such 
participants, if any, will be replaced to ensure that at least 45 participants receive the 
intended commercial drug product supply.   
An additional rationale for protocol Amendment 2 is clarification of dosing regimen and 
drug product supply used for treatment of participants weighing less than 40 kg on 
Substudies 1 and 2. This protocol Amendment 2 implements an updated dose range per 
body weight for participants weighing less than 40 kg as per the Investigator’s Brochure 
version 11 update [GlaxoSmithKline Document Number 2018N369930_03, 2019].  
Clarification is also provided that participants weighing less than 40 kg will only be 
treated with the intended commercial cell manufacturing process, and that screening of 
such participants may begin before commercial drug product supply is available.   

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Section # 
and Name 
Description of Change 
Brief Rationale 
Core protocol and throughout document 
 
Updated Investigator’s Brochure version 
from 10 to 11 
To update reference 
Substudy 1 
7.1.4 
GSK3377794 
Infusion 
GSK3377794 
Dose 
Pediatric Dosing 
Maximum of target dose range for 
participants weighing less than 40 kg 
amended from 0.125 to 0.2x109 
transduced cells/kg.  
Participants weighing less than 40 kg will 
only be treated with the intended 
commercial drug product supply.   
To match with IB version 11 update 
To clarify that GSK3377794 dosing per body 
weight for participants weighing less than 40 kg 
can only be provided from the commercial cell 
manufacturing process 
Substudy 2 
3.1 Substudy 2 
Background and 
Rationale 
5.1 Overall 
design 
5.2 Number of 
participants 
Updated language to allow for Substudy 
2 to start treatment eligible participants 
with currently registered drug product 
supply while restating the intent to dose 
at least 45 participants with commercial 
drug product supply. 
To start enrolling while ensuring that no delay 
could prevent first participants from receiving 
treatment in a timely manner. 
7.1.4 
GSK3377794 
Infusion 
GSK3377794 
Dose 
Pediatric Dosing 
Maximum of target dose range for 
participants weighing less than 40 kg 
amended from 0.125 to 0.2x109 
transduced cells/kg.  
Participants weighing less than 40 kg will 
only be treated with the intended 
commercial drug product supply.   
To match with IB version 11 update 
To clarify that GSK3377794 dosing per body 
weight for participants weighing less than 40 kg 
can only be provided from the commercial cell 
manufacturing process 
10.2 Sample 
size justification 
10.3 Populations 
for Analyses 
An additional modified Intent-To-Treat 
population (mITTc) is defined as a subset 
of the already existing mITT, to only 
include participants who received 
GSK3377794 infusion from commercial 
drug product supply.    
Primary Efficacy Analysis Population 
(PEAP) is also redefined to only include 
the first 45 participants who received 
GSK3377794 infusion from commercial 
drug product supply.  
PEAP used for sample size justifications 
instead of mITT 
To allow for separate analyses of all participants 
dosed with GSK3377794 (mITT) versus all 
participants dosed with GSK3377794 commercial 
drug product supply (mITTc) 
To ensure that the PEAP is only considering 
participants dosed with commercial drug product 
supply 
 
 

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14.3 Amendment 3 (06-APR-2020) 
Overall Rationale for Amendment 3:  
The primary rationale for protocol Amendment 3 is to address regulatory agency’s 
requests and integrate protocol clarification letters that were issued to date.  
Protocol amendment 3 addresses feedback from regulatory agencies by defining an end 
of study for the Master Protocol, by clarifying the hospitalization and monitoring 
requirements for T-cell infusion, and by clearly defining contraception requirements. 
Protocol amendment 3 also further clarifies schedule of assessments, washout periods 
prior to leukapheresis and prior to lymphodepletion for Substudy 1 and 2, requirement for 
availability of tocilizumab and treatment/management of pediatric participants.  Further 
data collection for all screened subjects, assessment of TGF- levels have been added.  
Protocol amendment 3 also updates eligibility criteria that participants from Substudies 1 
and 2 who are enrolled under clinical drug product supply need to weigh ≥40 kg. 
Conditions for rescreening of participants who have failed screening or withdrawn have 
been clarified such that, for patients who have previously completed protocol-specified 
target expression testing and/or leukapheresis, the Sponsor will confirm the eligibility and 
use of any cryopreserved leukapheresis and/or manufactured product on evaluation for an 
applicable substudy.  

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Section # and 
Name 
Description of Change 
Brief Rationale 
Core protocol 
1. Synopsis 
3.1 Study rationale 
Clarified that c259 is the specific 
retained clone from the TCR 
optimization, and that it is also called 
NY-ESO-1c259. 
To clarify language 
1. Synopsis 
5.1 Overall Design 
Clarified hospitalization instructions from 
T-cell infusion (on Day 1) and close 
monitoring requirements until Day 14. 
To clarify patient safety monitoring in response to 
regulatory agency’s request. 
1. Synopsis 
6.2 Rescreening 
(new) 
Clarified conditions for rescreening 
participants in the same or a different 
substudy. 
To clarify evaluation of rescreened participants 
and to reduce repetition of specific 
tests/procedures. 
1. Synopsis 
5.1 Overall Design 
12.7.9.1 
Management of 
Neutropenia 
Clarified and aligned wording relating to 
initiation of G-CSF on Day -3. 
To clarify initiation of G-CSFsupport. 
3.1 Study 
Rationale 
3.3 GSK3377794 
Relocated last paragraph of section to 
Section 3.3. 
Removed table of Clinical studies. 
To clarify background/IP sections and improve 
readability of document 
5.1 Overall Design 
Added that cryopreserved T-cell product 
from leukapheresis has a shelf-life of 2 
years. 
Clarified language for obtention of the 
pre-treatment tumor biopsy if not 
feasible to obtain fresh biopsy. 
To clarify language. 
To address site feedback and clarify acceptance 
and window for obtention of baseline biopsy. 
5.3 End of Master 
Protocol Definition 
Section 5.3,Section 5.3.1 and Section 
5.3.2.added to clarify End of Study for 
Individual Participants and End of the 
Master Protocol.   
To clarify End of Study and End of Master 
Protocol in response to regulatory agency’s 
request. 
6.1 Screen failure 
Added collection of disease 
characteristics, prior lines of anti-cancer 
treatment and performance status for all 
participants at target expression 
screening visit. 
To clarify that collection of medical history, prior 
anti-cancer line of treatment and performance 
status are required for screen failure participants. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
6.2 Rescreening 
(new) 
Specifed that rescreened participants 
will be assigned a new participant 
number. 
For participants who have previously 
completed protocol-specified target 
expression testing and/or leukapheresis, 
the Sponsor will confirm the eligibility 
and use of any cryopreserved 
leukapheresis and/or manufactured 
product on evaluation for an applicable 
substudy. 
To implement new participant number 
assignment for any rescreening. 
To clarify elibility for rescreened participants.  
9.2 Patient 
Reported 
Outcomes 
Clarified that patient reported outcome 
instruments in use for Substudies 1 and 
2 are only validated for adult 
populations. 
To clarify that patient reported outcomes in 
Substudies 1 and 2 are only required for adult 
participants. 
9.3.4 Vital signs 
Clarified that blood pressure, pulse 
measurements, respiratory rate, and 
body temperature should be assessed 
per institutional standards.  
To clarify requirements on vital signs 
assessments. 
9.3.9 Monitoring 
and Management 
of Replication-
Competent 
Lentivirus (RCL) 
using Vesicular 
Stomatitis Virus G 
protein (VSV-G) 
9.3.10 Testing for 
Persistence of 
Transduced T cells 
and Insertional 
Oncogenesis 
Theoretical risks for RCL and Insertional 
Oncogenesis requalified as potential 
risk. 
To harmonize with safety risk denomination. 
9.4 Adverse 
Events and 
Serious Adverse 
Events 
Updated definition for delayed adverse 
events as occurring either after disease 
progression or last Interventional Phase 
visit, whichever occurs first.   
To amend definition of delayed adverse events 
per updated FDA 2020a guidance. 
9.4.5 Pregnancy 
Clarified contraception period duration to 
specify a minimum of 12 months from 
start of T-cell infusion. 
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.   
To specify contraception requirements, in 
response to regulatory feedback. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
9.9.3 Cytokine 
Analyses 
12.7.5 
Management of 
Cytokine Release 
Syndrome 
Clarified that if cytokine release 
syndrome (CRS) is suspected, serum for 
cytokine analysis should be collected 
every day for the first week and 
approximately every other day thereafter 
until symptoms improve or an alternative 
diagnosis is confirmed.    
To specify cytokine collection requirements in 
case of suspected CRS. 
9.9.8 Stool 
Collection for 
Microbiome 
Analysis (new) 
Added plans to analyse gut microbiome.   To specify planned analysis of collected stool 
samples.  
12.3.4 Recording 
of Follow-Up of AE 
and SAE – 
Assessment of 
Intensity 
Clarified that CRS grading will be 
conducted according to [Lee, 2019] 
To clarify assessment of AE and SAE intensity of 
CRS. 
12.4.2 
Contraception 
guidance 
Added potential risks to fetus linked to 
treatment with fludarabine and 
cyclophosphamide. 
Added risk that cyclophosphamide 
treatment may result in partial or total 
sterility in male participants.   
To clarify risks to fetus and to male sterility linked 
to treatment with lymphodepleting chemotherapy 
regimen in response to regulatory agency’s 
request. 
12.7.2.2 Herpex 
Simplex and 
Varicella Zoster 
12.7.2.4 Hepatitis 
B prophylaxis 
Clarified that prophylaxis for herpex 
simplex and varicella zoster should be 
initiated prior to lymphodepletion. 
Clarified that posology provided for 
prophylaxis regimen is for adult 
participants (refer to label or institutional 
guidelines for posology on paediatrics). 
To clarify prophylaxis language. 
12.7.10 
Management of 
Guillain-Barré 
Syndrome (GBS) 
12.8 Appendix 8: 
Neurology 
Consultation – 
Further Guidelines 
for Signs and 
Symptoms 
Suggestive of 
Guillain-Barré 
Syndrome (new) 
Added cross reference to new Appendix 
8 for Neurology Consultation. 
Added Appendix 8 for further guidelines 
for Signs and Symptoms Suggestive of 
Guillain-Barré Syndrome (GBS) 
To clarify diagnosis of GBS. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Substudy 1 
2. Schedule of 
Activities (SoA) 
Clarified that patient reported outcome in 
use for Substudies 1 and 2 are only 
required for adult participants. 
Specified when triplicate ECGs are 
required. 
Clarified instructions on timing of Blood 
Pressure (BP) assessments,  cytokine 
collection and pre-treatment biopsy. 
Combined sampling for persistence and 
RCL testing. 
Added anlysis of TGF- in plasma 
sample. 
Added collection of stool sample at 
baseline visit and close to Week 6 visit in 
order  
To clarify instructions on study assessments.  
 
2.0 SOA – Table 3 
5.1 Overall Design 
– Part 3 
6.1 Inclusion 
criteria 18 
Clarified language for obtention of the 
pre-treatment tumor biopsy if not 
feasible to obtain fresh biopsy.   
To address site feedback and clarify acceptance 
and window for obtention of baseline biopsy. 
3.2.1 Risk 
Assessment 
GSK3377794 
Theoretical risks for ICANS, RCL and 
Insertional Oncogenesis requalified as 
potential risk   
To harmonize with safety risk denomination. 
6.1 Inclusion 
criterion 2 
Addition of weight requirement to be 
≥40 kg for any participant enrolled under 
clinical drug product supply. 
Clarification of requirement for creatinine 
clearance / GFR / serum creatinine on 
pediatric patients. 
To optimize participant safety with current dosing 
and formulation requirements.  
To clarify that pediatric patients with renal 
impairment are excluded. 
6.1 Inclusion 
criterion 7 
Amended text to clarify that biopsy 
sample should be available (instead of 
is) to perform NY-ESO-1 antigen 
expression analysis. 
To clarify that both tests may occur either in 
parallel or sequentially, pending availability of 
tumor biopsy sample for NY-ESO-1 antigen 
expression testing. 
6.1 Inclusion 
criteria – 
Leukapheresis 
Lymphodepletion 
and Treatment 
 
Clarified that Inclusion criteria 1-7 must 
apply again prior to leukapheresis 
eligibility screening 
Clarified that Inclusion criteria 1-15 must 
apply again prior to lymphodepletion 
eligibility screening 
To clarify instructions for leukapheresis eligibility. 
 
 
To clarify instructions for lymphodepletion 
eligibility. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
6.1 Inclusion 
criterion 12  
Table 4 
Renal 
Amended inclusion criteria for adequate 
renal organ function: 
- 
Clarified GFR formula 
- 
Additional criteria for pediatric 
patients, based on GFR or 
serum creatinine 
To clarify inclusion criterion for adequate renal 
organ function. 
6.2 Exclusion 
criterion 23 
7.5.1 Prohibited 
Concomitant 
Medication and 
Treatments 
Exclusion of participants who intend to 
receive live vaccine during the 3 month 
period following administration of 
GSK3377794.  
Administration of live vaccine during the 
period of infusion of fludarabine, 
cyclophosphamide or GSK3377794, and 
for at least three months after last dose 
of any of these agents is prohibited. 
To clarify exclusion criteria related to live 
vaccines, and prohibition of live vaccine 
administration during and after the period of 
infusion of lymphodepleting chemotherapy or 
GSK3377794, in response to regulatory agency’s 
request.  
6.2 Exclusion 
criteria – Table 5 
Washout Periods 
for Substudy 1 
Clarification for  washout periods for 
eligibility prior to leukapheresis and prior 
to lymphodepletion. 
To clarify that washout periods are also followed 
prior to leukapheresis. 
6.3.3 Screen 
Failures 
Amended to specify that rescreened 
participants will be assigned a new 
participant number. 
Added collection of disease 
characteristics, prior lines of anti-cancer 
treatment and performance status for all 
participants at target expression 
screening visit. 
To specify that a new participant number will be 
assigned for any rescreening. 
 
To clarify that collection of medical history, prior 
anti-cancer line of treatment and performance 
status are required for screen failure participants. 
6.3.4 Rescreening 
For participants who have previously 
completed protocol-specified target 
expression testing and/or leukapheresis, 
the Sponsor will confirm the eligibility 
and use of any cryopreserved 
leukapheresis and/or manufactured 
product on evaluation for Substudy 1. 
To clarify elibility for rescreened participants. 
7.1.2 Supportive 
Therapy and/or 
Standard of Care 
Line of Therapy 
before 
Lymphodepletion 
Specified that CYP3A4, CYP2D6 and/or 
P-glycoprotein (P-gp) inducers or 
inhibitors should only be used with 
caution when administered with 
doxorubicin. 
Clarified that use of doxorubicin in 
Substudy 1 is based on Investigator’s 
judgement in accordance with label and 
local institutional guidances 
To clarify potential drug-drug interactions with 
doxorubicin, in response to regulatory agency’s 
request. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
7.1.3 
Lymphodepleting 
Chemotherapy 
Clarified that Ideal Body Weight (IBW) 
and Adjusted Body Weight (ABW) may 
be calculated according to local 
institutional guidances.   
Clarified and harmonized wording about 
initiation of G-CSF on Day -3. 
Optimized language on dose 
adjustement as fludarabine dosing is 
only adjusted based on age and renal 
impairment considerations. Similarly 
cyclophosphamide dosing is only 
adjusted based on age and weight 
considerations.  
To clarify that provided formula for IBW and ABW 
are suggested and that local institutional 
guidelines are acceptable in assessment of 
adjustments to body surface area. 
To clarify instructions for lymphodepleting dose 
adjustments and timing of G-CSF support. 
7.1.4 
GSK3377794 
Infusion 
Corrected time between end of 
lymphodepletion and T-cell infusion to 
be four (4) days instead of two (2). 
Added that a minimum of 2 doses of 
tocilizumab must be available for each 
participant for administration within 2 
hours after T-cell infusion if needed for 
treatment of CRS. 
To align protocol language with rest of document. 
To include requirement for availability of 
tocilizumab. 
9.2 Patient 
Reported 
Outcomes 
Clarified that patient reported outcome 
instruments in use for Substudies 1 and 
2 are only validated for adult 
populations. 
To clarify that patient reported outcomes in 
Substudies 1 and 2 are only required for adult 
participants. 
10.2 Sample size 
justification – 
Population 
analysis 
Clarified that the Enrolled population is 
“All participants who passed all 
screening criteria for leukapheresis” 
To clarify description of enrolled population. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
Substudy 2 
2. Schedule of 
Activities 
Clarified that patient reported outcome in 
use for Substudies 1 and 2 are only 
required for adult participants. 
Specified when triplicate ECGs are 
required. 
Clarified instructions on timing of Blood 
Pressure (BP) assessments,  cytokine 
collection and pre-treatment biopsy. 
Combined sampling for persistence and 
RCL testing. 
Added anlysis of TGF- in plasma 
sample. 
Added collection of stool sample at 
baseline visit and close to Week 6 visit in 
order  
To clarify instructions on study assessments. 
2.0 SOA – Table 3 
5.1 Overall Design 
– Part 3 
6.1 Inclusion 
criteria 20 
Clarified language for obtention of the 
pre-treatment tumor biopsy if not 
feasible to obtain fresh biopsy.   
To address site feedback and clarify acceptance 
and window for obtention of baseline biopsy. 
3.2.1 Risk 
Assessment 
GSK3377794 
Theoretical risks for ICANS, RCL and 
Insertional Oncogenesis requalified as 
potential risk   
To harmonize with safety risk denomination. 
6.1 Inclusion 
criterion 2 
Addition of weight requirement to be 
≥40 kg for any participant enrolled under 
clinical drug product supply. 
Clarification of requirement for creatinine 
clearance / GFR / serum creatinine on 
pediatric patients. 
To optimize participant safety with current dosing 
and formulation requirements.  
To clarify that pediatric patients with renal 
impairment are excluded. 
6.1 Inclusion 
criterion 7 
Amended text to clarify that biopsy 
sample should be available (instead of 
is) to perform NY-ESO-1 antigen 
expression analysis. 
To clarify that both tests may occur either in 
parallel or sequentially, pending availability of 
tumor biopsy sample for NY-ESO-1 antigen 
expression testing. 
6.1 Inclusion 
criteria – 
Leukapheresis 
Lymphodepletion 
and Treatment 
 
Clarified that Inclusion criteria 1-7 must 
apply again prior to leukapheresis 
eligibility screening 
Clarified that Inclusion criteria 1-15 must 
apply again prior to lymphodepletion 
eligibility screening 
To clarify instructions for leukapheresis eligibility. 
 
 
To clarify instructions for lymphodepletion 
eligibility. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
6.1 Inclusion 
criterion 12  
Table 5 
Renal 
Amended inclusion criteria for adequate 
renal organ function: 
- 
Clarified GFR formula 
- 
Additional criteria for pediatric 
patients, based on GFR or 
serum creatinine 
To clarify inclusion criterion for adequate renal 
organ function. 
6.2 Exclusion 
criterion 22 
7.5.1 Prohibited 
Concomitant 
Medication and 
Treatments 
Exclusion of participants who intend to 
receive live vaccine during the 3 month 
period following administration of 
GSK3377794.  
Administration of live vaccine during the 
period of infusion of fludarabine, 
cyclophosphamide or GSK3377794, and 
for at least three months after last dose 
of any of these agents is prohibited. 
To clarify exclusion criteria related to live 
vaccines, and prohibition of live vaccine 
administration during and after the period of 
infusion of lymphodepleting chemotherapy or 
GSK3377794, in response to regulatory agency’s 
request. 
6.2 Exclusion 
criteria – Table 6 
Washout Periods 
for Substudy 2  
Clarification for  washout periods for 
eligibility prior to leukapheresis and prior 
to lymphodepletion. 
To clarify that washout periods are also followed 
prior to leukapheresis. 
6.3.3 Screen 
Failures 
Amended to specify that rescreened 
participants will be assigned a new 
participant number. 
Added collection of disease 
characteristics, prior lines of anti-cancer 
treatment and performance status for all 
participants at target expression 
screening visit. 
To specify that a new participant number will be 
assigned for any rescreening. 
 
To clarify that collection of medical history, prior 
anti-cancer line of treatment and performance 
status are required for screen failure participants. 
6.3.4 Rescreening 
For participants who have previously 
completed protocol-specified target 
expression testing and/or leukapheresis, 
the Sponsor will confirm the eligibility 
and use of any cryopreserved 
leukapheresis and/or manufactured 
product on evaluation for Substudy 1. 
To clarify elibility for rescreened participants. 
7.1.2 Supportive 
Therapy and/or 
Standard of Care 
Line of Therapy 
before 
Lymphodepletion 
Specified that CYP3A4, CYP2D6 and/or 
P-glycoprotein (P-gp) inducers or 
inhibitors should only be used with 
caution when administered with 
doxorubicin. 
To clarify potential drug-drug interactions with 
doxorubicin, in response to regulatory agency’s 
request. 

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Section # and 
Name 
Description of Change 
Brief Rationale 
7.1.3 
Lymphodepleting 
Chemotherapy 
Clarified that Ideal Body Weight (IBW) 
and Adjusted Body Weight (ABW) may 
be calculated according to local 
institutional guidances.   
Clarified and harmonized wording about 
initiation of G-CSF on Day -3. 
Optimized language on dose 
adjustement as fludarabine dosing is 
only adjusted based on age and renal 
impairment considerations. Similarly 
cyclophosphamide dosing is only 
adjusted based on age and weight 
considerations.  
To clarify that provided formula for IBW and ABW 
are suggested and that local institutional 
guidelines are acceptable in assessment of 
adjustments to body surface area. 
To clarify instructions for lymphodepleting dose 
adjustments and timing of G-CSF support. 
7.1.4 
GSK3377794 
Infusion 
Corrected time between end of 
lymphodepletion and T-cell infusion to 
be four (4) days instead of two (2). 
Added that a minimum of 2 doses of 
tocilizumab must be available for each 
participant for administration within 2 
hours after T-cell infusion if needed for 
treatment of CRS. 
To align protocol language wording with rest of 
document. 
To include requirement for availability of 
tocilizumab. 
9.2 Patient 
Reported 
Outcomes 
Clarified that patient reported outcome 
instruments in use for Substudies 1 and 
2 are only validated for adult 
populations. 
To clarify that patient reported outcomes in 
Substudies 1 and 2 are only required for adult 
participants. 
10.3 Populations 
for Analyses 
Clarified that the Enrolled population is 
“All participants who passed all 
screening criteria for leukapheresis” 
To clarify description of enrolled population. 
Throughout the document 
 
Minor edits 
To improve the quality of the protocol 
 
FDA 2020a and FDA 2020b 
To update references to new 2020 FDA 
guidelines for LTFU and RCL monitoring 
 

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14.4 Amendment 4 (03-DEC-2020) 
Overall Rationale for Amendment 4:  
The primary rationale for protocol Amendment 4 is to: 
1. Include Myxoid/Round Cell Liposarcoma (MRCLS) as a second translation-related 
sarcoma indication to Substudies 1 and 2. 
2. Allow fresh biopsies for NY-ESO-1 antigen expression screening, 
3. Allow for participants with high-risk locally advanced disease to be screened on 
Substudy 1,  
4. Amend analysis population definitions to align with program definitions. 

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Section # and Name 
Description of Change 
Brief Rationale 
Core protocol 
1. Synopsis 
3. Introduction 
5. Study Design 
6. Protocol population 
9.9 Biomarkers 
11. References 
“Myxoid/round cell liposarcoma” included 
as second translocation-related sarcoma 
indication for Substudies 1 and 2.  
Substudy 1 and 2 populations will 
now include HLA-A*02+ participants 
with NY ESO1+ advanced (metastatic 
or unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma.  
1. Synopsis 
4. Objectives and Endpoints 
 
Reformatted Secondary Objectves and 
Enpoints into “Secondary – Efficacy”, 
“Secondary – Safety” and “Secondary – 
Pharmacokinetics”. 
 
Removed Overall Survival (OS) from Core 
secondary objectives  
To clarify subcategories of secondary 
objectives. 
 
 
 
 
OS is a secondary objective for 
Substudy 2, but only an exploratory 
objective for Substudy 1.   
1. Synopsis 
5. Design 
 
Study Design schematic updated to include 
“Myxoid/round cell liposarcoma” in 
Substudies 1 and 2  
 
 
Total expected number of participants 
updated to approximately 80 for both 
substudies 1 and 2, and to approximately 
70 for substudy 2 to account for additional 
15 participants expected to be dosed with 
clinical drug product supply. 
 
 
Includes provision for allowing target 
expression screening, leukapheresis and 
manufacture to be conducted under 
separate GSK-sponsored protocol or 
substudy. 
Substudy 1 and 2 populations will 
now include HLA-A*02+ participants 
with NY ESO1+ advanced (metastatic 
or unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma. 
 
While sample sizes for key study 
deliverables (10 for Subtsudy 1 and 
approximately 55 for Substudy 2) do 
not change, the overall numbers must 
account for the expected 15 
additional participants to be dosed 
with clinical drug product supply 
before the switch to commercial drug 
product supply is complete. 
 
 
Will facilitate pre-screening, and 
considerations for re-allocation of 
participants onto other suited 
protocols when available. 
1. Synopsis 
5. Design 
Optimization of Treatment Fitness and 
Eligibility criteria prior to Lymphodepletion 
Removed requirement for repetition of 
all assessments for eligibility criteria 
that were already met prior to 
leukapheresis. Replaced by a 
Treatment Fitness assessment of the 
safety criteria in consultation with 
Medical Monitor.  

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Section # and Name 
Description of Change 
Brief Rationale 
5.1 Overall Design 
Provides more detailed Participant Journey 
 
Screening for Substudy 1 may now start at 
any time after diagnosis of high risk locally 
advanced disease (i.e. deeply seated, high 
grade, positive margins, large [³5 cm], or 
locally recurrent) 
 
HLA-typing and tumor antigen expression 
testing should be performed sequentially 
(considering the expected >50% attrition 
with HLA) but may also be performed in 
parallel at the discretion of the Investigator. 
 
Initiation of leukapheresis procedure now 
constitutes enrollment in the study. 
To clarify steps and align with the 
schematics 
 
 
Self-explanatory to allow for earlier 
screening of participants under 
Substudy 1 
 
 
 
 
Clarifies that preference for target 
expression is sequential (HLA-typing 
then antigen expression) but that 
parallel testing is allowed. 
 
 
 
 
This update to the definition is aligned 
with that to the substudy analysis 
populations. 
5.1 Overall Design 
6. Protocol population 
Allows for on-study fresh biopsies to be 
used for NY-ESO-1 antigen expression 
screening. If a fresh biopsy is obtained at 
screening and participant did not receive 
any supportive anticancer therapy, the 
same sample can be used for baseline. 
Allows for participants who have 
exhausted any representative tumor 
specimen to undergo biopsy 
collection on-study. 
8.1 Discontinuation of Study 
Intervention 
Optimized wording with references to 
relevant sections for dose administration, 
safety assessment and reporting, 
supportive care guidance on T-cell infusion 
and AEs of Special interests such as 
Cytokine Release Syndrome (CRS). 
Clarification of references. 
8.2.1 Temporary 
Discontinuation  
Clarified wording for liver toxicities during 
infusion with proper reference to section 
8.1. 
Clarification 
9.3.1.1 Mandated Study 
Pause Due to GBS 
Section removed because redundant with 
Section 8.5. 
Removed redundancy. 
9. Study Assessments and 
Procedures 
9.3.4 Vital Signs 
Optimized wording to make the order of 
assessments between vital signs, EKG and 
blood draws a recommendation rather than 
a requirement. 
Will allow sites to use local 
institutional guidance.  
9.4 Adverse Events and 
Serious Adverse Events 
Updated definition of Delayed AEs to align 
with updated FDA guidance [FDA, 2020a]. 
Updated definitions of 6 categories of 
delayed AEs per FDA. 

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Description of Change 
Brief Rationale 
9.4.5 Pregnancy 
For participants who have persisting 
GSK3377794 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. 
9.4.6 Cardiovascular 
Events and Death 
 
 
12.3.1 Definition of AE 
12.3.2 Definition of SAE 
All details for deaths including those 
attributed to progression of malignant 
disease will be reported. 
 
Any untoward medical occurrence even 
linked to progression of malignant disease 
will be reported, including SAEs, and SAEs 
that resulted in death. 
Clarified that SAEs that are linked to 
progression of malignant disease 
should be reported.  
9.8 Genetics 
9.9 Biomarkers 
Removed duplications between Gentetics 
and Biomarker sections 
Optimized wording 
9.9 Biomarkers 
Updated requirement for the on-study 
biopsy originally scheduled at Week 6, to 
be performed at Week 4 instead, with an 
extended period of collection (from Week 4 
until Week6)  
Optimization of timing for collection, 
as some tumors may have already 
shrunk too much by Week 6. 
9.9.1 Tumor Biopsy 
Added requirements for on-study tumor 
biopsies  
Clarification. 
9.9.2 Liquid Biopsies 
Added wording for analysis plan 
Clarification. 
9.9.9 Genetic Blood Sample 
(section added) 
Section added 
Added clarification on genetic 
analysis plan 

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Description of Change 
Brief Rationale 
Substudy 1 
Substudy 1 Title 
Substudy 1 Subtitle 
Titles and subtitles amended 
To include generic drugname 
“Letetresgene Autoleucel” and 
shortname “Lete-cel” 
To include additional indication of 
“Myxoid/round cell liposarcoma”  
1. Synopsis 
3. Introduction 
4. Objectives and Endpoints 
5. Study Design 
6. Study population 
10. Statistical 
considerations 
 
“Myxoid/round cell liposarcoma” included 
as second translocation-related advanced 
(metastatic or unresectable) sarcoma 
indication for Substudy 1.  
Substudy 1 population will now 
include HLA-A*02+ participants with 
NY ESO1+ advanced (metastatic or 
unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma.  
1. Synopsis 
5. Design 
 
Study Design schematic updated to include 
“Myxoid/round cell liposarcoma” in 
Substudy 1  
Substudy 1 population will now 
include HLA-A*02+ participants with 
NY ESO1+ advanced (metastatic or 
unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma. 
2. Schedule of Assessment 
Table 1 
Corrected reference in footnote #1. 
 
Footnote #4 has been clarified with a 
window for collection of optional Genetic 
Sample (from signature of screening 
consent until leukapheresis procedure). 
 
Footnote#8 clarifies that 7 days must be 
counted from the day of leukapheresis for 
the window of assessments. 
 
Footnote#9 has been added to specify that 
the second CD3 count should be preferably 
performed within 24 hours from 
leukapheresis procedure. 
Optimization of instructions. 

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Brief Rationale 
2. Schedule of Assessment 
Table 2 
Clarified that 1 month = 4 weeks on this 
calendar. 
 
Provided formula to clarify that Week N for 
N≥1 is to be scheduled on the 1st day of 
the week, that is on Day 7N-6  
 
Renamed Inclusion/Exclusion for treatment 
to “Treatment Fitness and 
Inclusion/Exclusion for Treatment Eligibility” 
Optimization of instructions. 
2. Schedule of Assessment 
Table 3 
Moved requirement for Week 6 on-study 
biopsy to Week 4 and added footnote #8 to 
allow for window of collection to be 
extended from Week 4 to Week 6 (from 
Day 21 to Day 39) 
 
Clarified in footnote#2 that PK, 
immunogenicity and Biomarker samples 
will not be collected at Week 10.  
Optimization of instructions. 
3.1  Substudy 1 
Background and Rationale 
for First Line Therapy with 
GSK3377794 
Updated background, added MRCLS 
section. 
 
3.2.1  Risk Assessment 
Updated safety profile of GSK3377794 
based on IB v12. 
Update. 
4. Objectives and Endpoints 
 
Reformatted Secondary Objectves and 
Enpoints into “Secondary – Efficacy”, 
“Secondary – Safety” and “Secondary – 
Pharmacokinetics”. 
To clarify subcategories of secondary 
objectives. 
 
 
 
 
To allow tools to assess MRCLS 
participants 
 
 
 
 
 
Optimized wording. 
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Description of Change 
Brief Rationale 
5.1 Overall Design 
Clarified that Drug product supply type 
(‘clinical’ vs ‘commercial’) will be recorded 
in the CRF as part of the route of synthesis. 
To allow for subgroup analyses 
between clinical and commercial 
supply. 
5.1 Overall Design 
Provides more detailed Participant Journey 
 
Screening for Substudy 1 may now start at 
any time after diagnosis of high risk locally 
advanced disease (i.e. deeply seated, high 
grade, positive margins, large [≥5 cm], or 
locally recurrent) 
 
HLA-typing and tumor antigen expression 
testing should be performed sequentially 
(considering the expected >50% attrition 
with HLA) but may also be performed in 
parallel at the discretion of the Investigator. 
 
Includes provision for allowing target 
expression screening, leukapheresis and 
manufacture to be conducted under 
separate GSK-sponsored protocol or 
substudy. 
To clarify steps and align with the 
schematics 
 
 
Self-explanatory to allow for earlier 
screening of participants under 
Substudy 1 
 
 
 
 
Clarifies that preference for target 
expression is sequential (HLA-typing 
then antigen expression) but that 
parallel testing is allowed. 
 
 
 
 
Will facilitate pre-screening, and 
considerations for re-allocation of 
participants onto other suited 
protocols when available. 
5.1 Overall Design 
6.1 Inclusion Criteria 
6.2 Exclusion Criteria 
Allows for on-study fresh biopsies to be 
used for NY-ESO-1 antigen expression 
screening. If a fresh biopsy is obtained at 
screening and participant did not receive 
any supportive anticancer therapy, the 
same sample can be used for baseline. 
 
Optimization of Treatment Fitness and 
Eligibility criteria prior to Lymphodepletion 
Allows for participants who have 
exhausted any representative tumor 
specimen to undergo biopsy 
collection on-study. 
 
 
 
 
 
Removed requirement for repetition of 
all assessments for eligibility criteria 
that were already met prior to 
leukapheresis. Replaced by a 
Treatment Fitness assessment of the 
safety criteria in consultation with 
Medical Monitor.  
5.2 Number of participants 
Clarified wording without any change to 
sample size 
Optimization 

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6.1 Inclusion criteria 
Amended inclusion #2 to include 
requirement to consult with Medical Monitor 
if participant is weighing <40kg and is 
scheduled to receive commercial drug 
supply. 
 
Amended Inclusion#3 to include 
translocation-specific requirements for 
MRCLS 
 
Amended Inclusion criteria #4 to allow for 
participants with high-risk locally advanced 
disease to be screened. 
 
Amended Inclusion #7 to allow for on-study 
fresh biopsy specimen for screening, and 
inclusion of reference to guidance on 
acceptable specimen in Section 5.1 
 
Added Inclusion #8 to ensure life 
expectancy at leukapheresis is ≥24 weeks 
 
Added Inclusion #9 to require diagnosis of 
advanced (metastatic or unresectable) 
disease prior to leukapheresis. 
 
Amended Inclusions #10 and #11 (formerly 
#8 and #9) to allow for HLA-typing and NY-
ESO-1 antigen expression test to be 
conducted under separate GSK-sponsored 
protocol or substudy. 
 
Amended Inclusion #12 (formerly #10) to 
exclude any evidence of clinically 
significant pericardial effusion. 
 
Amended Table 4 of Definitions of 
Adequate Organ Function: 
- to specify ANC must be measured without 
G-CSF support) 
- to remove requirement for CD3 count 
- to clarify Lymphocyte count is absolute 
(ALC) 
- to clarify steps to assess creatinine 
clearance for participants between 18 and 
65 
- to add a nutritional status criterion with 
Albumin (≥3.5 g/dL) 
 
Amended Inclusion #20 (formerly #18) to 
specify that fresh biopsy obtained at 
screening may be used at baseline if 
participant did not receive any supportive 
anti-cancer therapy in between.  
Addition to ensure safety oversight in 
treatment of participants weighing 
<40kg.  
 
 
 
 
Addition 
 
 
 
Allowing participants with earlier 
diagnosis to be screened on 
Substudy 1. 
 
 
Allows for fresh biopsies on study. 
 
 
 
 
 
New addition to ensure participant 
survival from screening to T-cell 
infusion. 
 
 
Ensure that participants candidates 
for leukapheresis have been 
diagnosed with advanced (metastatic 
or unresectable) disease. 
 
 
Will allow for easier pre-screening or 
transfer of participants between GSK-
sponsored protocols. 
 
 
 
 
 
Added safety precautions. 
 
 
 
Added clarity and safety precautions. 
 
 
 
 
 
 
 
 
 
 
 

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Section # and Name 
Description of Change 
Brief Rationale 
 
Added provision to only collect one 
fresh biopsy between screening and 
baseline visit if no supportive anti-
cancer therapy was given in between. 
7.1.3 Lymphodepleting 
Chemotherapy 
Clarified situations where Medical Monitor 
must e consulted to discuss 
Lymphodepleting regimen dose 
adjustments. 
 
Clarified that if creatine clearance is 
estimated that the same method as for 
adequate organ function should be used to 
consider fludarabine dose adjustments 
Added safety oversight and 
precautions. 
 
 
 
 
Added clarification. 
9.2.2 European 
Organization for Research 
and Treatment of Cancer 
Quality of Life 
Questionnaire 
Title amended to Item Library 31 (Disease 
Symptoms) 
Title amended per EORTC 
recommendation. 
9.2.7 European 
Organization for Research 
and Treatment of Cancer 
Quality of Life 
Questionnaire 
Title amended to Item Library 30 (Sensory 
Symptoms) 
Added to allow for MRCLS 
participants. 
10.2 Sample size 
justification 
Added that considerations will look at the 
pooled overall response rate (ORR) across 
both synovial sarcoma and myxoid/round 
cell liposarcoma populations. 
 
Populations for analysis: 
- 
Screened Population was amended to 
include “All participants who signed an 
ICF to participate in the study” 
- 
Enrolled and Intent-To-Treat (ITT) 
populations were amended to the 
same definition of  “All participants 
who started leukapheresis procedure” 
- 
Safety and modified Intent-To-Treat 
(mITT) populations were amended to 
the same definition of  “All participants 
who received any dose of 
GSK3377794”  
Optimization and standardization of 
reporting across the program. 

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Description of Change 
Brief Rationale 
Substudy 2 
Substudy 2 Title 
Substudy 2 Subtitle 
Titles and subtitles amended 
To include generic drugname 
“Letetresgene Autoleucel” and 
shortname “Lete-cel” 
To include additional indication of 
“Myxoid/round cell liposarcoma”  
1. Synopsis 
3. Introduction 
4. Objectives and Endpoints 
5. Study Design 
6. Study population 
10. Statistical 
considerations 
 
“Myxoid/round cell liposarcoma” included 
as second translocation-related sarcoma 
indication for Substudy 2.  
Substudy 2 population will now 
include HLA-A*02+ participants with 
NY ESO1+ advanced (metastatic or 
unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma.  
1. Synopsis 
5. Design 
 
Study Design schematic updated to include 
“Myxoid/round cell liposarcoma” in 
Substudy 2  
 
 
Footnote under schematic clarifies that 
Substudy 2 will accrue about approximately 
70 participants to account for additional 15 
participants expected to be dosed with 
clinical drug product supply. 
Substudy 2 population will now 
include HLA-A*02+ participants with 
NY ESO1+ advanced (metastatic or 
unresectable) synovial sarcoma or 
myxoid/round cell liposarcoma. 
 
While the sample size for the key 
deliverables on Substudy 2 of 
approximately 55 does not change, 
the overall numbers must account for 
the expected 15 additional 
participants to be dosed with clinical 
drug product supply before the switch 
to commercial drug product supply is 
complete. 
2. Schedule of Assessment 
Table 1 
Corrected reference in footnote #1. 
 
Footnote #4 has been clarified with a 
window for collection of optional Genetic 
Sample (from signature of screening 
consent until leukapheresis procedure). 
 
Footnote#8 clarifies that 7 days must be 
counted from the day of leukapheresis for 
the window of assessments. 
 
Footnote#9 has been added to specify that 
the second CD3 count should be preferably 
performed within 24 hours from 
leukapheresis procedure. 
Optimization of instructions. 

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Section # and Name 
Description of Change 
Brief Rationale 
2. Schedule of Assessment 
Table 2 
Clarified that 1 month = 4 weeks on this 
calendar. 
 
Provided formula to clarify that Week N for 
N≥1 is to be scheduled on the 1st day of 
the week, that is on Day 7N-6  
 
Renamed Inclusion/Exclusion for treatment 
to “Treatment Fitness and 
Inclusion/Exclusion for Treatment Eligibility” 
Optimization of instructions. 
2. Schedule of Assessment 
Table 3 
Moved requirement for Week 6 on-study 
biopsy to Week 4 and added footnote #8 to 
allow for window of collection to be 
extended from Week 4 to Week 6 (from 
Day 21 to Day 39) 
 
Clarified in footnote#2 that PK, 
immunogenicity and Biomarker samples 
will not be collected at Week 10.  
Optimization of instructions. 
3.1  Substudy 2 
Background and Rationale 
Updated background, added MRCLS 
section. 
 
4. Objectives and Endpoints 
 
Reformatted Secondary Objectves and 
Enpoints into “Secondary – Efficacy”, 
“Secondary – Safety” and “Secondary – 
Pharmacokinetics”. 
 
To clarify subcategories of secondary 
objectives. 
 
 
 
 
To allow tools to assess MRCLS 
participants 
 
 
 
 
 
Optimized wording. 
5.1 Overall Design 
Clarified that Drug product supply type 
(‘clinical’ vs ‘commercial’) will be recorded 
in the CRF as part of the route of synthesis. 
To allow for subgroup analyses 
between clinical and commercial 
supply. 
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Description of Change 
Brief Rationale 
5.1 Overall Design 
Provides more detailed Participant Journey 
 
HLA-typing and tumor antigen expression 
testing should be performed sequentially 
(considering the expected >50% attrition 
with HLA) but may also be performed in 
parallel at the discretion of the Investigator. 
 
Includes provision for allowing target 
expression screening, leukapheresis and 
manufacture to be conducted under 
separate GSK-sponsored protocol or 
substudy. 
To clarify steps and align with the 
schematics 
 
 
Clarifies that preference for target 
expression is sequential (HLA-typing 
then antigen expression) but that 
parallel testing is allowed. 
 
 
 
 
Will facilitate pre-screening, and 
considerations for re-allocation of 
participants onto other suited 
protocols when available. 
5.1 Overall Design 
6.1 Inclusion Criteria 
6.2 Exclusion Criteria 
Allows for on-study fresh biopsies to be 
used for NY-ESO-1 antigen expression 
screening. If a fresh biopsy is obtained at 
screening and participant did not receive 
any supportive anticancer therapy, the 
same sample can be used for baseline. 
 
Optimization of Treatment Fitness and 
Eligibility criteria prior to Lymphodepletion 
Allows for participants who have 
exhausted any representative tumor 
specimen to undergo biopsy 
collection on-study. 
 
 
 
 
 
Removed requirement for repetition of 
all assessments for eligibility criteria 
that were already met prior to 
leukapheresis. Replaced by a 
Treatment Fitness assessment of the 
safety criteria in consultation with 
Medical Monitor.  
5.2 Number of participants 
Clarified the need to update the accrual 
projections for Substudy 2 to approximately 
70 participants to account for 15 
participants expected to be treated with the 
clinical drug product supply without any 
change to sample size for the primary 
analysis of approximately 55 participants 
planned to receive commercial drug 
product supply. 
Amended. 

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6.1 Inclusion criteria 
Amended inclusion #2 to include 
requirement to consult with Medical Monitor 
if participant is weighing <40kg and is 
scheduled to receive commercial drug 
supply. 
 
Amended Inclusion#3 to include 
translocation-specific requirements for 
MRCLS 
 
Amended Inclusion criteria #4 to allow for 
MRCLS participants with advanced 
(metastatic or unresectable) disease. 
 
Amended Inclusion #5 to clarify that 
“Participants who received anthracycline-
based therapy in the neoadjuvant/adjuvant 
setting" must have progressed within 12 
months of completing the regimen to be 
eligible 
 
Amended Inclusion #7 to allow for on-study 
fresh biopsy specimen for screening, and 
inclusion of reference to guidance on 
acceptable specimen in Section 5.1 
 
Added Inclusion #8 to ensure life 
expectancy at leukapheresis is ≥24 weeks 
 
Amended Inclusions #9 and #10 (formerly 
#8 and #9) to allow for HLA-typing and NY-
ESO-1 antigen expression test to be 
conducted under separate GSK-sponsored 
protocol or substudy. 
 
Amended Inclusion #11 (formerly #10) to 
exclude any evidence of clinically 
significant pericardial effusion. 
 
Amended Table 5 of Definitions of 
Adequate Organ Function: 
- to specify ANC must be measured without 
G-CSF support) 
- to remove requirement for CD3 count 
- to clarify Lymphocyte count is absolute 
(ALC) 
- to clarify steps to assess creatinine 
clearance for participants between 18 and 
65 
- to add a nutritional status criterion with 
Albumin (≥3.5 g/dL) 
 
Amended Inclusion #21 (formerly #20) to 
specify that fresh biopsy obtained at 
screening may be used at baseline if 
Addition to ensure safety oversight in 
treatment of participants weighing 
<40kg.  
 
 
 
 
Addition 
 
 
 
Confirming that participants of either 
indication with advanced diagnosis 
may be screened on Substudy 2. 
 
Clarification. 
 
 
 
 
 
 
Allows for fresh biopsies on study. 
 
 
 
 
 
New addition to ensure participant 
survival from screening to T-cell 
infusion. 
 
 
Will allow for easier pre-screening or 
transfer of participants between GSK-
sponsored protocols. 
 
 
 
 
 
Added safety precautions. 
 
 
 
Added clarity and safety precautions. 
 
 
 
 
 
 
 
 
 
 
 

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Section # and Name 
Description of Change 
Brief Rationale 
participant did not receive any supportive 
anti-cancer therapy in between. 
 
Added provision to only collect one 
fresh biopsy between screening and 
baseline visit if no supportive anti-
cancer therapy was given in between. 
7.1.2 Supportive therapy 
Section amended for clarification 
Added clarification. 
7.1.3 Lymphodepleting 
Chemotherapy 
Clarified situations where Medical Monitor 
must e consulted to discuss 
Lymphodepleting regimen dose 
adjustments. 
 
Clarified that if creatine clearance is 
estimated that the same method as for 
adequate organ function should be used to 
consider fludarabine dose adjustments 
Added safety oversight and 
precautions. 
 
 
 
 
Added clarification. 
9.2.2 European 
Organization for Research 
and Treatment of Cancer 
Quality of Life 
Questionnaire 
Title amended to Item Library 31 (Disease 
Symptoms) 
Title amended per EORTC 
recommendation. 
9.2.7 European 
Organization for Research 
and Treatment of Cancer 
Quality of Life 
Questionnaire 
Title amended to Item Library 30 (Sensory 
Symptoms) 
Title amended per EORTC 
recommendation. 
10.1 Statistical hypotheses 
Changed conservative benchmark of 18% 
to the upper range of the historical ORR of 
13%. 
 
Added that “the primary analysis will be 
based on the combined data from both SS 
and MRCLS.  Additional subgroup 
analyses by indication may be prepared as 
appropriate.” 
Optimization. 
10.2 Sample size 
justification 
Updated justification using the new 
benchmark of 13%. 
Added wording that “Though a smaller 
sample size could be utilized for the 
efficacy assessment with adequate power 
>90%, the larger sample size has been 
implemented to allow for a more robust 
safety database.” 
Optimization. 

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Brief Rationale 
10.3 Populations for 
Analyses 
Amended definitions as below: 
- 
Screened Population was amended to 
include “All participants who signed an 
ICF to participate in the study” 
- 
Enrolled and Intent-To-Treat (ITT) 
populations were amended to the 
same definition of  “All participants 
who started leukapheresis procedure” 
- 
Safety population was amended to “All 
participants who received any dose of 
GSK3377794” 
- 
Modified ITT (mITT) population was 
amended to “All participants who 
received at least the minimum target 
dose of GSK3377794” with the 
minimum target dose being 1x10^9 
transduced T cells 
- 
mITTc was amended to “All 
participants who received at least the 
minimum target dose of GSK3377794 
from commercial drug product supply” 
- 
the Primary Efficacy Analysis 
Population (PEAP) was amended to 
“The first 45 participants who received 
at least the minimum target dose of 
GSK3377794 from commercial drug 
product supply”. 
Optimization of population definitions. 
10.5.5 Interim Analyses 
Added wording to specify that “The interim 
analysis will use efficacy data based on 
Investigators’ assessments instead of the 
independent central review assessments”. 
Clarification. 
 

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14.4 Amendment 5 (19-MAY-2021) 
Overall Rationale for Amendment 5: 
The primary rationale for protocol Amendment 5 is to: 
1. Inclusion of updated safety language: 
a. for increased monitoring of coagulation and cardiotoxicity biomarkers 
b. for management of CRS and ICANS 
c. for lymphodepleting regimen dose adjustements and assessment of renal 
function   
2. Update on Disease-specific translocation requirements 
3. Clarification of End of Interventional Phasephase, End of Follow-up phase and 
End of substudySubstudy definitions 
 

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Name 
Description of Change 
Brief Rationale 
Core protocol 
9.1.1 Evaluation of 
Anti-Cancer Activity 
Clarification that in cases where 
contrast enhanced CT is 
contraindicated, a Magnetic 
Resonance Imaging (MRI) of the 
abdomen/pelvis (with and without 
gadolinium contrast), and an MRI (with 
and without gadolinium contrast) or a 
non-contrast enhanced CT of the chest 
is acceptable.  
Clarification of imaging modalities.   
9.3.5 Cardiac 
Assessments 
Addition of serum troponin and 
N-terminal pro B-type natriuretic 
peptide (NT-proBNP) / BNP tests. 
Addition of cardiac biomarker tests as part of 
required baseline visit assessments.  
9.3.9.1. Testing for 
RCL in Clinical 
Studies  
And 
9.3.10. Testing for 
Persistence of 
Transduced T  cells 
and Insertional 
Oncogenesis 
Clarified language to align with Long-
term Follow-up Study 208750, 
including:   
- discontinuation of persistence/RCL 
monitoring at  ≥2 year post T-cell 
infusion  for participants whose 
transduced T cells are undetected for 2 
consecutive visit assessments 
- allow medical evaluations to take 
place via telemedicine (e.g. phone call 
or video conferences) and/or home 
healthcare where country and/or local 
regulations allow 
- added option of remote visits for 
years 6-15 
Clarification based on FDA guidance.  
9.4.5. Pregnancy 
For participants who have persisting 
GSK3377794 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. 
12.1.10 Remote 
Monitoring and 
Source Data 
Verification 
Addition of provision that when onsite 
monitoring is not permissible due to 
site/local restrictions (such as with 
epidemic and/or pandemic), remote 
monitoring may be employed that 
ensures all of the following 
requirements are met 
Clarification on remote monitoring.  
12.2 Appendix 2: 
Clinical Laboratory 
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. 
Additions of coagulation and cardiac biomarker 
tests.  

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Name 
Description of Change 
Brief Rationale 
12.3.4. Recording 
and Follow-Up of AE 
and SAE 
Clarified grading specifications for AEs 
and SAEs of CRS and ICANS. 
Assessment of intensity of AEs and SAEs 
12.7.1. T cell Infusion 
Symptom 
Management 
In participants with infusion-related 
reaction Grade ≤2, infusion may be 
restarted once resolved to Grade <1. 
The bag of cells that was being infused 
prior to reaction, cannot be used 
beyond 45 min after thawing. Infusion-
related reactions Grade 3 or higher 
during infusion should be reported to 
Sponsor promptly 
Clarification on restarting Infusion after 
temporary Infusion related reaction 
12.7.2.2 Herpes 
Simplex and Varicella 
Zoste and Epstein 
Barr virusr 
 
12.7.2.4 Hepatitis B 
prophylaxis 
 
 
 
12.7.2.6 Other Anti-
Microbial Prophylaxis 
Clarified that prophylaxis for herpex 
simplex and varicella zoster should be 
initiated prior to lymphodepletion. 
 
Clarified that additional considerations 
on Hepatitis B prophylaxis (acceptable 
regimens included) will be left to the 
Investigator’s discretion in accordance 
with label recommendations and 
institutional guidelines. 
Clarified that prolonged leukopenia 
may alert for latent viral infections 
 
If a patient presents with severe or 
gross hematuria consider checking for 
BK viruria and viremia. 
Optimizatino of Infection prophylaxis language. 
12.7.5. Management 
of Cytokine Release 
Syndrome 
Addition of monitoring requirement for 
suspected CRS, with chemistry, 
hematology, ferritin, coagulation, 
C-reactive protein, troponin and NT-
proBNP / BNP labs. 
Addition of monitoring requirement on 
left ventricular ejection fraction for 
suspected CRS. 
Clarified posology for tocilizumab and 
alternative options for participants not 
respondsing to tocilizumab. 
Additions of monitoring requirments for CRS 
accoding to SITC 2020 guideline on immune 
effector cell-related adverse events.  
12.7.8. Management 
of Immune Effector 
Cell-Associated 
Neurotoxicity 
Syndrome (ICANS) 
Addition of monitoring requirement for 
suspected ICANS, with chemistry, 
hematology, ferritin, coagulation and 
C-reactive protein. 
Clarification of ICANS management 
table. Addition that tocilizumab may 
worsen ICANS in some situations. 
Additions of monitoring requirements for ICANS 
accoding to SITC 2020 guideline on immune 
effector cell-related adverse events.  

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Section # and 
Name 
Description of Change 
Brief Rationale 
Substudy 1 
2. Schedule of 
Assessment 
Table 1 & Table 2 
Footnote #1 (Table 1) has been 
amended to state that consent for 
Leukapheresis and Treatment must be 
repeated if given more than 90 days 
prior to leukapheresis procedure. 
Footnote #13 (Table 1) Window for 
CT/MRI or FDG PET/CT scan 
performed as standard of care prior to 
study consent will be acceptable as 
long as assessment is done within 90 
days before leukapheresis.  
Footnote #14 (Table 1) has been 
added to state that MRI of the spine will 
be performed when clinically indicated. 
Added requirement forTroponin and 
NT-proBNP / BNP test prior to 
Lymphodepletion (Table 2) 
Added Coagulation assessments for 
baseline, Day 1 thru 4, Day 6, Day 8, 
and Day 15 (Table 2) 
Included requirement for suspected 
CRS or ICANS to monitor chemistry, 
hematology, ferritin, coagulation and 
C-reactive protein labs, daily for a week 
then every other day until symptoms 
are improving or an alternative 
diagnosis is confirmed. Included 
reuirement for monitoring of troponin 
and NT-proBNP / BNP labs for CRS 
Grade ≥2 as clinically indicated. 
Clarification of window for consent. 
 
 
 
 
Clarification of window for scans for eligibility 
 
 
 
 
 
Addition of MRI of spine if clinically indicated 
 
 
Addition of cardiac marker and coagulation 
tests. 
 
 
 
 
 
Clarification of schedule of assessment for 
suspected CRS or ICANS. 
3.2.1 Risk 
Assessment 
 
Updated risk assessment table: 
- to include risks of decreased vision 
and peripheral neuropathy for 
lymphodepleting chemotherapy 
(fludarabine/cyclophosphamide);  
- to include/amend risks of 
haematopoietic cytopenias, 
hypersensitivity, reactivation of 
previous viral infections after prolonged 
leukopenia, neutropenia (including fatal 
neutropenia) decreased vision, to 
GSK3377794 infusion.  
Safety update.  

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CONFIDENTIAL 
 
 
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310 
  
Section # and 
Name 
Description of Change 
Brief Rationale 
5.3 End of Study 
definition 
Clarified the end of interventional 
phase, and end of study for individual 
participants and the study as a whole in 
order to ensure continuous follow-up of 
participants until transition to long-term 
follow-up protocol 208750. 
Clarification.  
6.1 Inclusion criteria 
Amended Table 4 of Definitions of 
Adequate Organ Function: 
- to add footnote c  recommending 
consultation with hematologist prior to 
lymphodepletion in participants who 
have had a serious/significant 
bleeding/thrombosis history. 
- to add footnote d referring to Section 
7.5.2  for guideline on use of 
anticoagulant medications  
Added safety oversight, precautions and 
management guidelines. 
6.1 Inclusion criterion 
#20 (added) 
Hematologist consultation prior to 
lymphodepletion for participants with 
serious/significant bleeding/thrombosis 
history. 
Added hematologist consultation when 
indicated 
6.1 Inclusion #3  
Clarification on translocation 
requirement for inclusion of SS and 
MRCLS participants: Methods, such 
as, but not limited to, Fluorescence in 
situ hybridization (FISH) assay or Next 
Generation Sequencing (NGS) are 
commonly used to detect 
translocations. 
Clarification of methods of detection of 
translocations. 
7.1.1 Leukapheresis 
Clarification that a CD3 count of 
≥200/L is recommended to ensure 
adequate collection of T cells.  In 
situations where CD3 count is lower 
than 200, test is to be repeated and 
Sponsor is to be alerted, as more than 
one leukapheresis procedure may be 
needed.  
Clarification on CD3 count 
7.5.2. Permitted 
Concommitant 
Medication and 
Treatment 
Added recommendations for 
management of participants on 
therapeutic anticoagulants: 
Optimization of safety oversight and 
precautions. 

TMF-14132897 
CONFIDENTIAL 
 
 
208467 
 
311 
  
Section # and 
Name 
Description of Change 
Brief Rationale 
Substudy 2 
2. Schedule of 
Assessment 
Tables 1 & 2 
Footnote #1 (Table 1) has been 
amended to state that consent for 
Leukapheresis and Treatment must be 
repeated if given more than 90 days 
prior to leukapheresis procedure. 
Footnote #13 (Table 1) Window for 
CT/MRI or FDG PET/CT scan 
performed as standard of care prior to 
study consent will be acceptable as 
long as assessment is done within 90 
days before leukapheresis.  
Footnote #14 (Table 1) has been 
added to state that MRI of the spine will 
be performed when clinically indicated. 
Added requirement forTroponin and 
NT-proBNP / BNP test prior to 
Lymphodepletion (Table 2) 
Added Coagulation assessments for 
baseline, Day 1 thru 4, Day 6, Day 8, 
and Day 15 (Table 2) 
Included requirement for suspected 
CRS or ICANS to monitor chemistry, 
hematology, ferritin, coagulation and 
C-reactive protein labs, daily for a week 
then every other day until sympotms 
are improving or an alternative 
diagnosis is confirmed. Included 
reuirement for monitoring of troponin 
and NT-proBNP / BNP labs for CRS 
Grade ≥2 as clinically indicated. 
Clarification of window for consent. 
 
 
 
 
Clarification of window for scans for eligibility 
 
 
 
 
 
Addition of MRI of spine if clinically indicated 
 
 
Addition of cardiac marker and coagulation 
tests. 
 
 
 
 
 
Clarification of schedule of assessment for 
suspected CRS or ICANS. 
3.2.1 Risk 
Assessment 
 
Updated risk assessment table: 
- to include risks of decreased vision 
and peripheral neuropathy for 
lymphodepleting chemotherapy 
(fludarabine/cyclophosphamide);  
- to include/amend risks of 
haematopoietic cytopenias, 
hypersensitivity, reactivation of 
previous viral infections after prolonged 
leukopenia, neutropenia (including fatal 
neutropenia) decreased vision, to 
GSK3377794 infusion. 
Safety update.  

TMF-14132897 
CONFIDENTIAL 
 
 
208467 
 
312 
  
Section # and 
Name 
Description of Change 
Brief Rationale 
5.3 End of Study 
definition 
Clarified the end of interventional 
phase, end of follow-up phase, and end 
of study for individual participants and 
the study as a whole in order to ensure 
continuous follow-up of participants 
until transition to the long-term follow-
up protocol 208750. 
Clarification.  
6.1 Inclusion criteria 
Amended Table 4 of Definitions of 
Adequate Organ Function: 
- to add footnote c  recommending 
consultation with hematologist prior to 
lymphodepletion in participants who 
have had a serious/significant 
bleeding/thrombosis history. 
- to add footnote d referring to Section 
7.5.2  for guideline on use of 
anticoagulant medications  
Added safety oversight, precautions and 
management guidelines. 
6.1 Inclusion criterion 
#21 (added) 
Hematologist consultation prior to 
lymphodepletion for participants with 
serious/significant bleeding/thrombosis 
history. 
Added hematologist consultation when 
indicated 
6.1 Inclusion #3  
Clarification on translocation 
requirement for inclusion of SS and 
MRCLS participants: Methods, such 
as, but not limited to, Fluorescence in 
situ hybridization (FISH) assay or Next 
Generation Sequencing (NGS) are 
commonly used to detect 
translocations. 
Clarification of methods of detection of 
translocations. 
7.1.1 Leukapheresis 
Clarification that a CD3 count of 
≥200/L is recommended to ensure 
adequate collection of T cells.  In 
situations where CD3 count is lower 
than 200, test is to be repeated and 
Sponsor is to be alerted as more than 
one leukapheresis procedure may be 
needed.  
Clarification on CD3 count 
7.5.2. Permitted 
Concommitant 
Medication and 
Treatment 
Added recommendations for 
management of participants on 
therapeutic anticoagulants: 
Added safety oversight and precautions. 
 

Signature Page for  208467 TMF-14132897 v1.0
Signature Page for TMF-14132897 v1.0
Reason for signing: Approved
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Role: A
Date of signature: 04-Nov-2021 13:20:15 GMT+0000
PPD