Clinical trial NCT02992743
Conditions: Neoplasms
Keywords: Myxoid/ round cell liposarcoma Letetresgene autoleucel Immuno-oncology T Cell Receptor Leukapheresis NY-ESO-1 Adoptive TCR T-cell therapy
Sponsor: GlaxoSmithKline
Start date: 2016-12-06; Completion date: 2022-03-22
Enrollment: 23 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

Detailed description:
New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A\*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

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

Protocol documents:
SAP_002.pdf: 
C O N FI D E N TI A L  
T h e Gl a x o S mit h Kli n e gr o u p of c o m p a ni e s  
2 0 8 4 6 9  
1  
 
Di visi o n  
: W orl d wi de  De vel o p me nt  
I nf or m ati o n T y pe 
: Re p orti n g a n d A nal ysis Pla n  ( R A P) 
Title  
: Re p orti n g a n d A nal ysis Pla n f or A Pil ot St u d y of 
N Y -E S O -1 c2 5 9T Cells i n Partici pa nts  wit h  A d va nce d 
M y x oi d/  R o u n d Cell Li p osarc o ma  
St u d y N u m ber  
: 2 0 8 4 6 9  
C o m p o u n d N u m ber  : G S K 3 3 7 7 7 9 4  
A p pr o v al D ate  
: 0 5 M a y 2 0 2 2  
 
Descri pti o n:  
•  
T he p ur p ose of t his R A P is t o descri be t he pla n ne d a nal ys es a n d o ut p ut t o b e 
i ncl u de d i n t he fi nal Cli nical St u d y Re p ort f or Pr ot oc ol 2 0 8 4 6 9.  
•  
T his R A P is i nte n de d t o descri be t he pl a n ne d effi cac y a n d safet y a nal yses  
re q uire d f or t he st u d y.  
•  
T his R A P will be pr o vi de d t o t he st u d y tea m me m bers t o c o n ve y t he c o nte nt of 
i nteri m a nal ysis deli vera bles as well as  d eli vera bl e s f or t he pri mar y a n d fi n al 
a nal ys es . 
 
A ut h or(s):  
A ut h or  
D ate  
0 5 M a y 2 0 2 2  
Statisticia n ( C o nti n ge nt W or ker)   
( O nc ol o g y Cli nical Statistics) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o p yri g ht 2 0 2 2  t he Gla x o S mit h Kli ne gr o u p of c o m pa nies. All ri g hts r eser ve d.  
U na ut h orise d c o p yi n g or use of t his i nf or mati o n is pr o hi bite d .
P P D


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
2  
 
R A P Te a m  R e vie w C o nfir m ati o n s: 
( Met h o d: V ee v a V a ult A ut h ori n g W or kfl o w ) 
Re vie wer  
Pri nci pal Pr o gra m mer  
( O nc ol o g y Cli nical Pr o gra m mi n g) 
Me dical M o nit or  
( O nc ol o g y Cli nical) 
 
Cli nical Scie ntist  
( O nc ol o g y Cli nical) 
 
 
(Earl y P hase an d Cell & Ge ne T hera p y, P har ma Safet y ) 
 
, Cli nical Bi o mar ker Lea d 
( O nc ol o g y Cell T hera p y) 
(Cli nical P har mac ol o g y M o delli n g  & Si m ulati o n ) 
, Cli nical De vel o p me nt Lea d 
( O nc ol o g y Cli nical)  
Cli nic al St atistics a n d Cli nic al Pr o gr a m mi n g Li ne A p pr o v als : 
Met h o d: Vee v a V a ult T M F e Si g n at ure  
A p pr o ver  
  
( O nc ol o g y Cli nical Statistics ) 
 
  
( O nc ol o g y Cli nical Pr o gra m mi n g) 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
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TABLE OF CONTENTS 
PAGE 
TABLE OF CONTENTS .................................................................................................. 3 
1. 
INTRODUCTION ...................................................................................................... 6 
1.1. 
RAP Amendments ........................................................................................ 8 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION ................................................ 16 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan .......................... 16 
2.2. 
Study Objective(s) and Endpoint(s)............................................................. 17 
2.3. 
Study Design .............................................................................................. 19 
2.3.1. 
Retreatment ................................................................................. 20 
2.4. 
Statistical Analyses ..................................................................................... 21 
3. 
PLANNED ANALYSES .......................................................................................... 22 
3.1. 
Interim Analyses ......................................................................................... 22 
3.1.1. 
Interim Analysis of Futility ............................................................ 22 
3.1.2. 
Interim Analyses of Second “High Lymphodepletion” 
Cohort for Internal Decision Making ............................................. 23 
3.2. 
Primary Analyses ........................................................................................ 24 
3.3. 
Final Analyses ............................................................................................ 25 
4. 
ANALYSIS POPULATIONS ................................................................................... 26 
4.1. 
Protocol Deviations ..................................................................................... 27 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 28 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 28 
5.1.1. 
Retreatment ................................................................................. 28 
5.2. 
Baseline Definitions .................................................................................... 29 
5.3. 
Multicenter Studies ..................................................................................... 29 
5.4. 
Examination of Covariates, Other Strata, and Subgroups ........................... 29 
5.5. 
Multiple Comparison and Multiplicity ........................................................... 29 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 30 
6. 
STUDY POPULATION ANALYSES ....................................................................... 31 
6.1. 
Overview of Planned Study Population Analyses ........................................ 31 
6.2. 
Disposition of Participants ........................................................................... 31 
6.3. 
Protocol Deviations ..................................................................................... 32 
6.4. 
Demographic and Baseline Characteristics ................................................. 32 
6.5. 
Prior and Concomitant Medications ............................................................ 33 
6.6. 
Study Treatment Exposure ......................................................................... 33 
6.7. 
Anti-Cancer Therapies ................................................................................ 34 
6.7.1. 
Prior Anti-Cancer Therapies......................................................... 34 
6.7.2. 
On-Study Anti-Cancer Therapies ................................................. 35 
7. 
EFFICACY ANALYSES .......................................................................................... 36 
7.1. 
Primary Efficacy Analyses .......................................................................... 36 
7.1.1. 
Endpoint / Variables ..................................................................... 36 
7.1.2. 
Summary Measure ...................................................................... 38 


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
4  
 
7. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 3 8  
7. 1. 4.  
Str at e g y f or I nt er c urr e nt E v e nt s  ................................................... 3 8  
7. 1. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 3 8  
7. 2.  
S e c o n d ar y Effi c a c y A n al y s e s  ...................................................................... 3 9  
7. 2. 1.  
E n d p oi nt / V ari a bl e s  ..................................................................... 3 9  
7. 2. 2.  
Pr o gr e s si o n Fr e e S ur vi v al ( P F S)  ................................................. 3 9  
7. 2. 3.  
S u m m ar y M e a s ur e  ...................................................................... 4 3  
7. 2. 4.  
P o p ul ati o n of I nt er e st  ................................................................... 4 4  
7. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 4 4  
7. 3.  
E x pl or at or y Effi c a c y A n al y si s  ...................................................................... 4 4  
7. 4.  
I nt eri m A n al y s e s ......................................................................................... 4 7  
7. 4. 1.  
O v er all R e s p o n s e R at e ( O R R) wit h C o nfir m ati o n p er 
R E CI S T  v 1. 1 b y I n v e sti g at or A s s e s s m e nt .................................... 4 7  
7. 4. 2.  
P o p ul ati o n of I nt er e st  ................................................................... 4 7  
7. 4. 3.  
Str at e g y f or I nt er c urr e nt E v e nt s  ................................................... 4 7  
7. 4. 4.  
St ati sti c al A n al y s e s / M et h o d s  ..................................................... 4 7  
8.  
S A F E T Y A N A L Y S E S  ............................................................................................. 4 8  
8. 1.  
A d v er s e E v e nt s A n al y s e s  ........................................................................... 4 8  
8. 2.  
A d v er s e E v e nt s of S p e ci al I nt er e st A n al y s e s  .............................................. 5 0  
8. 2. 1.  
a n d Gr aft v er s u s H o st 
Di s e a s e ( G v H D)  ........................................................................... 5 2  
8. 3.  
Cli ni c al L a b or a t or y A n al y s e s ....................................................................... 5 2  
8. 3. 1.  
A n al y s e s of Li v er F u n cti o n T e st s ( L F T)  ........................................ 5 4  
8. 4.  
Ot h er S af et y A n al y s e s  ................................................................................ 5 5  
8. 4. 1.  
E C O G P erf or m a n c e St at u s  .......................................................... 5 5  
8. 4. 2.  
E C G  ............................................................................................. 5 5  
8. 4. 3.  
Vit al Si g n s  .................................................................................... 5 6  
8. 4. 4.  
Pr e g n a n ci e s  ................................................................................. 5 6  
8. 4. 5.  
R e pli c ati o n C o m p et e nt L e nti vir u s ( R C L)  ...................................... 5 6  
8. 4. 6.  
P B M C s  ........................................................................................ 5 6  
8. 4. 7.  
C O VI D -1 9  .................................................................................... 5 7  
9.  
P H A R M A C O KI N E TI C A N A L Y S E S  ......................................................................... 5 7  
9. 1.  
P er si st e n c e of N Y -E S O -1 c 2 5 9T  .................................................................... 5 7  
9. 1. 1.  
E n d p oi nt/ V ari a bl e s  ....................................................................... 5 7  
9. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 5 9  
9. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 5 9  
1 0.  BI O M A R K E R A N A L Y S E S  ...................................................................................... 6 0  
1 0. 1.  Bi o m ar k er A n al y s e s  .................................................................................... 6 0  
1 0. 1. 1.  
E n d p oi nt/ V ari a bl e s  ....................................................................... 6 0  
1 0. 1. 2.  
S u m m ar y M e a s ur e  ...................................................................... 6 0  
1 0. 1. 3.  
P o p ul ati o n of I nt er e st  ................................................................... 6 1  
1 1.  P O P U L A TI O N P H A R M A C O K I N E TI C ( P O P P K) A N A L YS E S  .................................. 6 1  
1 2.  P H A R M A C O KI N E TI C / P H A R M A C O D Y N A MI C A N A L Y S E S  ................................. 6 1  
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13. REFERENCES ....................................................................................................... 62 
14. APPENDICES ........................................................................................................ 63 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 63 
14.2. 
Appendix 2: Schedule of Activities .............................................................. 64 
14.2.1. 
Protocol Defined Schedule of Events ........................................... 64 
14.3. 
Appendix 3: Assessment Windows ............................................................. 65 
14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 66 
14.4.1. 
Study Phases .............................................................................. 66 
14.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 68 
14.5.1. 
Reporting Process ....................................................................... 68 
14.5.2. 
Reporting Standards .................................................................... 68 
14.6. 
Appendix 6: Derived and Transformed Data ............................................... 70 
14.6.1. 
General ........................................................................................ 70 
14.6.2. 
Study Population .......................................................................... 71 
14.6.3. 
Efficacy ........................................................................................ 71 
14.6.4. 
Safety .......................................................................................... 72 
14.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 73 
14.7.1. 
Premature Withdrawals ................................................................ 73 
14.7.2. 
Handling of Missing Data ............................................................. 73 
14.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 77 
14.8.1. 
Laboratory Values ........................................................................ 77 
14.8.2. 
ECG Parameters: ........................................................................ 77 
14.8.3. 
Vital Signs .................................................................................... 78 
14.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses ...................... 80 
14.10. Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses .................... 81 
14.11. Appendix 11: Abbreviations & Trademarks ................................................. 82 
14.11.1. Abbreviations ............................................................................... 82 
14.11.2. Trademarks ................................................................................. 83 
14.12. Appendix 12: List of Data Displays.............................................................. 84 
14.12.1. Data Display Numbering .............................................................. 84 
14.12.2. Mock Example Shell Referencing ................................................ 84 
14.12.3. Deliverables ................................................................................. 84 
14.12.4. Study Population Tables .............................................................. 85 
14.12.5. Efficacy Tables ............................................................................ 94 
14.12.6. Efficacy Figures ......................................................................... 102 
14.12.7. Safety Tables ............................................................................. 106 
14.12.8. Safety Figures ........................................................................... 138 
14.12.9. Biomarkers Tables ..................................................................... 139 
14.12.10. Biomarker Figures ..................................................................... 139 
14.12.11. Pharmacokinetic Tables ............................................................. 140 
14.12.12. Pharmacokinetic Figures ........................................................... 141 
14.12.13. ICH Listings ............................................................................... 143 
14.12.14. Non-ICH Listings ........................................................................ 167 
14.13. Appendix 13: Example Mock Shells for Data Displays .............................. 174 
14.14. Appendix 14: Combined Preferred Terms ................................................. 175 
14.15. Appendix 15: Adverse Event Collapsing Rules ......................................... 177 
 


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
6  
 
1.  
I N T R OD U C TI O N  
T he p ur p ose of t his R e p orti n g a n d A nal ysis P la n ( R A P) is t o descri be t he a nal yses t o b e 
i ncl u de d i n t he Cli nical St u d y Re p ort f or Pr ot oc ol 2 0 8 4 6 9 : 
Pr ot o c ol R e vi si o n C hr o n ol o g y:  
V ersi o n 01  
2 3 -M A Y -2 0 1 6  
Ori gi nal  
V ersi o n 02  ( A m e n d m e nt 1) 0 3 -O C T -2 0 1 6  
C h a n g e i n sc op e t o P h as e I/II pil ot st u dy  
N Y -E S O -1 c 25 9T h as n ot pr evi ously b e e n us e d i n myx oi d/ 
r o u n d c ell li p os arc o m a, t her efor e t h e sc o p e of A D P-0 0 1 1 -
0 0 7 h as b e e n c h a ng e d t o c o mpris e a pil ot st udy t o 
ev al u at e effic acy a nd  s afety. Th e st u dy will r ecr uit u p to 
1 5 p artici p ants . 
V ersi o n 03 ( A m e n d m e nt 2)  2 4 -J U L-2 0 1 8  
T h e f ollo wi n g c h a n ges h av e be e n m a de:  
•  U p d at es t o ti m e p eri ods t hat m ust el a pse b et w e en 
c essati o n of v ari o us t h er a pi es pri or t o l e uk ap h er esis 
a n d pri or t o i niti ati o n  of ly m p ho d e pl eti n g c h e m ot h er a py 
(“ was h-o ut” p eri o ds)  
•  Ty p o gr a phic al err ors h ave b e en c orr ect e d a nd ti mi n gs 
of assess m e nts h ave b e en clarifi e d  
•  O pti o n t o i ncr e as e t h e s a mpl e siz e, as w ell as t h e 
o pti o n to c h an g e t he ly m p h ode pl eti on r e gi m e n bas e d o n 
e m er gi ng d at a  
•  A d mi nistr ativ e ch a n g es t o ali gn wit h G S K pr oc ess es 
a n d pr oce d ur es.  
•  L a n g u a ge r el ati n g t o s erio us adv ers e ev e nt ( S A E) 
r e p orti n g a n d saf ety m o nit ori ng h as be e n u pd at e d. 
 
V ersi o n 04 ( A m e n d m e nt 3)  1 7 -O C T -2 0 1 8  
C h a n g es m a d e to t h e prot oc ol w er e r e q u est e d by F D A  as 
a r es ult of saf ety ev e nts w hic h i ncl ud e d 2 re p orts of  
G uill ai n -B arr é syn dr o m e i n partici p ants  w h o h av e 
r ec eive d ch e m oth er a py a n d G S K 3 3 7 7 7 9 4 duri n g cli nic al 
tri als 
V ersi o n 05 ( A m e n d m e nt 4)  1 8 -J U N-2 0 1 9  
Cl arificati o n o n d efi niti o ns of enr oll me nt a n d i nt ent t o  tr eat 
p o p ul ati o n.  D efi nitio n of ev alua bl e ch a n g ed t o r e quir e at 
l e ast 3 p ost b aseli ne dise as e ass ess me nts ( or 
pr o gr ess e d or di e d or wit h dr a w n fr o m t h e st u dy ) r at h er 
t h a n 2. 
V ersi o n 06 ( A m e n d m e nt 5)  1 3 -D E C -2 0 1 9  
T h e f ollo wi n g up d at es h av e b ee n  m a d e:  
•  A d diti o n/cl arific ati o n of d el ay ed A E d efi niti o n  
•  R evis e d g ui deli nes f or t h e man a g e m ent of 
•  R evis e d g ui deli nes f or t h e man a g e m ent of 
e nc e p hal o p at hy sy n dro m e  
•  A dj ust me nt t o ly mp h o d epl eti on r e gi me n f or s af ety 
p ur p os es  
 
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
7  
 
Pr ot o c ol R e vi si o n C hr o n ol o g y:  
V ersi o n 07 ( A m e n d m e nt 6)  1 7 -F E B -2 0 2 1  
T h e f ollo wi n g up d at es h av e b ee n m a d e:  
•  Pri m ary en d p oint t o be O R R bas e d u po n i nv esti g at or 
ass ess me nt r at her t h a n i n d e pe n d e nt r evi e w er 
ass ess me nt.  
•  A d d e d s ec o n d ary e nd p oi nt of O R R as ass ess e d by 
i n d e p e nd e nt r evi e w. 
•  I ns ert e d s eco n d ary e n d poi nt for P K pr ofil e. 
•  R e m ov e d s eco n d ary e n d poi nt f or d ev el o p me nt of 
c o m p ani o n di a g nostic ass ay. 
•  I ncl u de d g ui d a nc e f or m o nitorin g of r esp o nse p ost 2-
y e ars on tri al. 
•  U p d at e d d efi niti o n of ev al u a ble s u bjects i n Pr ot oc ol 
S ecti o n 3. 3 t o m a tch t h at pr ovi d e d i n Pr otoc ol S ectio n 
1 1. 2. 
•  D el et e d st at e me nt i n S ectio n 3. 3 t h at c o ntin u o us i nt eri m 
ass ess me nt of p artici p a nts b ey o n d 1 0 w o ul d “ be use d 
t o c o nti n u o usly ass ess O R R an d i nf or m d ecisi o ns 
r e g ar di n g e nr oll m e nt of a dditi on al s ubj ects”. 
•  Cl arifi e d  d efi niti o n of co m pl etio n of i nterv e nti o n al p h as e.  
•  Cl arifi e d c o mpl etio n of st u dy defi nitio n.  
•  R e m ov e d re q uir e m e nt for c onfir m ati on of dis e as e 
pr o gr essi o n.  
•  Cl arifi e d a n d ma d e c o nsist e nt d escripti o ns of I T T a n d 
mI T T p o p ul atio ns ( with n o c h an g e t o p op ul ati o n 
d efi niti o ns).  
•  U p d at e d d efi niti o n of I nt e nt -to-Tr e at p o p ul ati on.  
•  A d d e d st at e m e nt d escri bi n g pla n n e d s ec o nd i nt eri m 
a n alysis i n “ at l e ast 8 ev al u able” i n t h e hi g h 
ly m p ho d e pl eti on c o hort. 
•  Cl arifi e d d escri ptio n f or Ti m e to R es p o ns e e n dp oi nt.  
 
V ersi o n 08 ( A m e n d m e nt 7 ) 1 7 -F E B -2 0 2 1  
T his a m e n d m e nt w as site s p ecific o nly.  
T h e f ollo wi n g c h a n ges h av e be e n m a de:  
•  Pr ot oc ol S ecti on 7. 6 has b ee n a d d e d descri bi n g t h e 
p ot e nti al f or r etre at me nt f or thos e s ubj ects w h o h av e 
h a d a c o nfir me d 
 
 
V ersi o n 09 ( A m e n d m e nt 8)  1 8 -M A Y -2 0 2 1  
C h a n g es t o pr ot oc ol hav e be en m a d e i n r ef ere nc e t o 
D e ar I nv esti g ator L ett er d at e d 0 3 M ay 2 0 2 1 a n d Pr ot oc ol 
a n d I C F clarific ati on m e m or a nd u m d ate d  1 1 M ay 2 0 2 1 
r e g ar di n g miti g atio ns put i n plac e o n activ e st u di es of 
G S K 3 3 7 7 7 94 (l et etr es g en e a ut ol e ucel, let e -c el), f oll o wi n g 
t h e r ec ent S A Es of f at al ne utro p e ni a (1 ev ent) a n d 
d ecr e as e d visio n ( 1 ev e nt)  
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
8  
 
Pr ot o c ol R e vi si o n C hr o n ol o g y:  
V ersi o n 10 ( A m e n d m e nt 9)  0 4 -N O V -2 0 2 1  
C h a n g es t o t h e prot oc ol m ad e i n r ef er enc e t o D e ar 
I nv esti g at or L ett er dat e d 21 Oct 2 0 2 1 a n d Pr ot oc ol a n d 
I C F cl arific ati o n me m or an d u m d at e d 2 5 Oct 2 0 2 1 
r e g ar di n g s af ety miti g ati o ns i mpl e m e nt e d o n activ e 
st u di es of G S K 3 3 7 7 79 4. 
V ersi o n 11 ( A m e n d m e nt 
1 0 ) 
1 7 -D ec -2 0 2 1  
T h is a m e n d m e nt w as site s p ecific o nly.  
C h a n g es m a d e to s u bj ect eli gibility criteri a to allo w 
s ec o nd i nf usi on wit h let e-c el ( G S K 3 3 7 7 7 94) i n pati e nts 
w h o h av e r ec eiv e d ot h er a ntic a nc er t her a py aft er 
pr o gr essi o n post first l et e -cel inf usi on. 
1. 1.  
R A P A m e n d m e nt s  
Re visi o n c hr o n ol o g y:  
R A P S e cti o n  
A m e n d m e nt Det ail s  
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ Fi n al _ V 1  [0 5 -O C T -2 0 1 8 ] 
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ A m e n d m e nt _ Fi n al_ V 2  [2 0 -N O V -2 0 20 ] 
S ecti o n  1 
U p d at e d f or prot oc ol a me n d me nts 3, 4 & 5. 
S ecti o n  2 
•  C h a n g es t o pr ot oc ol defi n ed an alysis pl a n descri b e d.  
•  A d d e d
 
•  U p d at e d f or prot oc ol a me n d me nts 3, 4 & 5.  
 
S ecti o n  3 
•  U p d at e d f or outc o m e of i nt eri m a n alysis f or futility on 1 st 1 0 tr e at e d 
p articip a nts . 
•  D escri b ed int eri m an alys es of sec o nd “ Hi g h Ly m ph o d e pl eti on” co h ort . 
•  Cl arifi e d ti min g of pri m ary a n d fi n al an alys es.  
 
S ecti o n  4 
•  A d d e d e nr oll e d p o p ulati o n r e quir e d f or discl os ur e dis plays.  
•  U p d at e d I T T po p ul ati o n i n li n e wit h a m e nd e d prot oc ol . 
 
S ecti o n  5. 1 
•  C h a n g e d r e porti n g st a n dar d t o  i ncl ud e sec o nd “ Hi g h Ly m p hod e pl etio n” 
c o h ort. 
•  B as eli ne d efi nitio ns up d at ed to acc o m m od at e ti mi ng of ne w hi g h 
ly m p ho d e pl eti on r e gi m e n. 
 
S ecti o n  6 
•  Pri or a nti -c a ncer t h er a py r e porti n g u p dat e d to o nly c ou nt f ull li n es of 
t h er a py b et w e e n di a g n osis of a dv a nc e d/ met astatic dise as e a n d 
ly m p ho d e pl eti on, excl u di n g brid gi n g t her a pies a d mi nist er ed b et w e e n 
l e uk a ph er esis an d ly m p ho d e pleti o n. 
•  U p d at e d t o us e G S K dr u g r ather t h a n W H O Dr ug c o di n g . 
•  U p d at e d r e p orti n g i n li n e wit h c urr e nt G S K st a nd ar ds for N Y-E S O.  
 
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
9  
 
R A P S e cti o n  
A m e n d m e nt Det ail s  
S ecti o n  7 
•  Cl arifi e d th at r es p o ns es ( C R, P R) m ust b e c o nfir m e d , p er prot oc ol. 
•  Cl arifi e d th at o nly r es p o ns es fro m tr e at m e nt st art u ntil dis e ase 
pr o gr essi o n or i niti atio n of ne w a nti -c anc er th er a py s h oul d be c o nsi d er e d 
f or O R R, T T R, D O R, 
e n dp oi nts, vi a d efiniti on of b est over all 
r es p o ns e ( B O R). 
•  Cl arifi e d c o nsi d er ati o n of u nconfir m e d C R & u nc o nfir m e d P R as evi d e nc e 
f or st a bl e dis e as e. 
•  Cl arifi e d th at t o b e co nsid er e d evi d e nc e f or st a bl e dis e as e , a dis e as e 
ass ess me nt must b e at l east 28 d ays aft er T -c ell i nf usi o n. 
•  S p ecifie d h a ndli ng of p artici p ants wit h no m e as ur a bl e dis e ase at b as eli ne 
if s uch a n i nclusio n crit eri a d evi ati on s ho ul d occur. 
•  Cl arifi e d us e of i n de p e n de nt vs. i nvestig at or dis e as e ass ess m e nts. 
•  U p d at e d P F S c ens orin g r ules in li n e wit h c urre nt G S K onc ol ogy a n alysis 
pl a n t e m pl ate.  
•  A d d e d
 
•  Cl arifi e d us e an d met h o ds f or c alc ul atio n of 95 % c onfi d enc e i nt erv als.  
•  I nt eri m A nalys es s u b-s ecti o n u p d at e d for i nt eri m an alysis f or f utility o n 1st 
1 0 “ L o w Ly m p h o de pl eti o n” partici p ants an d i nt eri m a n alys es of s eco n d 
“ Hi g h Ly mp h o d epl eti o n” co h ort. 
•  U p d at e d r e p orti n g i n li n e wit h c urr e nt G S K st a nd ar ds for N Y -E S O.  
 
S ecti o n  8 
•  U p d at e d list of Adv ers e Ev e nts of S p eci al I nt er est ( A E SI) t o c urr e nt G S K 
st a n d ar d f or N Y-E S O.  
•  M ov e d d escri pti o n of “ De at hs a n d S eri o us A dvers e Eve nts” to m ai n 
“ A dv ers e Ev e nts A n alysis” s ecti o n t o av oid r e p etiti o n a n d delet e d s ecti on. 
•  U p d at e d r e p orti n g i n li n e wit h  c urr e nt G S K st a nd ar ds for N Y-E S O.  
•  A n alyses of cytoki nes, anti -N Y -E S O -1 a nti bo di es a n d ( m ost) p ersist e nce 
m ov e d t o s ep ar at e bi o mark er s ectio n.  
•  A n alyses of R eplic ati on C o m pet e nt L e ntivir us ( R C L) a dd e d.  
 
S ecti o n  1 0 
•  Cl arifi e d a n alys es of persist e nc e, cyt oki n es a n d anti-N Y -E S O -1 
a nti b o di es . 
 
A p p e n dix  2 
•  Sc h e d ule of activiti es u p dat e d p er pr ot oc ol a m e n d m e nt  5. 
 
A p p e n dix  4 
•  St u dy p h as e d efi niti o ns u p d ate d . 
 
A p p e n dix  6 
•  A d d e d d eriv atio ns for st udy p op ul ati on m eas ur es.  
•  A d d e d d eriv atio ns for ti me i n m o nt hs a n d dat e of l ast c o ntact.  
•  R e m ov e d d efi niti o ns d uplic at ed i n m ai n sectio ns.  
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CONFIDENTIAL 
 
208469 
10 
 
RAP Section 
Amendment Details 
Appendix 7 
• Updated reporting standards for missing data in line with current GSK 
reporting for NY-ESO. 
 
Appendix 8 
• Updated values of potential clinical importance in line with current GSK 
reporting for NY-ESO. 
 
Appendix 11 
• New abbreviations updated. 
 
Appendix 12 
• Updated reporting in line with current GSK standards for NY-ESO. 
• Identified displays to be produced for second interim analysis. 
 
Appendix 13 
• Updated mock shells in line with current GSK standards for NY-ESO. 
 
Appendix 14 
• New appendix detailing combined preferred terms. 
 
Appendix 15 
• New appendix detailing Adverse Event collapsing rules. 
 
Entire RAP 
• Made general edits in line with protocol and RAP template. 
• Typographical and grammatical corrections. 
 
 
 


CONFIDENTIAL 
 
208469 
11 
 
Reporting and Analysis Plan_208469_Amendment_Final_V3 [13-DEC-2021] 
Section 1 
• Updated for protocol amendments 7, 8 & 9. 
 
Section 2 
• Updated for protocol amendments 7, 8 & 9,  
including description of retreatment and retreatment interventional phase. 
 
Section 3 
• Detail on previous analyses added. 
• Primary analysis no longer optional and to exclude retreatment. 
 
Section 4 
• Updated enrolled population definition in line with amended protocol. 
• Updated description of analyses evaluated using each population. 
• Added mITT2 population for retreatment 2nd T-cell infusion. 
 
Section 5 
• Clarified that all analyses are by planned cohort. 
• Added definitions for retreatment baseline. 
 
Section 6 
• Specified derivation of study status using new “End of Study” CRF. 
• BSA calculation method specified as Dubois-Dubois. 
• Reporting of retreatment data at final analysis added. 
• Minor clarifications to anti-cancer therapy specifications. 
 
Section 7.1 
• Primary endpoint changed to be based on investigator assessment of 
response following protocol amendment 6. 
• Participants with no measurable disease at baseline by independent 
review to be considered as not evaluable (rather than considering non-
target response), matching handling for similar investigator assessments. 
• Clarified that confirmation of CR/PR must occur at least 28 days later 
inclusive (per GSK IDSL standards). 
• Clarified that minimum of 4 weeks for a BOR of SD is inclusive of day of 
T-cell infusion. 
• Clarified identification and handling of new anti-cancer therapy. 
• Following addition of retreatment, clarified that analysis is over the 
interventional phase (i.e. excluding retreatment). 
• Clarified requirements for confirmation of response, and added separate 
specification for Best Overall Response (BOR) without confirmation 
required for some displays. 
 
Section 7.2 & Section 7.3 
• BOR & ORR based on independent review now secondary endpoints 
following protocol amendment 6. 


C O N FI D E N TI A L  
 
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1 2  
 
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ A m e n d m e nt _ Fi n al_ V 3  [ 1 3-D E C -2 0 2 1] 
•  N ot e d t h at P F S ce ns ori n g  r ul es d o n ot n e e d u p d ati n g f or retre at m e nt 
si nc e o nly p artici pa nts th at pr ogr ess duri n g th e i nt erv enti o n al p h as e ar e 
c o nsid er e d for r etr e at m e nt. 
•  S p ecifie d t h at c o nfi d e nc e i nt erv als for K a pl an -M ei er esti m ates s h o ul d us e 
a g e n er aliz ati o n of t h e Br o ok mey er -Cr o wl ey m et h od u n d er a l o g -l o g 
tr a nsf or mati o n. 
•  Cl arifi e d th a
 is wit h c onfir mati on. 
•  A d d e d
 
•  Cl arifi e d th at
is li mit e d t o f ollo w-u p i n this  st udy. 
 
S ecti o n  8 
•  Cl arifi e d th at saf ety a n alys es will gr o u p l e uk a p h eres e d p artici p a nts 
acc or di n g t o t h e ly m ph o d e pl etio n c o h ort t h e partici p a nt w as e nr oll ed i nt o . 
•  R e p orti n g of r etr e at m e nt dat a at fi n al a n alysis a dd e d.  
•  I d e ntific atio n a nd a n alysis of Adv ers e Ev e nts of S p eci al I nt erest ( A E SI) 
u p d at e d i n li n e wit h c urr e nt G S K N Y-E S O st a n d ar ds.  
•  List o f Cli nic al L a b or atory T ests  u p d ate d.  
•  Cl arifi e d ti m ep oi nts f or s u m m ari es of c h a ng e fr o m b aseli ne an d w orst 
c as e post-bas eli n e , i nclu di ng excl usi on of r etr eat m ent d at a. 
•  A d d e d Pl ot of H e m at ol o gy D ata Ov er Ti m e . 
•  I d e ntific atio n of p artici p a nts sho wi n g > 1 % ge n e m ark e d P B M Cs at 1 ye ar 
or b ey o nd p ost 1 st T -c ell inf usio n t o excl ud e r etr e at m e nt d at a. 
•  C O VI D -1 9 r e p ortin g a d de d.  
•  I d e ntifie d A E dis pl ays th at us e c oll aps e d ev ents. 
 
S ecti o n  9 
•  P ersist enc e m ov ed fr o m bi o mark er s ecti on t o t his P K section.  
•  P h ar m ac oki n etic a n alysis of persiste nc e a d d e d.  
 
S ecti o n 1 0  
•  P ersist enc e m ov ed t o fr o m t his bi o m ark er to t h e P K s ecti o n. 
•
 
 
A p p e n dix  4 
•  C o nc o mita nt me dic ati ons d urin g r etr e at m e nt defi n ed.  
•  O n -St u dy A nti -C a ncer T h er apy/ S ur g ery d uri n g r etr e at m e nt defi n e d.  
•  R etr e at m e nt e m er ge nt a dv erse ev e nts d efi n e d  as t h os e wit h o ns et on or 
aft er st art of r etr eat m e nt ly m ph o d e pl eti o n. 
•  R etr e at m e nt assess m e nts/ d ata d efi n ed (f or exclusi on fr o m pri m ary 
a n alysis).  
 
A p p e n dix  5 
•  U p d at e d r ef ere nc es t o G S K I D S L St a n d ar ds. 
 
A p p e n dix  6 
•  R etr e at m e nt D ay d efi n e d  to i ndic at e ti m e si nc e 2nd T -c ell i nf usi o n 
(i ncl usiv e) i n listi n gs i ncl u din g r etr e at m e nt d at a. 
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
1 3  
 
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ A m e n d m e nt _ Fi n al_ V 3  [ 1 3-D E C -2 0 2 1] 
•  S p ecifie d m eth o ds f or calc ul atio n of B o dy M ass I nd ex ( B MI) a n d B o dy 
S urf ac e Ar e a ( B S A).  
 
A p p e n dix  8 
•  C orr ect e d sp ecific ati o n of v al ues of p ot e ntial cli nic al c o nc er n f or l a b test 
v al u es t h a n c a n b e gr a de d as gr a d e 2 or a b ove ( n ot gra d e 1 or a b ov e as 
pr evi o usly st ate d), a nd d elet ed Gr a d e  1 hyp ert e nsi o n fro m ta bl e of v al ues 
of v al ues of p ot e nti al cli nic al i m p ort a nc e ( P CI) f or bl o o d press ur e.  
 
A p p e n dix  1 2 
•  Pr evi o us “ S t atistical A n alysis C o m pl et e ” d eliv er a bl e r e pl ac ed by se p ar at e 
pri m ary a n d fi n al a n alysis d eliv er a bl es. 
•  I nstr ucti o ns f or dis plays t o r efres h or r ep e at/ ext e n d t o i ncl u de r etr e at me nt 
d at a at fi n al a n alysis a d de d.  
•  R etr e at m e nt s p ecific dis pl ays a d d e d f or fi n al a n alysis.  
•  Cl arificati o ns t o p ro gr a m mi n g n ot es arisin g fr o m dry r un . 
•  Mi n or r efi n e me nts t o s o m e dis pl ay titl es. 
•  A dj ust me nts to A E1 8 dis plays r e q uir e d for C S R i n -t ext t a bl es f oll o wi ng 
f e e d b ack fr o m st ak e h ol d ers. 
•  F at al A E r e p orti n g up d at e d i n li n e wit h c urr e nt G S K st an d ar ds.  
•  P ersist enc e ( previo usly r e p orte d as a bi o m ark er) n o w r e p orte d as P K. 
•
•  Tr e at m e nt d at es listi n g dr o p p ed as d etail i nc orp or at e d i nt o su bj ect st at us 
listin g. 
•  Listi ngs of l a b orat ory v al ues of p ot e nti al cli nic al c o nc er n dr opp ed ( as als o 
h av e listin gs of all l a bor at ory val u es for s ubj ects wit h a ny v alu e of 
p ot e nti al cli nic al i m p orta nc e).  
•  Listi ngs of r es po ns e assess me nts wit h a n d wit ho ut co nfir m ati o n 
c o ns oli d ate d. 
•
o nly t o be a n alys e d at fin al an alysis.  
 
A p p e n dix  1 3 
•  Cl arificati o ns a n d c orr ecti o ns arisi ng fr o m dry r u n.  
•  M ock i d e ntifi ers u p dat e d in line wit h dr aft N Y -E S O st a n dar d m ocks.  
•
 
•  U p d at e d P O P _L 5 “ Listi n g of Su bj ect Stat us”.  
•  A E SI m ocks u p d at e d.  
•  M ocks f or P K  a nalys es of p ersist e nc e a d de d.  “ Distri b uti o n of P e ak C ell 
Ex p a nsi o n” ch a n g ed fr o m b ox pl ot t o dot plot. 
•  Hi g h L evel R ac e a d d e d t o listin gs.  
•  C ust o m P O P_ T 4 m ock a d d e d f or “ S u m m ary of T ot al Tr ans duc e d T-c ells”. 
•  C ust o m S A F E _ L 6 m ock a d ded f or “ Listi n g of Q Tc V al ues of P ot e nti al 
Cli nic al I mp ort a nc e ” as r e pl ace m e nt f or O E C G 5 A w hic h is no w arc hiv e d.  
•  A d d e d S A F E _ F 3  “Pl ot of H e mat ol o gy D at a Ov er Ti m e ”. 
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
1 4  
 
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ A m e n d m e nt _ Fi n al_ V 3  [ 1 3-D E C -2 0 2 1] 
 
A p p e n dix  1 4 
•  Mi n or u p d a t e to c o m bi ne d pr eferr e d t er ms f or M e d D R A v 2 3.1 fr o m G S K 
S af ety R evi e w T e a m 0 9 -N O V -2 0 2 0. 
 
E ntir e R A P  
•  Mi n or cl arific ati o ns a n d c orr ecti o ns.  
•  Ty p o gr a phic al a n d gr a m m atical c orr ecti ons.  
 
 
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ A m e n d m e nt _ Fi n al_ V 4  
S ecti o n  1 
•  U p d at e d f or prot oc ol a me n d me nt  1 0 . 
 
S ecti o n 4  
•  A d d e d Scr e en e d 2 po p ul ati o n for 2nd T -c ell i nf usi on. 
 
S ecti o n 5  
•  Cl arifi e d th at r etre at e d partici pa nts ar e t o b e s u m m ariz e d  by t h e 
ly m p ho d e pl eti on c o hort t h e p artici p ant w as enr olle d i nt o.  
S ecti o n 6  
•  Cl arifi e d th at r etre at m ent scr ee n f ailur es will b e re p ort e d f or t h e fi n al 
a n alysis.  
•  Cl arifi e d th at f or retr e at m e nt partici pa nts t h e fin al en d of st u dy f or m will b e 
c o nsid er e d for s u bj ect st atus. 
•  Cl arifi e d th at listin gs of pr ot ocol d evi ati ons will b e ext e nd e d  to i nclu d e 
r etr e at m e nt d at a.  
•  U p d at e d t o i nclu d e t he f oll o win g listi n gs o n th e mIT T2 p o p ulati o n at t h e 
fi n al an alysis: listi ng of d e m o gr a p hic c h ar act eristics, listin g of pri or a nd 
c o nc o mit ant m e dic ati o ns, listi ng of bl oo d pr o ducts, listi n gs of 
ly m p ho d e pl eti on a n d T-c ell exp os ur e, listi n g of a nti-c a nc er ra di ot h era pi es, 
listin g of on-st udy a nti -c anc er th er a pi es a n d c a nc er-r el ate d sur gic al 
pr oc e d ures.  
•  Cl arifi e d th at listin gs of r esectio n bi o psi es will b e ext e n d ed to  i nclu d e 
r etr e at m e nt d at a.  
S ecti o n 7  
•
•  Cl arifi e d P F S w or di n g t o r e m ov e ‘ acc e pta bl e’ fr o m t h e d escripti o n of t h e 
i m a gin g m od aliti es. 
•  Cl arifi e d P F S C e ns ori ng r ul es T a bl e 1 to r ef er enc e ‘t w o or mor e’ miss ed 
sc h e dul e d assess m e nts i nst ea d of ‘ m or e t han t w o’.  
•  A d d e d K M P F S a nd O S r ates at s p ecific ti m e p oints t o t h e P F S s u m mary 
a n d O S s u m mary t abl es.  
•  A d d e d P F S a n d O S f oll o w -u p ti m e s u m mari es usin g t h e r evers e K M 
m et h o d.  
•  R e m ov e d s pi der pl ot f or r etr eat m e nt.  
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
1 5  
 
Re p orti n g a n d A n al y si s Pla n_ 2 0 8 4 6 9_ A m e n d m e nt _ Fi n al_ V 4  
S ecti o n 8  
•  U p d at e d t o i nclu d e t he f oll o win g listi n gs o n th e mI T T2 p o p ulati o n at t h e 
fi n al an alysis: A E listi n gs, listing of sy m pt o ms an d tr e at m e nts r el at e d to 
listi n g of t ociliz u ma b, listi n g of la b or atory d ata, listi ng of E C O G 
p erf or m a nc e st at us, listi n g of E C G v al u es, listin g of  vit al signs, a n d listi n g 
of R C L. Cl arifi ed t h at A E t abl es at t h e fi n al a n alysis will i ncl ud e 
r etr e at m e nt A Es.  
S ecti o n 9  
•  U p d at e d t o i nclu d e t he listi ng of p ersist e nc e o n t h e mI T T 2 po p ul atio n at 
t h e fi n al a n alysis.  
S ecti o n 1 0  
•  U p d at e d t o i nclu d e t he listi ng of i nt e grati o n sit e a n alysis d ata o n t h e 
mI T T 2 p o pul ati o n at t h e fin al an alysis.  
•  U p d at e d t o i nclu d e t he listi ng of a nti-N Y -E S O -1 anti b odi es on t h e mI T T2 
p o p ul ati o n at t h e fin al an alysis.  
A p p e n dix 1 2  
•  R etr e at m e nt s p ecific dis pl ays a d d e d or m o difi e d  for fi n al a n alysis. I n 
p artic ul ar, listin gs w er e a d d e d o n t h e mI T T 2 p op ul ati o n.  
•  Effic acy fi gur es r e m ove d f or the fi n al a n alysis.  
•  Effic acy K M t abl es u p d at e d fr o m T T E 1 m ock to E F F _ T 2.  
•  A d d e d n e w effic acy t abl es f or f oll o w -u p un d er E F F _ T3 m ock.  
•  Mi n or r efi n e me nts t o s o m e dis pl ay titl es.  
A p p e n dix 1 3  
•  U p d at e t o P O P_ L 4 t ext i n 4 t h c ol u m n to s pecify ‘ Ti m e si nce 
L e uk a ph er esis’  
•  U p d at e t o BI O _ L 4 to r e m ov e ‘( N or m al R a n g e )’ fr o m S h a n n on I n d ex 
c ol u mn h e ad er.  
•  U p d at e t o P O P_ L 2 t o a d d col u m ns f or c u mul ativ e dos e for 
ly m p ho d e pl eti on c h e m ot h era py. 
•  A d d e d E F F _ T 2 an d E F F _ T 3  m ocks.  
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
1 6  
 
2.  
S U M M A R Y O F K E Y P R O T O C O L I N F O R M A TI O N  
2. 1.  
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n  
Pr ot oc ol S ecti o n 3. 3  states t hat “E nr olle d s u bjects will be c o nsi dere d t h ose s u bjects w h o 
si g n t he tre at me nt c o nse nt, meet all eli gi bility re q uire me nts, a n d u n der g o a p heresis ”. I n 
t his R A P t he e nr olle d p o p ulati o n is defi ne d i n S ecti o n 4  as “a ll p artici p a nts w h o 
u n der we nt  le uk a p heresis”. 
Pr ot oc ol Secti o n  7. 6. 9 states defi nes a “ S afety Retre at me nt A n alysis Set ” w hic h “will 
c o nsist of all s u bjects w h o u n der g o retre at me nt  wit h G S K 3 3 7 7 7 9 4 ”. Si nce t his is 
i de ntical t o t he mI T T 2 p o p ulati o n als o defi ne d i n t hat secti o n of t he pr ot oc ol , a n d si nce 
S ecti o n 1 1. 2 of t he pr ot o c ol s pecifies t hat safet y a nal yses o v erall will be c o n d ucte d i n t he 
mI T T or I T T p o p ulati o ns a n d d oes n ot s pecif y a c orres p o n di n g safet y p o p ulati o n, 2 n d 
i nf usi o n safet y is re p orte d i n t he mI T T 2 p o p ulati o n f or c o nsiste nc y a n d t he Safet y 
Retreat me nt A nal ysis Set  defi ne d i n t he pr ot oc ol is n ot use d i n t his R A P.  
T he pr ot oc ol s pecifies (i n t he sc he d ule of pr oce d ures) t hat “B as eli ne asse ss me nts m ust be 
c o n d ucte d < 7 d a ys pri or t o ly m p h o de pleti n g c he m ot her a py. ” T his i nter v al has bee n use d 
i n data dis pla y la b els b ut t o acc o m m o date sc h e d uli n g of la bs a n d diseas e assess me nts  
(a n d f or c o nsiste nc y wit h t he ori gi nal v ersi o n of t his R A P use d f or t he i nteri m a nal ysis of 
f utilit y) t he da y b ef ore t his wi n d o w has bee n i ncl u de d a n d (as d escri b e d i n S ecti o n 5. 2  of 
t his R A P) t he last assess me nt wit h a n o n-missi n g val ue pri or t o i nitiati n g 
l y m p h o de pleti o n will be use d as baseli ne e ve n if it occ urre d m ore t ha n 7 da ys pri or t o 
i nitiati n g l y m p h o de pleti o n. 
Acc or di n g t o G S K sta n d ar ds, Listi n g of Race ( D M 9) is re q uire d  p er I C H E 3 . D ue t o 
differe n ces i n A d a pti m m u ne data c ollecti o n, o nl y Listi n g of De m o gra p hic C haracteristics 
( D M 2) will be dis pla ye d w hic h will i ncl u de hi g h l e vel race i nf or m ati o n. 
Pr ot oc ol S ecti o n 1 1. 1  n otes t hat “ if t he mI T T a n d I T T p o p ul ati o ns are i de ntic al, o nly 
res ults ass oci ate d wit h t he I T T p o p ul ati o n will be re p orte d”. T his is clarifie d i n t h is R A P 
i n t hat f or st u d y p o p ulati o n a nal ys es ( w h ere t h e I T T p o p ulati o n is t he pri mar y a nal ysis 
p o p ulati o n ) res ults pla n ne d f or b ot h I T T a n d mI T T p o p ulati o ns will o nl y b e re p ort e d f or 
t he I T T p o p ulati o n, a n d f or effic ac y a nal yses ( w here t he mI T T p o p ulati o n is t he pri mar y 
a nal ysis p o p ulati o n) res ults pla n ne d f or b ot h I T T a n d mI T T p o p ulati o ns will o nl y b e 
re p orte d f or t he m I T T p o p ulati o n. 
Pr ot oc ol S ecti o n 1 1. 3 states t hat “O R R will be s u m m arize d by t w o -si de d 9 5 % c o nfi de nce 
i nterv als usi n g ex act a n d Wils o n met h o ds. 9 5 % ( B ayesi a n) cre di ble i nter v als m ay als o be 
use d t o s u m m arize t he O R R .” I n t his a nal ysis pla n o nl y e x act c o nfi d e nce i nter vals are  
s pecifie d. 
Pr ot oc ol Secti o n  1 1. 4 states t hat “A dvers e eve nts wit h missi n g d ate of o nset will be 
c o nsi dere d t o h ave o cc urre d o n tre at me nt. ” I n t his R A P A Es wit h missi n g date of o nset 
b ut n o n -missi n g e n d date bef ore l y m p h o de pl eti o n start are n ot c o nsi d ere d as treat me nt 
e mer ge nt. ( See Secti o n  1 4. 4. 1. 3  f or details.) 
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Pr ot oc ol a p pe n di x 4 “ R E CI S T 1. 1 Criteri a f or Ev al u ati n g Res p o nse i n S oli d T u m ors ” i n 
t he ta ble “S u m m ar y of t he over all res p o nse st at us c alc ul ati o n at e ac h ti me p oi nt ” states 
“> 4 wks. C o nfir m ati o n ” is re q uire d f or C R a n d P R. I n t his a n al ysis pla n c o nfir mati o n 
m ust be at least 2 8 da ys later (i.e.  ≥4  w ks. c o nfir m ati o n), i n li ne wit h G S K I D S L 
sta n dar ds a n d t he ti mi n g s pecifie d i n t he pr ot oc ol sc he d ule of acti vities. 
2. 2.  
St u d y O bj e cti v e( s) a n d E n d p oi nt( s)  
O bj e cti ve s  
E n d p oi nt s  
Pri m ar y O bj e cti ve s  
Pri m ar y E n d p oi nt s  
•  
T o ev alu at e th e effic acy of 
a ut ol o go us  ge n etic ally mo difi ed 
T -c ells ( N Y-E S O -1 c 259T) i n 
HL A -A* 0 2: 0 1, H L A -A* 0 2: 0 5 an d/ or 
HL A -A* 0 2: 0 6 s u bjects wit h 
N Y -E S O -1 ex pr essi ng a dva nce d  
myx oi d/ r o un d c ell li p os arc o ma  
•  
Ov er all R es po ns e R at e 1 ( O R R) p er R E CI S T v 1. 1 by 
i nv esti g ator ass ess m e nt 
S e c o n d ar y O bje cti v e s  
S e c o n d ar y E n d p oi nt s  
•  
T o ev alu at e th e effic acy of 
a ut ol o go us ge n etic ally mo difi ed 
T -c ells ( N Y-E S O -1 c 259T) i n 
HL A -A* 0 2: 0 1, H L A -A* 0 2: 0 5 an d/ or 
HL A -A* 0 2: 0 6 s u bjects wit h 
N Y -E S O -1 ex pr essi ng a dva nce d 
myx oi d/ r o un d c ell li p os arc o ma  
•  
Ov er all R es po ns e R at e 1 ( O R R) p er R E CI S T v 1. 1 by  
i n d e p e nd e nt r evi e w 
•  
Ti m e t o R es p o ns e 2 
•  
D ur ati o n of R es p o ns e 2 
•  
Pr o gr essio n Fr e e S urviv al 2 
•  
T o ev alu at e th e s afety an d 
t ol er a bility of a ut ol o go us ge n etic ally 
m o difie d T -cells ( N Y-E S O -1 c 259T) i n 
HL A -A* 0 2: 0 1, H L A -A* 0 2: 0 5 an d/ or 
HL A -A* 0 2: 0 6 s u bjects wit h 
N Y -E S O -1 ex pr essi ng a dva nce d 
myx oi d/ r o un d c ell li p os arc o ma  
•  
A Es, i ncl u di ng S A Es  a n d A E SIs  
•  
L a b or at ory ass ess m e nts, includi n g ch e mistry  a n d  
h e m at ol o gy  
•  
R e plic ati o n c o m pet e nt l e ntivirus ( R C L)  
•  
I nst a nc es of i ns erti o nal o nc o ge n esis 
•  
I nci d enc e of a nti -N Y -E S O -1 c 259T a nti b o di es  
•  
E C G  
•  
T o c h ar act eriz e t h e i n viv o P K pr ofil e 
(l ev els, ex p a nsi o n, p ersist e nce) of 
N Y -E S O -1 s p ecific (c 2 5 9) c ells  
•  
M axi m u m tra ns ge n e ex p a nsi on ( C m ax ) 
•  
Ti m e t o C m ax  ( Tm ax ) 
•  
Ar e a u n d er t he ti m e c urv e fr o m z er o to ti me t A U C 0 -t, as 
d at a p er mit  
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1 8  
 
1Ov er all R es p o ns e R at e is b ase d o n c o nfir me d r es p o ns e d eter mi n e d at l east 4 w eeks p ost i niti al 
i d e ntific ati o n of r es p onse. 
2S ec o n d ary r es p o ns e e n dp oi nts m ay b e bas e d o n i nv esti g ator ass ess m e nt an d i nd e p e nd ent r evi e w.  
 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
 
Design Features 
• 
This is a pilot, open-label study of genetically engineered NY-ESO-1c259T 
cells in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 participants with 
Advanced Myxoid/ Round Cell Liposarcoma. 
• 
Participants with the HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 allele, 
whose tumor expresses the NY-ESO-1 antigen above the cut-off level 
according to the applied immunohistochemistry, and who meet study entry 
criteria will be eligible for enrollment. 
• 
The study is divided into three distinct phases:1) Screening, 2) Interventional, 
and 3) Long Term Follow-up. 
• 
The Screening Phase starts from the time the participant signs the screening 
ICF until the subject attends for second screening following antigen positivity.  
• 
Eligible participants then enter the Interventional Phase of the study (T-cell 
infusion) on signing the Treatment Informed Consent Form. 
• 
During the Interventional Phase, participants undergo leukapheresis to obtain 
cells for the manufacture of autologous NY-ESO-1c259 TCR bearing T-cells. 
• 
When the NY-ESO-1c259T cells are available, eligible participants undergo 
lymphodepleting chemotherapy with cyclophosphamide and fludarabine 
followed by infusion of a NY-ESO-1c259T cells on Day 1. 
• 
A NY-ESO-1c259T infused subject will be considered to have completed the 
interventional phase of the study when he/she has progression of disease, 
death, or has been followed-up for 2 years after NY-ESO-1c259T cell infusion, 
whichever is shorter. If necessary and upon discussion with the Sponsor, 
those patients who have not progressed after 2 years on study and who are 
continuing in Study 208469 may continue to undergo response assessments 
every 3 months as defined in Study 208469 per institutional standard of care. 
• 
All participants alive on completing the Interventional Phase of the study will 
be rolled over to a long-term follow-up (LTFU) Protocol (GSK208750) for 
observation of delayed AEs for 15 years post-infusion in accordance Food 


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Overview of Study Design and Key Features 
and Drug Administration (FDA) and European Medicines Agency (EMA) 
requirements for gene therapy clinical trials (or under the current protocol 
until the LTFU is available).  
• 
Up to 20 participants may be treated in total. 
Dosing 
• 
Lymphodepleting chemotherapy:  
o For the first 10 subjects, Fludarabine and Cyclophosphamide will be 
given at 30 mg/m2 and 600 mg/m2, respectively. The intervention will be 
3 consecutive days, starting 7 days prior to the T-cell infusion. Refer to 
Section 5.2 in protocol for the details. 
o For the next 10 subjects: Fludarabine will be given at 30mg/m2 for 4 
consecutive days starting 8 days prior to the T-cell infusion and 
Cyclophosphamide will be given at 900 mg/m2 for 3 consecutive days 
starting 7 days prior to the T-cell infusion. Refer to Section 5.2 in 
protocol for the details. 
• 
T-cell infusion: Within the range of 1 x 109 – 8 x 109 transduced cells 
Time & Events 
• 
[Refer to Appendix 2: Schedule of Activities] 
Treatment 
Assignment 
• 
Autologous T-cells transduced with lentivirus encoding enhanced TCR 
specific for NY-ESO-1 
Interim Analysis 
• 
There is no planned interim analysis before the first 10 participants are 
treated. 
• 
An interim analysis for futility was conducted after the first 10 participants had 
been treated and had at least 2 post baseline disease assessments or 
progressed (according to investigator assessment) or died or withdrawn from 
the study.  
• 
An interim analysis in the second “High lymphodepletion” cohort was 
performed to provide data for internal decision making after at least 8 
participants had at least 3 post baseline disease assessments or progressed 
(according to investigator assessment) or died or withdrawn from the study. 
2.3.1. 
Retreatment 
Section 7.6 of (site specific) protocol amendment 7 of 17-FEB-2021 introduced the 
option for participants to receive a second course of conditioning chemotherapy and 
NY-ESO-1c259T cell infusion under certain conditions: 
Conditions for retreatment include (see Protocol Section 7.6 for the complete list): 
• 
Subject had a confirmed CR or PR or SD ≥3 months following first GSK3377794 
infusion. 
• 
Subject’s disease subsequently progressed in >3 months after first infusion. 
• 
Sufficient cell dose is available from the original manufacturing procedure to allow 
for retreatment (i.e. subjects will not undergo repeat leukapheresis) and within shelf-
life specifications. 
Subjects being considered for retreatment will enter the retreatment interventional phase 
on completion of the interventional phase. 
All study procedures should be carried out as defined for initial treatment, including 
safety and response assessment, with the exception of leukapheresis which is not part of 
retreatment. 


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2 1  
 
Retreate d s u bjects will recei ve t he “ o pti o n 2” hi g h l y m p h o de pleti o n re gi me n re gar dl ess 
of w hat was recei ve d o n t he first i nf usi o n . 
S u bjects w h o meet eli gi bilit y f or a n d u n d er g o retr eat me nt will be c o nsi dere d t o ha ve  
co m plete d t he retr eat me nt i nter ve nti o nal p hase of t he st u d y w he n t he y ha v e pr o gressi o n 
of disease f oll o wi n g retreat me nt, deat h, or ha v e bee n f oll o we d -u p f or 2 years after 
re-treat me nt, w hic he v er is s h orter. T he s p o ns or m a y t er mi nate t he st u d y bef ore all 
retreate d s u bjects ha v e c o m plete d t he retreat me nt i nter ve nti o nal p hase. 
2. 4.  
St ati sti c al A n al y s e s  
T he st u d y is n ot p o were d t o c o n d uct a n y h y p ot hesis testi n g o n eit her pri mar y or 
sec o n dar y e n d p oi nts. All a nal ys es will be descri pti ve i n nat ure.  C o nti n u o us data will be 
s u m marize d b y statistics i ncl u di n g n, mea n, m e dia n, sta n dar d de viati o n, mi ni m u m  a n d 
ma xi m u m . Cate g orical data will be s u m marize d usi n g fre q ue nc y c o u nts a n d perce nt a ges 
or pr o p orti o ns . Gra p hi cal s u m maries of t he data will be prese nte d  as a p pr o priate . 
Ti me -t o-e ve nt e n d p oi nts will be s u m marize d as t he me dia n, a n d t he 2 5 t h a n d 7 5 t h 
perce ntiles a n d dis pla ye d gra p hicall y usi n g Ka pla n -Meier ( pr od uct -li mit) c ur ves if data 
warra nt.   
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
Protocol Section 11.2 specifies interim analyses of futility for ORR to start “once at least 
10 participants are evaluable”. This analysis was carried out under v1.0 of this RAP and 
is described in Section 3.1.1 below. 
The study having passed the futility boundary and the decision having been made to 
continue (after protocol amendment 2) to enroll a further 10 participants to be treated 
with a higher dose lymphodepletion regimen prior to infusion, no further formal interim 
analyses for futility are necessary. 
Interim analyses of accruing efficacy in the second group of participants may be 
conducted for internal decision making. These data looks will use the methods described 
in protocol Section 11.2 for the interim analyses of futility and will proceed as described 
in Section 3.1.2 below. 
3.1.1. 
Interim Analysis of Futility 
After the first 10 participants were treated (received T-cell infusion) and had at least 2 
post baseline disease assessments or progressed (according to investigator assessment) or 
died or were withdrawn from the study, the investigator-assessed Overall Response Rate 
(ORR) was evaluated to inform the decision of continuing enrollment up to 20 treated 
participants. 
This analysis was carried out under v1.0 of this RAP, on data as of 26-OCT-2018. 
The enrollment rules at the interim analysis are defined based on a Bayesian predictive 
adaptive design [Lee, 2008] that allows the study to be monitored more frequently at 
multiple stages. The criteria were based on a historical response rate of approximately 
20% versus a response rate of interest of 40%, but the sample size is not powered for any 
formal hypothesis testing.  Bayesian statistics were employed to calculate the predictive 
probability that the response rate was ≥40% and ≥20% at interim, assuming a weak beta 
(0.02, 0.08) prior for the binomially distributed data, equivalent to the information 
present in 0.1 participant. 
The protocol specified that if there were 1 or no confirmed responses in the 
10 participants assessed, then enrollment may stop after review of all available data; but 
that if there were 2 or more confirmed responses in the 10 participants, enrollment would 
continue up to 20 participants, with the final decision based on the totality of data. 
The overall response rate (according to investigator assessment) for these first 10 
participants was 2/10, above the futility stopping threshold. Based on the review of the 
totality of data it was decided to exercise the option introduced in protocol amendment 2 
of 24-JUL-2018 and continue enrollment with a second group of 10 participants to 
receive a higher dose “option 2” lymphodepletion regimen, referred to in this RAP as the 
“high lymphodepletion cohort”. 


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After the interim analysis of futility but before any interim analyses of efficacy in the 
second “high lymphodepletion” cohort, protocol amendment 4 updated the minimum 
number of post baseline disease assessments (for participants who had not progressed or 
died or withdrawn from the study) from 2 to 3. This amendment made the minimum 
follow-up required to be considered evaluable more consistent with other studies at 
around 12 weeks. 
3.1.2. 
Interim Analyses of Second “High Lymphodepletion” Cohort for 
Internal Decision Making 
Interim Analyses in the second “High lymphodepletion” cohort may be performed to 
provide data for internal decision making after at least 8 participants in this cohort are 
evaluable, where evaluable is defined as: received T-cell infusion and had at least 3 post 
baseline disease assessments or have progressed (according to investigator assessment) or 
died or withdrawn from the study. (Note that the definition of evaluable was updated in 
protocol amendment 4 – after the interim analysis of futility in the first ten infused 
participants but before any interim analyses of efficacy in the second cohort – to require 
at least 3 post baseline disease assessments rather than 2.) 
Such an analysis was carried out under v2.0 of this RAP and v6 (amendment 5) of the 
Protocol, on data as of 04-DEC-2020. 
The null hypothesis for the population represented by the high lymphodepletion cohort is 
H0: ORR=20%, versus alternative hypothesis H1: ORR=40%, the same as for the low 
lymphodepletion cohort. 
Further development may be approved if the posterior probability that the Overall 
Response Rate (ORR) by investigator assessment is greater than or equal to 0.2 is at 
least 0.95, assuming the same weak beta (0.02, 0.08) prior for the binomially distributed 
data as used for the interim analysis of futility in the low lymphodepletion cohort. 
Thresholds for the corresponding minimum number of confirmed responders required are 
given in table below. These rules are for guidance only. The final decision will be based 
on the totality of the data available. 
Analyses may be performed earlier with fewer than 8 evaluable participants if it is clear 
from the accumulated data what the decision at 8 evaluable participants would be. For 
example, if 4 participants in the second high lymphodepletion cohort have confirmed 
response (by investigator assessment) before 8 participants are evaluable, then an early 
interim analysis may be conducted. 


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Operating characteristics for these decision rules are as follows: 
Number of 
Evaluable 
Participants 
Threshold 
(#responders) 
for Go 
decision1 
Posterior 
Probability 
ORR≥0.2 at 
threshold. 
Probability of 
Go if true 
ORR=0.2 
Posterior 
Probability 
ORR≥0.4 at 
threshold. 
Probability of 
Go if True 
ORR=0.4 
4 
4 
1.000 
0.002 
0.999 
0.026 
5 
4 
0.998 
0.007 
0.971 
0.087 
6 
4 
0.993 
0.017 
0.908 
0.179 
7 
4 
0.982 
0.033 
0.815 
0.290 
8 
4 
0.966 
0.056 
0.704 
0.406 
9 
5 
0.989 
0.020 
0.821 
0.267 
10 
5 
0.980 
0.033 
0.728 
0.367 
11 
5 
0.967 
0.050 
0.628 
0.467 
12 
6 
0.988 
0.019 
0.749 
0.335 
1 For 8 or more evaluable participants, the threshold is the smallest number of responders 
such that the posterior probability that the population ORR is ≥0.2 is at least 0.95. For 
less than 8 evaluable participants, the threshold is set to that which would be required for 
a go decision with 8 evaluable participants. 
Summaries of DOR and PFS will be presented to support decision making if data 
warrant. Displays planned for these interim analyses are indicated in Appendix 12. 
The results of these data looks will guide further development of NY-ESO-1c259T but will 
not impact the conduct of the study. 
Such an interim analysis was conducted under version 2.0 of this RAP, version 6 of the 
protocol, on data as of 04-DEC-2020. 
3.2. 
Primary Analyses 
The planned primary analyses was performed after the completion of the following 
sequential steps: 
1. Enrollment is complete and all the enrolled participants that will receive 
NY-ESO-1c259T have received their first infusion. 
2. At least 9 or 90% of the NY-ESO-1c259T infused participants in each cohort 
(whichever is smaller) have completed the interventional phase (defined as 
confirmed disease progression [according to investigator assessment], death or 
follow-up for 2 years after first NY-ESO-1c259T infusion) or were withdrawn 


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(including lost to follow-up), and the remaining infused participants have at least 
three disease assessments after first NY-ESO-1c259T infusion. 
3. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management. 
Note that whilst protocol amendment 6 (and later) Section 4.3 allow “patients who have 
not progressed after 2 years on study and who are continuing in Study 208469 may 
continue to undergo response assessments every 3 months as defined in Study 208469 per 
institutional standard of care”, the protocol definition of completion of interventional 
phase is unchanged. Thus for the purposes of criteria 2 above, such subjects would be 
considered to have completed the interventional phase. 
Section 7.6 of (site specific) protocol amendment 7 of 17-FEB-2021 introduced the 
possibility for retreatment of participants under certain conditions, with exploratory 
objectives for safety and efficacy: Any retreatment data (as defined in Section 14.4.1.5) 
will be excluded from the primary analysis. 
3.3. 
Final Analyses 
The final analyses will be performed after the completion of the following sequential 
steps: 
1. Enrollment is complete and all the enrolled participants that will receive 
NY-ESO-1c259T have done so, including any retreatment 2nd infusion in this study. 
2. All of the NY-ESO-1c259T infused participants are no longer in follow-up in the 
study, having either transferred to the separate long-term follow-up protocol 
GSK208750 (ADP-0000-002), completed 15 years of long term follow-up in this 
study, has declined LTFU, died or withdrawn (including lost to follow-up). 
3. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management. 
Details of the planned displays for the final analysis are presented in Appendix 12: List of 
Data Displays. 


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4.  
A N A L Y SI S P O P U L A TI O N S  
P o p ul ati o n  
D efi niti o n / Crit eri a  
A n al y s e s E v al uat e d  
Scr e e n e d  
•  
All p artici p ants t hat si g n e d scre e ni n g i nf or me d 
c o ns ent.  
•  
Scr e e n i ng 
•  
P o p ul atio n 
i ncl usi o n/ excl usi o n 
E nr oll e d  
•  
All p artici p ants  w h o u n d er w e nt l e ukap h er esis . 
•  
S p ecific r e q uir e d 
St u dy P o p ul ati on 
dis plays.  
I nt e nt-to -Tr eat 
(I T T) 
•  
All  p artici p ants w h o u n d er w e nt l e ukap h er esis . 
•  
St u dy P o p ul ati on  
•  
Pri m ary S afety 
( w h er e a p pr o pri at e) 
•  
S e nsitivity f or 
Pri m ary Effic acy 
E n d p oi nt ( O R R)  
M o difie d I nte nt-
to -Tr e at ( m I T T) 
•  
All I T T p articip a nt s w h o r eceive d N Y -E S O -1 c 259T  c ell 
i nf usio n. 
•  
Pri m ary Effic acy  
( exc e pt at i nt eri m 
a n alys es)  
•  
Pri m ary S afety 
( w h er e a p pr o pri at e) 
•  
S e nsitivity  S af ety  
( w h er e a p pr o pri at e) 
•  
S u p p ortive St u dy 
P o p ul atio n  
All Ev alu a bl e  
•  
A ll p artici p ant s w h o rec eiv e d T -c ell i nf usi o n an d (h a d 
at l e ast 3 p ost b as eli n e dis e ase ass ess m e nts or [h av e 
pr o gr ess e d or di e d or wit h dr a w n fr o m t h e st u dy ]). 
•  
I nt eri m Futility  
A n alysis  (c o n d uct e d 
u n d er R A P v 1 w hic h 
r e q uir e d o nly 2 p ost-
b as eli n e dis e as e 
ass ess m e nts)  
•  
I nt eri m 
Ass ess m e nts of 
O R R  
A p p e n dix 1 2  d et ails t h e p o p ul ati o n t o b e us e d f or e ac h dis pl ay.  
 
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4.1. 
Protocol Deviations 
Protocol deviations will be tracked in accordance with the Protocol Deviation 
Specification Form by the study team throughout the conduct of the study and sent to the 
Data Manager and Biostatistics Leads in a spreadsheet. Protocol deviations will not be 
identified programmatically. 
Inclusion/exclusion criteria deviations will be based on data as recorded on the 
inclusion/exclusion page of the eCRF. 


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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
This is a single arm study with NY-ESO-1c259T. Data will be listed and summarized 
according to the GSK reporting standards, where applicable. For participants that entered 
the interventional phase and underwent leukapheresis, data will be summarized by the 
lymphodepletion cohort the participant was enrolled into and by study total: 
• Low lymphodepletion cohort: participants enrolled into the original 
lymphodepletion regimen specified prior to protocol amendment 2 consisting of 
3 days of cyclophosphamide 600mg/m2/day starting on day -7 and 3 days of 
fludarabine 30 mg/m2/day starting on day -7. 
• High lymphodepletion cohort: participants enrolled into the “option 2” 
lymphodepletion regimen introduced in protocol amendment 2 consisting of 
3 days of cyclophosphamide 900mg/m2/day starting on day -7 and 4 days of 
fludarabine 30 mg/m2/day) starting on day -8.  
Treatment Group Descriptions 
Data Displays for Reporting 
Description 
Order in TLF 
LOW LYMPHO DOSE + GSK794 
1 
HIGH LYMPHO DOSE + GSK794 
2 
Total 
3 
Note that for leukapheresed participants, grouping is by lymphodepletion cohort the 
participant was enrolled into, regardless of the actual lymphodepletion chemotherapy or 
NY-ESO-1c259T cell infusion subsequently received (or not). 
No analyses in this RAP are grouped according to the actual treatment received. 
For analyses in the screened population, participants who did not proceed to 
leukapheresis will be grouped as “No Treatment”. 
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects 
CDISC and GSK Data Display Standards terminology. 
5.1.1. 
Retreatment 
Participants that are retreated with a second course of conditioning chemotherapy and 
NY-ESO-1c259T cell infusion, will continue to be summarized by the lymphodepletion 
cohort the participant was enrolled into.  
This analysis plan and the treatment group descriptors described above do not 
accommodate for participants that were enrolled into the low lymphodepletion cohort and 
received the “option 2” high dose lymphodepletion regimen for retreatment, since there 
are no such retreated participants in which this scenario occurred. 


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5.2. 
Baseline Definitions 
Unless specified otherwise, the baseline value will be the latest assessment with a 
non-missing value (including unscheduled visits) prior to initiating lymphodepletion. 
Per-protocol, baseline assessments should occur less than 7 days prior to initiating 
lymphodepletion on day -8 (high lymphodepletion cohort) or day -7 (low 
lymphodepletion cohort). 
The initial identification of baseline will consider assessments within 7 days (inclusive) 
of initiating lymphodepletion. If a non-missing assessment within 7 days of initiating 
lymphodepletion is not available, then the last assessment with a non-missing value prior 
to initiating lymphodepletion would be used even if it occurred more than 7 days prior to 
initiating lymphodepletion. If an assessment is performed on the same date as the start of 
lymphodepleting chemotherapy and the time of assessment is not recorded, then the 
assessment will be assumed to have occurred prior to lymphodepletion and used as 
baseline. 
For participants who did not receive lymphodepleting chemotherapy during the study, 
baseline will be defined as the latest, non-missing collected value. 
Unless otherwise stated, if baseline data is missing, no derivation will be performed and 
baseline will be set to missing. 
For participants retreated with a second T-cell infusion, a baseline associated with 
retreatment lymphodepletion and infusion will be derived and used for all retreatment 
displays. For all endpoints except laboratory data, baseline will be as described for the 
initial infusion albeit the window for baseline will be ≤28 days prior to the initiation of 
retreatment lymphodepletion chemotherapy, instead of 7 days. For laboratory data 
(lymphocyte subset (CD3/CD4/CD8), hematology, chemistry, coagulation and 
urinalysis), baseline will be as described above for the initial infusion but prior to 
initiation of retreatment lymphodepletion. 
5.3. 
Multicenter Studies 
Data from all participating centers will be pooled prior to analysis. 
It is anticipated that participant accrual will be spread thinly across centers and 
summaries of data by center would be unlikely to be informative and will not, therefore, 
be provided. 
5.4. 
Examination of Covariates, Other Strata, and Subgroups 
No covariates or strata will be incorporated into analyses and no subgroup analysis will 
be performed. 
5.5. 
Multiple Comparison and Multiplicity 
No formal statistical testing will be performed; therefore, no adjustments for multiple 
comparisons or multiplicity are planned.  


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5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
14.3 
Appendix 3: Assessment Windows 
14.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
14.5 
Appendix 5: Data Display Standards & Handling Conventions 
14.6 
Appendix 6: Derived and Transformed Data 
14.7 
Appendix 7: Reporting Standards for Missing Data 
14.8 
Appendix 8: Values of Potential Clinical Importance 


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6.  
S T U D Y P O P U L A TI O N  A N A L Y S E S  
6. 1.  
O v er vi e w of Pl a n n e d St u d y P o p ul ati o n A n al y s e s  
T he st u d y p o p ulati o n a n al yses will be bas e d o n t he I nte nt-to -Treat  (I T T) p o p ulati o n, 
u nless ot her wise s pecifie d.  S o me st u d y p o p ulati o n a nal ys es will be re p eate d i n the mI T T 
p o p ulati o n.  If t h e mI T T a n d I T T p o p ulati o ns are i d e ntical, t he n res ults pla n ne d f or b ot h 
I T T a n d mI T T p o p ulati o ns will o nl y b e re p orte d f or t he I T T p o p ulati o n . 
St u d y p o p ul ati o n a nal yses i ncl u di n g a nal ys es of p artici pa nt ’s dis p ositi o n, pr ot oc ol 
de viati o ns, de m o gra p hic  a n d baseli ne c h aracteristi cs, pri or a n d c o nc o mita nt me dicati o ns, 
disease c h aracteristics at i nitial dia g n osis a n d at scree ni n g, pri or a n d o n -st u dy a nti -ca ncer 
t hera p y, pri or a nti -ca n cer ra di ot hera p y, pri or a n d o n -st u d y s ur gical pr oce d ures , disease 
b ur de n at bas eli n e a n d st u d y treat me nt e x p os ure will be base d o n G S K C ore D ata 
S ta n dar ds. Details of t he pla n ne d dis pla ys  are pres e nte d i n  A p pe n di x 1 2 : List of Data 
Dis pla ys . 
6. 2.  
Di s p o siti o n of P arti ci p a nt s  
A s u m mar y of t he n u m ber of partici pa nt s i n e ac h of t he a nal ysis p o p ulati o ns descri be d i n 
Secti o n 4  will be pr o vi de d. A listi n g of partici pa nt s e x cl u de d fr o m a nal ysis p o p ulati o ns 
will als o be pr o vi de d  det aili n g reas o n f or e x cl usi o n . 
A s u m mar y of scree ni n g stat us a n d reas o ns f or scree n fail ure t o get her wit h a listi n g of 
reas o ns f or scree n fail ure will be pr o vi de d usi n g t he scree ne d p o p ulati o n.  Per G S K 
re p orti n g sta n dar ds, parti ci pa nts w h o were rescree ne d will a p pear o nce i n t hese dis pla ys 
acc or di n g t o t heir fi nal stat us , wit h a n a d diti o nal listi n g detaili n g th eir m ulti ple 
scree ni n gs.  
O verall st u d y dis p ositi o n will be s u m marize d. F or partici pa nts w h o ha v e recei ve d T -cell 
i nf usi o n, t his will be base d o n st u d y stat us as rec or de d o n t he “ E n d of St u d y” f or m. If a n y 
partici pa nts ret ur n fr o m t he l o n g -t er m f oll o w-u p st u d y a n d are retreate d wit h 2 n d T -cell 
i nf usi o n, t his will be base d o n st u d y stat us as rec or de d o n t he sec o n d “ E n d of St u d y” 
f or m. Partici pa nts w h ose e n d of st u d y st at us is “ T R A N S F E R R E D T O S E P A R A T E 
L O N G -T E R M F O L L O W -U P S T U D Y ” will be c o nsi dere d t o ha ve c o m plete d t his st u d y.  
F or p artici pa nts w h o d o n ot recei ve T -cell i nf usi o n (f or w h o m n o “ E n d of St u d y” f or m is 
c o m plete d), t he “E n d of Treat me nt” f or m rec or ds t heir fi nal st u d y dis p ositi o n.  
I nter ve nti o nal p has e stat us will be su m mari ze d wit h reas o ns f or n o n -c o m pleti o n as 
ca pt ure d i n t he eC R F.  
A listi n g of s u bject stat us (i ncl u di n g le u ka p heresis, l y m p h o de pleti o n, T-cell i nf usi o n, 
i nter ve nti o nal p hase a n d o verall st u d y stat us) will be pr o vi de d . At t he fi n al a nal ysis t his 
listi n g will be e xte n de d t o i ncl u de t he fi nal stat us fr o m retr eate d partici pa nts.  
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6. 3.  
Pr ot o c ol D e vi ati o n s  
Im p ort a nt  pr ot oc ol de viati o ns will be s u m marize d a n d liste d.  
A se parate listi n g of i ncl usi o n/e x cl usi o n de viati o ns will als o be pr o vi de d.  
At t he fi nal a nal ysis b ot h  listi n gs will  be e xte n de d  t o i ncl u de retreat me nt data . 
6. 4.  
D e m o gr a p hi c a n d B a s eli n e C h ar a ct eri sti c s  
T he de m o gra p hi c c haract eristics (e. g., race, a ge, et h nicit y, se x, hei g ht, bas eli ne b o d y 
wei g ht , b o d y mass i n de x ( B MI) a nd b o d y s urface area  ( B S A) cal c ulate d b y t he f or m ula 
of D u b ois -D u b ois  [D u b ois , 1 9 1 6]) will be s u m marize d a n d liste d. A ge, hei g ht, wei g ht, 
B MI  a n d B S A will be s u m marize d  as c onti n u o us varia bles , w hile se x, race a n d et h nicit y 
will be s u m mariz e d as cate g ori cal varia bles . A ge will als o be cate g orize d a n d 
s u m marize d b y G S K I D S L sta n dar d as ≤1 8, 1 9 -6 4, ≥6 5 . See A p pe n di x 6  f or details of 
calc ulati o n of a ge . 
I n a se parate s u m mar y, a ge will als o be cate g orize d a n d s u m marize d b y  1 8 -6 4, 6 5 -8 4 a n d 
≥8 5 usi n g E u dra C T.  
Disease c h aracteristics at i nitial dia g n osis i ncl u di n g l ocati o n of disease, ti m e si nce i nitial 
dia g n osis  t o scree ni n g i n m o nt hs, % of m y x oi d cells, % of r o u n d cells,  hist ol o gical gra de , 
sta ge, a n d reci pr ocal c hr o m os o mal tra nsl ocati o n will be s u m marize d a n d liste d. D isease 
c haracteristics at scree ni n g i ncl u di ng H L A -A stat us, N Y -E S O -1 stat us, sta ge, ti me si nce 
metastatic disease t o scree ni n g i n m o nt hs, a n d n u m ber s of pri or ra di ot hera p y re gi me ns 
bet wee n dia g n osis of a d v a nce d dise ase a n d l e u ka p heresis a n d n u m bers of pri or s yste mic 
t hera p y re gi me ns bet wee n  dia g n osis of a d va nce d disease a n d le u ka p heresis will als o be 
s u m marize d a n d liste d. Date of (first) scree ni n g c o nse nt will be ta ke n as dat e of 
scree ni n g, wit h c alc ulati o n of ela pse d ti me i n m o nt hs as detaile d i n A p pe n di x 6 . 
A s u m mar y of diseas e b ur de n at bas eli ne, i ncl u di n g n u m ber of or ga ns i n v ol ve d  a n d 
l ocati o n of disease at bas eli ne, will be pr o d uce d. B ot h tar get a n d n o n-tar get lesi o ns at 
baseli ne will be i ncl u de d.  T hese wil l be base d o n t he i n vesti gat or’s baseli ne disease 
assess me nt.  
M e dical c o n diti o ns (hist or y a n d o n g oi n g) at scree ni n g will be liste d a n d s u m marize d. 
At t he fi nal a nal ysis  t he listi n g of de m o gra p hi cs will be re peate d o n t h e I T T p o p ulati o n 
e x cl u di n g retr eat me n t dat a.
 
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6. 5.  
Pri or a n d C o n c o mit a nt M e di c ati o n s  
All c o nc o mita nt me dicati o ns will be s u m marize d (f or t he mI T T P o p ulati o n o nl y), a n d all 
pri or a n d c o n c o mita nt me dicati o ns will be i ncl u de d i n a si n gle listi n g.  Defi niti o n of pri or 
a n d c o nc o mita nt me dicati o n st u d y p hases are pr o vi de d i n A p pe n di x 4 . N ote all 
s u m maries e x cl u de retreat me nt. 
M e dicati o ns will be c o de d usi n g  G S K Dr u g c o di n g  dicti o nar y, s u m marize d a n d liste d. 
T he s u m mar y of c o n c o mita nt me dicati o ns will s h o w t he n u m ber a n d p erce nt a ge of 
partici pa nt s ta ki n g c o nc o mita nt me dicati o n b y I n gre die nt. M ulti-i n gre die nt pr o d ucts will 
be s u m mariz e d b y t heir s e parat e i n gre die nts rat her t ha n as a c o m bi nati o n of i n gre di e nts. 
A nat o mical T hera pe utic C he mical ( A T C) classifi cati o n Le vel 1 ( B o d y S yst e m) 
i nf or mati o n will be i ncl u de d i n t he dataset creat e d b ut will n ot a p pear o n t he listi n g or 
s u m mar y.  
Me dicati o ns will als o be c o de d usi n g t he  W H O Dr u g dicti o nar y i n a se parat e dataset b ut 
t his will n ot be use d f or a n y of t he re p orti n g pla n ne d i n t his d ocu me nt.  
I n t he s u m mar y of c o n c o mita nt me dicati o ns, eac h partici pa nt  will be c o u nte d o nce wit hi n 
eac h u ni q ue i n gre die nt. F or e x a m ple, if a partici pa nt  ta kes A m o x ycilli n o n t w o se parate 
occasi o ns, t he partici pa nt  will be c o u nte d o nl y o n ce u n der t he i n gre die nt  ‘ A m o x ycilli n’. 
I n t he s u m mar y of c o n c o mita nt me dicati o ns, t he i n gre die nts will be s u m marize d b y t he 
base o nl y.  
At t he fi nal a nal ysis t he  pri or a n d c o n c o mita nt me dicati o ns listi n g will be re peat e d o n t he 
mI T T p o p ulati o n e x cl u di n g retreat me nt data.
. 
Bl o o d pr o d u cts will be s u m marize d a n d liste d.
 
6. 6.  
St u d y Tr e at m e nt E x p o s ur e  
St u d y treat me nts –  des cri be d i n S ecti on  5 of t he pr ot oc ol –  are le u ka p heresis, 
l y m p h o de pleti n g c h e m ot hera p y a n d N Y -E S O -1 c 2 5 9T cell i nf usi o n. 
D ose a d mi nistrati o n data f or l y m p h o d e pleti n g c he m ot hera p y , i ncl u di n g 
c ycl o p h os p ha mi de a n d fl u dara bi ne, will be pres e nte d i n a data listi n g.  At t h e fi nal 
a nal ysis t his listi n g will be re peate d  o n t he I T T p o p ulati o n e xcl u di n g retreat me nt data. A 
se parat e listi n g of  retreat me nt l y m p h o de pleti o n o n t he mI T T 2 p o p ul ati o n  will als o be 
prese nte d . B ot h listi n gs will i ncl u de t he c u m ulati ve d ose of l y m p h o de pleti o n per 
partici pa nt.   
At t he fi nal a nal ysis t he c u m ulati ve d ose  ( m g/ m2) f or t he 1st l y m p h o de pleti n g 
c he m ot hera p y acr oss all partici pa nts  will be s u m marize d usi n g n, mea n, st a n dar d 
de viati o n, me dia n, mi n a n d ma x.  
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N u m ber a n d p erce nta ge of partici pa nt s recei vi n g le u ka p heresis pr oce d ure, 
l y m p h o de pleti n g c h e m o t hera p y, a n d T-cell i nf usi o n will be s u m marize d  (e x cl u di n g 
retreat me nt). 
A listi n g of st u d y tr eat me nt will be pr o vi de d, i ncl u di n g o verall T -cell i nf usi o n star t a n d 
st o p date/ti me  ( o ver all b a gs), a vera ge v ect or  c o p y n u m ber per cell i n t he cell pr o d uct, 
t otal n u m ber of tra ns d uce d cells , a n d perce nt of cells tra ns d uce d . At t he fi nal a nal ysis t his 
listi n g will be re peate d o n t he I T T p o p ulati o n e x cl u di n g retreat me nt d ata.
 
T he t otal n u m ber of tr a ns d uce d T -cells will be s u m marize d usi n g n, mea n, sta n dar d 
de viati o n, me dia n , mi n a n d ma x . Als o, t he t otal n u m ber of tra ns d u ce d T -cells will be 
cate g orize d  i nt o < 1, > = 1 t o <= 8 , a n d >8  (x 1 0 9 cells). T his s u m mar y will e x cl u de a n y 
retreat me nt 2 n d T -cell i nf usi o ns . 
6. 7.  
A nti -C a n c er T h er a pi e s  
A nti -ca ncer t hera pies will be classifie d i nt o pri or a n d o n -st u d y p has es as descri be d i n 
A p pe n di x 4 . O nl y t h era pi es i nitiate d o n or after t he first da y of l y m p h o de pl eti o n 
c he mot hera p y are c o nsi d ere d o n -st u d y. N ot e t hat  a nti-ca ncer t hera pies gi v e n after first 
disease pr o gressi o n b ut bef ore first da y of retreat me nt l y m p h o de pleti o n c h e m ot hera p y t o 
partici pa nts re mai ni n g o n-st u d y f or retr eat me nt after t heir first disease pr o gressi o n b ut 
bef ore t h e first da y of  retreat me nt l y m p h o d e pleti o n are c o nsi d ere d o n-st u d y. Pri or 
t hera p y re gi me ns will be f urt her cl assifie d i nt o s u b -p hases at dat e of dia g n osis of 
a d va nce d ( metastatic/ u nr esecta ble) diseas e a n d date o f le u ka p heresis. 
6. 7. 1.  
Pri or A nti -C a n c er T h er a pi e s  
Pri or t hera p y t y pes as d efi ne d bel o w are s yste mic t hera p y (c o de d usi n g t he G S K Dr u g 
c o di n g dicti o nar y) , ra di ot hera p y, a n d ca n cer-rel ate d s ur ger y. 
Re gi me ns i nitiate d bef ore dia g n osis of a d va n ce d disease will n ot be i ncl u d e d i n 
s u m maries of pri or t hera pies. 
S u m maries of t he n u m bers of ra di ot hera p y a n d s yste mic a nti -ca ncer re gi me ns i nitiate d 
bet wee n dia g n osis of a d v a nce d dise ase a n d l e u ka p heresis will be pres e nte d as part of t he 
s u m mar y of disease c haracteristics at scree ni n g. 
S yste mic a nti -ca ncer t hera p y re gi me ns i nitiate d bet wee n  le u ka p h eresis a n d 
l y m p h o de pleti o n (as d efi ne d i n A p pe n di x 4 ) will be cate g orize d as eit her bri d gi n g 
(re gi me ns a d mi nistere d t o mai ntai n/sta bilize t he partici pa nt u ntil T-cell i nf usi o n ) or f ull 
li nes (re gi me ns a d mi nistere d wit h t he i nte nt of disease effect ) t hr o u g h G S K st u d y 
p h ysicia n re vie w.  
B ri d gi n g t hera pi es will be e x cl u de d fr o m s u m maries of pri or a nti -ca ncer t h era p y. 
T h u s, u nless ot her wise st ate d , s u m maries of pri or s yste mic a nti-ca ncer t hera pies will 
i ncl u de all t hera pies i nitiate d fr o m dia g n osis of a d va nce dise ase t o l y m p h o de pleti o n 
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e x ce pt t h ose i n t he le u ka p heresis t o l y m p h o de pl eti o n peri o d i de ntified as bri d gi n g 
t hera pies. ( N ot e t hat t his is e q ui vale nt t o all t hera pies fr o m dia g n osis of a d v a nce d dise ase 
t o le u ka p heresis pl us t hera pies i nitiate d bet wee n l e u ka p heresis a n d l y m p h o d e pleti o n 
i de ntifie d as f ull li nes.)  
A brea k d o w n of t he n u m ber of partici p a nts w h o recei ve d eac h cate g or y of pri or 
a nti-ca ncer t hera p y (s ur ger y, ra di ot hera p y, c h e m ot hera p y, etc.) will be pres e nte d.  
A nti -ca ncer t hera p y will be c o de d usi n g G S K Dr u g c o di n g dicti o nar y. T he n u m ber of 
partici pa nts recei vi n g pri or a nti-ca n cer t h era pies  will be s u m marize d b y  A T C Le v el 1 a n d 
i n gre di e nt. Bri d gi n g t hera pies will be si milarl y s u m marize d. 
A s u m mar y of t he n u m ber of pri or a nti -ca ncer t hera p y re gi me ns will als o be pr o d uce d.  
All pri or a nti -ca n cer t h era p y will be liste d, wit h s u b -p hase i n dicat e d  a n d bri d gi n g 
t hera pies fla g ge d. 
All a nti-ca ncer ra di ot hera p y (i ncl u di n g o n-st u d y) will be liste d, wit h o n -st u d y or pri or 
s u b-p hase i n dicate d.  At t he fi nal a nal ysis t his listi n g will be re peat e d  o n t he I T T 
p o p ulati o n e x cl u di n g retr eat me nt data.
All p ri or ca ncer-relate d s ur gic al pr oce d ures will be liste d, wit h s u b-p hase i n dicate d. 
T h ose s ur geri es carrie d o ut bet wee n dia g n osis of a d va nce d dise ase a n d l y m p h o de pleti o n 
will be s u m mariz e d b y i nte nt a n d site.  
 
6. 7. 2.  
O n -St u d y A nti -C a n c er T h er a pi e s  
T he n u m ber a n d p erce nta ge of partici p a nt s t hat recei ve d a n y o n -st u d y a nti-ca ncer t h era p y 
will be s u m mariz e d  t o get her wit h t he ti me fr o m T-cell i nf usi o n t o start of s u bse q ue nt 
a nti-ca ncer t hera p y f or t h ose t hat recei ve d o n-st u d y a nti-ca ncer t hera p y (e x cl u di n g 
retreat me nt). 
O n -st u d y s yste mic t hera pies will be c o de d usi n g t he G S K Dr u g  c o di n g dicti o nar y, t he n  
s u m marize d b y A T C Le v el 1 a n d i n gre die nt. 
Partici pa nt -le vel data d es cri bi n g all o n-st u d y a nti -ca ncer t hera pies a n d ca n cer -relate d 
s ur gic al pr oce d ures will be pr o vi de d i n se parate list i n gs. At t he fi nal a n al ysis  t his listi n g 
will  be re peat e d o n t he I T T p o p ulati o n e xcl u di n g o n -st u d y t hera pies after retreat me nt 
l y m p h o de pleti o n.
All r esecti o n bi o psies will be liste d.  At t he fi nal a n al ysis t his listi n g will be e xte n de d t o 
i ncl u de retr eat me nt data.  
C CI
C CI
C CI
C CI
C CI
C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
3 6  
 
7.  
E F FI C A C Y A N A L Y S E S  
T he pri mar y a n d s ec o n d ar y effic ac y a nal yses are o nl y c o n d u cte d o n t he 1 st i nf usi o n data. 
Lesi o n assess me nt met h o d a n d ti mi n g, a n d res p o nse deter mi nati o n f or all efficac y 
a nal ys es will be c o n d u cte d acc or di n g t o R E CI S T ( versi o n 1. 1) (Eis e n ha uer , 2 0 0 9) per 
Secti o n 1 6. 4 of t he Pr ot oc ol . As t his is a n o n -c o m parati ve st u d y, res p o ns es m ust be 
c o nfir me d. 
•  
T o be assi g ne d a c o nfir m e d res p o nse assess me nt of  Partial Res p o nse  (P R ) or 
C o m plete Res p o nse ( C R ), a c o nfir mat or y dis ease assess me nt s h o ul d be perf or me d 
n o less t ha n 4 wee ks ( 2 8 da ys) after t he criteria f or res p o nse are first met . 
 
7. 1.  
Pri m ar y E ffi c a c y A n al y s e s  
Listi n gs of R E CI S T v 1. 1 res p o n se as assesse d b y t he i n vesti gat or a n d i n de pe n de nt re vie w 
at eac h assess me nt d uri n g t he i nter v e nti o nal p has e (i.e. e x cl u di n g a n y retr eat me nt 
assess me nts) will be pr o vi de d, i ncl u di n g visit n u m ber, date of assess me nt, res p o nse da y, 
tar get a n d n o n-t ar get lesio n res p o nse, ne w lesi o n, a n d o verall res p o nse.  
7. 1. 1.  
E n d p oi nt / V ari a bl e s  
7. 1. 1. 1.  
B e st O v er all R e s p o n s e ( B O R)  wit h C o nfir m ati o n  p er R E CI S T  v 1. 1 b y 
I n v e sti g at or A s s e s s m e nt 
T he Best O verall Res p o nse  (B O R) wit h c o nfir mati o n f or a partici p a nt is defi ne d as t he 
best c o nfir me d res p o nse ( C o nfir me d C o m plete Res p o nse [ C R] > C o nfir me d Partial 
Res p o nse [ P R] > Sta ble Disease [ S D] > Pr o gressi ve Disease [ P D] > N ot E val ua ble [ N E]) 
fr o m treat me nt start d ate u ntil disease pr o gressi o n or i nitiati o n of ne w a nti-ca ncer 
t hera p y, w hich e ver is earlier, as assesse d b y t h e i n vesti gat or p er R E CI S T v 1. 1 Criteria  
d uri n g t he i nter ve nti o nal p hase . 
•  
I n cl usi o n criteria 6 re q uir es partici pa nts t o ha ve m eas ura bl e disease acc or di n g t o 
R E CI S T  v 1. 1 criteri a. If a partici pa nt has n o m eas ura ble diseas e at bas eli ne (a n d 
t heref ore n o tar get lesi o ns) t he n t he partici pa nt will be treate d as a n o n-res p o n der 
wit h B O R of N E ( n ot e v al ua ble) , re gar dl ess of a n y n o n-tar get r es p o nse ( of C R, 
N o n -C R/ N o n -P D or P D ). 
•  
A res p o nse of  C R  or P R is c o nfir me d if t he criteria f or eac h are met at a s u bse q ue nt 
ti me p oi nt at least 2 8 da ys later (b ut bef ore dise ase pr o gressi o n or i nitiati o n of ne w 
a nti-ca ncer t hera p y) , e x cl u di n g assess me nts t hat are n ot e val ua ble ( N E) or were  n ot 
d o ne . 
•  
Res p o nses of C R/ P R t hat d o n ot meet t he re q uir e me nts of c o nfir me d C R/ P R are still 
eli gi ble t o be c o nsi dere d f or a B O R wit h c o nfir mati o n of S D.  
C CI


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• 
To be considered evidence for a BOR with confirmation of Stable Disease (SD), a 
disease assessment meeting the RECIST 1.1 SD (or unconfirmed CR or unconfirmed 
PR) criteria must be after at least 28 days of follow-up post T-cell infusion (where 
the day of T-cell infusion is day 1). If the minimum of 4 weeks (28 days) for SD (or 
unconfirmed CR or unconfirmed PR) is not met, best response will depend on the 
subsequent assessments. For example, if an assessment of PD follows the assessment 
of SD and SD does not meet the minimum 4-week requirement the best response will 
be PD. Alternatively, participants lost to follow-up after an SD assessment not 
meeting the minimum time criteria will be considered not evaluable (NE) for BOR. 
• 
Disease assessments after new anti-cancer therapy will not be considered when 
deriving best overall response. 
• 
Anti-cancer therapies are per protocol Section 6.1 & Section 6.2: non- protocol 
chemotherapy, immune therapy, biological therapy (including targeted therapies 
with tyrosine kinase inhibitors or monoclonal antibodies), investigational 
anti-cancer therapy, locoregional therapies such as surgical resection or 
non-palliative radiotherapy. 
• 
If time is not collected and anti-cancer therapy starts on the same day as the 
disease assessment, it is assumed that the disease assessment occurred first. 
• 
New anti-cancer therapies are those classified as on-study (as defined in 
Appendix 4). 
7.1.1.2. 
Overall Response Rate (ORR) with Confirmation per RECIST v1.1 by 
Investigator Assessment 
The primary efficacy endpoint is the Overall Response Rate (ORR) with confirmation per 
RECIST v1.1 by investigator assessment, defined as the percentage of participants with a 
confirmed complete response (CR) or confirmed partial response (PR) as the BOR with 
confirmation, as assessed by the investigator per RECIST v1.1 Criteria during the 
interventional phase. 
7.1.1.3. 
Best Overall Response (BOR) without Confirmation per RECIST v1.1 by 
Investigator Assessment 
The Best Overall Response (BOR) without confirmation is required as supporting 
evidence for some displays. This is defined for a participant as the best response 
(Complete Response [CR] > Partial Response [PR] > Stable Disease [SD] > Progressive 
Disease [PD] > Not Evaluable [NE]) from treatment start date until disease progression 
or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the 
investigator per RECIST v1.1 Criteria during the interventional phase. 
• 
Inclusion criteria 6 requires participants to have measurable disease according to 
RECIST v1.1 criteria. If a participant has no measurable disease at baseline (and 
therefore no target lesions) then the participant will be treated as a non-responder 
with BOR of NE (not evaluable), regardless of any non-target response (of CR, 
Non-CR/Non-PD or PD). 
• 
To be considered evidence for a BOR of Stable Disease (SD), a disease assessment 
meeting the RECIST 1.1 SD criteria must be after at least 28 days of follow-up post 


CONFIDENTIAL 
 
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T-cell infusion (where the day of T-cell infusion is day 1). If the minimum of 
4 weeks (28 days) for SD is not met, best response will depend on the subsequent 
assessments, as described in Section 7.1.1.1 above for BOR with confirmation. 
• 
Disease assessments after new anti-cancer therapy will not be considered when 
deriving best overall response, as described in Section 7.1.1.1 above for BOR with 
confirmation. 
7.1.2. 
Summary Measure 
The number and percentage of participants in the analysis population of interest with the 
best overall response with confirmation in the following response categories at each 
assessment will be summarized: CR, PR, SD, PD and NE. The overall response rate and 
the corresponding two-sided exact (Clopper-Pearson) 95% CI will also be provided. 
Participants with unknown or missing responses will be treated as non-responders, i.e., 
these participants will be included in the denominator when calculating percentages of 
response.  
Percent change in the sum of target lesion diameters from baseline over the interventional 
phase for each subject will be shown in a spider plot. A waterfall plot showing the 
maximum percent reduction from baseline in target tumor measurement will be produced. 
Details of the planned displays are provided in Appendix 12 and are based on GSK data 
standards and statistical principles. 
7.1.3. 
Population of Interest  
The primary efficacy analyses will be based on the modified Intent-to-Treat (mITT) 
population. The Intent-to-Treat (ITT) is the sensitivity analysis population for the primary 
efficacy endpoint, ORR with confirmation by investigator assessment. If the mITT and 
ITT populations are identical, then results planned for both ITT and mITT populations 
will only be reported for the mITT population. 
7.1.4. 
Strategy for Intercurrent Events 
A composite strategy will be followed for participants who are not evaluable or have 
missing response who will be treated as non-responders; i.e. they will be included in the 
denominator when calculating the percentage. 
7.1.5. 
Statistical Analyses / Methods 
The study is not powered for either primary or secondary endpoints, therefore no 
statistical testing will be done.  


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7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
7.2.1.1. 
Best Overall Response (BOR) with Confirmation per RECIST v1.1 by 
Independent Review 
The BOR with confirmation described in Section 7.1.1.1 for the primary analysis based 
on the investigator assessments of response will be repeated based on response as 
assessed by independent review. 
7.2.1.2. 
Overall Response (ORR) with Confirmation per RECIST v1.1 by 
Independent Review 
The ORR with confirmation described in Section 7.1.1.2 for the primary analyses for 
BOR with confirmation based on the investigator assessments of response will be 
repeated for BOR with confirmation based on independent review as defined in 
Section 7.2.1.1. 
7.2.1.3. 
Time to (Confirmed) Response (TTR) 
Time to (confirmed) response (TTR) is defined as the interval of time (in months) 
between the date of 1st T-cell infusion and the first documented evidence of the 
confirmed response (PR or CR), in the subset of participants with a confirmed response 
of PR or CR as the BOR with confirmation. 
TTR with confirmation will be calculated for both investigator assessment and 
independent review. 
7.2.1.4. 
Duration of (Confirmed) Response (DOR) 
Duration of (confirmed) response (DOR) is defined as the interval of time (in months) 
from first documented evidence of the confirmed response (PR or CR) to the date of 
disease progression per RECIST 1.1 Criteria or death due to any cause, among 
participants with a confirmed response of PR or CR as the BOR.  
Censoring rules for DOR will follow those of the PFS (see Section 7.2.2). 
DOR with confirmation will be calculated for both investigator assessment and 
independent review. 
7.2.2. 
Progression Free Survival (PFS) 
Progression-free survival (PFS) is defined as the interval of time (in months) between the 
date of 1st T-cell infusion and the earlier of the date of disease progression per RECIST 
v1.1 Criteria or death due to any cause.  
PFS will be calculated for both investigator assessment and independent review. 


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If a participant has neither progressed nor died nor started new anti-cancer therapy, PFS 
will be censored at the date of the last adequate disease assessment. The imaging 
modalities for this study are: 
• Diagnostic-quality CT scan with oral and/or i.v. iodinated contrast of the chest and 
abdomen/pelvis (CT is the preferred modality for tumor assessments) 
• MRI of the abdomen/pelvis acquired before and after gadolinium contrast agent 
administration and a non-contrast enhanced CT of the chest, if a participant is 
contraindicated for contrast enhanced CT 
• MRI of the extremities per site standard of care, if clinically indicated. 
• Digital photographs of skin lesions including a ruler for estimating the size of the 
lesion. 
For participants who receive on-study 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 on-study anti-cancer therapy, 
PFS will be censored at the date of T-cell infusion. 
• 
If the start date of the on-study anti-cancer therapy is partial (i.e. either missing the 
day but has the month and year available or missing both day and month), the 
imputation rules described in Section 14.7 will be applied. No imputation will be 
made for completely missing dates. 
Anti-cancer therapy for efficacy censoring is as described in Section 7.1.1.1 above for 
BOR with confirmation. 
Inclusion criteria 6 requires participants to have measurable disease according to RECIST 
v1.1 criteria. If a participant has no measurable disease at baseline (and therefore no 
target lesions) then the participant will be considered censored at Day 1 for PFS (PFS 
follow-up ended), regardless of any non-target progression or new lesions. 
Per Protocol Section 7.6, only participants that progress during the interventional phase 
are considered for retreatment. Assuming such progression is per RECIST v1.1, no 
additional censoring rules are required to exclude retreatment disease assessments or 
deaths after retreatment. 
A summary of the assignments for progression and censoring dates for PFS are specified 
in Table 1. 


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Table 1 
PFS Censoring Rules 
Scenario 
Date of Event (Progression/Death) or 
Censored 
Event 
(Progression/Death) 
or Censored 
No baseline assessments4 
and the participant has not 
died 
Day 1 (NY-ESO-1c259T cell infusion) 
Censored 
(PFS follow-up ended) 
No adequate post-baseline 
assessments before start 
of new anti-cancer therapy 
and the participant has not 
died 
Day 1 (NY-ESO-1c259T cell infusion) 
Censored 
(PFS follow-up ended) 
Progression documented 
at or between scheduled 
visits 
Date of assessment of progression1 
Event 
With adequate post-
baseline assessment but 
no progression (or death)  
Date of last ’adequate’ assessment of response2 
Censored 
(PFS follow-up ongoing if 
still in interventional phase 
follow-up) 
With adequate post-
baseline assessment and 
new anticancer treatment 
started (prior to 
documented disease 
progression).3  
Date of last ‘adequate’ assessment of response2 (on or 
prior to starting anti-cancer therapy)  
Censored 
(PFS follow-up ended) 
Death before first 
scheduled assessment 
Date of death 
Event 
Death (regardless of 
having baseline 
assessment) before 
missing two scheduled 
assessments and no 
progression 
Date of death (Use rule below to determine missing two 
scheduled assessments) 
Event 


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Scenario 
Date of Event (Progression/Death) or 
Censored 
Event 
(Progression/Death) 
or Censored 
Death (regardless of 
having baseline 
assessment) or 
progression after two or 
more missed scheduled 
assessments 
Day 1 (NY-ESO-1c259T cell infusion) if there is no 
adequate post-baseline assessment or date of last 
‘adequate’ assessment of response (Prior to missed 
assessments): 
As the assessment schedule changes through the 
course of the protocol (i.e. every 4 weeks until week 12 
and then at week 24, month 9 and every 3 months until 
month 24), the following rules will be used for identifying 
extended loss to follow up or extended time without an 
adequate assessment (i.e. two or more missed 
assessments). 
• If PFS event is on or prior to day 91 (week 12 + 7-day 
window), then a participant will be identified as an 
extended loss to follow up if the participant did not 
have an adequate assessment during the time period 
of 66 days (4 weeks + 4 weeks + 7-day window + 3-
day window) prior to PFS event;  
• Else if PFS event is after day 91 (week 12 + 7-day 
window) and on or prior to day 175 (week 24 + 7 day 
window), then a participant will be identified as an 
extended loss to follow up if the participant did not 
have an adequate assessment during the time period 
of 126 days (4 weeks + 12 weeks + 7-day window + 
7-day window) prior to PFS event; 
• Else if PFS event is after day 175 (week 24+ 7-day 
window) and on or prior to day 288 (month 9 + 14-day 
window), then a participant will be identified as an 
extended loss to follow up if the participant did not 
have an adequate assessment during the time period 
of 211 days (Month 9 – Week 12 + 14-day window + 
7-day window) prior to PFS event; 
• Else if PFS event is after day 288 (month 9 + 14-day 
window), then a participant will be identified as an 
extended loss to follow up if the participant did not 
have an adequate assessment during the time period 
of 218 days (Month 12 – Week 24 + 14-day window + 
7-day window) prior to PFS event. 
PFS will be censored at the date of last adequate 
disease assessment of response or Day 1, whatever is 
later, prior to PD/death. 
Censored 
(PFS follow-up ended) 
 


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1 The earliest of (i) Date of radiological assessment showing new lesion (if progression is based on new lesion); or 
(ii) Date of radiological assessment showing unequivocal progression in non-target lesions, or (iii) Date of last 
radiological assessment of measured lesions (if progression is based on increase in sum of measured lesions) 
2 An adequate assessment is defined as an assessment where the response is CR, PR, or SD. 
3 If PFS event and new anti-cancer therapy occur on the same day assume the progression was documented first 
(e.g. outcome is progression and the date is the date of the assessment of progression). 
4 No baseline assessment defined as baseline scan performed outside of the window specified in Section 5.2 or no 
baseline scan at all. 
 
7.2.3. 
Summary Measure 
7.2.3.1. 
Best Overall Response (BOR) with Confirmation per RECIST v1.1 by 
Independent Review 
The primary analyses will be repeated for BOR with confirmation as assessed by 
independent review. 
Investigator-assessed and independent reviewer-assessed BOR with confirmation will be 
compared. 
7.2.3.2. 
Overall Response (ORR) with Confirmation per RECIST v1.1 by 
Independent Review 
The primary analyses will be repeated for BOR with confirmation as assessed by 
independent review. 
7.2.3.3. 
Time to (Confirmed) Response (TTR) 
If there are sufficient number of responses at time of primary or final analysis, time to 
(confirmed) response will be summarized descriptively using n, median, mean, min, max 
and quartiles in the subset of participants with a confirmed response of PR or CR as the 
BOR with confirmation. 
TTR will be presented for both investigator assessment and independent review, if data 
warrant. 
7.2.3.4. 
Duration of (Confirmed) Response (DOR) 
Duration of (Confirmed) Response (DOR) will be listed and summarized in months 
among the participants with confirmed response of PR or CR as the BOR with 
confirmation, using Kaplan-Meier quartile estimates along with two-sided 95% CIs using 
a generalization of the Brookmeyer-Crowley method [Brookmeyer, 1982] under a log-log 
transformation, if data warrant. 
Kaplan-Meier curve will also be produced. 
DOR will be presented for both investigator assessment and independent review. 


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
4 4  
 
7. 2. 3. 5.  
Pr o gr e s si o n  F r e e S ur vi v al ( P F S) 
P F S will be liste d a n d s u m marize d i n m o nt hs usi n g Ka pla n -Mei er q ua ntile esti mates 
al o n g wit h t w o-si de d 9 5 % CIs usi n g a ge neralizati o n of t he Br o o k me yer-Cr o wle y 
met h o d [Br o o k me yer , 1 9 8 2 ] u n der a l o g-l o g tr a nsf or mati o n, if data warra nt. At t he Fi nal 
a nal ysis, t he P F S rate at 3 m o nt hl y i nter vals ( 3 , 6, 9,  1 2, etc) a n d t he c orres p o n di n g t w o-
si de d 9 5 % C Is ( u n der a l o g-l o g tr a nsf or mati o n) will als o be esti mate d fr o m t he Ka pla n -
Meier a n al ysis .  
Ka pla n -Mei er c ur ve will als o be pr o d uce d.  
P F S will be prese nte d f or b ot h i n vesti gat or ass ess me nt a n d i n de pe n de nt r e vie w.  
In v esti gat or a n d i n de p e n de nt  re vie wer-assesse d P F S e ve nt or ce ns ori n g a n d ti mi n g will 
be  c o m pare d . A ti me wi n d o w of pl us or mi n us 7 da ys will be a p plie d w he n deter mi ni n g 
a gree m e nt i n ti mi n g. A s u m mar y of t he a gree me nt will be pr o d uce d, t o get her wit h a  
s u p p orti n g listi n g. 
At t he Fi nal a n al ysis, t he me dia n f oll o w -u p ti me f or P F S f or i n vesti gat or assess me nt will 
be s u m mariz e d i n m o nt hs  usi n g t he re verse Ka pla n -Meier met h o d. Patie nts w h o  ha d a P D 
or  die d will be ce ns or e d f or f urt her f oll o w -u p i n t he re verse K M P F S f oll o w -u p 
esti mates. T he Ka pla n -M eier q ua ntiles will be s u m marise d as a b o ve f or P F S.  
7. 2. 4.  
P o p ul ati o n of I nt er e st  
T he sec o n d ar y efficac y a nal yses will be base d o n t he m I T T p o p ul ati o n . 
7. 2. 5.  
St ati sti c al A n al y s e s / M et h o d s  
Details of t he pla n ne d dis pla ys are pr o vi d e d i n A p pe n di x 1 2  a n d are base d o n G S K data 
sta n dar ds a n d statistical pri nci ples. 
U nless ot her wise s pecifie d, e n d p oi nts / varia bles d efi ne d i n Secti o n 7. 2. 1  will be 
s u m marize d usi n g descri pti ve statistics, gra p hicall y prese nte d ( w here a p pr o priate) a n d 
liste d. 
7. 3.  
E x pl or at or y Effi c a c y A n al y si s  
C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
4 5  
 
C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
4 6  
 
C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
4 7  
 
7. 4.  
I nt eri m A n al y se s  
A n i nteri m a nal ysis f or f utilit y w as c o n d ucte d aft er t he first 1 0 partici pa nt s ha d bee n 
treate d a n d all 1 0 partici p a nt s were eval ua bl e , as d escri be d i n Se cti o n 3. 1. 1 , w he n t he 
O verall Res p o nse Rate ( O R R) as assesse d b y t he i n vesti gat or was e val u ate d . 
I nteri m a nal yses of t h e sec o n d “ hi g h l y m p h o d e pleti o n”  c o h ort f or i nter nal d ecisi o n 
ma ki n g w ere als o c o n d ucte d as descri b e d i n S ecti o n 3. 1. 2 , w he n t he O verall Res p o nse 
Rate ( O R R) as assess e d b y t he i n vesti gat or was  e val uate d . 
7. 4. 1.  
O v er all R e s p o n s e R at e ( O R R)  wit h C o nfir m ati o n p er R E CI S T  v 1. 1 
b y I n v e sti g at or A s s e s s m e nt  
T he e n d p oi nt assesse d at i nteri m a nal ys es is t he O verall Res p o nse Rate  ( O R R) wit h 
c o nfir mati o n per R E CI S T v 1. 1 as assesse d b y t he i n vesti gat or , d efi ne d as t he pr o p orti o n 
of partici pa nt s wit h an i n vesti gat or -assess e d  c o nfir me d c o m plete res p o nse ( C R) or 
c o nfir me d partial res p o ns e ( P R) as t he B O R , as assesse d b y t he i n vesti gat or per R E CI S T 
v 1. 1  Criteria d uri n g t he i nter ve nti o nal p hase . 
7. 4. 2.  
P o p ul ati o n of I nt er e st  
T he i nteri m a nal yses of O R R will be base d o n t he  all eval ua ble  p o p ulati o n . 
7. 4. 3.  
Str at e g y f or I nt er c urr e nt E v e nt s  
A c o m p osite strate g y will be f oll o we d f or partici p a nt s w h o are n ot e val ua bl e or ha ve 
missi n g res p o nse w h o will be treate d as n o n -res p o n ders; i.e. t he y will be i n cl u de d i n t he 
de n o mi nat or w he n calc ul ati n g t he O R R . 
7. 4. 4.  
St ati sti c al A n al y s e s / M et h o d s  
A s u m mar y of i n vesti gat or-assesse d b est res p o nse will be pr o vi de d i ncl u di n g n u m ber a n d 
perce nt a ge of p artici pa nt s i n eac h cate g or y of best res p o nse. T he O R R a n d t he 
c orres p o n di n g t w o-si d e d e x act ( Cl o p per -Pears o n) 9 5 % c o nfi de n ce i nter val  will als o be 
pr o vi de d .  
D O R a n d P F S (assess e d per R E CI S T 1. 1) will be s u m marize d i n m o nt hs usi n g 
Ka pla n -Mei er q ua rtile esti mates al o n g wit h t w o-si de d 9 5 % CIs, if data warra nt. 
Ka pla n -Mei er c ur ve s of P F S will als o be pr o d uce d. A listi n g of partici pa nt  best res p o nse 
i ncl u di n g n u m ber of p os t-baseli ne ass ess me nts, e v al ua ble f or i nteri m a nal ysis, a n d 
c o nfir me d a n d u n c o nfir m e d best res p o nse  will be pr o vi de d. A wat erfall pl ot  s h o wi n g t he 
ma xi m u m perce nt re d ucti o n fr o m baseli ne i n t u m or meas ure m e nt will be pr o d uce d.  
Details of t he pla n ne d dis pla y s are pr o vi d e d i n A p pe n di x 1 2  a n d are base d o n G S K data 
sta n dar ds a n d statistical pri nci ples. 
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8.  
S A F E T Y A N A L Y S E S  
T he safet y a nal yses will be base d o n t he Inte nt -to -Treat  p o p ula ti o n e x ce pt f or dis pla ys 
t hat are tr eat me nt de pe n d e nt w here t h e m o difie d I nte nt -to -Treat  p o p ulati o n will be use d , 
as detaile d i n  A p pe n di x 1 2 . 
Safet y a nal yses will gr o u p le u ka p herese d partici pa nts acc or di n g t o t he l y m p h o de pleti o n 
c o h ort t he partici p a nt was e nr olle d i nt o , as descri b e d i n Secti o n 5. 1 , re gar dless of t he 
act ual l y m p h o d e pleti o n c he m ot hera p y or N Y -E S O -1 c 2 5 9T cell i nf usi o n s u bse q ue ntl y 
recei v e d ( or n ot). 
U nless ot her wise s pecifie d, s u m maries will i ncl u de t otals acr oss b ot h t he l o w a n d hi g h 
l y m p h o de pleti o n d ose tr eat me nt gr o u ps as descri be d i n S ecti o n 5. 1 . 
A pl ot of d urati o n  of t he i nter ve nti o nal p hase i ncl u di n g S A Es, deat h, pr o gressi o n, a n d 
res p o nse will be pr o d u ce d (ex cl u di n g retr eat me nt) . 
8. 1.  
A d v er s e E v e nt s A n al y s e s  
A d verse e ve nts a n al ys es  i ncl u di n g t he a n al ysis of a d verse e ve nts ( A Es), Seri o us ( S A Es) 
a n d ot her si g nifica nt A Es will be base d o n G S K C ore D ata S ta n dar ds. T he details of t he 
pla n ne d dis pla ys are pr o vi de d  i n A p pe n di x 1 2 . 
A Es will be c o de d t o t he Preferre d Ter m  ( P T) le vel usi n g t he latest versi o n of t he 
Me dical Dicti o nar y f or R e g ul at or y Affairs (M e d D R A ). T he rel ati o ns hi p bet wee n 
Me d D R A S O C, P T, a n d Ver bati m Te xt will be liste d. 
Ta bles t hat s u m mariz e A Es b y S O C a n d P T will use  Me d D R A preferre d ter ms , as well as 
a n y a d vers e e v e nt ta bles re q uire d f or discl os ure . M ost ot her  A E ta bles will s u m marize 
A Es b y usi n g t he c o m bi ne d ter ms defi ne d i n A p pe n di x 1 4 , as detaile d i n t he 
pr o gra m mi n g n ot es i n A p pe n di x 1 2 . A s u m mar y of i nci de nce of a d v erse e ve nts b y 
Me d D R A preferre d gr o u pe d b y c o m bi ne d preferre d ter m will be pr o d uce d  t o i n dicate t he 
c o m bi ne d preferre d ter ms . 
A Es  will be gra de d b y t h e i n vesti gat or acc or di n g t o t he Nati o nal Ca ncer I nstit ute - 
C o m m o n T o xicit y Criteri a f or A d v erse E v e nts ( N CI -C T C A E) v 4. 0 3 . R efer t o Secti o n 8. 5 
a n d Secti o n 8. 6 of Pr ot oc ol f or t he defi niti o ns a n d t he gra di n g of 
 a n d Graft vers us H ost Disease (G v H D ). F oll o wi n g pr ot oc ol 
a me n d me nt  5
ve nts are gra de d usi n g t he A merica n S ociet y f or Tra ns pla ntati o n 
a n d Cell ular T hera p y gra di n g s yste m [ Lee , 2 0 1 9]. 
I n t he e C R F f or t his st u d y A d v erse E v e nts f or w hi c h t he gra d e c ha n ges o ver t he c o urse of 
t he e ve nt are e ntere d as m ulti ple  rec or ds, o ne rec or d per gra de . (If m ulti ple gra des are 
e x perie nce d o n t he s a me da y t h e n t he hi g hest gra d e f or t hat da y is r e p orte d.) Si milarl y, 
e ve nts w here ot her attri b utes s uc h as rel ate d ness c ha n ge o ver t h e c o urse of t he e ve nt will  
als o be e ntere d as m ulti ple rec or ds . F or a nal ys es re q uiri n g s u m maries of n u m bers or 
c haracteristics of i n di vi d ual e ve nts, t hese m ulti ple se q ue ntial se g me nts will be c olla pse d 
bac k i nt o a si n gl e e ve nt rec or d pri or t o a nal ysis usi n g t he al g orit h m detaile d i n A p pe n di x 
1 5 . 
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At t he fi nal a nal ysis retr eat me nt data will be i ncl u de d. S u m maries of A Es will re p ort o n 
c o m bi ne d 1 st a n d 2 n d i nf usi o n A E data. A E listi n gs will be re peat e d e x cl u di n g t he 
retreat me nt data.
A d verse E v e nts wit h o nset o n or after l y m p h o d e pleti o n c he m ot hera p y st art date are 
c o nsi dere d tr eat me nt e m er ge nt. ( See A p pe n di x 4  f or details.) T he fre q u e nc y a n d 
perce nt a ge of all A Es (all gra des) a n d (se p arat el y) all treat me nt e mer ge nt A Es will be 
s u m marize d a n d dis pla ye d i n desce n di n g or der of t otal i nci de nce b y S yst e m Or ga n Class 
(S O C ) a n d Preferre d Ter m (P T ). I n t h e S O C r o w, t he n u m ber of partici pa nt s wit h 
m ulti ple e ve nts u n der t he sa me s yst e m or ga n cl ass will be c o u nte d o nce. A se parat e 
s u m mar y of S A Es b y S O C a n d P T will be pr o d uce d detaili n g n u m b ers of p artici pa nts a n d 
n u m ber of occ urre nces . 
S u m mar ies of  t he n u m ber a n d perce nta ge of partici pa nts wit h A Es b y ma xi m u m gra d e 
will be pr o d uce d  as i n dicate d i n A p pe n di x 1 2 . I n t hese dis pla ys A Es will be s orte d b y 
c o m bi ne d P T i n de sce n di n g or der of t otal i nci de nce a n d will use t he f oll o wi n g al g orit h ms 
f or c o u nti n g partici pa nts: 
•  
Preferre d ter m r o w : Partici pa nts e x perie nci n g t he sa me A E preferre d ter m se veral 
ti mes wit h differe nt gra d es will o nl y be c o u nt e d o nce wit h t he ma xi m u m gra de.  
•  
A n y e ve nt r o w : Eac h partici pa nt wit h at least o ne A E will be c o u nte d o nl y o nce at 
t he ma xi m u m gra de n o matter h o w ma n y e v e nts t he y h a ve. 
S e parate s u m mari es will be pr o vi de d f or A Es  (a n d S A Es) relate d t o st u d y tr eat me nts: o ne 
f or l y m p h o d e pleti n g c he m ot hera p y-relate d ( S) A Es, o ne f or T-cell i nf usi o n -relate d 
( S) A Es, a n d o ne f or all st u d y treat me nt relat e d  ( S) A Es.  
A st u d y treat me nt -relate d A E is defi ne d as a n A E f or w hic h t he i n vesti gat or classifies t he 
relati o ns hi p t o st u d y treat me nt as “ Yes ”, w hic h i ncl u des “ Defi nitel y Relate d ”, “ Pr o ba bl y 
Relate d” or “ P ossi bl y Relate d”. A w orst -cas e sce n ari o a p pr oac h will be ta ke n t o ha n dle 
missi n g relate d n ess data, i.e. t he s u m mar y ta ble will i ncl u de e ve nts wit h t he relati o ns hi p 
t o st u d y treat me nt as ‘ Yes’ or missi n g.  
S u m maries of t otal i nci de nce a n d  fre q ue nc y a n d p erce nt a ge of gra de 3, 4, a n d 5 e ve nts 
will be prese nte d f or: all A Es, all treat me nt e mer ge nt A Es, all st u d y-tr eat m e nt relate d 
A Es, all T -cell relate d A Es, all l y m p h o de pleti o n rela te d A Es, a n d all seri o us A Es. 
A s u m mar y of n o n -seri o us A Es t hat occ urre d i n strictl y 5 % of t h e partici p a nt s or a b o ve 
will be  pr o vi de d  ( n o r o u n di n g f or t h e perce nta ge will be  use d i n ter ms of 5 % t hres h ol d, 
e. g. e ve nts wit h 4. 9 % i nci de nce rate s h o ul d n ot be i ncl u de d i n t his ta ble). T his s u m mar y 
will c o ntai n t he n u m ber a n d perce nt a ge of p artici p a nt s a n d t he n u m ber of o cc urre nces of 
c om m o n n o n -seri o us a d v erse e v e nts. T he s u m mar y ta ble will be dis pla ye d b y S O C a n d 
P T.  
A listi n g of dela ye d A Es as  a dj u dicate d b y G S K will be pr o vi de d. G S K a dj u dicate d A Es 
will be pr o vi de d as a n a d diti o nal data s o urce.  
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I n t he e ve nt t hat a p artici pa nt  has wit h dra w n c o ns e nt  f or pri mar y researc h use, n o data 
after t he wit h dra wal of c o nse nt date fr o m t his partici pa nt i ncl u di n g deat h is s u p p ose d t o 
a p pear i n t he d ata bas e a n d s h o ul d be part of t he data clea ni n g pr ocess. All d eat hs will be 
s u m marize d base d o n t he n u m ber a n d perce nt a ge of partici pa nt s. T his s u m mar y will 
classif y p artici pa nt s b y ti me of deat h r elati ve t o t he date of T -cell i nfusi o n  ( > 3 0 da ys or 
3 0 da ys) a n d pri mar y ca use of deat h ( disease u n d er st u d y, treat me nt  relate d t o xicit y, or 
ot her). A s u p p o rti ve listi n g will be ge n erat e d.  
8. 2.  
A d v er s e E v e nt s of S p e ci al I nt er e st A n al y s e s  
T he a d verse e v e nts of s p ecial i nterest  ( A E SI) are as foll o ws:  
•  
•  Hae mat o p oietic c yt o p e nias (i ncl u di n g p a nc yt o pe nia a n d a plastic a n ae mia)  
•  Graft vers us h ost disease ( G v H D)  
•  I m m u ne Effect or-Cell Ass ociate d Ne ur ot o xicit y S y n dr o me (I C A N S)  
•  G uillai n -Barre s y n dr o m e  
Lists of Me d D R A ter ms ba se d o n cli nical r e vie w will be use d t o i de ntif y eac h t y pe of 
e ve nt. F or eac h t y p e of e ve nt, b ot h f oc use d a n d c o m pre he nsi ve lists will be use d. I n 
a d diti o n , f or h ae mat o p oi etic c yt o pe nias , t hr ee disti nct s u bsets of t he f oc use d list 
c orres p o n di n g t o  N e utr o pe nia , T hr o m b oc yt o pe ni a  a n d Ane mia  will be c o nsi dere d , as 
well as  Fe brile ne utr o p e nia  i de ntifie d b y si n gle preferre d ter m. C ha n ges t o t he Me d D R A 
dicti o nar y m a y occ ur bet wee n t he start of t he st u d y a n d t h e ti me of re p orti n g a n d/ or 
e mer gi n g data fr o m o n -g oi n g st u dies ma y hi g hli g ht a d diti o nal a d verse e ve nts of s pecial 
i nterest, t heref ore t he list of ter ms t o be use d f or eac h e v e nt of i nterest a n d t he s pecific 
e ve nts of i nterest will be base d o n t he safet y re vi e w tea m ( S R T) a gree me nts i n pla ce at 
t he ti me of re p orti n g.  
A E SI ta bl es will be re p orte d f or t he mI T T p o p ulati o n , c o nsi deri n g o nl y tr eat me nt-
e mer ge nt e v e nts . 
T he details of t he pla n n e d dis pla ys are pr o vi de d i n A p pe n di x 1 2 . 
Listi n gs of A E SIs will be pr o d uce d f or eac h A E SI cate g or y usi n g t he f o c use d list , w hic h 
will i ncl u de le u ka p heresis date, l y m p h o de pl eti o n start date, T -cell i nf usi o n date, A E start 
date, A E e n d d ate, S A E c o de, gra de , relati o ns hi p t o st u d y treat me nt a n d o ut c o me of 
e ve nt. A  c orres p o n di n g  listi n g of h ae mat o p oietic c yt o pe nias i de ntifi e d usi n g t he 
c o m pre he nsi ve list will als o be pr o vi de d . 
At t he fi nal a nal ysis retr eat me nt data will be i ncl u de d . S u m maries of A E SIs will re p ort 
o n c o m bi ne d 1 st a n d 2 n d i nf usi o n A E data. A E SI listi n gs will be re peate d e x cl u di n g t he 
retreat me nt data.
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The number and percentage of participants with these events will be summarized by 
categories of AESI and preferred term, with one table for AESIs identified using the 
focused lists (using combined preferred terms) and another for AESIs identified using the 
comprehensive lists (not using combined preferred terms). 
A summary of event characteristics for each category of treatment emergent AESI as 
identified using the focused lists will be provided, including number of participants with 
any event, number of events, number of participants with any event that is serious, 
number of participants with any event that is related to study treatment, the outcome of 
the event and the maximum grade for the event. The percentage will be calculated in two 
ways, one with number of participants with event as the denominator and the other with 
total number of participants as the denominator. The worst-case approach will be applied 
at participant level for the event outcome and maximum grade, i.e. a participant will only 
be counted once as the worst-case from all the events experienced by the participant. For 
action taken to an event, participant will be counted once under each action, e.g. if a 
participant has an event leading to both study treatment discontinuation and dose 
reduction, the participant will be counted once under both actions. 
Summaries of onset and duration of the first occurrence will be created for each AESI, 
identified using the focused lists. For Haematopoietic cytopenias this will include an 
overall analysis of events in the focused list as well as separate analyses for cell lines 
describing events of Neutropenia, Thrombocytopenia and Anemia. A summary of onset 
and duration of the last occurrence of Haematopoietic cytopenias identified using the 
focused list will also be created. These summaries will exclude any retreatment emergent 
AESIs. 
In addition, summaries of time to resolution of clinically significant (Grade 3 and above) 
Haematopoietic cytopenias will be created separately for the focused list of PTs, 
Neutropenia, Anemia, Thrombocytopenia, and Febrile Neutropenia. This analysis will 
use Kaplan-Meier methodology to report the median time to resolution and probability of 
resolution of adverse events by study day 30 and study day 90 for three types of clinically 
significant events: Initial occurrences, Recurrences, and delayed onset events. These 
summaries will exclude any retreatment emergent AESIs. 
• 
Time to resolution is defined as the time (in days) between the date of 1st T-cell 
infusion and the AE resolution end date inclusive. 
• 
Initial occurrences are defined as treatment-emergent Grade 3 and above cytopenias 
which start on or before Day 30. 
• 
Recurrences are defined as treatment-emergent Grade 3 and above cytopenias which 
start after Day 30, in subjects which had an initial occurrence. 
• 
Delayed onset events are defined as treatment-emergent Grade 3 and above 
cytopenias which start after Day 30, in subjects which did not have an initial 
occurrence. 
For subjects which have multiple events, the worst-case event will be summarized. If the 
subject had an unresolved event, this is considered worst-case and the subject will be 
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e ve nt. A d diti o nall y, t he d urati o n of t he c h ose n w orst-case e v e nt will be s u m marize d 
se parat el y f or all t hree t y pes of A Es. 
S u bjects wit h u nres ol ve d e ve nts will be ce ns ore d at t he c o m pleti o n / wit h dra wal of t he 
i nter ve ntio nal p hase or date of last c o ntact if t he s u bject has n ot c o m plete d / wit h dra w n 
fr o m t he i nter ve nti o nal p hase. See bel o w f or detaile d ce ns ori n g r ules. 
S c e n ari o  
D at e of E v e nt ( A E R e s ol uti o n), or C e n s or e d  
E v e nt ( A E 
R e s ol uti o n), 
C e n s or e d  
A dv ers e ev e nt res olv e s ( A E en d 
d at e is p o p ul at e d)  
A dv ers e ev e nt e n d dat e  
Ev e nt  
A dv ers e ev e nt d o es n ot r es olve, 
a n d p artici pa nt c o m plet es or 
wit h dr a w als fr o m t he 
i nt erv enti o nal p h as e of t h e st udy 
I nt erv e nti o n al p h as e co m pl eti on/ wit h dr a w al 
d at e 
C e ns or e d  
A dv ers e ev e nt d o es n ot r es olve, 
a n d p artici pa nt is o n g oi n g i n t he 
i nt erv enti o nal p h as e of t h e st udy 
D at e of l ast c ont act  
C e ns or e d  
C haracteristics, O nset a n d D urati o n, a n d Ti me t o Res ol uti o n s u m maries will n ot be 
creat e d if t here are 0 or 1 A E SI i n t otal.  
8. 2. 1.  
a n d Gr aft v er s u s H o st 
Di s e a s e ( G v H D)   
Refer t o Secti o n 8. 5 a n d Secti o n 8. 6 of Pr ot oc ol f or t he defi niti o ns a n d t he gra di n g of 
a n d G v H D. T he listi n g of
E SIs will als o i ncl u de ti me fr o m i nf usi o n t o first 
( da ys) a n d ti me fr o m i nf usi o n t o ma x  
 ( da ys). Listi n gs of s y m pt o ms a n d 
treat me nts relat e d t o 
a n d (se paratel y) G v H D will be pr o d uce d fr o m t he A E SI f or ms, 
a n d a listi n g of all t ociliz u ma b a d mi nistrati o ns rec or de d as c o n c o mita nt me dicati o ns 
prese nte d as detaile d i n A p pe n di x 1 2 . 
At t he fi nal a nal ysis t he listi n g of s y m pt o ms a n d treat me nts relate d t o
a n d listi n g of 
t ociliz u ma b a d mi nistrati o ns will be re peat e d  o n t he I T T p o p ulati o n e x cl u di n g ret reat me nt 
data.
  
8. 3.  
Cli ni c al L a b or at or y A n al y s e s  
L a b orat or y e val uati o ns i ncl u di n g t he a nal yses of C he mistr y la b orat or y tests, He mat ol o g y 
la b orat or y tests, a n d ot her la b orat o r y tests will be base d o n G S K C ore D ata S ta n dar ds. 
T he details of t he pla n n e d  dis pla ys are i n A p pe n di x 1 2 . 
T he la b orat or y assess me nt s c o n d ucte d t o m o nit or partici pa nt  safet y are i n Ta ble 2 .  
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Table 2 
List of Clinical Laboratory Tests 
Hematology, Chemistry and Urinalysis Variables 
Clinical Chemistry 
Hematology 
Total Calcium 
Calcium corrected for Albumin 
Phosphorus 
Magnesium 
Albumin 
Bilirubin 
Alanine aminotransferase 
Aspartate aminotransferase 
Alkaline phosphatase 
LDH 
Sodium 
Potassium 
Bicarbonate 
Creatinine* 
Chloride 
Glucose 
BUN or Urea 
* In participants ≥65 years, add GFR 
Red blood cell count 
Hemoglobin 
Hematocrit 
Mean cell volume 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Platelet count 
White blood cell count 
White blood cell differential absolute counts of 
lymphocytes, monocytes, and neutrophils 
White blood cell differential percentages of 
lymphocytes, monocytes, and neutrophils 
 
Lymphocyte subsets 
Lymphocyte subsets including CD3 T-cell (absolute) 
count 
Other Tests 
Coagulation Screen 
Uric Acid 
C-reactive protein 
Prothrombin time or International Normalized Ratio  
Activated partial tissue thromboplastin time 
 
Pregnancy Test 
Thyroid Function Tests 
Serum beta-HCG or Urine test 
 
Thyroid Stimulating Hormone (TSH) 
Free T3 
Free T4 
 
Urinalysis 
Microbiology 
Glucose      
Ketones        
Specific gravity 
Protein        
Blood  
Microscopy  
Bilirubin      
pH   
 
Infectious disease screen 
HIV 1+2 antibody 
Hepatitis B surface antigen 
Hepatitis B core antibody – if positive, test for HBV 
DNA 
Hepatitis C antibody – if positive, test for HCV RNA 
HTLV 1+2 IgG 
CMV IgG  
EBV (EBNA) 
Treponema (Syphilis) 
Viral reactivation 
CMV DNA PCR – peripheral blood for detection of 
reactivation. In the event of suspected end organ CMV 
disease a biopsy may be required 
 
Laboratory grades will be reported using the CTCAE v4.03. 
Summary of the change from baseline using n, mean, median, standard deviation, 
minimum, and maximum will be provided. These summaries will exclude any 
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S u p p orti n g li ne gra p hs of ne utr o p hils, platelets, he m o gl o bi n, a n d l y m p h o c ytes o ver ti me 
will als o be pr o d uce d.  T h ese fi g ures will e x cl u de a n y retreat me nt assess me nts . 
S u m maries of w orst -case gra de i ncreas e fr o m bas eli ne gra de at Wee k  4 , Wee k 1 2 a n d 
acr oss all p ost -bas eli ne assess me nts will be pr o vi de d f or all t he la b t ests t hat are gra da bl e 
b y C T C A E v 4. 0 3 . T hes e s u m maries will dis pla y t he n u m ber a n d p erce nta ge of 
partici pa nt s wit h a ma xi m u m p ost-baseli ne gra de i ncreas e fr o m t heir b aseli ne gra de. 
 as gra d e 0. F or la b orat or y tests t hat  are gra de d 
f or b ot h l o w a n d hi g h val ues, s u m maries will be d o ne se paratel y a n d la bele d b y directi o n , 
e. g. s o di u m will be s u m mariz e d as h y p o n atre mia a n d h y p er natre mia. T hes e s u m maries 
will e x cl u de a n y retreat m e nt assess me nts . 
F or la b tests t hat are n ot gra da ble b y C T C A E v 4. 03 , s u m maries of w orst-case c ha n ges 
fr o m baseli ne wit h r es pect t o n or mal ra n ge will be ge nerate d. T h e w orst -case will be 
c h ose n fr o m all a v aila ble tests, i ncl u di n g sc he d ule d a n d u nsc he d ule d visits. Decreases t o 
l o w, c ha n ges t o n or mal or n o c ha n ges fr o m bas eli n e, a n d i ncreases t o hi g h  will be 
s u m marize d f or t he w orst-case p ost -b aseli ne. If a partici pa nt  has a d ecreas e t o l o w a n d a n 
i ncreas e t o hi g h d uri n g t h e sa me ti me i nter val, t he n t he partici pa nt  is c o u nt e d i n b ot h t he 
“ Decreas e t o L o w” cate g ories a n d t he “I n crease t o Hi g h” cate g ories. T hes e s u m maries 
will e x cl u de a n y retreat m e nt assess me nts . 
Se parate s u m mar y t a bles f or he mat ol o g y, c h e mistr y, ot her la b orat or y tests  will be 
pr o d uce d.  
A s u p p orti n g listi n g of l a b orat or y data f or partici pa nt s wit h a n y v al ue o utsi d e n or mal 
ra n ge will be pr o vi d e d. A se parate listi n g of la b orat or y data wit h c haracter val ues will 
als o be pr o vi de d.  At t he fi nal a nal ysis t hes e l isti n gs will be re peat e d o n t he I T T 
p o p ulati o n e x cl u di n g retr eat me nt data. 
Detaile d deri v ati o n of baseli ne as sess me nt is s pecifie d i n Secti o n 5. 2 . 
U nless ot her wise s pecifie d, t he de n o mi nat or i n perce nta ge calc ulati o n at eac h sc he d ule d 
visit will be base d o n t he n u m ber of p artici p a nt s wit h n o n-missi n g val ue at eac h 
partic ular visit.  
8. 3. 1.  
A n al y s e s of Li v er F u n cti o n T e st s ( L F T)  
Listi n gs of he pat o biliar y la b orat or y e v e nts i ncl u di n g p ossi ble H y’s la w cas es will be 
pr o vi de d  i n a d diti o n t o w hat has bee n d escri be d a b o ve, i ncl u di n g listi n gs of li ver 
m o nit ori n g a n d st o p pi n g e ve nts as well as a listi n g of s u bjects meeti n g he pat o biliar y 
la b orat or y criteria p ost-b aseli ne . 
P ossi ble H y’s la w cases are defi ne d as a n y ele vate d ( A L T ≥3 × U L N a n d  t otal 
bilir u bi n ≥2 × U L N ( wit h direct bilir u bi n  3 5 % of t otal bilir u bi n, if direct  bilir u bi n is 
meas ure d )) O R  ( A L T ≥3 × U L N a n d  I N R > 1. 5, if I N R is meas ure d). N ot e t hat I N R 
meas ure me nt is n ot re q uire d, a n d t he t hres h ol d val ue state d will n ot a p pl y t o partici pa nts 
recei vi n g a ntic o a g ula nts. 
C CI
C CI
C CI
C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
5 5  
 
A scatter pl ot of ma x i m u m t otal bilir u bi n vers us ma xi m u m A L T will be ge nerat e d. Als o 
a scatter pl ot of ma xi m u m vs b aseli ne f or A L T  will be pr o d uce d.  T hes e fi g ures will 
e x cl u de a n y retr eat me nt assess me nts.  
8. 4.  
Ot h er S af et y A n al y s e s  
T he a nal yses o f n o n -la b orat or y safet y test res ults i ncl u di n g E C Gs a n d vital si g n s will be 
base d o n  G S K C ore D ata Sta n dar ds , u nless ot her wise s pecifie d. T h e details of t he 
pla n ne d  dis pla ys are pres e nte d i n  A p pe n di x 1 2 . 
8. 4. 1.  
E C O G P erf or m a n c e St at u s  
Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G ) p erf or ma nce stat us will be s u m marize d at 
baseli ne a n d last ass ess me nt b y fre q u e nc y a n d p erce nta ge of partici pa nt s. A s u m mar y of 
c ha n ge fr o m baseli ne b y sc he d ule d visits will be perf or me d, as well as t he w orst -cas e 
p ost -baseli ne a n d t he b est -case p ost -b aseli ne c h a n ges d uri n g t h e st u d y (i m pr o ve d, n o 
c ha n ge, d eteri or ate d).  T h ese s u m maries will e xcl u de a n y retreat me nt ass ess me nts.  
A s u p p orti n g  listi n g will als o be pr o vi de d. At t he fi nal a nal ysis t his listi n g will  be 
re peat e d o n t he I T T p o p ulati o n e x cl u di n g retreat me nt data.
8. 4. 2.  
E C G  
A s u m mar y of t he n u m ber a n d perce nta ge of partici pa nt s w h o ha d n or mal a n d a b n or mal 
(cli nicall y si g nifica nt a n d n ot cli nicall y si g nifica nt) E C G fi n di n gs will be di s pla ye d b y 
sc he d ule d visits as well as f or t he w orst-case p ost -baseli ne. T he w orst -cas e will be 
c h ose n fr o m all a v aila ble E C G fi n di n gs, i ncl u di n g sc he d ule d a n d u ns c he d ule d visits.  
T hese s u m maries will e x cl u de a n y retreat me nt ass ess me nts.  
A s u m mar y of c h a n ge fr o m baseli ne i n E C G val ues will be pr o d uce d.  T his s u m mar y will 
e x cl u de a n y retr eat me nt assess me nts.  
T he n u m ber of p artici pa nt s wit h ma xi m u m Q Tc val ues (i.e., w orst-case) p ost -baseli ne 
relati ve t o baseli ne will be s u m marize d b y test (e. g., Q Tc F I nter val, A g gre gat e) a n d 
cate g or y. Als o, a s u m mar y b y a cat e g orizati o n of partici pa nt s’ ma xi m u m i ncreas e (i.e., 
w orst -cas e) i n Q Tc v al ue (e. g., Q Tc F I nt er val, A g gre gate) p ost -baseli ne rel ati ve t o 
baseli ne will be pr o d uce d  b y cate g or y  (e. g. I n crease of 3 1-6 0 ms ec fr o m baseli ne val ue) . 
T hese s u m maries will e x cl u de a n y retreat me nt ass ess me nts.  
S u m maries of Q Tc val u es will i nc or p orate c orrecti o ns base d o n Fr id erica ’s or Bazett’s 
f or m ula se paratel y ( wit h val ues referre d t o as Q T c F a n d Q Tc B, res pecti vel y) . 
Listi n gs o f a b n or mal E C G fi n di n gs a n d a listi n g of E C G val ues will be pr o vi de d. At t he 
fi nal a nal ysis t he listi n g of E C G val ues will be re peate d o n t he I T T p o p ulati o n e x cl u di n g 
retreat me nt.
 
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C O N FI D E N TI A L  
 
2 0 8 4 6 9  
5 6  
 
A fi g ure pl otti n g Q Tc s hift fr o m baseli ne t o w orst -case p ost baseli ne will b e pr o d uce d , 
wit h se parate pl ots f or t h e 2 c orrecti o n met h o ds ( Q Tc F a n d Q Tc B) . Pl ots wit hi n t he 
fi g ure will ha ve refere n ce li nes at 4 8 0 a n d 5 0 0 ms ec f or b ot h t he or di nate a n d t he 
a bscissa a x es. T here will be dia g o nal refere nce li nes at e q ualit y (i.e. a 4 5 -d e gree li ne), at 
e q ualit y pl us 3 0 msec, a n d at e q ualit y pl us 6 0 msec.  T hese fi g ures will e x cl u de a n y 
retreat me nt assess me nts. 
8. 4. 3.  
Vit al Si g n s  
A s u m mar y of c h a n ge fr o m baseli ne i n vital s i g ns will be pr o vi de d. Als o, a s u m mar y of 
w orst -cas e vital si g ns r es ults b y  P ote ntial Cli nical I m p ort a nce ( P CI , d efi ne d i n A p pe n di x 
8 ) criteria p ost-b aseli ne relati ve t o b aseli ne will be ge n erat e d. T hese s u m maries will 
e x cl u de a n y retr eat me nt assess me nts.  
A listi n g of vital si g ns wit h val ues of P CI  will be pr o vi de d . At t he fi nal a n al ysis t his 
listi n g will be re peate d o n t he I T T p o p ulati o n e x cl u di n g retreat me nt d ata. 
8. 4. 4.  
Pr e g n a n ci e s  
Pre g n a nc y ( or pre g n a nc y of a male partici pa nt ’s part ner) is n ot c o nsi dere d a n A E/ S A E 
u nless t here is reas o n t o belie ve t hat t he pre g na nc y ma y b e t he res ult of fail ure of t he 
c o ntrace pti ve bei n g use d d ue t o i nteracti o n wi t h t he st u d y dr u g. H o we v er, t he 
i n vesti gat or s hall re p ort all pre g n a ncies i m me diatel y t o t he S p o ns or. If p artici pa nt s or 
partici pa nt s’ part ner bec o me pre g na nt w hile o n t he st u d y, t he i nf or mati o n will be 
i ncl u de d i n t he narrati ves a n d n o se parate ta ble or listi n g will be pr o d uce d. 
8. 4. 5.  
R e pli c ati o n C o m p et e nt L e nti vir u s ( R C L)  
T he pr o p orti o n of partici pa nts w h o are R C L  p ositi ve will be s u m marize d. R C L is 
re p orte d as “ Ne gati ve” if c o pies of V S V-G are < 5 0 c o pies/ g g D N A . 
R C L res ults will als o be prese nte d i n a d ata listi n g.  At t he fi nal a nal ysis , t his listi n g will 
be re peate d  o n t he mI T T p o p ulati o n e xcl u di n g retr eat me nt data.
retreat me nt da y as defi ne d i n Secti o n 1 4. 6. 1 . 
8. 4. 6.  
P B M C s  
T he pr o p orti o n of patie nts s h o wi n g > 1 % ge ne m ar ke d P eri p heral B l o o d M o n o n uclear 
C ells ( P B M Cs) at o ne year or be y o n d  p ost  1 st T -cell i nf usi o n (e x cl u di n g persiste nce 
meas ure me nts after 2 n d i nf usi o n i n retreat e d parti ci pa nts) will be s u m mari ze d if data 
warra nt.  
F urt her details of t he ha n dli n g of persiste nce d ata are gi ve n i n t he P har mac o ki netic 
S ecti o n 9 . 
C CI
C CI
C CI
C CI
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8.4.7. 
COVID-19 
A listing of all COVID-19 assessments, including test date and result, along with 
symptom assessments will be provided. 
9. 
PHARMACOKINETIC ANALYSES 
9.1. 
Persistence of NY-ESO-1c259T 
Following protocol amendment 6, characterization of the in vivo pharmacokinetic profile 
(levels, cell expansion, persistence) of NY-ESO-1 specific (c259) cells is a secondary 
objective of the study. 
9.1.1. 
Endpoint/Variables 
GSK3377794 T-cell vector copies (persistence) in the peripheral blood will be measured 
in participants by quantitation of transduced cells by PCR of transgene from DNA 
extracted from PBMC. 
9.1.1.1. 
Drug Concentration Measures 
The following calculations will be performed: 
copies/cell is calculated with the following formula: 
copies/cell=(copies/µg) x (0.0000063 µg gDNA/cell) 
Percent gene marked peripheral blood mononuclear cells (PBMCs) = (copies/cell) *100 
The final reported result of copies/µg gDNA is calculated as follows: 
copies/µg gDNA=copies per well/µg gDNA per well 
For persistence value below the lower limit of quantification (LLOQ), the following rules 
will be applied: 
Reported Copies 
per cell Result 
Reported Copies 
per g gDNA 
Result 
Reported Result 
Set Value for 
Copies per cell 
Set Value for 
Copies per g 
gDNA 
<0.0003 
<50.0 
Negative 
0 
0 
<0.0003 
<50.0 
Detectable, 
<LLOQ 
0.0003 
50 
Note, sometimes values for copies per cell and copies per g gDNA might be different 
than above as it depends on the input of DNA, but rule would be the same: 
- 
If interpretive reported result is negative, set values at 0.  
- 
If interpretive reported result is “Detectable, <LLOQ”, set values at LLOQ (If 
<XXX, set at XXX) 


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The unit for persistence will be “Copies/µg of gDNA” 
Time to loss of 25% of peak cell expansion will be calculated as the time since 1st T-cell 
infusion corresponding to observing at least 25% loss of peak cell expansion. If time to 
25% loss of peak cell expansion is not observed, the last observed time will be reported 
with a “+” appended to the numerical result. The same procedure will be followed for 
50% and 75%. 
Duration of detectable persistence is defined as time from 1st T-cell infusion until 
persistence is no longer detectable. Persistence above the assay limit of detection but 
below the lower limit of quantification is considered for the duration determination, i.e. 
the time window from infusion until the first instance persistence falls below the 
detection limit and the interpretive reported result is “Negative.” If persistence for a given 
subject remains detectable (“Positive” or “Detectable, LLOQ”) at their last sample 
collection timepoint, the last observed time is reported and considered as right-censored 
with a “+” appended to the numerical result. Note, transduced T-cells frequently persist 
beyond the follow-up period, and hence, the reported duration is directly influenced by 
length of time the patient is on-study. 
9.1.1.2. 
Derived Pharmacokinetic Parameters 
The following PK parameters will be derived: 
• 
Cmax: Peak cell expansion during the interventional phase (i.e. excluding retreatment) 
• 
Tmax: Time to peak cell expansion during the interventional phase (i.e. excluding 
retreatment) 
• 
AUC0–28d: Area under the plasma concentration-time curve from 1st T-cell infusion to 
day 28 
The area under the plasma concentration-time curve from 1st T-cell infusion to day 28 
(AUC0–28d) will be determined using the linear trapezoidal rule for each increasing 
concentration trapezoid and the logarithmic trapezoidal rule for each decreasing 
concentration trapezoid. AUC0–28d will not be calculated for participants without a 
concentration measurement within 4 days of day 28. 
Derivation will be the responsibility of the Statistics and Programming group at 
PAREXEL under the direction of the Clinical Pharmacology Modelling and Simulation 
(CPMS) Department at GSK. 
Peak cell expansion during the interventional phase (Cmax), time to peak cell expansion 
(Tmax), and as data permit, AUC0–28d will be summarized overall and for responders and 
non-responders using descriptive statistics and dot plots. 


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
5 9  
 
9. 1. 2.  
S u m m ar y M e a s ur e  
S pi der pl ots will be use d t o gra p hi call y s u m marize persiste nce (c o pies/µ g g D N A) o ver 
ti me f or eac h partici pa nt b y res p o n ders a n d n o n-res p o n ders. T hese fi g ures will e x cl u de 
a n y retr eat me nt assess me nts.  
A listi n g of persiste nce will be pr o vi de d a n d will i ncl u de c oefficie nt of v ari ati o n, n u m ber 
of p ositi ve re plicates, c o pies/cell, c o pies/ µ g g D N A, perce nt ge ne mar ke d cells of 
P B M Cs  ( %), i nter preti ve res ult, C ma x , Tma x , A U C 0 – 2 8 d, d urati o n of detecti ble persiste nce 
a n d ti me t o l oss of 2 5 %/ 5 0 %/ 7 5 % pea k  cell e x pa nsi o n . 
F or eac h of t h ese para meters, e x ce pt T ma x , t he f oll o wi n g s u m mar y statistics will be 
calc ulate d: n, me dia n, mi ni m u m, ma xi m u m, arit h metic mea n, 9 5 %  c o nfi de nce i nter val 
f or t he arit h metic me a n, sta n dar d de viati o n, c oeffi cie nt of vari ati o n (c oefficie nt of 
variati o n ( C V) = 1 0 0 *(s qrt (e x p( S D 2) - 1))) [ N O T E: S D = S D of nat ural l o g tra nsf or me d 
data]), ge o metric mea n, 9 5 %  c o nfi de n ce i nter val f or t he g e o metri c mea n a n d sta n dar d 
de viati o n of nat ural l o garit h micall y tra nsf or me d d ata. Data will be s u m marize d b y 
l y m p h o de pleti o n re gi men  a n d o verall.  
F or T ma x , calc ulati o ns will i ncl u de n, me dia n, ma xi m u m, mi ni m u m, arit h metic mea n, 
9 5 %  c o nfi de n ce i nter val, a n d sta n dar d de viati o n. Data will be s u m marize d b y 
l y m p h o de pleti o n re gime n  a n d o verall.  
T hese s u m maries will e x cl u de a n y retreat me nt ass ess me nts.  
At t he fi nal a nal ysis t he listi n g of persiste nce will be re peate d  o n t he mI T T p o p ulati o n 
e x cl u di n g retr eat me nt dat a. 
9. 1. 3.  
P o p ul ati o n of I nt er e st  
All a nal ys es of persiste nce will be base d o n t h e mI T T p o p ul ati o n, u nless ot he r wise 
s pecifie d. 
C CI
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C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
6 0  
 
1 0.  
BI O M A R K E R A N A L Y S E S  
1 0. 1.  
Bi o m ar k er A n al y s e s  
1 0. 1. 1.  
E n d p oi nt/ V ari a bl e s  
, i m m u n o hist oc he mistr y a n d a nti -N Y E S O a nti b o d y f or m ati o n ma y b e re p orte d 
if data warra nt. A n y a d diti o nal 
1 0. 1. 2.  
S u m m ar y M e a s ur e  
1 0. 1. 2. 1.  
I nt e gr ati o n Sit e A n al y si s 
If persiste nce, as d etecte d b y t he prese n ce of vect or se q ue nces ( W P R E or Psi D N A 
c o pies), is pres e nt i n > 1 % of P B M C at 1 year or be y o n d p ost  1 st T -cell i nf usi o n , 
Ne xt -Ge n Se q ue nci n g of D N A fr o m t he partici pa nt’s P B M Cs will be perf or me d f or 
i nte grati o n site a nal ysis t o assess cl o nalit y a n d possi ble i nserti o nal o nc o ge nesis . 
A s u m mar y of t he n u m ber of s u bjects wit h a n y n u m ber of cl o nes wit h > 2 0 % a b u n da nce 
will be s u m mariz e d  (e x cl u di n g a n y retreat me nt assess me nts ). A s u p p orti n g listi n g will be 
pr o vi de d.  
T w o di versit y i n dices, S ha n n o n di versit y i n d e x a n d Gi ni i n de x, will be re p orte d i n t he 
data listi n g. T hese i n dices ca n hel p s u m marize t he c o m p ositi o n of a p o p ulati o n of cl o nes. 
S ha n n o n di versit y is a m eas ure m e nt t hat re prese nts t he u ncertai nt y a b o ut t h e i de ntit y of a 
si n gle s pecies wit hi n t he p o p ulati o n [S ha n n o n , 1 9 4 8]. T he Gi ni i n de x ca n hel p detect t he 
si milarit y i n a b u n da nce of differe nt cl o nes acr oss t he p o p ulati o n [ Gi ni , 1 9 1 4]. 
At t he fi nal a nal ysis t he listi n g of i nte grati o n site a nal ysis will be re p eate d o n t he mI T T 
p o p ulati o n e x cl u di n g t he retreat me nt data.
C CI
C CI
C CI
C CI
C CI
C CI
C CI


C O N FI D E N TI A L  
 
2 0 8 4 6 9  
6 1  
 
1 0. 1. 3.  
P o p ul ati o n of I nt er e st 
T he pri mar y bi o mar ker a nal yses will be base d o n t h e mI T T p o p ul ati o n, u nless ot her wise 
s pecifie d. 
1 1.  
P O P U L A TI O N P H A R M A C O K I N E TI C ( P O P P K) 
A N A L Y S E S  
N ot a p plica ble  i n t his R A P b ut ma y be des cri be d i n a se parate Bi o mar ker A nal ysis Pla n.  
1 2.  
P H A R M A C O KI N E TI C / P H A R M A C O D Y N A MI C 
A N A L Y S E S  
N ot a p plica ble  i n t his R A P b ut ma y be des cri be d i n a se parate Bi o mar ker A nal ysis Pla n.  
 
C CI


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13. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics, 1982;38:29–41. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et. al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
European Journal of Cancer, 2009;45:228–247. 
Dubois D, Dubois EF. A formula to estimate the approximate surface area if height and 
weight be known. Arch Intern Med. 1916;17:863-871. 
Gini C. Sulla misura della concentrazione e della variabilita dei caratteri. Transactions of 
the Real Istituto Veneto di Scienze. 1914; LIII:1203 
Lee DW, Santomasso BD, Locke FL. ASTCT Consensus Grading for Cytokine Release 
Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of 
Blood and Marrow Transplantation, 2019;25:625–38. 
Lee J J and Liu D D. A predictive probability design for phase II cancer clinical trials. 
Clinical Trials, 2008;5:93–106. 
Shannon, C. A mathematical theory of communication. Bell Syst. Tech. J. 1948;27:379–
423, 623–656. 


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14. 
APPENDICES 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Specification document. 
 


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14.2. 
Appendix 2: Schedule of Activities 
14.2.1. 
Protocol Defined Schedule of Events 
See protocol Section 7.3. 
 


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14.3. 
Appendix 3: Assessment Windows 
No assessment window will be applied. 


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14.4. 
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events 
14.4.1. 
Study Phases 
14.4.1.1. 
Study Phases for Concomitant Medication 
Study Phase 
Definition 
Prior 
End date of medication is not missing and is before the start date of lymphodepletion 
OR lymphodepletion chemotherapy start date is missing 
Concomitant 
Any medication that is not a prior 
NOTES:  
• 
Please refer to Appendix 7 for handling of missing and partial dates for concomitant medication. Use the rules 
in this table if concomitant medication date is completely missing. 
 
Concomitant medications during retreatment will be identified those concomitant 
medications (as defined above) for which: End date of medication is missing OR End 
date of medication is non-missing and is on or after start date of retreatment 
lymphodepletion. 
14.4.1.2. 
Study Phases for Anti-Cancer Therapy/Surgery 
Study Phase 
Definition 
On-Study 
Start date is on or after the first day of lymphodepletion chemotherapy  
(both start date and lymphodepletion chemotherapy start date not missing). 
Prior 
Not classified as On-Study. 
NOTES:  
• 
Please refer to Appendix 7 for handling of missing and partial dates for anti-cancer therapy 
The prior phase will be further subdivided into sub-phases as follows: 
Study Phase 
Definition 
prior to advanced 
diagnosis 
If classified as prior and entered on the screening visit 2 eCRF with start date 
missing or before the date of diagnosis of metastatic disease. 
advanced diagnosis to 
leukapheresis 
If classified as prior and entered on the screening visit 2 eCRF with start date on 
or after the date of diagnosis of metastatic disease. 
leukapheresis to 
lymphodepletion 
If classified as prior and not entered on the screening visit 2 eCRF. 
NOTES:  
• 
Please refer to Appendix 7 for handling of missing and partial dates for anti-cancer therapy 
On-Study Anti-Cancer Therapy/Surgeries during retreatment will be identified those on-
study Anti-Cancer Therapy/Surgeries (as defined above) for which the start date is on or 
after the first day of retreatment lymphodepletion chemotherapy (both start date and 
retreatment lymphodepletion chemotherapy start date not missing). 
 


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14.4.1.3. 
Treatment Emergent Flags for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
If AE onset date is on or after lymphodepletion chemotherapy start date. 
(Lymphodepletion Start Date ≤ AE Start Date) 
• 
If AE onset date is missing and AE end date is before the lymphodepletion start 
date, then the AE will not be classified as Treatment-Emergent. If AE onset date 
is missing and AE end date is either missing or on or after lymphodepletion start 
date, then the AE will be classified as treatment-emergent  
• 
Partially missing AE onset and end dates will be imputed following rules in 
Section 14.7.2.1 for determining Treatment Emergent AEs. 
Retreatment 
Emergent 
• 
If AE onset date is on or after retreatment lymphodepletion chemotherapy start 
date. 
(Retreatment Lymphodepletion Start Date ≤ AE Start Date) 
• 
If AE onset date is missing and AE end date is before the retreatment 
lymphodepletion start date, then the AE will not be classified as Retreatment 
Treatment-Emergent. If AE onset date is missing and AE end date is either 
missing or on or after retreatment lymphodepletion start date, then the AE will 
be classified as retreatment-emergent.  
• 
Partially missing AE onset and end dates will be imputed following rules in 
Section 14.7.2.1 for determining Treatment Emergent AEs, but using 
retreatment lymphodepletion start date as the reference date. 
• 
If the participant did not start retreatment lymphodepletion chemotherapy then 
no AEs are retreatment emergent. 
• 
Note that retreatment emergent AEs are also treatment emergent. 
 
14.4.1.4. 
Medical History 
Study Phase 
Definition 
Past 
Medical condition is not marked as ongoing on eCRF  
Current 
Medical condition is not past 
14.4.1.5. 
Retreatment Assessments/Data 
Retreatment assessments/data will be identified for a participant as: 
• 
data entered on a retreatment specific eCRF (even if the participant was not 
retreated), and 
• 
records for events entered on other eCRF forms (e.g. Adverse Events)  
with start dates on or after the date of start of retreatment lymphodepletion 
chemotherapy (for participants who start retreatment lymphodepletion 
chemotherapy). 
Detailed specifications (including handling of partial event dates) will be included in 
dataset specifications. 
 


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14.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
14.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: arprod\GSK3377794\mid208469 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.1]. 
Generation of RTF Files 
• 
RTF files will be generated for IA2 and the primary and final analyses. 
14.5.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.24: General Principles 
• 
5.01 to 5.09: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings. 
• 
While text within this RAP uses the term “participant”, all data displays (Tables, Figures, and 
Listings) will use the term “subject”, reflecting CDISC and GSK Data Display Standards terminology. 
Formats 
• 
GSK IDSL Statistical Principles (4.24) for decimal places (DP’s) will be adopted for reporting of data 
based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  


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Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables and figures, except in cases where worse-
case post-baseline is calculated. 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
 


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14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
For cytokines, as some samples taken at baseline were analyzed repeatedly alongside samples from 
subsequent visits, where there are multiple analyses of the baseline sample, the first analysis should 
be taken as the baseline value. 
• 
Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented. 
• 
For character variables, if multiple assessments on different days are reported for the same 
scheduled assessment, then the worst-case assessment for that scheduled assessment will be 
analyzed. 
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance 
summary tables. 
Study Day 
• 
Calculated as the number of days from 1st T-cell infusion date: 
• 
Ref Date = Missing 
→ Study Day = Missing  
• 
Ref Date < 1st T-cell infusion Date → Study Day = Ref Date – 1st T-cell infusion Date 
• 
Ref Data ≥ 1st T-cell infusion Date → Study Day = Ref Date – 1st T-cell infusion Date + 1  
Retreatment Day 
• 
Calculated as the number of days from 2nd T-cell infusion date: 
• 
Ref Date = Missing 
→ Study Day = Missing  
• 
Ref Date < 2nd T-cell infusion Date → Study Day = Ref Date – 2nd T-cell infusion Date 
• 
Ref Data ≥ 2nd T-cell infusion Date → Study Day = Ref Date – 2nd T-cell infusion Date + 1  
Change from Baseline 
• 
Change from Baseline = Post-Baseline Visit Value – Baseline 
• 
% Change from Baseline= 100 x (Post-Baseline Visit Value – Baseline) / Baseline 
• 
Maximum Increase/Decrease from Baseline = maximum (Increase/Decrease from Baseline) 
• 
If either the Baseline or Post-Baseline Visit Value is missing, Change from Baseline and % Change 
from Baseline is set to missing 
Date of Response 
• For post-baseline disease assessments, the date of response (PR, CR) is assigned to the latest date 
of disease assessments; for other response categories (SD, NE, PD), the date of response is 
assigned to the earliest date of disease assessments.    
Date of New Anti-Cancer Therapy 
• 
Derived as the earliest date of on-study anti-cancer therapy, radiotherapy (where applicable) or 
cancer-related surgical procedure (where applicable). 
• Missing or partial dates will be imputed for derivation of new anti-cancer therapy following rules 
specified in section Appendix 7. 
 


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14.6.2. 
Study Population 
Age 
• 
For participants with a 1st T-cell infusion date, age is derived using 1st T-cell infusion date as the 
reference date. For ITT participants without a 1st T-cell Infusion date, date of eligibility for 
leukapheresis is used as the reference date. 
Body Mass Index (BMI) 
• 
(Weight in kg) / (Height in meters)2 
Body Surface Area (BSA) (m2) (Dubois-Dubois Formula) 
• 
0.007184 * Height(cm)0.725 * Weight(kg)0.425 
Time Since Initial Diagnosis to Screening 
• 
Time (in months) since initial diagnosis to screening will be calculated as: 
       (Date of (last) Screening Consent - Date of Initial Diagnosis +1) / 30.4375  
Time Since Metastatic Disease to Screening 
• 
Time (in months) since metastatic disease to screening will be calculated as: 
        (Date of (last) Screening Consent - Date of Diagnosis of Metastatic Disease +1) / 30.4375  
On-study Treatment Follow-up Time 
• 
Time (in months) from T-cell infusion to end of follow-up will be calculated as: 
        (Date of Death/Last Contact - T-cell Infusion Date -+1) / 30.4375  
14.6.3. 
Efficacy 
Refer to Section 7 for endpoint derivation information. 
Secondary and Exploratory Duration and Time to Endpoints 
Durations and intervals in months 
• 
Durations and intervals to be presented in months will be calculated in days and converted to months 
by dividing by 30.4375. 
 
Secondary Endpoints 
Date of Last Contact 
• 
Last date in all SDTM domains 
• 
If patient died, the last contact date should be death date. 
• 
Dates after date of death will be excluded. Future dates will be excluded. 
• 
SDTM domain SE and SUPPBE will be excluded and SDTM variables DM.BRTHDTC, 
MH.MHSTDTC, SV.SVENDTC, SV.SVSTDTC,  DM.RFPENDTC,  _ALL_.ANALDTC, DV.DVDTC, 
DV.DVSTDTC and any other external source data dates (such as RS.RSDTC where 
RSEVAL=’INDEPENDENT ASSESSOR’) as necessary will be excluded 
• 
Partial and missing dates will not be imputed for the purpose of deriving date of last contact 
 
 


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14.6.4. 
Safety 
Adverse Events 
AEs of Special Interest 
See Section 8.2. 
Duration of AE 
• 
Calculated as the number of days from AE Start Date to AE Stop Date: 
o AE Start Date = Missing 
→ Elapse Time = Missing  
o AE Stop Date = Missing 
→ Elapse Time = Missing 
o Otherwise 
→ Elapsed Time = AE Stop Date – AE Start Date + 1 
Imputed dates will not be used to calculated AE duration 
 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
7 3  
 
1 4. 7.  
A p p e n di x 7: R e p orti n g St a n d ar d s f or Mi s si n g D at a  
1 4. 7. 1.  
Pr e m at ur e Wit h dr a w al s  
El e m e nt  
R e p orti n g D et ail  
G e n er al  
•  
C o m pl etio n of th e i nterv e nti o nal p h as e is d efin e d  f or t h e p urp os es of a n alysis as 
h avi n g r ec eiv e d N Y -E S O -1 c259T  c ell i nf usi o n a n d b ee n f oll o we d-u p u ntil confir m e d 
pr o gr essi o n of dis e ase , d e ath or f or 2 ye ars aft er N Y -E S O -1 c25 9T  c ell i nf usi on, 
w hic h ever is s h orter.  
•  
All av ail a bl e d ata fr o m p artici pa nts  w h o w er e wit h dr a w n fr o m t h e st udy will b e liste d 
a n d all av ail a bl e pla n n e d d at a will b e i nclu d e d i n s u m m ary t abl es an d fi gur es, u nl ess 
ot h er wis e s p ecifi ed.   
1 4. 7. 2.  
H a n dli n g of Mi s si n g D at a  
El e m e nt  
R e p orti n g D et ail  
G e n er al  
•  
Missi n g dat a occ urs w h e n a ny r e q u este d d at a is n ot pr ovi d ed, l e a di n g t o bl a nk fi el ds 
o n t h e coll ecti on i nstr u m ent: 
o  T h es e dat a will b e in dic at e d by t h e us e of a “ bl a nk” i n p articip a nt  listi ng dis pl ays. 
U nl ess all dat a f or a s p ecific visit ar e missi ng i n w hi c h c as e th e d at a is exclu d e d 
fr o m t h e ta bl e.  
o  A ns w ers s uc h as “ Not a pplic abl e” a n d “ N ot ev al u a bl e” ar e not c o nsi d er ed t o b e 
missi n g dat a a nd s h oul d be dis pl aye d as s uc h.  
O utliers  
•  
A ny p artici p ants  exclu d e d fro m t h e su m mari es a n d/ or st atistic al a n alys es wil l b e 
d oc u me nt e d al o n g wit h t h e reas o n f or excl usi o n in t h e cli nic al st u dy r e port.  
1 4. 7. 2. 1.  
H a n dli n g of Mi s si n g  a n d P arti al D at e s  
I m p ute d p artial dates ca n  be use d  t o deri ve st u d y d a y, d urati o n, or el a pse d ti me varia bles 
u nless ot her wise s pecifie d .
 
I m p ute d d ates will n ot be dis pla ye d i n listi n gs, n or will a n y st u d y da ys, d urati o ns or 
ela pse d ti me varia bles deri ve d fr o m i m p ute d dates . F or listi n gs t he S D T M c haract er dat e 
varia bles will be dis pla ye d . T he i m p ute d dates ca n be use d f or s orti n g t he data f or 
listi n gs. I n a d diti o n,  partial dates ma y be i m p ute d f or ‘sl otti n g’ data t o st u d y p has es (see 
Secti o n  1 4. 4. 1 ) or f or s p ecific a nal ysis p ur p oses as o utli ne d bel o w.  
T he partial date i m p utati o n will f oll o w A Da M c o n ve nti o ns. T he A Da M a p pr oac h is t o 
p o p ulate t he n u meric d ate varia bles wit h t he i m p ute d date a n d  a d d a fla g v aria ble t o t he 
dataset t hat i n dicates t he le vel of i m p utati o n.  
T he fla g varia ble ca n c o ntai n t he val ues: bla n k, ' D', ' M', ' Y'.  
bla n k: i n dicates t hat n o i m p utati o n was d o ne  
D =' Da y': i n dicat es t hat t he da y p orti o n of t he d ate is i m p ute d  
M =' M o nt h': i n dicates t hat t he m o nt h a n d da y p orti o ns of t he date are i m p ute d  
Y =' Year': i n dicates t hat t he e ntire dat e ( year, m o nt h, a n d da y) is i m p ute d  
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Example of date variables:  
XYZDTC - character date variable 
XYZDT - numeric date variable 
XYZDTF – date imputation flag variable 
Details on imputing partial dates for specific datasets are outlined below. 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. 
Adverse 
Events 
• 
Imputations in the adverse events dataset are used for slotting events to the 
appropriate study time periods and for sorting in data listings. Imputed dates will not 
be used to calculated AE duration. 
• 
Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
 
Missing start day 
• 
If lymphodepletion start date is missing (i.e. participant did not 
start lymphodepletion), then set start date = 1st of month. 
• 
Else if lymphodepletion start date is not missing: 
o 
If month and year of start date = month and year of 
lymphodepletion start date then 
▪ 
If stop date contains a full date and stop date is 
earlier than lymphodepletion start date then set start 
date= 1st of month. 
▪ 
Else set start date = lymphodepletion start date. 
o 
Else set start date = 1st of month. 
Missing start day 
and month 
• 
If lymphodepletion start date is missing (i.e. participant did not 
start lymphodepletion), then set start date = January 1st. 
• 
Else if lymphodepletion start date is not missing: 
o 
If year of start date = year of lymphodepletion start date 
then 
▪ 
If stop date contains a full date and stop date is 
earlier than lymphodepletion start date then set start 
date = January 1st. 
▪ 
Else set start date = lymphodepletion start date.       
o 
Else set start date = January 1st. 
Missing stop day  
Last day of the month will be used. 
Missing stop day 
and month 
No Imputation 
Completely missing 
start/end date 
No imputation 
•
Anti-Cancer 
Therapy and 
Radiotherapy 
• 
Completely missing start or end dates will remain missing, with no imputation 
applied. 
• 
If partial start date contains a year only set to January 1st. 
• 
If partial start date contains a month and year set to the 1st of the month. 
• 
No imputation for partial end dates will be performed. 
Surgical 
Procedures 
• 
No Imputation for completely missing dates 
• 
If partial date contains a year only set to January 1st. 
• 
If partial date contains a month and year set to the 1st of the month 


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Element 
Reporting Detail 
Concomitant 
Medications/ 
Blood 
Products 
o These imputation rules will be used for classifying a medication as prior or 
concomitant 
o Completely missing start dates will not be imputed 
o Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
 
Missing start day 
• 
If study lymphodepletion date is missing (i.e. participant did not 
start lymphodepletion), then set start date = 1st of month. 
• 
Else if lymphodepletion start date is not missing: 
o 
If month and year of start date = month and year of 
lymphodepletion start date then 
▪ 
If stop date contains a full date and stop date is earlier 
than lymphodepletion start date then set start date= 1st 
of month. 
▪ 
Else set start date = lymphodepletion start date. 
o 
Else set start date = 1st of month. 
Missing start day 
and month 
• 
If lymphodepletion start date is missing (i.e. participant did not 
start lymphodepletion), then set start date = January 1st. 
• 
Else if lymphodepletion start date is not missing: 
o 
If year of start date = year of lymphodepletion start date 
then 
▪ 
If stop date contains a full date and stop date is earlier 
than lymphodepletion start date then set start date = 
January 1st. 
▪ 
Else set start date = lymphodepletion start date.       
• 
Else set start date = January 1st. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on the month 
and year)  
Missing end day and 
month 
A '31' will be used for the day and 'Dec' will be used for the month. 
Completely missing 
start/end date 
No imputation 
•
New Anti-
Cancer 
Therapy/ 
Radiotherapy/ 
Surgical 
Procedures 
for Efficacy 
Evaluation 
(e.g., 
response rate, 
time to event) 
• 
Start dates for on-study anti-cancer therapy, radiotherapy (where applicable), and surgical 
procedures (where applicable) will be temporarily imputed in order to define event and 
censoring rules for progression-free survival, response rate, or duration of response (i.e. 
start date for new anti-cancer therapy). Dates will only be imputed when a month and year 
are available but the day is missing. The imputed dates will not be stored on the anti-cancer 
therapy, radiotherapy, or surgical procedure datasets. The following rules will be used to 
impute the date when partial start dates are present on anti-cancer therapy radiotherapy, 
and/or surgical procedures datasets. 
• 
Completely missing start dates will remain missing, with no imputation applied; 
• 
Partial start dates will be imputed using the following convention: 
o 
If both month and day are missing, no imputation will be applied (note the eCRF 
should only allow for missing day); 
o 
If only day is missing: 
• 
If partial start date falls in the same month as the T-cell infusion, then assign 
to earlier of (date of T-cell infusion+1, last day of month).  
• 
If partial start date falls in the same month as the participant’s last 
assessment and the participant’s last assessment is progressive disease 
(PD), then assign to earlier of (date of disease assessment+1, last day of 
month).  
• 
If both conditions above are met, then assign to later of the 2 dates;  
• 
Otherwise, impute missing day to the first of the month. 


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Element 
Reporting Detail 
• 
Completely or partial missing end dates will remain missing, with no imputation applied. 
 


C O N FI D E N TI A L  
 
 
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7 7  
 
1 4. 8.  
A p p e n di x 8: V al u e s of P ot e nti al Cli ni c al I m p ort a n c e  
T o i de ntif y v al ues of p ot e ntial cli nical i m p orta nce, Nati o nal Ca ncer I nstit ute C o m m o n 
Ter mi n ol o g y Criteri a f or A d verse E v e nts ( N CI -C T C A E v 4. 0 3) will be use d t o assi g n 
gra des f or la b orat or y para meters i ncl u di n g cli nical c he mistr y, h e mat ol o g y, li ver f u ncti o n 
tests, t h yr oi d f u ncti o n tests, pa ncreatic e nz y me t ests, Q Tc ( Bazett’s or Fri dericia’s) 
val ues, a n d vital si g n s ( heart rate, bl o o d press ur e, te m perat ur e). 
1 4. 8. 1.  
L a b or at or y V al u e s  
Refere n ce ra n ges f or all l a b orat or y p ara met ers c oll ecte d t hr o u g h o ut t he st u d y are 
pr o vi de d b y t he la b orat or y. A la b orat or y v al ue t hat is o utsi de t he refere nce ra n ge is 
c o nsi dere d eit her hi g h a b n or mal ( val ue a b o ve t he u p per li mit of t he refere n ce ra n ge) or 
l o w a b n or mal ( val u e bel o w t he l o wer li mit of t he refere nce ra n ge). T h e la b orat or y 
refere nce ra n ges will be pr o vi de d o n t he listi n gs of la b orat or y d ata. Cli nical la b orat or y 
test res ults o utsi de of t he refere nce ra n ge will be fl a g ge d i n t he listi n gs.  
T o i de ntif y la b orat or y v al ues of p ote ntial cli nical i m p orta nce, Nati o nal Ca n cer I nstit ute 
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts ( N CI -C T C A E v 4. 0 3 ) will be use d t o 
assi g n gra des t o t he rele v a nt la b orat or y p ara met ers. N CI -C T C A E v 4. 0 3  ca n be f o u n d at  
htt p://cte p.ca ncer. g o v/r e p orti n g/ctc. ht ml.   
F or la b orat or y data w hic h are n ot liste d i n t he N CI -C T C A E v 4. 0 3, a s u m mar y of val u es 
o utsi de t he n or mal ra n ge will be pr o vi de d . 
F or la b test val u es t hat ca n be gra de d, v al ues of gra de 2  or a b o v e are defi ne d as 
 
 F or la b test val u es t hat ca n n ot be gra de d, val u es o ut of t he 
n or mal ra n ge are d efi ne d as val ues of p ote ntial cli nical c o ncer n.  F or la b  tests re p orte d 
descri pti vel y as ‘ N or mal’, ‘ A b n or mal, n ot cli nicall y si g nifica nt’, or ‘ A b n or mal, cli nicall y 
si g nifica nt’ (s uc h as u ri nal ysis), res p o nses of ‘ A b n or mal, cli nicall y si g nifi ca nt’ will be 
c o nsi dere d as of p ote ntial cli nical c o ncer n.  
1 4. 8. 2.  
E C G P ar a m et e r s: 
T o i de ntif y Q Tc ( Bazett’s or Fri dericia’s) val ues of p ote ntial cli nical i m p orta nce, 
N CI -C T C A E v 4. 0 3  will be use d t o assi g n gra d es (see a d v erse e ve nt ‘ El ectr ocar di o gra m 
Q T c orrecte d i nter val pr ol o n ge d’). T he eC R F c ollects eit her Q Tc B or Q Tc F . N ote t hat 
t here is a sli g ht i nc o nsist e nc y bet w ee n N CI -C T C A E v 4 . 03  a n d I C H E 1 4 ( A bs ol ute Q Tc 
i nter val pr ol o n gati o n). It was deci de d t o ali g n wit h C T C A E f or t he o nc ol o g y sta n dar d 
cate g ories.  
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7 8  
 
T he f oll o wi n g criteri a will be use d t o fla g electr ocar di o gra m ( E C G)  val ues t hat are val u es 
of p ote ntial cli nical i m p orta nce:  
1 4. 8. 3.  
Vit al Si g n s  
T o i de ntif y h eart rate val ues of p ote ntial cli nical i m p orta nce, N CI-C T C A E v 4. 0 3  will be 
use d t o assi g n cate g ori es t hat ali g n wit h t he gra des f or ‘ Si n us bra d ycar dia’, ‘ Si n us 
tac h ycar dia’, ‘ S u pra ve ntric ular tac h ycar dia’, a n d ‘ Ve ntric ular t ac h ycar dia’. 
T he f oll o wi n g criteri a will be use d t o fla g vital si g n val ues t hat are val ues of p ote ntial 
cli nical i m p orta nce:  
Vit al Si g n P ar a meter  
P ote nti al Cli nic al I m p o rt a nce ( P CI) R a n ge  
Decrease fr o m baseli ne 
Heart Rate  
Decrease t o < 6 0  b p m  
I n crease fr o m baseli ne 
Heart Rate  
I n crease t o > 1 0 0 b p m  
 
T o i de ntif y bl o o d pr ess ure val ues of p ote ntial cli nical i m p orta nce, N CI -C T C A E v 4. 0 3  
will be use d t o assi g n cat e g ories t hat ali g n wit h t he gra des f or ‘ H y perte nsi o n’: 
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To identify temperature values of potential clinical importance, NCI-CTCAE v4.03 will 
be used to assign categories that align with the grades for ‘Hypothermia’ and ‘Fever’: 
Vital Sign Parameter 
Potential Clinical Importance (PCI) Range 
Unit 
Increase from baseline 
temperature 
Increase to 38 
Degrees 
C 
Decrease from baseline 
temperature 
Decrease to 35 
Degrees 
C 
 
To identify respiratory rate of potential clinical importance, NCI-CTCAE v4.03 will be 
used to assign categories that align with the grades for ‘Respiratory’: 
Vital Sign Parameter 
Potential Clinical Importance (PCI) Range 
Unit 
Increase from baseline 
respiratory rate 
Increase to >30 
Breaths/
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14.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses 
Not applicable. 


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14.10. 
Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses 
Not applicable. 


C O N FI D E N TI A L  
 
 
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8 2  
 
1 4. 1 1.  
A p p e n di x 1 1 : A b br e vi ati o n s & Tr a d e m ar k s  
1 4. 1 1. 1.  
A b br e vi ati o n s  
A b br e vi ati o n  
D e s cri pti o n  
A D a M  
A n alysis D ata M o del  
A E  
A dv ers e Ev e nt  
A E SI  
A dv ers e Ev e nts of S peci al Int er est  
A L T  
Al a ni n e a mi n otra nsfer as e  
A & R  
A n alysis a n d R ep orti ng  
A T C  
A n ato mic al T h er ap e utic C he mic al  
B MI  
B o dy M ass I n dex  
B S A  
B o dy S urf ace Ar ea  
B O R  
B est Over all R es p ons e  
C DI S C  
Cli nic al D at a I nt erc ha n ge Sta n dar ds C o nsorti u m  
CI  
C o nfi d enc e I nt erval  
C M V  
C yt o m e g al ovir us 
C R  
C o m pl et e R esp ons e  
C R P  
C -r e activ e P r otei n 
C S  
Cli nic al St atistics  
C S R  
Cli nic al St u dy Re p ort  
C T C A E  
C o m m o n T oxicity Crit eria f or A dv ers e Ev e nts  
C T R  
Cli nic al Tri al R e gist er  
C V  
C o effici e nt of V ari ati on  
D B F  
D at a bas e Fr eez e  
D B R  
D at a bas e R ele as e  
D O R  
D ur ati o n of  R esp o nse  
D P  
D eci m al Pl ac es  
E C G  
E l ectr oc ar di ogr a m 
E C O G  
E ast er n C o op er ativ e O ncol o gy Gr ou p  
e C R F  
El ectr o nic C ase R e p ort F or m  
E M A  
E ur o p e a n M e dici n es A ge ncy  
F D A  
F o o d a n d Dr u g A d mi nistr atio n  
F D A A A  
F o o d a n d Dr u g A d mi nistr atio n Cli nic al R es ults Discl os ur e R e q uire m ents  
G S K  
Gl ax o S mit h Kli ne  
Gv H D  
Gr aft v ers us Host Dis e ase  
I A 
I nt eri m A nalysis 
I C A N S 
I m m u n e Eff ector-C ell Ass oci at e d Ne ur otoxicity Sy ndr o m e  
I C H 
I nt er nati o nal C o nf er e nce o n H ar m o niz ati o n  
I D S L 
I nt e gr at ed D ata Sta n dar ds Li br ary 
I M M S 
I nt er nati o nal M o dul es M a nag e m e nt Syst e m 
I P 
I nv esti gati o nal Pr od uct 
I T T 
I nt e nt-to -Tr e at  
I N R 
I nt er nati o nal N or m aliz e d Rati o  
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
8 3  
 
A b br e vi ati o n  
D e s cri pti o n  
L F T  
Liv er F u ncti on T est  
L L O Q  
L o w er L i mit of Q u a ntitati o n 
L T F U  
L o ng -T er m F oll o w -U p  
L V E F  
L eft V e ntric ul ar Ej ecti on Fr acti o n  
M e d D R A  
M e dic al Dicti o n ary for R e gul at ory Affairs  
mI T T  
M o difi e d Int e nt-to -Tr e at  
N CI  
N ati o n al Ca nc er Instit ut e  
N E  
N ot Ev al ua bl e  
O R R  
Ov er all R es p ons e Rat e  
P B M C s 
P eri p h er al B l o o d M o no nucl e ar C ell s 
P CI  
P ot e nti al Cli nic al I m port a nce  
P C R  
P oly m er as e C hai n R eacti on  
P D  
Pr o gr essiv e Dis eas e  
P F S  
Pr o gr essi o n Fr e e Surviv al  
P R  
P arti al R es p o ns e  
P T  
Pr ef erre d Ter m  
Q C  
Q u ality C o ntr ol  
Q Tc F  
Fr e d eric a’s Q T I nt erv al C orrect e d f or H eart R ate  
Q Tc B  
B az ett’s Q T I nterv al C orr ecte d for H e art R at e  
R A P  
R e p orti n g & A n alysis Pl an  
R C L  
R e plic ati o n Co m p ete nt L entivir us  
R E CI S T  
R es p o nse E val u atio n C rit eria i n S oli d T u m ors 
R T F  
Ric h T ext F or mat  
S A C  
St atistic al An alysis C o m pl ete  
S A E  
S eri o us A dv ers e Ev ent  
S D  
St a bl e Dis e as e  
S D T M  
St u dy Dat a Ta bul ati o n M o del  
S O C  
Syst e m Or g a n Cl ass  
S O P  
St a nd ar d O p er ati o n Pr oc edur e  
S R T  
S af ety R evi e w T ea m  
T A  
T h er a p e utic Are a  
T C R  
T -c ell R ec e pt ors 
T F L  
T a bl es, Fi gur es & Listi n gs  
T T R  
Ti me t o R es po ns e  
U L N  
U p p er L i mit of N or mal  
U L O Q  
U p p er Li mit of Q u a ntific ati on 
W H O  
W orl d H e alt h Org a niz ati o n  
1 4. 1 1. 2.  
Tr a d e m ar k s  
Tr a d e m ark s of t h e Gl a x o S mit h Kli n e 
Gr o u p of C o m p a ni e s  
 
Tr a d e m ark s n ot o w n e d  by t h e 
Gl a x o S mit h Kli n e G r o u p of C o m p a ni e s  
N O N E  
 
S A S  
C CI


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14.12. 
Appendix 12: List of Data Displays 
14.12.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.0010 to 1.0310 
 
Efficacy 
2.0010 to 2.0175 
2.0180 to 2.0390 
Safety 
3.0010 to 3.0716 
3.0720 to 3.0780 
Biomarker 
3.0830 to 3.0840 
 
Pharmacokinetic 
4.0010 to 4.0020 
4.0030 to 4.0070 
Section 
Listings 
ICH Listings 
0010 to 0570 
Other Listings 
0580 to 0730 
Note that display numbering from the previous version of the RAP has been retained for 
compatibility across reporting efforts, resulting in non-uniform increments between 
successive displays where displays have been dropped, added or moved. 
14.12.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 13. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Biomarker 
BIO_Fn 
BIO_Tn 
BIO_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
14.12.3. 
Deliverables 
Delivery 
Description 
IFA 
Interim Futility Analysis 
IA2 
Second Interim Analyses for Internal Decision Making 
PRY 
Primary Analysis (excluding retreatment) 
FNL* 
Final Analysis (if there are participants ongoing in interventional phase follow-up at time of primary 
analysis then these displays are to be refreshed at the final analysis but still excluding retreatment data) 
FNL 
Final Analysis 
 
At the primary analysis, displays should be marked as “Protocol: 208469 Primary 
Analysis (excluding retreatment)”. 


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14.12.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Subject Disposition 
1.0010 
ITT 
[Non-Standard] 
POP_T2 
Summary of Subject Status (ITT) 
ICH E3, FDAAA, EudraCT 
Note (in footnote) any deaths after 
lymphodepletion start before T-cell 
infusion. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
PRY, FNL 
1.0020 
mITT 
[Non-Standard] 
POP_T2 
Summary of Subject Status (mITT) 
ICH E3, FDAAA, EudraCT 
If same population as ITT, don’t produce 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
PRY, FNL 
1.0025 
mITT 
[Non-Standard] 
POP_T3 
Summary of Interventional Phase Status 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IA2, PRY, 
FNL* 
1.0030 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen 
Failure 
Journal Requirements 
Show only categories collected in eCRF, 
in order presented in the eCRF. 
Since eCRF only allows selection of one 
reason, change ES6 label “Reason(s) for 
Failure” to “Reason for Failure” and omit 
“Subjects may have more than on 
reason…” footnote. 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
1.0040 
ITT 
[Non-Standard] 
POP_T1 
Summary of Leukapheresis, Lymphodepletion, and T-cell 
Infusion 
Add number of participants infused with 
minimum dose of 1 x10^9 transduced cells 
IFA, IA2, PRY 
1.0050 
Enrolled 
NS1 
Summary of Number of Subjects by Country and Site ID 
(Enrolled Population) 
EudraCT/Clinical Operations 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 
1.0052 
mITT 
NS1 
Summary of Number of Subjects by Country and Site ID 
(mITT) 
Plain Language Summary (PLS) 
PRY 
Populations Analyzed 
1.0060 
Screened 
SP1A 
Summary of Study Populations  
IDSL 
Screened, Enrolled, ITT, mITT. Include 
“All Evaluable” for IFA & IA2. 
Extend at final analysis to include 
additional rows for "Screened for Second 
T-cell infusion" (Screened2) and "Modified 
Intent-to-Retreat (mITT2)" population and 
append " – Including Retreatment" to the 
title. 
IFA, IA2, PRY, 
FNL 
Protocol Deviations 
1.0070 
ITT 
DV1 
Summary of Important Protocol Deviations 
ICH E3 
PRY 
Demographic and Baseline Characteristics 
1.0080 
ITT 
DM1 
Summary of Demographic Characteristics (ITT) 
ICH E3, FDAAA, EudraCT 
Report baseline height, weight, BMI, and 
BSA 
Include footnote “Note: BSA was 
calculated using the Dubois-Dubois 
formula.” 
IFA, IA2, PRY, 
FNL* 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Report High Level Race not Race Detail 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
1.0090 
mITT 
DM1 
Summary of Demographic Characteristics (mITT) 
ICH E3, FDAAA, EudraCT 
Report baseline height, weight, BMI and 
BSA 
Include footnote: “Note: BSA was 
calculated using the Dubois-Dubois 
formula.” 
Report High Level Race not Race Detail 
If same population as ITT, don’t produce 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " - 
Excluding Retreatment" to the title. 
IA2, PRY, 
FNL* 
1.0100 
Enrolled 
DM11 
Summary of Age Ranges 
EudraCT 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " - 
Excluding Retreatment" to the title. 
PRY, FNL* 
Disease Characteristics 
1.0110 
ITT/mITT 
LA1 
Summary of Disease Burden at Baseline 
ICH E3 
Includes target and non-target lesions 
Use ITT for IFA and IA2 and use mITT for 
PRY 
IFA, IA2, PRY 
1.0120 
ITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis (ITT) 
ICH E3 
Primary Neoplasm Type Under Study, 
location of disease, time since initial 
diagnosis to screening (months), % of 
myxoid cells, % of round cells, histological 
IFA, IA2, PRY 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
grade, stage, and reciprocal chromosomal 
translocation. 
Add footnote “Time from initial diagnosis 
to date of screening informed consent is 
displayed.” 
1.0130 
mITT 
DC1 
Summary of Disease Characteristics at Initial Diagnosis 
(mITT) 
ICH E3 
Primary Neoplasm Type Under Study, 
location of disease, time since initial 
diagnosis to screening (months), % of 
myxoid/round cells, histological grade, 
stage, and reciprocal chromosomal 
translocation. 
Add footnote “Time from initial diagnosis 
to date of screening informed consent is 
displayed.” 
If same population as ITT, don’t produce 
IA2, PRY 
1.0140 
ITT 
DC2 
Summary of Disease Characteristics at Screening (ITT) 
ICH E3 
HLA status (Positive/Negative), HLA allele 
status (One HLA allele positive, Two HLA 
alleles positive), NY-ESO-1 status, 
disease stage at screening, time since 
metastatic disease to screening (months), 
number of prior radiotherapy regimens 
between advanced diagnosis and 
leukapheresis, number of prior systemic 
therapy regimens between advanced 
diagnosis and leukapheresis. 
Break down “Number of Prior Systemic 
Therapy Regimens…” into 
{0,1,2,3,4,5,6,>6}. 
IFA, IA2, PRY, 
FNL 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " - 
Excluding Retreatment" to the title. 
1.0150 
mITT 
DC2 
Summary of Disease Characteristics at Screening (mITT) 
ICH E3 
HLA status (Positive/Negative), HLA allele 
status (One allele positive, two alleles 
positive, Positive – ambiguous), NY-ESO-
1 status, disease stage at screening, time 
since metastatic disease to screening 
(months), number of prior radiotherapy 
regimens between advanced diagnosis 
and leukapheresis, number of prior 
systemic therapy regimens between 
advanced diagnosis and leukapheresis. 
Break down “Number of Prior Systemic 
Therapy Regimens…” into 
{0,1,2,3,4,5,6,>6}. 
If same population as ITT, don’t produce. 
 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " - 
Excluding Retreatment" to the title. 
IA2, PRY, FNL 
Medical Conditions and Concomitant Medications 
1.0160 
ITT 
MH4 
Summary of Medical Conditions (ITT) 
ICH E3  
Include conditions pre-printed on the CRF 
that occur (as printed unless coded) and 
other conditions specified by the 
investigator (as coded). 
PRY 
1.0170 
mITT 
MH4 
Summary of Medical Conditions (mITT) 
ICH E3  
PRY 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Include conditions pre-printed on the CRF 
that occur (as printed unless coded) and 
other conditions specified by the 
investigator (as coded). 
If same population as ITT, don’t produce 
1.0180 
mITT 
CM8 
Summary of Concomitant Medications (mITT) 
ICH E3 
Summarise only concomitant (as defined 
in Section 14.4.1.1) Concomitant 
Medications, with footnote “Note: 
Concomitant medications are those 
initiated after (or ongoing at) 
lymphodepletion.” 
Use GSK Drug Coding Dictionary 
PRY 
1.0190 
mITT 
BP1A 
Summary of Blood Products on Treatment 
 
PRY 
Anti-Cancer Therapy 
1.0200 
ITT 
AC1 
Summary of Prior Anti-Cancer Therapy (ITT) 
IDSL 
Add footnote: “Note: Includes all anti-
cancer therapy from regimens initiated 
between diagnosis of advanced disease 
and lymphodepletion except bridging 
therapies.” 
IA2, PRY 
1.0210 
mITT 
AC1 
Summary of Prior Anti-Cancer Therapy (mITT) 
IDSL 
Add footnote: “Note: Includes all anti-
cancer therapy from regimens initiated 
between diagnosis of advanced disease 
and lymphodepletion except bridging 
therapies.” 
If same population as ITT, don’t produce 
IA2, PRY 
1.0220 
mITT 
FAC1 
Summary of On-Study Anti-Cancer Therapy 
IDSL 
PRY 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Summarise “Time From T-cell Infusion to 
Start of Subsequent Anti-Cancer Therapy” 
where FAC1 shell has “Time from Study 
Treatment Discontinuation”. 
1.0230 
ITT 
CM1 
Summary of Prior Dictionary Coded Anti-Cancer Therapy 
(ITT) 
IDSL 
Use GSK Drug Coding Dictionary 
Add footnote: “Note: Includes all anti-
cancer therapy from regimens initiated 
between diagnosis of advanced disease 
and lymphodepletion except bridging 
therapies.” 
IA2, PRY 
1.0240 
mITT 
CM1 
Summary of Prior Dictionary Coded Anti-Cancer Therapy 
(mITT) 
IDSL 
Use GSK Drug Coding Dictionary 
Add footnote: “Note: Includes all anti-
cancer therapy from regimens initiated 
between diagnosis of advanced disease 
and lymphodepletion except bridging 
therapies.” 
If same population as ITT, don’t produce 
IA2, PRY 
1.0245 
mITT 
CM1 
Summary of Dictionary Coded Bridging Therapy (mITT) 
Use GSK Drug Coding Dictionary 
Summarise all prior therapies identified as 
bridging per Section 6.7.1. 
Add footnote: “Note: Includes all anti-
cancer therapy initiated between 
leukapheresis and lymphodepletion 
identified as bridging.” 
IA2, PRY 
1.0250 
mITT 
CM1 
Summary of On-Study Dictionary Coded Anti-Cancer Therapy 
IDSL 
Use GSK Drug Coding Dictionary 
PRY 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
1.0260 
ITT 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(ITT) 
IDSL 
Break down “Number of Chemotherapy 
Regimens” into {0,1,2,3,4,5,6,>6}. 
Add footnote: “Note: Includes all anti-
cancer regimens initiated between 
diagnosis of advanced disease and 
lymphodepletion except bridging 
therapies.” 
PRY 
1.0270 
mITT 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(mITT) 
IDSL 
Break down “Number of Chemotherapy 
Regimens” into {0,1,2,3,4,5,6,>6}. 
Add footnote: “Note: Includes all anti-
cancer regimens initiated between 
diagnosis of advanced disease and 
lymphodepletion except bridging 
therapies.” 
If same population as ITT, don’t produce 
PRY 
Surgical Procedures 
1.0280 
ITT 
OSP1 
Summary of Prior Cancer Related Surgical Procedures (ITT) 
IDSL 
Report Surgery Intent and Site of Surgery 
Add footnote: “Note: Includes all cancer 
related surgeries between diagnosis of 
advanced disease and lymphodepletion.” 
For surgeries recorded at the baseline 
visit on the “On Study Cancer Related 
Surgery Since Screening” where intent is 
not collected, report intent as UNKNOWN, 
with footnote “Note: UNKNOWN intent 
includes procedures recorded at the 
IA2, PRY 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
baseline visit for which intent is not 
collected.” 
1.0290 
mITT 
OSP1 
Summary of Prior Cancer Related Surgical Procedures 
(mITT) 
IDSL 
Report Surgery Intent and Site of Surgery 
Add footnote: “Note: Includes all cancer 
related surgeries between diagnosis of 
advanced disease and lymphodepletion.” 
For surgeries recorded at the baseline 
visit on the “On Study Cancer Related 
Surgery Since Screening” where intent is 
not collected, report intent as UNKNOWN, 
with footnote “Note: UNKNOWN intent 
includes procedures recorded at the 
baseline visit for which intent is not 
collected.” 
If same population as ITT, don’t produce 
IA2, PRY 
1.0300 
mITT 
OSP1 
Summary of On-Study Cancer Related Surgical Procedures 
IDSL 
Report Site of Surgery 
PRY 
Exposure 
1.0310 
mITT 
POP_T4 
Summary of Total Transduced T-cells 
Add total column. 
Report total number of transduced T-cells 
in 10^9 cells and categorize it into: 
<1, >=1 to <=8, >8 
IA2, PRY 
1.0312 
mITT 
POP_T4 
Summary of Exposure to Lymphodepletion Chemotherapy 
Add total column. 
Remove sections on T-cell infusion.  
Add summary statistics (n, mean, SD, 
median, Min, Max) for cumulative dose 
(mg/m^2) for Cyclophosphamide and 
Fludarabine separately, with row labels 
FNL* 


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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
‘Cyclophosphamide Cumulative Dose 
(mg/m^2)’ and ‘Fludarabine Cumulative 
Dose (mg/m^2).   
 
For the final analysis only, include 1st T-
cell infusion data. Append " - Excluding 
Retreatment" to the title. 
14.12.5. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Overall Response Rate (ORR) 
2.0010 
mITT 
RE1a 
Summary of Independent Reviewer-Assessed Best Response 
with Confirmation (RECIST 1.1 Criteria) (mITT) 
Add total column 
Add Overall Response Rate (CR+PR) 
Include exact (Clopper Pearson) 95% CI 
for overall response rate (CR+PR) 
Per Section 2.3.1, omit all hypothesis 
testing sections: p-value for response rate 
and sections for response rate 
differences, odds ratio and homogeneity 
(marked as optional in IDSL shell). 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 


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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.0020 
ITT 
RE1a 
Summary of Independent Reviewer-Assessed Best Response 
with Confirmation (RECIST 1.1 Criteria) (ITT) 
If same population as mITT, don’t 
produce. 
Add total column 
Add Overall Response Rate (CR+PR) 
Include exact (Clopper Pearson) 95% CI 
for overall response rate (CR+PR) 
Per Section 2.3.1, omit all hypothesis 
testing sections. 
PRY 
2.0030 
mITT / All 
Evaluable 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria) (mITT) 
Use mITT for PRY & FNL and All 
Evaluable for IFA & IA2. 
For IA2, remove “(mITT)” from title. 
Add total column 
Add Overall Response Rate (CR+PR) 
Include exact (Clopper Pearson) 95% CI 
for overall response rate (CR+PR) 
Per Section 2.3.1, omit all hypothesis 
testing sections. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IFA, IA2, PRY, 
FNL* 
2.0040 
ITT 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation (RECIST 1.1 Criteria) (ITT) 
If same population as mITT, don’t 
produce. 
Add total column 
Add Overall Response Rate (CR+PR) 
Include exact (Clopper Pearson) 95% CI 
for overall response rate (CR+PR) 
Per Section 2.3.1, omit all hypothesis 
testing sections. 
IA2, PRY 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
9 6  
 
Effi c a c y: T a bl es  
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e S h ell  Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
2. 0 0 5 0  
mI T T  
R E 4  
S u m m ary of C o m paris on of I nv estig at or -Ass ess e d an d 
I n d e p e n de nt R evi e w er -Assesse d B est R esp o nse ( wit h 
C o nfir m atio n) ( R E CI S T 1. 1 Crit eri a)  
Ad d t ot al c ol u m n  
P R Y , F NL* 
2. 0 0 6 0  
mI T T  
R E 1 a  
S u m m ary of I n de p e n d ent R evie w er -Ass ess e d B est R es po nse 
wit h o ut C o nfir m atio n ( R E CI S T 1. 1 Crit eri a) 
Ad d t ot al c ol u m n  
Per S ecti o n 2. 3. 1 , o mit all hy p ot h esis 
t esti n g s ecti o ns. 
P R Y  
2. 0 0 7 0  
mI T T  
R E 1 a  
S u m m ary of I nv esti g at or-Ass ess e d B est R es po ns e wit h o ut 
C o nfir m atio n ( R E CI S T 1. 1 Criteri a) 
Ad d t ot al c ol u m n  
Per S ecti o n 2. 3. 1 , o mit all hy p ot h esis 
t esti n g s ecti o ns. 
P R Y  
C CI


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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Time to Event 
2.0100 
mITT 
[Non-Standard] 
EFF_T1 
Summary of Independent Reviewer-Assessed Time to 
Response (RECIST 1.1 Criteria) 
Subset of subjects with confirmed BOR of 
CR or PR 
Add mean 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
2.0110 
mITT 
[Non-Standard] 
EFF_T1 
Summary of Investigator-Assessed Time to Response 
(RECIST 1.1 Criteria) 
Subset of subjects with confirmed BOR of 
CR or PR 
Add mean 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IA2, PRY, 
FNL* 


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98 
 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.0120 
mITT 
TTE1a 
Summary of Independent Reviewer-Assessed Duration of 
Response (RECIST 1.1 Criteria) 
Subset of subjects with confirmed 
response 
Add total column 
Unit = Months 
Per Section 2.3.1, omit all hypothesis 
testing sections. 
Include footnotes: 
• “Note: Duration of Response is defined 
as the interval between the initial date of 
confirmed response (Partial Response / 
Complete Response) and the date of 
progressive disease or death among 
subjects with a confirmed response per 
RECIST 1.1.” 
• 'Censored, follow-up ongoing' includes 
subjects that had not progressed or died 
but were still in interventional phase 
follow-up and had not initiated new anti-
cancer therapy. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 


CONFIDENTIAL 
 
 
208469 
99 
 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.0130 
mITT 
TTE1a 
Summary of Investigator-Assessed Duration of Response 
(RECIST 1.1 Criteria) 
Subset of subjects with confirmed 
response 
Add total column 
Unit = Months 
Per Section 2.3.1, omit all hypothesis 
testing sections: Hazard Ratio estimate 
and 95%CI (marked as optional in IDSL 
shell). 
Include footnotes: 
• “Note: Duration of Response is defined 
as the interval between the initial date of 
confirmed response (Partial Response / 
Complete Response) and the date of 
progressive disease or death among 
subjects with a confirmed response per 
RECIST 1.1.” 
• 'Censored, follow-up ongoing' includes 
subjects that had not progressed or died 
but were still in interventional phase 
follow-up and had not initiated new anti-
cancer therapy. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 


CONFIDENTIAL 
 
 
208469 
100 
 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
2.0140 
mITT 
[Non-Standard] 
EFF_T2 
Summary of Independent Reviewer-Assessed Progression 
Free Survival (RECIST 1.1 Criteria) 
Include total column  
Unit = Months 
For the PFS rates include a separate 
section for each 3 month interval (3, 6, 9, 
12, etc). Use the latest PFS time to 
determine which intervals to include.  
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
2.0150 
mITT 
[Non-Standard] 
EFF_T2 
Summary of Investigator-Assessed Progression Free Survival 
(RECIST 1.1 Criteria) 
Include total column 
Unit = Months 
For the PFS rates include a separate 
section for each 3 month interval (3, 6, 9, 
12, etc). Use the latest PFS time to 
determine which intervals to include.   
For IA2: If at time of data cut there are <5 
PDs in the high lympho cohort then do not 
present (leave blank) percentiles for that 
cohort and footnote “Note: Percentiles 
(median, quartiles) and the corresponding 
CIs for the HIGH LYMPHO + GSK794 
group are not presented as data are 
immature.”. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IFA, IA2, PRY, 
FNL* 
2.0155 
mITT 
[Non-Standard] 
EFF_T3 
Summary of Interventional Phase Follow-up 
Follow the reverse KM method as 
described in Section 7.2.3.5. 
EXCLUDING retreatment data and 
append “ - Excluding Retreatment” to the 
title 
FNL 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 0 1  
 
Effi c a c y: T a bl es  
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e S h ell  Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
2. 0 1 6 0  
mI T T  
O T T E1  
S u m m ary of C o m paris on of I nv estig at or -Ass ess e d an d 
I n d e p e n de nt R evi e w er-Assesse d Pr o gr essi o n Ev e nt Ti min g 
or Ce ns ori ng Ti mi n g ( R E CI S T 1. 1 Crit eri a)  
I ncl u d e [ o pti o n al] f o ot n ot e t ext: “T h e ti m e 
wi n d o w f or c o m pl et e a gr e e m e nt i n ti mi n g 
is pl us/ mi n us 7 d ays.” 
W h er e I N V is P D a n d I R C is c e ns or e d, 
cl assify u n d er “I N V P D e arli er t h a n I R C ” 
as “ P D by I N V, C e ns or e d by I R C”, ev e n if 
c e ns ori n g d at e is b ef or e t h e P D d at e ( e. g. 
d u e t o i nc o m pl et e I R C r e a ds f or i n -str e a m 
d at a) . Si mil arly,  if I R C is P D a n d I N V is 
c e ns or e d. 
P R Y  
C CI


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208469 
102 
 
14.12.6. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
Overall Response Rate (ORR) 
2.0180 
mITT 
[Non-Standard] 
EFF_F1 
Spider Plot of Independent Reviewer-Assessed Percent 
Change from Baseline in Sum of Target Lesion Diameters 
(by Lymphodepletion Regimen) 
Plot by cohort. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY 
2.0190 
mITT 
[Non-Standard] 
EFF_F1 
Spider Plot of Independent Reviewer-Assessed Percent 
Change from Baseline in Sum of Target Lesion Diameters 
Plot both cohorts combined on same 
axes. 
PRY 
2.0200 
mITT / All 
Evaluable 
[Non-Standard] 
EFF_F1 
Spider Plot of Investigator-Assessed Percent Change from 
Baseline in Sum of Target Lesion Diameters (by 
Lymphodepletion Regimen) 
Use mITT for PRY & FNL and All 
Evaluable for IFA & IA2 
Plot by cohort. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IFA, IA2, PRY,  
2.0210 
mITT / All 
Evaluable 
[Non-Standard] 
EFF_F1 
Spider Plot of Investigator-Assessed Percent Change from 
Baseline in Sum of Target Lesion Diameters 
Use mITT for PRY and All Evaluable for 
IFA & IA2 
Plot both cohorts combined on same 
axes, with cohort differentiated by color 
and best confirmed response by symbol. 
IFA, IA2, PRY 
2.0220 
mITT 
RE8b 
Independent Reviewer-Assessed Maximum Percent 
Reduction from Baseline in Sum of Target Lesion Diameters 
(by Lymphodepletion Regimen) 
Label with participant ID 
Plot by cohort. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY 


CONFIDENTIAL 
 
 
208469 
103 
 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
2.0230 
mITT 
RE8b 
Independent Reviewer-Assessed Maximum Percent 
Reduction from Baseline in Sum of Target Lesion Diameters 
Label x-axis with participant ID 
Plot both cohorts combined on same 
axes, with cohort differentiated by color 
and best confirmed response by shading. 
Annotate end of bar with participants best 
confirmed response. 
PRY 
2.0240 
mITT / All 
Evaluable 
RE8b 
Investigator-Assessed Maximum Percent Reduction from 
Baseline in Sum of Target Lesion Diameters (by 
Lymphodepletion Regimen) 
Label x-axis with participant ID 
Use mITT for PRY and All Evaluable for 
IFA & IA2 
Plot by cohort. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IFA, IA2, PRY 
2.0250 
mITT / All 
Evaluable 
RE8b 
Investigator-Assessed Maximum Percent Reduction from 
Baseline in Sum of Target Lesion Diameters 
Label x-axis with participant ID 
Use mITT for PRY and All Evaluable for 
IFA & IA2 
Plot both cohorts combined on same 
axes, with cohort differentiated by color 
and best confirmed response by shading. 
Annotate end of bar with participants best 
confirmed response. 
IFA, IA2, PRY 


CONFIDENTIAL 
 
 
208469 
104 
 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
Time to Event 
2.0260 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Independent 
Reviewer-Assessed Duration of Response (RECIST 1.1 
Criteria) (by Lymphodepletion Regimen) 
Subset of subjects with confirmed 
response  
Plot by cohort. 
Include 95% (Hall-Wellner) confidence 
Bands if data warrant. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY 
2.0270 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Independent 
Reviewer-Assessed Duration of Response (RECIST 1.1 
Criteria) 
Subset of subjects with confirmed 
response  
Plot both cohorts on same axes, with 
cohort differentiated by color and labelled 
so clear which is which even in 
monochrome print. 
PRY 
2.0290 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Investigator-
Assessed Duration of Response (RECIST 1.1 Criteria) (by 
Lymphodepletion Regimen) 
Subset of subjects with confirmed 
response 
Plot by cohort. 
Include 95% (Hall-Wellner) confidence 
Bands if data warrant. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY 
2.0300 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Investigator-
Assessed Duration of Response (RECIST 1.1 Criteria) 
Subset of subjects with confirmed 
response 
Plot both cohorts on same axes, with 
cohort differentiated by color and labelled 
so clear which is which even in 
monochrome print. 
PRY 


CONFIDENTIAL 
 
 
208469 
105 
 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
2.0320 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Independent 
Reviewer-Assessed Progression Free Survival (RECIST 1.1 
Criteria) (by Lymphodepletion Regimen) 
Plot by cohort. 
Include 95% (Hall-Wellner) confidence 
Bands if data warrant. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY 
2.0330 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Independent 
Reviewer-Assessed Progression Free Survival (RECIST 1.1 
Criteria) 
Plot both cohorts on same axes, with 
cohort differentiated by color and labelled 
so clear which is which even in 
monochrome print. 
PRY 
2.0350 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Investigator-
Assessed Progression Free Survival (RECIST 1.1 Criteria) 
(by Lymphodepletion Regimen) 
Plot by cohort. 
Include 95% (Hall-Wellner) confidence 
Bands if data warrant. 
For IA2: If at time of data cut there are <5 
PDs in the high lympho cohort then do not 
present (leave blank) K-M curves for that 
cohort and footnote “Note: Curves for the 
HIGH LYMPHO + GSK794 group are not 
presented as data are immature.” 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IFA, IA2, PRY,  
2.0360 
mITT 
TTE10 
Graph of Kaplan-Meier Survival Curves of Investigator-
Assessed Progression Free Survival (RECIST 1.1 Criteria) 
Plot both cohorts on same axes, with 
cohort differentiated by color and labelled 
so clear which is which even in 
monochrome print. 
IA2, PRY 


CONFIDENTIAL 
 
 
208469 
106 
 
14.12.7. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Adverse Events (AEs) 
3.0010 
ITT 
AE13 
Adverse Event Overview (ITT) 
Add total column. 
Remove “AEs leading to permanent 
discontinuation of study treatment”. 
IFA  
3.0020 
mITT 
AE13 
Adverse Event Overview (mITT) 
Add total column. 
Remove “AEs leading to permanent 
discontinuation of study treatment”. 
IFA  
3.0030 
ITT 
AE1 
Summary of Adverse Events by System Organ Class and 
Preferred Term 
ICH E3 
Add total column. 
Do not use combined PT terms. 
IA2, PRY 
3.0040 
mITT 
AE1 
Summary of Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term 
ICH E3 
Add total column. 
Do not use combined PT terms. 
Include footnote “Note: Treatment 
Emergent is defined as onset on or after 
lymphodepletion chemotherapy start 
date.” 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 
3.0050 
ITT 
OAE07 
Summary of Adverse Events by Maximum Grade and by 
Preferred Term – Post-Lymphodepletion Period (ITT) 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
IFA 


CONFIDENTIAL 
 
 
208469 
107 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0060 
mITT 
OAE07 
Summary of Adverse Events by Maximum Grade and by 
Preferred Term – Post-Lymphodepletion Period (mITT) 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
IFA 
3.0070 
ITT 
OAE07 
Summary of Adverse Events by Maximum Grade 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Use combined PT with footnote 
“Preferred terms are combined as 
shown in Table 3.0140” and “Adverse 
Event” (rather than “Preferred Term”) as 
header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
IA2, PRY 
3.0075 
ITT 
AE18 
Summary of Adverse Events by Maximum Grade Category  
• Summarise by combined PT (only – not 
within SOC) with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” 
(rather than “System Organ Class” & 
“Preferred Term”) as header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4 (as AE18 IDSL 
mock had prior to v21). 
• Include Total columns (overall Total & 
3+4+5 over both cohorts). 
PRY 


CONFIDENTIAL 
 
 
208469 
108 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0080 
mITT 
OAE07 
Summary of Treatment Emergent Adverse Events by 
Maximum Grade  
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Use combined PT with footnote 
“Preferred terms are combined as 
shown in Table 3.0140” and “Adverse 
Event” (rather than “Preferred Term”) as 
header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
• Footnote definition of treatment 
emergent per Table 3.0040. 
• Repeat at final analysis including 
retreatment data and append " - 
Including Retreatment" to the title. 
IA2, PRY, FNL 
3.0085 
mITT 
AE18 
Summary of Treatment Emergent Adverse Events by 
Maximum Grade Category  
• Summarise by combined PT (only – not 
within SOC) with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” 
(rather than “System Organ Class” & 
“Preferred Term”) as header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4 (as AE18 IDSL 
mock had prior to v21). 
• Include Total columns (overall Total & 
3+4+5 over both cohorts). 
• Footnote definition of treatment 
emergent per Table 3.0040. 
PRY 


CONFIDENTIAL 
 
 
208469 
109 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0090 
mITT 
OAE07 
Summary of Study-Treatment Related TEAEs by Maximum 
Grade 
ICH E3 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Treatment related including all 
lymphodepletion regimens and T-cell 
infusion. 
• Use combined PT with footnote 
“Preferred terms are combined as 
shown in Table 3.0140” and “Adverse 
Event” (rather than “Preferred Term”) as 
header. 
• Add footnote: Note: Study-treatment 
related AEs are defined as adverse 
events that are related to either T-cell 
infusion, cyclophosphamide or 
fludarabine. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
• Repeat at final analysis including 
retreatment data and append " - 
Including Retreatment" to the title. 
IA2, PRY, FNL 


CONFIDENTIAL 
 
 
208469 
110 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0095 
mITT 
AE18 
Summary of Study-Treatment Related Adverse Events by 
Maximum Grade Category 
• Summarise by combined PT (only – not 
within SOC) with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” 
(rather than “System Organ Class” & 
“Preferred Term”) as header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4 (as AE18 IDSL 
mock had prior to v21). 
• Include Total columns (overall Total & 
3+4+5 over both cohorts). 
• Footnote definition of study-treatment 
related AEs per Table 3.0090. 
PRY 
3.0100 
mITT 
OAE07 
Summary of T-cell Infusion Related TEAEs by Maximum 
Grade 
ICH E3 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Use combined PT with footnote 
“Preferred terms are combined as 
shown in Table 3.0140” and “Adverse 
Event” (rather than “Preferred Term”) as 
header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
• Repeat at final analysis including 
retreatment data and append " - 
Including Retreatment" to the title. 
IA2, PRY, FNL 


CONFIDENTIAL 
 
 
208469 
111 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0110 
mITT 
OAE07 
Summary of Lymphodepletion-Related Adverse Events by 
Maximum Grade 
ICH E3 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Use combined PT with footnote 
“Preferred terms are combined as 
shown in Table 3.0140” and “Adverse 
Event” (rather than “Preferred Term”) as 
header. 
• Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
• Repeat at final analysis including 
retreatment data and append " - 
Including Retreatment" to the title. 
PRY, FNL 
3.0120 
ITT 
AE15 
Summary of Common (>=5%) Non-serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Subjects and Occurrences) 
FDAAA, EudraCT 
Add total column. 
• Do not combine PT Terms. 
• Add footnote - Multiple events recorded 
with a common preferred term and 
continuous or overlapping start/end 
dates are considered as a single event.  
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
PRY, FNL 
3.0130 
mITT 
AE3 
Summary of Non-Serious Study-Treatment Related TEAEs by 
Overall Frequency 
Add total column. 
• Do not combine PT Terms. 
• Add footnote - “Multiple events recorded 
with a common preferred term and 
continuous or overlapping start/end 
dates are considered as a single event.” 
• Footnote definition of study-treatment 
related AEs per Table 3.0090. 
PRY, FNL 


CONFIDENTIAL 
 
 
208469 
112 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0140 
ITT 
AE1 
Summary of Adverse Events Grouped by Similarity of Preferred 
Terms 
Add total column. 
Use combined PT term AEs  
Only include all combined PT term AEs. 
Remove overall “ANY EVENT” and 
synonym level “Any Event” rows. 
SOC from AE1 should be combined PT 
Term. 
PT term from AE1 should be the 
MEDDRA PT term. 
Label column “Synonym/Preferred Term” 
rather than “System Organ 
Class/Preferred Term” (where / indicates 
newline and indent as in AE1) 
If combined AE does not appear then 
include a 0 count. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 
Adverse Events of Special Interest (AE of SI) 
3.0150 
ITT 
AE5B 
Summary of Adverse Events of Special Interest 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Replace SOC with AESI category (use 
AESI category names from current SRT 
AESI specification document if these differ 
to those in Section 8.2). 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” (rather 
than “Preferred Term”) as header. 
IFA 


CONFIDENTIAL 
 
 
208469 
113 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0160 
mITT 
AE5B 
Summary of Adverse Events of Special Interest – Post-
Lymphodepletion Period 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Replace SOC with AESI category (use 
AESI category names from current SRT 
AESI specification document if these differ 
to those in Section 8.2). 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” (rather 
than “Preferred Term”) as header. 
IFA 
3.0170 
mITT 
AE5B 
Summary of Treatment Emergent Adverse Events of Special 
Interest by Maximum Grade (Focused List) 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Use combined PT identified in the focused 
list with footnote “Preferred terms are 
combined as shown in Table 3.0140” and 
“Adverse Event” (rather than “Preferred 
Term”) as header. 
Replace SOC with AESI category (use 
AESI category names from current SRT 
AESI specification document if these differ 
to those in Section 8.2). 
Footnote definition of treatment emergent 
per Table 3.0040. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 


CONFIDENTIAL 
 
 
208469 
114 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0180 
mITT 
AE5B 
Summary of Treatment Emergent Adverse Events of Special 
Interest by Maximum Grade (Comprehensive List) 
• Add total “by group” page with 
subheading “Treatment: Total (N=XXX)”. 
• Do Not Use combined PT. 
• Replace SOC with AESI category (use 
AESI category names from current SRT 
AESI specification document if these 
differ to those in Section 8.2). 
• Footnote definition of treatment 
emergent per Table 3.0040. 
IA2, PRY 
3.0190 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent Graft 
versus Host Disease (GvHD) 
• Add total column. 
• Use Focused Scope List. 
• Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
• Footnote – “Multiple events recorded 
with a common preferred term and 
continuous or overlapping start/end 
dates are considered as a single event.” 
• Report for all subjects and for all 
subjects with event. 
• Report characteristics, outcome, 
number of occurrences and max grade 
• Do not create if 1 or fewer participants 
have event (default to listing). 
• Footnote definition of treatment 
emergent per Table 3.0040. 
PRY 


CONFIDENTIAL 
 
 
208469 
115 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0200 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent 
Haematopoietic Cytopenias (Focused List) 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Report for all subjects and for all subjects 
with event. 
Report characteristics, outcome, number 
of occurrences and max grade. 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
PRY, FNL 


CONFIDENTIAL 
 
 
208469 
116 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0220 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent Immune 
Effector-Cell Associated Neurotoxicity Syndrome (ICANS) 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Report for all subjects and for all subjects 
with event. 
Report characteristics, outcome, number 
of occurrences and max grade. 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 1 7  
 
S af et y : T a bl e s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
C CI


CONFIDENTIAL 
 
 
208469 
118 
 
Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0240 
mITT 
ESI1 
Summary of Characteristics of Treatment Emergent Guillain-
Barre Syndrome 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Report for all subjects and for all subjects 
with event. 
Report characteristics, outcome, number 
of occurrences and max grade. 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0250 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Graft versus Host Disease (GvHD) 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60) 
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0260 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Haematopoietic Cytopenia (Focused 
List) 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0272 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Haematopoietic Cytopenia 
(Neutropenia) 
Add total column. 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0274 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Haematopoietic Cytopenia 
(Thrombocytopenia) 
Add total column. 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0276 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Haematopoietic Cytopenia (Anemia) 
Add total column. 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0278 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Haematopoietic Cytopenia (Febrile 
Neutropenia) 
Add total column. 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0280 
mITT 
ESI2B 
Summary of Onset and Duration of the First Treatment 
Emergent Occurrence of Immune Effector-Cell Associated 
Neurotoxicity Syndrome (ICANS) 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 2 2  
 
S af et y : T a bl e s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
3. 0 3 0 0  
mI T T  
E SI 2 B  
S u m m ary of Ons et a n d D ur at io n of t h e First Tre at m ent 
E m er g e nt Occurr e nce of G uillai n -B arr e S y ndr o m e 
Ad d t ot al c ol u m n.  
Us e F oc us e d Sc o p e List.  
F o ot n ot e –  “ Pr ef err e d t er ms i d e ntifi e d i n 
t h e F oc us e d list ar e s u m m ariz e d”. 
F o ot n ot e –  “ M ulti pl e ev e nts r ec or d e d wit h 
a c o m m o n pr ef err e d t er m a n d c onti n u o us 
or ov erl a p pi n g st art/ e n d d at es ar e 
c o nsi d er e d as a si n gl e ev e nt.” 
Ti m e t o o ns et ( d ays) ( -8 - -1, 1 -1 4, 1 5 -3 0, 
3 1 -6 0, > 6 0)  
D ur ati o n ( d ays) ( 1 -3 0, 3 1 -9 0, > 9 0)  
O ns et fr o m first T -c ell i nf usi o n 
D o n ot cr e at e if 1 or f e w er p artici p a nts 
h av e ev e nt ( d ef a ult t o listi n g).  
F o ot n ot e d efi niti o n of tr e at m e nt e m er g e nt 
p er T a bl e  3. 0 0 4 0 . 
P R Y  
C CI


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Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0320 
mITT 
ESI2B 
Summary of Onset and Duration of the Last Treatment 
Emergent Occurrence of Haematopoietic Cytopenias 
(Focused List) 
Add total column. 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Time to onset (days) (-8 - -1, 1-14, 15-30, 
31-60, >60)  
Duration (days) (1-30, 31-90, >90) 
Onset from first T-cell infusion 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0380 
mITT 
[Non-Standard] 
SAFE_T1 
Summary of Time to Resolution and Recurrence of Grade 3 
or Above Treatment Emergent Haematopoietic Cytopenias 
(Focused List) 
Use Focused Scope List. 
Footnote – “Preferred terms identified in 
the Focused list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0382 
mITT 
[Non-Standard] 
SAFE_T1 
Summary of Time to Resolution and Recurrence of Grade 3 
or Above Treatment Emergent Haematopoietic Cytopenias 
(Neutropenia) 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0384 
mITT 
[Non-Standard] 
SAFE_T1 
Summary of Time to Resolution and Recurrence of Grade 3 
or Above Treatment Emergent Haematopoietic Cytopenias 
(Thrombocytopenia) 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0386 
mITT 
[Non-Standard] 
SAFE_T1 
Summary of Time to Resolution and Recurrence of Grade 3 
or Above Treatment Emergent Haematopoietic Cytopenias 
(Anemia) 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0388 
mITT 
[Non-Standard] 
SAFE_T1 
Summary of Time to Resolution and Recurrence of Grade 3 
or Above Treatment Emergent Haematopoietic Cytopenias 
(Febrile Neutropenia) 
Use Focused Scope Sub-List. 
Footnote – “Preferred terms identified in 
the Focused sub-list are summarized”. 
Footnote – “Multiple events recorded with 
a common preferred term and continuous 
or overlapping start/end dates are 
considered as a single event.” 
Do not create if 1 or fewer participants 
have event (default to listing). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
Serious and Other Significant Adverse Events 
3.0425 
ITT 
ESI1 
Summary of Characteristics of Serious Adverse Events 
Add total column. 
Report for all subjects and for all subjects 
with event. 
Report characteristics, outcome, number 
of occurrences and max grade. 
IA2 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0430 
ITT 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Subjects and Occurrences)  
FDAAA, EudraCT 
Add total column. 
Do not use combined PT term. 
Update row text to “Number of Study-
treatment related SAEs” and “Number of 
Study-treatment related Fatal SAEs” 
instead of drug-related. 
Footnote definition of study-treatment 
related AEs per Table 3.0090. 
Add Footnote – “Multiple events recorded 
with a common preferred term and 
continuous or overlapping start/end dates 
are considered as a single event.” 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 
3.0440 
ITT 
OAE07 
Summary of Serious Adverse Events by Maximum Grade 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” (rather 
than “Preferred Term”) as header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
IA2, PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0445 
ITT 
AE18 
Summary of Serious Adverse Events by Maximum Grade 
Category  
Summarise by combined PT (only – not 
within SOC) with footnote “Preferred terms 
are combined as shown in Table 3.0140” 
and “Adverse Event” (rather than “System 
Organ Class” & “Preferred Term”) as 
header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4 (as AE18 IDSL 
mock had prior to v21). 
Include Total columns (overall Total & 
3+4+5 over both cohorts). 
PRY 
3.0450 
mITT 
OAE07 
Summary of Serious Treatment Emergent Adverse Events by 
Maximum Grade 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” (rather 
than “Preferred Term”) as header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
Footnote definition of treatment emergent 
per Table 3.0040. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0455 
mITT 
AE18 
Summary of Serious Treatment Emergent Adverse Events by 
Maximum Grade Category 
Summarise by combined PT (only – not 
within SOC) with footnote “Preferred terms 
are combined as shown in Table 3.0140” 
and “Adverse Event” (rather than “System 
Organ Class” & “Preferred Term”) as 
header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4 (as AE18 IDSL 
mock had prior to v21). 
Include Total columns (overall Total & 
3+4+5 over both cohorts). 
Footnote definition of treatment emergent 
per Table 3.0040. 
PRY 
3.0460 
mITT 
OAE07 
Summary of Study-Treatment Related Serious TEAEs by 
Maximum Grade 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Treatment related including all 
lymphodepletion regimens and T-cell 
infusion. 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” (rather 
than “Preferred Term”) as header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
Footnote definition of study-treatment 
related AEs per Table 3.0090. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0465 
mITT 
AE18 
Summary of Study-Treatment Related Serious Adverse 
Events by Maximum Grade Category 
Summarise by combined PT (only – not 
within SOC) with footnote “Preferred terms 
are combined as shown in Table 3.0140” 
and “Adverse Event” (rather than “System 
Organ Class” & “Preferred Term”) as 
header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4 (as AE18 IDSL 
mock had prior to v21). 
Include Total columns (overall Total & 
3+4+5 over both cohorts). 
Footnote definition of study-treatment 
related AEs per Table 3.0090. 
PRY 
3.0470 
mITT 
OAE07 
Summary of T-cell Infusion Related Serious TEAEs by 
Maximum Grade 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140” and “Adverse Event” (rather 
than “Preferred Term”) as header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
IA2, PRY, FNL 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0480 
mITT 
OAE07 
Summary of Lymphodepletion-Related Serious Adverse 
Events by Maximum Grade 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Use combined PT with footnote “Preferred 
terms are combined as shown in 
Table 3.0140 and “Adverse Event” (rather 
than “Preferred Term”) as header. 
Present grades 3+4+5 combined (as in 
AE5B) rather than 3+4. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
PRY, FNL 
3.0525 
mITT 
AE20 
Summary of Serious Fatal and Non-Fatal Study-Treatment 
Related TEAEs by Overall Frequency 
Plain Language Summary (PLS) 
Add total column. 
Do NOT use combined PT. 
Add Footnote – “Multiple events recorded 
with a common preferred term and 
continuous or overlapping start/end dates 
are considered as a single event.” 
Footnote definition of study-treatment 
related AEs per Table 3.0090. 
Repeat at final analysis including 
retreatment data and append " - Including 
Retreatment" to the title. 
PRY, FNL 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Deaths 
3.0530 
mITT 
DD1 
Summary of Deaths 
IDSL 
Add total column. 
Report “Time from T-cell Infusion to 
Death” with median, min, max, 1st Q, 3rd 
Q in months, >30 days or <=30 days 
(rather than “Time from Last Dose to 
Death”). 
Only report Alive at Last Contact (do not 
report follow up ongoing/ended) 
Report primary cause of death categories 
corresponding to those captured on 
eCRF. 
-Disease Under Study 
-Treatment Related toxicity 
-Other 
Extend at final analysis to include 
retreatment data, replace "Time from T-
cell Infusion to Death" with "Time from 
Last T-cell Infusion to Death" and append 
" - Including Retreatment" to the title. 
PRY, FNL 
Laboratory: Chemistry 
3.0540 
mITT 
LB1 
Summary of Chemistry Changes from Baseline  
ICH E3. 
Don’t show baseline for tests with no post-
baseline values. 
Add total panel. 
Add footnote “Summary statistics for 
baseline are summarizing the baseline 
value, while at subsequent times the 
change from baseline is summarized.” 
PRY 


CONFIDENTIAL 
 
 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0550 
mITT 
OLB9C 
Summary of Worst-Case Chemistry Results by Maximum 
Grade Increase Post-Baseline Relative to Baseline 
ICH E3 
Include total panel. 
Report Week 4 & Week 12 visits plus 
Worst-case post-baseline only. 
For labs that are gradable by CTCAE 
v4.03. 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 
3.0560 
mITT 
OLB11C 
Summary of Worst-Case Chemistry Results Relative to 
Normal Range Post-Baseline Relative to Baseline 
ICH E3 
Include total panel. 
Report Week 4 & Week 12 visits plus 
Worst-case post-baseline only. 
For labs that are not gradable by CTCAE 
Add footnote “Only tests that are not 
gradable by CTCAE are summarized.” 
PRY 
Laboratory: Hematology 
3.0570 
mITT 
LB1 
Summary of Hematology Changes from Baseline 
ICH E3.  
Don’t show baseline for tests with no post-
baseline values. 
Add total panel. 
Add footnote “Summary statistics for 
baseline are summarizing the baseline 
value, while at subsequent times the 
change from baseline is summarized.” 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0580 
mITT 
OLB9C 
Summary of Worst-Case Hematology Results by Maximum 
Grade Increase Post-Baseline Relative to Baseline 
ICH E3 
Include total panel. 
Report Week 4 & Week 12 visits plus 
Worst-case post-baseline only. 
For labs that are gradable by CTCAE 
v4.03. 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 
3.0590 
mITT 
OLB11C 
Summary of Worst-Case Hematology Results Relative to 
Normal Range Post-Baseline Relative to Baseline 
ICH E3 
Include total panel. 
Report Week 4 & Week 12 visits plus 
Worst-case post-baseline only. 
For labs that are not gradable by CTCAE 
Add footnote “Only tests that are not 
gradable by CTCAE are summarized.” 
PRY 
Laboratory: Other Tests 
3.0600 
mITT 
LB1 
Summary of Other Laboratory Changes from Baseline  
ICH E3 
Don’t show baseline for tests with no post-
baseline values. 
Add total panel. 
Add footnote “Summary statistics for 
baseline are summarizing the baseline 
value, while at subsequent times the 
change from baseline is summarized.” 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0610 
mITT 
OBL9C 
Summary of Worst-Case Other Laboratory Results by 
Maximum Grade Increase Post-Baseline Relative to Baseline 
ICH E3 
Include total panel. 
Report Week 4 & Week 12 visits plus 
Worst-case post-baseline only. 
For labs that are gradable by CTCAE 
If there are no “other” labs gradable by 
CTCAE then do not produce this display. 
PRY 
3.0620 
mITT 
OLB11C 
Summary of Worst-Case Other Laboratory Results Relative to 
Normal Range Post-Baseline Relative to Baseline 
ICH E3 
Include total panel. 
Report Week 4 & Week 12 visits plus 
Worst-case post-baseline only. 
For labs that are not gradable by CTCAE 
If there are no “other” labs not gradable by 
CTCAE then do not produce this display. 
Add footnote “Only tests that are not 
gradable by CTCAE are summarized. 
PRY 
Performance Status 
3.0630 
mITT 
PS1A 
Summary of ECOG Performance Status 
ICH E3 
Add total column. 
Just summarize at baseline and last-
assessment 
IA2, PRY 
3.0640 
mITT 
PS3A 
Summary of Change in ECOG Performance Status from 
Baseline 
ICH E3 
Add total column. 
Include best and worst case 
PRY 


CONFIDENTIAL 
 
 
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Safety: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
ECG 
3.0650 
mITT 
EG1 
Summary of ECG Findings 
IDSL 
Add total column. 
Do not include screening visit. 
“Clinically significant change from 
baseline” in this standard shell is not 
collected in this study so cannot be 
reported: drop from display. 
PRY 
3.0660 
mITT 
EG10A 
Summary of Maximum QTc Values Post-Baseline Relative to 
Baseline by Category 
IDSL 
Use CTCAE grade categories rather than 
the standard ICH E14 categories given in 
the body of the mock, and include all 
optional “increase” categories, with 
CTCAE grade footnote. 
Include total panel. 
Report Baseline and Worst Case Post-
Baseline only. Do not report by visit. 
QTcB and QTcF reported in the same 
table but summarized separately. 
QTcB and QTcF values should not be 
derived. 
PRY 
3.0670 
mITT 
EG2 
Summary of Change from Baseline in ECG Values by Visit 
IDSL 
Include total panel. 
QTcF and QTcB reported separately 
Add footnote “Summary statistics for 
baseline are summarizing the baseline 
value, while at subsequent times the 
change from baseline is summarized.” 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.0680 
mITT 
EG11A 
Summary of Maximum Increase in QTc Values Post-Baseline 
Relative to Baseline by Category 
IDSL 
Include total panel. 
Report Worst Case Post-Baseline only. 
Do not report by visit. 
QTcB and QTcF reported in the same 
table but summarized separately. 
QTcB and QTcF values should not be 
derived. 
PRY 
Vital Signs 
3.0690 
mITT 
VS1 
Summary of Change from Baseline in Vital Signs 
ICH E3 
Don’t show baseline for tests with no post-
baseline values. 
Include total panel. 
Include weight, temp, DBP, SBP pulse 
rate, respiratory rate. 
Add footnote “Summary statistics for 
baseline are summarizing the baseline 
value, while at subsequent times the 
change from baseline is summarized.” 
PRY 
3.0700 
mITT 
OVT1C 
Summary of Worst-Case Heart Rate Results Relative to 
Normal Range Post-Baseline Relative to Baseline 
IDSL 
Include total panel. 
Do not summarize by visit 
PRY 
3.0710 
mITT 
OVT2C 
Summary of Worst-Case Blood Pressure Results by 
Maximum Grade Increase Post-Baseline Relative to Baseline 
IDSL 
Include total panel. 
Do not summarize by visit 
PRY 


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Replication Competent Lentivirus (RCL) & Gene Marked PBMCs 
3.0714 
mITT 
[Non-Standard] 
SAFE_T3 
Summary of Replication Competent Lentivirus Positive 
Add footnote “Note: n reflects the number 
of subjects with RCL assessed post T-cell 
infusion.” 
Count number of subjects with a “RCL 
Interpretation” POSITIVE at any 
assessment post-infusion, and present 
with “Count” row label in SAFE_T3 mock 
replaced with “Positive”. 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 
3.0716 
mITT 
[Non-Standard] 
SAFE_T3 
Summary of Subjects Showing >1% Gene Marked PBMCs 1 
Year Post-Treatment 
Label- >1% Gene Marked PBMCs 1 Year 
Post-treatment 
Define 1 year conservatively as at least 
360 days since infusion or month 12 visit. 
Use n row to indicate #subjects with 
persistence captured 1 year post-
treatment. 
Add footnote “Note: n reflects the number 
of subjects with persistence measured 1 
year post T-cell infusion.” 
PRY 


CONFIDENTIAL 
 
 
208469 
138 
 
14.12.8. 
Safety Figures 
Safety: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Duration Plots 
3.0720 
mITT 
[Non-Standard] 
SAFE_F1 
Plot of Duration on Interventional Phase with Prior Therapy 
Information (by Lymphodepletion Regimen) 
Add T-cell Dose 
Plot by cohort. 
IFA, IA2, PRY 
Laboratory 
3.0730 
mITT 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
eDISH (by Lymphodepletion Regimen) 
IDSL 
Plot by cohort. 
PRY 
3.0740 
mITT 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin – 
eDISH 
IDSL 
Plot both cohorts combined on same 
axes, with cohort differentiated by color. 
PRY 
3.0750 
mITT 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT (by 
Lymphodepletion Regimen) 
IDSL  
Plot by cohort. 
PRY 
3.0760 
mITT 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT 
IDSL  
Plot both cohorts combined on same 
axes, with cohort differentiated by color. 
PRY 
3.0765 
mITT 
[Non-Standard] 
SAFE_F3 
Plot of Hematology Data Over Time (by Lymphodepletion 
Regimen) 
Plot by parameter by cohort. 
Produce a separate plot for neutrophils, 
lymphocytes, platelets, and hemoglobin. 
X-axis units should be days starting at day 
-14.and ending at day 90, with day 1 (T-
cell) indicated as axis tick and vertical line. 
PRY 
ECG 
3.0770 
mITT 
EG12 
QTc Shifts from Baseline to Worst-Case Post Baseline (by 
Lymphodepletion Regimen) 
IDSL 
Plot by QTc type (Bazett or Fridericia) and 
cohort. 
PRY 


CONFIDENTIAL 
 
 
208469 
139 
 
Safety: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
3.0780 
mITT 
EG12 
QTc Shifts from Baseline to Worst-Case Post Baseline 
IDSL  
Plot by QTc type (Bazett or Fridericia). 
Plot both cohorts combined on same 
axes, with cohort differentiated by color. 
PRY 
14.12.9. 
Biomarkers Tables 
Biomarker: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Biomarkers 
3.0830 
mITT 
[Non-Standard] 
SAFE_T3 
Summary of Subjects Showing Monoclonality of Genetically 
Modified T-cell Population 
Label: Monoclonality of Genetically 
Modified T-cell Population 
Use n row to indicate #subjects with 
clonality data. 
Add footnote “Note: n reflects the number 
of subjects with clonality assessed.” 
PRY 
Anti-NY-ESO-1 Antibodies 
3.0840 
mITT 
[Non-Standard] 
BIO_T4 
Summary of Anti-NY-ESO-1 TCR(c259) Antibodies (ATA) 
Refresh at the final analysis and only 
include 1st T-cell infusion data. Append " 
– Excluding Retreatment" to the title. 
PRY, FNL* 
 
14.12.10. Biomarker Figures 
None. 


CONFIDENTIAL 
 
 
208469 
140 
 
14.12.11. Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Persistence of NY-ESO-1c259T 
4.0010 
mITT 
[Non-Standard] 
PK_T1 
Summary of Derived Persistence Parameters 
Report overall and by responders vs. non-
responders per investigator-assessed best 
response with confirmation. 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”. 
Add footnote: “Note: Samples collected 
within 4 days of day 28 are treated as day 
28 when calculating AUC0-28d” 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
4.0020 
mITT 
[Non-Standard] 
PK_T2 
Summary of Log-Transformed Derived Persistence 
Parameters 
Report overall and by responders vs. non-
responders per investigator-assessed best 
response with confirmation. 
Add total “by group” page with subheading 
“Treatment: Total (N=XXX)”.. 
Add footnote: “Note: Samples collected 
within 4 days of day 28 are treated as day 
28 when calculating AUC0-28d” 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
 


CONFIDENTIAL 
 
 
208469 
141 
 
14.12.12. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Persistence of NY-ESO-1c259T 
4.0030 
mITT 
[Non-Standard] 
PK_F4 
Distribution of Peak Cell Expansion (by Lymphodepletion 
Regimen) 
Side by side dot-plots for responders vs. 
non-responders, per investigator-
assessed best response with confirmation. 
Include footnote “Note: Responders are 
subjects with investigator-assessed best 
response with confirmation (per RECIST 
1.1 criteria) of Partial Response or 
Complete Response.”. 
Plot by cohort. 
X-axis and Y-axis should be same for 
each cohort. 
PRY 
4.0040 
mITT 
[Non-Standard] 
PK_F1 
Persistence Profile by Subject (by Lymphodepletion Regimen) 
By responders and non-responders per 
investigator-assessed best response with 
confirmation. 
Plot by cohort. 
Present with x-axis sufficient to see all 
follow-up. 
X-axis and Y-axis should be same for 
each cohort. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
IA2, PRY, 
FNL* 
4.0050 
mITT 
[Non-Standard] 
PK_F1 
Persistence Profile by Subject 
By responders and non-responders per 
investigator-assessed best response with 
confirmation. 
Plot both cohorts combined on same 
axes, with cohort differentiated by color. 
Present with x-axis sufficient to see all 
follow-up. 
IA2, PRY 


CONFIDENTIAL 
 
 
208469 
142 
 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
X-axis and Y-axis should be same as for 
corresponding “by Lymphodepletion 
Regimen” plot. 
4.0060 
mITT 
[Non-Standard] 
PK_F1 
Persistence Profile by Subject (Truncated at 20 Days) (by 
Lymphodepletion Regimen) 
By responders and non-responders per 
investigator-assessed best response with 
confirmation. 
Plot by cohort. 
Y-axis should be same as for complete 
profile plot in Figure 4.0040. 
IA2, PRY 
4.0070 
mITT 
[Non-Standard] 
PK_F1 
Persistence Profile by Subject (Truncated at 20 Days) 
By responders and non-responders per 
investigator-assessed best response with 
confirmation. 
Plot both cohorts combined on same 
axes, with cohort differentiated by color. 
X-axis and Y-axis should be same as for 
corresponding “by Lymphodepletion 
Regimen” plot. 
IA2, PRY 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 4 3  
 
1 4. 1 2. 1 3.  I C H Li sti n g s  
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
S u bj e ct Di s p o siti o n  
0 0 1 0  
Scr e e n e d  
E S 7  
Listi ng of R e as o ns f or Scr ee n F ail ur e  
J o ur n al G ui d eli n es 
O nly i ncl u d e s u bj ects t h at  e nt er e d 
scr e e ni n g; d o n ot i ncl u d e “ R u n-I n” 
el e m e nts or o pti o n al c ol u m n “ Ty p e of 
F ail ur e”  
I ncl u d e s u bj ects t h at p ass e d scr e e ni n g 
b ut w er e n ot e nr oll e d as w ell as scr e e n 
f ail ur es, wit h f o ot n ot e: “N ot e: I ncl u d es 
scr e e n f ail ur es (s u bj ects w h o di d n ot m e et 
H L A or a nti g e n crit eri a) as w ell as 
s u bj ects t h at p ass e d scr e e ni n g b ut w er e 
n ot e nr oll e d (si g n e d tr e at m e nt i nf or m e d 
c o ns e nt, m et eli gi bility crit eri a a n d 
l e uk a p h er es e d) f or ot h er r e as o ns.” 
R e p ort as c a pt ur e d o n C R F.  
P R Y  
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 4 4  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 0 1 5  
Scr e e n e d  
E S 9  
Listi ng of S u bj ects W h o Wer e R escr e e n ed  
I ncl u d e f o ot n ot e: “N ot e: D at e S u bj ect 
Ent er e d i nt o Tri al is d at e of 
l e uk a p h er esis.” 
I ncl u d e f o ot n ot e: “N ot e: I ncl u d es scr e e n 
f ail ur es (s u bj ects w h o di d n ot m e et H L A or 
a nti g e n crit eri a) as w ell as s u bj ects t h at 
p ass e d scr e e ni n g b ut w er e n ot e nr oll e d 
(si g n e d tr e at m e nt i nf or m e d c o ns e nt, m et 
eli gi bility crit eri a a n d l e uk a p h er es e d) f or 
ot h er r e as o ns. ” 
P R Y  
0 0 2 0  
I T T 
E S 2  
Listi ng of R e as o ns f or St u dy Wit h dr a w al  
I C H E3 
D o n ot i ncl u d e c ol u m ns “ R e as o n T er m(s)”, 
“W as a f oll o w-u p p h o n e c o nt act att e m pt e d 
3 ti m es ? ” & “ 
W as a f oll o w -u p c ertifi e d l ett er m ail e d ? ” 
fr o m G S K st a n d ar d m ock as n ot c oll ect e d 
i n t his st u dy. 
W h er e pri m ary r e as o n is O T H E R, a p p e n d 
“ Ot h er, S p ecify” t ext (s e p ar at e d by “: “). 
P R Y, F NL  
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 4 5  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
I ncl u d e f o ot n ot e: “Pri m ary r e a s o n f or 
st u dy wit h dr a w al is as i n dic at e d by t h e 
i nv esti g at or o n t h e " E n d of St u dy" C R F 
(f or s u bj ects t h at r ec eiv e d T-c ell i nf usi o n) 
or t h e " E n d of Tr e at m e nt" C R F. T h e 
o pti o ns av ail a bl e o n t h es e C R Fs ar e as 
pr es e nt e d i n t h e S u m m ary of S u bj ect 
St at us ( T a bl e 1. 0 0 1 0 ). ” 
Ext e n d at fi n al a n alysis t o i ncl u d e 
r etr e at m e nt d at a, fl a g mI T T 2 s u bj ects wit h 
a n ast erisk, a n d f o ot n ot e: "* = mI T T 2 
s u bj ects. A p p e n d '/ R etr e at m e nt D ay' t o 
e ac h st u dy d ay a n d o nly p o p ul at e o n 
r ec or ds d uri n g r etr e at m e nt ass ess m e nt 
p eri o d . A p p e n d  " - I ncl u di n g R etr e at m e nt " 
t o t h e titl e. 
0 0 3 0  
I T T 
[ N o n-St a n d ar d]  
P O P _ L 5  
Listi ng of S u bj ect Stat us  
IC H E 3  
Ext e n d at fi n al a n alysis t o i ncl u d e 
r etr e at m e nt d at a, fl a g mI T T 2 s u bj ects wit h 
a n ast erisk, a n d f o ot n ot e: "* = mI T T 2 
s u bj ects., a n d a p p e n d " - First I nf usi o n 
a n d St u dy C o m pl eti o n" t o t h e titl e.  
I A 2, P R Y, F NL 
C CI


CONFIDENTIAL 
 
 
208469 
146 
 
ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Populations Analysed 
0040 
Screened  
SP3 
Listing of Subjects Excluded from Any Population 
ICH E3 
Include columns to indicate exclusion (‘Y’) 
from Enrolled, ITT, and mITT populations. 
Drop “Date of Deviation/ Study day” and 
“Category/Coded Term” columns. 
Populate “Criteria” column with reason for 
exclusion from first: “SUBJECT NOT 
LEUKAPHERESED”, “SUBJECT NOT 
LEUKAPHERESED”, “SUBJECT NOT 
INFUSED”. 
Extend at final analysis to include 
additional column for exclusion from 
"Modified Intent-to-Retreat" (mITT2) 
population with reason for exclusion (if 
participant is in mITT) of "SUBJECT NOT 
REINFUSED" and append " - Including 
Retreatment" to the title. 
PRY, FNL 
Protocol Deviations 
0050 
ITT 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
Extend at final analysis to include 
retreatment data, flag mITT2 subjects with 
an asterisk, and footnote: "* = mITT2 
subjects. Append '/Retreatment Day' to 
each study day and only populate on 
records during retreatment assessment 
period . Append " – Including 
Retreatment" to the title. 
PRY, FNL 
0060 
ITT 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria 
Deviations 
ICH E3 
PRY, FNL 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 4 7  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
Ext e n d at fi n al a n alysis t o i ncl u d e  
r etr e at m e nt d at a  a n d  a p p e n d "  –  I ncl u di n g 
R etr e at m e nt  " t o t h e titl e. 
De m o gra p hi c a n d Ba seli n e C h ar a ct eri sti c s  
0 0 7 0  
I T T 
D M 2  
Listi ng of D e mo gr a p hic C h aract eristics  
I C H E3 
Ad d B MI, B S A a n d Hi g h L ev el R ac e  
I ncl u d e f o ot n ot e: “ N ot e: B S A w as 
c alc ul at e d usi n g t h e D u b ois-D u b ois 
f or m ul a.” 
List O T H E R Hi g h L ev el R ac e wit h “If 
Ot h er, pl e as e s p ecify” fr e e t ext a p p e n d e d 
( e g. “ O T H E R: M O R E T H A N O N E R A C E”). 
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi on d at a a n d  
a p p e n d "  –  Excl u di n g R etr e at m e nt " t o t h e 
titl e. 
P R Y , F NL* 
Pri or a n d C o n c o mit a nt M e dic ati o n s  
0 0 8 0  
I T T 
B P 4  
Listi ng of Blo o d Pr o d ucts  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt " t o t h e 
titl e. 
P R Y, F NL * 
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 4 8  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 0 9 0  
I T T 
C M 3  
Listi ng of M e dic ati ons  
I D SL 
I ncl u d e all c oll ect e d m e dic ati o ns, d o n ot 
s u bs et o n c o nc o mit a nt m e dic ati o ns st u dy 
p h as e.  
R e pl ac e “ St art e d Pr e -Tri al” c ol u m n wit h 
“ Pri or / C o nc o mit a nt” (i d e ntifi e d p er 
Ap p e n dix 4 ). 
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt " t o t h e 
titl e. 
P R Y, F NL * 
E x p o s ure  
0 1 1 0  
I T T 
[ N o n-St a n d ar d]  
P O P _ L 2  
Listi ng of Exp os ure t o Ly m p hod e pl etio n C h e mot h er a py  
I C H E3 
Cycl o p h os p h a mi d e  & Fl u d ar a bi n e  o nly.  
I ncl u d e d os e p er u nit b o dy s urf ac e ar e a 
( m g/ m2 ). 
C u m ul ativ e d os e is t o o nly b e p o p ul at e d 
o n t h e first r o w f or e ac h s u bj ect. R efr es h 
at t h e fi n al a n alysis a n d o nly i ncl u d e 1st 
ly m p h o d e pl eti o n d at a, a n d a p p e n d " - 
Excl u di n g R etr e at m e nt" t o t h e titl e. 
I A 2, P R Y, 
F NL * 
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 4 9  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 1 2 0  
I T T 
[ N o n-St a n d ar d]  
P O P _ L 1  
Listi ng of Exp os ure t o T-cell Inf usi o n 
I C H E3 
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
u p d at e titl e " Listi n g of Ex p os ur e t o T -c ell 
I nf usi o n –  Excl u di n g R etr e at m e nt ". 
I A 2, P R Y, 
F NL * 
A d v er s e E v e nt s  ( AE s) 
0 1 3 0  
I T T 
A E 8  
Listi ng of All A dv ers e Ev ents  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R e p ort ti m e fr o m first T-c ell I nf usi o n 
Us e “ Ti m e Si nc e T -c ell I nf usi o n” i nst e a d of 
“ Ti m e Si nc e 1st D os e/ Ti m e Si nc e L ast 
D os e”.  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T -c ell i nf usi o n d at a, a n d 
a p p e n d " - Excl u di n g R etr e at m e nt " t o t h e 
titl e. 
P R Y, F NL * 
C CI
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 0  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 1 4 0  
I T T 
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of  D elay e d  Adv erse Eve nts  
I C H E3 
List ev e nts c oll a ps e d p er A p p e n dix 1 5 . 
Sort by U S U BJI D, A E D E C O D, A S T D T, 
A E N D T  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt " t o t h e 
titl e. 
P R Y, F NL * 
0 1 5 0  
I T T 
A E 7  
Listi ng of S u bj ect N u m b ers f or I n divi d u al A dv ers e Ev ents  
I C H E3 
All A Es  
R e p e at at fi n al a n alysis i ncl u di n g 
r etr e at m e nt d at a a n d a p p e n d " - I ncl u di n g 
R etr e at m e nt" t o t h e titl e.  
P R Y, F NL  
0 1 6 0  
I T T 
A E 2  
Listi ng of R elati o ns hi p B et w e en A dv erse Ev e nt Syst e m 
Or g a n Cl ass es, Pr ef err ed T er ms, a nd V er b ati m T ext  
I D SL 
R e p e at at fi n al a n alysis i ncl u di n g 
r etr e at m e nt d at a a n d a p p e n d " - I ncl u di n g 
R etr e at m e nt" t o t h e titl e.  
P R Y, F NL  
A d v er s e E v e nt s of S p eci al I nt ere st  ( A E of SI) 
0 1 7 0  
mI T T  
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of Tr eat m e nt E m er g ent Gr aft vers us H ost Dis e ase 
( Gv H D) A dv erse Ev e nts 
Us e F oc us e d Sc o p e List  
Sort by U S U BJI D, A E D E C O D, A S T D T, 
A E N D T  
F o ot n ot e d efi niti o n of tr e at m e nt e m er g e nt 
p er T a bl e  3. 0 0 4 0 . 
I A 2, P R Y, 
F NL * 
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 1  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt ” t o titl e. 
0 1 8 0  
mI T T  
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of Tr eat m e nt E m er g ent H a e m at o p oi etic Cyt o pe ni as  
( F oc us ed List) 
Us e F oc us e d Sc o p e List  
Sort by U S U BJI D, A E D E C O D, A S T D T, 
A E N D T  
F o ot n ot e d efi niti o n of tr e at m e nt e m er g e nt 
p er T a bl e  3. 0 0 4 0 . 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt” t o titl e. 
I A 2, P R Y, 
F NL * 
0 1 9 0  
mI T T  
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of Tr eat m e nt E m er g ent H a e m at o p oi etic Cyt o pe ni as  
( Co m pr e h e nsiv e List) 
Us e C o m pr e h e nsiv e  Sc o p e List  
Sort by U S U BJI D, A E D E C O D, A S T D T, 
A E N D T  
I A 2, P R Y, 
F NL * 
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 2  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
F o ot n ot e d efi niti o n  of tr e at m e nt e m er g e nt 
p er T a bl e  3. 0 0 4 0 . 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt” t o titl e. 
0 2 0 0  
mI T T  
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of  Tr eat m e nt E m er g ent I m m u ne Eff ector-C ell 
Ass oci at e d N e urot oxicity Sy ndr o m e (I C A N S)  
Us e F oc us e d Sc o p e List  
Sort by U S U BJI D, A E D E C O D, A S T D T, 
A E N D T  
F o ot n ot e d efi niti o n of tr e at m e nt e m er g e nt 
p er T a bl e  3. 0 0 4 0 . 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt” t o titl e. 
I A 2, P R Y, 
F NL * 
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 3  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 2 2 0  
mI T T  
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of Tr eat m e nt E m er g ent G uill ai n -B arre S y n dr o m e 
( G B S) A dv ers e Ev e nts 
Us e F oc us e d Sc o p e List  
Sort by U S U BJI D, A E D E C O D, A S T D T, 
A E N D T  
F o ot n ot e d efi niti o n of tr e at m e nt e m er g e nt 
p er T a bl e  3. 0 0 4 0 . 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d "  –  
Excl u di n g R etr e at m e nt”  t o titl e. 
I A 2, P R Y, 
F NL * 
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 4  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
S eri o u s a n d Ot her Si g nifi c a nt A d v er s e E v e nt s  
0 2 3 5  
I T T 
[ N o n-St a n d ar d]  
S A F E _ L 1  
Listi ng of S erio us A dv erse Eve nts  
 
I A 2 
0 2 4 0  
I T T 
A E 8  
Listi ng of N o n -Fat al S eri o us Adv ers e Ev e nts  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R e p ort ti m e fr o m first T-c ell I nf usi o n 
Us e “ Ti m e Si nc e T -c ell I nf usi o n” i nst e a d of 
“ Ti m e Si nc e 1st D os e/ Ti m e Si nc e L ast 
D os e”.  
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt”  t o titl e. 
P R Y, F NL * 
0 2 5 0  
I T T 
A E 1 4  
Listi ng of R e as o ns f or C o nsi deri n g as a S eri ous A dv ers e 
Ev e nt  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
P R Y, F NL  
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 5  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
E xcl u di n g Retreat me nt” t o titl e. 
0 2 5 5  
I T T 
P A N 1 2  
Listi ng of C O VI D -1 9 Ass ess me nts a nd Sy m pt o ms 
Ass ess m e nts  
If d at a exists 
R e p e at at fi n al a n alysis i ncl u di n g 
r etr e at m e nt d at a a n d a p p e n d " - I ncl u di n g 
R etr e at m e nt" t o t h e titl e.  
P R Y, F NL  
De at h s  
0 2 6 0  
I T T 
D T H3  
Listi ng of D e aths  
I C H E3 
R e pl ac e “ Ti m e Fr o m L ast D os e” c ol u m n of 
st a n d ar d m ock wit h “ Ti m e Fr o m T-c ell 
I nf usi o n” a n d excl u d e “N o. of  Cycl es/  L ast 
D os e  ( u nit)” c ol u m n. 
I A 2 
0 2 6 2  
I T T 
D D 3  
D e at h Pr ofil e  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d.  
If d at a w arr a nt. 
e C R F o nly c oll ects Y E S| N O f or s ec o n d ary 
c a us e of d e at h. 
R e p e at at fi n al a n alysis i ncl u di n g 
r etr e at m e nt d at a a n d a p p e n d " - I ncl u di n g 
R etr e at m e nt" t o t h e titl e.  
P R Y, F NL  
He p at o bili ar y ( Li v er)  
0 2 7 0  
I T T 
LI V E R 5  
Listi ng of Liv er M o nitori n g/ Stop pi n g Eve nt R e p orti n g  
I D SL 
R e pl ac e c ol u m ns “ Ti m e Si nc e First/ L ast 
D os e ( d ays)” of LI V E R 5 m ock wit h “ Ti m e 
Si nc e T -c ell I nf usi o n”. 
P R Y  
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 6  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 2 8 0  
I T T 
LI V E R 1 3  
Listi ng of  S u bj ects M eeti n g H e p at o bili ary L a b or atory Crit eri a 
P ost -B as eli n e  
I D SL 
P R Y  
0 2 8 2  
I T T 
LI V E R 1 5  
Liv er St op pi n g Ev e nt Pr ofil e  
I D SL 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R e pl ac e “ St art D at e of Tr e at m e nt” a n d 
“ En d D at e of Tr e at m e nt” of LI V E R 1 5 m ock 
wit h “ D at e of T -c ell I nf usi o n” a n d r e p ort 
“ Ti m e Si nc e First T-c ell I nf usi o n …” & 
“ Ti m e fr o m L ast T-c ell I nf usi o n …” f or 
“ Ti m e Si nc e First D os e …” & “ Ti m e fr o m 
L ast D os e …”.  
P R Y  
L a b orat ory  
0 2 9 0  
I T T  
L B 5 A  
Listi ng of All  C h e mistry  D at a for S u bj ects wit h A ny V alu e of 
P ot e nti al Cli nic al I m p ort anc e/ O utsid e N or m al R a n g e  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt”  t o titl e 
P R Y, F NL * 
0 3 0 0  
I T T 
L B 5 A  
Listi ng of All H e m atol o gy D at a f or S u bj ects with A ny V al u e 
of P ot e ntial Cli nic al I m port a nce/ O utsi d e N or m al R a n ge  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt” t o titl e. 
P R Y, F NL * 
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 7  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 3 1 0  
I T T 
L B 5 A  
Listi ng of All Oth er L a bor at ory D at a f or S u bj ects wit h A ny 
V al u e of P ote nti al Cli nic al I m port a nc e/ O utsi d e N or m al 
R a n g e  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt”  t o titl e. 
P R Y, F NL * 
0 3 5 0  
I T T 
L B 1 4  
Listi ng of La b or at ory D at a with C h ar act er R esults  
I C H E3 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt”  t o titl e. 
P R Y, F NL * 
0 3 6 0  
I T T 
U R 2  
Listi ng of Uri nalysis D at a f or Su bj ect s wit h A ny V al ue of 
P ot e nti al Cli nic al I m p ort anc e  
I C H E3 
I ncl u d e “ A g e ( Y e ars)/ S ex/ Hi g h L ev el 
R ac e” t o t h e ri g ht of t h e S u bj ect I d. 
c ol u m n ( as i n ot h er listi n gs), ev e n t h o u g h 
n ot i ncl u d e d i n t h e U R 2 st a n d ar d m ock.  
R efr es h at t h e fi n al a n alysis t o i ncl u d e 1st 
T -c ell I nf usi o n d at a o nly, a p p e n d " –  
Excl u di n g R etr e at m e nt”  t o titl e. 
P R Y, F NL * 
C CI
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 8  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
Re pli c ati o n C o m p et e nt L e ntivir u s ( R C L)  
0 3 6 5  
mI T T  
L B 5 A  
Listi ng of V S V -G D N A ( R C L) D at a  
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d.  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt”  t o t h e 
titl e. 
P R Y, F NL * 
Bi o m ark er s a n d P h ar m a c oki n eti c  
0 3 6 8  
I T T 
[ N o n-St a n d ar d]  
BI O _ L 2  
Listi ng of I m m u no hist oc he mistry D at a  
 
P R Y  
0 3 8 0  
mI T T  
[ N o n-St a n d ar d]  
P K _ L 1  
Listi ng of P ersiste nc e D ata  
Ad d C m ax , Tm ax , d ur ati o n of d et ect a bl e 
p ersist e nc e, A U C 0 -2 8 d, ti m e t o l oss of 
2 5 %, 5 0 % a n d 7 5 % of p e ak c ell 
ex p a nsi o n.  
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e. 
I A 2, P R Y, 
F NL*  
C CI
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 5 9  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 3 8 5  
mI T T  
[ N o n-St a n d ar d]  
BI O _ L 4  
Listi ng of I nt e gr atio n Sit e A n alysis D at a  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt” t o t h e 
titl e. 
P R Y, F NL * 
0 4 0 0  
mI T T  
[ N o n-St a n d ar d]  
BI O _ L 3  
Listi ng of A nti -N Y -E S O -1 T C R(c 2 5 9) A ntib o dies ( A T A)  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt” t o t h e 
titl e. 
P R Y, F NL * 
P erf or m a n c e St at u s  
0 4 1 0  
I T T 
P S 5 A  
Listi ng of E C O G P erf or m a nc e St at us  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt” t o t h e 
titl e. 
I A 2, P R Y, 
F NL*  
E C G  
0 4 2 0  
I T T 
E G 3  
Listi ng of All E C G V al ues f or S u bj ects wit h A ny V al ue of 
P ot e nti al Cli nic al I m p ort anc e  
I D SL 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
U p d at e P CI f o ot n ot e t o us e o nc ol o gy 
d efi niti o n “ … Cli nic al I m p ort a nc e is d efi n e d 
as Gr a d e 2 or Hi g h er  ( Q Tc > 4 8 0), or Q Tc 
i ncr e as e of > 3 0 ms ec …” ( as i n O E C G 5 A).  
P R Y , F NL* 
C CI
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 6 0  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt” t o t h e 
titl e 
0 4 3 0  
I T T 
E G 5  
Listi ng of All E C G Fi ndi n gs f or S u bj ects wit h an A b n or m al 
E C G Fi n di ng  
I D SL 
I ncl u d e “ Hi g h L ev el R ac e” r at h er t h a n 
“ R ac e D et ail” si nc e l att er n ot c oll ect e d. 
“ Cli nic ally si g nific a nt c h a n g e fr o m 
b as eli n e” a n d “ Cli nic ally Si g nific a nt 
Ab n or m ality” i n t his st a n d a r d s h ell ar e n ot 
c oll ect e d i n t his st u dy s o c a n n ot b e 
r e p ort e d: dr o p fr o m dis pl ay. 
P R Y  
0 4 4 0  
I T T 
S A F E _ L 6  
Listi ng of Q Tc V al u es of P ot e nti al Cli nic al I m port a nc e  
List “ Hi g h L ev el R ac e” r at h er t h a n “ R ac e”.  
List by Q Tc c orr ecti o n m et h o d, B az ett or 
Fri d erici a . 
P R Y  
Vit al Si g n s  
0 4 5 0  
I T T 
O V T 7 A  
Listi ng of Vital Si gns wit h Val ues of P ot enti al Cli nic al 
I m p ort a nc e 
I D SL 
I n a d diti o n t o O V T 7 A s p ecifi e d vit al si g ns, 
i ncl u d e “ R es pir at ory R at e ( br e at hs/ mi n)”. 
P R Y, F NL*  
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 6 1  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
I ncl u d e f o ot n ot e f or bl o o d pr ess ur e gr a d e 
c ol u m ns p er I D S L s p ec. of "[ 1] Gr a d es 
w er e d eriv e d b as e d o n n u m eric crit eri a as 
d efi n e d i n C T C A E V 4. 0 3 a n d di d n ot t ak e 
i nt o c o nsi d er ati o n of cli nic al si g ns or 
sy m pt o ms, c o nc o mit a nt m e dic ati o n us a g e 
w hic h is n e e d e d f or t h e fi n al gr a d e 
ass oci at e d wit h t h e a dv ers e ev e nt."  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  Excl u di n g R etr e at m e nt” t o t h e 
titl e. 
Re s p o n s e  
0 4 6 0  
mI T T / All 
Ev al u a bl e  
R E 1 2  
Listi ng of I nv esti g ator-Ass ess ed S u bj ect B est R es p o ns e f or 
I nt eri m R evi e w ( R E CI S T 1. 1 Crit eri a ) 
Sort by T -c ell i nf usi o n d at e. 
Us e mI T T f or I A 2  
a n d All Ev al u a bl e f or I F A  
I F A, I A 2 
0 4 9 0  
I T T 
R E 5  
Listi ng of I nd e p e nd e nt R evi e wer -Ass ess e d R es p o ns es 
wit h o ut  a n d wit h C o nfir m atio n ( R E CI S T 1. 1  Crit eri a ) 
D o n ot i ncl u d e t h e o pti o n al “ C A[ 2]” 
(Pr o gr essiv e Dis e as e by cli nic al 
ass ess m e nt ) or “ Or g a ns of P D” c ol u m ns. 
R at h er t h a n o n e “ B est R es p” r o w, i ncl u d e 
t w o, o n e “ B est U nc o nfir m e d R es p o ns e”, 
t h e s ec o n d “ B est C o nfir m e d R es p o ns e”. 
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e . 
P R Y, F NL*  
0 5 0 0  
I T T 
R E 5  
Listi ng of I nv esti g ator -Ass ess ed R es p o ns es with o ut  an d 
wit h C o nfir mati o n ( R E CI S T 1.1  Crit eri a ) 
D o n ot i ncl u d e t h e o pti o n al “ C A[ 2]” 
(Pr o gr essiv e Dis e as e by cli nic al 
ass ess m e nt ) or “ Or g a ns of P D” c ol u m ns. 
P R Y, F NL*  
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 6 2  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
R at h er t h a n o n e “ B est R es p” r o w, i ncl u d e 
t w o, o n e “ B est U nc o nfir m e d R es p o ns e”, 
t h e s ec o n d “ B est C o nfir m e d R es p o ns e”. 
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e . 
Ti m e t o Ev e nt  
0 5 1 0  
mI T T  
T T E9  
Listi ng of  I nv esti g ator-Ass ess ed Ti m e to R es p ons e  
( R E CI S T 1. 1 Crit eri a ) 
Us e T -c ell i nf usi o n d at e 
I ncl u d e o pti o n al “ A g e/ S ex/ R ac e” c ol u m n 
wit h “ Hi g h L ev el R ac e” r at h er t h a n “ R ac e 
D et ail” si nc e l att er n ot c oll ect e d.  
O mit “ St at us” fr o m t h e h e a d er.  
I ncl u d e o pti o n al “N e w A nti -C a nc er 
T h er a py St art D at e ” c ol u m n. 
As T T R is n ot a s urviv al a n alysis a n d ar e 
o nly listi n g ti m e t o r es p o ns e f or 
r es p o n d ers, r e m ov e “or C e ns ori n g” fr o m 
“ Ev e nt or C e ns ori n g D at e”. 
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e . 
I A 2, P R Y, 
F NL*  
0 5 2 0  
mI T T  
T T E9  
Listi ng of  I nd e p e nd e nt R evi e wer-Ass ess e d  Ti m e to 
R es p o nse  ( R E CI S T 1. 1 Crit eria ) 
Us e T -c ell i nf usi o n d at e 
P R Y, F NL*  
C CI


CONFIDENTIAL 
 
 
208469 
163 
 
ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Include optional “Age/Sex/Race” column 
with “High Level Race” rather than “Race 
Detail” since latter not collected. 
Omit “Status” from the header. 
Include optional “New Anti-Cancer 
Therapy Start Date” column. 
As TTR is not a survival analysis and are 
only listing time to response for 
responders, remove “or Censoring” from 
“Event or Censoring Date”. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
0530 
mITT / All 
Evaluable 
TTE9 
Listing of Investigator-Assessed Duration of Response 
(RECIST 1.1 Criteria) 
Include optional “Age/Sex/Race” column 
with “High Level Race” rather than “Race 
Detail” since latter not collected. 
Add Initial Confirmed Response 
Use mITT for PRY & IA2  
and All Evaluable for IFA 
Use T-cell infusion date 
Include optional “New Anti-Cancer 
Therapy Start Date” column. 
Include footnotes: 
• “Note: Duration of Response is defined 
as the interval between the initial date of 
confirmed response (Partial Response / 
Complete Response) and the date of 
progressive disease or death among 
subjects with a confirmed response per 
RECIST 1.1.” 
• 'Censored, follow-up ongoing' includes 
subjects that had not progressed or died 
IFA, IA2, PRY, 
FNL* 


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Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
but were still in interventional phase 
follow-up and had not initiated new anti-
cancer therapy. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
0540 
mITT 
TTE9 
Listing of Independent Reviewer-Assessed Duration of 
Response (RECIST 1.1 Criteria) 
Include optional “Age/Sex/Race” column 
with “High Level Race” rather than “Race 
Detail” since latter not collected. 
Add Initial Confirmed Response 
Use T-cell infusion date 
Include optional “New Anti-Cancer 
Therapy Start Date” column. 
Include footnotes: 
• “Note: Duration of Response is defined 
as the interval between the initial date of 
confirmed response (Partial Response / 
Complete Response) and the date of 
progressive disease or death among 
subjects with a confirmed response per 
RECIST 1.1.” 
• 'Censored, follow-up ongoing' includes 
subjects that had not progressed or died 
but were still in interventional phase 
follow-up and had not initiated new anti-
cancer therapy. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
0550 
mITT 
TTE9 
Listing of Investigator-Assessed Progression Free Survival 
(RECIST 1.1 Criteria) 
Include optional “Age/Sex/Race” column 
with “High Level Race” rather than “Race 
Detail” since latter not collected. 
IA2, PRY, 
FNL* 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 6 5  
 
I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e 
S h ell  
Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
Us e T -c ell i nf usi o n d at e 
I ncl u d e o pti o n al “N e w A nti -C a nc er 
T h er a py St art D at e ” c ol u m n. 
I ncl u d e f o ot n ot e: 
•  ' C e ns or e d, f oll o w-u p o n g oi n g' i ncl u d es 
s u bj ects t h at h a d n ot pr o gr ess e d or di e d 
b ut w er e still i n i nt erv e nti o n al p h as e 
f oll o w-u p a n d h a d n ot i niti at e d n e w a nti -
c a nc er t h er a py. 
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e.  
0 5 6 0  
mI T T  
T T E9  
Listi ng of I nd e p e nd e nt R evi e wer-Ass ess e d  Pr ogr essi o n 
Fr e e S urviv al  ( R E CI S T 1. 1 Crit eri a ) 
I ncl u d e o pti o n al “ A g e/ S ex/ R ac e” c ol u m n 
wit h “ Hi g h L ev el R ac e” r at h er t h a n “ R ac e 
D et ail” si nc e l att er n ot c oll ect e d.  
Us e T -c ell i nf usi o n d at e 
I ncl u d e o pti o n al “ N e w A nti -C a nc er 
T h er a py St art D at e ” c ol u m n. 
I ncl u d e f o ot n ot e: 
•  ' C e ns or e d, f oll o w-u p o n g oi n g' i ncl u d es 
s u bj ects t h at h a d n ot pr o gr ess e d or di e d 
b ut w er e still i n i nt erv e nti o n al p h as e 
f oll o w-u p a n d h a d n ot i niti at e d n e w a nti -
c a nc er t h er a py. 
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e . 
P R Y, F NL*  
C CI


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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Exclude optional “New Anti-Cancer 
Therapy Start Date” column. 
Include retreatment data, flag mITT2 
subjects with an asterisk, and footnote: "* 
= mITT2 subjects.  Append "Including 
Retreatment" to the title. 


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14.12.14. Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Disease Characteristics 
0580 
ITT 
DC3 
Listing of Disease Characteristics at Initial Diagnosis 
Report Primary Neoplasm Type Under 
Study, location of disease, date of initial 
diagnosis / time since initial diagnosis to 
screening (months), % of myxoid cells, % 
of round cells, histological grade, stage, 
and reciprocal chromosomal translocation. 
Add footnote “Time from initial diagnosis 
to date of screening informed consent is 
displayed.” 
PRY 
0590 
ITT 
[Non-Standard] 
POP_L4 
Listing of Disease Characteristics at Screening 
Report HLA status (date, allele 1, allele 2), 
NY-ESO-1 biopsy date and status, stage, 
date of metastatic disease / time since 
metastatic disease to screening (months), 
and number of radiotherapy / systemic 
therapy regimens prior to lymphodepletion 
 
Refresh at the final analysis and only 
include anti-cancer radiotherapy up until 
end of first interventional phase and 
append " – Excluding Retreatment” to 
the title. 
PRY, FNL 
Anti-Cancer Therapy 
0600 
ITT 
AC6 
Listing of Prior Systemic Anti-Cancer Therapy 
Include prior sub-phase (per Appendix 4) 
and flag bridging therapies. 
Include “Best Response” (from eCRF) but 
not “Reason for Stopping” (as not 
collected for prior systemic therapy). 
PRY 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 6 8  
 
N o n -I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e S h ell  Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 6 1 0  
I T T 
A C 7  
Listi ng of A nti -C a nc er Radi ot her a py  
I ncl u d e pri or s u b-p h as e or “o n -st u dy” ( p er 
Ap p e n dix 4 ). 
I ncl u d e “ D os e” b ut n ot “ B est R es p o ns e” 
( as n ot c oll ect e d f or pri or r a di ot h er a py). 
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e a nti-c a nc er r a di ot h er a py u p u ntil 
e n d of first i nt erv e nti o n al p h as e, a n d 
a p p e n d "  –  E xcl u di n g Retreat me nt” t o 
t h e titl e. 
P R Y, F NL * 
0 6 2 0  
I T T 
F A C 3  
Listi ng of O n -St u dy A nti -C a ncer T h er a py  
I ncl u d e “ Ti m e t o Pr o gr essi o n ( D ays)” b ut 
n ot 
D ays)”.  
N ot e: I ncl u d es b ot h r a di ot h er a py a n d 
syst e mic t h er a py a n d s ur g ery .  
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e a nti-c a nc er t h er a py u p u ntil e n d of 
first i nt erv e nti o n al p h as e, a n d a p p e n d "  –  
E xcl u di n g Retreat me nt” t o t h e titl e. 
P R Y, F NL * 
C CI
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 6 9  
 
N o n -I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e S h ell  Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
M e di c al C o n diti o n s 
0 6 3 0  
I T T 
M H 2  
Listi ng of M e dic al C o nditi ons  
R e m ov e “ St at us” c ol u m n of st a n d ar d 
m ock a n d r e pl ac e wit h “ O n g oi n g ?” fl a g as 
c oll ect e d o n e C R F. 
P R Y  
S y m pt o m s, C o n c o mit a nt M e di c ati o n s a n d Pr o ce d ur e s Rel at e d t o  A d v er s e E ve nt s of S p e ci al I nt er e st  
0 6 4 2  
I T T 
[ N o n-St a n d ar d]  
S A F E _ L 4  
Listi ng of Sy m pt o ms an d M edic ati o ns R el ate d t o Gr aft 
v ers us H ost Dis e ase ( Gv H D) 
 
P R Y  
0 6 5 0  
I T T 
C M 3  
Listi ng of T ociliz u m a b  
List o nly t ociliz u m a b a d mi nistr ati o ns.  
R e pl ac e “ St art e d Pr e -Tri al” c ol u m n wit h 
“ Pri or / C o nc o mit a nt” (i d e ntifi e d p er 
Ap p e n dix 4 ). 
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e 1st T-c ell i nf usi o n d at a, a n d 
a p p e n d "  –  E xcl u di n g Retreat me nt” t o 
t h e titl e. 
I A 2, P R Y, 
F NL * 
C CI
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 7 0  
 
N o n -I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e S h ell  Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
S ur gi c al Pr o c e d ure s  
0 6 6 0  
I T T 
O S P 3  
Listi ng of Pri or C a nc er -R elat ed S ur gic al Pr oc ed ur es  
List S ur g ery I nt e nt a n d Sit e a n d  D at e of 
Sur g ery.  
I ncl u d e pri or s u b-p h as e or “o n -st u dy” ( p er 
Ap p e n dix 4 ) i n pl ac e of “ Ti m e P oi nt”. 
I ncl u d e f o ot n ot e: “ S ur g ery I nt e nt is n ot 
c oll ect e d f or pr oc e d ur es r ec or d e d at t h e 
b as eli n e visit.”  
P R Y  
0 6 7 0  
I T T 
O S P 3  
Listi ng of O n -St u dy C a nc er -Rel at e d S ur gic al Pr oc ed ur es  
List Sit e a n d D at e of S ur g ery.  
I ncl u d e pri or s u b-p h as e or “o n -st u dy” ( p er 
Ap p e n dix 4 ) i n pl ac e of " Ti m e P oi nt". 
O mit “ S ur g ery I nt e nt” as n ot c oll ect e d o n 
o n -st u dy f or ms. 
R efr es h at t h e fi n al a n alysis a n d o nly 
i ncl u d e o n-st u dy s ur gic al pr oc e d ur es u p 
u ntil e n d of first i nt erv e nti o n al p h as e, a n d 
a p p e n d "  –  E xcl u di n g Retreat me nt” t o 
t h e titl e. 
P R Y, F NL * 
C CI


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 7 1  
 
N o n -I C H: Li sti n g s 
N o.  
P o p ul ati o n  
I D S L / 
E x a m pl e S h ell  Titl e   
Pr o gra m mi n g N ot e s  
D eli v er a bl e  
0 6 7 2  
I T T 
O S P 3  
Listi ng of R esectio n Bi opsi es  
Us e Listi n g 0 6 6 0 as b as e a n d:  
•  r e m ov e ti m e p oi nt, cl assific ati o n, a n d 
tr a nsiti o n s ur g ery c ol u m n. 
•  r e pl ac e “ S ur g ery I nt e nt” wit h ” Ty p e of 
Sa m pl e O bt ai n e d”, a n d “ Sit e of  S ur g ery” 
wit h “ A n at o mic al L oc ati o n”  
Ext e n d at fi n al a n alysis t o i ncl u d e 
r etr e at m e nt d at a, fl a g mI T T 2 s u bj ects wit h 
a n ast erisk, a n d f o ot n ot e: "* = mI T T 2 
s u bj ects. A p p e n d '/ R etr e at m e nt D ay' t o 
e ac h st u dy d ay a n d o nly p o p ul at e o n 
r ec or ds d uri n g r etr e at m e nt ass ess m e nt 
p eri o d . A p p e n d "I ncl u di n g R etr e at m e nt " 
t o t h e titl e 
P R Y, F NL  
Re s p o n s e 
0 6 8 0  
I T T 
L A 5  
Listi ng of I nv esti g ator -Ass ess ed L esio n Ass ess m e nts 
( R E CI S T 1. 1 Crit eri a) 
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e . 
I A 2, P R Y, 
F NL*  
0 6 9 0  
I T T 
L A 5  
Listi ng of I nd e p e nd e nt R evi e wer -Ass ess e d Lesio n 
Ass ess m e nts ( R E CI S T 1. 1 Crit eri a)  
R efr es h at fi n al a n alysis E X C L U DI N G 
r etr e at m e nt d at a a n d a p p e n d “ - Excl u di n g 
R etr e at m e nt” t o t h e titl e.  
P R Y, F NL*  
C CI


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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
0700 
ITT 
RE9 
Listing of Subjects with a Difference between Investigator-
Assessed and Independent Reviewer-Assessed Best 
Response (with Confirmation) (RECIST 1.1 Criteria) 
Do not include (optional) “Comment” 
columns. 
RE9 mock has “Best Response [1] without 
CT Scans…” for independent reviewer. 
Since the independent reviewer for this 
study does not assess response with and 
without CR scans, delete “without CT 
Scans” from column header. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
0710 
ITT 
RE7 
Listing of Response Assessments for Subjects with a 
Difference between Investigator-Assessed and Independent 
Reviewer-Assessed Best Response (with Confirmation) 
(RECIST 1.1 Criteria) 
Do not include the optional “CA[2]” 
(Progressive Disease by clinical 
assessment), “PD” or “Organs of PD” 
columns. 
Use “Planned Time” rather than “Time”. 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
0720 
ITT 
RE7 
Listing of Response Assessments for Subjects with a 
Difference between Investigator-Assessed and Independent 
Reviewer-Assessed Best Response (without Confirmation) 
(RECIST 1.1 Criteria) 
Do not include the optional “CA[2]” 
(Progressive Disease by clinical 
assessment), “PD” or “Organs of PD” 
columns. 
Use “Planned Time” rather than “Time”. 
PRY 


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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
Time to Event 
0730 
mITT 
OTTE2 
Listing of Comparison of Investigator-Assessed and 
Independent Reviewer-Assessed Progression Event Timing 
or Censoring Timing (RECIST 1.1 Criteria)  
Add “High Level Race” to Age/Sex 
column. 
Change randomization date to “Date of T-
cell Infusion” 
Include footnote: “Note: The time window 
for complete agreement in timing is 
plus/minus 7 days.” 
Refresh at final analysis EXCLUDING 
retreatment data and append “ - Excluding 
Retreatment” to the title. 
PRY, FNL* 
 


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14.13. 
Appendix 13: Example Mock Shells for Data Displays 
Data Display Specification will be made available on request. 
 


C O N FI D E N TI A L  
 
 
2 0 8 4 6 9  
1 7 5  
 
1 4. 1 4.  
A p p e n di x 1 4 : C o m bi n e d Pr ef err e d T er m s 
T h e c o m bi ne d ter ms f or Me d D R A Versi o n  2 4 . 1 are liste d bel o w . C ha n ges t o t he 
Me d D R A dicti o nar y ma y occ ur bet w ee n t he st art of t he st u d y a n d  t he ti me of re p orti n g 
a n d/ or e mer gi n g d ata fr o m o n -g oi n g st u dies ma y hi g hli g ht a d diti o nal c o m bi ne d ter ms , 
t heref ore t he list of c o m bi ne d preferre d ter ms will be base d o n t he s afet y re vie w tea m 
( S R T) a gree m e nts i n place at t he ti me of re p orti n g. 
C o m bi n e d T er m  
M e d D R A Pr ef err e d t er m  
P T C o d e  
A n a e mi a/ R ed bl oo d c ell co u nt d ecr e as e d  
A n a e mi a 
1 0 0 0 2 0 34  
 
R e d bl o o d c ell c o unt d ecr e ased  
1 0 0 3 8 1 53  
1 0 0 5 2 0 15  
 
Cyt oki ne st or m  
1 0 0 5 0 6 85  
Ac ut e G V H D - Skin  
Ac ut e gr aft v ersus host dis e ase i n 
ski n 
1 0 0 6 6 2 62  
Ac ut e G V H D - Gut ( Liv er a n d Int esti ne)  
Ac ut e gr aft v ersus host dis e ase i n 
liv er 
1 0 0 6 6 2 63  
 
Ac ut e gr aft v ersus host dis e ase i n 
i nt esti n e 
1 0 0 6 6 2 64  
Ac ut e G V H D  - Ot h er (L u n g, B o n e M arr o w, not 
s p ecifi e d) 
Ac ut e gr aft v ersus host dis e ase  
1 0 0 6 6 2 60  
 
Ac ut e gr aft v ersus host dis e ase or al  
1 0 0 8 3 5 13  
Chr o nic G V H D -  Ski n  
C hr o nic gr aft v ers us h ost dis eas e i n 
ski n 
1 0 0 7 2 1 59  
Chr o nic G V H D - G ut ( Liv er and I nt esti n e)  
C hr o nic gr aft v ers us h ost dis eas e i n 
liv er 
1 0 0 7 2 1 60  
 
C hr o nic gr aft v ers us h ost dis eas e i n 
i nt esti n e 
1 0 0 7 2 1 58  
Chr o nic G V H D Ot h er -  ( L u n g, B o n e M arr o w, n ot 
s p ecifi e d) 
C hr o nic gr aft v ers us h ost dis eas e  
1 0 0 6 6 2 61  
 
C hr o nic gr aft v ers us h ost dis eas e i n 
ey e 
1 0 0 8 3 7 57  
 
C hr o nic gr aft v ers us h ost dis eas e or al  
1 0 0 8 3 5 14  
 
C hr o nic gr aft v ers us h ost dis eas e i n 
l u n g 
1 0 0 8 6 0 41  
Uns p ecifi e d G V H D - Ski n  
Gr aft vers us h ost dise as e i n ski n  
1 0 0 6 4 6 75  
Uns p ecifi e d G V H D - G ut ( Liv er a n d I nt esti ne)  
Gr aft vers us h ost dise as e i n liv er  
1 0 0 6 4 6 76  
 
Gr aft vers us h ost  dise as e i n 
g astr oint esti n al tr act  
1 0 0 7 5 1 60  
Uns p ecifi e d G V H D - Ot h er (L un g, B o n e Marr o w, 
n ot s p ecifie d)  
Gr aft vers us h ost dise as e  
1 0 0 1 8 6 51  
 
Gr aft vers us h ost dise as e i n ey e  
1 0 0 7 4 5 63  
 
Gr aft vers us h ost dise as e i n lun g  
1 0 0 6 7 7 42  
 
Pr o p hyl axis a g ainst graft  v ersus h ost 
dis e as e  
1 0 0 5 3 2 39  
 
Tr a nsf usi o n ass oci ate d gr aft vers us 
h ost dis e as e  
1 0 0 7 0 8 95  
 
E n gr aft m e nt syn dr o m e  
1 0 0 5 0 6 84  
L e uk o pe ni a/ Whit e bl o o d c ell decr e ase d  
W hit e bl o o d cell c o u nt d ecre as e d  
1 0 0 4 7 9 42  
 
L e uk o pe ni a  
1 0 0 2 4 3 84  
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Combined Term 
MedDRA Preferred term 
PT Code 
Lymphopenia/Lymphocyte count decreased  
Lymphocyte count decreased 
10025256 
CD4 lymphocytes decreased  
10007839 
CD8 lymphocytes decreased  
10056283 
 
Lymphopenia 
10025327 
Neutropenia/Neutrophil count decreased  
Neutrophil count decreased 
10029366 
Neutropenia 
10029354 
Rash/Rash maculo-papular 
Rash maculo-papular 
10037868 
Rash 
10037844 
Rash erythematous 
10037855 
Thrombocytopenia/Platelet count decreased  
Platelet count decreased 
10035528 
Thrombocytopenia 
10043554 
 
 
 
Immune effector cell-associated neurotoxicity 
syndrome (ICANS) 
Immune effector cell-associated 
neurotoxicity syndrome 
10083347 
 
Encephalopathy 
10014625 
 


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14.15. 
Appendix 15: Adverse Event Collapsing Rules 
1. Collapsing AE Segments with a Common AE Preferred Term (PT) into Unique 
Events based on the Start and End Dates  
For each unique subject, the AE records (segments) with the same AE preferred term will 
be collapsed into one unique AE event based on the start and end dates below. 
1.1. Multiple AE Segments with Overlapped or Continuous Start/End Dates 
Multiple AE segments with a common preferred term (PT, 
variable=ADAE.AEDECOD) that occurred around the same time; defined as: 
If a segment starts no more than one day (i.e., ≤ 1 day) prior, on, or after the 
previous segment’s end date, it is considered as an ‘event’. 
If the gap between the start date of a segment and the end date of previous 
segment is greater than one complete day (i.e., > 1 day), then consider these 
segments as different events.  
If partial start or end dates for any AE segments, then consider these segments as 
separate events. 
*** NOTE: Handling of partial dates or completely missing dates 
Partial dates or completely missing dates will not be imputed.  
The reason for not using imputed dates is due to the small number of partial / or 
completely missing dates. Furthermore, using imputed dates might create 
additional error of up to 30 days off for the AE start or AE end dates, and can be 
up to 60 days off for the duration of AE.  
1.2. Sort Adverse Events (AE)  
For any AE event identified above: 
Sort the AEs segments by study ID (ADAE.STUDYID), unique subject ID 
(ADAE.USUBJID), AE preferred term (ADAE.AEDECOD), AE start date 
(ADAE.AESTDTC), and AE end date (ADAE.AEENDTC). The sorting will 
include all AE segments with complete or partial start / end dates. 
 


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1.3. 
Create Derived Variables in ADAE ADaM SAS Dataset 
Based on the ADAE dataset after sorting per step 1.2 above, for each unique 
subject, create the following derived variables in the ADAE ADaM SAS dataset: 
1) 
ANL01FL: Flag for the unique AE 
a) Collapsed AE Segments 
For collapsed AE segments. based on the ADAE dataset after 
sorting per step 1.2 above:  
• 
derive the flag variable: ANL01FL=”Y” on the first record 
for each collapsed AE (i.e. the earliest segment within 
each collapsed AE with the same ADAE.AEDECOD) . In 
case if the AE segment of the collapsed AEs started before 
Lymphodepletion and ending after it, then populate the 
ANL01FL=’Y’ on very first Treatment emergent record. If 
there is only one record (segment) which started before 
lymphodepletion and ended after lymphodepletion then 
populate ANL01FL=’Y’ on that record only.  
• 
Otherwise ANL01FL="" (Missing). 
 
b) AE Events Comprised of a Single Row (No Collapsing Needed) 
• 
derive the flag variable: ANL01FL=”Y” for each single 
segment AE event. 
 
2) 
EVTSEQ: Sequence number of each unique AE with the same PT 
Create a sequence number, EVTSEQ, for each unique AE within 
the same ADAE.AEDECOD. 
For each unique subject within each unique AE preferred term, this 
variable will be recorded as the sequential number to identify all 
unique adverse events (including both single segment events 
(i.e., no collapsing needed) and collapsed events from multiple 
segments) based on the sorting order chronologically 
addressed under step 1.2 above. 
a) Collapsed AE Segments 
Each collapsed AE and its corresponding composed segments will 
have the same sequence numbers (i.e., if multiple segments/records 
are qualified for being collapsed into one unique AE (i.e., all those 
records will have same value for the derived variable EVTSEQ for 
that corresponding subject within the same collapsed AE). 
b) Single Segment AE Records 


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Each single segment AE event (i.e., un-collapsed event) will have 
different unique sequence number separately . 
c) AE Segments with partial start or end dates  
Each AE segment with partial start or end dates will have different 
unique sequence number starting from 99XXX, where XXX=001, 
002, ...  
* NOTE: For those subjects who received 2 T-cell infusions, the sequential number will 
be based on both infusion periods combined (i.e., the assigned sequential number will be 
independent of T-cell infusion periods). 
3) 
EVTENDT: End Date for each unique AE  
a) Collapsed AE Segments 
• 
=ADAE.AENDT (end date) of the last segment of the collapsed 
event (i.e., the segment with the latest ADAE.AENDT within the 
same collapsed AE for each unique subject). 
• 
This should be populated on the segment with ANL01FL=’Y’ 
only (i.e., the segment with earliest ADAE.ASTDT of each 
collapsed AE). 
 
• 
Note: If any of the segments have missing end date (i.e., 
unresolved) then the derived EVTENDT will be missing, and 
hence cannot calculate duration of event (please see derived 
variable: EVTDUR under item 4) below). 
 
b) Single Segment AE Records 
=ADAE.AENDT (end date) of each single segment event (i.e. un-
collapsed record). 
 
4) 
EVTDUR: Duration of each unique AE 
a) Collapsed AE Segments when AE segment started on or after 
lymphodepletion or Un-collapsed AEs. 
• 
Collapsed AE Segments 
o Where ANL01FL=’Y’ then EVTDUR = AESTDT-
EVTENDT+ 1. 
o = Missing, if missing end date for the derived 
variable EVTENDT (i.e., AEOUT=unresolved with 
missing AEENDTC for any of the segments within 
the same collapsed AE). 
• 
Single Segment AE records 
o EVTDUR = AESTDT-EVTENDT (i.e., = 
AEENDT) + 1. 
o = Missing, if missing end date (i.e., missing 
AEENDT and hence EVTENDT due to 


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AEOUT=unresolved for the corresponding, single 
segment record (i.e., un-collapsed AE record). 
b) Collapsed AE Segments when AE segment started before 
lymphodepletion and ends after it. 
• 
Where ANL01FL=’Y’ then EVTDUR = 
LYMPHDT(Lymphodepletion date) - EVTENDT+ 1. 
• 
= Missing, if missing end date for the derived variable 
EVTENDT (i.e., AEOUT=unresolved with missing 
AEENDTC for any of the segments within the same 
collapsed AE). 
 
5) 
EVTOUT: Outcome of each unique AE  
a) Collapsed AE Segments 
Derive this variable for the record with ANL01FL=”Y” only 
• 
EVTOUT should be derived variable as worst output 
for an event based on the hierarchy: Fatal > Not 
Recovered/Not Resolved > Recovering/Resolving with 
sequale > Recovering/Resolving > Recovered/Resolved, 
with Fatal being the worst.  
b) Un-collapsed AE records 
• 
EVTOUT=ADAE.AEOUT for each unique, un-collapsed 
AE record.   
 
 
6) 
EVTREL: Relatedness of each unique AE to Study Drug 
a) Collapsed AE Segments 
Derive this variable for the record with ANL01FL=”Y” only 
• 
EVTREL=’Y’ when any of the segments within the same 
collapsed AE was related to any study drug (i.e., 
ADAE.AREL=”Y” for any segment within the same 
collapsed AE).   
• 
Otherwise EVTREL=”N” if all of the segments within the 
same collapsed AE were not related to any study drug 
(ADAE.AREL=”N”  for all segments within the same 
collapsed AE). 
b) Un-collapsed AE Records 
• 
EVTREL=’ADAE.AREL for each unique, un-collapsed AE 
record.  
 
7) 
 EVTSAE: Seriousness of each unique AE Event (take the worst) 
a) Collapsed AE Segments 
Derive this variable for the record with ANL01FL=”Y” only 
• 
EVTSAE=’Y’ when any of the segments within the same 
collapsed AE  EVENT(i.e., ADAE.AESER=”Y” for any 
segment within the same collapsed AE).   


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• 
Otherwise EVTSAE=”N” if all of the segments within the 
same collapsed AE were not SERIOUS 
(ADAE.AESER=”N”  for all segments within the same 
collapsed AE). 
b) Un-collapsed AE Records 
• 
EVTSAE=’ADAE.AESER for each unique, un-collapsed 
AE record.  
 
8) 
EVTSDY: Event start day  
a) Collapsed AE Segments when AE segment started before 
lymphodepletion and ends after it. 
Derive this variable for the record with ANL01FL=”Y” only  
• 
Populate as day on the study lymphodepletion started  w.r.t 
T -cell as follows: LYMPH1DT-TRTSDT. 
• 
If in case any of the date is missing ( 1st lymphodepletion 
date or t-cell infusion date use -8. 
b) Collapsed AE Segments when AE segment started on or after 
lymphodepletion. 
• 
EVTSDY =ASTDY.  
c) Un-collapsed AE Records  
• 
EVTSDY=ASTDY. 
 
9) 
EVTMGR: Maximum grade of each unique AE Event (take the 
worst) 
a) Collapsed AE Segments 
Derive this variable for the record with ANL01FL=”Y” only  
• 
Populate EVTMGR with grade out of each segment(record) 
within the event.  
b) Un-collapsed AE Records 
• 
EVTMGR=ADAE.AETOXGR for each unique, un-
collapsed AE record.  
Additional Notes: 
• 
For any collapsed AEs and single segment records with missing or partial start 
and/or end dates,  
o EVTDUR= missing and will be excluded from the calculation for the summary 
statistics of AE duration. 
 
• 
AOCCPFL: Flag for the first (ONSET) occurrence of preferred term  
o This variable is a GSK standard variable in the ADAE ADaM SAS data set, which 
can be used to capture the first AE onset date for each unique AE preferred term.  
o If there are multiple AEs (AEDECODs) within same AESI on the same date, 
select the record with the max. duration. This is as per the GSK std. Macro. 
Macro remove the missing dates records. 
o We are not creating the Last occurrence of AESI as can be done for sorting 
the AE start date and Duration and take the last record.  


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o For Onset Day and Last Onset Day, please use EVTSDAY for table 
programming. 
 

Prot_000.pdf: 
TMF-14208393 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
208469 
1 
 
TITLE PAGE 
Protocol Title: A Pilot Study of NY-ESO-1c259T Cells in Subjects with Advanced 
Myxoid/ Round Cell Liposarcoma 
Protocol Number: 208469 (ADP-0011-007) / Amendment 10  
Compound Number or Name: GSK3377794 (NY-ESO-1c259T, letestregene 
autoleucel, lete-cel) 
Development Phase: Phase 1 / 2 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
 
Regulatory Agency Identifying Number(s): 
EudraCT: 2016-002245-37 
IND: 14603 
 
Approval Date: 17-DEC-2021 
 
 
 
 
 
Copyright 2021 the GSK group of companies. All rights reserved. Unauthorized copying 
or use of this information is prohibited. 
 


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SPONSOR SIGNATORY 
Protocol Title: A Pilot Study of NY-ESO-1c259T Cells in Subjects with Advanced 
Myxoid/ Round Cell Liposarcoma 
Protocol Number: 208469 (ADP-0011-007) / Amendment 10 
Compound Number or Name: GSK3377794 (NY-ESO-1c259T, letestregene 
autoleucel, lete-cel) 
 
 
 
Carsten Goessl, MD 
Vice President 
Clinical Development, Cell and Gene Therapies 
Oncology Research and Development  
GlaxoSmithKline 
 
Date 
 
 
The signed page is a separate document. 
Medical Monitor Name and Contact Information: can be found in the Study 
Reference Manual 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Date of Original Protocol: 23 May 2016 
Amendment 
Version 
Date 
Reason for Change 
1 
02 
03-OCT-2016 
Change in scope to Phase I/II pilot study. See Section 
16.6 for further details 
2 
03 
24-JUL-2018 
The following changes have been made: 
• 
Updates to time periods that must elapse 
between cessation of various therapies prior to 
leukapheresis and prior to initiation of 
lymphodepleting chemotherapy (“wash-out” 
periods) 
• 
Typographical errors have been corrected and 
timings of assessments have been clarified 
• 
Option to increase the sample size, as well as 
the option to change the lymphodepletion 
regimen based on emerging data 
• 
Administrative changes to align with GSK 
processes and procedures. 
• 
Language relating to serious adverse event 
(SAE) reporting and safety monitoring has 
been updated. 
See Section 16.7 for further details 
3 
04 
17-OCT-2018 
 
Changes made to the protocol were requested by FDA 
as a result of safety events which included 2 reports of 
Guillain-Barré syndrome in subjects who have received 
chemotherapy and GSK3377794 during clinical trials. 
4 
5 
18-JUN-2019 
Clarification on definitions of enrolment and intent to 
treat population. 
5 
06 
13-DEC-2019 
The following updates have been made: 
• 
Addition/clarification of delayed AE definition 
• 
Revised guidelines for the management of 
CRS 
• 
Revised guidelines for the management of 
encephalopathy syndrome 
• 
Adjustment to lymphodepletion regimen for 
safety purposes 
See Section 16.10 for detailed list of changes details. 
6 
07 
17-FEB-2021 
The following changes have been made: 
• 
Update of primary endpoint to be ORR based 
upon investigator assessment rather than 
ORR based upon independent review resulting 
in consistency between interim and final 
analyses 
• 
Insertion of secondary endpoint of ORR as 
assessed by independent review 
See Section 16.11 for detailed list of changes 
7 
08 
17-FEB-2021 
The following changes have been made: 
Section 7.6 has been added describing the potential for 
retreatment for those subjects who have had a 
confirmed CR or PR or SD ≥3 months and have residual 
manufactured drug product for a second infusion. 
 


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Amendment 
Version 
Date 
Reason for Change 
8 
09 
18-MAY-2021 
• 
Changes to protocol have been made in 
reference to Dear Investigator Letter dated 
03 May 2021 and Protocol and ICF clarification 
memorandum dated 11 May 2021 regarding 
mitigations put in place on active studies of 
GSK3377794 (letetresgene autoleucel, lete-
cel), following the recent SAEs of fatal 
neutropenia (1 event) and decreased vision (1 
event)  
• 
See Section 16.13 for detailed list of changes 
 
9 
10 
04-NOV-2021 
• 
Changes to the protocol made in reference to 
Dear Investigator Letter dated 21 Oct 2021 
and Protocol and ICF clarification 
memorandum dated 25 Oct 2021 regarding 
safety mitigations implemented on active 
studies of GSK3377794. 
• 
See Section 16.14 for detailed list of changes 
10 
11 
17-DEC-2021 
• 
Changes made to subject eligibility criteria to 
allow second infusion with lete-cel 
(GSK3377794) in patients who have received 
other anticancer therapy after progression post 
first lete-cel infusion. 
• 
See Section 16.15 for detailed list of changes 
 
 
 


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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
SPONSOR SIGNATORY ................................................................................................ 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
TABLE OF CONTENTS .................................................................................................. 5 
1. 
BACKGROUND AND STUDY RATIONALE ........................................................... 22 
1.1. 
Adoptive T Cell Therapy ............................................................................. 22 
1.2. 
Adoptive Immunotherapy with NY-ESO-1 Specific T Cells and 
Supporting Data in Sarcoma ....................................................................... 23 
1.3. 
Myxoid/Round Cell Liposarcoma ................................................................ 24 
1.4. 
Rationale for NY-ESO-1c259T for Myxoid/ Round Cell Liposarcoma ......... 25 
2. 
TRIAL OBJECTIVES AND ENDPOINTS ................................................................ 26 
2.1. 
Trial Objectives and Endpoints ................................................................... 26 
3. 
INVESTIGATIONAL PLAN ..................................................................................... 28 
3.1. 
Overall Study Design .................................................................................. 28 
3.2. 
Components of Study Design ..................................................................... 29 
3.2.1. 
Study Phases .............................................................................. 29 
3.2.2. 
Screening for HLA and NY-ESO-1 ............................................... 29 
3.2.3. 
T-Cell Manufacturing ................................................................... 30 
3.2.4. 
Lymphodepletion ......................................................................... 31 
3.2.5. 
T-Cell Infusion ............................................................................. 31 
3.2.6. 
Rationale for NY-ESO-1c259T Cell Dose .................................... 32 
3.3. 
Target Enrolment and Study Duration ......................................................... 32 
3.4. 
Sites ........................................................................................................... 33 
3.5. 
Benefit: Risk Assessment ........................................................................... 33 
3.5.1. 
Benefit Assessment ..................................................................... 33 
3.5.2. 
Risk Assessment ......................................................................... 34 
3.5.3. 
Overall Benefit: Risk Conclusion .................................................. 36 
4. 
SELECTION OF STUDY POPULATION ................................................................ 36 
4.1. 
Subject Inclusion Criteria ............................................................................ 36 
4.2. 
Subject Exclusion Criteria ........................................................................... 39 
4.3. 
Completion of the Interventional Phase ...................................................... 42 
4.3.1. 
Long-Term Follow-up ................................................................... 43 
4.4. 
Subject Withdrawal ..................................................................................... 43 
5. 
STUDY TREATMENTS .......................................................................................... 45 
5.1. 
Leukapheresis ............................................................................................ 45 
5.2. 
Lymphodepleting Chemotherapy ................................................................ 45 
5.2.1. 
Fludarabine Dose Adjustment for Renal Impairment .................... 49 
5.2.2. 
Cyclophosphamide Dose Adjustment .......................................... 49 
5.2.3. 
Mesna .......................................................................................... 50 
5.3. 
T Cell Infusion ............................................................................................. 50 


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6. 
CONCOMITANT MEDICATION AND TREATMENT .............................................. 51 
6.1. 
Prohibited Concomitant Medication and Treatment ..................................... 51 
6.2. 
Permitted Concomitant Medication and Treatment ..................................... 52 
6.3. 
Restrictions ................................................................................................. 52 
6.3.1. 
Contraception .............................................................................. 52 
7. 
SCHEDULE OF ASSESSMENTS AND PROCEDURES ........................................ 56 
7.1. 
HLA and Antigen Screening ........................................................................ 56 
7.1.1. 
Tumor tissue requirements .......................................................... 56 
7.2. 
Screen Failures........................................................................................... 57 
7.3. 
Schedule of Procedures .............................................................................. 55 
7.4. 
Clinical Assessments and Procedures ........................................................ 66 
7.4.1. 
Demographics ............................................................................. 66 
7.4.2. 
Disease History............................................................................ 66 
7.4.3. 
Medical History ............................................................................ 66 
7.4.4. 
Physical Examination and Vital Signs .......................................... 66 
7.4.5. 
Performance Status ..................................................................... 66 
7.4.6. 
Clinical Safety Assessments ........................................................ 66 
7.4.7. 
Laboratory Assessments ............................................................. 67 
7.4.8. 
Cardiac Assessments .................................................................. 67 
7.4.9. 
Pulmonary Assessments ............................................................. 68 
7.4.10. 
Monitoring for Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) ................................................. 69 
7.4.11. 
Tumor Response Assessments ................................................... 69 
7.4.12. 
Long-Term Follow-up ................................................................... 70 
7.5. 
Correlative Studies and Research Assessments ......................................... 70 
7.5.1. 
Pharmacogenetics Sample .......................................................... 72 
7.5.2. 
Cytokine and Soluble Factors Analysis ........................................ 72 
7.5.3. 
Tumor Biopsies ............................................................................ 72 
7.5.4. 
NY-ESO-1c259T TCR+ Cell Persistence .................................... 73 
7.5.5. 
NY-ESO-1c259T TCR+ Cell Phenotype and Activity ................... 73 
7.5.6. 
Liquid Biopsy Collection and Analysis .......................................... 74 
7.5.7. 
Request for Autopsy for Death Following Administration of 
Gene Transfer Agents.................................................................. 74 
7.6. 
Retreatment ................................................................................................ 75 
7.6.1. 
Benefit:Risk Assessment ............................................................. 76 
7.6.2. 
Lymphodepletion and T-Cell Infusion ........................................... 77 
7.6.3. 
Study Procedures ........................................................................ 77 
7.6.4. 
Completion of Retreatment / Second Treatment 
Interventional Phase .................................................................... 77 
7.6.5. 
Long-Term Follow-Up .................................................................. 77 
7.6.6. 
Response Assessment ................................................................ 77 
7.6.7. 
Objectives .................................................................................... 78 
7.6.8. 
Statistical Methods ....................................................................... 78 
7.6.9. 
Retreatment Study Populations ................................................... 78 
8. 
SUPPORTIVE CARE GUIDANCE .......................................................................... 78 
8.1. 
T Cell Infusion Symptom Management ....................................................... 79 
8.2. 
Infection ...................................................................................................... 79 
8.2.1. 
Pneumocystis Carinii Pneumonia ................................................ 79 
8.2.2. 
Herpes Simplex and Varicella-Zoster ........................................... 79 
8.2.3. 
Cytomegalovirus .......................................................................... 79 


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8.2.4. 
Hepatitis B Prophylaxis ................................................................ 80 
8.2.5. 
Treponema .................................................................................. 80 
8.2.6. 
Other Anti-Microbial Prophylaxis .................................................. 80 
8.3. 
Hematologic and Blood Product Support .................................................... 80 
8.3.1. 
Blood Product Irradiation ............................................................. 80 
8.3.2. 
CMV Screened Blood Products ................................................... 81 
8.4. 
Management of Autoimmunity .................................................................... 81 
8.5. 
Management of Cytokine Release Syndrome ............................................. 81 
8.6. 
Management of Graft-versus-Host Disease (GvHD) ................................... 84 
8.6.1. 
Diagnosis of GvHD ...................................................................... 85 
8.6.2. 
Grading of GvHD ......................................................................... 86 
8.6.3. 
Management of GvHD ................................................................. 87 
8.7. 
Chemotherapy Symptom Management ....................................................... 88 
8.7.1. 
Management of Neutropenia........................................................ 88 
8.7.2. 
Management of Pancytopenia with Bone Marrow Failure / 
Aplastic Anemia ........................................................................... 89 
8.7.3. 
Management of Guillain-Barré Syndrome (GBS) ......................... 90 
9. 
RECORDING ADVERSE EVENTS ........................................................................ 92 
9.1. 
Time Period for Collecting AE and SAE Information ................................... 93 
9.2. 
Definition of Adverse Event ......................................................................... 93 
9.2.1. 
Assessment of Intensity ............................................................... 94 
9.2.2. 
Assessment of Causality .............................................................. 94 
9.3. 
Reporting Serious Adverse Events (SAEs) ................................................. 95 
9.4. 
Reporting Criteria During Long Term Follow-Up (Years 1-15) ..................... 96 
9.5. 
Progression of Underlying Malignancy ........................................................ 98 
9.6. 
Regulatory Reporting Requirements for SAEs ............................................ 98 
9.7. 
Cardiovascular and Death Events ............................................................... 98 
9.7.1. 
Definition of Cardiovascular Events ............................................. 99 
9.8. 
Management of Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) ..................................................................................... 99 
9.8.1. 
Grading of ICANS ...................................................................... 100 
9.8.2. 
Management of ICANS .............................................................. 101 
9.9. 
Pregnancy ................................................................................................ 103 
9.10. 
Preexisting Condition ................................................................................ 104 
9.11. 
Laboratory Test Abnormalities as Adverse Events .................................... 104 
10. SAFETY MONITORING ....................................................................................... 105 
10.1. 
Safety Review Team ................................................................................. 105 
10.1.1. 
Mandated Study Pause Due to GBS .......................................... 105 
10.2. 
Stopping Rules ......................................................................................... 105 
10.3. 
Monitoring and Management of Replication-Competent Lentivirus 
(RCL) ........................................................................................................ 106 
10.3.1. 
Testing for RCL in clinical studies .............................................. 107 
10.3.2. 
Safety Monitoring - Results ........................................................ 107 
10.3.3. 
Persistence and Insertional Oncogenesis Testing and 
Monitoring .................................................................................. 107 
10.3.4. 
Testing for Persistence of Gene Marked Cells in Clinical 
Studies ...................................................................................... 108 
10.3.5. 
Testing for Insertional Oncogenesis ........................................... 108 
10.3.6. 
Monitoring and management for Demyelinating 
Neuropathy and other Neurological events ................................ 109 


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11. STATISTICAL AND DATA ANALYSIS ................................................................. 109 
11.1. 
Study Populations ..................................................................................... 109 
11.2. 
Statistical Methods for Interim Analysis ..................................................... 109 
11.3. 
Statistical Methods for Efficacy Endpoints................................................. 110 
11.4. 
Statistical Methods for Safety Parameters ................................................ 111 
11.5. 
Other Analyses ......................................................................................... 112 
12. CLINICAL SUPPLIES ........................................................................................... 112 
12.1. 
Packaging and Labelling ........................................................................... 112 
12.2. 
Standard Policies and Product Return ...................................................... 112 
12.3. 
Storage and Handling ............................................................................... 113 
12.4. 
Product Accountability .............................................................................. 113 
13. DATA HANDLING AND RECORD KEEPING ....................................................... 113 
13.1. 
Data Management .................................................................................... 113 
13.2. 
Case Report Forms .................................................................................. 114 
13.3. 
Site Documentation and Source Data ....................................................... 114 
13.4. 
Data Retention and Availability ................................................................. 115 
14. STUDY MONITORING ......................................................................................... 115 
14.1. 
Audits and Inspections .............................................................................. 115 
15. REGULATORY AND ETHICAL CONSIDERATIONS ........................................... 116 
15.1. 
Competent Authority Submissions ............................................................ 116 
15.2. 
Independent Ethics Committees ............................................................... 116 
15.3. 
Local Regulations/Declaration of Helsinki ................................................. 116 
15.4. 
Informed Consent ..................................................................................... 116 
15.5. 
Confidentiality ........................................................................................... 117 
15.6. 
Protocol Adherence .................................................................................. 117 
15.7. 
Study Suspension, Study Termination and Study Completion................... 117 
15.8. 
Public Posting of Study Information .......................................................... 118 
15.9. 
Clinical Study Report ................................................................................ 118 
15.10. Publication Policy ...................................................................................... 118 
16. APPENDICES ...................................................................................................... 119 
16.1. 
List of Abbreviations and Definitions of Terms .......................................... 119 
16.2. 
ECOG Performance Status ....................................................................... 122 
16.3. 
Laboratory Tests and ECG ....................................................................... 123 
16.4. 
RECIST 1.1 Criteria for Evaluating Response in Solid Tumors ................. 124 
16.5. 
Liver Safety Required Actions and Follow up Assessments ...................... 130 
16.6. 
Summary of Changes from Protocol Version 1.0 to Version 2.0 ................ 132 
16.7. 
Summary of Changes from Protocol Version 2.0 to Version 3.0 ................ 134 
16.8. 
Summary of Changes from Protocol Version 3.0 to Version 4.0 ................ 136 
16.9. 
Summary of Changes from Protocol Version 4.0 to Version 5.0 ................ 137 
16.10. Summary of Changes from Protocol Version 5.0 to Version 6.0 ................ 139 
16.11. Summary of Changes from Protocol Version 6.0 to Version 7.0 ................ 143 
16.12. Summary of Changes from Protocol Version 7.0 to Version 8.0 ................ 145 
16.13. Summary of Changes from Protocol Version 8.0 to Version 9.0 ................ 146 
16.14. Summary of Changes from Protocol Version 9.0 to Version 10.0 .............. 148 
16.15. Summary of Changes from Protocol Version 10.0 to Version 11.0 ............ 150 
17. LIST OF REFERENCES ...................................................................................... 151 


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SYNOPSIS 
Title 
A Pilot Study of NY-ESO-1c259T Cells in Subjects with 
Advanced Myxoid/ Round Cell Liposarcoma 
Short Title 
NY-ESO-1c259T cells for Myxoid/ Round Cell Liposarcoma 
Protocol Number 
GSK208469 (ADP-0011-007) 
Phase 
I / II 
Methodology 
This is an open label pilot study of gene modified 
autologous T cells for the treatment of advanced myxoid/ 
round cell liposarcoma. 
Subjects with the HLA-A*02:01, HLA-A*02:05 and/or HLA-
A*02:06 allele, whose tumor expresses the NY-ESO-1 
antigen above the cut-off level according to the applied 
immunohistochemistry, and who meet study entry criteria 
will be eligible for enrollment. Following enrollment, subjects 
will undergo leukapheresis for collection of autologous cells 
for processing and manufacture into the NY-ESO-1c259 T cell 
investigational product. 
Once the NY-ESO-1c259T cells have been manufactured 
subjects will receive lymphodepleting chemotherapy via two 
possible options. Option 1 (first 10 subjects) will involve 
lymphodepleting chemotherapy with fludarabine and 
cyclophosphamide on Days -7 to -5 and the study therapy 
by a single intravenous infusion on Day 1. Option 2 
(second 10 subjects) will involve lymphodepleting 
chemotherapy with fludarabine on Days -8 to -5 and 
cyclophosphamide on Days -7 to -5 and the study therapy 
by a single intravenous infusion on Day 1. In Option 2, 
dose and regimen for lymphodepleting chemotherapy will 
be adjusted for subjects ≥60 years of age. There is no 
Day 0 in this protocol. Lymphodepletion may be given as 
outpatient treatment. The T cell infusion should be given 
as an inpatient procedure. Subjects may be hospitalized 
for follow-up care post T-cell infusion at the discretion of 
the investigator. Subjects will receive growth factor 
support with granulocyte colony stimulating factor (G-CSF) 
from 24 hours following lymphodepleting chemotherapy 
until neutrophil count recovery. 
Subjects will have the following study visits: Screening 
(visits 1 and 2), Leukapheresis, Baseline (Day -14 to Day -
9), Lymphodepleting Chemotherapy (Day -8 or -7 to Day -
5), NY-ESO-1c259T cell infusion and immediate post infusion 
monitoring (Day 1 through Day 8), weekly until Week 6 post 
infusion, at 8, 10, 12, 16, 20 and 24 weeks, and then every 
3 months until disease progression, death or until 2 years 
after NY-ESO-1c259T cell infusion, whichever is shorter. 
Subjects will undergo disease monitoring by MRI or CT 
scan at screening, baseline, 4, 8, 12 and 24 weeks, and 
then every 3 months until progression of disease or until 2 


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years after NY-ESO-1c259T cell infusion, whichever is 
shorter. Investigators will assess tumor response according 
to RECIST v1.1 for clinical decision making and for 
determination of the primary endpoint. Scans will also be 
sent to a vendor for independent assessment of tumor 
response according to RECIST v1.1. Scans will be held 
until review requested by Sponsor. 
A tumor specimen (most recent archival or fresh biopsy) 
will be required to screen for NY-ESO-1 expression prior 
to leukapheresis. Tumor biopsies for research studies will 
be requested at Baseline (if a fresh biopsy was acquired at 
Screening another biopsy need not be taken at Baseline), 
Week 8 and upon disease progression with the exception 
for subjects with no safely accessible tumor tissue. 
Subjects who have received NY-ESO-1c259T cell infusion 
will complete the interventional phase of the study upon 
disease progression, death or having been followed-up for 
2 years after NY-ESO-1c259T cell infusion, whichever is 
shorter. NY-ESO-1c259T cell infused subjects who are alive 
on completing or withdrawing from the interventional 
phase will continue to be monitored in one of two ways: 
either via transfer to the Long Term Follow-Up (LTFU) 
protocol GSK208750 (ADP-0000-002) to monitor for gene 
therapy-related delayed adverse events for 15 years, in 
accordance with regulatory requirements for gene therapy 
clinical trials; or via continuance in the current trial until the 
LTFU protocol is available.  If necessary, and upon 
discussion with the Sponsor, those patients who have not 
progressed after 2 years on study and who are continuing 
in Study 208469 may continue to undergo response 
assessments per institutional standard of care.   
Subjects who have achieved a confirmed CR or PR or SD 
lasting ≥3 months in response to their first NY-ESO-1c259T 
cell infusion and have disease progression more than 3 
months post infusion may be offered the option for 
retreatment if they have sufficient residual manufactured 
cells for a second T cell infusion.  Retreatment involves all 
study procedures associated with the first infusion with the 
exception of leukapheresis and has exploratory efficacy 
and safety and tolerability objectives.  
Initially, 10 subjects will be treated/infused in this study. If 
further characterization of the treatment in this indication is 
required, a further 10 subjects may be treated/infused. 
The Sponsor may also decide to close the study at any 
time based on safety or efficacy. 
Study Duration 
Study enrollment is expected to continue for approximately 
24 months. The study will be considered completed when 
the last subject has been rolled over into the LTFU 
protocol GSK208750 (ADP-0000-002), has completed 
long term follow-up in this study, has declined LTFU, 


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has been withdrawn from this study (including lost to 
follow-up), or has died. 
Study Center(s) 
This is a multi-center study, including approximately 10 
sites. Additional sites may be added at the discretion of 
the Sponsor. 
Number of subjects 
The target enrollment for this trial is up to 20 subjects 
treated, depending on emerging data. Up to 20 subjects 
may be treated/infused in total. 
Objectives: 
Endpoints: 
Primary 
To evaluate the efficacy of autologous genetically modified 
T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 subjects with NY-ESO-1 expressing 
advanced myxoid/ round cell liposarcoma 
x
Overall Response Rate1 (ORR) per RECIST 
v1.1 by investigator assessment 
Secondary 
To evaluate the efficacy of autologous genetically modified 
T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 subjects with NY-ESO-1 expressing 
advanced myxoid/ round cell liposarcoma 
x
Overall Response Rate1 (ORR) per RECIST 
v1.1 by independent review 
x
Time to Response2 
x
Duration of Response2 
x
Progression Free Survival2 
To evaluate the safety and tolerability of autologous 
genetically modified T cells (NY- ESO-1c259T) in HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 subjects with 
NY-ESO-1 expressing advanced myxoid/ round cell 
liposarcoma 
x
AEs, including SAEs and AESIs 
x
Laboratory assessments, including chemistry 
and hematology   
x
Replication competent lentivirus (RCL) 
x
Instances of insertional oncogenesis 
x
Incidence of anti-NY-ESO-1c259T antibodies 
x
ECG 
To characterize the in vivo PK profile (levels, expansion, 
persistence) of NY-ESO-1 specific (c259) cells 
x
Maximum transgene expansion (Cmax) 
x
Time to Cmax (Tmax) 
x
Area under the time curve from zero to time t 
AUC(0-t), as data permit 
Exploratory 
CCI


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CCI


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Subject Inclusion Criteria  
A subject must meet the following inclusion criteria to be 
eligible for participation in this study: 
1. 
Subject (or legally authorized representative) has 
voluntarily agreed to participate by giving written 
informed consent in accordance with ICH GCP 
guidelines and applicable local regulations. 
2. 
Subject has agreed to abide by all protocol required 
procedures including study related assessments, 
and management by the treating institution for the 
duration of the study and long-term follow-up. 
3. 
Subject is ≥18 years of age at the time of signing the 
study informed consent 
4. 
Subject has a diagnosis of high grade myxoid 
liposarcoma / myxoid round cell liposarcoma 
confirmed histologically and by the presence of the 
reciprocal chromosomal translocation t(12;16) 
(q13;p11) or t(12; 22) (q13;q12). 
5. 
Subject has advanced (metastatic or inoperable) 
high grade myxoid liposarcoma / myxoid round cell 
liposarcoma. Inoperable refers to a tumor lesion in 
which clear margins cannot be obtained without 
leading to significant functional compromise 
6. 
Subject has measurable disease according to 
RECIST v1.1 criteria. 
7. 
Subject must be HLA-A*02:01, HLA-A*02:05 and/or 
HLA-A*02:06 positive. 
8. 
Subject's tumor (either the most recent archival 
specimen or a fresh biopsy) shows positive NY-
ESO-1 expression defined as ≥30% of cells that are 
2+ or 3+ by immunohistochemistry. All samples 
must have been pathologically reviewed by a GSK 
designated central laboratory. 
9. 
Subject must have previously received or be 
intolerant to anthracycline based therapy for 
advanced (metastatic or inoperable) disease. 
Subjects who received neoadjuvant/adjuvant 
anthracycline based therapy and progressed within 
6 months of completion of therapy will be eligible. 
10. Subject has an ECOG Performance Status 0-1. 
11. Subject has a left ventricular ejection fraction ≥45%. 
12. Subject is fit for apheresis and has adequate venous 
access for the cell collection. 
13. Male or Female. Contraceptive use by men or 
women should be consistent with local regulations 
regarding the methods of contraception for those 
participating in clinical studies. 
• 
Male Participants:  
 
Male participants are eligible to participate if 
they agree to the following during the 


TMF-14208393 
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intervention period starting at the first dose of 
chemotherapy for at least 12 months after 
receiving the T-cell infusion, or 4 months after 
there is no evidence of persistence/ gene 
modified cells in the subject’s blood, whichever 
is longer. 
• 
Refrain from donating sperm  
 
Plus either: 
• 
Be abstinent from heterosexual or homosexual 
intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) 
and agree to remain abstinent  
 
OR 
• 
Must agree to use contraception/barrier as 
detailed below: 
- 
Agree to use a male condom and 
should also be advised of the benefit 
for a female partner to use a highly 
effective method of contraception as a 
condom may break or leak when 
having sexual intercourse with a 
woman of childbearing (WOCBP) 
potential who is not currently pregnant. 
- 
Agree to use male condom when 
engaging in any activity that allows for 
passage of ejaculate to another 
person. 
 
• 
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 6.3.1  
 
OR 
• 
Is a WOCBP (as defined in Section 6.3.1) who 
will agree to use a barrier method (male 
condom) and use a contraceptive method that is 
highly effective (with a failure rate of <1% per 
year), as described in Section 6.3.1 during the 
intervention period and for at least 12 months 
after receiving the T-cell infusion.  In the event 
that there is evidence of persistence/gene-
modified cells in the participant’s blood, 
contraception usage should continue until 2 
consecutive persistence tests show that 
GSK3377794 is below the level of detection in 
blood.  WOCBP should also agree not to donate 
eggs (ova, oocytes) for the purpose of 
reproduction during this period. The investigator 


TMF-14208393 
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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 the first 
dose of study intervention. 
 
If a urine test cannot be confirmed as negative 
(e.g., an ambiguous result), a serum pregnancy 
test is required. In such cases, the participant 
must be excluded from participation if the serum 
pregnancy result is positive. 
14. Subject must have adequate organ function as 
indicated by the laboratory values in the table below: 
System 
Laboratory Value 
Hematological 
Absolute Neutrophil count 
(ANC) 
≥ 1.5 x109/L (without G-CSF 
support) 
Platelets 
≥ 100 x109/L 
Hemoglobin 
≥ 80 g/L (without 
transfusion support within 7 
days prior to leukapheresis) 
Coagulation 
Prothrombin Time or INR 
≤ 1.5x upper limit of normal 
(ULN) unless receiving 
therapeutic anticoagulation. 
Partial Thromboplastin Time 
(PTT) 
≤ 1.5x upper limit of normal 
(ULN) unless receiving 
therapeutic anticoagulation. 
Renal 
Calculated or measured 
creatinine clearance 1 
≥ 40 mL/min 
1. 
• 
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 
Chronic kidney disease Epidemiology 
Collaboration (CKD-EPI) equation and 
adjusting the result by multiplying with (Body 


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Surface Area [BSA]/1.73) to obtain a CrCl in 
mL/min.  
Step 1: estimated glomerular filtration rate (GFR) 
to be obtained from the CKD-EP) formula:  
 
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,  
a 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 creatinine clearance in 
mL/min 
Estimated CrCl (mL/min) = Estimated GFR 
(mL/min/1.73 m2) × BSA (m2) / 1.73   
To calculate the BSA for fludarabine dosing, use 
actual body weight. An adjusted body weight may 
be required for cyclophosphamide.  
• 
Participants ≥65 years of age must have renal 
function measured either by 24-hour urine 
creatinine collection or by nuclear medicine 
ethylenediaminetetraacetic acid (EDTA) GFR 
measurement, according to standard practice at the 
treating institution. 
. 
Subject Exclusion Criteria 
A subject meeting any of the following criteria is not 
eligible for participation in the study: 
1. 
Subject has received or plans to receive the 
following excluded therapy/treatment within the 
following periods prior to leukapheresis or 
lymphodepleting chemotherapy: 
Treatment/Therapy Required 
Wash-out 
Prior to 
Leukapheresis
Required Wash-
out Prior to 
Lymphodepletion
Cytotoxic 
chemotherapy 
3 weeks 
3 weeks 
Small 
Molecules/Tyrosine 
1 week 
1 week 


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kinase inhibitor (TKI) 
such as pazopanib. 
Treatment/Therapy 
Required 
Wash-out Prior 
to 
Leukapheresis 
Required Wash-
out Prior to 
Lymphodepletion 
Immune therapy 
(including 
monoclonal antibody 
therapy, checkpoint 
inhibitors, 
biologics) 
2 weeks 
2 weeks 
Experimental anti-
cancer Vaccine 
2 months in the 
absence of 
tumor 
response, or 
the subject 
should be 
excluded if their 
disease is 
responding to 
an 
experimental 
vaccine given 
within 6 months 
2 months in the 
absence of tumor 
response, or the 
subject should be 
excluded if their 
disease is 
responding to an 
experimental 
vaccine given 
within 6 months 
Gene therapy using 
an integrating vector 
Any use of 
previous gene 
therapy using 
an integrating 
vector is not 
permitted 
Any use of 
previous gene 
therapy using an 
integrating vector 
is not permitted 
Allogeneic 
hematopoietic stem 
cell 
transplant (HSCT) 
Any allogeneic 
HSCT is 
not permitted 
Any allogeneic 
HSCT is 
not permitted 
Corticosteroids or 
any other 
immunosuppressive 
therapy. Use of 
topical steroids is not 
excluded. 
2 weeks 
2 weeks 
Investigational 
treatment 
4 weeks 
4 weeks 
Duration of any other anti-cancer therapies must be 
discussed with the Sponsor Study Physician 
2. 
Radiotherapy within the following periods prior to 
leukapheresis or lymphodepleting chemotherapy 
(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 


TMF-14208393 
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investigator’s opinion would predispose patients to 
prolonged cytopenia after lymphodepletion): 
Treatment/Therapy Required 
Wash-out 
Prior to 
Leukapheresis
Required Wash-
out Prior to 
Lymphodepletion
Radiotherapy that 
involves the lung 
(V20 exceeding 30% 
lung volume) or 
pericardium (>20Gy). 
Exception for a 
lesser dose or 
radiation exposure to 
lung/mediastinum 
than stated, 
administered within 4 
weeks prior to 
lymphodepletion. 
Electron beam 
radiotherapy to 
superficial structures 
in the chest is 
permitted. 
N/A 
3 months 
Radiation to vital 
organs (e.g., liver, 
kidney) 
N/A 
4 weeks 
Radiation to the 
pelvis 
4 weeks 
4 weeks 
Whole Brain 
Radiotherapy 
(WBRT) or Brain 
Stereotactic 
Radiosurgery (SRS) 
N/A 
2 weeks 
Radiotherapy to the 
target lesions 
N/A 
3 months prior to 
lymphodepleting 
chemotherapy. A 
lesion with 
unequivocal 
progression may 
be considered a 
target lesion. 
There is no 
washout period for 
palliative radiation 
to non-target 
organs. 
 
3. 
Subject that has toxicity from previous anti-cancer 
therapy must have recovered to ≤ Grade 1 (except 
for non-clinically significant toxicities, e.g., alopecia, 
vitiligo). Subjects with Grade 2 toxicities that are 


TMF-14208393 
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deemed stable or irreversible (e.g., peripheral 
neuropathy) can be enrolled. 
4. 
Subject has history of allergic reactions attributed to 
compounds of similar chemical or biologic 
composition to fludarabine, cyclophosphamide or 
other agents used in the study. 
5. 
Subject has history of chronic or recurrent (within the 
last year prior to screening) severe autoimmune or 
immune mediated disease requiring steroids or other 
immunosuppressive treatments. 
6. 
Subject has known active brain or leptomeningeal 
metastases. Subjects with prior history of brain 
metastasis who have undergone local therapy (i.e., 
metastasectomy and/or radiation) and show no 
evidence of local recurrence or progression over the 
past 3 months prior to screening are eligible. 
7. 
Subject has other prior malignancy that is not in 
complete remission. 
8. 
Subject has electrocardiogram (ECG) showing 
clinically significant abnormality at Screening or an 
average QTc interval (Fridericia's or Bazett's 
formula) >450 msec in males and >470 msec in 
females (>480 msec for subjects with Bundle Branch 
Block (BBB)). 
9. 
Subject has uncontrolled intercurrent illness 
including, but not limited to: 
- 
Ongoing or active infection, including but 
not limited to systemic fungal infection; EBV 
and CMV IgG seropositive patients who 
have a positive PCR 
- 
Prior or active demyelinating disease 
- 
Clinically significant cardiac disease 
defined by congestive heart failure New 
York Heart Association (NYHA) Class 3 or 
Class 4 
- 
Uncontrolled clinically significant arrhythmia 
in last 6 months 
- 
Acute Coronary Syndrome (ACS) (angina 
or MI) in last 6 months 
- 
Interstitial lung disease (subjects with 
existing pneumonitis as a result of radiation 
are not excluded, however, subjects must 
not be oxygen dependent). 
10. Subjects who in the opinion of the Investigator will 
be unlikely to fully comply with protocol 
requirements. 
11. ALT>2.5 times ULN without documented liver 
metastases/tumor infiltration  
 
OR  


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Total Bilirubin > 1.5 x ULN (isolated bilirubin 
>1.5xULN is acceptable if bilirubin is fractionated 
and direct bilirubin <35%) 
12. Subject has active infection with HIV, HBV, HCV or 
HTLV as defined below: 
- 
Positive serology for HIV 
- 
Active hepatitis B infection as demonstrated 
by test for hepatitis B surface antigen. 
Subjects 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 test for hepatitis C RNA. 
Subjects 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 
- 
Positive serology for HTLV 1 or 2. 
Re-screening for infectious disease markers is 
not required at baseline (prior to 
lymphodepletion) 
13. Subject is pregnant or breastfeeding. 
Study Product, Dose, Route, Regimen 
The investigational product (IP) in this study is autologous 
genetically modified NY-ESO-1c259T cells (GSK3377794; 
letestregene autoleucel; lete-cel). 
The dose of NY-ESO-1c259T will be within the range of 1 x 
109 – 8 x 109 transduced cells. If the manufactured cell 
dose is less than the minimum dose of 1 x 109 transduced 
cells, 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. 
The cells will be administered by a single intravenous 
infusion on Day 1. Prior to administration of IP subjects 
treated under Option 1 will receive lymphodepleting 
chemotherapy consisting of fludarabine and 
cyclophosphamide on Days -7 to -5. Subsequently, 
subjects treated under Option 2 will receive 
lymphodepleting chemotherapy consisting of fludarabine 
on Days -8 to -5 and cyclophosphamide on Days -7 to -5. 
Reference therapy 
None 
Statistical Methodology 
After 10 evaluable subjects, response will be evaluated 
using Bayesian posterior predictive probabilities to inform 
clinical decision making to continue enrollment up to 20 
evaluable subjects. 


TMF-14208393 
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The primary analysis population for safety will be the 
intention to treat population (ITT), where appropriate, 
defined as all subjects who underwent leukapheresis, and 
the modified intention to treat population (mITT), where 
appropriate, defined as all subjects who received NY-
ESO-1c259T cell infusion. The primary analysis population 
for efficacy will be the mITT population. 
The primary endpoint for efficacy is Overall Response 
Rate (ORR) defined as the proportion of subjects with a 
confirmed complete response (CR) or confirmed partial 
response (PR) via investigator assessment per RECIST 
v1.1 criteria relative to the total number of subjects in the 
analysis population. 
ORR will be summarized by two-sided 95% confidence 
intervals using exact and Wilson methods. 95% 
(Bayesian) credible intervals may also be used to 
summarize the ORR. 
Time to event endpoints will be summarized and displayed 
graphically using Kaplan-Meier (K-M) methodology to 
estimate the median, and the 25th and 75th percentiles if 
data warrant. Two-sided 95% confidence intervals will be 
produced. Overall Survival will be assessed at fixed time 
points such as 1 year and 2 years using K-M methods if 
data warrant. 
Descriptive statistics will be provided for disposition, 
demographic and safety data. 
All adverse events will be listed and coded by MedDRA. 
The number and percent of subjects reporting any adverse 
events will be tabulated by system organ class and 
preferred term. Adverse events will be further classified by 
toxicity (using CTCAE Version 4.0). 
 


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1. 
BACKGROUND AND STUDY RATIONALE 
1.1. 
Adoptive T Cell Therapy 
Adoptive T cell therapy (ACT) is a treatment that uses a cancer subject’s own T 
lymphocytes with anti-tumor activity, expanded in vitro and re-infused into the subject. 
The ultimate objective of the process is the stimulation and expansion of potent and 
antigen-specific T cell immunity. There are numerous recent publications and reviews of 
adoptive T cell therapy [Kalos, 2013; Klebanoff, 2016; Maus, 2014; Morgan, 2010; 
Rosenberg, 2008]. 
The first observations that immune system engagement can lead to antitumor effects are 
often attributed to William Coley, who observed regression of sarcoma following severe 
bacterial infections in the 1890s. Further observations of the spontaneous regression of 
malignant melanoma lesions initially led to the use of T cells isolated from tumor-
infiltrating lymphocytes (TILs). Cell therapy using tumor-reactive TILs has resulted in 
approximately 50% objective clinical regression in melanoma subjects [Dudley, 2005; 
Besser, 2010]. This therapy, however, has been limited by the requisite surgery to 
procure tumor-reactive TIL, by ex vivo identification and expansion of these cells (TILs 
could be generated from only 50% of resected samples) and by the failure to reproducibly 
isolate similar cells from other cancer types. 
Adoptive transfer of bulk T lymphocytes, obtained from the periphery and expanded ex 
vivo to generate large numbers of cells prior to reinfusion into subjects, is an alternative 
strategy for adoptive T cell therapy [Rapoport, 2005]. However, tumor cells are well 
known to be immunologically selected for low antigen presentation and the majority of 
tumor antigens are normally expressed self-antigens. Hence, the natural T cell receptors 
(TCRs) that recognize self- tumor antigens may be of low affinity. The high tolerance to 
tumor antigens with normal and/or developmental expression combined with the potent 
immunosuppressive microenvironment often present at the tumor site is manifest in most 
cases by suboptimal activation in terms of antitumor activity such that ‘‘native’’ T cells 
may not be sufficient to induce tumor cell death in most subjects with advanced 
malignancy. Higher affinity TCRs allow T cells to respond to lower levels of antigen; this 
is important for tumor immunotherapy where the tumor microenvironment has adapted 
itself to reduce expression of antigen and also decrease expression of MHC class I 
molecules [Marincola, 2000; Barrett, 2009]. 
Gene-transfer-based strategies have therefore been developed to overcome the 
consequences of immune tolerance on the tumor-specific T cell repertoire. These 
approaches provide the potential to redirect T cells to effectively target tumors by the 
transfer of antigen-specific affinity- optimized T cell receptors. The majority of clinical 
approaches have employed T cells engineered to stably express transgenes via virus-
based transduction. Virus-mediated gene transfer approaches typically employ vectors 
that are derived from gamma retroviruses or more recently lentiviruses. 
Rational high-throughput genetic mutagenesis approaches have resulted in the ability to 
molecularly engineer TCRs with substantially higher affinities for target antigens. TCR-
based engineering approaches have certain inherent biological advantages, most notably 


TMF-14208393 
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that essentially all cellular proteins can be targeted because the approach is not limited to 
the targeting of cell surface epitopes, and the primary T cell activation signal is delivered 
in a physiological context, which may be relevant for optimal functionality of the infused 
T cells. Additional details are provided in the NY-ESO-1c259T Investigator Brochure. 
1.2. 
Adoptive Immunotherapy with NY-ESO-1 Specific T Cells 
and Supporting Data in Sarcoma 
NY-ESO-1 is a member of the cancer-testis family of tumor antigens. An HLA-A2 
binding peptide corresponding to amino acids 157 to 165 of NY-ESO-1 (SLLMWITQC) 
can be recognized by NY-ESO-1 reactive T cells and NY-ESO-1 epitopes are also 
recognized in the context of multiple HLA class II restriction elements. Several studies 
have demonstrated antibodies against NY-ESO-1 in patients with cancer. NY-ESO-1 may 
be particularly immunogenic. 
T cells recognizing the immunodominant class I restricted HLA-A2 binding peptide have 
been used to clone a specific T cell receptor capable of recognizing this MHC restricted 
antigen. Further genetic engineering enhanced the affinity of this T cell receptor toward 
the SLLMWITQC peptide bound to HLA-A2. The result is an enhanced affinity T cell 
receptor designated as 1G4α95:LY TCR (c259 TCR), which shows pre-clinical activity 
in vitro and in vivo against NY-ESO-1 expressing HLA-A2+ tumors. The c259 TCR 
mediates efficient recognition by CD8+ T cells of the HLA-A2 bound peptide 157-165 
and also mediates sufficient avidity to render CD4+ T cells capable of recognizing the 
157-165 peptide in the context of HLA-A2. This co-receptor independent recognition 
implies high avidity of the 1G4α95:LY TCR, a potentially important property of 
clinically active T cell receptors. The enhanced TCR binds with similar affinity to HLA-
A2 subtypes HLA-A*2:01, HLA-A*02:05, and HLA-A*02:06. 
NY-ESO-1c259 SPEAR T cells (Specific Peptide Enhanced Affinity Receptor T cells) 
were initially investigated in collaboration with Surgery Branch of the National Cancer 
Institute (NCI) where the T cells were modified using a retroviral vector, expanded using 
NCI cell processing methods and administered in conjunction with IL2 following a 
lymphodepleting chemotherapy regimen consisting of cyclophosphamide (60 mg/kg/day 
for two days) and fludarabine (25 mg/m2/day for five days). HLA-A2 subjects with NY-
ESO-1 expressing (2-4+ intensity ≥ 50% of cells) synovial sarcoma (n=18) and 
melanoma (n=20) were enrolled in the study [Robbins, 2014]. Objective clinical 
responses were reported in 11 of 18 (61%) synovial sarcoma subjects with estimated 
overall 3- and 5- year survival rates of 38% and 14% respectively. Objective clinical 
responses were also reported in 11 of 20 subjects (55%) with melanoma, while the 
corresponding estimated 3- and 5- year survival rates for subjects with melanoma were 
both 33%. 
The Adaptimmune/GSK sponsored clinical trial, “A Pilot Study of Genetically 
Engineered NY- ESO-1 Specific NY-ESO-1c259T in HLA-A2+ Patients with Synovial 
Sarcoma” (ADP-04511; NCT01343043) was designed based on the NCI study, following 
publication of the preliminary study data [Robbins, 2008]. The current study differs from 
the original NCI study in that the T cells are transduced using a lentiviral vector, the 
product is manufactured using a proprietary cell processing technique in a central GMP 


TMF-14208393 
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manufacturing site and the T cells are administered without the use of concomitant IL2. 
Confirmed responses (CR and PR) in Cohort 1 were observed in 6 of 15 subjects enrolled 
(40%), 6 of 12 (50%) subjects who received NY-ESO-1c259T and 6 of 10 (60%) subjects 
who received at least a billion transduced cells. The median duration of response (DOR) 
was approximately 31 weeks with a range of 13 weeks-72 weeks (data cut-off of 
31 August 2016). All subjects in this ongoing clinical trial, ADP-04511, are HLA-A2 
(HLA-A2*02:01, HLA-A*02:05, and/or HLA-A*02:06) positive subjects with NY-ESO-
1 expressing synovial sarcomas. 
A recent immunohistochemistry study of NY-ESO-1 expression in tissue microarrays of 
1132 intermediate and malignant mesenchymal tumors [Endo, 2015] confirmed strong 
expression (2 - 3+ in >50% tumor cells) in 49% of synovial sarcomas and also indicated 
expression in 88% of myxoid liposarcomas. This raises the possibility that myxoid 
liposarcomas may also be amenable to adoptive T cell therapy with NY-ESO-1c259T 
cells. 
1.3. 
Myxoid/Round Cell Liposarcoma 
Sarcomas are rare malignant tumors originating from mesenchymal cells and their 
precursors, and represent ~1% of all cancers in adults worldwide each year (10% of 
cancers in children, and 8% of cancers in adolescents) and ~2% of cancer related 
mortality [Singer, 2000; Amankwah, 2013]. It is estimated that 11,930 new soft tissue 
sarcomas will be diagnosed (6,610 cases in males and 5,320 cases in females) in the 
United States in 2015, and approximately 4,870 Americans (2,600 males and 2,270 
females) are expected to die of soft tissue sarcomas [Siegel, 2015]. Estimated incidence 
of soft tissue sarcoma in Europe averages 4 per 100,000 per year [Casali, 2009]. Soft 
tissue sarcomas (STS) consist of approximately 50 different histological subtypes. 
Myxoid/ round cell liposarcoma (MRCLS) 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 [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 


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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 and 
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 and 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 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 (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 2015 
prescribing information). 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]. 
1.4. 
Rationale for NY-ESO-1c259T for Myxoid/ Round Cell 
Liposarcoma 
Subjects with MRCLS who relapse after anthracycline-based therapy have few 
therapeutic options. The occurrence of diffuse and high intensity expression of 
NY-ESO-1, the anti-tumor activity of NY-ESO-1c259T in synovial sarcoma, combined 
with a manageable safety profile is the basis of this clinical trial designed to evaluate the 
activity and safety in myxoid/round cell liposarcoma (MRCLS). NY-ESO-1c259T has not 
previously been used for the treatment of MRCLS, therefore this pilot study will evaluate 
safety and efficacy in this indication. 


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Objectives 
Endpoints 
Primary 
To evaluate the efficacy of autologous genetically modified 
T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 subjects with NY-ESO-1 expressing 
advanced myxoid/ round cell liposarcoma 
x
Overall Response Rate1 (ORR) per RECIST v1.1 
by investigator assessment 
Secondary 
To evaluate the efficacy of autologous genetically modified 
T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 
and/or HLA-A*02:06 subjects with NY-ESO-1 expressing 
advanced myxoid/ round cell liposarcoma 
x
Overall Response Rate1 (ORR) per RECIST v1.1 
by independent review 
x
Time to Response2 
x
Duration of Response2 
x
Progression Free Survival2 
To evaluate the safety and tolerability of autologous 
genetically modified T cells (NY- ESO-1c259T) in HLA-
A*02:01, HLA-A*02:05 and/or HLA-A*02:06 subjects with 
NY-ESO-1 expressing advanced myxoid/ round cell 
liposarcoma 
x
AEs, including SAEs and AESIs 
x
Laboratory assessments, including chemistry 
and hematology   
x
Replication competent lentivirus (RCL) 
x
Instances of insertional oncogenesis 
x
Incidence of anti-NY-ESO-1c259T antibodies 
x
ECG 
To characterize the in vivo PK profile (levels, expansion, 
persistence) of NY-ESO-1 specific (c259) cells 
x
Maximum transgene expansion (Cmax) 
x
Time to Cmax (Tmax) 
x
Area under the time curve from zero to time t 
AUC(0-t), as data permit 
Exploratory 
CCI


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Objectives 
Endpoints 
1Overall Response Rate is based on confirmed responses determined at least 4 weeks post initial identification of 
response. 
2Secondary response endpoints may be based on investigator assessment and independent review.  
CCI


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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design 
This is a Phase I/II open label pilot study of genetically engineered NY-ESO-1c259 T in 
HLA- A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive subjects with NY-ESO-1 
expressing advanced (metastatic or inoperable) cytogenetically confirmed myxoid/ round 
cell liposarcoma. Inoperable refers to a tumor lesion in which clear margins cannot be 
obtained without leading to significant functional compromise. A maximum of 20 
subjects will be treated/infused on this study. 
Subjects will be screened for the presence of HLA-A*02:01, HLA-A*02:05, HLA-
A*02:06 and NY-ESO-1 expression on the tumor (Section 7.1). The Screening Phase of 
the study starts from the time the subject signs the study Screening Informed Consent 
Form until the subject attends for second screening following antigen positivity. The 
subject then signs the Treatment Informed Consent Form prior to any further study tests 
or procedures and transfers to the Interventional Phase of the study which runs from the 
time of treatment consent until disease progression, death or 2 years after 
NY-ESO-1c259T cell infusion, whichever is shorter (completion of the interventional 
phase, see Section 4.3). NY-ESO-1c259T cell infused subjects alive on completing or 
withdrawing from the interventional phase will continue to be monitored in one of two 
ways: either via transfer to the Long Term Follow-Up (LTFU) protocol GSK208750 
(ADP 0000-002) to monitor for gene therapy related delayed adverse events for 15 years, 
in accordance with regulatory requirements for gene therapy clinical trials; or via 
continuation in the current trial until the LTFU protocol is available. If necessary and 
upon discussion with the Sponsor, those patients who have not progressed after 2 years 
on study and who are continuing in Study 208469 may continue to undergo response 
assessments every 3 months as defined in Study 208469 per institutional standard of care.   
Subjects will be screened for enrolment into the study according to the eligibility criteria 
in Section 4. Following enrolment, subjects will undergo leukapheresis for collection of 
autologous cells for processing and manufacture into the NY-ESO-1c259T cell 
investigational product. Leukapheresis should be performed as soon as possible after the 
subject is determined to be eligible for study participation. 
Prior to the administration of lymphodepleting chemotherapy all eligibility criteria will 
be reconfirmed and baseline tumor assessment obtained. When the NY-ESO-1c259T cells 
are available, subjects will undergo lymphodepleting chemotherapy with 
cyclophosphamide and fludarabine (Section 5.2) followed by infusion of NY-ESO-
1c259T cells (Section 5.3) on Day 1. Lymphodepletion may be given as outpatient 
treatment. The T cell infusion should be given as an inpatient procedure. Subject may be 
hospitalized for follow-up care post T-cell infusion at the discretion of the investigator. 
Subjects will receive growth factor support with Granulocyte Colony Stimulating Factor 
(G-CSF) from 24 hours following lymphodepleting chemotherapy until neutrophil count 
recovery. 


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Efficacy, safety, and biomarker assessments to be conducted at each visit are outlined in 
the Schedule of Procedures (Table 4). Efficacy will be assessed by local and independent 
review using RECIST v1.1 criteria as described in Section 7.4.9 and Section 16.4. To 
allow time for the immune response to become apparent and for potential transient 
inflammatory reaction of the disease to the treatment (‘tumor flare’), response will not be 
assessed before 4 weeks post infusion of NY-ESO-1c259T, unless there is unequivocal 
clinical evidence of deterioration. 
Figure 1 
Schematic for Study GSK208469 
 
3.2. 
Components of Study Design 
3.2.1. 
Study Phases 
The study is divided into Screening and Interventional phases. The screening phase 
evaluates subjects for HLA type and tumor antigen expression. Subjects enter the 
Screening phase on signing the screening consent form at Visit 1. 
If the subject screens positive for the relevant HLA alleles and has adequate tumor 
antigen expression, they may enter the interventional phase of the study which contains 
all other study tests and procedures. Subjects enter the Interventional phase on signing the 
treatment consent form at Visit 2 and remain in this phase until completion or 
withdrawal, as described in Section 4.3 and Section 4.4. 
3.2.2. 
Screening for HLA and NY-ESO-1 
NY-ESO-1c259T specifically recognizes the HLA-A*02:01, HLA-A*02:05, and HLA-
A*02:06- restricted NY-ESO-1 peptide antigen HLA-A*02-SLLMWITQC; therefore, 
this protocol will select for subjects with these three HLA-A2 allelic variants and whose 
tumor expresses the NY-ESO-1 antigen. 


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The prevalence of HLA sub-types varies between populations. Information on the 
prevalence of HLA-A2 allelic variants in specific populations is available in the Allele 
Frequency Net Database (www.allelefrequencies.net). It is recommended that 
investigators review the database for HLA-A2 allelic variants relevant to the subject 
population at their site. 
3.2.3. 
T-Cell Manufacturing 
GSK3377794 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 
[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]).  
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).   
Selected qualified manufacturing sites will prepare the expanded T cells for subjects 
enrolled at all sites. Utilizing anti-CD3/CD28 mAb coated magnetic beads, T cells are 
enriched, activated and expanded in a closed system (12-14 days). T cells are then 
transduced with the lentiviral vector. The manufacturing process initiates in a static tissue 
culture bag, followed by transfer to a Wave bioreactor for additional expansion under 
perfusion conditions. At the end of the culture, cells are depleted of magnetic beads, 
washed, concentrated, and cryopreserved. Release testing takes approximately an 
additional 4 weeks. Therefore, cell product typically is ready to be returned to the site 
approximately 42-45 days after subject apheresis. Shipment to clinical sites will ideally 
be before the start of lymphodepleting chemotherapy, exceptions will be made for non-
US sites that are unable to store genetically modified cells. In these cases, the cells may 


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be shipped to the site immediately prior to the infusion and stored in the validated 
cryoshipper. After the ex vivo activation and expansion, the final cellular product is 
typically >90% T lymphocytes since the culture conditions do not support the growth of 
macrophages, NK or B cells. By the end of the culture period, B cells comprise 
approximately < 2%, NK cells comprise approximately < 2%, and macrophages 
approximately < 1% of the total culture. Additional details are provided in the NY-ESO-
1c259T Investigator Brochure. 
3.2.4. 
Lymphodepletion 
The incorporation of lymphodepletion prior to adoptive T cell therapy may enhance 
immune reconstitution by the transferred cells and increase tumor specific responses. 
Immune reconstitution is enhanced through homeostatic mechanisms that facilitate 
expansion of T lymphocytes [Baccala, 2005] and facilitate trafficking of the engineered T 
cells [Pinthus, 2004]. Lymphodepletion also enhances the activity of the adoptively 
transferred cells via the removal of inhibitory factors such as regulatory T cells [Wolf, 
2003] and can activate antigen presenting cells through the induction of inflammatory 
cytokines and induction of tumor apoptosis with resulting cross presentation of tumor 
antigens to T cells. 
Recent evidence suggests that preparation for successful engraftment and expansion of 
gene modified adoptive cellular therapy depends not just on the depth of cytoreduction 
but additionally on the specific action of some cytotoxic drugs. Recent studies in 
lymphoma, chronic leukemia and acute leukemia using adoptive cellular therapy 
including a chimeric antigen receptor showed increased T cell expansion, persistence and 
disease-free survival when fludarabine was added in to a previously cyclophosphamide-
only preparative regimen [Turtle, 2016]. Based on the results from our previous clinical 
research using combination fludarabine-cyclophosphamide lymphodepleting 
chemotherapy and the increasing evidence that fludarabine may be a necessary 
component, the lymphodepleting regimen in this study consists of fludarabine 
30mg/m2/day and cyclophosphamide 600mg/m2/day intravenously for three consecutive 
days. This regimen will be used for the first 10 subjects (Cohort 1). Based on emerging 
data and analysis, the lymphodepleting regimen for the subsequent 10 subjects (Cohort 
2), if expanded, was changed to fludarabine 30mg/m2/day for 4 days and 
cyclophosphamide 900mg/m2/day intravenously for 3 days, beginning on day -8. Age 
related modifications to the lymphodepletion regimen will be made as outlined in Section 
5.2. 
3.2.5. 
T-Cell Infusion 
The investigational product in this study is the infusion of autologous T cells transduced 
with lentivirus encoding enhanced TCR specific for NY-ESO-1 (see Section 5.3 for 
administration details). 


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3.2.6. 
Rationale for NY-ESO-1c259T Cell Dose 
Activity seems to be indirectly related to dose administered (depending also on cell 
expansion and persistence) although high T cell doses may be associated with an 
increased risk of adverse events (e.g., cytokine release). Total T cell doses up to ~100 x 
109 cells [Robbins, 2011] have been used although the actual products may differ 
depending on manufacturing methods. Conversely, doses as low as 0.015 x 109 (15 
million) cells may also be effective [Porter, 2011]. 
Current experience with NY-ESO-1c259T is with total cell doses in the range of ~<1 – 15 
x 109 transduced cells with a transduction level of ~18 – 75%. 
The dose of NY-ESO-1c259T will be within the range of 1 x 109 – 8 x 109 transduced 
cells, which will be administered by a single intravenous infusion on Day 1. The 
minimum transduced cell dose is 1 x 109 cells. If the manufactured transduced cell dose is 
less than the minimum dose, 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 total dose in the target range. 
3.3. 
Target Enrolment and Study Duration 
A target of 10 subjects infused with potential expansion up to 20 subjects is considered 
appropriate for evaluating preliminary efficacy (antitumor activity) and safety in this 
phase I/II study of subjects with a rare, orphan disease. 
Potential subjects will first sign a screening consent to screen for HLA and antigen 
testing. It is expected that approximately 50% of subjects will be HLA negative, and 20% 
of these subjects will be NY-ESO negative. Therefore, it is expected that up to 60 
subjects may sign the screening consent. Once HLA and antigen testing are confirmed, 
subjects will return for the second screening visit, at which time the treatment consent 
will be signed, and the remainder of eligibility requirements will be verified. Enrolled 
subjects will be considered those subjects who sign the treatment consent, meet all 
eligibility requirements, and undergo apheresis. Based on information gathered from the 
pilot sarcoma study, it is expected that there will be some subjects who undergo apheresis 
but do not receive manufactured cells. Therefore, in this study, approximately 26 subjects 
may be enrolled in order to obtain the target number of 20 subjects treated with 
manufactured product. Up to 13 subjects may be enrolled in order to obtain the target 
number of 10 subjects treated with manufactured product in Cohort 1, and up to 13 
subjects may be enrolled in order to obtain the target number of 10 subjects treated with 
manufactured product in Cohort 2. Once the target number of patients have manufactured 
product in each cohort, the study will be closed for enrolment and apheresis.  In the event 
that a subject has manufactured product and is not able to receive treatment, an apheresis 
slot may then be opened for a screen positive patient to be enrolled. 
Expansion from n=10 to a maximum of n=20 may be done to better characterize safety, 
efficacy and tolerability, based on the clinical evaluation of the emerging data (See 
Section 11). In addition, more subjects may be enrolled for those who do not receive the 


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minimum cell dose or who do not receive the T-cell infusion to better characterize safety, 
efficacy and tolerability as part of this expansion. 
The confirmed overall response rate per RECIST v1.1 by investigator review will be 
evaluated after the first 10 subjects are evaluable, defined as have been treated and had at 
least 3 post-baseline disease assessments or have progressed or died or were withdrawn 
from the study. 
In the event that 1 or no responses are observed in these 10 evaluable subjects from the 
first cohort then no further enrolment will occur.  
Once 10 subjects have been enrolled screening may continue but no further subjects will 
enroll, undergo leukapheresis or lymphodepletion until a decision is made to expand the 
study. As enrolment nears 10 subjects the Sponsor and Investigators will discuss whether 
further screening is appropriate. 
Criteria for suspending the study for safety are outlined in Section 10.2. 
The study will be considered completed when the last subject has been rolled over into 
the LTFU protocol GSK208750 (ADP-0000-002), has completed long term follow-up in 
this study, has declined LTFU, has been withdrawn from study (including lost to follow-
up), or died, as detailed in Section 4.3. 
3.4. 
Sites 
The study will be conducted in approximately 10 sites. The number of centers is 
necessary to ensure recruitment in this rare population. Additional sites may be added at 
the discretion of the Sponsor. 
3.5. 
Benefit: Risk Assessment 
The results of Clinical and Non-Clinical studies conducted with NY ESO-1c259T are 
summarized in the Investigator Brochure. This section outlines the potential benefits and 
risks, and the risk mitigation strategy for this study. 
3.5.1. 
Benefit Assessment 
The NY-ESO-1 cancer testis antigen is expressed in 80% of patients with MRCLS [Endo, 
2015]. This is the first study to evaluate the safety and efficacy of NY ESO-1c259T in 
MRCLS. 
A patient’s T cells can be genetically engineered to recognize tumor antigens. The TCR 
approach to engineered T cell therapy is attractive because TCRs are capable of 
recognizing not only cell surface proteins (as is the case with CARs) but also any internal 
protein, since TCRs recognize peptide fragments in the context of HLA. In addition, the 
TCR approach mimics the natural function of the T cell by recruiting the endogenous 
signaling molecules and adhering to correct spatial orientation between the T cell and its 


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target. These aspects may contribute to enhanced safety and activity of TCR engineered 
cells. 
Objective responses have been observed in subjects with sarcoma, myeloma and 
melanoma [Robbins, 2015; Rapoport, 2015; D'Angelo, 2015]. In subjects with 
unresectable synovial sarcoma, 12 subjects were treated with NY-ESO-1c259T and six 
responded (1 CR and 5 PR). Median duration of response was more than 6 months 
[D'Angelo, 2015]. In the NCI sponsored trial, 11 of 18 subjects (61%) with synovial 
sarcoma demonstrated objective clinical responses. The estimated overall 3- and 5-year 
survival rates for patients with synovial sarcoma were 38% and 14% respectively 
[Robbins, 2015]. 
MRCLS and synovial sarcoma share certain similarities in that they are both translocation 
sarcomas with a high intensity NY-ESO-1 antigen expression. The efficacy observed in 
synovial sarcoma supports the investigation of NY ESO-1c259T cells in patients with 
MRCLS. 
3.5.2. 
Risk Assessment 
The known safety profile of NY ESO-1c259T is updated annually in the Investigator 
Brochure. Current AEs are based on N=103 subjects enrolled as of January 2020. All 
subjects (100%) experienced at least 1 TEAE after infusion with GSK3377794 
(letestregene autoleucel; lete-cel). Most subjects (98%) had at least one Grade 3 AE; in 
83% of the subjects, the Grade 3 AEs were considered by the investigator to be related to 
GSK3377794 treatment. TEAEs which occurred in >50% of all subjects following 
GSK3377794 infusion were nausea (80%), anemia/RBC decreased (79%), 
neutropenia/neutrophil count decreased (79%), leukopenia/WBC decreased (78%), 
pyrexia (74%), thrombocytopenia/platelet count decreased (74%), fatigue (73%), diarrhea 
(57%), lymphopenia/lymphocyte count decreased (53%), and decreased appetite (50%). 
Grade 3 and 4 AEs which occurred in >50% of all subjects following GSK3377794 
infusion were leukopenia/WBC decreased (75%), neutropenia/neutrophil count decreased 
(71%), thrombocytopenia/platelet count decreased (59%),anemia/RBC decreased (57%), 
and lymphopenia/lymphocyte count decreased (50%). There has been one report of fatal 
bone marrow failure after initial bone marrow recovery. 
There have been 31 reports of CRS (grades 1-4) from subjects who received NY-ESO-
1c259T cells, all of which resolved. Twenty-nine subjects had CRS following a single 
infusion of NY-ESO-1c259T cells and 4 out of 15 subjects had CRS after their second 
infusion.  Onset of CRS symptoms typically occurs within 2 weeks from the T-cell 
infusion, coinciding with maximal in vivo T-cell expansion. 
Overall, GvHD (grades 1-3, including GvHD in gastrointestinal tract and GvHD in skin) 
has been reported in 7 subjects who received NY-ESO-1c259T cells, and all cases have 
resolved.  All 7 subjects had multiple myeloma:  6 subjects (Study ADP-
01411/NCT01352286) had previously undergone ASCT, while the 7th subject (Study 
208470) had not.  Although there is a probable association with autologous stem cell 


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transplant, symptoms such as rash, colitis and diarrhea have been reported in other NY-
ESO-1c259T studies.  
The Investigator Brochure contains detailed safety information (GSK Document Number 
RPS-CLIN-024388. 
To manage the risk of CRS and GvHD in the NY-ESO-1c259T program, GSK is 
implementing specific AE pages in the electronic case report form (eCRF) to carefully 
document the events and to enable evaluation and identification of potential risk factors. 
To help Investigators manage CRS and GvHD, GSK has developed treatment guidance 
based on published literature which is included in the protocol (see Section 8). Study sites 
are expected to have access to physicians with expertise in bone marrow transplantation 
and infectious diseases for consultation in the event of a subject developing either CRS or 
GvHD-like symptomatology. 
The protocol also includes guidance on the irradiation of transfused blood products to 
minimize the possibility of transfusion-related GvHD. 
Sponsor is also monitoring reports of recurrent pancytopenia after initial bone marrow 
recovery following pre-conditioning chemotherapy and NY ESO-1c259T cell infusion. In 
order to manage this risk, Sponsor has developed standard protocol guidance on the 
management of pancytopenia with bone marrow failure following initial bone marrow 
recovery. Management of bone marrow failure (aplastic anemia) and related cytopenias is 
challenging, with no clearly established guidelines regarding immunosuppression. 
Therefore, treatment is largely supportive, including transfusions and treatment of 
infections. Guidance includes a recommendation to consult with physicians with 
expertise in the management of aplastic anemia and infectious diseases. 
The potential risks of replication competent lentivirus (RCL) and insertional oncogenesis 
(IO) are being monitored in accordance with FDA guidance. 
Acute inflammatory demyelinating polyneuropathy / Guillain Barré Syndrome (GBS) 
developed in two subjects who received the NY-ESO-1C259T cells following infusion. 
Therefore, subjects with prior or active demyelinating disease will be excluded from the 
study. Neurologic consultation is required for patients with Grade 2 or higher neurologic 
events of a ≥7-day duration. Additionally, any potential future recurrence of GBS will 
lead to a pause in study enrolment and stopping treatment until further investigation. 
Potential risk associated with lymphodepletion chemotherapy and TCR T-cell infusion. 
There have been 2 reports of unexpected cardiac arrest. The first occurred 5 months 
after T-cell infusion and was confounded by hypotension due to poor oral intake and 
concurrent renal insufficiency. The second occurred approximately 1 week after T-cell 
infusion in the setting of  a recent fungal catheter line infection, concurrent treatment 
with caspofungin and multifocal pneumonia / edema seen on chest CT. Participants with 
significant cardiac risk factors or with CRS ≥ Grade 2 will 
receive close cardiac monitoring (Section 7.4.8).  Participants with lung 
metastases should be considered for pulmonary consultation prior 
to lymphodepletion; participants deemed at high risk of pulmonary complications should 


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be monitored closely (Section 7.4.9). Central lines should be closely monitored for 
infection (Section 8.2). Systemic fungal infections are excluded (Exclusion 9) Monitoring 
of risk of increased cardiac toxicity with the use of anti-microbials (Core Section 8.2.6)  
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 8.3   
Additional experience in clinical trials is required to confirm the incidence of these and 
other risks. The goal of the risk mitigation strategies is to maximize the chance of 
therapeutic benefit while mitigating and better understanding the risks of treatment with 
NY-ESO-1c259T-cell therapy. 
3.5.3. 
Overall Benefit: Risk Conclusion 
Data from preclinical studies support the efficacy, specificity, and safety of NY-ESO-
1c259T cells (Investigator Brochure). Clinical data from subjects summarized in the 
Investigator Brochure and the NCI study [Robbins, 2015] demonstrate the safety and 
activity of NY-ESO-1c259T sufficiently to support the clinical investigation of this 
product in MRCLS. The design of the study aims to evaluate the overall benefit:risk of 
using the treatment in a new indication by evaluating efficacy and safety in an initial pilot 
study. 
4. 
SELECTION OF STUDY POPULATION 
Subjects will be assessed for and must meet eligibility for study participation prior to 
leukapheresis (i.e., at Screening Visit 2) AND prior to lymphodepleting chemotherapy 
(i.e., at Baseline). 
4.1. 
Subject Inclusion Criteria 
A subject must meet the following inclusion criteria to be eligible for participation in this 
study: 
1. Subject (or legally authorized representative) has voluntarily agreed to participate by 
giving written informed consent in accordance with ICH GCP guidelines and 
applicable local regulations. 
2. Subject has agreed to abide by all protocol required procedures including study 
related assessments, and management by the treating institution for the duration of 
the study and long-term follow-up. 
3. Subject is ≥18 years of age at the time of signing the study informed consent 
4. Subject has a diagnosis of high grade myxoid liposarcoma / myxoid round cell 
liposarcoma confirmed histologically and by the presence of the reciprocal 
chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12). 


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5. Subject has advanced (metastatic or inoperable) high grade myxoid liposarcoma / 
myxoid round cell liposarcoma. Inoperable refers to a tumor lesion in which clear 
margins cannot be obtained without leading to significant functional compromise 
6. Subject has measurable disease according to RECIST v1.1 criteria. 
7. Subject must be HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive. 
8. Subject's tumor (either the most recent archival specimen or a fresh biopsy) shows 
positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by 
immunohistochemistry. All samples must have been pathologically reviewed by a 
GSK designated central laboratory. 
9. Subject must have previously received or be intolerant to anthracycline based 
therapy for advanced (metastatic or inoperable) disease. Subjects who received 
neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of 
completion of therapy will be eligible. 
10. Subject has an ECOG Performance Status 0-1. 
11. Subject has a left ventricular ejection fraction ≥45%. 
12. Subject is fit for apheresis and has adequate venous access for the cell collection. 
13. Male or Female. Contraceptive use by men or women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies. 
• 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 4 months after there is no evidence 
of persistence/ gene modified cells in the subject’s blood, whichever is longer. 
• Refrain from donating sperm  
 
Plus either: 
• Be abstinent from heterosexual or homosexual intercourse as their preferred and 
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent  
 
OR 
• Must agree to use contraception/barrier as detailed below: 
- Agree to use a male condom and should also be advised of the benefit for 
a female partner to use a highly effective method of contraception as a 
condom may break or leak when having sexual intercourse with a woman 
of childbearing (WOCBP) potential who is not currently pregnant. 


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- Agree to use male condom when engaging in any activity that allows for 
passage of ejaculate to another person. 
 
• 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 6.3.1  
 
OR 
• Is a WOCBP (as defined in Section 6.3.1) who will agree to use a barrier method 
(male condom) and use a contraceptive method that is highly effective (with a 
failure rate of <1% per year), as described in Section 6.3.1 during the intervention 
period and for at least 12 months after receiving the T-cell infusion.  In the event 
that there is evidence of persistence/gene-modified cells in the participant’s blood, 
contraception usage should continue until 2 consecutive persistence tests show 
that GSK3377794 is below the level of detection in blood.  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 the first dose of study 
intervention. 
 
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a 
serum pregnancy test is required. In such cases, the participant must be excluded 
from participation if the serum pregnancy result is positive. 
14. Subject must have adequate organ function as indicated by the laboratory values in 
the table below: 
System 
Laboratory Value 
Hematological 
Absolute Neutrophil count (ANC) 
≥ 1.5 x109/L (without G-CSF support) 
Platelets 
≥ 100 x109/L 
Hemoglobin 
≥ 80 g/L (without transfusion support within 7 
days prior to leukapheresis) 
Coagulation 
Prothrombin Time or INR 
≤ 1.5x upper limit of normal (ULN) unless 
receiving therapeutic anticoagulation. 
Partial Thromboplastin Time (PTT) 
≤ 1.5x upper limit of normal (ULN) unless 
receiving therapeutic anticoagulation. 
Renal 
Calculated or measured creatinine clearance 1 
≥ 40 mL/min 


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1  
• 
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 Chronic kidney disease Epidemiology Collaboration (CKD-EPI) equation and adjusting the 
result by multiplying with (Body Surface Area [BSA]/1.73) to obtain a CrCl in mL/min.  
Step 1: estimated glomerular filtration rate (GFR) to be obtained from the CKD-EPI formula [Levey, 2009]:  
 
Estimated GFR (mL/min/1.73m2) = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 
1.159 [if black]  
where:  
Scr is serum creatinine in mg/dL,  
κ is 0.7 for females and 0.9 for males,  
a 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 creatinine clearance in mL/min 
Estimated CrCl (mL/min) = Estimated GFR (mL/min/1.73 m2) × BSA (m2) / 1.73   
To calculate the BSA for fludarabine dosing, use actual body weight. An adjusted body weight may be required 
for cyclophosphamide, refer Section 5.2.2. for further details.  
 
• 
Participants ≥65 years of age must have renal function measured either by 24-hour urine creatinine collection or 
by nuclear medicine ethylenediaminetetraacetic acid (EDTA) GFR measurement, according to standard practice 
at the treating institution 
 
 
4.2. 
Subject Exclusion Criteria 
A subject meeting any of the following criteria is not eligible for participation in the 
study: 
1. Subject has received or plans to receive the following excluded therapy/treatment 
within the following periods prior to leukapheresis or lymphodepleting 
chemotherapy: 


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Treatment/Therapy 
Required Wash-out Prior 
to Leukapheresis 
Required Wash-out Prior 
to Lymphodepletion 
Cytotoxic chemotherapy 
3 weeks 
3 weeks 
Small Molecules/Tyrosine kinase 
inhibitor (TKI) such as pazopanib. 
1 week 
1 week 
Treatment/Therapy 
Required Wash-out Prior to 
Leukapheresis 
Required Wash-out Prior to 
Lymphodepletion 
Immune therapy (including monoclonal 
antibody therapy, checkpoint inhibitors, 
biologics) 
2 weeks 
2 weeks 
Experimental anti-cancer Vaccine 
2 months in the absence of 
tumor response, or the 
subject should be excluded 
if their disease is 
responding to an 
experimental vaccine given 
within 6 months 
2 months in the absence of 
tumor response, or the 
subject should be excluded 
if their disease is 
responding to an 
experimental vaccine given 
within 6 months 
Gene therapy using an integrating vector Any use of previous gene 
therapy using an 
integrating vector is not 
permitted 
Any use of previous gene 
therapy using an integrating 
vector is not permitted 
Allogeneic hematopoietic stem cell 
transplant (HSCT) 
Any allogeneic HSCT is 
not permitted 
Any allogeneic HSCT is 
not permitted 
Corticosteroids or any other 
immunosuppressive therapy. Use of 
topical steroids is not excluded. 
2 weeks 
2 weeks 
Investigational treatment 
4 weeks 
4 weeks 
Duration of any other anti-cancer therapies must be discussed with the Sponsor Study Physician 
 
2. Radiotherapy within the following periods prior to leukapheresis or 
lymphodepleting chemotherapy (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): 
Treatment/Therapy 
Required Wash-out 
Prior to Leukapheresis 
Required Wash-out 
Prior to 
Lymphodepletion 
Radiotherapy that involves the lung (V20 
exceeding 30% lung volume) or pericardium 
(>20Gy). Exception for a lesser dose or 
radiation exposure to lung/mediastinum than 
stated, administered within 4 weeks prior to 
lymphodepletion. Electron beam radiotherapy 
to superficial structures in the chest is 
permitted. 
N/A 
3 months 


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Treatment/Therapy 
Required Wash-out 
Prior to Leukapheresis 
Required Wash-out 
Prior to 
Lymphodepletion 
Radiation to vital organs (e.g., liver, kidney) 
N/A 
4 weeks 
Radiation to the pelvis 
4 weeks 
4 weeks 
Whole Brain Radiotherapy (WBRT) or Brain 
Stereotactic Radiosurgery (SRS) 
N/A 
2 weeks 
Radiotherapy to the target lesions 
N/A 
3 months prior to 
lymphodepleting 
chemotherapy. A lesion 
with unequivocal 
progression may be 
considered a target 
lesion. There is no 
washout period for 
palliative radiation to 
non-target organs. 
 
3. Subject that has toxicity from previous anti-cancer therapy must have recovered 
to ≤ Grade 1 (except for non-clinically significant toxicities, e.g., alopecia, 
vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible 
(e.g., peripheral neuropathy) can be enrolled. 
4. Subject has history of allergic reactions attributed to compounds of similar 
chemical or biologic composition to fludarabine, cyclophosphamide or other 
agents used in the study. 
5. Subject has history of chronic or recurrent (within the last year prior to screening) 
severe autoimmune or immune mediated disease requiring steroids or other 
immunosuppressive treatments. 
6. Subject has known active brain or leptomeningeal metastases. Subjects with prior 
history of brain metastasis who have undergone local therapy (i.e., 
metastasectomy and/or radiation) and show no evidence of local recurrence or 
progression over the past 3 months prior to screening are eligible. 
7. Subject has other prior malignancy that is not in complete remission. 
8. Subject has electrocardiogram (ECG) showing clinically significant abnormality 
at Screening or an average QTc interval (Fridericia's or Bazett's formula) >450 
msec in males and >470 msec in females (>480 msec for subjects with Bundle 
Branch Block (BBB)). 
9. Subject has uncontrolled intercurrent illness including, but not limited to: 
- Ongoing or active infection including but not limited to systemic fungal 
infection; EBV and CMV IgG seropositive patients who have a positive PCR 


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- Prior or active demyelinating disease 
- Clinically significant cardiac disease defined by congestive heart failure New 
York Heart Association (NYHA) Class 3 or Class 4 
- Uncontrolled clinically significant arrhythmia in last 6 months 
- Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months 
- Interstitial lung disease (subjects with existing pneumonitis as a result of 
radiation are not excluded, however, subjects must not be oxygen dependent). 
10. Subjects who in the opinion of the Investigator will be unlikely to fully comply 
with protocol requirements. 
11. ALT>2.5 times ULN without documented liver metastases/tumor infiltration  
 
OR  
 
Total Bilirubin > 1.5 x ULN (isolated bilirubin >1.5xULN is acceptable if 
bilirubin is fractionated and direct bilirubin <35%) 
12. Subject has active infection with HIV, HBV, HCV or HTLV as defined below: 
- Positive serology for HIV 
- Active hepatitis B infection as demonstrated by test for hepatitis B surface 
antigen. Subjects 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 test for hepatitis C RNA. 
Subjects 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 
- Positive serology for HTLV 1 or 2. 
 
Re-screening for infectious disease markers is not required at baseline (prior 
to lymphodepletion) 
13. Subject is pregnant or breastfeeding. 
4.3. 
Completion of the Interventional Phase 
A NY-ESO-1c259T infused subject will be considered to have completed the 
interventional phase of the study when he/she has progression of disease (see Section 
7.4.11 for tumor response assessments), death, or has been followed-up for 2 years after 
NY-ESO-1c259T cell infusion, whichever is shorter.    


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All NY-ESO-1c259T infused subjects alive on completing or withdrawing from the 
interventional phase will continue into long-term follow-up (LTFU) for observation of 
delayed adverse events as described in Section 7.4.12.  If necessary and upon discussion 
with the Sponsor, those patients who have not progressed after 2 years on study and who 
are continuing in Study 208469 may continue to undergo response assessments every 3 
months as defined in Study 208469 per institutional standard of care.   
This study will be considered complete when the last subject has been rolled over into the 
LTFU protocol GSK208750 (ADP-0000-002), has completed long term follow-up in this 
study, has declined LTFU, has been withdrawn from study (including lost to follow-up), 
or died. 
4.3.1. 
Long-Term Follow-up 
All participants will be followed for survival and for 15 years after T-cell (GSK3377794) 
infusion to permit observation of delayed AEs in accordance with FDA requirements for 
gene therapy clinical trials [FDA Guidance, 2006b; FDA Guidance, 2010; FDA 
Guidance, 2020].  Delayed AEs are defined as those events that fall into one or more of 
the 6 categories listed below and which occur either more than one year following 
GSK3377794 infusion or after disease progression, whichever occurs first.  In the event a 
subject has not progressed 1 year following GSK3377794 infusion, delayed AEs will be 
collected in Interventional Phase of study.  Delayed AEs which occur post progression 
will be collected as part of the LTFU phase of the current study or in the LTFU Study 
(208750), contingent upon formal transfer of subject to Study 208750.   
• New malignancies 
• New incidence or exacerbation of a pre-existing neurologic disorder 
• New incidence or exacerbation of a prior rheumatologic or other autoimmune 
disorder 
• New incidence of immune-related hematologic disorder 
• Serious infections (including opportunistic) 
• Unanticipated illness and/or hospitalization deemed related to gene modified cell 
therapy 
4.4. 
Subject Withdrawal 
A subject may withdraw from the study at any time for any reason without prejudice to 
his/her future medical care by the physician or institution. However, the Investigator must 
make every reasonable effort to keep each subject on study for the whole duration of the 
trial. In cases where the subject is deemed ‘lost to follow-up’, the investigator or designee 
must make every effort to regain contact with the subject; e.g., 3 documented attempts, 
one of which must be a certified letter to the subject’s last known mailing address or local 
equivalent methods. These contact attempts should be documented in the subject’s 


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medical records. Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with the primary reason as ‘Lost to Follow-
up’. 
If a participating subject withdraws consent, all final end-of-study assessments should be 
performed, if possible, on the day the decision is made to take the subject off-study or as 
soon as possible thereafter. All the results of the evaluations and observations, together 
with a description of the reasons for study withdrawal, must be recorded in the medical 
records and electronic Case Report Form (eCRF). The following are justifiable reasons 
for the investigator to withdraw a subject from study: 
• Subject withdraws consent. 
• Initiation of alternative anti-cancer therapy with no plans to initiate treatment with 
NY-ESO-1c259T cells 
Refer to Section 9.1 and Section 9.2 for continued monitoring of AEs/SAEs following 
study procedures. 
If a subject who has consented to participate in pharmacogenetic research withdraws 
from the clinical study for any reason other than lost to follow-up, the subject will be 
given the following options concerning the pharmacogenetics sample, if already 
collected: 
• Pharmacogenetics research continues as per the subject’s consent; or 
• Any remaining sample is destroyed 
If a subject withdraws consent from the pharmacogenetics research or requests sample 
destruction, the investigator must complete the appropriate documentation to request 
sample destruction within the timeframe specified by GSK and maintain the 
documentation in the site study records. In either case, GSK will only keep study 
information collected/generated up and until that point. 
If the subject voluntarily discontinues from treatment due to toxicity, ‘adverse event 
(AE)’ will be recorded as the primary reason for permanent discontinuation on the eCRF. 
All subjects who discontinue from study treatment will have safety assessments at the 
time of discontinuation and during post-study treatment follow-up as specified in the 
Schedule of Procedures Table (see Section 7.3). 
 
 
 


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5. 
STUDY TREATMENTS 
5.1. 
Leukapheresis 
Subjects who complete screening procedures defined in Section 7 and who meet 
eligibility criteria defined in Section 4 will be eligible to undergo leukapheresis to obtain 
starting material for the manufacture of autologous NY-ESO-1c259T. 
Prior to leukapheresis, an absolute lymphocyte count ≥ 0.5 x 109/L and a CD3 
lymphocyte count ≥ 0.2 x 109/L is recommended. For collection of starting material, a 
large-volume non-mobilized PBMC collection should be performed according to 
institutional standard procedures. 2 -3 blood- volumes should be processed per procedure 
with a goal of the procedure being collection of 1.0 x 108 PBMC/kg body weight, and a 
minimum of 1.5 x 107 PBMC/kg. In cases where the minimum number of PBMC is not 
collected or the T cells are not able to be infused back to the subject, a second 
leukapheresis may be performed. Citrate anticoagulant should be used. Prophylaxis 
against adverse effects of citrate anticoagulant (e.g., CaCl2 infusions) should be used at 
the discretion of the investigator. The collected leukapheresis product will then be 
transported for manufacture as detailed in the Study Procedures Manual (SPM). 
Once NY-ESO-1c259T cell product has been manufactured eligible subjects will proceed 
to have lymphodepleting chemotherapy and infusion of the study therapy as detailed in 
Section 5.2 and Section 5.3. 
5.2. 
Lymphodepleting Chemotherapy 
Prior to the administration of lymphodepleting chemotherapy all eligibility criteria will 
be reconfirmed and baseline tumor assessment obtained. 
When the NY-ESO-1c259T cells have completed manufacture and have fulfilled release 
criteria, fludarabine and cyclophosphamide will be used as lymphodepleting 
chemotherapy prior to administration of the study treatment as described in Section 5.3. 
Appropriate IV hydration should be administered and Mesna given to prevent urotoxicity 
while cyclophosphamide is administered, according to institutional guidelines; a 
suggested schedule is shown in Section 5.2.2. Other premedication (e.g., anti-emetics) 
may also be provided in accordance with institutional standards. Steroids may be used as 
anti-emetics for cyclophosphamide but must be discontinued no later than Day -3. G-CSF 
should be given to all subjects from 24 hours after the last dose of cyclophosphamide 
until resolution of neutropenia in accordance with ASCO guidelines or institutional 
practice (see Section 8.7.1). 
Dose and regimen for lymphodepleting chemotherapy is adjusted for participants 
≥60 years of age, as specified in Table 2, Option 2.  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: 


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- 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) 
 
On admission for lymphodepleting chemotherapy subjects should commence 
antimicrobial and antifungal prophylaxis in line with ASCO Guidelines [Flowers, 2013] 
or institutional standard practice (see Section 8.2). 
 


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Table 2 
Treatment Schema 
Lymphodepleting chemotherapy (Option 1: First 10 Subjects) 
Recommended supportive medication 
Day 
Drug 
Dose 
Route 
Administration 5 
Hydration: Ensure adequate hydration and 
antiemetic provision prior to commencing 
cyclophosphamide infusions 
Mesna: may be given per institutional guidelines or 
as recommended in Section 5.2.2 
G-CSF: start 24 hours post final cyclophosphamide 
until resolution of neutropenia3 
Cell therapy premedication: premedication with 
acetaminophen and diphenhydramine should be 
given 30 - 60 minutes prior to the NY-ESO-1c259T 
infusion according to institutional practice 
-7 
Fludarabine1 
30 mg/m2 
IV 
in 50 – 100 ml 0.9% NaCl over 30 mins 4 
Cyclophosphamide 
600 mg/m2 
IV 
in 100 – 250 ml 0.9% NaCl over 1 hour 
-6 
Fludarabine1 
30 mg/m2 
IV 
in 50 – 100 ml 0.9% NaCl over 30 mins 4 
Cyclophosphamide 
600 mg/m2 
IV 
in 100 – 250 ml 0.9% NaCl over 1 hour 
-5 
Fludarabine1 
30 mg/m2 
IV 
in 50 – 100 ml 0.9% NaCl over 30 mins 4 
Cyclophosphamide 
600 mg/m2 
IV 
in 100 – 250 ml 0.9% NaCl over 1 hour 
-4 
start G-CSF 
-3 
-2 
-1 
16 
NY-ESO-1c259T infusion2 
NS = Normal Saline 
1. Fludarabine dose will be adjusted in renal impairment as described in Section 5.2.1 
2. Administration of NY-ESO1c259T infusion is described in Section 5.3 
3. 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 
4. Concentration ≤1mg/mL 
5. Or per institutional guidelines 
6. There is no Day 0; T cell infusion takes place on Day 1 
 


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Lymphodepleting chemotherapy (Option 2: Based on emerging data) 
Recommended supportive medication 
Day Drug 
Dose 
Dose for participants 
≥60 years old 
Route Administration 5 
Hydration: Ensure adequate hydration and antiemetic provision prior to 
commencing cyclophosphamide infusions 
Mesna: may be given per institutional guidelines or as recommended in Section 
5.2.2 
G-CSF: start 24 hours post final cyclophosphamide until resolution of 
neutropenia3 
Cell therapy premedication: premedication with acetaminophen and 
diphenhydramine should be given 30 - 60 minutes prior to the NY-ESO-1c259T 
infusion according to institutional practice 
-8 
Fludarabine1 
30 mg/m2 none 
IV 
in 50 – 100 ml 0.9% NaCl 
over 30 mins 4 
-7 
Fludarabine1 
30 mg/m2 30 mg/m2 
IV 
in 50 – 100 ml 0.9% NaCl 
over 30 mins 4 
Cyclophosphamide 
900 
mg/m2 
600 mg/m2 
IV 
in 100 – 250 ml 0.9% NaCl 
over 1 hour 
-6 
Fludarabine1 
30 mg/m2 30 mg/m2 
IV 
in 50 – 100 ml 0.9% NaCl 
over 30 mins 4 
Cyclophosphamide 
900 
mg/m2 
600 mg/m2 
IV 
in 100 – 250 ml 0.9% NaCl 
over 1 hour 
-5 
Fludarabine1 
30 mg/m2 30 mg/m2 
IV 
in 50 – 100 ml 0.9% NaCl 
over 30 mins 4 
Cyclophosphamide 
900 
mg/m2 
600 mg/m2 
IV 
in 100 – 250 ml 0.9% NaCl 
over 1 hour 
-4 
start G-CSF 
-3 
-2 
-1 
1 6 
NY-ESO-1c259T infusion2 
NS = Normal Saline 
1. Fludarabine dose will be adjusted in renal impairment as described in Section 5.2.1. Fludarabine dose will not be adjusted by body weight per American Society for Blood and 
Marrow Transplantation (ASBMT) guidelines that recommend dosing based upon BSA using total body  weight [Bubalo, 2014], unless required otherwise by institutional 
guidelines 
2. Administration of NY-ESO1c259T infusion is described in Section 5.3 
3. 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 
4. Concentration ≤1mg/mL 
5. Or per institutional guidelines 
6. There is no Day 0; T cell infusion takes place on Day 1 
 


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5.2.1. 
Fludarabine Dose Adjustment for Renal Impairment 
This adjustment needs to be applied for patients treated under either Option 1 or Option 
2.  Patients ≥ 60 years of age receiving an age-adjusted dose will have the renal 
adjustment applied to the modified dose for age.  Dose of fludarabine will be adjusted for 
subjects with renal dysfunction as follows: 
Table 3 
Fludarabine dose adjustment 
Creatinine clearance 
Fludarabine dose 
≥80mL/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 4.1 Inclusion 14 for calculation steps 
before comparing to the thresholds given above. 
If estimating CrCl using the CKD-EPI equation, adjust the result by multiplying with 
(BSA/1.73) to obtain a CrCl in mL/min. For fludarabine dosing, to calculate BSA, use actual 
body weight.   
Creatinine clearance must be reassessed prior to lymphodepletion for use in these 
calculations. 
 
5.2.2. 
Cyclophosphamide Dose Adjustment 
This adjustment needs to be applied to all doses, on top of the age-related modification.  If 
the participant’s weight is greater than 175% Ideal Body Weight (IBW), then calculate 
cyclophosphamide dose based on BSA calculated using the Adjusted Body Weight (ABW). 
These adjustments need to be applied on top of any age-related or tumour-related 
modifications.  
Calculating Ideal Body Weight 
 
Estimated IBW in Kg 
Males 
IBW = (0.9 x Height in cm) - 88 
Females 
IBW = (0.9 x Height in cm) - 92 
Estimation of IBW may be performed per local institutional guidelines instead, if required. 
 
 


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Calculating Adjusted Body Weight  
If the actual body weight is greater than 175% of the calculated IBW, calculate the ABW: 
ABW = IBW + 0.4 x (actual weight - IBW) 
Estimation of ABW 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. 
 
5.2.3. 
Mesna 
Mesna should be administered according to institutional practice or as recommended 
below: 
120 mg/m2 (20% cyclophosphamide dose) as an IV bolus at T=0, 3, 6 and 9 hours 
relative to cyclophosphamide administration. 
5.3. 
T Cell Infusion 
On Day 1, the subject will receive NY-ESO-1c259T by intravenous infusion (please note 
there is no Day 0 in the schedule). Prior to infusion, two clinical personnel, in the 
presence of the subject, will independently verify and confirm that the information on the 
infusion bag label is correctly matched to the subject, as per the participating center’s 
blood bank procedures. 
Subjects will be premedicated with antihistamine and acetaminophen (paracetamol) 30-
60 minutes prior to the T cell infusion according to institutional practice. Steroids must 
not be administered as premedication for T cell infusion. 
NY-ESO-1c259T must not be thawed until immediately prior to infusion. The cells can be 
thawed either in a water bath at the subject’s bedside or in a centralized facility, 
according to institutional standard procedures. The cells must be infused without delay 
and, if thawed centrally, must be transported to the subject by appropriately trained 
clinical staff, to preserve the chain of custody. The cell product must not be washed or 
otherwise processed. The infusion should commence immediately after thawing, or 
immediately upon delivery to the bedside if thawed centrally and should be completed 
within 45 minutes of thawing to minimize exposure of the cell product to cryoprotectant. 
If the cells are provided in multiple bags, the second bag must not be thawed until half of 
the first has been infused without reaction. The same principles should be applied to any 
subsequent bags. 
If after thawing, the inner infusion bag is damaged or leaking, the PI and Sponsor should 
be notified and the cells should not be infused. 


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NY-ESO-1c259T will be administered using a dual spike infusion set by gravity over 15-
30 minutes in the absence of reaction. It is recommended that the cells are infused 
without a filter; however, if a filter is required by institutional practice the pore size must 
not be smaller than 170 µm. Infusion pumps must not be used. For administration of the 
cells, 100 - 250 ml of 0.9% sodium chloride should be connected to the second lumen of 
the infusion set, used to prime the line, and then the lumen closed. On completion of the 
infusion of a bag of NY-ESO-1c259T, the main line should be closed and approximately 
50ml saline transferred into the cell bag, and then infused to minimize the loss of cells. 
This process should be repeated for each cell bag if multiple bags are provided. On 
completion of the cell infusion the set should be flushed using additional saline from the 
attached bag. 
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 (see Section 8). 
Steroid treatment should be avoided unless medically required. In the event a subject 
develops a febrile episode following the infusion, appropriate cultures and medical 
management should be initiated, with attention to the initiation of empirical antibiotic 
treatment in the case of febrile neutropenia. 
The day of T cell infusion may be delayed in subjects with significant complications of 
chemotherapy if according to the investigator it is in the best interests of the subject. The 
timing of all assessments post-infusion will be calculated with reference to the T-cell 
infusion date. Cytopenias alone should not be a reason to delay T-cell infusion unless 
complications are present. 
Vital signs will be recorded prior to the infusion and at 5, 15 and 30 minutes, and at 1, 
1.5, 2 and 4 hours after the infusion has started. 
6. 
CONCOMITANT MEDICATION AND TREATMENT 
Starting at the time the subject signs the treatment informed consent form at Visit 2, all 
concomitant medications taken during the study, including prescription and over-the-
counter (OTC) medications and herbal remedies, will be recorded in the eCRF. 
Indication, dose, route and frequency will also be recorded. Any changes to concomitant 
medications should be recorded throughout the study in the eCRF. 
The full history of prior anti-cancer therapy for each subject will be recorded in the 
eCRF. 
6.1. 
Prohibited Concomitant Medication and Treatment 
The following treatments are prohibited from the start of lymphodepleting chemotherapy: 
non- protocol chemotherapy, immune therapy, biological therapy (including targeted 
therapies with tyrosine kinase inhibitors or monoclonal antibodies), or investigational 
anti-cancer therapy. 


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During the interventional phase of the study until PD is confirmed subjects should also 
not undergo other anticancer locoregional therapies such as surgical resection, excisional 
biopsies or non-palliative radiotherapy.  
See Section 4.2 for washout and excluded treatments prior to leukapheresis or 
lymphodepleting therapy. 
The use of systemic steroids may abrogate the effects of the T cell therapy and therefore 
use is discouraged unless it is required to manage cytokine release syndrome (CRS) (see 
Section 8.5 for CRS treatment recommendations) or other significant immune-mediated 
adverse events. According to local standard of care, steroids may be used as anti-emetics 
for cyclophosphamide but must be discontinued no later than 3 days prior to infusion of 
the IP (Day -3). Topical cutaneous steroids and inhaled steroidal treatments are permitted. 
6.2. 
Permitted Concomitant Medication and Treatment 
Lesion sites previously requiring radiotherapy should be recorded prior to 
lymphodepletion.  
Palliative radiation for pain relief to non-measurable lesions or non-target lesions present 
at baseline is permitted during the study. However, lesion sites requiring radiotherapy 
after the 
T-cell infusion should be evaluated to determine if the need is due to disease progression 
rather than pain palliation. 
Other treatment that the investigator considers necessary for a subject’s welfare may be 
administered during the interventional phase of the study at the discretion of the 
investigator in keeping with standards of medical care and in adherence to the protocol. 
Before immunizing a subject at high risk for vaccine-preventable disease (or member of 
the subject’s household) with a live vaccine, consult an infectious disease specialist or 
clinical practice guidelines (e.g., CDC Clinical Practice Guidelines for Vaccination of the 
Immunocompromised Host). Before immunizing a subject against SAR-CoV-2 (COVID-
19) it is requested that you contact the study Sponsor. 
6.3. 
Restrictions 
6.3.1. 
Contraception 
NY-ESO-1c259T may have adverse effects on a fetus in utero. Furthermore, it is not 
known if NY-ESO-1c259T has transient adverse effects on the composition of sperm. 


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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 enrolment. 
 


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Male participants: 
Male participants must agree to the following during the intervention period starting at 
the first dose of chemotherapy for at least 12 months after receiving the T -cell infusion, 
or 4 months after there is no evidence of persistence/ gene modified cells in the subject’s 
blood, whichever is longer. 
• Refrain from donating sperm  
Plus either: 
• Be abstinent from heterosexual or homosexual intercourse as their preferred and 
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent  
 
OR 
• Must agree to use contraception/barrier as detailed below: 
- Agree to use a male condom and should also be advised of the benefit for 
a female partner to use a highly effective method of contraception as a 
condom may break or leak, when having sexual intercourse with a woman 
of childbearing potential who is not currently pregnant. 
• Agree to use male condom when engaging in any activity that allows for passage 
of ejaculate to another person. 
 
Female participants: 
WOCBP must 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 below 
from the day of study medication initiation (or 14 days prior to the initiation of study 
medication for oral contraception) throughout the intervention period up to 12 months 
after receiving T -cell infusion.   In the event that there is evidence of persistence/gene-
modified cells in the participant’s blood, contraception usage should continue until 2 
consecutive persistence tests show that GSK3377794 is below the level of detection in 
blood.  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 the first dose of study 
intervention. 
Subjects who are WOCBP must use a barrier method (male condom) and should comply 
with one of the following: 


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CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
Intrauterine device (IUD) 
Intrauterine hormone-releasing system (IUS)c 
Bilateral tubal occlusion 
Vasectomized partner 
Note: Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole 
sexual partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not, 
an additional highly effective method of contraception should be used. Spermatogenesis cycle is 
approximately 90 days. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationc 
- oral  
- intravaginal 
- transdermal  
- injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
- oral  
- injectable 
Sexual abstinence 
Note: Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the 
participant 
a. Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from 
those when used consistently and correctly. 
c. Male condoms must be used in addition to hormonal contraception. If locally required, in accordance 
with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited 
to those which inhibit ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of 
contraception. Male condom and female condom should not be used together (due to risk of failure with 
friction) 
 
Subjects 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.  
If there is any question that a subject of childbearing potential will not reliably comply 
with the requirements for contraception, that subject should not be entered into the study. 
The IB and Informed consent also contain language describing the risks and 
contraceptive guidelines described above. 


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7. 
SCHEDULE OF ASSESSMENTS AND PROCEDURES 
The Schedule of Procedures for the study is provided in (Table 4). On completion of the 
Interventional Phase of this study subjects will transfer to the LTFU protocol 
(GSK208750(ADP-0000-002)) or may be followed on the current protocol until the 
LTFU protocol is available. A subject will have the same Subject ID in this study 
(GSK208469 (ADP-0011-007)), and in the LTFU Protocol (GSK208750 (ADP-0000-
002)). Refer to the SRM for further details on assignment of Subject ID. 
Subjects will be assigned a unique subject number upon signing the tissue screening 
informed consent (Section 7.1) according to procedures outlined in the SPM. The number 
assigned at screening will serve as the subject ID upon qualification and enrolment into 
the interventional phase of the study. 
Study procedures performed as part of standard of care prior to signing informed consent 
can be used for screening if they were performed within a medically reasonable period of 
time prior to signing the informed consent (see Schedule of Procedures, Table 4, for 
additional details). 
7.1. 
HLA and Antigen Screening 
Subjects that are identified by the investigator as possible candidates for the trial must 
consent to initial screening tests that will first confirm that the subject is HLA-A*02:01, 
HLA-A*02:05 and/or HLA-A*02:06 positive (by using high resolution HLA typing for 
the A locus) with NY-ESO-1 positive tumor prior to conducting the remaining study 
screening procedures. 
Blood samples will be submitted for HLA typing at a central laboratory to determine 
eligibility. Prior or local HLA typing results may not be used to determine eligibility. 
An archival tumor sample may be submitted for determination of NY-ESO-1 expression, 
in which case, the biopsy from the most current setting is preferred. If an archival 
specimen is unavailable, the subject must undergo a new biopsy.  
The subjects’ tumor will be tested for NY-ESO-1 antigen expression by 
immunohistochemistry (IHC) using a CLIA-certified Clinical Trial Assay (CTA). Testing 
will be completed at a central laboratory contracted by the Sponsor.  
Additional biomarkers related to the activity of NY-ESO-1c259T may also be analyzed 
for exploratory purposes. 
7.1.1. 
Tumor tissue requirements 
A formalin-fixed, paraffin embedded (FFPE) tumor block from the most current setting is 
preferred for the NY-ESO-1 test. If biopsies taken at multiple time points (i.e., primary 
diagnosis, progression/relapse, etc.) are available, a tissue sample from the most recent 
biopsy should be submitted. Any blocks submitted will be returned to the sites upon 
request once sufficient sample has been sectioned to conduct the NY-ESO-1 test for 


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inclusion into the study and the necessary validations required for the development of the 
regulatory approved test. 
If the site is unable to send a tissue block, then tissue slides taken from a single block and 
serially collected may be submitted. 
If no archived biopsy is available, a new biopsy, preferably from a metastatic lesion is 
required. 
Details regarding the collection and processing of the screening biopsy, sample 
requirements and instructions for sample shipment to the central lab for NY-ESO-1 IHC 
analysis are located in the SPM. 
7.2. 
Screen Failures 
A screen failure log documenting the investigator’s assessment of each screened subject 
with regard to the protocol’s inclusion and exclusion criteria is to be maintained by the 
investigator. 
Screen Failure data including demographics, disease history, HLA typing, NY-ESO 
expression and reason for failing screening will be collected in the eCRF. 
 


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7.3. 
Schedule of Procedures 
Table 4 
Schedule of Procedures (Screening and Intervention) 
Screening 
1 
Interventional phase 
Screening Leuka- 
pheresis
Base 
Line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
Visit Number 1 
2 
3 
4 
(5)23 5 
(6) 
6 
(7) 
7 
(8) 
8 
(9) 
9 
(10) 
10 
(11) 
11 
(12) 
12 
(13) 
13 
(14) 
14 
(15) 
15 
(16) 
16 
(17) 
17 
(18) 
18 
(19) 
19 
(20) 
20 
(21) 
21 
(22) 
22 
(23) 
23 
(24) 
24 
(25) 
Every 3 
Months 
through 
Yr 220,25 
Completion 
or 
withdrawal 
4 
Visit window 
± 1 day 
± 3 days 
± 7 days 
±14d±14d 
Day 
-14 to -
9 
-8 
-7 -6 
-5 
1 
2 
3 
4 
5 
8 
Week 
2 
3 
4 
5 
6 
8 
10 
12 
16 
20 
24 
Month 
9 
12 
Clinical assessments 
Informed 
consent 2 
X 
X 
Inclusion/ 
exclusion 
X 
X 
X 
Demographics X 


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Screening 
1 
Interventional phase 
Screening Leuka- 
pheresis
Base 
Line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
Disease History 
X 
Medical history 
X 
Adverse events 
X 
X 
X 
X 
X X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical 
examination 
X 
X 
X 
X 
X 
Prior anti-
cancer therapies 
X 
X 
Concomitant 
medications 
X 
X 
X 
X 
X X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG 
performance 
status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs / 
weight 
X8 
X 
X5 
X X 
X 
X 
X 
X 
X 


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Screening
1 
Interventional phase 
Screening Leuka- 
pheresis 
Base 
line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
Visit Number 1 
2 
3 
4 
(5)23 5 
(6) 
6 
(7) 
7 
(8) 
8 
(9) 
9 
(10)
10 
(11) 
11 
(12) 
12 
(13) 
13 
(14) 
14 
(15) 
15 
(16) 
16 
(17) 
17 
(18) 
18 
(19) 
19 
(20) 
20 
(21) 
21 
(22) 
22 
(23) 
23 
(24) 
24 
(25) 
Every 3 
Months 
through 
Yr 220,25 
Completion 
or 
withdrawal 
4 
Visit window 
± 1 day 
± 3 days 
± 7 days 
±14d±14d 
Day 
-14 to -9 -8 
-7 -6 
-5 
1 
2 
3 
4 
5 
8 
Week 
2 
3 
4 
5 
6 
8 
10 12 16 
20 24 
Month 
9 
12 
ECG21 
X 
X 
X 
X 
X 
Echo / MUGA 
X6 
Brain MRI 
X6 
X22 
X22 
CT / MRI7 
X6 
X 
X 
X 
X 
X 
X 
X 
X 
HLA typing2 
X 
NY-ESO-1 
expression 
(most recent 
X 


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Screening
1 
Interventional phase 
Screening Leuka- 
pheresis 
Base 
line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
archival or 
fresh biopsy) 2 
Hematology 
X 8 
X 
X 
X X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Biochemistry 
X 8 
X 
X 
X X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lymphocyte 
Subsets 
X 8 
Coagulation10 
X 8 
X 
Pregnancy 
test10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis10 
X 8 
X 
Infectious 
disease screen 
11 
X 
CMV PCR 12 
X 
X 
X 
X 
X 
X 
Lipase10 
X 
Thyroid 
function 
tests10 
X 


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Screening
1 
Interventional phase 
Screening Leuka- 
pheresis 
Base 
line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
Visit Number 
1 
2 
3 
4 
(5)23 5 
(6) 
6 
(7) 
7 
(8) 
8 
(9) 
9 
(10)
10 
(11) 
11 
(12) 
12 
(13) 
13 
(14) 
14 
(15) 
15 
(16) 
16 
(17) 
17 
(18) 
18 
(19) 
19 
(20) 
20 
(21) 
21 
(22) 
22 
(23) 
23 
(24) 
24 
(25) 
Every 3 
Months 
through 
Yr 220,25 
Completion 
or 
withdrawal 
4 
Visit window 
± 1 day 
± 3 days 
± 7 days 
±14d±14d
Day 
-14 to -9 -8 
-7 -6 
-5 
1 
2 
3 
4 
5 
8 
Week 
2 
3 
4 
5 
6 
8 
10 12 16 20 24 
Month 
9 
12 
C-reactive protein 
(CRP)13 
X 
X 
X 
X 
X 
X 
Uric acid 
X 
X 
GFR14 
X 
X 
Vector copies 
(Persistence) for 
safety20 
X9 
X 
X 
X 
VSV-G DNA 
(RCL) for safety20 
X9 
X 
X 
X 
X 


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Screening
1 
Interventional phase 
Screening Leuka- 
pheresis 
Base 
line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
Leukapheresis15 
X 
Fludarabine 
(X) X X 
X 
Cyclophosphamide 
X X 
X16 
NY-ESO-1c259T 
infusion 
X 
ICE 
X24 
X24 
Tumor biopsy 17 
X 
X 
X 
Pharmacogenetic 
whole blood 
sample 
X18 
PBMC (functional 
assays, immuno-
phenotyping) 
X 
X9 
X 
X 
X 
X 
X 
X 
X 
 


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Screening 
1 
Interventional phase 
Screening Leuka- 
pheresis 
Base 
line3 
Lymphodepleting 
Chemotherapy 
T-cell 
infusion
Post-infusion Assessments 
Visit Number 
1 
2 
3 
4 
(5)23 
5 
(6) 
6 (7) 7 (8) 8 (9) 
9 
(10) 
10 
(11) 
11 
(12) 
12 (13) 13 
(14) 
14 
(15) 
15 
(16) 
16 
(17) 
17 
(18) 
18 
(19) 
19 
(20) 
20 
(21) 
21 
(22) 
22 
(23) 
23 
(24) 
24 
(25) 
Every 3 
Months 
through 
Yr 220,25 
Completion 
or 
withdrawal 
4 
Visit window 
± 1 day 
± 3 days 
± 7 days 
±14d±14d 
Day 
-14 to -9 -8 
-7 -6 
-5 
1 
2 
3 
4 
5 
8 
Week 
2 
3 
4 
5 
6 
8 
10 12 16 20 24 
Month 
9 
12 
Cytokine 
analyses 19 
X 
X9 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-NY-ESO-1 
TCR Antibodies 
(Immunogenicity 
Sample)25 
X9 
X 
X 
X 
X 
X 
X 
X 
X 
Exosome and 
ctDNA 
collection (liquid 
biopsy) 
X 
X 
X 
X 
X 
Vector copies 
(Persistence) for 
research 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1. 
Visit 2 screening assessments should be completed within 28 days of leukapheresis unless otherwise specified below. 
2. 
Written subject informed consent must be obtained prior to performing any protocol procedures. An initial tissue screening informed consent will be signed prior to obtaining a blood sample for HLA 
testing and tumor tissue for tumor antigen testing. The treatment informed consent will be signed prior to all other screening procedures. 


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3. 
Baseline assessments must be conducted < 7 days prior to lymphodepleting chemotherapy. 
4. 
If a subject withdraws consent or completes the interventional phase, all procedures and assessments listed in the completion or withdrawal visit must be performed, unless performed within the 
previous 30 days. 
5. 
Timed vital signs (temperature, pulse, respirations and blood pressure (BP) on day of T cell infusion should be taken pre-infusion, and at 5, 15 and 30 minutes (±2 minutes), and 1, 1.5, 2, and 4 hours 
(±5 minutes) after the infusion has started. 
6. 
Information regarding CT/ MRI scans, ECHO/MUGA scans, performed as standard of care assessments within 4 weeks prior to screening (prior to study consent) will be acceptable. CT/MRI scans 
performed at Screening are for eligibility purposes only and not for response determination.  Scans performed at Baseline and later timepoints will be used for response determination. 
7. 
If a subject is found to have a clinical response by imaging, a follow-up confirmation scan must be done at least 4 weeks following the scan where response is first seen. If a response is observed at 
week 12 or subsequent visit, the subject should attend for confirmation scan 4 weeks later, in advance of the next scheduled scan. 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 8.5). 
8. 
Within 7 days of leukapheresis. Lymphocyte subsets to include absolute CD3 count. 
9. 
Samples to be collected Day 1 pre-infusion. 
10. Additional tests may be done at any time if clinically indicated. 
11. Testing for infectious disease markers is required only at Screening (Visit 2) and does not need to be repeated at Baseline to satisfy the inclusion / exclusion criteria. Subjects who are hepatitis B 
surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA. Subjects who are HCV antibody positive must have negative HCV RNA. 
12. CMV IgG seropositive subjects only 
13.  If cytokine release syndrome is suspected, CRP levels should be measured every day for the first week and approximately every other day thereafter until symptoms are improving or an alternative 
diagnosis is confirmed. 
14. Renal function will be estimated using the Cockcroft-Gault formula at Screening (Visit 2) for all subjects. At Baseline subjects <65 years may have creatinine clearance estimated using the Cockcroft-
Gault formula. Subjects ≥65 years of age must have renal function measured either by 24-hour urine creatinine collection or by nuclear medicine GFR measurement according to standard practice at 
the treating institution. 
15.  Screening prior to leukapheresis will meet regional legislative requirements. 
16. G-CSF should be given from 24 hours after the last dose of cyclophosphamide until resolution of neutropenia in accordance with ASCO guidelines or institutional practice. Long-acting (pegylated) G-
CSF may be substituted according to institutional practice as described in Section 8.7.1 
17. Core needle biopsies for research are required at baseline, Week 8, and at progression, with the exception of subjects for whom there is no safely accessible tumor tissue. Archival tissue may be 
used for screening. The baseline biopsy should be collected as close to the start of lymphodepleting chemotherapy as possible, but no more than two months prior. Exosome/ ctDNA samples should 
match biopsy time points. 
18.  If pharmacogenetics sample collection is not done at baseline, it may be done at any other subsequent visit while the subject is in the interventional phase of the study. Collection of a 
pharmacogenetics sample is optional and all subjects who participate must provide consent for pharmacogenetics blood sample collection. 
19. Pre-infusion, Week 3, Week 8, and Week 12 blood collection is for both Cytokine and Immunogenicity responses and is collected in one 3 mL tube. If CRS is suspected, cytokines should be collected 
every day for the first week and approximately every other day thereafter until symptoms are improving or an alternative diagnosis is confirmed.  
20. Vector copies for safety samples are collected Day 1 (pre-infusion) and then every 6 months post-infusion up to 5 years (Section 10.3.4 for more details). For RCL, samples are collected Day 1 (pre-
infusion), and at Week 12, Week 24, and 1 year post-infusion and then annually for up to 15 years. 
21. ECG on the day of T-cell Infusion (Day 1) may be performed at any time pre-infusion. 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 clinically significant cardiovascular risk factors (as per Section 
7.4.8) will undergo evaluation by a cardiologist prior to lymphodepletion. 
22. Brain MRI (or CT Scan if MRI not feasible) should be obtained in all subjects at the time of screening. Baseline Brain MRI should be repeated if more than 4 months have elapsed prior to 
lymphodepletion. 
23. Revised lymphodepletion schedule only given if cohort expands and lymphodepletion regimen changes. 


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24. ICE should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving treatment and then at least through Day 8 according to the schedule of procedures. Subjects with known brain 
metastases should be monitored at least twice per day for the first 5 days following NY-ESO- 1c259T cell infusion. If a subject is found to 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. 
25. Samples for TCR antibodies are to be taken on the day of T-cell infusion (Day 1), at Weeks 3, 5, 8, 12, and 24, at Months 9, 12, 18 and 24, and at study completion or withdrawal.   
 


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Table 5 
Schedule of Procedures in Long-Term Follow-up Phase prior to Transfer to LTFU  Study 208750 
Time post-infusion 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Years 6-15 
Months3 
6 
12 
18 
24 
30 
36 
42 
48 
54 
60 
Annually 
Visit window± 2 
weeks 
± 3 months 
± 6 months 
Safety Assessments 
Medical History and Physical Exam1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mutagenic agents, other investigational agents or anti-
cancer therapies1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events and Serious Adverse Events2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X3 
Serum chemistry 
X 
X 
X 
X 
X 
X 
X 
X3 
Pregnancy Test (for WOCBP)4 
<===========================X4==========================> 
Central Lab 
VSV-G DNA (RCL) for safety5 
X 
X 
X 
X 
X 
X 
X 
X 
Vector Copies (Persistence) for safety6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X3 
Other Assessments 
Survival Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1. 
New medical history/medications/chemotherapies. 
2. 
Adverse event collection is limited to: 
• 
New malignancies 
• 
New incidence or exacerbation of a pre-existing neurologic disorder 
• 
New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder 
• 
New incidence of an immune-related hematologic disorder 
• 
Serious infections (including opportunistic) 
• 
Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy 


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3. 
In year 6-15, laboratory assessments are performed for as long as persistence is analyzed. If persistence samples are discontinued (Section 10.3.3 and Section 10.3.4) then laboratory assessments 
are discontinued. 
4. 
For WOCBP, pregnancy testing should be conducted during contraception period only as defined in Section 4.1, Inclusion Criteria. When pregnancy testing is performed at visits where hematology 
sample is collected, blood pregnancy testing will be done. At visits where hematology testing is not performed, urine pregnancy test is acceptable unless serum testing is required by local regulation 
or IRB/IEC. 
5. 
Samples for RCL (VSV-G copies) are collected as described in Section 10.3.1. 
6. 
Samples for persistence are collected as described in Section 10.3.3, and Section 10.3.4. 
 


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7.4. 
Clinical Assessments and Procedures 
7.4.1. 
Demographics 
Demographic data including age, gender, race and ethnicity will be collected at 
screening. 
7.4.2. 
Disease History 
The following information will be recorded in the eCRF for myxoid/ round cell 
liposarcoma: primary tumor type, date of initial diagnosis, location of disease at initial 
diagnosis, stage at initial diagnosis, type of histology, histological grade, results of any 
historical molecular testing performed (if available), date of diagnosis of metastatic 
disease, location of disease, stage at screening. 
7.4.3. 
Medical History 
Relevant medical history will be recorded at screening in the subject’s medical record 
and eCRF. 
7.4.4. 
Physical Examination and Vital Signs 
At baseline, subjects will undergo a physical examination including weight, height and 
measurement of vital signs (temperature, heart rate, respiratory rate, and blood pressure). 
The frequency of physical examination, weight and vital signs assessments at subsequent 
visits is specified in the Schedule of Procedures (Table 4). 
7.4.5. 
Performance Status 
At baseline, performance status will be measured using the ECOG performance scale (see 
Section 16.2). It is recommended, where possible, that a subject’s ECOG be assessed by 
the same person throughout the study. The frequency of the ECOG assessment is 
specified in the Schedule of Procedures (see Section 7.3). 
7.4.6. 
Clinical Safety Assessments 
Subjects will be assessed for AEs throughout the study. Specific grading systems for 
Cytokine Release Syndrome (CRS) and Graft versus Host Disease (GvHD) are described 
in Section 8.5 and Section 8.6 AEs are to be graded by NCI Common Terminology 
Criteria for Adverse Events (CTCAE) Version 4.0. All AEs must be recorded in the 
eCRF. 
Details on assessing and reporting AEs and SAEs are described in Section 9. 


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7.4.7. 
Laboratory Assessments 
All laboratory assessments will be performed locally at the site, and laboratory reference 
ranges must be provided to Sponsor before the study initiates. 
The following assessments will be conducted in order to monitor subject safety. Refer to 
Section 16.3 for listing of lab tests 
• Hematology 
• Biochemistry 
• Coagulation 
• C-reactive Protein 
• CMV viremia (see Section 8.2.1) 
• Urinalysis 
 
Female subjects of childbearing potential (WOCBP must have a negative pregnancy test 
at screening, within 24 hours prior to starting lymphodepleting chemotherapy, and 
monthly thereafter during the interventional phase of the study as indicated in  
Section 7.3. 
Please refer to Schedule of Procedures for additional information regarding the frequency 
of these assessments. 
7.4.8. 
Cardiac Assessments 
All cardiac assessments will be performed locally at the site. 
The following assessments will be conducted in order to monitor subject safety: 
• An ECHO or MUGA scan will be performed at screening to determine eligibility. 
Additional scans will be performed only if clinically indicated. NOTE: the same 
method of cardiac evaluation must be used consistently for any follow-up scans. 
• ECGs: refer to Section 16.3 for the ECG parameters required 
Please refer to Schedule of Procedures (Table 4) for information regarding the frequency 
of these assessments. 
For subjects with cardiac or pericardial disease at baseline, inpatient telemetry monitoring 
will be carried out for a minimum of three and up to seven days post [TCR] infusion. 
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  


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– 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 treatment with NY-ESO-1c259T infusion will continue to be 
monitored through normal proactive Pharmacovigilance to determine causality. 
Supportive care for these participants will be provided per standard clinical practice 
guidelines. 
7.4.9. 
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. 
 


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7.4.10. 
Monitoring for Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) 
Brain MRI (or CT Scan if MRI not feasible) should be obtained in all subjects at the time 
of screening. Baseline brain MRI should be repeated if more than 4 months have elapsed 
prior to lymphodepletion. 
Immune Effector Cell-Associated Encephalopathy (ICE) should be measured on the day 
of NY-ESO-1c259T infusion prior to receiving treatment and then at least through Day 8 
according to the schedule of procedures. Subjects with known brain metastases should be 
monitored at least twice per day for the first 5 days following NY-ESO-1c259T infusion. 
If a subject 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. 
7.4.11. 
Tumor Response Assessments 
Tumor assessments for response and progression will be evaluated at Baseline (within 1 
week prior to chemotherapy), Week 4, Week 8, Week 12, Week 24, and every 3 months 
until  disease progression and again at study completion/withdrawal, according to the 
RECIST v 1.1 criteria (Section 16.4). 
Imaging scans of the chest, abdomen and pelvis should be performed at Baseline and all 
subsequent visits. Acceptable imaging modalities for this study include: 
• Diagnostic-quality CT scan with oral and/or i.v. iodinated contrast of the chest 
and abdomen/pelvis (CT is the preferred modality for tumor assessments) 
• MRI of the abdomen/pelvis acquired before and after gadolinium contrast agent 
administration and a non-contrast enhanced CT of the chest, if a subject is 
contraindicated for contrast enhanced CT 
• MRI of the extremities per site standard of care, if clinically indicated. 
• Digital photographs of skin lesions including a ruler for estimating the size of the 
lesion. 
The same imaging modality and image-acquisition protocol (including the use of IV 
contrast) should be used consistently across all time points for individual subjects to 
allow uniform comparison of lesions. Prior to starting the study, a detailed imaging 
acquisition protocol (Site Imaging Manual) will be provided to the sites to describe the 
requirements for image acquisition and the standardized procedure for the transfer of 
image data to the central vendor. 
To allow time for the immune response to become apparent and for potential transient 
inflammatory reaction of the disease to the treatment (‘tumor flare’), response will not be 
assessed before 4 weeks post infusion of NY-ESO-1c259T, unless there is unequivocal 
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[PR]) should be confirmed by repeat imaging scan performed 4 weeks (but not earlier) 
after the criteria for response were first met. 
Confirmatory scans should be completed in advance of the next scheduled visit if the next 
scan is due more than 4 weeks after the response is first observed. 
Investigators will assess tumor response according to RECIST v1.1 for clinical decision 
making and for determination of the primary endpoint. Tumor measurements at site 
should be performed by the same radiologist (to the extent that this is feasible). 
Throughout the study the same imaging technique should be used in order to allow 
accurate comparisons to be made. 
A central vendor will collate study images. Review and interpretation of tumor response 
according to RECIST v1.1 will be conducted by an appropriately qualified, trained and 
experienced reviewer. 
A written Site Imaging Manual will be provided to sites to describe the imaging 
acquisition protocol and standardized procedure for the transfer of image data to the 
central vendor. The Site Imaging Manual will also describe the procedures for CT/MRI 
data handling after the images have been received by the central vendor from the sites.  
The study has the option to collect and hold scans for review at a later date rather than 
advancing to read and report upon receipt by the central vendor. 
7.4.12. 
Long-Term Follow-up 
All subjects will be followed for 15 years from time of T cell infusion for observation of 
delayed adverse events in accordance FDA and EMA requirements for gene therapy 
clinical trials. [FDA Guidance, 2006b; FDA Guidance, 2010; FDA Guidance, 2020]. 
Subjects will be seen and laboratory analysis conducted at 3, 6, and 12 months in the first 
year post-infusion. Subjects will be seen in the clinic and samples taken every 6 months 
in years 2 -5 and then annually from years 6-15. Assessments will include medical 
history, physical exam, and reporting of adverse events, plus exposure to mutagenic 
agents, anti-tumor agents and other medicinal products. Assessments will be collected 
under GSK208469 (ADP-0011-007) while subjects are on the interventional phase.  After 
completion of the Study 208469 interventional phase, assessments may be collected 
either under the LTFU protocol GSK208750 (ADP-0000-002) or under the current 
protocol until the LTFU GSK208750 is available. 
Reporting criteria for AEs related to gene therapy during LTFU are described in 
Section 9.4. 
7.5. 
Correlative Studies and Research Assessments 
Correlative studies and research assays will be performed during the trial with the aim of 
monitoring the biological parameters that influence the outcome of the treatment, such as 
T Cell phenotype, function and persistence of the engineered infused cells as well as 
evaluate candidate biomarkers and correlate with clinical response to treatment. These 


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studies will be performed on tumor biopsies, serum/plasma and fractionated PBMC 
samples collected according to the schedule of procedures. All samples will be processed 
and/or frozen following trial specific SOPs and analyzed either by central laboratory 
facilities contracted by the Sponsor or by the Sponsor itself at the Sponsor’s facilities. 
Documentation for sample receipt, processing and storage, and primary data from the 
research analyses will be collected and stored at the Central Lab or at GSK as 
appropriate. 
Research studies conducted on blood samples may include, but are not limited to the 
following: 
• Flow cytometry to analyze cell subsets and persistence of engineered T cells 
• PCR to measure persistence of T cells 
• Genomic sequencing to assess T cell clonality through TCR Vbeta and Valpha 
sequencing and integration site analysis 
• Meso-Scale Discovery platform to measure serum cytokine levels 
As new technologies and data emerge, other assays relevant to the study objectives may 
be performed. 
Biopsy research studies may include: 
• DNA and RNA analysis including PCR and in-situ hybridization to measure 
infiltration of T cells 
• Genomic sequencing to assess T cell clonality through TCR Vbeta and Valpha 
sequencing 
• Tissue expression of the target antigen (NY-ESO-1 and LAGE-1a) 
• Tissue analysis for immune cell infiltrate and functional biomarkers (by single or 
multiplexed IHC) and gene expression profile (including by Nanostring or next-
gen sequencing of RNA) 
• Tissue analysis to determine the evolution of the mutation profile of the tumor 
over the course of the therapy by DNA sequencing analysis 
• As new technologies and data emerge, other assays relevant to the study 
objectives may be performed 
If a subject has an adverse event, an additional biopsy (for example skin, GI tract, bone 
marrow, tumor) or blood (serum and PBMC) samples may be requested with the 
objective of gaining an understanding of the underlying etiology of the ongoing adverse 
event. For this purpose, the above described research tests may be performed on these 
samples. 


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7.5.1. 
Pharmacogenetics Sample 
A whole blood sample for pharmacogenetic research may be obtained at any time 
throughout the study (refer to Table 4) in addition to any blood samples taken for the 
clinical study. The pharmacogenetic sample is labelled (or “coded”) with a study specific 
number that can be traced or linked back to the subject by the investigator or site staff. 
Coded samples do not carry personal identifiers (such as name or social security number). 
The blood sample will be taken on a single occasion unless a duplicate sample is required 
due to inability to utilize the original sample. The blood sample can be taken at baseline 
or at any point during the interventional phase of the study providing that the subject has 
given written informed consent for pharmacogenetics research. 
The Pharmacogenetic sample may be used to investigate the association of candidate or 
genome-wide genetic variants with efficacy (ORR, DOR) and safety such as but not 
limited to Cytokine Release Syndrome frequency/severity/duration. 
7.5.2. 
Cytokine and Soluble Factors Analysis 
Serum is collected at baseline, and at each visit post infusion up to 8 weeks, to allow for 
measurement of cytokines in the blood. Serum is also collected from subjects with 
suspected cytokine release syndrome (CRS), samples being taken approximately every 
other day until symptoms are improving or an alternative diagnosis is confirmed. Details 
regarding serum collection are provided in the SPM. 
Cytokines, growth factors and soluble receptors including but not limited to IL-6, IFN-γ, 
TNF-α, IL-2Rα, IL-10, IL-13, IL-1Rα, IL-8, IL-12, IL-15, IL-2, and GM-CSF are 
measured utilizing a multiplexed Luminex assay. 
GLP measurement of the cytokine subset IL-1β, IL-10, IL-6, TNF-α, and IFN-γ is 
performed. All other measurements are exploratory. 
Serum samples may also be used to investigate as the presence of antibodies to NY -
ESO-1c259T. 
7.5.3. 
Tumor Biopsies 
The efficacy of immunotherapy of cancer is conditioned by the infiltration of tumors by 
activated tumor-specific T cells. The activity of these T cells will in turn be affected by 
the presence in the tumor of an immunosuppressive environment (e.g., regulatory T 
cells). Therefore, the direct evaluation of the “immune landscape” inside the tumor is of 
great value for understanding and optimizing cancer immunotherapy. For this reason, 
core needle biopsies are mandated at screening, baseline (to evaluate the immune status 
of the tumor before T cell infusion), Week 8 (at the expected time of an active anti-tumor 
response by infused T cells) and at the time of documented disease progression, with the 
exception of subjects for whom there is no safely accessible tumor tissue. 
Archival tissue may be used for the screening biopsy, although fresh tissue is preferred. If 
fresh tissue is provided at screening, and sufficient material is available for research 


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studies, the baseline biopsy can be omitted. Otherwise the baseline biopsy material 
should be collected any time between two months and 2 weeks prior to the start of 
lymphodepleting chemotherapy, with preference for a biopsy to be taken closer to the 
time of infusion. Tumor tissue should either be taken from non-target lesions or from 
target lesions >2cm and when possible the same lesion(s) should be biopsied at both 
screening and subsequent time points. The apparent clinical or scan status of the lesion(s) 
biopsied should be noted at the time (e.g., decreased, stable, increased size or activity). 
If feasible, biopsy material should be collected at the time of documented disease 
progression, ideally on lesions that have progressed. 
Additional details regarding the tumor biopsy collection is provided in the SPM. 
In subjects who have effusions, should there be a clinical requirement for removal of the 
effusion fluid at any time during study, samples are requested to be collected for GSK for 
translational research studies. If available, effusion fluid should be collected in addition 
to and not instead of the requested tumor biopsies. 
Clinically obtained effusion samples have been shown to be a rich source of tumor cells, 
tumor infiltrating leukocytes and soluble factors. Effusion fluid collected in this protocol 
will be used to interrogate soluble and cellular components of the tumor 
microenvironment before and after T cell infusion to address mechanisms of sensitivity 
or resistance to therapy. 
7.5.4. 
NY-ESO-1c259T TCR+ Cell Persistence 
The primary research assays for the trial involve monitoring for the persistence of infused 
engineered cells in the subjects and for correlation of this with potential therapeutic 
effect. Persistence is also monitored long term as a safety measure (Section 10.3.3). Two 
well established methodologies will be used to measure the cells; quantitative polymerase 
chain reaction (qPCR) and flow cytometry (FCM). 
• Quantitation of NY-ESO-1c259T TCR+ cells by PCR of transgene from DNA 
extracted from frozen PBMC. This will be used as a measure of 
pharmacokinetics.  
• Quantitation of NY-ESO-1c259T TCR expression cells by flow cytometry (FCM) 
from frozen PBMC 
7.5.5. 
NY-ESO-1c259T TCR+ Cell Phenotype and Activity 
A range of assays will be performed to elucidate the phenotype and activity of the gene-
modified T cells before (manufactured product) and after infusion in the blood (and 
tumor if resection is performed). The assays performed will depend upon availability of 
sample and clinical / scientific significance. The following assays may be performed 
(analysis may not be limited to these assays; additional assays may be added as they 
become available). 


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• Phenotype analysis for determination of T cell lineages in manufactured cell 
product prior to infusion and in the blood (and tumor if resection performed) post 
infusion over time 
• Quantitation of the senescence and activation status of immune subsets from 
PBMC 
• Quantitation of soluble factors reflecting in vivo function of NY-ESO-1c259T 
TCR+ T cells 
• Anti-gene modified T cell immune responses (tertiary assay). 
• Ex-vivo activity of transduced cells at different time points to assess potential 
anergy of those cells. 
• Analysis of Gene expression profile to reflect activity of the cells 
7.5.6. 
Liquid Biopsy Collection and Analysis 
Recognizing that tumor biopsies cannot always be obtained safely, we set out to 
investigate whether alternative safer approaches can provide similarly valuable 
information. Therefore, in addition to tumor biopsies, liquid biopsies will be collected in 
parallel, covering complementary materials that might provide information about 1) the 
tumor microenvironment (inflammatory or immunosuppressive profile) and 2) the 
immune response mediated by the NY-ESO-1 TCR- transduced T cells. These materials 
are cell-free DNA (cfDNA) and exosomes (source of stable mRNA). 
Exosomes (produced by all cells, including tumor cells and immune cells) and cfDNA 
(produced by dying tumor cells) will be used to monitor both the molecular signature of 
the tumor burden and the immune response. The analysis of exosomes and cfDNA will 
allow: 
• Estimation of the global tumor mutational burden and genomic profiling from 
cfDNA. 
• RNA expression profiles including expression of NY-ESO-1 and LAGE-1a 
mRNA from exosomes. 
• Systemic assessment of the immune response (gene expression by cytotoxic and 
regulatory immune cells) from exosomes. 
7.5.7. 
Request for Autopsy for Death Following Administration of Gene 
Transfer Agents 
In accordance with FDA and EMEA guidance [FDA, 2006a; EMEA, 2009] all subjects 
who are enrolled in this trial are asked to consent to autopsy and autopsies be requested 
of the families for all subjects who die during participation in studies after administration 


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of gene transfer agents. To assure compliance, guidelines for performing an autopsy are 
provided in the SPM. 
7.6. 
Retreatment 
Subjects who achieved a confirmed CR or PR or SD ≥3 months following first 
GSK3377794 infusion will have an option to receive a second course of conditioning 
chemotherapy and GSK3377794 under the following conditions: 
• 
Subject had a confirmed CR or PR or SD ≥3 months following first GSK3377794 
infusion 
• 
Subject’s disease subsequently progressed in >3 months after first infusion 
• 
Eligibility based on NY-ESO-1 expression from fresh biopsy is confirmed (from 1st 
infusion progression biopsy optimally obtained prior to receipt of any additional 
systemic anti-cancer therapy). In cases where second lete-cel infusion is permitted 
after patients have received subsequent anti-cancer therapies post-progression from 
first lete-cel infusion, a recent biopsy sample collected after progression from recent 
anti-cancer therapy should be confirmed for NY-ESO-1 expression.  If acquisition of 
a post-progression biopsy sample is not feasible, alternatives may be discussed with 
the medical monitor. 
• 
Subject continues to meet the original study eligibility criteria with the exception of  
o Exclusion criterion 1: prior GSK3377794 use in this study as defined in 
Section 4 and per Section 7.6.1. and 
o Inclusion criterion 12: Subject is fit for apheresis and has adequate venous 
access for the cell collection 
• 
Screening assessments must be repeated if clinically indicated, as determined by the 
investigator, to confirm eligibility 
• 
Subject has not received systemic anti-cancer therapy for the treatment of sarcoma 
with the exception of bridging therapy which is permitted. If subjects have received 
subsequent anti-cancer therapies post-progression from first lete-cel infusion, 
administration of second lete-cel infusion may be permissible on a case-by-case basis 
upon discussion with the medical monitor. 
• 
Subject did not experience a Grade 4 CRS event or Grade 4 neurologic toxicity after 
the first GSK3377794 infusion  
• 
Toxicities related to conditioning chemotherapy with the exception of alopecia, have 
resolved to ≤Grade 1 or returned to baseline prior to retreatment 
• 
Sufficient cell dose is available from the original manufacturing procedure to allow 
for retreatment (i.e. subjects will not undergo repeat leukapheresis) and within shelf-
life specifications. No new leukapheresis or manufacture will be performed. 
The decision to administer retreatment must be made in consultation with the medical 
monitor. In addition, a discussion regarding benefits and risks of retreatment should occur 


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with the subject prior to performing any study-related procedures or treatment. This 
conversation should also be recorded in the subject’s source document. 
Subjects must be reconsented prior to performing any study related procedures or 
treatment.  
A maximum of 1 retreatment course may occur per subject. Subjects who are retreated 
must follow the same treatment schedule and procedural requirement per the initial 
retreatment. Data will be captured in the retreatment eCRF.  
7.6.1. 
Benefit:Risk Assessment 
See Section 3.5. 
Allowance for retreatment is based on clinical experience across multiple studies of CAR 
and TCRs and prior experience from the lete-cel program.  In 2 studies conducted at the 
pediatric [Lee, 2015] and Surgery Branch [Kochenderfer, 2015] of the National Cancer 
Institute (NCI) 6 subjects were re-treated upon progression. Three of the re-treated 
subjects (indolent lymphoma/leukemia) experienced durable responses to retreatment 
after an initial response and disease progression.  Gauthier et al, [Gauthier, 2021] 
demonstrated that second infusions of CAR-T therapy were both feasible and induced 
responses in 39% of subjects, including CRs in 20%.  Evidence of tumor regression post 
disease progression following a second infusion of TILs was demonstrated by Tran el al, 
[Tran, 2014] in a subject with cholangiocarcinoma. Similarly Hegde et al [Hegde, 2020] 
reported a second remission (CR) in a child with rhabdomyosarcoma following 
retreatment with HER2 CAR T cells following progression 6 months post first CAR T 
infusion.  
In sponsored trials, a total of sixteen (16) subjects [11 subjects in Study 208466 
(MRCLS) (formerly ADP-04511), 4 subjects in Study 209393 (multiple myeloma) 
(formerly ADP-01411), and 1 subject in Study 208749 (NSCLC) have received a second 
infusion of GSK3377794 after progressive disease following response (or prolonged 
stable disease) to their initial infusion. There were no fatal SAEs reported among subjects 
who received a second infusion of GSK3377794. Although the data is limited, the safety 
profile following a second infusion of GSK3377794 is consistent with that of all subjects 
infused.  
In Study 208466, many of the subjects who underwent initial treatment with 
GSK3377794 demonstrated clinical benefit, with measurable tumor regression by 
RECIST 1.1 and investigator assessment observed in one third (33%) of subjects. On 
retreatment, 1 CR, 1 PR, and multiple SD were observed. In Study 208749 1 subject 
received a second infusion post progression and achieved SD.  
Data from preclinical studies support the efficacy, specificity, and safety of GSK3377794 
(Investigator Brochure). Clinical data from subjects who have undergone a second 
infusion demonstrate the safety and activity sufficiently to support retreatment.  


TMF-14208393 
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7.6.2. 
Lymphodepletion and T-Cell Infusion  
Lymphodepletion and T-cell infusion follow the same procedures as outlined in Section 
3.2 and in Section 5.2 and Section 5.3. 
7.6.3. 
Study Procedures 
All study procedures should be carried out as defined for initial treatment, including 
safety and response assessment, with the exception of leukapheresis which is not part of 
retreatment or second treatment. See Section 7, Table 4. Assessments will follow the 
same schedule as for the first infusion. 
7.6.4. 
Completion of Retreatment / Second Treatment Interventional 
Phase 
Per Section 4.3, a GSK3377794 infused subject will be considered to have completed the 
interventional phase of the study when he/she has progression of disease (see Section 
7.4.11 for tumor response assessments), death, or has been followed-up for 2 years after 
GSK3377794 infusion, whichever is shorter.  
Subjects being considered for retreatment will enter the retreatment interventional phase 
on completion of the interventional phase.  
Subjects who meet eligibility for and undergo retreatment will be considered to have 
completed the retreatment interventional phase of the study when they have progression 
of disease following retreatment, death, or have been followed-up for 2 years after re-
treatment, whichever is shorter. The sponsor may terminate the study before all retreated 
subjects have completed the retreatment interventional phase.  In such cases, these 
ongoing subjects will transfer to long term follow-up at that time.  
All subjects alive on completing or withdrawing from the retreatment interventional 
phase will continue into long-term follow-up (LTFU) for observation of delayed adverse 
events as described in Section 7.4.12.  If necessary and upon discussion with the Sponsor, 
those subjects who have not progressed after 2 years post retreatment and who are 
continuing in Study 208469 may continue to undergo response assessments every 
3 months as defined in Study 208469 per institutional standard of care.   
7.6.5. 
Long-Term Follow-Up 
See Section 4.3.1 for details of long-term follow-up. For subjects who undergo 
retreatment, timing starts from second infusion of GSK3377794. 
7.6.6. 
Response Assessment 
Response assessment will be followed as per Section 7, Table 4. Assessments will follow 
the same schedule as for the first infusion. 


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8.1. 
T Cell Infusion Symptom Management 
Mild transient symptoms have been observed following infusion of engineered T cells. 
The management of these symptoms is suggested but should not necessarily be confined 
to the below. 
• Fever, chills, headache and temperature elevations will be managed with 
acetaminophen. It is recommended all subjects that develop fever or chills have a 
blood culture drawn. 
• Nausea and vomiting may be treated with a non-steroidal anti-emetic of choice. 
• Hypotension will initially be managed by intravenous fluid administration and 
further measures as dictated by standard medical practice. 
• Hypoxemia will initially be managed with supplemental oxygen and further 
measures as dictated by standard medical practice. 
8.2. 
Infection 
Subjects should receive prophylaxis against Pneumocystis pneumonia, herpes simplex, 
and varicella zoster as per institution guidelines. In addition, measures to treat and 
prevent infection may be provided in accordance with institution guidelines. In particular, 
fever and neutropenia should be aggressively managed as well as pre-emptive influenza 
therapy and other standard therapies for immunocompromised hosts. For participants 
with indwelling central lines, consider increased surveillance to monitor for catheter-
associated infections. 
8.2.1. 
Pneumocystis Carinii Pneumonia 
Subjects should receive prophylaxis against Pneumocystis pneumonia according to 
institutional guidelines. Single strength trimethoprim sulfamethoxazole daily is the 
recommended first line agent, starting at day 28 for one year. Other regimens including 
atovaquone (1500mg daily with food) or aerosolized pentamidine (300mg every four 
weeks) are also acceptable, e.g., in case of sulfonamide allergy. 
8.2.2. 
Herpes Simplex and Varicella-Zoster 
All subjects should receive prophylaxis with acyclovir (800mg twice daily) or 
valacyclovir (500mg twice daily) for one year, or in accordance with institutional 
guidelines. 
8.2.3. 
Cytomegalovirus 
Subjects will be screened for cytomegalovirus (CMV) seropositivity at study entry. CMV 
seropositive subjects will be monitored for CMV viremia by CMV DNA PCR as shown 
in Table 4 until 60 days post infusion of NY ESO 1c259T. In the event CMV viremia is 


TMF-14208393 
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80 
 
observed a specialist in infectious disease should be consulted and treatment initiated if 
necessary according to institutional practice. 
If a subject experiences prolonged or recurrent pancytopenia or lymphopenia additional 
monitoring for viral reactivation should be considered and treatment for viral infection 
initiated if necessary. A strategy for management of pancytopenia or bone marrow failure 
is described in Section 8.7.2. 
8.2.4. 
Hepatitis B Prophylaxis 
Subjects will be screened for hepatitis B (HBV) at study entry. Subjects who are hepatitis 
B core antibody positive must receive prophylaxis against viral reactivation using 
institutional protocols. Prophylaxis should be initiated prior to lymphodepleting therapy 
and continued for 6 months. 
8.2.5. 
Treponema 
Subjects will be screened for treponema (syphilis) at study entry. Subjects with positive 
screening results should be evaluated by an infectious diseases consultant. If determined 
to have syphilis infection, the subject should be treated before lymphodepletion 
chemotherapy. 
8.2.6. 
Other Anti-Microbial Prophylaxis 
Antibacterial and antifungal prophylaxis should follow institutional standards for 
autologous bone marrow transplants. If a participant requires anti-microbial treatment 
associated with risk of cardiac toxicity, consider close monitoring of cardiac function 
(Section 7.4.8). 
8.3. 
Hematologic and Blood Product Support 
Blood product support should be provided to maintain: 
• platelets >10 x109/L in the in-patient setting and platelets >20 x109/L in the out-
patient setting 
• Hb >8.0 g/dL  
or as clinically indicated in the judgement of the Investigator (in accordance with 
institutional practice).  
See AABB Guideline on platelet transfusion [Kaufman, 2015]. 
8.3.1. 
Blood Product Irradiation 
Bone marrow suppression can be a consequence of transfusion associated GvHD. To 
minimize the possibility of transfusion associated GvHD, all blood products transfused 


TMF-14208393 
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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 study T cell infusion or until lymphocyte count returns to ≥1.0 
x109/L (whichever is longer) must be irradiated. In addition, if a subject requires systemic 
steroids or immunosuppression for the treatment of toxicity, irradiated blood products 
must be given until recovery of immune function. 
8.3.2. 
CMV Screened Blood Products 
Subjects will be screened for CMV seropositivity on study entry. In order to reduce the 
risk of primary CMV infection all subjects (i.e., both CMV seropositive and -negative 
subjects) should receive leukoreduced blood products where possible (excluding the 
study T cell infusion). Where leukoreduced blood is not available, CMV IgG negative 
subjects must only receive blood products from CMV-seronegative donors from study 
entry to study completion or withdrawal. 
8.4. 
Management of Autoimmunity 
Subjects should be monitored throughout the trial for potential autoimmune reactions in 
response to the genetically engineered T cells that could include skin toxicity, liver 
toxicity, colitis, eye toxicity etc. If autoimmunity is suspected, the PI should be contacted 
and every attempt should be made to biopsy the affected organ to clarify whether the 
symptoms are related to the NY- ESO-1 T cell therapy. If the subject sustains persistent 
Grade 2, or Grade 3 or 4 autoimmunity, consideration should be given to administration 
corticosteroid therapy, either topically (e.g., skin, eyes) or systemically, as clinically 
indicated. 
8.5. 
Management of Cytokine Release Syndrome 
Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been 
observed following administration of antibodies and adoptive T-cell therapies for cancer. 
It is defined clinically by symptoms many of which mimic infection including pyrexia, 
nausea, diarrhea, headache, fatigue, tachycardia, hypotension, transaminitis, rash and 
dyspnea. It is important to evaluate the subject for concurrent infections. Potentially life-
threatening complications of CRS include cardiac dysfunction, adult respiratory distress 
syndrome, neurologic toxicity, renal and/or hepatic failure and disseminated intravascular 
coagulation. CRS may also be associated with findings of macrophage activation 
syndrome or occur coincident with tumor lysis syndrome. 
CRS 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]. 
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 


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Grade Clinical Presentation for Grading 
Assessment1,2 
Management Guidelines 
1 
Vigilant supportive care4 
Assess for infection and treat5 
2 
Monitor cardiac and other organ 
function 
Vigilant supportive care4 
Assess for infection and treat5 
Treat hypotension with fluid and 
pressors 
Administer O2 for hypoxia6 
Consider administering tocilizumab ± 
corticosteroids7  
3 
Monitor participant very closely for 
cardiac and other organ dysfunction. 
Most likely will require monitoring in an 
intensive care unit (ICU). 
Vigilant supportive care4 
Assess for infection and treat5 
Treat hypotension with fluid and 
pressors6. Administer O2 for hypoxia. 
Administer tocilizumab ± 
corticosteroids7 
4 
Manage participant in ICU 
Intensive supportive care including 
mechanical ventilation, fluids, pressors, 
antibiotics and other measures as 
required6 
Administer tocilizumab ± 
corticosteroids7 
5 
 
 Fever is defined as temperature 38°C not attributable to any other cause. In patients who have CRS then receive 
antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent 
CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 
 CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. 
 
 
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
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 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. 
 Supportive care includes:  monitor fluid balance, maintain adequate hydration and blood pressure  
 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.  
 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. 
 Other immunosuppressor agents may be used, including TNFα and IL-1R inhibitors.  
Source: [Lee, 2019] 
 
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Subjects may receive a repeat dose if clinical signs and symptoms do not improve within 
24-48 hours. 
Side effects attributed to chronic use of tocilizumab in rheumatologic disease include 
transaminitis, thrombocytopenia, elevated cholesterol and low-density lipoproteins, 
neutropenia and increased infections but acute infusional toxicities have not been 
reported in CRS use [Lee, 2014; Lee, 2019]. 
Subjects unresponsive to tocilizumab or experiencing severe neurological symptoms 
(e.g., confusion, delirium, seizure, etc.) may require treatment with steroids. Lee, 2014 
and Lee, 2019 recommend steroids as second-line therapy for CRS as the response to 
tocilizumab may be more rapid and owing to the potential of steroids to attenuate the 
anti-tumor effects of the adoptive T-cell therapy. However, in subjects with grade 3 or 4 
CRS associated with neurologic dysfunction without significant hemodynamic instability 
or other life-threatening symptomatology, consideration may be given to the use of 
corticosteroids as a preferred first-line immunosuppressive therapy. High doses (e.g., 
2 mg/kg/day prednisone equivalent) may be required. 
If cytokine release syndrome is suspected, a physician with expertise in the management 
of subjects following bone marrow transplantation should be consulted. If high dose 
corticosteroids are required, treatment should generally be continued for at least 5 days 
followed by tapering doses over several weeks. 
Please refer to the most recent version of the product label for tocilizumab. 
If CRS is suspected, participants deemed to have significant cardiovascular risk factors 
(per Section 7.4.8) should be considered for 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 must 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. 
8.6. 
Management of Graft-versus-Host Disease (GvHD) 
Autologous graft-versus-host disease (GvHD) has been described in association with 
adoptive transfer of ex-vivo expanded/co-stimulated autologous T cells [Rapoport, 2009], 


TMF-14208393 
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as well as infusion of T cells with engineered specificity for NY-ESO-1 and LAGE-1a 
[Garfall, 2013], following high-dose chemotherapy and autologous stem cell transplant 
(ASCT) in patients with multiple myeloma. There is the potential for subjects who 
receive lymphodepleting therapy followed by engineered autologous T-Cell infusion to 
experience GvHD and/or autoimmune GvHD-like symptomatology. Autologous GvHD 
is typically milder than classic (allogeneic) GvHD [Kline, 2008] and is usually 
manageable with treatment. However, severe cases (including fatalities) have been 
reported [Fidler, 2012]. There are no published guidelines for the management of 
autologous GvHD. However, lessons can be drawn from published cases reports and 
guidelines for the diagnosis and management of acute GvHD following allogeneic 
transplant [Dignan, 2012]. 
8.6.1. 
Diagnosis of GvHD 
The diagnosis of GvHD is predominantly based on clinical findings and is often one of 
exclusion. Many of these symptoms can also occur in the setting of the preparative 
regimen as well as with cytokine release syndrome. 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 cytopenias are common toxicities in the NY-ESO-1c259T 
program where we have the most clinical experience. Mild (Grade 1 or 2) transient 
transaminitis without cholestasis has been observed. 
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, cytokine 
release syndrome, and 
effects of chemotherapy or 
radiation 
Apoptosis at base of 
epidermal rete pegs, 
dyskeratosis, exocytosis of 
lymphocytes, satellite 
lymphocytes adjacent to 
dyskeratotic epidermal 
keratinocytes and perivascular 
lymphocytic infiltration in the 
dermis. 
GI 
Secretory diarrhea is most 
common but nausea, vomiting, 
anorexia, weight loss and 
abdominal pain can also 
occur. Diarrhea can be 
copious. 
Bleeding may result from 
mucosal ulceration and ileus 
may ensue. 
Side effects of 
chemotherapy or other 
drugs and infection of the GI 
tract 
Patchy ulcerations, apoptotic 
bodies at crypt bases, crypt 
ulceration and flattening of 
surface epithelium 


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Organ Findings/Symptoms 
Differential Diagnosis 
Histopathology 
Liver 
Cholestatic pattern of liver 
injury including elevated 
conjugated bilirubin, alkaline 
phosphatase and GGTP. 
Subjects may present with 
jaundice, with pruritis in more 
severe cases. 
Veno-occlusive disease of 
the liver, viral infections, 
drug toxicity and sepsis. 
Endothelialitis, lymphocytic 
infiltration of the portal areas, 
pericholangitis and bile-duct 
destruction. 
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indices, which are protected by third party copyright laws and therefore have been excluded.
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Grade 
Management Strategy 
I 
Subjects with grade I disease are not likely to require systemic treatment. Cutaneous 
GvHD may respond to topical steroid creams. Antihistamines may be helpful in 
subjects with pruritis. Subjects should be reviewed frequently for other organ 
manifestations of GvHD. 
II 
Treat skin symptoms with topical steroids. For GI symptoms - optimize anti-diarrheal 
regimen, dietary restrictions, volume replacement and consider initiation of non- 
absorbable steroids. For refractory or progressive symptoms consider systemic 
steroids as outlined below. 
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*) 
IV 
Methylprednisolone two (2) mg/kg per day* 
* The use of ‘nonabsorbable’ steroids (Budesonide and beclomethasone) can be considered for acute intestinal GvHD 
in order to reduce the dose of systemic steroids 
 
If high dose corticosteroids are required, treatment should generally be continued for at 
least 5 days followed by tapering doses over several weeks. A physician with expertise in 
infectious diseases in immunocompromised hosts should be consulted, and prophylactic 
antimicrobials should be considered. 
Second line treatment can be considered for subjects who have failed to respond for 5 
days or have progressive symptoms after 3 days. There is no clear second-line agent that 
is preferred for steroid refractory GvHD. General guidelines for second-line treatment 
based on grade are provided below and should be considered in conjunction with input 
from the consulting physician with bone marrow transplant expertise. 
For steroid refractory skin rash, topical tacrolimus may also be useful. 
Most allogeneic transplant subjects concurrently receive calcineurin inhibitors in part as 
prophylaxis against GvHD. Therefore, for grade II-IV disease refractory to high dose 
steroids, the addition of a calcineurin inhibitor can be considered. 
Otherwise, there are several additional second line treatment options for which there is 
currently limited and/or evolving supporting data. Treating physicians can refer to the 
Haemato-oncology Task Force of the British Committee for Standards in Hematology 
and the British Society for Blood and Marrow Transplantation guideline for diagnosis 
and management of acute graft- versus-host disease [Dignan, 2012]. 
8.7. 
Chemotherapy Symptom Management 
Cyclophosphamide and fludarabine are used as pre-conditioning lymphodepleting 
chemotherapy in this study. Symptoms associated with the use of fludarabine and 
cyclophosphamide are included in the product label for the respective drugs. Refer to the 
most current product label. 
8.7.1. 
Management of Neutropenia 
The pre-conditioning chemotherapy is intended to cause lymphodepletion, however, 
neutropenia is also common. Prophylactic use of G-CSF (e.g., filgrastim) should be used 
in all subjects for the management of neutropenia according to ASCO guidelines. G-CSF 
should be given starting 24 hours after the administration of chemotherapy and continued 
until reaching an absolute neutrophil count (ANC) of at least 2 to 3 x109/L. 


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Long-acting (pegylated) G-CSF may be given in preference to short acting daily G-CSF 
in accordance with institutional standard practice. Pegylated G-CSF will be given as one 
dose 24 hours post the final dose of cyclophosphamide. 
8.7.2. 
Management of Pancytopenia with Bone Marrow Failure / 
Aplastic Anemia 
Pancytopenia with bone marrow failure /aplastic anemia has been reported after initial 
bone marrow recovery from high-dose chemotherapy followed by infusion of 
NY-ESO-1c259T cells. Bone marrow recovery following lymphodepletion will be 
defined as: 
• Absolute neutrophil count ≥ 1 x109/L for 2 consecutive measurements 
approximately 7 days apart, and 
• Platelet count ≥ 20 x109/L without transfusion support for one week. 
Aplastic anemia is a rare hematological disorder characterized by pancytopenia and a 
hypocellular marrow. Patients 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: absolute neutrophil count < 0.5 
x109/L, absolute reticulocyte count < 60 x109/L, and platelet count < 20 x109/L, 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 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. Please refer to Section 7.5 (Correlative Studies 
and Research Assessments). Details on tissue collections, kit use and shipment 
information can be found in the SPM. 
• A matched peripheral blood sample should be collected in parallel with the bone 
marrow sample and provided to the Sponsor. Please refer to Section 8.6 (Management 
of Graft- versus-Host Disease) regarding bone marrow suppression as a feature of 
GvHD. 


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• 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 8.6.3 (Management of Graft-versus-Host Disease) regarding bone 
marrow suppression as a feature of GvHD. 
8.7.3. 
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. 
Figure 2 
Case assessment for possible Guillain Barre Syndrome using 
diagnostic and prognostic tools supported by medical diagnosis 
and/or medical treatment 
 
*Please refer to algorithm for treatment described in Figure 3. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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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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  
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 
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 
Modified Erasmus GBS Outcomes Score (mEGOS) 
Parameters required at hospital admission and 7 days later [Walgaard, 2011]:  


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• 
Age at onset 
• 
Preceding diarrhea (in 4 weeks preceding onset of weakness) 
• 
Medical Research Council sum score 
8.7.3.1. 
Summary of diagnosis and treatment for GBS 
Additional information on the diagnosis and management of GBS (Figure 1) can be 
found in a review article on GBS [Willison, 2016].  
Figure 3 
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. 
 
9. 
RECORDING ADVERSE EVENTS 
Timely, accurate and complete reporting and analysis of safety information from clinical 
studies are crucial for the protection of subjects and is mandated by regulatory agencies 
worldwide. The Sponsor has established standard operating procedures in conformity 
with regulatory requirements worldwide to ensure appropriate reporting of all safety 
information; all clinical studies conducted by the Sponsor or its affiliates will be 
conducted in accordance with those procedures. The investigator (or designee) is 
responsible for detecting, documenting and reporting events that meet the definition of an 
AE or SAE. Individual AEs should be evaluated by the investigator and should be 


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reported to the Sponsor as appropriate. This includes the evaluation of its intensity, the 
causality between the investigational medicinal product and/or concomitant therapy and 
the adverse event and seriousness. 
The Sponsor has to keep detailed records of all AEs reported by the investigator(s) and to 
perform an evaluation with respect to causality, seriousness, and expectedness. 
9.1. 
Time Period for Collecting AE and SAE Information 
AEs and SAEs will be collected at the time points specified in Section 7.3 (Schedule of 
Procedures). 
• Any SAE, any AE related to study procedure or AE leading to withdrawal from 
the study will be collected from signature of the subject Screening ICF. 
• All AEs and SAEs will be collected and reported from the time of leukapheresis 
until the subject has completed or withdrawn from the interventional phase of the 
study. All SAEs must be collected through 90 days following T cell infusion, or 
30 days following T cell infusion if the participant initiates new anticancer 
therapy, whichever is earlier. 
• All SAEs have to be reported to sponsor within 24 h of Investigator learning 
about them. 
• During LTFU (15 years post infusion), subjects will only be monitored for those 
emerging clinical conditions defined in Section 9.4. 
All AEs should be followed until: 
• Resolved or improved to baseline. 
• Investigator confirms no further improvement can be expected. 
• Death. 
9.2. 
Definition of Adverse Event 
In accordance with the International Conference of Harmonization (ICH), an AE is any 
untoward medical occurrence in a subject or clinical investigation subject who receives a 
pharmaceutical product. The event does not necessarily have a causal relationship with 
study treatment to be an AE. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not 
considered related to the medicinal (investigational) product. Pre-existing conditions 
which worsen during the study are to be reported as AEs. For guidance on reporting of 
laboratory test abnormalities as AE, refer to Section 9.9. 


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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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• Possibly related – There is evidence of exposure to the investigational product; 
the temporal sequence of the AE onset relative to T cell infusion is plausible; or 
the AE could have been due to another equally likely cause. 
• Probably related – There is evidence of exposure to the investigational product; 
the temporal sequence of the AE onset relative to T cell infusion is plausible; the 
AE shows a pattern consistent with previous knowledge of the investigational 
product; or the AE is more likely explained by the investigational product than 
any other cause. 
• Certainly related – There is evidence of exposure to the investigational product; 
the temporal sequence of the AE onset relative to T cell infusion is plausible; the 
AE shows a pattern consistent with previous knowledge of the investigational 
product, or the AE is most likely explained by the investigational product and any 
other cause is improbable. 
The investigator may change his/her opinion of causality if additional information is 
received and amend the SAE eCRF accordingly. The investigator causality assessment is 
one of the criteria GSK use to determine regulatory reporting requirements for an SAE. 
9.3. 
Reporting Serious Adverse Events (SAEs) 
An SAE is any adverse event that: 
• Is fatal (results in death; death is the outcome, not the event). 
• Is life-threatening (the term “Life-threatening” refers to an event in which the 
subject was at immediate risk of death at the time of the event; it does not refer to 
an event which could hypothetically have caused a death had it been more 
severe). 
• Requires in-subject hospitalization or prolongation of existing hospitalization. 
• Results in a persistent or significant incapacity or substantial disability. 
• Is a congenital anomaly/birth defect. 
• Is medically significant or requires intervention to prevent one or the outcomes 
listed above. 
Medical and scientific judgment should be exercised in deciding if an adverse event is of 
significant enough medical importance to be classified as serious outside the above 
definitions. Important medical events are those that may not be immediately life 
threatening, but are clearly of major clinical significance. They may jeopardize the 
subject and may require intervention to prevent one of the other serious outcomes noted 
above. For example, drug overdose or abuse, a seizure that did not result in inpatient 
hospitalization or intensive treatment of bronchospasm in an emergency department 


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would typically be considered serious. In this case event will be reported using the 
serious criteria of clinically significant or requires intervention. 
Additional protocol-defined criteria 
• Any Grade ≥3 cytokine release syndrome or GvHD and all cases of Guillain-
Barré syndrome or acute inflammatory demyelinating polyneuropathy must be 
reported as an SAE within 24 hours. 
• Neutropenia grade 4 lasting ≥28 days 
The study will comply with all local regulatory requirements and adhere to the full 
requirements of the ICH Guideline for Clinical Safety Data Management, Definitions and 
Standards for Expedited Reporting, Topic E2. 
All SAEs have to be reported to sponsor within 24 h of Investigator learning about them. 
An SAE must be recorded by completing the SAE eCRF form within the electronic data 
capture (EDC) system. In addition, an SAE Worksheet must be completed and submitted 
to GSK within 24 hours by e-mail to OAX37649@GSK.com and 
RD_NYESOSAE@gsk.com (or fax: +44 (0) 20 8754 7822). The SAE eCRF must be 
completed by the investigator with as much information as is available. The minimum 
reporting criteria for an SAE include: 
• Identifiable subject (Subject ID) 
• Serious Adverse Event 
• Suspect medicinal product 
• Relationship to investigational product 
• Identifiable reporting source (PI acknowledgment of the report and his/her 
signature is required) 
The investigator will assess the causal relationship between the SAE and investigational 
product according to his/her best clinical judgement. The investigator will also assess the 
causal relationship between the SAE and the lymphodepleting chemotherapy. Further 
details can be found in the SPM. 
9.4. 
Reporting Criteria During Long Term Follow-Up (Years 1-15) 
Due to the nature of the treatment, subjects are required to be followed for up to 15 years 
after treatment with genetically modified T cells according to FDA and EMA guidance 
[FDA, 2006b; EMEA, 2009; FDA, 2020]. Subjects will be followed according to the 
schedule outlined in Table 4.  Delayed AEs are defined as those events that fall into one 
or more of the 6 categories listed below and which occur either more than one year 
following GSK3377794 infusion or after disease progression, whichever occurs first.  In 
the event a subject has not progressed 1 year following GSK3377794 infusion, delayed 


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AEs will be collected in Interventional Phase of study. Delayed AEs which occur post 
progression will be collected as part of the LTFU phase of the current study or in the 
LTFU Study (208750), contingent upon formal transfer of subject to Study 208750.: 
• New Malignancies 
• New incidence or exacerbation of a pre-existing neurological disorder 
• New incidence or exacerbation of a prior rheumatologic or other autoimmune 
disorder 
• New incidence of immune-related hematologic disorder 
• Serious infections (including opportunistic) 
• Unanticipated illness or hospitalization deemed related to gene modified cell 
therapy 
A detailed narrative description of the event should include the date of diagnosis and the 
nature of the diagnosis for all AEs. If the diagnosis is cancer, record the type and stage of 
the cancer. If the cancer is metastatic, list the metastatic sites. If a new malignancy is 
recorded in a vector target cell type, tumor cells will be evaluated for vector sequences. If 
the tumor is positive for vector sequences or the surrogate sample is positive for vector 
sequences and is confirmed in accordance to this protocol, clonality analysis will be 
performed. If no evidence of oligo- or monoclonality is observed, a summary report of 
any and all analysis for the pattern of vector integration will be assembled, and submitted 
within the annual report of the INDs listed on this protocol under which the subject(s) 
evaluated originally received their treatment. If evidence of oligo- or monoclonality is 
observed, an information amendment will be submitted within 30 days to the INDs listed 
on this protocol under which the subject(s) evaluated originally received their treatment. 
Adverse events should be recorded in the eCRF using a diagnosis or possible diagnosis, 
and rated for intensity, causality and seriousness. If photographs are requested by the 
Sponsor of e.g., a rash AE, the subject will sign a Medical Photograph Release prior to 
any photographs being taken. Suspected unexpected serious adverse reactions (SUSARs) 
deemed related to the gene modified cells will be reported to the Regulatory Agencies 
and shared with Investigators as necessary in the form of Investigational new drug safety 
reports (INDSRs). 
All AEs should be followed until: 
• Resolved or improved to baseline. 
• Investigator confirms no further improvement can be expected. 
• Death 


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9.5. 
Progression of Underlying Malignancy 
Progression of underlying malignancy is not reported as an AE if it is clearly consistent 
with the suspected progression of the underlying cancer. Clinical symptoms of 
progression may be reported as AEs if the symptom cannot be determined as exclusively 
due to the progression of disease the underlying malignancy or does not fit the expected 
pattern of progression for the disease under study. 
If there is any uncertainty about an AE being due only to the disease under study, it 
should be reported as an AE or SAE. 
9.6. 
Regulatory Reporting Requirements for SAEs 
The Sponsor has legal obligations for expedited reporting of certain events to Regulatory 
Authorities, IRBs/ Research Committees (RC) and other study participants. GSK will 
comply with all GCP and country specific regulatory requirements relating to safety 
reporting to the regulatory authorities, IRBs/RCs and investigators. 
Investigator safety reports for suspected unexpected serious adverse reactions (SUSARs) 
are prepared and distributed according to local regulatory requirements and GSK policy. 
These safety reports are forwarded to investigators as necessary in the form of INDSRs. 
An investigator who receives an INDSR describing a SAE(s) or other specific safety 
information (e.g., summary or listing of SAEs) from GSK will file it with the IB and 
notify their IRB/RC if appropriate, in accordance with local requirements. 
On request of a competent authority in whose territory the clinical trial is being 
conducted, the Sponsor will submit detailed records of all adverse events which are 
reported to him by the relevant investigator(s). 
9.7. 
Cardiovascular and Death Events 
For any cardiovascular events detailed below and all deaths 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 CV (including sudden cardiac death) and non-
CV 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. 


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9.7.1. 
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 
9.8. 
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. 
CRES occurring within the first 5 days after immunotherapy may be concurrent with high 
fever and CRS symptoms. This form of CRES tends to be of shorter duration, lower 
grade (grade 1–2, see Table 2), and is generally reversible with anti-IL-6 therapy. CRES 
presenting as delayed neurotoxicity with seizures or episodes of confusion can occur 
three or four weeks after 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 of TCR T cells. 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. 


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Grade 
Treatment 
1 
x
Vigilant supportive care; aspiration precautions; IV hydration 
x
Withhold oral intake of food, medicines, and fluids, and assess swallowing 
x
Convert all oral medications and/or nutrition to IV or enteral tube if swallowing is impaired 
x
Avoid medications that cause central nervous system depression 
x
Evaluate for other contributing causes and treat accordingly 
x
Neurology consultation including fundoscopic exam to assess for papilloedema 
x
MRI of the brain with and without contrast (CT scan of the brain if MRI is not feasible). Further 
testing if indicated such as diagnostic lumbar puncture with measurement of opening pressure if 
increased intracranial pressure is suspected, or MRI of the spine if the subject has focal 
peripheral neurological deficits 
x
Institute levetiracetam therapy and consider EEG if seizure activity is suspected 
x
Consider anti-IL-6 therapy with tocilizumab 8 mg/kg1 IV or siltuximab 11 mg/kg IV, if Grade 1 
persists beyond 24 hours, or worsening and associated with concurrent CRS 
2 
x
Supportive care and neurological work-up as described for grade 1 ICANS 
x
Anti-IL-6 therapy if associated with concurrent CRS 
x
Consider dexamethasone 10 mg IV every 6 h or methylprednisolone 1 mg/kg IV every 12 h if 
refractory to anti-IL-6 therapy, or for ICANS without concurrent CRS; once initiated continue 
corticosteroids until improvement to grade 1 ICANS and then taper 
x
Consider transferring patient to ICU if ICANS associated with grade ≥2 CRS 
3 
x
Supportive care and neurological work-up as indicated for grade 1 ICANS 
x
ICU transfer is recommended 
x
Anti-IL-6 therapy if associated with concurrent CRS if not administered previously 
x
Corticosteroids as outlined for grade 2 ICANS if symptoms worsen despite anti-IL-6 therapy, or 
for ICANS without concurrent CRS; continue corticosteroids until improvement to grade 1 ES and 
then taper 
x
Stage 1 or 2 papilloedema with CSF opening pressure <20 mmHg should be treated 
corticosteroid regimen as per Grade 4 below. 
x
Consider repeat neuroimaging (CT or MRI) every 2–3 days if patient has persistent grade ≥3 
ICANS 
4 
x
Supportive care and neurological work-up as indicated for grade 1 ICANS 
x
Consider neurosurgical consultation for patients with evidence of increased intracranial pressure 
x
ICU monitoring; consider mechanical ventilation for airway protection 
x
Anti-IL-6 therapy and repeat neuroimaging as described for grade 3 ICANS 
x
High-dose corticosteroids continued until improvement to grade 1 ICANS and then taper; for 
example, methylprednisolone IV 1 g/day for 3 days, followed by rapid taper at 250 mg every 12 h 
for 2 days, 125 mg every 12 h for 2 days, and 60 mg every 12 h for 2 days 
Abbreviations: CRS = cytokine release syndrome; CSF = cerebrospinal fluid; CT = computed tomography; 
EEG = electroencephalogram; ICANS= Immune Effector Cell-Associated Neurotoxicity Syndrome; ICU = intensive care 
unit; IL-6 = interleukin-6; IV = intravenous; MRI = magnetic resonance imaging. 
1. Maximum amount of tocilizumab per dose is 800mg. 
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receiving the investigational product, or four months after there is no evidence of 
persistence/gene modified cells in the subject’s blood, whichever is longer. 
Pregnancy (or pregnancy of a male subject’s partner) is not considered an AE/SAE unless 
there is reason to believe that the pregnancy may be the result of failure of the 
contraceptive being used due to interaction with the study drug. However, the 
investigator shall report all pregnancies immediately to the Sponsor. A woman who 
becomes and remains pregnant during the study will be discontinued from the 
interventional phase as exposure to radiation from imaging studies would be 
contraindicated in this setting. The subject would enter into the LTFU protocol 
GSK208750 (ADP-0000-002). The outcome of the pregnancy must also be reported to 
the Sponsor. The contraception guidelines in the inclusion criteria of this protocol should 
continue to be followed during the LTFU. 
If a pregnancy is reported, the investigator should inform GSK within 24 hours of 
learning of the pregnancy. 
9.10. 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study and must be 
recorded in the subject’s Medical History. A preexisting condition should be recorded as 
an adverse event if the frequency, intensity, or the character of the condition worsens 
during the study period. 
9.11. 
Laboratory Test Abnormalities as Adverse Events 
Out of range laboratory test results which meet any of the following criteria, should be 
reported as adverse events: 
• 
Any CTCAE lab value ≥ Grade 3 should be recorded as an AE. Grade 1 and 2 
laboratory abnormalities do not require reporting unless an investigator 
considers that an event of these grades is clinically significant 
• 
Any Grade 4 CTCAE lab value based solely on numerical criteria (e.g., white 
blood cells decreased) should be reviewed to determine whether it should be 
reported as a serious adverse event. 
Table 11 
Timelines for Safety Reporting 
Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
All SAEs 
24 hours 
SAE data collection 
tool 
24 hours 
Updated SAE data 
collection tool 
“CV events” and/or “death” Initial and follow up 
reports to be 
completed within 
one week of when 
the cardiovascular 
“CV events” and/or 
“death” data collection 
tool(s) if applicable 
Initial and follow up 
reports to be 
completed within one 
week of when the 
cardiovascular event or 
death is reported 
Updated “CV events” 
and/or “death” data 
collection tool(s) if 
applicable 


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Initial Reports 
Follow-up Information on a Previous 
Report 
Type of Event 
Time Frame 
Documents 
Time Frame 
Documents 
event or death is 
reported 
Pregnancy 
24 Hours 
Pregnancy  
Notification Form 
2 Weeks 
Pregnancy Follow-up 
Form 
 
10. 
SAFETY MONITORING 
10.1. 
Safety Review Team 
A SRT will be implemented in this study. In line with routine pharmacovigilance, a GSK 
SRT will review safety data, including clinical laboratory parameters and AEs, at 
appropriate intervals during the period of study conduct. Recommendations on study 
modification, halting the study and/or pausing enrolment will be provided by the SRT. A 
SRT charter, defining roles and accountabilities and the process for safety review and 
meeting frequency, will be available. 
10.1.1. 
Mandated Study Pause Due to GBS 
The occurrence of any event of GBS will mandate a pause in enrolment and stopping 
treatment for all participant within the GSK3377794 studies. 
10.2. 
Stopping Rules 
If the following events occur, further enrolment to the study will be suspended and the 
regulatory authorities informed: 
• Any death occurs that is deemed to be probably or definitely related to the 
investigational medication/cell product by the principal investigator and study 
sponsor; 
 
Or 
• Two (2) or more grade 4 autoimmune events deemed probably or definitely 
related to the investigational medication/cell product by the principal investigator 
and study sponsor;  
• Any event of Guillain-Barre syndrome (GBS) as diagnosed by a neurologist 
according to diagnostic guidance for GBS [Fokke, 2014]. 
 
Or 
• An apheresis confirmed positive biological replication competent lentivirus 
(RCL) occurs (see Section 10.3.2). 


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Following assessment by Sponsor, enrolment and dosing may resume if agreed upon by 
the Sponsor and regulatory authorities, if applicable. 
10.3. 
Monitoring and Management of Replication-Competent 
Lentivirus (RCL) 
Replication Competent Lentivirus (RCL) is a theoretical risk associated with the use of 
lentiviral vectors; no RCL has ever been detected in vitro or in vivo. The risk is derived 
from the detection of replication competent retrovirus (RCR) during the use of early γ -
retroviral vector packaging systems which were inadequately designed to avoid 
recombination events between the vector and packaging components [Miller, 1990]. 
Updated γ-retroviral packaging systems have not been associated with RCR. However, in 
a study with Rhesus monkeys, three out of 10 animal died of lymphomas at around 6 
months after transplantation of vector transduced bone marrow cells contaminated with 
replication-competent virus [Donahue, 1992]. Therefore, RCR/L must continue to be 
rigorously evaluated in vector and cell lots, and in subjects post infusion with any product 
involving a retrovirus [FDA Guidance, 2006b; EMEA Guideline, 2009]. 
A RCL may be generated during the production phase or subsequently after introduction 
of vector transduced cells into the subject. RCL may be generated by homologous or non- 
homologous recombination between the transfer vector and packaging elements, or 
endogenous retroviral elements [Chong, 1998; Garrett,  2000]. A RCL resulting from the 
production phase of the lentivirus used in this trial is highly unlikely since elements are 
incorporated in the design of the vector system that minimize vector recombination and 
generation of RCL. Nevertheless, generation of an RCL by recombination with an 
endogenous virus (i.e., HIV) in the subject following infusion of the vector product 
remains a theoretical possibility. The consequences of such recombination events could 
be neutral, could reduce the replication rate or pathogenicity of the subject's endogenous 
virus, or could increase the replication rate or pathogenicity of the subject's endogenous 
virus. Since the development of a strain with increased pathogenicity would pose greater 
risk to both the subject and their close contact(s), periodic monitoring for RCL is 
conducted during the course of the trial and during the 15 year follow up. 
Regulatory agencies and the gene therapy community have previously discussed 
measures to be taken should an RCL be confirmed in a subject [FDA Guidance, 2006b; 
EMEA Guideline, 2009]. However, because the probability and characteristics of an RCL 
are unknown, no concrete plans have been put in place. As of the writing of this protocol 
it is agreed that the subject must be isolated until an understanding of how to manage the 
subject becomes clear. 
Approaches that have been discussed for managing the subject are the following: 
1. Provide targeted antiretroviral therapies based on genotyping of the RCL. 
2. Intensive follow up of subject in consultation with gene therapy experts, study 
investigators, HIV physicians, FDA and NIH. 


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10.3.1. 
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: 
1. The cell product will be tested by or under the direction of the facility responsible for 
the manufacturing and release of the vector 
2. Subject PBMCs which will be collected prior to infusion of transduced T cells and 
then at 3, 6, and 12 months post treatment. If vector persistence is undetected for two 
consecutive visit assessments and the participant is ≥2 years post-infusion, samples 
for RCL and persistence of gene modified cells will be discontinued. If VSV-G DNA 
copies are detected at any time point in the first year post-infusion, the safety 
monitoring protocol (Section 10.3.2) will be triggered and subject samples will 
continue to be tested for VSV-G DNA copies until VSV-G DNA copies are not 
detected for 3 consecutive annual assessments, then subject samples will be collected 
annually until year 15 and archived at GSK’s centralized biorepository. 
10.3.2. 
Safety Monitoring - Results 
If a positive VSV-G DNA signal is obtained, the study investigator will be informed and 
the subject scheduled for a retest as soon as possible and no later than one month after the 
initial positive result was reported to the Sponsor. A review by Sponsor will take place. 
If the second test is positive, infusions for all subjects receiving cells modified with the 
same vector lot will be postponed. The subject with the confirmed positive VSV-G signal 
will be scheduled for leukapheresis and a biological RCL 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 test is positive, all infusions will be halted. An action plan will be 
discussed with regulatory authorities and other experts as appropriate. Additional subjects 
will not be treated with NY-ESO-1c259T cells until such time as a plan is completed, 
reviewed, and agreed upon with regulatory authorities. 
10.3.3. 
Persistence and Insertional Oncogenesis Testing and Monitoring 
Monitoring for insertional oncogenesis follows the recommendations described in FDA 
and EMA guidance [FDA Guidance, 2006b; EMEA Guideline, 2009]. Insertional 
oncogenesis is a theoretical risk in T cells transduced with a lentiviral vector. T cells 
appear resistant to transformation by integrating viruses [Cattoglio, 2010; Newrzela, 
2008]. However, there are cases of resulting oncogenesis with γ-retroviral transduced 
stem cells. Four of nine subjects with X- linked severe combined immunodeficiency 
(SCID-X1) treated with retrovirus transduced stem cells were found to have insertion 
near the LMO2 proto-oncogene promoter, leading to aberrant transcription and 
expression of LMO2 which resulted in acute T-cell lymphoblastic leukemia [Hacein-Bey-


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Abina, 2003; Hacien-Bey-Abina, 2014]. Additionally, two subjects treated for X- linked 
chronic granulomatous disease (X-CGD) with retroviral transduced stem cells 
demonstrated insertional activation of the EVI1 transcription factor which resulted in 
genetic instability, monosomy 7 and clonal progression toward myelodysplasia [Stein, 
2010]. Monitoring for insertional oncogenesis follows the recommendations set forth in 
the FDA and EMEA guidances [FDA, 2006a; FDA, 2006b; EMEA Guideline, 2009]. 
10.3.4. 
Testing for Persistence of Gene Marked Cells in Clinical Studies 
Peripheral blood mononuclear cells (PBMCs) samples will be collected and used as the 
“surrogate sample” for monitoring persistence of gene modified cells in subjects at 3, 6, 9 
and 12 months post-infusion, then every 6 months until 5 years post-infusion and every 
year from year 6 post infusion in accordance with the FDA and EMA guidance [FDA, 
2006a; FDA, 2006b; EMEA Guideline, 2009]. The samples will be tested using a PCR-
based method to detect the presence of the Psi gene, which is part of the lentiviral vector 
used to transduce T cells. Detection of Psi DNA copies reflects persistence of the 
genetically modified T cells. If at 1 year or beyond post-infusion greater than 1% PBMCs 
test positive for the vector sequence, then the subject’s PBMCs will be evaluated for 
integration site analysis (see below). If vector persistence is undetected for two 
consecutive visit assessments and the participant is ≥2 years post-infusion, samples for 
RCL and persistence of gene modified cells will be discontinued. All other assessments 
such as hematology and chemistry may also be stopped. Note: Samples for RCL must 
continue to be collected and archived annually for up to 15 years post infusion. The 
subject will continue to be followed by the investigator, local oncologist or local 
physician, by phone call or survey for up to 15 years post-infusion. The investigator will 
be the primary physician responsible for continued follow-up of the subject for the 
duration of the LTFU whenever possible. If contact with the investigator becomes no 
longer feasible, follow up can be transitioned to a local physician, preferably an 
oncologist. 
10.3.5. 
Testing for Insertional Oncogenesis 
If persistence, as detected by the presence of a vector sequence (Psi DNA copies), is 
present in >1% of PBMC at 1 year or beyond post-infusion, DNA from the subject’s 
PBMCs will be sent for integration site analysis. Integration site analysis assesses 
clonality and the possibility of insertional oncogenesis. This integration site analysis 
method, used in previous clinical trials[Hacien-Bey-Abina, 2014], uses sonic length 
quantitation, an accurate method of measuring relative clonal abundance [Berry, 2012]. 
Clonality is defined as follows: 1) monoclonality is 1 predominant clone at ≥5% of 
transduced T cells; 2) oligoclonality is defined as 2-5 predominant clones, each at ≥5% of 
transduced T cells; and 3) polyclonality is defined as no single predominant clone of ≥5% 
of transduced T cells. 
If there is clonal dominance in the genetically modified T cell population (either 
monoclonality or oligoclonality) the persistence assessment will be repeated within 3 
months on a new sample. If the repeated analysis demonstrates: 1) persistent 
monoclonality, 2) evidence of insertional oncogenesis or 3) clonal expansion, there will 
be a review by the Sponsor to develop a monitoring plan specific to the health care risk 


TMF-14208393 
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and strategies to inform appropriate subjects, investigators, and regulators of the findings. 
If the integration site analysis indicates polyclonality of the genetically modified T cell 
population, then screening continues as scheduled. 
10.3.6. 
Monitoring and management for Demyelinating Neuropathy and 
other Neurological events 
Obtain a neurological consultation for participants with Grade 2 or higher neurologic 
events of a ≥ 7 day duration. Participants who develop signs and symptoms consistent 
with GBS must be evaluated by a neurologist to provide expert recommendations to 
guide appropriate diagnostic workup such as EMG, lumbar puncture, infectious panel to 
guide management and follow up 
11. 
STATISTICAL AND DATA ANALYSIS 
The objectives and endpoints for this study are described in Section 2. Section 11 
focusses on key aspects for the analysis and reporting of the primary and secondary 
efficacy and safety endpoints. Details for the analysis of all endpoints (including 
exploratory endpoints) will be provided in the Reporting and Analysis Plan (RAP).  
11.1. 
Study Populations 
Intent-to-Treat (ITT) population: This population comprises all subjects who underwent 
leukapheresis. The ITT population is the primary analysis population for safety 
endpoints, where appropriate. 
Modified Intent-to-Treat (mITT) population: All ITT subjects who received NY-ESO-
1c259T cell infusion comprises this population. The mITT population is the primary 
analysis population for efficacy endpoints and the primary analysis population for safety 
endpoints, where appropriate. 
If the mITT and ITT populations are identical, only results associated with the ITT 
population will be reported. 
11.2. 
Statistical Methods for Interim Analysis 
The enrolment rules at the interim analysis are defined based on a Bayesian predictive 
adaptive design [Lee, 2008] that allows the study to be monitored more frequently at 
multiple stages. The criteria will be based on a historical response rate of approximately 
20% versus a response rate of interest of 40%, but the sample size is not powered for any 
formal hypothesis testing. Bayesian statistics will be employed to calculate the predictive 
probability that the response rate will be ≥40% and ≥20% at interim assuming a beta 
prior for the binomially distributed data. Predictive probability calculates the probability 
that the response rate will be ≥40% or ≥20% at the end of study given the responses that 
have already been observed. A weak prior beta (0.02, 0.08) is used, which is equivalent to 
the information present in 0.1 participant. 


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Interim analyses for ORR will start once at least 10 participants are evaluable. 
Participants are evaluable if they had at least 3 post baseline disease assessments or 
progressed or died or withdrawn from the study. The observed number of participants 
with confirmed investigator assessed response of PR or CR, per RESIST 1.1, will be 
compared with the stopping region in Table 12. Enrolment may stop if the stopping rule 
is met. Final decision will be based on the totality of data. For example, if there is 1 or no 
confirmed responses out of 10 evaluable subjects, enrolment may stop after review of all 
available data; if there are 2 or more confirmed responses out of 10 evaluable subjects, 
enrolment will continue up to 20 subjects. 
Table 12 
Futility Stopping Rules for Expansion Cohort 
Number of 
Evaluable 
Subjects 
Stop for Futility if No. of confirmed 
PR+CR is Less than or Equal to This 
Number 
Prob. Of 
Continuing if True 
ORR=0.2 
Prob. Of 
Continuing if True 
ORR=0.4 
10 
1 
63.1% 
95.1% 
11 
2 
37.7% 
87.4% 
 
If expanded, interim analyses in the second cohort of 10 infused subjects (receiving the 
modified option 2 lymphodepletion regimen) may be conducted for internal decision 
making once at least 8 subjects are evaluable. 
The Reporting and Analysis Plan will describe the planned interim analyses in greater 
detail. 
11.3. 
Statistical Methods for Efficacy Endpoints 
The study is not powered for either primary or secondary endpoints, hence there are no 
analyses to test hypotheses. 
The primary analysis population for efficacy will be the mITT population. The ITT 
population will be used as a secondary population for analysis. 
The following methods will be used for assessing efficacy at the end of the interventional 
phase. Full details will be provided in the RAP. 
The primary endpoint for efficacy is Overall Response Rate (ORR) defined as the 
proportion of subjects with a confirmed complete response (CR) or partial response (PR) 
per RECIST v1.1 criteria by investigator assessment relative to the total number of 
subjects in the analysis population. 
ORR will be summarized by two-sided 95% confidence intervals using exact and Wilson 
methods. 95% (Bayesian) credible intervals may also be used to summarize the ORR. 
A sensitivity analysis will be conducted on ORR using the independent assessment of 
response per RECIST v1.1. 


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Subjects with unknown or missing response will be treated as non-responders, i.e., they 
will be included in the denominator when calculating the proportion of responders. 
The ORR will be evaluated in the context of additional efficacy parameters such as time 
to confirmed response, duration of response, PFS and overall survival. 
The secondary (efficacy) endpoints are defined below: 
• Time to Response: the interval between T-cell infusion to the initial date of the 
confirmed response, in the subset of participants with a confirmed response of PR 
or CR. 
• Duration of Response: the interval between the initial date of the confirmed 
response to the date of progressive disease or death, among subjects with a 
confirmed response of PR or CR. 
• Progression Free Survival (PFS): the interval between the date of T cell infusion 
and the earliest date of disease progression or death due to any cause. 
Duration of Response and Progression Free Survival endpoints will be summarized and 
displayed graphically using Kaplan-Meier (K-M) methodology to estimate the median, 
and the 25th and 75th percentiles if data warrant. Two-sided 95% confidence intervals 
will be produced. Overall Survival will be assessed at fixed time points such as 1 year 
and 2 years using K-M methods if data warrant. 
The following censoring rules will be applied for the various time to event endpoints. 
• Duration of response: subjects who are still alive and who do not have a 
documented disease progression date will be censored at the date of the last 
assessment. 
• Progression free survival: subjects who do not have a documented date of disease 
progression or death will be censored at the date of the last assessment. 
11.4. 
Statistical Methods for Safety Parameters 
The primary analysis population for safety will be the ITT population, with the mITT 
used as necessary. 
The following methods will be used for summarizing safety. Full details will be provided 
in the RAP. 
Descriptive statistics will be provided for disposition, demographic, safety, imaging, and 
cytokine assessments. Continuous data will be summarized including means, medians, 
standard deviations, and ranges, while categorical data will be summarized using 
frequency counts and percentages. Graphical summaries of the data may be presented. 
The safety profile will be based on adverse events reported, vital signs measurements, 
clinical laboratory measurements and ECG recordings. 


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Adverse Events: All adverse events will be listed and coded by MedDRA. The number 
and percent of subjects reporting any adverse events will be tabulated by system organ 
class and preferred term. Adverse events with missing date of onset will be considered to 
have occurred on treatment. Adverse events will be further classified by toxicity (using 
CTCAE Version 4.0), relationship to treatment and seriousness. Tables and/or narratives 
of any death, or serious adverse event, including early withdrawals will be provided, 
should they occur. 
Vital Signs: Vital signs will be listed for each subject, summaries of vital signs data over 
time may be provided. 
Electrocardiogram: Electrocardiogram data will be listed for each subject. Fridericia’s or 
Bazett’s correction will be used to adjust QT for RR. Summaries of ECG intervals will be 
provided. 
Clinical Laboratory Tests: Clinical chemistry, hematology, persistence, RCL, circulating 
cytokines and anti-NY-ESO-1c259T antibody data will be listed for each subject. Values 
outside the normal laboratory reference ranges will be flagged as high or low on the 
listings (if applicable). Laboratory abnormalities will be graded using CTCAE version 
4.0. 
11.5. 
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 
analyzed using population PK approaches. If performed, the population PK analysis and 
pharmacodynamic analyses will be presented separately from the main clinical study 
report (CSR). 
12. 
CLINICAL SUPPLIES 
12.1. 
Packaging and Labelling 
Selected, qualified manufacturing sites will manufacture, package and label cell product 
for each individual subject in accordance with applicable regulatory requirements. 
Labels will include batch number, protocol number, number of transduced cells, the 
subject’s unique study identification number. 
12.2. 
Standard Policies and Product Return 
Investigational product must be received by a designated person at the site, handled and 
stored safely and properly, and kept in a secure location to which only the investigator 
and designated personnel have access. Investigational product is to be dispensed only in 
accordance with the protocol. The investigator is responsible for keeping accurate records 
of the investigational product received from the Sponsor, the amount dispensed to and 
any unused investigational product remaining at the conclusion of the study. Contact the 


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Sponsor or designee regarding any questions concerning the investigational product. At 
the end of the study or as dictated by protocol or process, all clinical supplies including 
partial and empty containers must be returned as indicated. 
Sites should contact the Sponsor or designee for specific instructions for investigational 
product returns or destruction and appropriate documentation for drug accountability. 
12.3. 
Storage and Handling 
The subject’s T cell product that is received at the site from the manufacturer will be 
stored at ≤-130°C until being ordered by the investigator (or designee) to be infused. The 
cells will be thawed and infused as specified in Section 5.3. 
12.4. 
Product Accountability 
The investigational product provided for this study is for use only as directed in the 
protocol. It is the investigator/institution’s responsibility to establish a system for 
handling study treatments, including investigational product, so as to ensure that: 
• Deliveries of investigational product are correctly received and recorded by a 
responsible person 
• Such deliveries are recorded 
• Investigational product is handled and stored safely and properly as stated on the 
label 
• Investigational product is only dispensed to study subjects in accordance with the 
protocol 
• Any unused product is accounted for in the sites records before returning to the 
Sponsor (or designee) 
At the end of the study, it must be possible to reconcile delivery records with records of 
usage and destroyed stock. Records of usage should include the identification of the 
person to whom the investigational product was dispensed, the quantity and date of 
dispensing. This record is in addition to any drug accountability information recorded on 
the eCRF. Any discrepancies must be accounted for on the appropriate forms. 
13. 
DATA HANDLING AND RECORD KEEPING 
13.1. 
Data Management 
An Electronic Data Capture (EDC) system will be used to collect data pertaining to this 
trial. Trial data will be captured through an eCRF. Within the EDC system the eCRF data 
will be entered by the site staff and all source document verification and data cleaning 
will be performed by the sponsor or designee (e.g., CRO). 


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The specifications for the EDC system will be documented and approved before the EDC 
system is released for live use. The validation of the eCRF data will be defined in a Data 
Management Plan. As data are entered into the eCRF, the validation checks will be 
performed and where necessary, queries will be raised. All queries raised will be held in 
the EDC database. 
The EDC system is a validated software program that has been designed to comply with 
CFR21 Part 11 requirements. All users will access the system via unique user name and 
password. A full audit history of all actions performed within the system is maintained. 
User accounts ensure that each user can only perform the tasks applicable to their role 
and only have access to the data applicable to their role. 
Standard coding dictionaries, WHO Drug and MedDRA will be used to code medications 
and adverse events. 
When all data have been entered and all data cleaning is complete the data will be locked 
and made available for analysis and reporting. 
On completion of the study all eCRF data, including all associated queries and audit 
history, will be made available in PDF format to both the study Sponsor and the sites. 
13.2. 
Case Report Forms 
For each subject enrolled, the completed eCRF must be reviewed and signed by the 
principal investigator or authorized delegate. If a subject withdraws from the study, the 
reason must be noted on the eCRF. 
The investigator should ensure the accuracy, completeness, legibility, and timeliness of 
the data reported to the Sponsor in the eCRFs and in all required reports. 
13.3. 
Site Documentation and Source Data 
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented and the study data to be subsequently verified. These 
documents are classified into two different categories: (1) Investigator Site File (ISF) and 
(2) subject specific source documents. 
The investigator is responsible for maintaining a complete and accurate ISF containing 
essential documents as required by ICH GCP. 
Source documents contain the results of original observations and activities of a clinical 
investigation. Source documents include but are not limited to subject medical 
records/progress notes, appointment book, original laboratory reports, ECG printouts, 
CT/MRI scans, pathology and special assessment reports, and signed informed consent 
forms. In no circumstances is the eCRF to be considered source data. 
The investigator must ensure the availability of source documents from which the 
information on the eCRF was derived. 


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The investigator must permit authorized representatives of the Sponsor, the respective 
national, local or foreign regulatory authorities, the IRB/IEC and auditors to inspect 
facilities and to have direct access to the ISF and all source documents relevant to this 
study regardless of the type of media. 
13.4. 
Data Retention and Availability 
The Investigator must keep all essential study documents including source data on file for 
at least 25 years after completion or discontinuation of the study. After that period of time 
the documents may be destroyed, subject to local regulations. 
The investigator will not dispose of any records relevant to this study without written 
permission from the Sponsor. If the investigator cannot guarantee the archiving 
requirement at the investigational site for any or all of the documents, such study records 
may be transferred upon request to Sponsor or its designee. 
Should the investigator wish to assign the study records to another party or move them to 
another location, the Sponsor must be notified in writing in advance. 
Study documentation is subject to inspection by the Sponsor, its representatives and 
regulatory agencies and must be stored in such a way that it can be accessed/retrieved 
within a reasonable timeframe at a later date. 
14. 
STUDY MONITORING 
Study Monitoring will be conducted by the sponsor or designated CRO. 
It is understood that the responsible monitor will contact and visit the investigator 
regularly and will be allowed, on request, to inspect all records of the trial (e.g., eCRFs, 
ISF, source documents) provided that subject confidentiality is maintained in accordance 
with local requirements. 
It will be the monitors (or designees) responsibility to inspect the eCRFs at regular 
intervals throughout the study, to verify the adherence to the protocol and the 
completeness, consistency and accuracy of the data being entered. The monitor (or 
designee) should have direct access to subject source documents to verify the entries on 
the eCRF. The investigator (or designee) agrees to cooperate with the monitor (or 
designee) to ensure that any discrepancies detected are resolved. 
14.1. 
Audits and Inspections 
The sponsor or its representatives may conduct audits at investigative sites including, but 
not limited to facilities where the study is being conducted, investigational product 
handling and accountability, presence of required documents, the informed consent 
process and comparison of eCRFs with source documents. 
All study documentation including source data must be available for audit. 


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The investigator agrees to cooperate fully with audits conducted at a convenient time in a 
reasonable manner. 
Regulatory agencies may also inspect investigative sites during or after the study. The 
investigator (or designee) should contact GSK immediately if this occurs, and provide 
copies of correspondence relating to requests for an inspection of the site facilities. 
15. 
REGULATORY AND ETHICAL CONSIDERATIONS 
15.1. 
Competent Authority Submissions 
GSK or its authorized representatives will be responsible for ensuring that appropriate 
competent authority approvals are obtained according to local country requirements. 
Competent authority approval (or notification as applicable) will be obtained before 
initiation of the study. 
15.2. 
Independent Ethics Committees 
The final study protocol and subject informed consent documentation will be approved 
by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and any 
other site level committee deemed appropriate by the institution. Approval from each 
applicable committee will be received in writing before initiation of the study. 
Protocol amendments must also be approved by the IRB/IEC (and other committees as 
applicable) before implementation, except in the case of changes made to protect subjects 
from immediate hazard, which may be implemented immediately. 
15.3. 
Local Regulations/Declaration of Helsinki 
The investigator will ensure that this study is conducted in full compliance with the 
principals of the “Declaration of Helsinki” or with the laws and regulations of the country 
in which the research is conducted, whichever, affords the greater protection to the 
subject. The study must fully adhere to the principles outlined in “Guideline for Good 
Clinical practice” ICH Tripartite Guideline (January 1997) or with local law if it affords 
greater protection to the subject. 
15.4. 
Informed Consent 
It is the responsibility of the investigator to obtain written informed consent from all 
study subjects prior to any study related procedures being performed. All consent 
documentation must be in accordance with applicable regulations and ICH GCP. 
Documentation must include the dated signature of both the subject (or the subject’s 
parents or legally authorized representative as applicable) and the person conducting the 
consent discussion. If the subject is illiterate, an impartial witness should be present 
during the consent discussion, and the consent signed and dated by the witness, the 
subject, and the person conducting the consent discussion. The consent form should be 
translated and communicated to the subject in a language that is understandable to the 


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subject. Certified translations of the informed consent documentation will be provided as 
applicable. 
A copy of the signed and dated informed consent should be provided to the subject before 
participation in the study. 
Tests performed as standard of care prior to documentation of consent may be used for 
screening results as appropriate. 
15.5. 
Confidentiality 
The confidentiality of records that may identify subjects will be protected in accordance 
with applicable laws, regulation and guidelines. 
The investigator must ensure that each subject’s anonymity is maintained and protected 
from unauthorized parties. On eCRFs or other documents submitted to the Sponsor, 
subjects must not be identified by their names, but by a unique identification code 
allocated to them to ensure confidentiality on all study documentation. Subjects will 
retain this unique number throughout the study. 
The investigator will keep a subject enrolment log showing subject unique identification 
codes, names and addresses in the ISF. 
The Sponsor and/or its representatives accessing subject records and data at site will take 
all reasonable precautions to maintain subject confidentiality. 
15.6. 
Protocol Adherence 
The investigator (or designee) must sign the protocol to confirm acceptance and 
willingness to comply with the study protocol. 
The investigator or designee will not deviate from the protocol unless necessary to 
eliminate an apparent immediate hazard to the safety, rights or welfare of any study 
subject. In the event of a protocol deviation for any reason, the investigator will promptly 
report the deviation to the Sponsor in writing. 
15.7. 
Study Suspension, Study Termination and Study 
Completion 
The Sponsor may suspend or terminate the study at any time for any reason. If the study 
is suspended or terminated the Sponsor will ensure that applicable sites, regulatory 
agencies and IRBs/IECs are notified as appropriate. 
If the investigator stops/terminates study at their site the Sponsor must be notified. The 
Sponsor will ensure that regulatory agencies and IRBs/IECs are notified as appropriate. 
The Sponsor will ensure that End of Study declarations are made to the relevant 
regulatory agencies/IECs in accordance with local regulations. 


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15.8. 
Public Posting of Study Information 
The Sponsor is responsible for posting appropriate study information on applicable 
clinical study registry websites. Information included in clinical study registries may 
include participating investigator’s names and contact information. 
15.9. 
Clinical Study Report 
The results of the study will be presented in an integrated Clinical Study Report (CSR) 
according to ICH guideline E3: Structure and Content of Clinical Study Reports. 
15.10. 
Publication Policy 
The investigator may not submit the results of the study for publication or present the 
results of the study without the prior written agreement of the Sponsor in accordance with 
the Clinical Trial Agreement. The results of this study will be published as a whole once 
all subjects have completed the study and the study results have been analyzed. Interim 
publications of data from the study may be made if mutually agreed between Sponsor and 
the investigators. Agreement will not be provided by Sponsor when in the Sponsor’s view 
interim publications would introduce bias or lead to any misrepresentation or 
inaccuracies in data. 
Authorship will be determined in conformance with the International Committee of 
Medical Journal Editors (ICMJE) guidelines and/or publication guidelines if applicable. 
 


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16. 
APPENDICES 
16.1. 
List of Abbreviations and Definitions of Terms 
The following abbreviations and specialist terms are used in this study protocol. 
Abbreviations and Specialist Terms 
ABW 
Adjusted Body Weight 
ACS 
Acute Coronary Syndrome 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
ASBMT 
American Society for Blood and Marrow Transplantation 
ASCO 
American Society of Clinical Oncology 
ASCT 
Autologous stem cell transplant 
ATG 
BBB 
Antithymocyte globulin 
Bundle branch block 
BP 
Blood pressure 
BSA 
Body surface area 
CAR 
Chimeric Antigen Receptors 
CKD-EPI 
Chronic kidney disease Epidemiology Collaboration 
CMV 
Cytomegalovirus 
cm 
centimeter 
CR 
Complete Response 
CrCl 
Creatinine clearance 
CRP 
CRO 
C-reactive protein 
Contract Research Organization 
CRS 
CSR 
Cytokine release syndrome 
Clinical Study Report 
CT 
CTA 
Computerized tomography 
Clinical Trials Assay 
CTCAE 
CV 
Common Terminology Criteria for Adverse Events 
Cardiovascular 
DILI 
Drug-induced liver injury 
dL 
deciliter 
DNA 
DOR 
Deoxyribonucleic acid 
Duration of response 
EC 
ECG 
Ethics Committee 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
eCRF 
Eastern Cooperative Oncology Group 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EDTA 
Ethylenediaminetetraacetic acid 
eGFR 
Estimated Glomerular filtration rate 
EMG 
Electromyography 
FCM 
FCBP 
Flow cytometry 
Female of childbearing potential 
FDA 
Food and Drug Administration 
FFPE 
GBS 
Formalin-fixed, paraffin embedded 
Guillain-Barré Syndrome 
GCP 
G-CSF 
Good Clinical Practice 
Granulocyte-Colony Stimulating Factor 
GGTP 
GMP 
Gamma-glutamyl transpeptidase 
Good Manufacturing Practice 
GvHD 
Graft-versus-Host Disease 


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Gy 
Grey 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C virus 
HIV 
Human Immunodeficiency Virus 
IBW 
Ideal body weight 
ICF 
Informed Consent Form 
ICH 
ICU 
International Conference on Harmonization 
Intensive Care Unit 
ID 
IHC 
Identifier 
Immunohistochemistry 
IND 
INL 
Investigational New Drug application 
Investigator Notification Letters 
INR 
International Normalized Ratio 
IO 
IP 
Insertional Oncogenesis 
Investigational Product 
IRB 
ITT 
Institutional Review Board 
Intent-to-Treat population 
mITT 
Modified Intent-to-Treat population 
IV 
Intravenous 
Kg 
kilogram 
LDH 
LTFU 
Lactic acid dehydrogenase 
Long term follow-up 
max 
Maximum 
mg 
miligram 
MHC 
Major histocompatibility complex 
min 
Minute/Minimum 
mL 
Mililiter 
MRCLS 
Myxoid/round cell liposarcoma 
MRI 
MUGA 
Magnetic resonance imaging 
Multiple-gated acquisition scan 
NCI 
National Cancer Institute 
NIH 
NS 
National Institutes of Health 
Normal Saline 
OS 
OTC 
Overall survival 
Over the counter 
ORR 
PBMC 
Overall response rate 
Peripheral blood mononuclear cell 
PCR 
PD 
Polymerase chain reaction 
Progressive Disease 
PET 
Positron emission tomography 
PFS 
PT 
Progression free survival 
Prothrombin time 
PTT 
PR 
Partial thromboplastin time 
Partial response 
RAP 
SAE 
Reporting and analysis plan 
Serious adverse event 
Scr 
Serum Creatinine 
SD 
SIN 
Stable Disease 
Self-inactivating 
SOP 
Standard operating procedure 
SPM 
SUSAR 
Study Procedures Manual 
Suspected, unexpected serious adverse reaction 
TCR 
TILs 
T cell receptors 
Tumor-infiltrating lymphocytes 
RAC 
Recombinant DNA Advisory Committee 
RCL 
Replication competent lentivirus 
RCR 
RECIST 
Replication competent retrovirus 
Response Evaluation Criteria in Solid Tumors 


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RNA 
ULN 
Ribonucleic acid 
Upper limit of normal 
WBC 
White blood cell 
WOCBP 
Woman of childbearing potential 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
None 
 


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16.3. 
Laboratory Tests and ECG 
Hematology, Chemistry and Urinalysis Variables 
Clinical Chemistry 
Hematology 
Calcium  
Phosphorus  
Magnesium  
Albumin  
Bilirubin 
Alanine aminotransferase  
Aspartate aminotransferase  
Alkaline phosphatase  
LDH 
Sodium  
Potassium  
Bicarbonate  
Creatinine  
Chloride  
Glucose  
BUN or Urea 
Red cell count 
Hemoglobin 
Hematocrit 
Mean cell volume 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration  
Platelet count 
White blood cell count & differential count (percent & 
absolute) 
Lymphocyte subsets 
Lymphocyte subsets including CD3 T cell (absolute) count 
Other Tests 
Coagulation Screen 
Uric Acid 
C-reactive protein 
Prothrombin time or International Normalized Ratio  
Activated partial tissue thromboplastin time 
Pregnancy Test 
Thyroid Function Tests 
Serum beta-HCG or Urine test 
Thyroid Stimulating Hormone (TSH)  
Free T3 
Free T4 
Urinalysis 
Microbiology 
Glucose  
Ketones  
Specific gravity  
Protein 
Blood  
Microscopy 
Bilirubin  
pH 
Infectious disease screen  
HIV 1+2 antibody  
Hepatitis B surface antigen 
Hepatitis B core antibody – if positive, test for HBV DNA 
Hepatitis C antibody – if positive, test for HCV RNA HTLV 1+2 
IgG 
CMV IgG  
EBV (EBNA) 
Treponema (Syphilis) 
Viral reactivation 
CMV DNA PCR – peripheral blood for detection of 
reactivation. In the event of suspected end organ CMV 
disease a biopsy may be required 
ECG Parameters 
Heart Rate  
Heart Rhythm  
PR Interval  
RR Interval  
QRS Interval 
QTc Interval (if initial reading is abnormal, the average of 3 readings over 5 minutes; Fridericia’s or Bazett’s correction) 
 
 


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16.4. 
RECIST 1.1 Criteria for Evaluating Response in Solid 
Tumors 
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up. CT is the best 
currently available and reproducible method to measure lesions selected for response 
assessment. MRI is also acceptable in certain situations (e.g., for body scans but not for 
lung). Ultrasound (US) should not be used to measure tumor lesions. The same modality 
should be used when comparing or making assessments. 
Clinical lesions will only be considered measurable when they are superficial and ≥10 
mm in diameter as assessed using calipers. For the case of skin lesions, documentation by 
color photography, including a ruler to estimate the size of the lesion, is recommended. 
Tumor markers alone cannot be used to assess response. If markers are initially above the 
upper normal limit, they must normalize for a subject to be considered in complete 
response. 
Cytology and histology can be used in rare cases (e.g., for evaluation of residual masses 
to differentiate between Partial Response and Complete Response or evaluation of new or 
enlarging effusions to differentiate between Progressive Disease and Response/Stable 
Disease). 
Use of endoscopy and laparoscopy is not advised. However, they can be used to confirm 
complete pathological response. 
All baseline evaluations should be performed as closely as possible to the beginning of 
treatment and never more than 4 weeks before the beginning of the treatment. 
Measurable lesions 
Must be accurately measured in at least one dimension (longest diameter in the plane of 
measurement is to be recorded) with a minimum size of: 
• 10 mm by CT scan (CT scan slice thickness no greater than 5 mm; when CT scans 
have slice thickness >5 mm, the minimum size should be twice the slice 
thickness). 
• 10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable). 
Measurable lesions 
• Malignant lymph nodes to be considered pathologically enlarged and measurable, 
a lymph node must be ≥15 mm in short axis when assessed by CT scan (CT scan 
slice thickness is recommended to be no greater than 5 mm). At baseline and in 
follow-up, only the short axis will be measured and followed. 


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• Lytic bone lesions or mixed lytic-blastic lesions with identifiable soft tissue 
components that can be evaluated by cross-sectional imaging techniques such as 
CT or MRI can be considered measurable if the soft tissue component meets the 
definition of measurability described above. 
• ‘Cystic lesions’ thought to represent cystic metastases can be considered 
measurable if they meet the definition of measurability described above. 
However, if non-cystic lesions are present in the same subject, these are preferred 
for selection as target lesions. 
Non-measurable lesions 
Non-measurable lesions are all other lesions, including small lesions (longest diameter 
<10 mm or pathological lymph nodes with 10 to <15 mm short axis), as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: 
leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory breast 
disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal 
organomegaly identified by physical examination that is not measurable by reproducible 
imaging techniques. 
• Blastic bone lesions are non-measurable. 
• Lesions with prior local treatment, such as those situated in a previously irradiated 
area or in an area subjected to other loco-regional therapy, are usually not 
considered measurable unless there has been demonstrated progression in the 
lesion. Study protocols should detail the conditions under which such lesions 
would be considered measurable. 
Target Lesions 
• All measurable lesions up to a maximum of two lesions per organ and five lesions 
in total, representative of all involved organs, should be identified as target lesions 
and recorded and measured at baseline. 
• Target lesions should be selected on the basis of their size (lesions with the 
longest diameter) and be representative of all involved organs, as well as their 
suitability for reproducible repeated measurements. 
• All measurements should be recorded in metric notation using calipers if 
clinically assessed. A sum of the diameters (longest for non-nodal lesions, short 
axis for nodal lesions) for all target lesions will be calculated and reported as the 
baseline sum diameters, which will be used as reference to further characterize 
any objective tumor regression in the measurable dimension of the disease. If 
lymph nodes are to be included in the sum, only the short axis will contribute. 
Non-target Lesions 
All lesions (or sites of disease) not identified as target lesions, including pathological 
lymph nodes and all non-measurable lesions, should be identified as non-target lesions 


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and be recorded at baseline. Measurements of these lesions are not required, and they 
should be followed as ‘present’, ‘absent’ or in rare cases, ‘unequivocal progression’. 
Evaluation of Target Lesions 
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) must have reduction in short axis to <10 mm 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target 
lesions, taking as reference the baseline sum diameters 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target 
lesions, taking as reference the smallest sum on study (this includes the baseline sum if 
that is the smallest on study). In addition to the relative increase of 20%, the sum must 
also demonstrate an absolute increase of at least 5 mm. The appearance of one or more 
new lesions is also considered progression. Determination of PD will not be made prior 
to the Day 60 evaluation. 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum diameters while on study 
Evaluation of Non-Target Lesions 
Complete Response (CR): Disappearance of all non-target lesions and normalization of 
tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short 
axis) 
If tumor markers are initially above the upper normal limit, they must normalize for a 
subject to be considered in complete clinical response. 
Non-CR/Non-PD (Stable Disease, SD): Persistence of one or more non-target lesion(s) 
and/or maintenance of tumor marker level above the normal limits. 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions. Unequivocal progression should not normally 
trump target lesion status. It must be representative of overall disease status change, not a 
single lesion increase. 
Special notes on the assessment of target lesions 
• Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded even if the nodes regress to below 10 mm on study. When 
lymph nodes are included as target lesions, the ‘sum’ of lesions may not be zero 
even if complete response criteria are met since a normal lymph node is defined 
as having a short axis of <10 mm. 
• Target lesions that become ‘too small to measure’. While on study, all lesions 
(nodal and non-nodal) recorded at baseline should have their actual measurements 
recorded at each subsequent evaluation, even when very small. However, 


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sometimes lesions or lymph nodes become so faint on a CT scan that the 
radiologist may not feel comfortable assigning an exact measure and may report 
them as being ‘too small to measure’, in which case a default value of 5 mm 
should be assigned. Lesions that split or coalesce on treatment. When non-nodal 
lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a 
plane between them may be maintained that would aid in obtaining maximal 
diameter measurements of each individual lesion. If the lesions have truly 
coalesced such that they are no longer separable, the vector of the longest 
diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’. 
Evaluation of non-target lesions 
Complete Response (CR): Disappearance of all non-target lesions and normalization of 
tumor marker levels. All lymph nodes must be non-pathological in size (<10 mm short 
axis). 
Non-CR / Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of 
tumor marker levels above normal limits. 
Progressive Disease (PD): Unequivocal progression of existing non-target lesions. 
• When subject has measurable disease. To achieve ‘unequivocal progression’ on 
the basis of the non-target disease, there must be an overall level of substantial 
worsening in non-target disease such that, even in presence of SD or PR in target 
disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy. A modest ‘increase’ in the size of one or more non-
target lesions is usually not sufficient to qualify for unequivocal progression 
status. 
Progressive Disease (PD): Unequivocal progression of existing non-target lesions. 
• When subject has only non-measurable disease. There is no measurable disease 
assessment to factor into the interpretation of an increase in non-measurable 
disease burden. Because worsening in non-target disease cannot be easily 
quantified, a useful test that can be applied is to consider if the increase in overall 
disease burden based on change in non-measurable disease is comparable in 
magnitude to the increase that would be required to declare PD for measurable 
disease. Examples include an increase in a pleural effusion from ‘trace’ to ‘large’ 
or an increase in lymphangitic disease from localized to widespread. 
New lesions 
The appearance of new malignant lesions denotes disease progression: 
• The finding of a new lesion should be unequivocal (i.e., not attributable to 
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thought to represent something other than tumor, especially when the subject’s 
baseline lesions show partial or complete response). 
• If a new lesion is equivocal, for example because of its small size, continued 
therapy and follow-up evaluation will clarify if it represents truly new disease. If 
repeat scans confirm there is definitely a new lesion, then progression should be 
declared using the date of the initial scan. 
• A lesion identified on a follow-up study in an anatomical location that was not 
scanned at baseline is considered a new lesion and disease progression. 
It is sometimes reasonable to incorporate the use of FDG-PET scanning to complement 
CT in assessment of progression (particularly possible ‘new’ disease). New lesions on the 
basis of FDG-PET imaging can be identified according to the following algorithm: 
No FDG-PET at baseline and a positive FDG-PET at follow-up: 
• If the positive FDG-PET at follow-up corresponds to a new site of disease 
confirmed by CT, this is PD. 
• If the positive FDG-PET at follow-up is not confirmed as a new site of disease on 
CT, additional follow-up CT scans are needed to determine if there is truly 
progression occurring at that site (if so, the date of PD will be the date of the 
initial abnormal FDG - PET scan). 
• If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease 
on CT that is not progressing on the basis of the anatomic images, this is not PD. 
Summary of the overall response status calculation at each time point: 
Target Lesions 
Non-Target 
Lesions 
New Lesions Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-CR  
Non-PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not evaluated No 
PR 
PR 
Non-CR  
Non-PD 
Not evaluated 
No 
PR 


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Target Lesions 
Non-Target 
Lesions 
New Lesions Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
SD 
Non-CR  
Non-PD 
Not evaluated 
No 
SD 
Documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or No 
PD 
No prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
*See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
**Only for non-randomized trials with response as primary endpoint. 
***In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease 
progression 
 
Confirmation 
In non-randomized trials where response is the primary endpoint, confirmation of PR and 
CR is required to ensure responses identified are not the result of measurement error. 
This will also permit appropriate interpretation of results in the context of historical data 
where response has traditionally required confirmation in such trials. 
In the case of SD, measurements must have met the SD criteria at least once after study 
entry at a minimum interval (in general not less than 6–8 weeks) that is defined in the 
study protocol. 
Where progression is equivocal, confirmation of PD is required unless there is an 
immediate medical need to initiate anti-cancer therapy before a confirmatory scan can be 
arranged. 
Missing Assessments and Inevaluable Designation 
When no imaging/measurement is done at all at a particular time point, the subject is not 
evaluable (NE) at that time point. If only a subset of lesion measurements are made at an 
assessment, usually the case is also considered NE at that time point, unless a convincing 
argument can be made that the contribution of the individual missing lesion(s) would not 
change the assigned time point response. This would most likely happen in the case of 
PD. 
https://www.eortc.be/Recist/documents/RECISTGuidelines.pdf 


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16.5. 
Liver Safety Required Actions and Follow up Assessments 
Liver Safety: Required Actions and Follow-up Assessments.  
Level 1 Monitoring 
In the event that the subject develops elevations in LFT parameters as defined below, an 
increase to liver chemistry monitoring i.e., at weekly intervals, will apply. 
Liver Chemistry Monitoring Criteria Level 1 
Criteria 
Actions 
ALT ≥3x ULN but ALT <5x ULN and bilirubin 
<2xULN, without symptoms believed to be related 
to liver injury, or hypersensitivity 
• 
Notify the GSK medical monitor within 24 hours of learning 
of the abnormality to discuss participant safety. 
• 
Participant must return weekly for repeat liver chemistries 
(ALT, AST, alkaline phosphatase, bilirubin) until they 
resolve, stabilize or return to within baseline 
• 
If, during monitoring, ALT increases to  5xULN, or 
remains ≥3x ULN for ≥4 weeks, or if total bilirubin 
increases to ≥2xULN, refer to Level 2 monitoring guidance 
below. 
• 
If, after 4 weeks of monitoring, ALT <3xULN and bilirubin 
<2xULN, monitor participants twice monthly until liver 
chemistries normalize or return to within baseline. 
 
Level 2 Monitoring 
In the event that the subject develops elevations in LFT parameters as defined below, an 
increase to liver chemistry monitoring at more frequent intervals i.e., twice weekly, will 
apply. 
Liver Chemistry Monitoring Criteria Level 2 
ALT-absolute 
ALT ≥5xULN 
ALT Increase 
ALT ≥3xULN that persists for 4 weeks 
Bilirubin1, 2 
ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) 
INR2 
ALT ≥3xULN and INR>1.5 
Symptomatic3 
ALT ≥3xULN and associated with symptoms (new or 
worsening) believed to be related to liver injury or 
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Required Actions and Follow up Assessments 
Actions 
Follow Up Assessments 
• 
Report the event to GSK within 24 hours 
• 
Complete the CRF and complete an SAE data 
collection tool if the event also meets the criteria 
for an SAE2 
• 
Perform liver event follow up assessments 
• 
Monitor the participant until liver chemistries 
resolve, stabilize, or return to within baseline 
(pre-Gene Therapy) (see MONITORING below) 
MONITORING: 
For bilirubin or INR criteria: 
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin, INR) and perform 
liver event follow up assessments within 24 hrs. 
• 
Monitor 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) 
• 
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). 
• 
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 
computerized tomography) and 
/or liver biopsy to evaluate liver disease; complete 
Liver Imaging and/or Liver Biopsy CRF Forms 
1. Serum bilirubin fractionation should be performed if testing is available. Additionally, if serum bilirubin fractionation 
testing is unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin 
elevations and suggesting liver injury. 
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 
 
 
 


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16.6. 
Summary of Changes from Protocol Version 1.0 to Version 
2.0 
Section of 
Version 1.0 
Section of 
Version 2.0 
Change 
Title 
Title 
Change of title to reflect alteration in scope to a pilot study 
Synopsis 
Synopsis 
Updated with new study title, phase, details of long-term follow up protocol, study 
duration, number of subjects, statistical methodology, editorial changes 
1.2 
1.2 
Updated historical data for IP 
1.4 
1.4 
Change to rationale to reflect pilot study 
3.1 
3.1 
Study design changed to reflect patient numbers. Updated definition of inoperable 
disease. 
Clarification on consent process. 
3.2.1 
3.2.1 
Definition of screening and interventional phases added. Obsolete wording on 
futility removed. 
3.2.3 
3.2.3 
Time of manufacturing amended to reflect product release only after full release 
testing is performed. 
3.2.4 
3.2.4 
Reference updated 
3.3 
3.3 
Updated with new design and rationale for potentially expanding study enrolment 
3.4 
3.4 
Number of clinical sites updated to reflect change in study design 
3.5.1 
3.5.1 
References updated 
3.5.3 
3.5.3 
Risk: benefit updated to reflect change to pilot study 
4.1 
4.1 
Definition of “inoperable” included to clarify criterion 
Detail added to clarify Gilbert syndrome Biopsy requirement updated 
Requirements for contraception moved to own section. Wording added to allow for 
country- specific requirements. 
4.2 
4.2 
Explanation added to clarify wash-out periods are prior to leukapheresis and 
lymphodepletion. 
Radiotherapy wording updated to specify palliation to lesions rather than organs. 
Requirement for triplicate ECGs moved to ECG / lab test section. 
4.3 
4.3 
Information on long-term follow up protocol added 
4.4 
4.4 
Criteria for subject withdrawal updated 
5.1 
5.1 
Recommendations for clinical care of leukapheresis patients added – minimum 
recommended lymphocyte and T cell counts. 
Wording for hypocalcemia prophylaxis updated. 
5.2 
5.2 
Instructions for administration of lymphodepleting chemotherapy updated. Volume 
of chemotherapy infusions updated. 
Clarification on timing of T cell infusion added. 
5.2.2 
5.2.2 
Recommended regimen for Mesna updated 
6 
6 
Timing for concomitant medication collection start / stop clarified 
6.1 
6.1 
Information on long term follow up protocol provided 
- 
6.2.1 
New section defining females of childbearing potential and requirements for 
contraception added 
7 
7 
Information on assignation of Subject ID and long term follow up protocol provided 
7.1 
7.1 
Information on centralized HLA screening provided 
7.3 
7.3 
Lymphocyte subsets test added 
Disease history collection clarified – Screening 2 only 
Concomitant medications clarified – Screening 2-onwards 
Renal function testing requirements updated 
7.4.2 
7.4.2 
Typo corrected 
7.4.9 
7.4.9 
Clarification on independent response assessment provided 
7.4.10 
7.4.10 
Further information on long term follow up provided 
new 
8.2.1 
Information on prophylaxis against pneumocystis carinii pneumonia provided 
new 
8.2.2 
Information on prophylaxis against HSV and VSV provided 
new 
8.2.5 
Information on screening for Treponema provided 


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Section of 
Version 1.0 
Section of 
Version 2.0 
Change 
new 
8.2.6 
General recommendation for anti-microbial prophylaxis provided 
9.1 
9.1 
Collection period for AEs and SAEs redefined 
9.4 
9.4 
Information on long term follow up protocol added 
9.7 
9.7 
Clarification on recommendations for breastfeeding provided 
Information on long term follow up protocol added 
new 
10.1 
Information on data safety monitoring plan added 
new 
10.2 
Study stopping rules added 
10.3.2 
10.3.2 
Actions on positive RCL test updated 
10.3.4 
10.3.4 
Clarification on provision of LTFU follow-up provided 
10.3.5 
10.3.5 
Information on specifics of testing for insertional oncogenesis added 
11.1 
11.1 
Study populations clarified 
11.2 
11.2 
Information on statistical basis for analysis of the updated pilot study provided. 
Information on Bayesian and frequentist methods for analysis of ORR added 
Details provided on potential expansion of the study beyond n=10 added 
11.3 
11.3 
Statistical methods for assessing endpoints updated 
11.4 
11.4 
Statistical methods for assessing safety updated 
12.2 
12.2 
Editorial changes 
12.3 
12.3 
Storage temperature requirements updated 
16.1 
16.1 
Glossary updated 
16.3 
16.3 
Laboratory test and ECG table updated to allow BUN instead of urea testing. 
Lymphocyte subsets test added 
Treponema test amended to broaden methodologies allowed 
QT testing clarified 
16.4 
16.4 
Details of confirmatory scans updated 
17 
17 
References updated 
 
 


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16.7. 
Summary of Changes from Protocol Version 2.0 to Version 
3.0 
Section of Version 2.0 
Section of Version 3.0 
Change 
Synopsis 
Synopsis 
Updated exclusion criteria to include revised therapy 
washout periods required prior to leukapheresis and 
lymphodepletion 
4.2 
4.2 
Updated exclusion criteria to include revised therapy 
washout periods required prior to leukapheresis and 
lymphodepletion 
5.2.1 
5.2.1 
Corrected typographical error – full fludarabine dose was 
previously at GFR >80mL/min which left the dose required 
at exactly 80mL/min undefined; changed to ≥80 mL/min 
7.3 
7.3 
Schedule of procedures updated 
Adverse Events to be collected from Visit 2 in line with 
protocol Section 9.1 
Additional column added to differentiate Year 1 post-
infusion assessments from subsequent assessments and 
allow for clarified explanation of research sampling at 
these time points. 
Footnotes updated: 
1) Updated to clarify that only Visit 2 screening 
assessments are required to occur within a specified time 
prior to leukapheresis 
5) Typographical error corrected; vital signs are to be 
measured at time points after start of T cell infusion, not 
end of infusion 
7.3 
7.3 
7) Timing of response / progression confirmatory scan 
clarified 
17) Updated to include timings for baseline biopsy 
specified in Section 7.5.3 
Additional footnotes added: 
Specifies that Day 1 ECG is to be performed pre-infusion 
Provides timings for persistence testing stated in Section 
10.3.4 
Provides timings for RCL testing stated in Section 10.3.4 
Provides visit frequency for subjects >1yr post-infusion 
7.4.9 
7.4.9 
Timing of response / progression confirmatory scan 
clarified 


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Section of Version 2.0 
Section of Version 3.0 
Change 
16.3 
16.3 
HBV surface antigen added in line with inclusion 
/ exclusion criteria 
Information added on when triplicate ECG testing is 
needed 
 


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16.8. 
Summary of Changes from Protocol Version 3.0 to Version 
4.0 
Section of Version 3.0 
Section of Version 4.0 
Change 
3.5.3 
3.5.3 
Update to risk assessment to add additional risk of 
Guillain-Barré syndrome and other demyelinating 
neuropathies. 
4.2 
4.2 
Addition of Prior or active demyelinating disease as an 
exclusion criterion. 
9.3 
9.3 
Addition of all cases of Guillain-Barré syndrome or acute 
demyelinating neuropathy as a reportable SAE within 24 
hours. 
N/A 
10.1.1 
Addition of Mandated Study Pause due to GBS 
N/A 
10.3.6 
Addition of Monitoring and Management for 
Demyelinating Neuropathy and other Neurological events 
 


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16.9. 
Summary of Changes from Protocol Version 4.0 to Version 
5.0 
Rationale for Amendment 
The purpose of this amendment is to provide clarification on definitions of enrolment and intent to treat population.   
Summary of Changes  
The following details the changes made for the current protocol version 05. Bolded text has been added and text with 
strikethrough has been deleted.  Minor typographical or editorial changes were also made, none of which impact the 
overall content or interpretation of the protocol.    
Change 01 
Section:  Synopsis, Methodology 
Initially, 10 subjects will be enrolled treated/infused in this study. If further characterization of the treatment in this 
indication is required, up to a further 10 subjects may be enrolled treated/infused. The Sponsor may also decide to 
close the study at any time based on safety or efficacy. 
Change 02 
Section:  Synopsis, Number of subjects 
The target enrolment for this trial is up to 20 subjects, depending on emerging data. Up to 20 subjects may be enrolled 
treated/infused in total. 
Change 03 
Section:  Synopsis, Statistical Methodology  
After 10 evaluable subjects, response will be evaluated using Bayesian posterior predictive probabilities to inform 
clinical decision making to continue enrolment to up to 20 evaluable subjects. 
The primary analysis population for safety and efficacy will be the intention to treat population (ITT) defined as all 
subjects who enrolled and were apheresed in this study. 
Change 04 
Section 3.2.3 T-Cell Manufacturing (2nd paragraph) 
At the end of the culture, cells are depleted of magnetic beads, washed, concentrated, and cryopreserved. Release 
testing takes approximately an additional 8-10 days 4 weeks. Therefore, cell product typically is ready to be returned to 
the site approximately 28 42-45 days after subject apheresis. 
Change 05 
Section 3.3 Target Enrolment and Study Duration 
A target enrolment of 10 subjects infused with potential expansion up to 20 subjects is considered appropriate for 
evaluating preliminary efficacy (antitumor activity) and safety in this phase I/II study of subjects with a rare, orphan 
disease. 
Potential subjects will first sign a screening consent to screen for HLA and antigen testing. It is expected that 
approximately 50% of subjects will be HLA negative, and 20% of these subjects will be NY-ESO negative. Therefore, it 


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is expected that up to 60 subjects may sign the screening consent. Once HLA and antigen testing are confirmed, 
subjects will return for the second screening visit, at which time the treatment consent will be signed, and the 
remainder of eligibility requirements will be verified. Enrolled subjects will be considered those subjects who sign the 
treatment consent, meet all eligibility requirements, and undergo apheresis. Based on information gathered from the 
pilot sarcoma study, it is expected that there will be some subjects who undergo apheresis but do not receive 
manufactured cells. Therefore, in this study, approximately 26 subjects may be enrolled in order to obtain the target 
number of 20 subjects treated with manufactured product. Up to 13 subjects may be enrolled in order to obtain the 
target number of 10 subjects treated with manufactured product in cohort 1, and up to 13 subjects may be enrolled in 
order to obtain the target number of 10 subjects treated with manufactured product in cohort 2. Once the target number 
of patients have manufactured product in each cohort, the study will be closed for enrolment and apheresis.  In the 
event that a subject has manufactured product and is not able to receive treatment, an apheresis slot may then be 
opened for a screen positive patient to be enrolled. 
4th paragraph: 
The confirmed overall response rate per RECIST V1.1 by independent investigator review will be evaluated after the 
first 10 enrolled subjects have been treated and the last ongoing subject has at least 8 12 weeks of follow up or has 
progressed. 
Change 06 
Section 11.1 Study Populations 
Intent-to-Treat (ITT) population: This population comprises all eligible subjects who were enrolled in the trial (i.e., all 
subjects who signed the treatment informed consent and underwent apheresis). The ITT population is the primary 
analysis population for efficacy and safety evaluations. 
Change 07 
Section 11.2 Statistical Methods for Interim Analysis 
Participants are evaluable if they had at least 2 3 post baseline disease assessments or progressed or died or 
withdrawn from the study. 


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16.10. 
Summary of Changes from Protocol Version 5.0 to Version 
6.0 
Rationale for Changes: 
• 
The purpose of this amendment is the following: 
• 
Addition/clarification of delayed AE definition 
• 
Revised guidelines for the management of CRS 
• 
Revised guidelines for the management of encephalopathy syndrome 
• 
Adjustment to lymphodepletion regimen for safety purposes 
• 
Various clarifications and administrative updates 
 
Additions are marked in red, deletions are marked with strikethrough. 
Change 1 
Synopsis 
Option 1 (first 10 subjects) will involve lymphodepleting chemotherapy with fludarabine and cyclophosphamide on Days -7 
to -5 and the study therapy by a single intravenous infusion on Day 1. Option 2 (second 10 subjects) will involve 
lymphodepleting chemotherapy with fludarabine on Days -8 to -5 and cyclophosphamide on Days -7 to -5 and the study 
therapy by a single intravenous infusion on Day 1. 
Change 2 
Synopsis 
Dose and regimen for lymphodepleting chemotherapy will be adjusted for subjects ≥60 years of age. 
Change 3 
Synopsis 
The target treatment enrolment for this trial is up to 20 subjects treated, depending on emerging data. Up to 20 
subjects may be treated/infused in total. 
Change 4 
Synopsis 
Exclusion #2: Radiotherapy within the following periods prior to leukapheresis or lymphodepleting chemotherapy (study 
team should consider prior cumulative radiotherapy totaling <25% of body surface area). 
Change 5 
Synopsis 
Exclusion #9: Ongoing or active infection. EBV and CMV IgG seropositive patients who have a positive PCR 
Change 6 
Synopsis 
The primary analysis population for safety and efficacy will be the intention to treat population (ITT), where appropriate, 
defined as all subjects who enrolled and were apheresed in this study and the modified intention to treat population 
(mITT), where appropriate, defined as all subjects who were treated in this study. The primary analysis population for 
efficacy will be the mITT population. 
Change 7 
Section 2, Table 1 
• 
AEs, including SAEs and AESIs 
Change 8 
Section 3.2.4 
Age related modifications to the lymphodepletion regimen will be made as outlined in Section 5.2. 
Change 9 
Section 3.3 
Expansion from n=10 to a maximum of n=20 may be done to better characterize safety, efficacy 
and tolerability, based on the clinical evaluation of the emerging data (See Section 11). In 
addition, more subjects may be enrolled for those who do not receive the minimum cell dose or 


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who do not receive the T-cell infusion may be replaced to better characterize safety, efficacy and 
tolerability as part of this expansion. 
Change 10 
Sections 3.5.1, 3.5.2 
Safety profile updated based on latest IB. 
Change 11 
Section 4.2 
Exclusion #2: Radiotherapy within the following periods prior to leukapheresis or lymphodepleting chemotherapy (study 
team should consider prior cumulative radiotherapy totaling <25% of body surface area). 
Change 12 
Section 4.2 
Exclusion #9: Ongoing or active infection. EBV and CMV IgG seropositive patients who have a positive PCR 
Change 13 
Section 4.3 
A subject will be considered to have completed the interventional phase of the study when he/she has confirmed 
progression of disease (see Section 7.4.10 for tumor response assessments), withdrawal of consent, death, or 2 
years after NY-ESO-1C259T cell infusion, whichever is shorter. 
Change 14 
Section 4.3.1 
Long-Term Follow-up – new section 
Change 15 
Section 5.2 
Dose and regimen for lymphodepleting chemotherapy is adjusted for participants 60 years of age, 
as specified in Table 2, Option 2.  For participants with documented history of severe and/or 
prolonged cytopenia (anemia, thrombocytopenia, or leukopenia), the investigator should discuss with 
the sponsor’s medical monitor or designee to determine the need for dose modification of the 
lymphodepletion regimen. 
Change 16 
Table 2, Option 2 – lymphodepletion dose for participants 60 years old added 
Change 17 
Section 5.2.1 
This adjustment needs to be applied to all doses. Patients ≥ 60 years of age receiving an age adjusted dose, will 
have the renal adjustment applied to the modified dose for age.   
Change 18 
Section 6.3.1 
Subjects randomized to Arm 2 must also use effective contraception for at least 4 months after the last dose of 
pembrolizumab. 
Change 19 
Section 7 
Administrative updates 
Change 20 
Section 7.4, Table 4 
Multiple changes within SoA 
CARTOX ICE 
Cytokine analyses & humoral anti-infused cell response 
Anti-NY-ESO-1 TCR Antibodies (Immunogenicity Sample) (Day 1, Wk 3, Wk 5, Wk 8, Wk 12, Wk 24, M9, M12, 
Completion or WD) 
Exosome and ctDNA collection (liquid biopsy) (Additional at D8 & W4) 
Change 21 
Section 7.4, Table 4 footnotes 
#13. If cytokine release syndrome is suspected, CRP levels should be measured every day for the first week and 
approximately every other day thereafter until symptoms are improving or an alternative diagnosis is confirmed. 


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#17. Core needle biopsies for research are planned required at baseline, Week 8, and at progression, with the 
exception of subjects for whom there is no safely accessible tumor tissue. Archival tissue may be used for screening. 
The baseline biopsy may should be collected any time between two months and 2 weeks prior to the start of 
lymphodepleting chemotherapy. 
#19. Pre-infusion, Week 3, Week 8, and Week 12 blood collection is for both Cytokine and  Immunogenicity responses, 
and is collected in one 3 ml tube. If CRS is suspected, cytokines should be collected every day for the first week and 
approximately every other day thereafter until symptoms are improving or an alternative diagnosis is confirmed. 
Pre-infusion and Week 8 blood collection is for both Cytokine and Humoral anti-infused cell responses, and is collected 
in one 3 ml tube. 
#20. Vector copies for safety samples are collected Day 1 (pre-infusion) and then every 6 months post-infusion up to 5 
years (Section 10.3.4 for more details). For RCL, samples are collected Day 1 (pre-infusion), and at Week 12, Week 
24, and 1 year post-infusion and then annually for up to 15 years. 
Vector copies for safety samples are collected Day 1 (pre-infusion) and then every 6 months post-infusion up to 5 
years. For RCL, samples are collected Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion and 
then annually. 
#24. CARTOX 10 ICE should be measured on the day of NY-ESO-1c259T cell infusion prior to receiving treatment 
and then at least through Day 8 according to the schedule of procedures. Subjects with known brain metastases should 
be monitored at least twice per day for the first 5 days following NY-ESO- 1c259T cell infusion. If a subject is found to 
have ES ICANS, the CARTOX 10 ICE should be used at least twice per day until resolution or stable. It can also be 
used at later visits if indicated. 
Change 21 
Section 7.4.9 
Monitoring for ES Monitoring for Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
CARTOX-10 Immune Effector Cell-Associated Encephalopathy (ICE) should be measured on the day of NY-
ESO-1c259T infusion prior to receiving treatment and then at least through Day 8 according to the schedule of 
procedures… If a subject is found to have ES ICANS, the CARTOX-10 ICE should be used at least twice per day 
until resolution or stable. 
Change 22 
Section 7.4.10 
For subjects who have new lesions, response by irRECIST (Nishino 2013) will be assessed by the investigator for 
exploratory purposes. For new lesions, information on whether the lesion is measurable or non-measurable will be 
recorded in the eCRF. The measurements of measurable lesions will also be recorded. 
Change 23 
Section 7.5 
• 
Luminex MSD to measure serum cytokine levels 
• 
Tissue analysis for immune cell infiltrate and functional biomarkers (by single or multiplexed IHC) and gene 
expression profile (including by Nanostring or next-gen sequencing of RNA) 
• 
Tissue analysis to determine the evolution of the mutation profile of the tumor over the course of the therapy 
by DNA sequencing analysis 
Change 24 
Section 7.5.3 – change of core needle biopsies from requested to mandated 
Change 25 
Section 7.5.4 
Quantitation of NY-ESO-1c259T TCR+ cells by PCR of transgene from DNA extracted from frozen PBMC. This 
will be used as a measure of pharmacokinetics. 
Change 26 
Section 7.5.6 – testing clarifications 
Change 27 
Section 8.5, Table 6 
entire table updated  


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CRS grading updated 
Change 28 
Section 8.7.3 
Management of Guillain-Barré Syndrome (GBS) section added with specific instructions on assessments, 
grading, and treatment. 
Change 29 
Section 9.1 
All AEs and SAEs will be collected and reported from the time the subject signs a treatment informed 
consent form of leukapheresis until the subject has completed the interventional phase of the study. 
Regardless of study end for a participant, all SAEs must be collected through 90 days following T cell 
infusion, or 30 days following T cell infusion if the participant initiates new anticancer therapy, 
whichever is earlier. 
Change 30 
Section 9.4 
Delayed AEs are defined as those events that fall into one or more of the 6 categories listed below and which occur 
either more than one year following GSK3377794 infusion or after disease progression, whichever occurs first.  In the 
event a subject has not progressed 1 year following GSK3377794 infusion, delayed AEs will be collected in 
Interventional Phase of study. Delayed AEs which occur post progression will be collected as part of the LTFU phase 
of the current study or in the LTFU Study (208750), contingent upon formal transfer of subject to Study 208750. 
Subjects with confirmed disease progression will transfer to a LTFU protocol GSK208750 (ADP-0000-2) for 
continued monitoring of gene therapy related adverse events. Emergence of any of the following new clinical 
conditions reported or observed and the action taken will be reported to the Sponsor: 
Change 31 
Sections 9.8, 9.8.1 
Management of Encephalopathy Syndrome Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
Section updated to reflect updated management guidelines and grading of ICANS 
Change 32 
Section 10.2 
Any event of Guillain-Barre syndrome (GBS) as diagnosed by a neurologist according to diagnostic 
guidance for GBS [Fokke, 2014]. 
Change 33 
Section 10.3.4 
Note: Samples for RCL must continue to be collected and archived annually for up to 15 years post infusion. 
Change 34 
Sections 11.1, 11.3, 11.4 
The ITT population is the primary analysis population for  safety endpoints, where appropriate efficacy and safety 
evaluations. 
The mITT population is the primary secondary analysis population for efficacy endpoints and the primary analysis 
population for and safety endpoints, where appropriate. 
The primary analysis population for efficacy will be the mITT population. The mITT population will be 
used as a secondary population for analysis. 
The primary analysis population for safety will be the ITT population, with the mITT used as necessary. 


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Study 208469:  List of Changes included in Protocol Amendment 6 
Section 
Change 
Rationale 
Section 2 
Updated primary endpoint of ORR to be based 
on investigator assessment rather than 
independent reviewer assessment 
Align method of assessment of primary 
endpoint of ORR for overall analysis with 
that for interim analysis to provide 
consistency between the two analyses 
Section 2 
Inserted secondary endpoint of ORR as 
assessed by independent review 
Clarify that secondary ORR efficacy 
endpoint assessment to be conducted by 
independent review 
Section 2 
Inserted secondary endpoint for PK profile  
Clarify terms for monitoring persistence of 
NY-ESO-1c259T cells  
Section 2 
Removed secondary endpoint for development 
of companion diagnostic assay and removed 
references to companion diagnostic assay 
throughout protocol amendment 
Clarify that assay development is not being 
undertaken 
Section 2 
Exploratory objective /endpoint - Replaced term 
“persistence” with “PK profile” 
Provide greater clarity for what parameters 
are to be assessed 
Section 2 
Section 2 
Updated pharmacogenetic endpoint 
Expand analysis from cytokine genes to 
entire genome – consistent with program 
objective/endpoint 
Section 3.1, 
Section 4.3 
Included guidance for monitoring of response 
post 2-years on trial 
Provide guidance to permit ongoing 
monitoring of responding patients 
supporting broader understanding of drug 
activity 
Section 3.2.3 
Updated background information for 
GSK3377794 in T-cell manufacturing section 
Provide more comprehensive description of 
GSK3377794 and ongoing clinical trials 
Section 3.3 
Update plans for enrollment into Option 1 and 
update definition of study complete 
Provide clarification to enrollment plans 
and to definition of study completion 
Section 3.3  
Updated definition of evaluable subjects in 
Section 3.3 to match that provided in Section 
11.2 Interim Analysis 
Establish consistency 
Section 3.3 
Deleted statement in Section 3.3 that continuous 
interim assessment of participants beyond 10 
would “be used to continuously assess ORR and 
inform decisions regarding enrollment of 
additional subjects”. 
Clarify to align description of interim 
analyses with those planned following 
introduction of the high lymphodepletion 
regimen for the expansion cohort in 
amendment #2: 
Section 3.5.2 
Updated Risk Assessment section with safety 
data from most recent GSK3377794 Investigator 
Brochure Version 12 
Ensure most up-to-date risk information is 
included in protocol 
CCI


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Study 208469:  List of Changes included in Protocol Amendment 6 
Section 
Change 
Rationale 
Section 3.5.2. 
Included US adopted name (USAN) of 
GSK3377794 – letestregene autoleucel (lete-cel 
as appropriate throughout protocol 
Include USAN drug name 
Section 4.1, 
Section 6.3.1 
Updated requirements for female contraception 
Provide most up-to-date program-level 
guidance for duration of female subject 
contraception use 
Section 4.3 
Clarified definition of completion of interventional 
phase 
Prior definition unclear and not sufficiently 
comprehensive  
Section 4.3 
Clarified completion of study definition  
Prior definition unclear and not sufficiently 
comprehensive.  
Section 6.1 
Clarified consequence of subject receiving new 
anti-cancer therapy while on study  
 
 
Provide clear description of impact of active 
patient receiving anti-cancer therapy while 
continuing in the interventional portion of 
the study. 
Section 7.3, 
Table 4 
Corrected heading to column describing activities 
to be completed in Years 1 and 2.  Prior title not 
consistent with safety assessment intent and 
tumor assessment scan interval defined in 
Section 7.4.10 
Ensure correct safety and tumor 
assessment frequency included in protocol. 
Section 7.3, 
Table 4 
Added a footnote clarifying frequency of sample 
collection for TCR antibody analyses 
Ensure correct sample collection frequency 
included in protocol  
Section 7.4.10, 
multiple protocol 
sections 
Removed requirement for confirmation of 
disease progression 
Confirmation of disease progression not 
required by RECIST v 1.1.  Not updated in 
prior protocol amendment 5 when 
irRECIST was removed from protocol. 
Section 11.1 
Clarified and made consistent descriptions of ITT 
and mITT populations (with no change to 
population definitions) 
Improve protocol text used to describe 
these two populations. 
Section 11.1 
Updated definition of Intent-to-Treat population  
Define ITT population and clarify meaning 
of “enrolled” 
Section 11.2 
Added statement describing planned second 
interim analysis in “at least 8 evaluable” in the 
high lymphodepletion cohort.  
Clarify to align description of interim 
analyses with those planned following 
introduction of the high lymphodepletion 
regimen for the expansion cohort in 
amendment #2: 
Section 11.3 
Clarified description for Time to Response 
endpoint  
Clarify which subjects suitable for this 
analysis.  Analysis had previously been 
incorrectly described as a survival analysis. 
Section 11.3 
Updated information for secondary efficacy 
endpoints throughout section 
Clarify which efficacy endpoints are used in 
study  
Throughout 
amendment 
Clarified text for improved ease of understanding 
and corrected formatting  
Enhance reader comprehension and 
improve document readability 
Throughout 
amendment 
document 
Format of entire document updated from 
Adaptimmune style to GSK standard protocol 
format 
Bring document into compliance with GSK 
formatting standards 
 


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16.12. 
Summary of Changes from Protocol Version 7.0 to Version 
8.0 
The primary purpose of this amendment is to add the potential for a second infusion for 
eligible subjects with sufficient residual cell product.   
The following table details all changes and rationale: 
Study 208469:  List of Changes included in Protocol Amendment 7 
Section 
Change 
Rationale 
Section 7.6 
Incorporated Section 7.6 describing potential for 
retreatment for subjects who meet specific 
criteria and have sufficient residual cells 
Provide the opportunity for subjects who 
have a confirmed CR or PR or SD ≥3 
months, have disease progression >3 
months post T cell infusion, and have 
adequate residual cells for a second NY-
ESO-1c259T cell infusion to receive a 
second T cell infusion.  The intent is to 
provide those patients who have benefitted 
from the drug product a retreatment 
opportunity in a setting where efficacy, 
safety, and tolerability can be followed as 
exploratory objectives.  
 
 
 


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16.13. 
Summary of Changes from Protocol Version 8.0 to Version 
9.0 
The primary purpose of this amendment is to make changes to protocol in reference to Dear 
Investigator Letter dated 03 May 2021 and Protocol and ICF clarification memorandum dated 
11 May 2021 regarding mitigations put in place on active studies of GSK3377794 
(letetresgene autoleucel, lete-cel), following the recent SAEs of fatal neutropenia (1 event) 
and decreased vision (1 event).  
 
The following table details all changes and rationale: 
Study 208469:  List of Changes included in Protocol Amendment 8 
Section 
Change 
Rationale 
Synopsis: 
Subject inclusion 
criteria 
 
Section 4.1, 
Subject Inclusion 
Criteria 
Updated Inclusion criterion 14, Definitions of 
Adequate Organ Function, Renal: provided 
further guidance on assessing accurate Renal 
function with below changes:  
 
1. 
Guidance for assessment of Renal 
function in participants who are ≥18 
and <65 years of age  
2. 
Guidance for assessment of Renal 
function in participants who are ≥65 
years of age 
 
Additional guidance is provided for precise 
calculations of Creatinine clearance and 
assessment of renal impairment prior to 
initiating lymphodepleting chemotherapy. 
Dose adjustments for fludarabine and 
cyclophosphamide will be performed based 
on the revised calculations using the 
guidelines provided through this change in 
the protocol. 
Synopsis: 
Subject 
Exclusion 
Criteria 
 
Section 4.2, 
Subject 
Exclusion 
Criteria 
Removed (study team should consider prior 
cumulative radiotherapy totalling <25% of body 
surface area) and replaced it with 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 
The intent of this criterion was to exclude 
subjects who have undergone radiotherapy 
that exceeded a minimum bone marrow 
exposure. The change will apply to any 
radiotherapy (ie. including palliative, 
adjuvant or neoadjuvant); this exclusion is 
modified in the protocol amendment to 
further quantify exposure to aid in 
assessment of bone marrow reserve. 
Section 5.2, 
Lymphodepleting 
Chemotherapy 
Further guidance provided on identifying 
participants requiring dose modifications for 
lymphodepleting chemotherapy. 
 
Table 2, footnote 1: clarification provided on 
fludarabine dose adjustment. 
 
Table 3: CrCl range of 30 – 80 mL/min is divided 
into >50 – 80 mL/min with corresponding 
fludarabine dose of 20 mg/m2 and 30 – 50 
mL/min with corresponding fludarabine dose of 
15 mg/m2.  
 
Added section 5.2.2, Cyclophosphamide Dose 
Adjustment. 
 
 
This clarification allows identifying 
participants who may require dose 
modifications due to other reasons. 
For Clarification 
Further guidelines were provided for 
accurate calculation of creatinine clearance 
and dose adjustment for lymphodepleting 
chemotherapy. 
 
Additional guidelines provided for 
cyclophosphamide dose adjustment and 
additional guidelines for calculating ideal 
and adjusted body weight.. 


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Study 208469:  List of Changes included in Protocol Amendment 8 
Section 
Change 
Rationale 
Section 9.3, 
Reporting 
Serious Adverse 
Events 
Addition to SAE defining criterion of AE of 
special interest: Neutropenia grade 4 lasting ≥28 
days 
Neutropenia grade 4 lasting ≥28 days will 
now be considered an AE of special 
interest, and must be reported to the 
Sponsor within 24 hours, as per 
established process outlined in protocol 
section 9.3 
 
 
 


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16.14. 
Summary of Changes from Protocol Version 9.0 to Version 
10.0 
The primary purpose of this amendment is to make changes to protocol in reference to Dear 
Investigator Letter dated 21-Oct-2021 and Protocol and ICF clarification memorandum dated 
25-Oct-2021 regarding mitigations put in place on active studies of GSK3377794 
(letetresgene autoleucel, lete-cel).  
 
The following table details all changes and rationale: 
Study 208469:  List of Changes included in Protocol Amendment 9 
Section 
Change 
Rationale 
Section 3.5.2. 
Risk 
Assessment 
Updated Risk Assessment to include the risk of 
Cardiac Arrest and reference to guidelines for 
management of patients with significant cardiac 
risk factors and known lung metastasis. Updated 
guidelines for infection prophylaxis 
Clarification provided based on mitigation 
plan in relation to the safety events. 
Synopsis: 
Subject 
Exclusion 
criteria 
 
Section 4.2, 
Subject 
Exclusion 
Criteria 
Updated Exclusion criterion 9, to include 
clarification for active ongoing infections 
including but not limited to systemic fungal 
infections 
 
Clarification provided based on mitigation 
plan in relation to the safety events. 
Section 7.3 
Schedule of 
Assessments 
Footnote 7: Added clarification on requirement 
for ECHO/MUGA at the onset of CRS and the 
need for continuous temeletry monitoring for a 
minimum of 3 days. 
Footnote 21: Added clarification on frequency of 
ECG and requirement for ECG in patients with 
clinically significant cardiovascular risk factors 
To monitor for cardiovascular events in 
patients with clinically significant 
cardiovascular risk factors.  
Section 7.4.8 
Cardiac 
Assessments 
Included further detail for assessment of patients 
with clinically significant cardiovascular risk 
factors, including clinical evaluations prior to 
lymphodepletion 
To monitor for cardiovascular events in 
patients with clinically significant 
cardiovascular risk factors.  
Section 7.4.9 
Pulmonary 
Assessments 
Added section for pulmonary assessments in 
patients with known lung metastasis. Provided 
guidelines for close monitoring of such 
participants post-infusion and if CRS is 
suspected 
To monitor for safety events in patients with 
lung involvement.  
Section 8.2 
Infection 
 
 
Section 8.2.6 
Other Anti-
Microbial 
Prophylaxis 
Included clarification for increased surveillance of 
participants with indwelling catheters to monitor 
for catheter-associated infections. 
 
Guidelines for close monitoring for cardiac 
function in participants requiring treatment with 
anti-microbials associated with cardiac toxicity 
 
To monitor for catheter-associated 
infections. 
 
 
 
To monitor for cardiac toxicity associated 
with anti-microbial use 
Section 8.3 
Hematologic and 
Blood Product 
Support 
Added guidelines for blood product support for 
low platelet count in in-patient and out-patient 
settings. 
For management of thrombocytopenia in 
in-patient and out-patient setting. 


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Section 8.5 
Management of 
Cytokine 
Release 
Syndrome 
Added guidelines for managing CRS in patients 
with clinically significant cardiovascular risk 
factors. 
 
Added guidelines for cardiac assessments during 
suspected CRS. 
To monitor for cardiovascular events in 
patients with CRS  
 
 
 


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16.15. 
Summary of Changes from Protocol Version 10.0 to Version 
11.0 
The primary purpose of this amendment is to make changes to protocol section 7.6 to remove 
the language around anticancer therapies post-progression after first infusion of lete-cel 
(GSK3377794).  
 
The following table details all changes and rationale: 
Study 208469:  List of Changes included in Protocol Amendment 10 
Section 
Change 
Rationale 
Synopsis and 
Section 2.1 Trial 
Objectives and 
Endpoints 
Updated table to reflect Exploratory Efficacy and 
Safety Objectives to align with protocol Section 
7.6.7. Objectives 
For consistency between protocol main 
body and synopsis sections 
Section 7.5.1. 
Pharmacogenetics 
Sample 
Updated language regarding potential usage of 
pharmacogenetics sample to investigate the 
association of candidate or genome-wide 
genetic variants with efficacy and safety. 
Updates made in order to align with all 
lete-cel (GSK3377794) studies. 
Section 7.6. 
Retreatment 
Included additional clarification on second lete-
cel infusion eligibility requirement. 
• 
Inclusion of language to allow 
patients to receive second lete-cel 
infusion after receiving subsequent 
anticancer therapies post-
progression from first lete-cel 
infusion 
• 
Inclusion of language to allow 
collection of biopsy sample post-
progression from recent anticancer 
therapy for eligibility determination 
for second lete-cel infusion 
To allow second infusion in patients who 
have achieved clinical benefit from first 
lete-cel infusion and have received 
subsequent anticancer therapies post-
progression from first lete-cel infusion 
Section 10.3.1. 
Testing for RCL in 
Clinical Studies 
 
Section 10.3.4. 
Test for 
persistence of gne 
marked cells in 
clinical studies 
Updated language regarding testing for 
persistence and RCL in patients who have two 
consecutive negative test results and are 2 
years and beyond post lete-cel (GSK3377794) 
infusion. 
 
Updates made in order to align with all 
lete-cel (GSK3377794) studies. 


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Signature Page for  208469 TMF-14208393 v1.0
Signature Page for TMF-14208393 v1.0
Reason for signing: Approved
Name: Carsten Goessl
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Date of signature: 17-Dec-2021 15:59:10 GMT+0000