A Phase III Open-label, Multicenter Trial of Maintenance Therapy With Avelumab (MSB0010718C) Versus Continuation of First-line Chemotherapy in Subjects With Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro-esophageal Junction
Phase: PHASE3
Conditions: Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction
Sponsor: EMD Serono Research & Development Institute, Inc.

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1/ 1 5 0
Cli nic al Tri al Pr ot oc ol
Cli nic al Tri al Pr ot oc ol N u m ber
E M R 1 0 0 0 7 0- 0 0 7
Title
A P hase III o pe n -la bel, m ultice nter trial of mai nte na nce 
t hera py 
wit h 
a vel u ma b 
( M S B 0 0 1 0 7 1 8 C) 
vers us 
c o nti n uati o n of first-li ne c he m ot hera p y i n s u bjects wit h 
u nresecta ble, 
l ocall y 
a d va nce d 
or 
metastatic, 
a de n ocarci n o ma 
of 
t he 
st o mac h, 
or 
of 
t he 
gastr o -es o p ha geal j u ncti o n 
S h ort Tri al N a me
J A V E LI N Gastric 1 0 0
P h ase
III
I N D N u m ber
E u dr a C T N u m ber
2 0 1 5 -0 0 3 3 0 0 -2 3
C o or di n ati n g I n vesti g at or
S p o ns or
F or all c o u ntries e xce pt t he U S A:
Merc k K Ga A,
Fra n kf urter Str. 2 5 0
6 4 2 9 3 Dar msta dt, Ger ma n y
F or sites i n t he U S A:
E M D Ser o n o Researc h & De vel o p me nt I nstit ute, I nc.
4 5 A Mi d dlese x T ur n pi ke, 
Billerica, M A 0 1 8 2 1- 3 9 3 6 , U S A
Me dical Res p o nsi ble:
E M D Ser o n o Researc h & De vel o p me nt I nstit ute, I nc.
4 5 A Mi d dlese x T ur n pi ke, 
Billerica, M A 0 1 8 2 1- 3 9 3 6 , U S A
+ 1 9 7 8 4 3 5 1 2 5 3
Cli nic al Tri al Pr ot oc ol Versi o n
1 7 J ul y 2 0 1 9/ Versi o n 7 . 0
Re pl aces Versi o n
2 1 J u ne 2 0 1 8 / Versi o n 6. 0
T his d oc u me nt is t he pr o pert y of Merc k K G a A, Dar msta dt, Ger ma n y,  or o ne of its s u bsi diaries.  It 
is i nte n de d f or restricte d use o nl y  an d m a y  not – i n f ull or part – be passe d o n, re pr o d uce d, 
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
P P D
P P D

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2/ 1 5 0
p u blis he d or use d wit h o ut e x press per missi o n of Merc k K G a A, Dar msta dt, Ger ma n y,  or its 
s u bsi diar y.  C o p y rig ht © 2 0 1 9 b y  Merc k KG a A, or its s u bsi diar y.  All ri g hts reser ve d.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3/ 1 5 0
Pr ot oc ol T a ble of C o nte nts
Pr ot oc ol Ta ble of C o nte nts .................................................................................................. 3
Ta ble of I n -Te xt Ta bles ....................................................................................................... 8
Ta ble of I n -Te xt Fi g ures ...................................................................................................... 8
List of A b bre viati o ns ........................................................................................................... 9
1
S y n o psis ..............................................................................................1 2
2
S p o ns or, I n vesti gat ors a n d Trial A d mi nistrati ve Str uct ure ................ 4 0
2. 1
I n vesti gati o nal Sites............................................................................ 4 0
2. 2
Trial C o or di nati o n / M o nit ori n g ......................................................... 4 0
2. 3
Re vie w C o m mittees............................................................................ 4 1
2. 3. 1
I n de pe n de nt Data M o nit ori n g C o m mittee .......................................... 4 1
2. 3. 2
I n de pe n de nt Ra di ol o gist ..................................................................... 4 1
3
Bac k gr o u n d I nf or mati o n ..................................................................... 4 1
3. 1
Gastric Ca ncer .................................................................................... 4 1
3. 2
Pr o gra m me d Deat h Rece pt or a n d L i ga n ds......................................... 4 2
3. 3
A vel u ma b ............................................................................................ 4 2
3. 3. 1
Safet y .................................................................................................. 4 3
3. 3. 2
P har mac o ki netic Res ults ..................................................................... 4 3
3. 4
Rati o nale f or t he C urre nt Cli nical Trial .............................................. 4 5
3. 4. 1
Data fr o m A nti -P D -1/ P D -L 1  T hera pies i n Gastric Ca ncer ................ 4 6
3. 5
S u m mar y  of t he O verall Be nefit a n d Ris k.......................................... 4 7
4
Trial O bjecti ves .................................................................................. 4 8
4. 1
Pri mar y  O bjecti ves ............................................................................. 4 8
4. 2
Sec o n dar y  O bjecti ves ......................................................................... 4 8
5
I n vesti gati o nal Pla n ............................................................................ 4 9
5. 1
O verall Trial Desi g n a n d Pla n ............................................................ 4 9
5. 1. 1
O verall Desi g n .................................................................................... 4 9
5. 1. 2
Trial treat m e nt A d mi nistrati o n a n d Sc he d ule ..................................... 5 3
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4/ 1 5 0
5. 1. 3
D ose M o dificati o n a n d A d verse Dr u g Reacti o ns Re q uiri n g 
Treat me nt Disc o nti n uati o n ................................................................. 5 4
5. 2
Disc ussi o n of Trial Desi g n ................................................................. 5 7
5. 2. 1
Rati o nale S u p p orti n g t he C h oice of t he First -li ne C he m ot hera p y...... 5 7
5. 2. 2
Rati o nale f or E xcl usi o n of H E R 2 P ositi ve P o p ulati o n ....................... 5 8
5. 2. 3
Rati o nale f or S witc hi n g S u bjects fr o m C he m ot hera p y t o 
A vel u ma b ............................................................................................ 5 8
5. 2. 4
J ustificati o n of O pe n-la bel St u d y Desi g n........................................... 5 8
5. 2. 5
Rati o nale f or t he Pri mar y E n d p oi nt.................................................... 5 9
5. 2. 6
Trial Peri o ds ........................................................................................ 5 9
5. 2. 7
I ncl usi o n of S pecial P o p ulati o ns ........................................................ 6 0
5. 3
Selecti o n of Trial P o p ulati o n ..............................................................6 0
5. 3. 1
I ncl usi o n Criteria................................................................................ 6 0
5. 3. 2
E xcl usi o n Criteria ............................................................................... 6 1
5. 4
Criteria f or I nitiati o n of Trial Treat me nt ............................................ 6 3
5. 5
Criteria f or S u bject Wit h dra wal .......................................................... 6 4
5. 5. 1
Wit h dra wal fr o m Trial T hera p y.......................................................... 6 4
5. 5. 2
Wit h dra wal fr o m t he Trial .................................................................. 6 5
5. 6
Pre mat ure Ter mi nati o n of t he Trial .................................................... 6 5
5. 7
Defi niti o n of E n d of Trial ................................................................... 6 6
6
I n vesti gati o nal Me dici nal Pr o d uct a n d Ot her Dr u gs Use d i n t he 
Trial ..................................................................................................... 6 6
6. 1
Descri pti o n of t he I n vesti gati o nal Me dici nal Pr o d uct ........................ 6 6
6. 1. 1
I n d ucti o n C he m ot hera py .................................................................... 6 6
6. 1. 2
A vel u ma b ............................................................................................ 6 6
6. 1. 3
Mai nte na nce C he m ot hera p y ...............................................................6 6
6. 1. 4
Best S u p p orti ve Care .......................................................................... 6 7
6. 2
D osa ge a n d A d mi nistrati o n................................................................ 6 7
6. 2. 1
A vel u ma b D osa ge a n d A d mi nistrati o n ............................................... 6 7
6. 2. 2
C he m ot hera p y D osa ge a n d A d mi nistrati o n ........................................ 6 8
6. 3
Assi g n me nt t o Treat me nt Gr o u ps....................................................... 7 0
6. 4
N o n -i n vesti gati o nal Me dici nal Pr o d ucts t o be Use d .......................... 7 0
6. 5
C o nc o mita nt Me dicati o ns a n d T hera pies ........................................... 7 1
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5/ 1 5 0
6. 5. 1
Per mitte d Me dici nes ...........................................................................7 1
6. 5. 2
Pr o hi bite d Me dici nes .......................................................................... 7 2
6. 5. 3
Ot her I nter ve nti o ns ............................................................................. 7 2
6. 5. 4
S pecial Preca uti o ns ............................................................................. 7 3
6. 5. 5
Ma na ge me nt of S pecific A d verse E ve nts or A d verse Dr u g 
Reacti o ns ............................................................................................. 8 3
6. 6
Pac ka gi n g a n d La beli n g of t he I n vesti gati o nal Me dici nal Pr o d uct .... 8 3
6. 7
Pre parati o n, Ha n dli n g, a n d St ora ge of t he I n vesti gati o nal 
Me dici nal Pr o d uct ............................................................................... 8 4
6. 8
I n vesti gati o nal Me dici nal Pr o duct Acc o u nta bilit y ............................. 8 4
6. 9
Assess me nt of I n vesti gati o nal Me dici nal Pr o d uct C o m plia nce ......... 8 6
6. 1 0
Bli n di n g.............................................................................................. 8 6
6. 1 1
E mer ge nc y  U n bli n di ng....................................................................... 8 6
6. 1 2
Treat me nt of O ver d ose ....................................................................... 8 6
6. 1 3
Me dical Care of S u bjects after E n d of Trial ....................................... 8 6
7
Trial Pr oce d ures a n d Assess me nts ...................................................... 8 7
7. 1
Sc he d ule of Assess me nts .................................................................... 8 7
7. 1. 1
Scree ni n g a n d Baseli ne Pr oce d ures a n d Assess me nts ........................ 8 7
7. 1. 2
I n d ucti o n P hase Treat me nt Peri o d...................................................... 8 8
7. 1. 3
Ra n d o mizati o n/ Re -baseli ne ................................................................ 9 0
7. 1. 4
Mai nte na nce P hase Treat me nt Peri o d
................................................ 9 1
7. 1. 5
E n d of Treat me nt ................................................................................ 9 4
7. 1. 6
Safet y  F oll o w-u p Visit ........................................................................ 9 5
7. 1. 7
L o n g -ter m F oll o w- u p.......................................................................... 9 6
7. 1. 8
Bl o o d Dra ws f or Cli nical Assess me nts.............................................. 9 6
7. 2
De m o gra p hic a n d Ot her Baseli ne C haracteristics .............................. 9 6
7. 2. 1
De m o gra p hic Data .............................................................................. 9 6
7. 2. 2
Dia g n osis of Gastric Ca ncer ...............................................................9 6
7. 2. 3
Me dical Hist or y .................................................................................. 9 7
7. 2. 4
Vital Si g ns a n d P h y sical E xa mi nati o n................................................ 9 7
7. 2. 6
Ot her Baseli ne Assess me nts ...............................................................9 8
7. 3
Efficac y  Assess me nts ......................................................................... 9 8
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6/ 1 5 0
7. 4
Assess me nt of Safet y................................ ..........................................9 9
7. 4. 1
A d verse E ve nts ................................................................................. 1 0 0
7. 4. 2
Pre g na nc y  a n d I n Uter o Dr u g E x p os ure........................................... 1 0 5
7. 4. 3
Cli nical L a b orat or y Assess me nts ..................................................... 1 0 5
7. 4. 4
Vital Si g ns, P h y sical E xa mi nati o ns, a n d Ot her Assess me nts........... 1 0 7
7. 5. 1
B o d y Fl ui d(s) .................................................................................... 1 0 8
7. 7
Ot her Assess me nts ............................................................................ 1 1 1
7. 7. 1
S u bject -re p orte d O utc o mes / Q ualit y of Life ................................... 1 1 1
8
Statistics ............................................................................................ 1 1 1
8. 1
Sa m ple Size ...................................................................................... 1 1 1
8. 2
Ra n d o mizati o n .................................................................................. 1 1 3
8. 3
E n d p oi nts .......................................................................................... 1 1 3
8. 3. 1
Pri mar y  E n d p oi nt.............................................................................. 1 1 3
8. 3. 2
Sec o n dar y  E n d p oi nts........................................................................ 1 1 3
8. 3. 3
Safet y E n d p oi nts ............................................................................... 1 1 4
8. 4
A nal y sis Sets..................................................................................... 1 1 5
8. 5
Descri pti o n of Statistical A nal y ses ................................................... 1 1 6
8. 5. 1
Ge neral C o nsi derati o ns ..................................................................... 1 1 6
8. 5. 2
A n al ysis of Pri mar y E n d p oi nt .......................................................... 1 1 8
8. 5. 3
A nal y sis of Sec o n dar y E n d p oi nts..................................................... 1 1 9
8. 5. 5
A nal y sis of Safety E n d p oi nts ............................................................ 1 2 2
8. 5. 6
Re p orti n g of Ot her Cli nical Data of I nterest .................................... 1 2 4
8. 6
I nteri m a n d A d diti o nal Pla n ne d A nalys es ........................................ 1 2 5
9
Et hical a n d Re g ulat or y  As pects........................................................1 2 7
9. 1
Res p o nsi bilities of t he I n vesti gat or ................................ ..................1 2 7
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7/ 1 5 0
9. 2
S u bject I nf or mati o n a n d I nf or me d C o nse nt ................................ .....1 2 7
9. 3
S u bject I de ntificati o n a n d Pri vac y .................................................... 1 2 8
9. 4
E mer ge nc y  Medical S u p p ort a n d S u bject Car d................................ 1 2 8
9. 5
Cli nical Trial I ns ura nce a n d C o m pe nsati o n t o S u bjects ................... 1 2 9
9. 6
I n de pe n de nt Et hics C o m mittee or I nstit uti o nal Re vie w B oar d........ 1 2 9
9. 7
Healt h A ut h orities ............................................................................. 1 3 0
1 0
Trial Ma na ge me nt ............................................................................. 1 3 0
1 0. 1
Case Re p ort F or m Ha n dli n g .............................................................1 3 0
1 0. 2
S o urce Data a n d S u bject Files .......................................................... 1 3 0
1 0. 3
I n vesti gat or Site File a n d Arc hi vi n g................................................. 1 3 1
1 0. 4
M o nit ori n g, Q ualit y Ass ura nce a n d I ns pecti o n b y Healt h 
A ut h orities........................................................................................ 1 3 1
1 0. 5
C ha n ges t o t he Cli nic al Trial Pr ot oc ol .............................................. 1 3 1
1 0. 6
Cli nical Trial Re p ort a n d P u blicati o n P olic y .................................... 1 3 2
1 0. 6. 1
Cli nical Trial Re p ort ......................................................................... 1 3 2
1 0. 6. 2
P u blicati o n ........................................................................................ 1 3 2
1 1
Refere nces Cite d i n t he Te xt .............................................................1 3 2
1 2
A p pe n dices ....................................................................................... 1 3 5
A p pe n di x I
Si g nat ure Pa ges a n d Res p o nsi ble Pers o ns f or t he Trial.................... 1 3 6
Si g nat ure Pa ge – Pr ot oc ol L ea d ....................................................................................... 1 3 7
Si g nat ure Pa ge – C o or di nati n g I n vesti gat or.................................................................... 1 3 8
Si g nat ure Pa ge – Pri nci pal I n vesti gat or ........................................................................... 1 3 9
S p o ns or Res p o nsi ble Pers o ns n ot Na me d o n t he C o ver Pa ge ......................................... 1 4 0
A p pe n di x II
G ui da nce o n C o ntrace pti o n ..............................................................1 4 1
A p pe n di x III
Pr ot oc ol A me n d me nts a n d L ist of C ha n ges ..................................... 1 4 2
Pr ot oc ol Versi o n 7. 0 S u m mar y  of C ha n ges..................................................................... 1 4 2
Rati o nale f or C ha n ges ...................................................................................................... 1 4 2
Pr ot oc ol Versi o n 7. 0 Detaile d L ist of C ha n ges ...............................................................1 4 3
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8/ 1 5 0
T a ble of I n-Te xt T a bles
Ta ble 1 
Sc he d ule of Assess me nts – Scree ni n g a n d I n d ucti o n P hase 
( O pe n-la bel C he m ot hera p y Treat me nt P hase) f or 
O xali plati n + Ca pecita bi ne ................................................................. 2 1
Ta ble 2 
Sc he d ule of Assess me nts – Scree ni n g a n d I n d ucti o n P hase ( O pe n-
la bel C he m ot hera py Treat me nt P hase) f or O xali plati n + 5-
Fl u or o uracil ( 5 -F U) ............................................................................ 2 4
Ta ble 3
Sc he d ule of Assess me nts – Mai nte na nce P hase a n d F oll o w -U p –
O xali plati n + Ca pecita bi ne ................................................................. 2 6
Ta ble 4
Sc he d ule of Assess me nts – Mai nte na nce P hase a n d F oll o w -U p -
O xali plati n + 5- Fl u or o uracil ( 5 -F U) ................................................... 3 0
Ta ble 5
Sc he d ule of Assess me nts:  Mai nte na nce P hase a n d F oll o w -U p -
Best S u p p orti ve Care O nl y ................................................................. 3 3
Ta ble 6
Sc he d ule of Assess me nts – Mai nte na nce P hase a n d F oll o w - u p –
A vel u ma b ............................................................................................ 3 6
Ta ble 7
Sc he d ule of Assess me nts – P har mac o ki netic, 
 
 a n d 
 Sa m pli n g d uri n g Mai nte na nce a n d 
O pe n -la bel Treat me nt P hases ( A vel u ma b ar m o nl y).......................... 3 9
Ta ble 8
D ose M o dificati o n Ge neral G ui deli nes f or C he m ot hera p y ................ 5 7
Ta ble 9
All o we d T hera p y Re gi me ns ...............................................................7 0
Ta ble 1 0
Treat me nt M o dificati o n f or S y m pt o ms of I nf usi o n- relate d 
Reacti o ns Ass ociate d wit h A vel u ma b ................................................ 7 4
Ta ble 1 1
Ma na ge me nt of I mm u ne -relate d A d verse E ve nts .............................. 7 7
Ta ble 1 2
Cli nical L a b orat or y Assess me nts ..................................................... 1 0 6
Ta ble 1 3
Pla n ne d La n -De Mets ( O’ Brie n -Fle mi n g) Efficac y  B o u n daries of 
O S ..................................................................................................... 1 2 6
T a ble of I n-Te xt Fi g ures
Fi g ure 1
Sc he matic of Trial Desi g n .................................................................. 5 2
Fi g ure 2
Assess me nt a n d I nitial Ma na ge me nt of T u m or L ys is S yn dr o me ....... 7 6
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9/ 1 5 0
List of A b bre vi ati o ns
5- F U
fl u or o uracil
A D C C
a nti b o d y-de pe n de nt cell -me diate d c y t ot o xicit y
A D R
ad verse d r u g reacti o n
A E
ad verse eve nt
A E SI
ad verse eve nt of special interest
A L T
ala ni ne ami n otra nsferase
A N C O V A
anal ys is of co varia nce
A S T
as partate ami n otra nsferase
A U C ta u
area u n der t he co nce ntrati o n -ti me cur ve
β- h C G
β- h u ma n c h ori o nic g o na d otr o pi n
B O R
Best O verall Res p o nse
B S C
b est s u p p orti ve care
CI
co nfi de nce inter val
C ma x
m a xi m u m co nce ntrati o n o bser ve d
C mi n
tr o u g h co nce ntrati o n
C H M P
C o m mittee f or Me dici nal Pr o d ucts f or H u ma n Use
C R
co m plete res p o nse
C R A
cli nical researc h ass ociate
C R O
co ntract researc h o r ga nizati o n
C T
co m p ute d t o m o gra p h y
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
c T n I
car diac tr o p o ni n I
c T nT
car diac tr o p o ni n T
E C G
electr ocar di o gra m
E C O G P S
Easter n C o o perati ve O nc ol o g y  Gr o u p p erf or ma nce stat us
e C R F
electr o nic case re p ort for m
E O R T C
E ur o pea n Or ga nizati o n f or Researc h a n d Treat me nt of Ca ncer
E Q - 5 D-5 L
E ur o pea n Q ualit y  of Li fe 5- Di me nsi o ns 5 Le vels Q uesti o n naire
F F P E
f or mali n-fi xe d p araffi n-e m be d de d
FI S H
fl u oresce nce i n sit u h y bri dizati o n
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 / 1 5 0
F S H
follicle -sti m ulati n g hor m o ne
G C P
G o o d Cli nical Practice
G EJ
g astr o -es o p ha geal j u ncti o n
G G T
g a m ma -gl uta m y ltra nsferase
H 1
hista mi ne H 1 r ece pt or
H B V
h e patitis B vir us
H C V
h e patitis C vir us
H E R 2 + 
h u ma n e pi der mal gr o wt h fact or rece pt or 2 p ositi ve
H R Q o L
Healt h -Relate d Q ualit y  of Life
I B
I n vesti gat or’s Br oc h ure
I CF
inf or me d co nse nt for m
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n
I D M C
I n de pe n de nt Data M o nit ori n g C o m mittee
I E C
I n de pe n de nt Et hics C o m mittee
I H C
im m u n o hist oc he mistr y
I M P
in vesti gati o nal m e dici nal p r o d uct
I P M P
I nte grate d Pr oject Ma na ge me nt Pla n
ir A E
im m u ne -relate d a d verse eve nt
I RB
I nstit uti o nal Re vie w B oar d
I T T
i nte nt-t o-treat
I V
intra ve n o us(l y)
I W R S
interacti ve w e b res p o nse sys te m
L F T
li ver f u ncti o n test
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
M RI
m a g netic res o na nce ima gi n g
N CI
Nati o nal Ca ncer I nstit ute
N C C N
Nati o nal C o m pre he nsi ve Ca ncer Net w or k
N S C L C 
n o n- s mall cell lu n g ca ncer
O R R
o bjecti ve res p o nse rate
O S
O verall S ur vi val
P D
p r o gressi ve d isease
P D -1
p r o gra m me d d eat h 1 (rece pt or)
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 / 1 5 0
P D -L( 1 a n d 2)
p r o gra m me d d eat h li ga n d ( 1 a n d 2)
P F S
Pr o gressi o n -free S ur vi val
P P
p er- pr ot oc ol
P R
p artial res p o nse
Q o L
q ualit y  of life
Q Tc
correcte d Q T inter val
R E CI S T
Res p o nse E val uati o n Criteria i n S oli d T u m ors
S A E
seri o us a d verse eve nt
S A P
statistical anal y sis p la n
S D
sta ble d isease
S O C
sta n dar d of care
S U S A R
sus pecte d u ne x pecte d seri o us ad verse reacti o ns
S w M
switc h -mai nte na nce
t1/ 2
ter mi nal h alf-life
T 4
free th y r o xi ne
T E A E
treat me nt-e mer ge nt ad verse eve nt
T E S A E 
t reat me nt-e mer ge nt seri o us a d verse e ve nt
T S H
th y r oi d-sti m ulati n g hor m o ne
U L N
u p per li mit of n or mal
U S A
U nite d States of A merica
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 / 1 5 0
1
S y n o psis
Cli nic al Tri al Pr ot oc ol N u m ber
E M R 1 0 0 0 7 0 - 0 0 7
Title
A 
P hase 
III 
o pe n -la bel, m ultice nter 
trial of 
mai nte na nce t hera p y wit h a vel u ma b ( M S B 0 0 1 0 7 1 8 C) 
vers us c o nti n uati o n of first-li ne c he m ot hera p y in 
s u bjects wit h 
u nresecta ble, l ocally a d va nce d or 
metastatic, a de n ocarci n o ma of t he st o mac h, or of t he 
gastr o -es o p ha geal j u ncti o n
Tri al P h ase
III
I N D N u m ber
F D A c o vere d tri al
Yes
E u dr a C T N u m ber
2 0 1 5 -0 0 3 3 0 0 -2 3
C o or di n ati n g I n vesti g at or
S p o ns or
F or all c o u ntries e xce pt t he U S A:
Merc k K Ga A,
Fra n kf urter Str. 2 5 0
6 4 2 9 3 Dar msta dt, Ger ma n y
F or sites i n t he U S A:
E M D Ser o n o Researc h & De vel o p me nt I nstit ute, I nc.
4 5 A Mi d dlese x T ur n pi ke
Billerica, Massac h usetts 0 1 8 2 1 - 3 9 3 6
U S A
Tri al ce nters/c o u ntries
T he trial will be c o n d ucte d at a p pr o xi matel y  2 3 0 sites 
gl o ball y i n N ort h A merica, S o ut h A merica, 
Asia 
Pacific, a n d E ur o pe , wit h a p pr o xi matel y 47 sites i n t he 
U S A .
Pl a n ne d tri al peri o d
(first s u bject i n-l ast s u bject o ut)
First s u bject i n: Q 4, 2 0 1 5
Last s u bject o ut: Q 3, 2 0 1 9
Tri al Re gistr y
Cli nical Trials. g o v
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI
P P D

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 / 1 5 0
O bjecti ves:
Pri m ar y o bjecti ves: T he pri mar y  objecti ves are t o de m o nstrate s u peri orit y of mai nte na nce 
t hera py wit h a vel u ma b vers us c o nti n uati o n of first-li ne c he m ot hera p y wit h re gar d t o O verall 
S ur vi val ( O S) i n all ra n d o mize d s u bjects or i n P D -L 1 + s u bjects w h o ha ve n ot pr o gresse d o n 
first-li ne c he m ot hera py.
Sec o n d ar y o bjecti ves:

T o de m o nstrate s u peri orit y of mai nte na nce t hera p y wit h a vel u ma b vers us c o nti n uati o n of 
first-li ne c he m ot hera p y wit h re gar d t o Pr o gressi o n -Free S ur vi val ( P F S) as per Res p o nse 
E val uati o n Criteria i n S oli d T u m ors versi o n 1. 1 ( R E CIS T v 1. 1) acc or di n g t o I nvesti gat or 
assess me nt.

T o de m o nstrate s u peri orit y of mai nte na nce t hera p y wit h a vel u ma b vers us c o nti n uati o n of 
first-li ne c he m ot hera p y wit h re gar d t o o bjecti ve res p o nse rate ( O R R) as per R E CI S T v 1. 1
a n d per I n vesti gat or assess me nt .

T o c o m pare t he s u bject-re p orte d o utc o mes / q ualit y  of life ( Q o L) of s u bjects w he n treate d 
wit h a vel u ma b vers us c o nti n uati o n of first -li ne c he m ot hera p y as assesse d b y  t he E ur o pea n 
Q o L 5- di me nsi o ns 5- le vels q uesti o n naire (E Q -5 D -5 L ), a n d t he E ur o pea n Or ga nizati o n f or 
Researc h a n d Treat me nt of Ca ncer ( E O R T C) Q L Q- C 3 0 a n d m o d ule Q L Q -S T O 2 2 .

T o deter mi ne t he safet y a n d t olera bilit y of a vel u ma b .
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 / 1 5 0
Met h o d ol o g y:
T his is a m ultice nter, i nter nati o nal, ra n d o mize d, o pe n -la bel P hase III trial of a vel u ma b i n 
s u bjects wit h a d va nce d ( u nresecta ble, l ocall y ad va nce d or metastatic) a de n ocarci n o ma of t he 
st o mac h, or of t he gastr oes o p ha geal j u ncti o n ( G EJ) w h o are treat me nt naï ve a n d ha ve n ot ye t 
recei ve d c he m ot hera py f or t he treat me nt of metastatic or l ocall y a d va nce d disease.  
T his st u d y incl u des a S cree ni n g peri o d, I n d ucti o n P hase, Mai nte na nce P hase, a n d F oll o w -u p 
P hase .
T he act ual n u m ber of s u bjects e nr olle d i n t he I n d ucti o n P hase will be dri ve n b y  obser ve d 
i n d ucti o n fail ure rates a n d will be s uc h t o all o w f or a p pr o xi matel y 46 6 s u bjects t o b e 
ra n d o mize d i n t he M ai nte na nce P hase. S u bject s e nr olle d i n t he I nd ucti o n P hase will recei ve 
i n d ucti o n c he m ot hera p y c o m prise d of o xali plati n a n d eit her 5-fl u or o uracil ( 5-F U) or 
ca pecita bi ne (I n d ucti o n P hase) f or 1 2 wee ks.  F oll o wi n g t he I n d ucti o n P hase, s u bjects w h o 
e x perie nce a c o m plete res p o nse ( C R), partial res p o nse ( P R), or sta ble disease ( S D) will e nter 
t he Mai nte na nce P hase a n d be ra n d o ml y assi g ne d t o recei ve eit her a vel u ma b, or c o nti n uati o n 
of t he sa me c he m ot hera p y re gi me n fr o m t he I n ducti o n P hase ( Mai nte na nce P hase).
T he d ose a n d sc he d ule of t he c he m ot hera p y d uri n g t he I n d ucti o n P hase are as f oll o ws or i n 
acc or da nce t o t he la bel i nstr ucti o ns a n d per l ocal g ui deli nes:

O xali plati n at 8 5 m g/ m 2 i ntra ve n o us (I V) o n D a y  1 wit h le uc o v ori n 2 0 0 m g/ m 2 I V o n Da y 1
( or e q ui vale nt le v ole uc o v ori n d ose ) f oll o we d b y  5-F U at 2 6 0 0 m g / m2 I V co nti n u o us 
i nf usi o n o ver 2 4 h o urs o n Da y  1, gi ve n e ver y 2 wee ks (f or u p t o 1 2 wee ks)
O R

O xali plati n at 8 5 m g/ m 2 I V o n Da y  1 wit h le uc o v ori n 4 0 0 m g/ m 2 I V on Da y 1 ( or e q ui vale nt 
le v ole uc o v ori n d ose) f oll o we d b y  5-F U at 4 0 0 m g / m2 I V p us h o n Da y  1 an d 2 4 0 0 m g/ m 2
I V co nti n u o us i nf usi o n o ver 4 6- 4 8 h o urs (Da y s 1 a n d 2) gi ve n e ver y 2 wee ks (f or u p t o 
1 2 wee ks)
O R

O xali plati n at 1 3 0 m g/ m 2 I V on Da y 1 wit h ca pe cita bi ne at 1 0 0 0 m g/ m 2, t wice dail y  for 
2 wee ks f oll o we d b y a 1-wee k rest peri o d gi ve n e ver y  3 wee ks (f or u p t o 1 2 wee ks).  
L ocal la bel a n d g ui deli nes s h o ul d be f oll o we d f or s pecific starti n g d oses d ue t o re nal or he patic 
i m pair me nts a n d f or s u bse q ue nt d ose m o dificati o ns d ue t o differe nt t o xicities.
U p o n c o m pleti o n of c he m ot hera p y i n t he I n d ucti o n P hase, s u bjects wit h o ut disease pr o gressi o n 
(s u bjects wit h S D, P R, or C R) will be eli gi ble f or ra n d o mizati o n t o t he Mai nte na nce P hase 
w here t he y  will recei ve eit her a vel u ma b, or c o nti n ue t he sa me re gi me n of c he m ot hera p y fr o m 
t he In d ucti o n P hase.  
Treat me nt d uri n g t he Mai nte na nce P hase are as f oll o ws:
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 5 / 1 5 0
1.
F or s u bjects ra n d o mly assi g ne d t o a vel u ma b: a vel u ma b will be gi ve n at a d ose of 
1 0 m g/ k g as a 1 -h o ur I V i nf usi o n o nce e ver y  2 wee ks u ntil disease pr o gressi o n
2.
F or 
s u bjects 
ra n d o ml y 
assi g ne d 
t o c he m ot hera p y:  the 
sa me 
re gi me n of 
o xali plati n -fl u or o p yri mi di ne d o u blet as i n t he I n d ucti o n P hase will be c o nti n ue d u ntil 
disease pr o gressi o n.

S u bjects w h o are n ot dee me d eli gi ble t o recei ve f urt her c he m ot hera p y will 
recei ve best s u p p orti ve care ( B S C) al o ne wit h n o acti ve t hera p y.  Pri or t o 
ra n d o mizati o n, In vesti gat ors m ust s pecif y  B S C treat me nt f or t hese s u bjects.   

F or s u bjects recei vi n g c he m ot hera p y ( o xali plati n + 5- F U or o xali plati n + 
ca pecita bi ne), d ose m o dificati o ns after t he starti n g d ose are all o we d if t he 
c o nti n uati o n of t he o xali plati n -fl u or o p yri mi di ne d o u blet, or a c o m p o ne nt 
t here of, is pr o hi bite d b y t o xicit y.  For s u bjects i nt olera nt t o f urt her o xali plati n, 
si n gle-a ge nt ca pecita bi ne or 5- F U + le uc o v ori n will be a n o pti o n f or d ose 
m o dificati o n.
S u bjects will ret ur n t o t he cli nic at re g ular i nter vals f or assess me nts.  T u m or meas ure me nts b y 
c o m p ute d t o m o gra p hy ( C T) sca n or ma g netic res o na nce i ma gi n g ( M RI) will be perf o r me d 
e ver y 6 wee ks f or t he first 1 2 m o nt hs a n d e ver y 1 2 wee ks t hereafter t o deter mi ne res p o nse t o 
treat me nt.  Cli nical decisi o n ma ki n g 
a n d st u d y en d p oi nt e val uati o n will be base d o n 
I n vesti gat or assess me nt of t he sca ns usi n g R E CI S T v 1. 1 .  
St u d y  treat me nt will c o nti n ue u ntil:

Disease pr o gressi o n 

Si g nifica nt cli nical deteri orati o n (cli nical pr o gressi o n) b y  In vesti gat or’s o pi ni o n 

U nacce pta ble t o xicit y  b y In vesti gat or’s o pi ni o n, or

A n y  criteri o n f or wit h dra wal fr o m t he trial or trial treat me nt is f ulfille d.
S u bjects recei vi n g a vel u ma b m a y  co nti n ue treat me nt past t he i nitial deter mi nati o n of disease 
pr o gressi o n per R E CI S T versi o n 1. 1 as l o n g t he f oll o wi n g criteria are met:

I n vesti gat or-assesse d cli nical be nefit, wit h o ut a n y ra pi d disease pr o gressi o n

T olera nce of trial treat me nt

Sta ble Easter n C o o perati ve O nc ol o g y  Gr o u p perf or ma nce stat us ( E C O G P S [ P S = 0 or 1])

Treat me nt b e y o n d pr o gressi o n will n ot dela y  an i m mi ne nt i nter ve nti o n t o pre ve nt seri o us 
c o m plicati o ns of disease pr o gressi o n (f or e xa m ple, ce ntral ner v o us s yste m metastases).
T he decisi o n t o c o nti n ue a vel u ma b treat me nt b e y o n d pr o gressi o n s h o ul d be disc usse d wit h t he 
M e dical M o nit or a n d d oc u me nte d i n t he st u d y rec or ds.
F or s u bjects c o nti n ui n g a vel u ma b after i nitial pr o gressi ve disease (P D ), a ra di o gra p hic 
assess me nt s h o ul d be perf or me d wit hi n 6 wee ks of ori gi nal P D t o deter mi ne w het her t here has 
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 6 / 1 5 0
bee n a decrease i n t he t u m or size, or c o nti n ue d P D.  T he assess me nt of cli nical be nefit s h o ul d 
be bala nce d b y  cli nical j u d g me nt as t o w het her t he s u bject is cli nicall y deteri orati n g a n d 
u nli kel y  t o recei ve a n y be nefit fr o m c o nti n ue d treat me nt wit h a vel u ma b.
F or s u bjects recei vi n g a vel u ma b, if disc o nti n uati o n occ urs d ue t o pr o gressi o n a n d a defi niti ve 
dia g n osis/ra di o gra p hic c o nfir mati o n is n ot ma de at the ti me of disc o nti n uati o n, a sec o n d 
i ma gi n g sca n m a y  be all o we d f or c o nfir mati o n of pr o gressi o n.  If pr o gressi o n at t he sec o n d 
i ma gi n g sca n is n ot c o nfir me d a n d t he s u bject wis hes t o restart, t he s u bject will be all o we d t o 
c o nti n ue recei vi n g a vel u ma b as lo n g as t he y meet t he criteria f or c o nti n uati o n of treat me nt 
be y o n d pr o gressi o n. 
If t he I n vesti gat or feels t hat t he s u bject c o nti n ues t o ac hie ve cli nical be nefit b y  co nti n ui n g 
treat me nt, t he s u bject s h o ul d re mai n o n t he trial a n d c o nti n ue t o recei ve m o nit ori n g acc or di n g 
t o t he Sc he d ule of Assess me nts.
A n y  ad diti o nal c o nti n uati o n of a vel u ma b pl us B S C b e y o n d f urt her pr o gressi o n m ust be 
disc usse d a n d a gree d u p o n wit h t he M e dical M o nit or.  Furt her disease pr o gressi o n is defi ne d 
as a n a d diti o nal i ncrease i n t u m or b ur de n of 2 0 % a n d ≥ 5 m m a bs ol ute i ncrease i n t u m or b ur de n 
fr o m ti me of i nitial P D.   T his i ncl u des a n i ncrease i n t he s u m of all tar get lesi o ns a n d/ or t he 
de vel o p me nt of ne w meas ura ble lesi o ns.  
S u bjects recei vi n g a vel u ma b w h o ha ve e x perie nce d a C R s h o u l d be treate d f or a mi ni m u m of 
1 2 m o nt hs or u ntil disease pr o gressi o n or u nacce pta ble t o xicit y, after c o nfir mati o n of res p o nse.   
I n case a s u bject wit h a c o nfir me d C R rela pses after st o p pi n g treat me nt, b ut pri or t o t he e n d of 
t he trial, 1 re-i nitiati o n of treat me nt is all o we d at t he discreti o n of t he I nvesti gat or a n d after 
a gree me nt wit h t he Me dical M o nit or.  T o be eli gi ble f or retreat me nt, t he s u bject m ust n ot ha ve 
e x perie nce d a n y t o xicit y that le d t o treat me nt disc o nti n uati o n of t he i nitial a vel u ma b t hera p y.   
S u bjects w h o re-i nitiate treat me nt will sta y on trial a n d will be treate d a n d m o nit ore d acc or di n g 
t o t he pr ot oc ol a n d f oll o w t he Sc he d ule of Assess me nts u ntil disease pr o gressi o n .
S u bjects i n t he m ai nte na nce c he m ot hera p y ar m will recei ve trial treatme nt u ntil P D per 
R E CI S T v 1. 1, si g nifica nt cli nical deteri orati o n (cli nical pr o gressi o n), u nacce pta ble t o xicit y, 
wit h dra wal of c o nse nt, or if a n y criteri o n f or wit h dra wal fr o m t he trial or trial treat me nt is 
f ulfilled.  
O n -st u d y su bject ma na ge me nt a n d st ud y  en d p oi nt e val uati o n will be base d o n I nvesti gat or 
assess me nts.  
S u bjects will atte n d cli nic visits at re g ular i nter vals t o recei ve trial treat me nt a n d f or efficac y 
a n d safet y assess me nts.
After c o m pleti o n of t he Mai nte na nce P hase, s u bjects will e nter t he F oll o w -u p P hase.  
Pl a n ne d n u m ber of s u bjects:
A p pr o xi matel y  4 6 6 s u bjects are pla n ne d t o be ra n d o ml y assi g ne d i nt o t he Mai nte na nce P hase.
T he act ual n u m ber of s u bjects e nr olle d i n t he I n d ucti o n P hase will be dri ve n b y  obser ve d 
i n d ucti o n fail ure rates a n d will be s uc h t o all o w f or a p pr o xi matel y 4 6 6 patie nts t o be 
ra n d o mize d i n t he M ai nte na nce P hase. 
At t he ti me of t his pr ot oc ol a me n d me nt, s ubject 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 7 / 1 5 0
e nr oll me nt i n t he Mai nte na nce P hase is c o m plete, wit h
4 9 9 s u bjects ra n d o mize d i nt o t he 
Mai nte na nce P hase .
Pri m ar y e n d p oi nt:  
T he pri mar y  e n d p oi nt of t he trial is:

O S, defi ne d as t he ti me (i n m o nt hs) fr o m ra n d o mizati o n t o t he date of deat h, re gar dless of 
t he act ual ca use of t he s u bject’s deat h .
Sec o n d ar y e n d p oi nts:  
T he ke y  sec o n dar y e n d p oi nts are:

P F S
defi ne d as t he ti me (i n m o nt hs) 
fr o m ra n d o mizati o n t o t he date of t he first 
d oc u me ntati o n of disease pr o gressi o n ( per RE CI S T v 1. 1 a n d as e val uate d b y  In vesti gat or) 
or deat h d ue t o a n y ca use ( w hic he ver occ urs first).

Best O verall Res p o nse ( B O R) i n Mai nte na nce P hase acc or di n g t o R E CI S T v 1. 1 a n d per 
I n vesti gat or assess ment.
Ot her sec o n dar y  e n d p oi nts i ncl u de s u bject-re p orte d o utc o mes / Q o L (assesse d b y t he E Q- 5 D-
5 L , E O R T C Q L Q-C 3 0, a n d E O R T C m o d ule Q L Q- S T O 2 2 q uesti o n naires).
S afet y e n d p oi nts:
Safet y  en d p oi nts i ncl u de a d verse e ve nts ( A Es), assesse d t hr o u g h o ut t he trial a n d e val uate d 
usi n g t he Nati o nal Ca ncer I nstit ute ( N CI) C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
( C T C A E) v 4. 0 3, p h y sical e xa mi nati o ns, cli nical la b orat or y assess me nts, c o nc o mita nt 
me dicati o ns, vital si g ns, electr ocar di o gra m ( E C G) para meters, a n d E C O G P S.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 8 / 1 5 0
Di a g n osis a n d ke y i ncl usi o n a n d e xcl usi o n criteri a:
Ke y i ncl usi o n criteri a
Male or fe male s u bjects a ge d ≥ 1 8 years, wit h a n E C O G P S of 0 t o 1 at trial e ntr y, wit h t he 
a vaila bilit y of a rece ntl y-o btai ne d ( wit hi n 6 m o nt hs) bi o ps y  fr o m a n o n -irra diate d area, 
f or mali n-fi xe d, paraffi n -e m be d de d ( F F P E) bl oc k c o ntai ni n g t u m or tiss ue or a mi ni m u m of 
1 0 ( prefera bly 2 5) u nstai ne d t u m or sli des (c ut wit hi n 1 wee k) s uita ble f or P D -L 1  ex pressi o n 
assess me nt, at least 1 meas ura ble t u m or lesi o n, a n d wit h hist ol o gicall y c o nfir me d u nresecta ble, 
l ocall y a d va nce d or metastatic, a de n ocarci n o ma of t he st o mac h or t he G EJ.
Ke y e xcl usi o n criteri a
Pri or t hera py wit h a n y a nti b o d y or dr u g tar geti n g T- cell c ore g ulat or y pr otei ns, c o nc urre nt 
a ntica ncer treat me nt, or i m m u n os u p pressi ve a ge nts.  
Ot her e xcl usi o n criteria: se vere 
h y perse nsiti vit y  reacti o ns t o m o n ocl o nal a nti b o dies ( Gra de ≥ 3 N CI -C T C A E v 4. 0 3), a n y 
hist or y  of a na p h yla xis or u nc o ntr olle d ast h ma (t hat is, 3 or m ore feat ures of partiall y  co ntr olle d 
ast h ma), persisti n g t o xicit y relate d t o pri or t hera p y of Gra de ≥ 2 N CI -C T C A E v 4. 0 3 a n d pri or 
c he m ot hera p y f or u nresecta ble l ocall y a d va nce d or metastatic a de n ocarci n o ma of t he st o mac h 
or G EJ.
I n vesti g ati o n al Me dici n al Pr o d uct: d ose/ m o de of a d mi nistr ati o n / d osi n g sc he d ule:
A vel u ma b will be a d mi nistere d as a 1- h o ur I V inf usi o n at 1 0 m g/ k g o nce e ver y 2-wee k 
treat me nt c ycle u ntil P D or u nacce pta ble t o xicit y.  T o miti gate i nf usi o n-relate d reacti o ns, 
p re me dicate patie nts wit h a n a nti hista mi ne a n d wit h paraceta m ol (aceta mi n o p he n) pri or t o t he 
first 4 i nf usi o ns of a vel u ma b.  P re me dicati o n s h o ul d be a d mi nistere d f or s u bse q ue nt a vel u ma b 
d oses base d u p o n cli nical j u d g me nt a n d prese nce/se verit y of pri or i nf usi o n reacti o ns.  T his 
re gi me n m a y  be m o difie d base d o n l ocal treat me nt sta n dar ds a n d g ui deli nes as a p pr o priate 
pr o vi de d it d oe s n ot i ncl u de s yste mic c ortic oster oi ds a n d has t o be rec or de d as c o nc o mita nt 
me dicati o n.
Refere nce t her a p y: d ose/ m o de of a d mi nistr ati o n/ d osi n g sc he d ule: C he m ot hera p y d uri n g 
t he Mai nte na nce P hase will be a d mi nistere d acc or di n g t o t he f oll o wi n g r ules:
1.
F or 
s u bjects 
ra n d o ml y 
assi g ne d 
t o c he m ot hera p y:  the 
sa me 
re gi me n of 
o xali plati n -fl u or o p yri mi di ne d o u blet as i n t he I n d ucti o n P hase will be c o nti n ue d u ntil 
disease pr o gressi o n.

S u bjects w h o are n ot dee me d eli gi ble t o recei ve f urt her c he m ot hera p y will 
recei ve B S C al o ne wit h n o acti ve t hera py.  Pri or t o ra n d o mizati o n, I nvesti gat ors 
m ust s pecif y  B S C treat me nt f or t hese s u bjects.

F or s u bjects recei vi n g c he m ot hera p y ( o xali plati n + 5- F U or o xali plati n + 
ca pecita bi ne) d ose m o dificati o ns after t he starti n g d ose are all owe d if t he 
c o nti n uati o n of t he o xali plati n -fl u or o p yri mi di ne d o u blet, or a c o m p o ne nt 
t here of, is pr o hi bite d b y t o xicit y.  For s u bjects i nt olera nt t o f urt her o xali plati n, 
si n gle-a ge nt ca pecita bi ne or 5- F U + le uc o v ori n will be a n o pti o n f or d ose 
m o dificati o n.
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 9 / 1 5 0
T hera p y will be a d mi nistere d u ntil disease pr o gressi o n, u nacce pta ble t o xicit y, or f or t he 
acce pte d ma xi mal d urati o n of t he a ge nt(s) selecte d.
T hera p y will be st o p pe d after t he first o n- treat me nt ra di ol o gical e val uati o n of disease 
pr o gressi o n.
Pl a n ne d tri al a n d tre at me nt d ur ati o n per s u bject:
I n this trial, treat me nt wit h c he m ot hera p y d uri n g t he I n d ucti o n P hase will last f or 1 2 wee ks, 
f oll o we d by t he Mai nte na nce P hase wit h eit her a vel u ma b or c o nti n uati o n of t he sa me re gi me n 
of c he m ot hera p y fr o m t he I n d uctio n P hase, w hic h will c o nti n ue u ntil disease pr o gressi o n or 
u nacce pta ble t o xicit y.  Su bjects recei vi n g a vel u ma b d uri n g t he Mai nte na nce 
P hase m a y 
c o nti n ue
treat me nt past t he i nitial deter mi nati o n of disease pr o gressi o n acc or di n g t o 
R E CI S T v 1. 1 if t he y meet t he criteria prese nte d u n der Met h o d ol o g y  (I n vesti gat or-assesse d 
be nefit; t olera nce of treat me nt; sta ble E C O G P S ; a n d d oes n ot dela y  ot her i m mi ne nt 
i nter ve nti o n).  S u bjects recei vi n g a vel u ma b w h o ha ve e x perie nce d a C R s h o ul d be treate d f or 
a mi ni m u m 
of 1 2 m o nt hs or u ntil disease pr o gressi o n or u nacce pta ble t o xicit y, after 
c o nfir mati o n of res p o nse.
St atistic al met h o ds: 
T he pri mar y  o bjecti ves of t his trial are t o de m o nstrate s u peri ority o f mai nte na nce t hera py wit h 
a vel u ma b vers us c o nti n uati o n of first-li ne c he m ot hera p y wit h re gar d t o O S i n all ra n d o mize d 
s u bjects or i n P D -L 1 + s u bjects w h o ha ve n ot pr o gresse d o n first-li ne c he m ot hera p y.   T he 
pri mar y  en d p oi nt i n t his st u d y is O S . A n i m bala nce d t ype I err or all ocati o n will be use d f or 
t he 2 pri mar y  hy p ot heses a n d c o ntr ol o verall fa mil y wise t ype I err or rate at 2. 5 % ( 1-si de d) 
wit h 0. 5 % ( 1-si de d) all ocate d t o P D -L 1 + s u bjects a n d 2 % ( 1-si de d) all ocate d t o all ra n d o mize d 
s u bjects.
T he sa m ple size f or t his st u d y is dri ve n b y  the pri mar y  en d p oi nt of O S . T he sa m ple size is 
base d o n calc ulati o n ass u mi n g a n 1 8- m o nt h e nr oll me nt peri o d i n t he M ai nte na nce P hase a n d 
f oll o w- u p of a p pr o xi matel y 18 m o nt hs after e nr oll me nt c o m pleti o n.
Ap pr o xi matel y 4 6 6 
s u bjects will be e nr olle d a n d ra n d o mize d usi n g 1: 1 ra n d o mizati o n rati o, stratifie d b y  re gi o n 
( Asia vs. n o n- Asia) i n t he Mai nte na nce P hase. T he act ual n u m ber of s u bjects e nr olle d i n t he 
I n d ucti o n P hase will be dri ve n b y  obser ve d i n d ucti o n fail ure rates a n d will be s uc h t o all o w f or 
a p pr o xi matel y 4 6 6 patie nts t o be ra nd o mize d i n t he M ai nte na nce P hase .
At t he ti me of t his 
pr ot oc ol a me n d me nt, s u bject e nr oll me nt i n t he Ma i nte na nce P hase is c o m plete, wit h 4 9 9 
s u bjects ra n d o mize d i nt o t he Mai nte na nce P hase.
F or t he O S
i n all ra n d o mize d s u bjects, ass u mi n g a me dia n d urati o n of 1 0. 5 m o nt hs i n t he 
c o ntr ol ar m a n d 1 5 m o nt hs i n t he a vel u ma b ar m c orres p o n di n g t o a hazar d rati o of 0. 7 0 a n d a 
dr o p -o ut rate of 5 %, t he n 3 5 6 e ve nts are re q uire d t o ac hie ve 9 0 % p o wer of t he l o g -ra n k test at 
a 1-si de d o verall 2 % al p ha le vel . 
T he data c ut-off f or t he pri mar y  a nal ys is will ta ke place o n a pr os pecti vel y -deter mi ne d date, 
u p o n w hic h t he tar get n u m ber of 3 5 6 O S e ve nts i n all ra n d o mize d s u bjects are pr oject e d t o 
ha ve bee n reac he d a n d t he last s u bject ra n d o mize d i n t he st u d y h as bee n f oll o we d f or at least 
1 8 m o nt hs
fr o m ra n d o mizati o n. T his calc ulati o n i ncl u des a n i nteri m efficac y anal ys is a n d 
assu mes it will be perf or me d after 7 5 % of O S e ve nts ha ve bee n o bser ve d . F or O S i n all 
D oc u me nt N o.
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 0 / 1 5 0
ra n d o mize d s u bjects, the i nteri m a n d pri mar y a nal ys es will f oll o w a se q ue ntial al p ha s pe n di n g 
f u ncti o n a p pr oac h de vel o pe d b y  La n a n d De Mets usi n g a n O’ Brie n a n d Fle mi n g b o u n dar y  
f u ncti o n. A p pl yi n g t his a p pr oac h wit h a n ass u me d 2 6 7 a n d 3 5 6 o bser ve d e ve nts, res pecti vely,
1- si de d si g nifica nce le vels of 0. 0 0 7 2 a n d 0. 0 1 7 8 f or t he i nteri m a n d fi nal a nal yses will preser ve 
a n o verall ty pe I err or rate of 2 % f or O S i n all ra n d o mize d s u bjects.
F or O S i n P D -L 1 + s u bjects, at pla n ni n g sta ge a pre vale nce rate of 3 5 % i n all ra n d o mize d 
s u bjects wa s ass u me d, a n d a me dia n O S of 1 9. 3 m o nt hs i n t he a vel u ma b ar m c orres p o n di n g t o 
a hazar d rati o of 0. 5 4.
T he st u d y will be c o nsi dere d s uccessf ul if t he n ull h y p ot hesis testi n g f or O S i n eit her all 
ra n d o mize d s u bjects or P D-L 1 + s u bjects will be rejecte d as statisticall y si g nifica nt.
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 1 / 1 5 0
T a ble 1
Sc he d ule of Assess me nts 
–
Scree ni n g a n d I n d ucti o n P h ase (O pe n -l a bel C he m ot her a p y 
Tre at me nt P h ase ) f or 
O x ali pl ati n + C a pecit a bi ne
Scree ni n g
I n d ucti o n P h ase (-4/ + 2 d a ys) a
E n d -of -Tre at me nt b
S afet y F oll o w -u p 
Visit
D a y -2 8 t o E nr oll me nt
C ycle 1  
C ycle 2  
C ycle 3  
C ycle 4 c
Wit hi n 7 D a ys of 
Decisi o n t o Disc o nti n ue 
Tre at me nt
3 0 D a ys after L ast 
Tre at me nt 
( ± 5 d a ys)
W 1  
W 4
W 7
W 1 0
D 1
D 2 2
D 4 3
D 6 4
Writte n i nf or me d c o nse nt
X
I ncl usi o n / e xcl usi o n criteria
X
Me dical hist or y
X
Disease hist or y
X
De m o gra p hic data
X
S u bject -re p orte d o utc o mes / q ualit y of life 
assess me nts d
X
X d
P h ysical e xa mi nati o n 
X
X
X
X
X
X
Vital si g ns (i ncl u di n g hei g ht at Scree ni n g)
X
X
X
X
X
X
Wei g ht
e
X
X
X
X
X
X
E C O G P S f
X
X
X
X
X
X
1 2 -lea d E C G
X
X
C o nc o mita nt me dicati o ns 
C ollecte d fr o m Scree ni n g t hr o u g h E n d -of -Treat me nt Visit
C o nc o mita nt pr oce d ures
C ollecte d fr o m Scree ni n g t hr o u g h E n d -of -Treat me nt Visit 
A E a n d S A E c ollecti o n
C ollecte d fr o m I nf or me d C o nse nt t hr o u g h E n d -of -Treat me nt Visit b
X
S a m ples a n d L a b or at or y Assess me nts
He mat ol o g y a n d he m ostase ol o g y g
X
X
X
X
X
X
X
F ull ser u m c he mistr y h
X
X
C ore ser u m c he mistr y h
X
X
X
X
X
Uri nal ysis i
X
X
X
β- h C G pre g na nc y test j
X
X
X
X
X
X
H B V a n d H C V test k
X
T 4 a n d T S H
X
X
X
D oc u me nt N o.
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 2 / 1 5 0
D osi n g
Pre me dicati o n p
X
X
X
X
C he m ot hera p y a d mi nistrati o n
X
X
X
X
A E = a d verse e ve nt; β - hC G = β -h u ma n c h ori o nic g o na d otr o pi n; C T = c o m p ute d t o m o gra p h y; D = da y; E C G = electr ocar di o gra m, E C O G P S = Easter n C o o perati ve O nc ol o g y Gr o u p Perf or ma nce 
Stat us; E O T = e n d of treat me nt; H B V = he patitis B vir us; H C V = he patitis C vir us; I C F = i nf or me d c o nsent f or m; 
; 
; R N A = ri b o n ucleic 
aci d; S A E = seri o us a d verse e ve nt; T 4 = free t h yr o xi ne; T S H = t h yr oi d-sti m ulati n g h or m o ne; W = wee k.
a
A ti me wi n d o w of u p t o 4 da ys bef ore or 2 da ys after t he sc he d ule d Da y 1 visit ( -4 / + 2 d a y s) will be per mitte d f or all trial pr oce d ures f or t he Da y 1 visit of eac h c ycle.  S u bjects s h o ul d als o 
ret ur n t o t he trial site as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y.
b
S u bjects w h o disc o nti n ue t he I n d ucti o n P hase d ue t o a n y reas o n will ha ve a n E O T visit wit hi n 7 da ys of t he decisi o n t o disc o nti n ue c he m ot hera p y.  All s u bjects w h o d o n ot e nter t he Mai nte na nce 
P hase will ha ve a 3 0- da y after last treat me nt Safet y F oll o w -u p visit.  S u bj ects e nteri n g t he Mai nte na nce P hase will ha ve t he Re -baseli ne visit (Ta ble 3 t o Ta ble 6 as a p plica ble).  S u bjects wit h 
a n A E o n g oi n g at t he E O T visit m ust be f oll owe d u p f or fi nal o utc o me u ntil t h e 3 0 -da y Safet y F oll o w -u p visit .  S u bjects wit h a n S A E o n g oi n g at t he 3 0 -da y Safet y F oll o w -u p visit m ust be 
m o nit ore d a n d f oll o we d u p b y t he I n vesti gat or u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject
is d oc u me nte d as “l ost t o f oll o w-u p.”   
c
S u bjects w h o c o m plete C ycle 4 w ill ret ur n t o cli nic f or t he Re -baseli ne visit (see Ta ble 3 t o Ta ble 6 de pe n di n g o n re gi me n).  T he Re -baseli ne visit is t o occ ur -1 0 t o -1 da ys bef ore t he first 
a d mi nistrati o n i n t he Mai nte na nce P hase .
d
S u bject -re p orte d o utc o mes / q ualit y of  life assess me nts s h o ul d be c o m plete d b y  su bjects after t he I C F is si g ne d a n d pri or t o a n y st u d y-relate d pr oce d ures at t he i n dicate d visits.  T he assess me nts 
s h o ul d be c o n d ucte d at Scree ni n g; i n t he e ve nt t hat t his d oes n’t occ ur, it ca n be d o ne at C ycle 1 ( Da y 1) pri or t o treat me nt.
e 
T he d ose of c he m ot hera p y will be calc ulate d base d o n t he wei g ht or b o d y s urface area, as a p plica ble, of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he da y of dr u g a d mi nistrati o n. 
f 
If t he Scree ni n g E C O G P S was perfor m e d wit hi n 3 da ys pri or t o C ycle 1 Da y 1, it d oes n ot ha ve t o be re peate d at C ycle 1 Da y 1.
g  
He mat ol o g y (i ncl u di n g C o m plete Bl o o d C o u nt) a n d he m o stase ol o g y assess me nts are detaile d i n Ta ble 1 2 .  F ollicle-sti m ulati n g h or m o ne at Scree ni n g, if a p plica ble ( Secti o n 7. 1. 1 ).  C o m plete 
bl o o d c o u nt res ults m ust als o be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
h
F ull c he mistr y a n d c ore ser u m c he mistr y sa m ples are detaile d i n  Ta ble 1 2 .  Sa m ples f or c he mistr y res ults m ust be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
i
A f ull uri nal ysis is re q uire d at Scree ni n g a n d t he E O T visit (see  Ta ble 1 2 f or details).
j 
β- hC G m ust be deter mi ne d fr o m ser u m at Scree ni n g a n d fr o m eit her uri ne or ser u m sa m ple t hereafter as re q uire d per l ocal g ui deli nes.  Res ults of t he m ost rece nt pre g na nc y test ha s t o be 
a vaila ble pri or t o ne xt d osi n g.
k
A n H B V s urface a nti ge n a n d a nti-H C V tests m ust be perf or me d at Scree ni n g t o e xcl u de s u bjects wit h he patitis i nfecti o n.  If t he a nti-H C V a nti b o d y test is p ositi ve, t he i nfecti o n m ust b e 
c o nfir me d b y a n H C V R N A test.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 3 / 1 5 0
p
A nti -e metic pre me dicati o ns s h o ul d be a d mi nistere d i n acc or da nce wit h eit her t he 2 0 0 6 A merica n S ociet y of Cli nical O nc ol o g y g ui deli nes or l ocal i nstit uti o nal g ui deli nes.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 4 / 1 5 0
T a ble 2
Sc he d ule of Assess me nts 
–
Scree ni n g a n d I n d ucti o n P h ase ( O pe n-l a bel C he m ot her a p y 
Tre at me nt 
P h ase) f or 
O x ali pl ati n + 5- Fl u or o ur acil ( 5 -F U)
Scree ni n g
I n d ucti o n P h ase (-4/ + 2 d a ys) a
E n d -of -
Tre at me nt b
S afet y F oll o w -u p 
Visit
D a y -2 8 t o 
E nr oll me nt
C ycle 1  
C ycle 2  
C ycle 3  
C ycle 4
C ycle 5
C ycle 6 c
Wit hi n 7 D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt
3 0 D a ys after L ast 
Tre at me nt
( ± 5 d a ys)
W 1
W 3
W 5
W 7
W 9
W 1 1
D 1
D 1 5
D 2 9
D 4 3
D 5 7
D 7 1
Writte n i nf or me d c o nse nt
X
I ncl usi o n / e xcl usi o n 
criteria
X
Me dical hist or y
X
Disease hist or y
X
De m o gra p hic data
X
S u bject -re p orte d 
o utc o mes / q ualit y of life 
assess me nts d
X
X d
P h ysical e xa mi nati o n 
X
X
X
X
X
X
X
X
Vital si g ns (i ncl u di n g 
hei g ht at Scree ni n g)
X
X
X
X
X
X
X
X
Wei g ht
e
X
X
X
X
X
X
X
X
E C O G P S f
X
X
X
X
X
X
X
X
1 2 -lea d E C G
X
X
C o nc o mita nt me dicati o ns 
C ollecte d fr o m Scree ni n g t hr o u g h E n d -of - Treat me nt Visit
C o nc o mita nt pr oce d ures
C ollecte d fr o m Scree ni n g t hr o u g h E n d -of -Treat me nt Visit 
A E a n d S A E c ollecti o n
C ollecte d fr o m I nf or me d C o nse nt t hr o u g h E n d-of -Treat me nt Visit b
X
S a m ples a n d L a b or at or y Assess me nts
He mat ol o g y a n d 
he m ostase ol o g y g
X
X
X
X
X
X
X
X
X
F ull ser u m c he mistr y h
X
X
C ore ser u m c he mistr y h
X
X
X
X
X
X
X
Uri nal ysis i
X
X
X
β- h C G pre g na nc y testj
X
X
X
X
X
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 5 / 1 5 0
H B V a n d H C V test k
X
T 4 a n d T S H
X
X
X
Res p o nse Assess me nts
D osi n g
Pre me dicati o n p
X
X
X
X
X
X
C he m ot hera p y 
a d mi nistrati o n
X
X
X
X
X
X
A E = a d verse e ve nt; β - hC G = β -h u ma n c h ori o nic g o na d otr o pi n; C T = c o m p ute d t o m o gra p h y; D = da y; E C G = electr ocar di o gra m, E C O G P S = Easter n C o o perati ve O nc ol o g y Gr o u p Perf or ma nce 
Stat us; E O T = e n d of treat me nt; H B V = he patitis B vir us; H C V = he patitis C vir us; I C F = i nf or me d c o nsent f or m; 
;
; R N A = ri b o n ucleic 
aci d; S A E = seri o us a d verse e ve nt; T 4 = free t h yr o xi ne; T S H = t h yr oi d-sti m ulati n g h or m o ne; W = wee k.
a
A ti me wi n d o w of u p t o 4 da ys bef ore or 2 d a y s after t he sc he d ule d Da y 1 visit ( -4 / + 2 da ys) will be per mitte d f or all trial pr oce d ures f or t he Da y 1 visit of eac h c ycle.  S u bjects s h o ul d als o 
ret ur n t o t he trial site as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y.
b
S u bjects w h o disc o nti n ue t he I n d ucti o n P hase d ue t o a n y reas o n will ha ve a n E O T visit wit hi n 7 da ys of t he decisi o n t o disc o nti n ue c he m ot hera p y.  All s u bjects w h o d o n ot e nter t he Mai nte na nce 
P hase will ha ve a 3 0- da y after last treat me nt Safet y F oll o w- u p visit.  S u bj ects e nteri n g t he Mai nte na nce P hase will ha ve t he Re- baseli ne visit (Ta ble 3 t o Ta ble 6 as a p plica ble).  S u bjects wit h 
a n A E o n g oi n g at t he E O T visit m ust be f oll owe d u p f or fi nal o utc o me u ntil t he 3 0 -da y Safet y F oll o w -u p visit .  S u bjects wit h a n S A E o n g oi n g at t he 3 0 -da y Safet y F oll o w -u p visit m ust be 
m o nit ore d a n d f oll o we d u p b y t he I n vesti gat or u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject
is d oc u me nte d as “l ost t o f oll o w-u p.”   
c
S u bjects w h o c o m plete C ycle 6 will ret ur n t o cli nic f or t he Re -baseli ne visit (see Ta ble 3 t o Ta ble 6 d e pe n di n g o n re gi me n).  T he Re -baseli ne visit is t o occ ur -1 0 t o -1 da ys bef ore t he first 
a d mi nistrati o n i n t he Mai nte na nce P hase .
d
S u bject -re p orte d o utc o mes / q ualit y of life assess me nts s h o ul d be c o m plete d b y s u bjects after t he I C F is si g ne d a n d pri or t o a n y st u d y -relate d pr oce d ures at t he i n dicate d visits.  T he assess me nts 
s h o ul d be c o n d ucte d at Scree ni n g; i n t he e ve nt t hat t his d oes n’t occ ur, it ca n be d o ne at C ycle 1 ( Da y 1) pri or t o treat me nt.
e 
T he d ose of c he m ot hera p y will be calc ulate d base d o n t he wei g ht or b o d y s urface area, as a p plica ble, of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he da y of dr u g a d mi nistrati o n. 
f 
If t he Scree ni n g E C O G P S was perfor m e d wit hi n 3 da ys pri or t o C ycle 1 Da y 1, it d oes n ot ha ve t o be re peate d at C ycle 1 Da y 1.
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI
C CIC CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 6 / 1 5 0
g
He mat ol o g y (i ncl u di n g C o m plete Bl o o d C o u nt) a n d he m o stase ol o g y assess me nts are detaile d i n Ta ble 1 2 .  F ollicle-sti m ulati n g h or m o ne at Scree ni n g, if a p plica ble (Secti o n  7. 1. 1 ).  C o m plete 
bl o o d c o u nt res ults m ust als o be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
h
F ull c he mistr y a n d c ore ser u m c he mistr y sa m ples are detaile d i n  Ta ble 1 2 .  Sa m ples f or c he mistr y res ults m ust be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
i
A f ull uri nal ysis is re q uire d at Scree ni n g a n d t he E n d-of -Treat me nt visit (see  Ta ble 1 2 f or details).
j 
β- hC G m ust be deter mi ne d fr o m ser u m at Scree ni n g a n d fr o m eit her uri ne or ser u m sa m ple t hereafter as re q uire d per l ocal g ui deli nes.  Res ults of t he m ost rece nt pre g na nc y test ha s t o be 
a vaila ble pri or t o ne xt d osi n g
k
A n H B V s urface a nti ge n a n d a nti-H C V tests m ust be perf or me d at Scree ni n g t o e xcl u de s u bjects wit h he patitis i nfecti o n.  If t he a nti-H C V a nti b o d y test is p ositi ve, t he i nfecti o n m ust be 
c o nfir me d b y a n H C V R N A test.
p
A nti -e metic pre me dicati o ns s h o ul d be a d mi nistere d i n acc or da nce wit h eit her t he 2 0 0 6 A merica n S ociet y of Cli nical O nc ol o g y g ui deli nes or l ocal i nstit uti o nal g ui deli nes.
T a ble 3
Sc he d ule of Assess me nts – M ai nte n a nce P h ase a n d F oll o w -U p – O x ali pl ati n + C a pecit a bi ne
M ai nte n a nce P h ase ( -4/ + 2 d a ys) a
E n d of Tre at me nt
F oll o w -u p b
Re -
b aseli ne 
( D a y - 1 0 
t o 
D a y -1) c
V 1  
V 2  
V 3  
V 4  
V 5
E n d -of -Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -ter m 
F oll o w -u p
W 1
D a y 1
W 4
D a y 
2 2
W 7
D a y 
4 3
W 1 0
D a y 
6 4
W 1 3
D a y 
8 5
U ntil 
Pr o gressi o n
Wit hi n 7 D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 
3 0 D a ys after L ast 
Tre at me nt ( ± 5 d a ys) e
P h o ne C all
9 0 D a ys after 
L ast Tre at me nt 
( ± 1 wee k)
E ver y 1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k) 
St u d y Pr oce d ures
Re vie w eli gi bilit y Criteria f
X
P h ysical e xa mi nati o n g
X  
X  
X  
X  
X  
X
6 wee ks
X
X
Vital si g ns
X  
X  
X  
X  
X  
X
3 wee ks
X
X
Wei g ht
h
X  
X  
X  
X  
X  
X
3 wee ks
X
X
E C O G P S i
X  
X  
X  
X  
X  
X
3 wee ks
X
X
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 7 / 1 5 0
M ai nte n a nce P h ase ( -4/ + 2 d a ys) a
E n d of Tre at me nt
F oll o w -u p b
Re -
b aseli ne 
( D a y - 1 0 
t o 
D a y -1) c
V 1  
V 2  
V 3  
V 4  
V 5
E n d -of -Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -ter m 
F oll o w -u p
W 1
D a y 1
W 4
D a y 
2 2
W 7
D a y 
4 3
W 1 0
D a y 
6 4
W 1 3
D a y 
8 5
U ntil 
Pr o gressi o n
Wit hi n 7 D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 
3 0 D a ys after L ast 
Tre at me nt ( ± 5 d a ys) e
P h o ne C all
9 0 D a ys after 
L ast Tre at me nt 
( ± 1 wee k)
E ver y 1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k) 
1 2 -lea d E C G
X
X
S u bject -re p orte d o utc o mes / 
q ualit y of life assess me nts j
X  
X j
X  
X
X
6 wee ks
X
X
C o nc o mita nt me dicati o ns 
a n d pr oce d ures 
C ollecte d t hr o u g h t he 3 0 -da y Safet y F oll o w -u p Visit
A nti -ca ncer t hera p y b
X
X
X
A E c ollecti o n
All A Es are c ollecte d t hr o u g h t he 3 0 -da y Safet y F oll o w -u p Visit; 
Treat me nt -relate d n o n-seri o us A Es are c ollecte d u ntil t he 9 0-da y Safet y F oll o w -u p P h o ne Call b
X
S A E c ollecti o n
All S A Es are d oc u me nte d u ntil t he 9 0- da y Safet y F oll o w -u p P h o ne Call;
O n g oi n g S A Es at t he 9 0- da y Safet y F oll o w -u p Call will be f oll o we d b
X
S a m ples a n d L a b or at or y Assess me nts
He mat ol o g y a n d 
he m ostase ol o g y k
X  
X  
X  
X  
X  
X
3 wee ks
X
X
F ull ser u m c he mistr y l
X
X
X
C ore ser u m c he mistr y l
X  
X  
X  
X  
X
3 wee ks
Uri nal ysis m
X  
X
X
X
1 2 wee ks
X
X
β- h C G pre g na nc y test n
X  
X  
X  
X  
X  
X
3 wee ks
X
X
T 4 a n d T S H
X
X
X
6 wee ks
X
X
Car diac tr o p o ni n o
X  
X  
X  
X  
X  
X
Res p o nse Assess me nts
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 8 / 1 5 0
M ai nte n a nce P h ase ( -4/ + 2 d a ys) a
E n d of Tre at me nt
F oll o w -u p b
Re -
b aseli ne 
( D a y - 1 0 
t o 
D a y -1) c
V 1  
V 2  
V 3  
V 4  
V 5
E n d -of -Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -ter m 
F oll o w -u p
W 1
D a y 1
W 4
D a y 
2 2
W 7
D a y 
4 3
W 1 0
D a y 
6 4
W 1 3
D a y 
8 5
U ntil 
Pr o gressi o n
Wit hi n 7 D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 
3 0 D a ys after L ast 
Tre at me nt ( ± 5 d a ys) e
P h o ne C all
9 0 D a ys after 
L ast Tre at me nt 
( ± 1 wee k)
E ver y 1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k) 
Ra n d o mizati o n r
X
D osi n g
Pretreat me nt
X  
X  
X  
X  
X
3 wee ks
C he m ot hera p y 
a d mi nistrati o n
X  
X  
X  
X  
X
3 wee ks
A E = a d verse e ve nt; β - hC G = β -h u m a n c h ori o nic g o na d otr o pi n; C R = c o m plete res p o nse; C T = c o m p ute d t o m o gra p h y; E C G = electr ocar di o gra m, E C O G P S = Easter n C o o perati ve O nc ol o g y Gr o u p 
Perf or ma nce Stat us; E O T = e n d of treat me nt; I M P = i n vesti gati o nal me dici nal pr o d uct; I C F = i nf or me d c o nse nt f or m; 
 P D = pr o gressi ve disease; 
 
 P R = partial res p o nse; R E CI S T = Res p o nse E val uati o n Criteria i n S oli d T u m ors versi o n 1. 1; S A E = seri o us a d verse e ve nt; S D = s ta ble disease; T4 = free t h yr o xi ne; T S H = t h yr oi d-
sti m ulati n g h or m o ne; W = wee k.
a
A ti me wi n d o w of u p t o 4 da ys bef ore or 2 da ys after t he sc he d ule d Da y 1 visit (-4 / + 2 da ys) will be per mitte d f or all trial pr oce d ures f or t he Da y 1 visit of eac h c ycle.  S u bjects s h o ul d als o ret ur n 
t o t he trial site as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y.
b
All s u bjects will ha ve a n E O T visit wit hi n 7 da ys after t he decisi o n t o disc o nti n ue st u d y treat me nt.  All A Es will be d oc u me nte d u ntil t he 3 0 -da y Safet y F oll o w - up visit.  S u bjects wit h a n o n g oi n g 
S A E at t he 3 0 -da y Safet y F oll o w -u p visit m ust be m o nit ore d a n d f oll o we d u p u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n.  After t his visit, all S A Es a n d all treat me nt -relate d n o n-seri o us A Es 
nee d t o b e d oc u me nte d u ntil t he 9 0 -da y Safet y F oll o w -u p P h o ne Call.  S u bjects wit h a n o n g oi n g S A E at t he 9 0- da y Safet y F oll o w -u p C all m ust be m o nit ore d a n d f oll o we d b y t he I n vesti gat or u ntil 
sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is d oc u me nte d as “l ost t o f oll o w-u p”.  At 9 0 da ys f oll o wi n g t he last treat me nt, s u bjects will be c o ntacte d b y tele p h o ne t o c ollect 
i nfor mati o n o n ne w or o n g oi n g S A Es a n d treat me nt -relate d n o n-seri o us A Es.  A n y S A E assesse d as relate d t o I M P m ust be re p orte d w he ne ver it occ urs, irres pecti ve of t he ti me ela pse d si nce t he 
last a d mi nistrati o n of I M P.  S u bjects wit h o ut pr o gressi ve disease at E n d -of -Treat me nt visit will be f oll o we d u p f or disease pr o gressi o n ( C T / M RI sca ns e ver y 6 wee ks [ ± 1 wee k] , a n d after 1 2 m o nt hs 
e ver y 1 2 wee ks [ ± 1 wee k] ) u ntil P D.  In a d diti o n, s u bjects will be f oll o we d e ver y 1 2 wee ks f or s ur vi val (i ncl u di n g assess me nt of a n y f urt her a nti-ca ncer t hera p y).  The s ur vi val f oll o w-u p will 
c o nti n ue u ntil 5 years after t he last s u bject recei ves t he last d ose of trial dr u g (see Secti o n  7. 1. 5 f or details).  
c
S u bjects w h o disc o nti n ue treat me nt d ue t o a n y reas o n d uri n g t he Re -baseli ne peri o d a n d bef ore ra n d o mizati o n will ha ve a n E O T visit wit hi n 7 da ys of t he decisi o n t o disc o nti n ue c he m ot hera p y 
a n d a 3 0 -da y Safet y F oll o w -u p visit i n acc or da nce wit h t he I n d ucti o n P hase S c he d ule of A ssess me nts.
d
T u m or e val uati o n at t he E n d -of -Treat me nt visit s h o ul d o nl y be perf or me d if n o disease pr o gressi o n has bee n d oc u me nte d pre vi o usl y .
e
If a n ot her a nti ne o plastic t hera p y is a d mi nistere d bef ore t he e n d of t his 3 0 -da y peri o d, t he Safet y F oll o w - up visit s h o ul d be c o n d ucte d, if p ossi ble, pri or t o t he start of t his ne w t hera p y.
f
E nr oll me nt a n d ra n d o mizati o n i nt o t he Mai nte na nce P hase will be d o ne after t he c o nfir mati o n of f ulfilli n g all i ncl usi o n criteria ( Secti o n 5. 3. 1 ) wi t h o ut matc hi n g a n y e xcl usi o n criteria ( Secti o n 5. 3. 2 ).
g
T he p h ysical e xa mi nati o n will occ ur e ver y 3 wee ks u ntil Wee k 1 3, a n d e ver y 6 wee ks t hereafter.
h
T he d ose of c he m ot hera p y will be calc ulate d base d o n t he wei g ht or b o d y s urface area, as a p plica ble, of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he da y of dr u g a d mi nistrati o n. 
i
If t he Re-baseli ne E C O G P S was perf or me d wit hi n 3 da ys pri or t o Da y 1, it d oes n ot ha ve t o be re peate d at Da y 1.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
2 9 / 1 5 0
j
S u bject -re p orte d o utc o mes / q ualit y of life assess me nts s h o ul d be c o m plete d b y s u bjects pri or t o a n y st u d y-relate d pr oce d ures at t he i n dicate d visits.  T he assess me nts s h o ul d be c o n d ucte d at Re-
baseli ne; i n t he e ve nt t hat t his d oes n’t occ ur, it ca n be d o ne at Visit 1 ( Da y 1) pri or t o treat me nt.
k
He mat ol o g y (i ncl u di n g C o m plete Bl o o d C o u nt) a n d he m o stase ol o g y assess me nts are detaile d i n Ta ble 1 2 .  F ollicle-sti m ulati n g h or m o ne at Scree ni n g, if a p plica ble ( Secti o n 7. 1. 1 ).  C o m plete bl o o d 
c o u nt res ults m ust als o be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.  
l
F ull c he mistr y a n d c ore ser u m c he mistr y sa m ples are detaile d i n  Ta ble 1 2 .  Sa m ples f or c he mistr y res ults m ust be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
m
A f ull uri nal ysis is re q uire d at t he E n d-of -Treat me nt visit a n d t he Re -baseli ne visit a n d a basic uri nal ysis at all ot her i n dicate d visits (see  Ta ble 1 2 f or details).
n
β- h C G s h o ul d be deter mi ne d fr o m eit her u ri ne or ser u m sa m ple.  Res ults of t he m ost rece nt pre g na nc y test has t o be a vaila ble pri or t o ne xt d osi n g.
o
Car diac tr o p o ni n le vels will be c ollecte d fr o m R e- baseli ne u p t o 1 2 wee ks i n t he M ai nte na nce P has e (see Ta ble 1 1 ).  
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 0 / 1 5 0
T a ble 4
Sc he d ule of Assess me nts – M ai nte n a nce P h ase a n d F oll o w -U p - O x ali pl ati n + 5- Fl u or o ur acil ( 5 -F U)
M ai nte n a nce P h ase
(-4/ + 2 d a ys) a
E n d of 
Tre at me nt
F oll o w -u p b
Re -
b aseli ne 
( D a y -
1 0 t o 
D a y -1) c
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7
E n d -of -
Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -
ter m 
F oll o w -u p
W 1
D a y 1
W 3
D a y 
1 5
W 5
D a y 
2 9
W 7
D a y 
4 3
W 9
D a y 
5 7
W 1 1
D a y 
7 1
W 1 3
D a y 
8 5
U ntil 
Pr o gressi o n
Wit hi n 7 
D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 3 0 
D a ys after 
L ast 
Tre at me nt
( ± 5 d a ys)e
P h o ne C all 9 0 
D a ys after L ast 
Tre at me nt ( ± 1 
wee k)
E ver y   
1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k)
St u d y Pr oce d ures
Re vie w of eli gi bilit y criteria f
X
P h ysical e xa mi nati o n g
X  
X  
X  
X  
X  
X  
X  
X
6 wee ks
X
X
Vital si g ns
X  
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
Wei g ht
h
X  
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
E C O G P S i
X  
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
1 2 -lea d E C G
X
X
S u bject -re p orte d o utc o mes / 
q ualit y of life assess me nts j
X  
X j
X
X
X
6 wee ks
X
X
C o nc o mita nt me dicati o ns a n d 
pr oce d ures
C ollecte d t hr o u g h t he 3 0 -da y Safet y F oll o w -u p Visit
A nti -ca ncer t hera p yb
X
X
X
A E c ollecti o n
A Es are c ollecte d t hr o u g h t he 3 0 -da y Safet y F oll o w -u p Visit;
Treat me nt -relate d n o n-seri o us A Es are c ollecte d u ntil t he 9 0-da y Safet y F oll o w -u p P h o ne Call b
X
S A E c ollecti o n
All S A Es are d oc u me nte d u ntil t he 9 0- da y Safet y F oll o w -u p P h o ne Call,
O n g oi n g S A Es at t he 9 0- da y Safet y F oll o w -u p Call will be f oll o we d
b
X
S a m ples a n d L a b or at or y Assess me nts
He mat ol o g y a n d 
he m ostase ol o g y k
X  
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
F ull ser u m c he mistr y l
X
X
X
C ore ser u m c he mistr y l
X  
X  
X  
X  
X  
X  
X
2 wee ks
Uri nal ysis m
X  
X
X
X
1 2 wee ks
X
X
β- h C G pre g na nc y test n
X  
X
X
X
X
4 wee ks
X
X
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 1 / 1 5 0
M ai nte n a nce P h ase
(-4/ + 2 d a ys) a
E n d of 
Tre at me nt
F oll o w -u p b
Re -
b aseli ne 
( D a y -
1 0 t o 
D a y -1) c
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7
E n d -of -
Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -
ter m 
F oll o w -u p
W 1
D a y 1
W 3
D a y 
1 5
W 5
D a y 
2 9
W 7
D a y 
4 3
W 9
D a y 
5 7
W 1 1
D a y 
7 1
W 1 3
D a y 
8 5
U ntil 
Pr o gressi o n
Wit hi n 7 
D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 3 0 
D a ys after 
L ast 
Tre at me nt
( ± 5 d a ys)e
P h o ne C all 9 0 
D a ys after L ast 
Tre at me nt ( ± 1 
wee k)
E ver y   
1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k)
T 4 a n d T S H
X
X
X
6 wee ks
X
X
Car diac tr o p o ni n o
X  
X  
X  
X  
X  
X  
X  
X
Res p o nse Assess me nts
Ra n d o mizati o n r
X
D osi n g
Pretreat me nt
X  
X  
X  
X  
X  
X  
X
2 wee ks
C he m ot hera p y a d mi nistrati o n
X  
X  
X  
X  
X  
X  
X
2 wee ks
A E = a d verse e ve nt; β - hC G = β -h u ma n c h ori o nic g o na d otr o pi n; C R = c o m plete res p o nse; C T = c o m p ute d t o m o gra p h y; E C G = electr ocar di o gra m, E C O G P S = Easter n C o o perati ve O nc ol o g y 
Gr o u p Perf or ma nce Stat us; E O T = e n d of treat me nt; I M P = i n vesti gati o nal me dici nal pr o d uct; I C F = i nf or me d c o nse nt f or m; 
; P D = pr o gressi ve disease; 
 
 P R = partial res p o nse; R E CI S T = Res p o nse E val uati o n Criteria i n S oli d T u m ors versi o n 1. 1; S A E = seri o us a d verse e ve nt; S D = sta ble disease; T 4 = free t h yr o xi ne; T S H = 
t h yr oi d-sti m ulati n g h or m o ne; W = wee k.
a
A ti me wi n d o w of u p t o 4 da ys bef ore or 2 da ys after t he sc he d ule d Da y 1 visit ( -4 / + 2 da ys) will be per mitte d f or all trial pr oce d ures f or t he Da y 1 visit of eac h c ycle.  S u bjects s h o ul d als o ret ur n 
t o the trial site as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y. 
b
All s u bjects will ha ve a n E O T visit wit hi n 7 da ys after t he decisi o n t o disc o nti n ue st u d y treat me nt.  All A Es will be d oc u me nte d u ntil t he 3 0 -da y Safet y F oll o w - up visit.  S u bjects wit h a n o n g oi n g 
S A E at t he 3 0 -da y Safet y F oll o w -u p visit m ust be m o nit ore d a n d f oll o we d u p u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n.  After t his visit, all S A Es a n d all treat me nt -relate d n o n-seri o us A Es 
nee d t o b e d oc u me nte d u ntil t he 9 0 -da y Safet y F oll o w -u p P h o n e C all.  Su bjects wit h a n o n g oi n g S A E at t he 9 0- da y Safet y F oll o w -u p C all m ust be m o nit ore d a n d f oll o we d b y t he I n vesti gat or 
u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is d oc u me nte d as “l ost t o f oll o w-u p”.  At 9 0 da ys f oll o wi n g t he last treat me nt, s u bjects will be c o ntacte d b y tele p h o ne t o c ollect 
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 2 / 1 5 0
i nf or mati o n o n ne w or o n g oi n g S A Es a n d treat me nt-relate d n o n-seri o us A Es.  A n y S A E assesse d as relate d t o I M P m ust be re p orte d w he ne ver it occ urs, irres pecti ve of t he ti me ela pse d si nce t he 
last a d mi nistrati o n of I M P.  Su bjects wit h o ut pr o gressi ve disease at E n d -of -Treat me nt visit will be f oll o we d u p f or disease pr o gressi o n ( C T / M RI sca ns e ver y 6 wee ks [ ± 1 wee k] , a n d after 
1 2 m o nt hs, e ver y 12 wee ks [ ± 1 wee k] ) u ntil P D.  In a d diti o n, s u bjects will be f oll o we d e ver y 1 2 wee ks f or s ur vi val (i ncl u di n g assess me nt of a n y furt her a nti-ca ncer t hera p y).  The s ur vi val 
f oll o w-u p will c o nti n ue u ntil 5 years after t he last s u bject recei ves t he last d os e of trial dr u g (see Secti o n  7. 1. 5 f or details).  
c
S u bjects w h o disc o nti n ue treat me nt d ue t o a n y reas o n d uri n g t he Re -baseli ne peri o d a n d bef ore ra n d o mizati o n will ha ve a n E O T visit wit hi n 7 da ys of t he decisi o n t o disc o nti n ue c he m ot hera p y 
a n d a 3 0 -da y Safet y F oll o w -u p visit i n acc or da nce wit h t he I n d ucti o n P hase S c he d ule of A ssess me nts.
d
T u m or e val uati o n at t he E n d -of -Treat me nt visit s h o ul d o nl y be perf or me d if n o disease pr o gressi o n has bee n d oc u me nte d pre vi o usl y .
e
If a n ot her a nti ne o plastic t hera p y is a d mi nistere d bef ore t he e n d of t he 3 0- da y peri o d, t he 3 0-da y Safet y F oll o w -U p visit s h o ul d be c o n d ucte d, if p ossi ble, pri or t o t he start of a n y ne w t hera p y.
f
E nr oll me nt a n d ra n d o mizati o n i nt o t he Mai nte na nce P hase will be d o ne after t he c o nfir mati o n of f ulfilli n g all i ncl usi o n criteria ( Secti on 5. 3. 1 ) wit h o ut matc hi n g a n y e xcl usi o n criteria 
( Secti o n 5. 3. 2 ).
g 
T he p h ysical e xa mi nati o n will occ ur e ver y 2 wee ks u ntil Wee k 1 3, a n d e ver y 6 wee ks t hereafter. 
h 
T he d ose of c he m ot hera p y will be calc ulate d base d o n t he wei g ht or b o d y s urface area, as a p plica ble, of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he da y of dr u g a d mi nistrati o n. 
i
If t he Re- baseli ne E C O G P S was perf or me d wit hi n 3 da ys pri or t o Da y 1, it d oes n ot ha ve t o be re peate d at Da y 1.
j
S u bject -re p orte d o utc o mes / q ualit y of life assess me nts s h o ul d be c o m plete d b y s u bjects pri or t o a n y st u d y-relate d pr oce d ures at t he i n dicate d visits.  The assess me nts s h o ul d be c o n d ucte d at 
Re -baseli ne; i n t he e ve nt t hat t his d oes n’t occ ur, it ca n be d o ne at Visit 1 ( Da y 1) pri or t o treat me nt.
k
He mat ol o g y (i ncl u di n g C o m plete Bl o o d C o u nt) a n d he m o stase ol o g y assess me nts are detaile d i n Ta ble 1 2 .  Follicle -sti m ulati n g h or m o ne at Scree ni n g, if a p plica ble ( Secti o n 7. 1. 1).  Co m plete 
bl o o d c o u nt res ults m ust als o be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.  
l
F ull c he mistr y a n d c ore ser u m c he mistr y sa m ples are detaile d i n  Ta ble 1 2 .  Sa m ples f or c he mistr y res ults m ust be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
m
A f ull uri nal ysis is re q uire d at t he E n d-of -Treat me nt visit a n d t he Re -baseli ne visit a n d a basic uri nal ysis at all ot her i n dicate d visits (see  Ta ble 1 2 f or details).
n 
β- h C G s h o ul d be deter mi ne d fr o m eit her u ri ne or ser u m sa m ple.  Res ults of t he m ost rece nt pre g na nc y test nee d t o be a vaila ble pri or t o ne xt d osi n g.
o
Car diac tr o p o ni n le vels will be c ollecte d fr o m R e- baseli ne u p t o 1 2 wee ks i n t he M ai nte na nce P hase (see Ta ble 1 1 ).  
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 3 / 1 5 0
T a ble 5
Sc he d ule of Assess me nts:  M ai nte n a nce P h ase a n d F oll o w -U p - Best S u p p orti ve C are O nl y
Re -b aseli ne 
( D a y -1 0 t o 
D a y -1) c
Tre at me nt P h ase (-4/ + 2 d a ys) a
E n d -of -Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -
ter m 
F oll o w -
u p b
V 1  
V 2  
V 3  
V 4  
V 5
U ntil 
Pr o gressi o n
Wit hi n 7
D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 
3 0 D a ys after L ast 
Tre at me nt ( ± 5 d a ys) e
P h o ne C all 9 0 
D a ys after L ast 
Tre at me nt ( ± 1 
wee k)
E ver y 1 2 
Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k)
W 1  
W 4  
W 7
W 1 0  
W 1 3
D 1
D 2 2  
D 4 3  
D 6 4  
D 8 5
St u d y Pr oce d ures
Re vie w eli gi bilit y criteria f
X
P h ysical e xa mi nati o n g
X  
X  
X  
X  
X  
X
6 wee ks
X
X
Vital si g ns
X  
X  
X  
X  
X  
X
3 wee ks
X
X
Wei g ht
h
X  
X  
X  
X  
X  
X
3 wee ks 
X
X
E C O G P S i
X  
X  
X  
X  
X  
X
3 wee ks
X
X
1 2 -lea d E C G
X
X
S u bject -re p orte d o utc o mes / q ualit y 
of life assess me nts j
X  
X j
X  
X
X
6 wee ks
X
X
A nti -ca ncer t hera p y b
X
X
X
C o nc o mita nt me dicati o ns a n d 
pr oce d ures
C ollecte d t hr o u g h t he 3 0- da y Safet y F oll o w -u p Visit
A E c ollecti o n
A Es are c ollecte d t hr o u g h t he Safet y F oll o w -u p Visit;
Treat me nt -relate d n o n-seri o us A Es are c ollecte d u ntil t he 9 0-da y Safet y F oll o w -u p P h o ne Call b
X
S A E c ollecti o n
All S A Es are d oc u me nte d u ntil t he 9 0 -da y Safet y F oll o w -u p P h o ne Call,
O n g oi n g S A Es at t he 9 0 -da y Safet y F oll o w -u p Call will be f oll o we d b
X
S a m ples a n d L a b or at or y Assess me nts
He mat ol o g y a n d he m ostase ol o g y k
X  
X  
X  
X  
X  
X
3 wee ks
X
X
F ull ser u m c he mistr y l
X
X
X
C ore ser u m c he mistr y l
X  
X  
X  
X  
X
3 wee ks
Uri nal ysis m
X  
X
X
X
1 2 wee ks
X
X
Β- h C G pre g na nc y test n
X
T 4 a n d T S H
X
X
X
6 wee ks
X
X
Car diac tr o p o ni n o
X  
X  
X  
X  
X  
X
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 4 / 1 5 0
Re -b aseli ne 
( D a y -1 0 t o 
D a y -1) c
Tre at me nt P h ase (-4/ + 2 d a ys) a
E n d -of -Tre at me nt 
Visit
S afet y F oll o w -u p
L o n g -
ter m 
F oll o w -
u p b
V 1  
V 2  
V 3  
V 4  
V 5
U ntil 
Pr o gressi o n
Wit hi n 7
D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit 
3 0 D a ys after L ast 
Tre at me nt ( ± 5 d a ys) e
P h o ne C all 9 0 
D a ys after L ast 
Tre at me nt ( ± 1 
wee k)
E ver y 1 2 
Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k)
W 1  
W 4  
W 7
W 1 0  
W 1 3
D 1
D 2 2  
D 4 3  
D 6 4  
D 8 5
Ra n d o mizati o n r
X
A E = a d verse e ve nt, β- h C G = β -h u ma n c h ori o nic g o na d otr o pi n, C R = c o m plete res p o nse, C T = c o m p ute d t o m o gra p h y, D = Da y, E C G = electr ocar di o gra m, E O T = e n d of treat me nt; E C O G- P S = 
Easter n C o o perati ve O nc ol o g y Gr o u p Perf or ma nce Stat us, I C F = i nf or me d c o nse nt f or m, I M P = i n vesti gati o nal me dici nal pr o d uct, 
P D = pr o gressi ve disease, 
, P R = partial res p o nse, R E CI S T = Res p o nse E val ua ti o n Criteria i n S oli d T u m ors versi o n 1. 1, S A E = seri o us a d verse e ve nt, S D = sta ble disease, T4 = free t h yr o xi ne, 
T S H = t h yr oi d sti m ulati n g h or m o ne, V = visit, W = Wee k.
a
A ti me wi n d o w of u p t o 4 da ys bef ore or 2 da ys after t he sc he d ule d Da y 1 visit ( -4 / + 2 da ys) will be per mitte d f or all trial pr oce d ures f or t he Da y 1 visit of eac h c ycle.  S u bjects s h o ul d als o ret ur n 
t o t he trial site as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y. 
b
All s u bjects will ha ve a n E O T visit wit hi n 7 da ys after t he decisi o n t o disc o nti n ue st u d y treat me nt.  All A Es will be d oc u me nte d u ntil t he 3 0 -da y Safet y F oll o w - up visit.  S u bjects wit h a n o n g oi n g 
S A E at t he 3 0 -da y Safet y F oll o w -u p visit m ust be m o nit ore d a n d f oll o we d u p u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n.  Aft er t his visit, all S A Es a n d all treat me nt-relate d n o n-seri o us A Es 
nee d t o be d oc u me nte d u ntil t he 9 0 -da y Safet y F oll o w -u p P h o n e Call.  S u bjects wit h a n o n g oi n g S A E at t he 9 0- da y Safet y F oll o w -u p Call m ust be m o nit ore d a n d f oll o we d b y t he I n vesti gat or u ntil 
sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is d oc u me nte d as “l ost t o f oll o w-u p ”.  At 9 0 da ys f oll o wi n g the last treat me nt, s u bjects will be c o ntacte d b y tele p h o ne t o c ollect 
i nf or mati o n o n ne w or o n g oi n g S A Es a n d treat me nt-relate d n o n-seri o us A Es.  S u bjects wit h o ut pr o gressi ve disease at E n d-of -Treat me nt visit will be f oll o we d u p f or disease pr o gressi o n ( C T / M RI 
sca ns e ver y 6 wee ks [ ± 1 wee k] , a n d aft er 1 2 m o nt hs e ver y 1 2 w ee ks [ ± 1 wee k] ) u ntil P D.  I n a d diti o n, s u bjects will be f oll o we d e ver y 1 2 wee ks f or s ur vi val (i ncl u di n g assess me nt of a n y f urt her 
a nti-ca ncer t hera p y).  T he s ur vi val f oll o w-u p will c o nti n u e u ntil 5 years after t he last s u bject recei ves t he last d ose of trial dr u g (see Secti o n  7. 1. 5 f or details).
c
S u bjects w h o disc o nti n ue treat me nt d ue t o a n y reas o n d uri n g t he Re -baseli ne peri o d a n d bef ore ra n d o mizati o n will ha ve a n E O T visit wit hi n 7 da ys of t he decisi o n t o disc o nti n ue c he m ot hera p y 
a n d a 3 0 -da y Safet y F oll o w -u p visit i n acc or da nce wit h t he I n d ucti o n P hase S c he d ule of A ssess me nts.
d
T u m or e val uati o n at t he E n d -of -Treat me nt visit s h o ul d o nl y be perf or me d if n o disease pr o gressi o n has bee n d oc u me nte d pre vi o usl y .
e
If a n ot her a nti ne o plastic t hera p y is a d mi nistere d bef ore t he e n d of t he 3 0- da y peri o d, t he 3 0- da y Safet y F oll o w -U p visit s h o ul d be c o n d ucte d, if p ossi ble, pri or t o t he start of t his ne w t hera p y.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 5 / 1 5 0
f
E nr oll me nt a n d ra n d o mizati o n i nt o t he Mai nte na nce P hase will be d o ne after t he c o nfir mati o n of f ulfilli n g all i ncl usi o n criteria ( Secti o n 5. 3. 1 ) wit h o ut matc hi n g a n y e xcl usi o n criteria ( Secti o n 5. 3. 2 ).
g
T he p h ysical e xa mi nati o n will occ ur e ver y 3 wee ks u ntil Wee k 1 3, a n d e ver y 6 wee ks t hereafter.
h
T he d ose of B S C will be calc ulate d base d o n t he wei g ht or b o d y s urface area, as a p plica ble, of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he da y of dr u g a d mi nistrati o n. 
i
If t he Re-baseli ne E C O G P S was perf or me d wit hi n 3 da ys pri or t o Da y 1, it d oes n ot ha ve t o be re peate d at Da y 1.
j
S u bject -re p orte d o utc o mes / q ualit y of life assess me nts s h o ul d be c o m plete d b y s u bjects pri or t o a n y st u d y-relate d pr oce d ures at t he i n dicate d visits.  T he assess me nts s h o ul d be c o n d ucte d at Re-
baseli ne; i n t he e ve nt t hat t his d oes n’t occ ur, it ca n be d o ne at Visit 1 ( Da y 1) pri or t o treat me nt.
k
He mat ol o g y (i ncl u di n g C o m plete Bl o o d C o u nt) a n d he m o stase ol o g y assess me nts are detaile d i n Ta ble 1 2 .  F ollicle-sti m ulati n g h or m o ne at Scree ni n g, if a p plica ble ( Secti o n 7. 1. 1 ).  C o m plete bl o o d 
c o u nt res ults m ust als o be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.  
l
F ull c he mistr y a n d c ore ser u m c he mistr y sa m ples are detaile d i n  Ta ble 1 2 .  Sa m ples f or c he mistr y res ults m ust be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
m
A f ull uri nal ysis is re q uire d at t he E n d-of -Treat me nt visit a n d t he Re -baseli ne visit a n d a basic uri nal ysis at all ot her i n dicate d visits (see  Ta ble 1 2 f or details).
n β - hC G s h o ul d be deter mi ne d fr o m eit her u ri ne or ser u m sa m ple.  Res ults of t he m ost rece nt pre g na nc y test nee ds t o be a vaila ble pri or t o ne xt d osi n g.
o
Car diac tr o p o ni n le vels will be c ollecte d fr o m R e- baseli ne u p t o 1 2 wee ks i n t he M ai nte na nce P hase see Ta ble 1 1 ).  
D oc u me nt N o.
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 6 / 1 5 0
T a ble 6
Sc he d ule of Assess me nts – M ai nte n a nce P h ase a n d F oll o w -u p – A vel u m a b
A vel u m a b Tre at me nt ( -4/ + 2 d a ys) a
E n d of 
Tre at me nt
F oll o w -u p b
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7
E n d -of -
Tre at me nt 
Visit
S afet y F oll o w -u p Visit
L o n g -ter m 
F oll o w -u p
Re -b aseli ne 
( D a y -1 0 t o 
D a y -1) c
W 1
D a y 1
W 3
D a y 
1 5
W 5
D a y 2 9
W 7
D a y 4 3
W 9
D a y 5 7
W 1 1
D a y 7 1
W 1 3
D a y 
8 5
U ntil 
Pr o gres -
si o n
Wit hi n 7 
D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit
3 0 D a ys 
after L ast 
Tre at me n
t ( ± 5 
d a ys) e
P h o ne C all
9 0 D a ys 
after L ast 
Tre at me nt 
( ± 1 w e e k)
E ver y   
1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k)
St u d y Pr oce d ures
Eli gi bilit y criteria f
X
P h ysical e xa mi nati o n g
X
X  
X  
X  
X  
X  
X  
X
6 wee ks
X
X
Vi tal si g ns
X
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
We i g hth
X
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
E C O G P S i
X
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
1 2 -lea d E C G
X
X
S u bject -re p orte d o utc o mes / 
q ualit y of life assess me nts j
X
X j
X
X
X
6 wee ks
X
X
A nti -ca ncer t hera p y b
X
X
X
C o nc o mita nt me dicati o ns a n d 
pr oce d ures
C ollecte d t hr o u g h t he 3 0- da y Safet y F oll o w -u p Visit
A E c ollecti o n
A Es are c ollecte d t hr o u g h t he Safet y F oll o w -u p Visit
Treat me nt -relate d n o n-seri o us A Es are c ollecte d u ntil t he 9 0-da y Safet y F oll o w -u p P h o ne Call b
X
S A E c ollecti o n
All S A Es are d oc u me nte d u ntil t he 9 0- da y Safet y F oll o w -u p P h o ne Call,
O n g oi n g S A Es at t he 9 0 -da y Safet y F oll o w -u p Call will be f oll o we d b
X
S a m ples a n d L a b or at or y Assess me nts
He mat ol o g y a n d 
he m ostase ol o g y k
X
X  
X  
X  
X  
X  
X  
X
2 wee ks
X
X
F u ll ser u m c he mistr yl
X
X
X
C ore ser u m c he mistr y l
X  
X  
X  
X  
X  
X  
X
2 wee ks
Uri nal ysis m
X
X
X
X
1 2 wee ks
X
X
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 7 / 1 5 0
A vel u m a b Tre at me nt ( -4/ + 2 d a ys) a
E n d of 
Tre at me nt
F oll o w -u p b
V 1  
V 2  
V 3  
V 4  
V 5  
V 6  
V 7
E n d -of -
Tre at me nt 
Visit
S afet y F oll o w -u p Visit
L o n g -ter m 
F oll o w -u p
Re -b aseli ne 
( D a y -1 0 t o 
D a y -1) c
W 1
D a y 1
W 3
D a y 
1 5
W 5
D a y 2 9
W 7
D a y 4 3
W 9
D a y 5 7
W 1 1
D a y 7 1
W 1 3
D a y 
8 5
U ntil 
Pr o gres -
si o n
Wit hi n 7 
D a ys of 
Decisi o n t o 
Disc o nti n ue 
Tre at me nt d
Visit
3 0 D a ys 
after L ast 
Tre at me n
t ( ± 5 
d a ys) e
P h o ne C all
9 0 D a ys 
after L ast 
Tre at me nt 
( ± 1 w e e k)
E ver y   
1 2 Wee ks 
after L ast 
Tre at me nt 
( ± 2 w e e k)
β- h C G pre g na nc y test n
X
X
X
X
X
4 wee ks
X
X
T 4 a n d T S H
X
X
X
6 wee ks
X
X
Car diac tr o p o ni n o
X
X  
X  
X  
X  
X  
X  
X
Res p o nse Assess me nts
Ra n d o mizati o n r
X
D osi n g
Pretreat me nt s
X  
X  
X  
X  
X  
X  
X
2 wee ks
A v el u ma b s,t
X  
X  
X  
X  
X  
X  
X
2 wee ks
A E = a d verse e ve nt; β - hC G = β -h u ma n c h ori o nic g o na d otr o pi n; C R = c o m plete res p o nse; C T = c o m p ute d t o m o gra p h y; E C G = electr ocar di o gra m, E C O G P S = Easter n C o o perati ve O nc ol o g y 
Gr o u p Perf or ma nce Stat us; E O T = e n d of treat me nt; I M P = i n vesti gati o nal me dici nal pr o d uct;
; P D = pr o gressi ve disease; P R = partial res p o nse; R E CI S T = 
Res p o nse E val uati o n Criteria i n S oli d T u m ors versi o n 1. 1; S A E = seri o us a d verse e ve nt; T 4 = free t h yr o xi ne; T S H = t h yr oi d-sti m ulati n g h or m o ne; W = wee k.
a
A ti me wi n d o w of u p t o 4 da ys bef ore or 2 da ys after t he sc he d ule d Da y 1 visit (-4 / + 2 da ys) will be per mitte d f or all trial pr oce d ures f or t he Da y 1 visit of eac h c ycle.  Su bjects s h o ul d als o 
ret ur n t o t he trial site as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y.
b
All s u bjects will ha ve a n E O T visit wit hi n 7 da ys after t he decisi o n t o disc o nti n ue st u d y treat me nt.  All A Es will be d oc u me nte d u ntil t he 3 0-da y Safet y F oll o w - up visit.  S u bjects wit h a n o n g oi n g 
S A E at t he 3 0 -da y Safet y F oll o w - u p visit m ust be m o nit ore d a n d f oll o we d u p u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n.  Aft er t his visit, all S A Es a n d all treat me nt-relate d n o n-seri o us 
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 8 / 1 5 0
A Es nee d t o be d oc u me nte d u ntil t he 9 0 -da y Safet y F oll o w -u p P h o ne Call.  Su bjects wit h a n o n g oi n g S A E at t he 9 0- da y Safet y F oll o w -u p Call m ust be m o nit ore d a n d f oll o we d b y t he I n vesti gat or 
u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is d oc u me nte d as “l ost t o f oll o w-u p”.  At 9 0 da ys f oll o wi n g t he last treat me nt, s u bjects will be c o ntacte d b y tele p h o ne t o 
c ollect i nf or mati o n o n ne w or o n g oi n g S A Es a n d treat me nt -relate d n o n-seri o us A Es.  A n y S A E assesse d as relate d t o I M P m ust be re p orte d w he ne ver it occ urs, irres pecti ve of t he ti me ela pse d 
si nce t he last a d mi nistrati o n of I M P.  S u bjects wit h o ut pr o gressi ve disease at E n d-of -Treat me nt visit will be f oll o we d u p f or disease pr o gressi o n ( C T / M RI sca ns e ver y 6 wee ks [ ± 1 wee k] , a n d 
after 1 2 m o nt hs, e ver y 1 2 wee ks [ ± 1 wee k] ) u ntil P D.  I n a d diti o n, s u bjects will be f oll o we d e ver y 1 2 wee ks f or s ur vi val (i ncl u di n g assess me nt of a n y f urt her a nti-ca ncer t hera p y).  T he s ur vi val 
f oll o w-u p will c o nti n ue u ntil 5 years after t he last s u bject recei ves t he last d ose of trial dr u g (see Secti o n  7. 1. 5 f or details).
c
S u bjects w h o disc o nti n ue treat me nt d ue t o a n y reas o n d uri n g t he R e- baseli ne peri o d a n d bef ore ra n d o mizati o n will ha ve a n E O T visit wit hi n 7 da ys of t he decisi o n t o disc o nti n ue c he m ot hera p y 
a n d a 3 0 -da y Safet y F oll o w -u p visit i n acc or da nce wit h t he I n d ucti o n P hase S c he d ule of A ssess me nts.
d
T u m or e val uati o n at t he E n d -of -Treat me nt visit s h o ul d o nl y be perf or me d if n o disease pr o gressi o n has bee n d oc u me nte d pre vi o usl y .
e
If a n ot her a nti ne o plastic t hera p y is a d mi nistere d bef ore t he e n d of t he 3 0- da y peri o d, t he 3 0- da y Safet y F oll o w -u p visit s h o ul d be c o n d ucte d, if p ossi ble, pri or t o t he start of t his ne w t hera p y.
f
E nr oll me nt a n d ra n d o mizati o n i nt o t he Mai nte na nce P hase will be d o ne aft er t he c o nfir mati o n of f ulfilli n g all i ncl usi o n criteria ( Secti o n  5. 3. 1 ) wit h o ut matc hi n g a n y e xcl usi o n criteria ( Secti o n 
5. 3. 2 ).
g 
T he p h ysical e xa mi nati o n will occ ur e ver y 2 wee ks u ntil Wee k 1 3, a n d e ver y 6 wee ks t hereafter.
h
T he d ose of a vel u ma b will be calc ulate d base d o n t he wei g ht of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he da y of  dr u g a d mi nistrati o n. T he d ose of a vel u ma b use d f or t he pre vi o us 
a d mi nistrati o n ca n be re peate d if t he c ha n ge i n t he s u bject’s wei g ht is 1 0 % or less t ha n t he wei g ht use d f or t he last d ose ca lc ulati o n.
i
If t he Re-baseli ne E C O G P S was perf or me d wit hi n 3 da ys pri or t o Da y 1, it d o es n ot ha ve t o be re peate d at Da y 1.
j
S u bject -re p orte d o utc o mes / q ualit y of life assess me nts s h o ul d be c o m plete d b y s u bjects pri or t o a n y st u d y-relate d pr oce d ures at t he i n dicate d visits.  T he assess me nt s s h o ul d be c o n d ucte d at Re-
baseli ne; i n t he e ve nt t h at t his d oes n’t occ ur, it ca n be d o ne at Visit 1 ( Da y 1) pri or t o treat me nt. 
k
He mat ol o g y (i ncl u di n g C o m plete Bl o o d C o u nt) a n d he m o stase ol o g y assess me nts are detaile d i n Ta ble 1 2 .  Follicle -sti m ulati n g h or m o ne at Scree ni n g, if a p plica ble ( Secti o n 7. 1. 1 ).  Co m plete 
bl o o d c o u nt res ults m ust als o be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.  
l
F ull c he mistr y a n d c ore ser u m c he mistr y sa m ples are detaile d i n  Ta ble 1 2 .  Sa m ples f or c he mistr y res ults m ust be a vaila ble a n d re vie we d pri or t o d ose a d mi nistrati o n.
m
A f ull uri nal ysis is re q uire d at t he E n d-of -Treat me nt visit a n d t he Re -basel i ne visit a n d a basic uri nal ysis at all ot her i n dicate d visits (see Ta ble 1 2   f or details).
n 
β- h C G s h o ul d be deter mi ne d fr o m eit her u ri ne or ser u m sa m ple.  Res ults of t he m ost rece nt pre g na nc y test nee ds t o be a vaila ble pri or t o ne xt d osi n g.
o
Car diac tr o p o ni n le vels wil l be c ollecte d fr o m R e- baseli ne u p t o 1 2 wee ks i n t he M ai nte na nce P hase. ( See Ta ble 1 1 )  
s
Pre me dicat e patie nts wit h a n a nti hista mi ne a n d wit h paraceta m ol (aceta mi n o p he n) pri or t o t he first 4 i nf usi o ns of a vel u ma b.   Pre me dicati o n s h o ul d be a d mi nistere d f or s u bse q ue nt a vel u ma b 
d oses base d u p o n cli nical j u d g me nt a n d prese nce/se verit y of pri or i nf usi o n reacti o ns.  T his re gi me n ma y be m o difie d base d o n l ocal treat me nt sta n dar ds a n d g ui deli nes as a p pr o priate pr o vi de d 
it d oes n ot i ncl u de s yste mic c ortic oster oi ds a n d has t o be rec or de d as c o nc o mita nt me dicati o n.
t
S u bjects will recei ve a vel u ma b as l o n g as E C O G P S re mai ns sta ble, a n d if i n t he o pi ni o n of t he I n vesti gat or, t he s u bject will be nefit fr o m c o nti n ue d treat me nt, a n d if t here are n o ne w s y m pt o ms 
or w orse ni n g of e xisti n g s y m pt o ms.  S u bjects recei vi n g a vel u ma b will re mai n o n -treat me nt u ntil P D.   S u bjects w h o ha ve e x perie nce d i nitial disease pr o gressi o n ma y c o nti n ue treat me nt wit h 
a vel u ma b if t he f oll o wi n g criteria are met: In vesti gat or belie ves t hat t he s u bject will e x perie nce cli nical be nefit fr o m t he treat me nt; t here is n o u nacce pta ble t o xicit y res ulti n g fr o m t he treat me nt; 
t he s u bject’s E C O G P S is sta ble ( P S = 0 or 1); a n d treat me nt be y o n d pr o gressi o n will n ot dela y a n i m mi ne nt i nter ve nti o n t o pre ve nt seri o us c o m plicati o ns of disease pr o gressi o n.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
3 9 / 1 5 0
T a ble 7
Sc he d ule of Assess me nts –
, 
, a n d  
 S a m pli n g d uri n g 
M ai nte n a nce a n d O pe n -l a bel Tre at me nt P h ases ( A vel u m a b ar m o nl y)
; E O T = e n d of treat me nt; Hrs = h o urs; 
; P K = p har mac o ki netics; V = visit; W = Wee k.
a.
S u bjects c o m pleti n g t he last cycle of t he I n d ucti o n P hase will e nter t he Re- baseli ne peri o d pri or t o Da y 1 of t he Mai nte na nce P hase.  
b.
If a n ot her a nti ne o plastic t hera p y is a d mi nistere d bef ore t he e n d of t h e 3 0 -da y peri o d, t he 3 0 -Da y Safet y F oll o w - up visit s h o ul d be c o n d ucte d, if p ossi ble, pri or t o t he start of t his ne w t hera p y.
D oc u me nt N o.
O bject N o.
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 0 / 1 5 0
2
S p o ns or, I n vesti g at ors a n d Tri al A d mi nistr ati ve Str uct ure
T he S p o ns or of t his cli nical trial wit h a vel u ma b is E M D Ser o n o Researc h & De vel o p me nt 
I nstit ute, I nc. ( E M D Ser o n o R & D), Billerica, M A, i n t he U nite d States of A merica (U S A ) a n d 
Merc k K G a A, Dar msta dt, Ger ma n y, i n rest of w orl d.
A c o ntract researc h or ga nizati o n ( C R O),
 (f or merl y 
 
 
U S A, will u n derta ke t he o pe rati o nal as pects of t his trial. Details of s uc h str uct ures a n d ass ociate d 
pr oce d ures will be defi ne d i n a se parate I nte grate d Pr oject Ma na ge me nt Pla n (I P M P) mai ntai ne d 
b y
.  The I PM P will be pre pare d b y  the 
Cli nical Pr oject Ma na ger i n c o o perati o n 
wit h ot her
 O perati o nal Tea m Lea ds .
2. 1
I n vesti g ati o n al Sites
T he trial will be c o n d ucte d at a p pr o xi matel y 2 3 0 sites i n N ort h A merica, S o ut h A merica, Asia 
Pacific , a n d E ur o pe, wit h a p pr o xi matel y 4 7 sites i n t he U S A.
2. 2
Tri al C o or di n ati o n / M o nit ori n g
T he S p o ns or will c o or di nate t he trial a n d will utilize t he s u p p ort of C R Os f or s o me acti vities of 
t he trial.  S p o ns or will perf or m o versi g ht of t he acti vities perf or me d by t he C R Os.
T he Cli nical Trial S u p plies de part me nt of t he S p o ns or will s u p pl y the trial me dicati o n of 
a vel u ma b.  Pac ka gi n g a n d distri b uti o n of cli nical s u p p lies will be perf or me d b y t he Cli nical Trial 
S u p plies de part me nt of t he S p o ns or.   First -li ne c he m ot hera p y will be s u p plie d b y  t he st u d y ce nter 
or b y  t he Sp o ns or, acc or di n g t o l ocal la ws a n d re g ulati o ns.
S u bject e nr ollme nt
will be ma na ge d b y  an i nteracti ve we b res p o nse s yste m (I W R S).  T he 
C o or di nati n g I n vesti gat or 
 
e prese nts all I nvesti gat ors f or decisi o ns a n d disc ussi o ns 
re gar di n g t his trial, c o nsiste nt wit h t he I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) T o pic E 6 
G o o d Cli nical Practice ( G C P, hereafter referre d t o as I C H G C P).  The C o or di nati n g I n vesti gat or 
will pr o vi de e x pert me dical i n p ut a n d a d vice relati n g t o trial desi g n a n d e xec uti o n a n d is 
res p o nsi ble f or t he re vie w a n d si g n-off of t he cli nical trial pr ot oc ol.
Safet y  la b orat or y assess me nts will be perf or me d ce ntrally .  L o cal la b orat ories ma y be use d at t he 
discreti o n of t he I n vesti gat or as cli nicall y n ee de d f or safet y ma na ge me nt of t he s u bject, a n d res ults 
fr o m t he l ocal la b orat ories will be e ntere d i n t he electr o nic case re p ort f or ms (e C R Fs) per t he e C R F 
C o m pleti o n G ui deli nes; h o we ver, ce ntral la b orat or y res ults m ust als o be c ollecte d.  Uri nal ys is a n d 
uri ne pre g na nc y  testi n g will be d o ne l ocally o nl y .
 
 a n d 
 assess me nts will b e 
perf or me d u n der t he res p o nsi bilit y a n d / or s u per visi o n of t he S p o ns or.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
P P D
P P D
P P D
P P D
P P D
P P D
P P D
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 1 / 1 5 0
T he Gl o bal Dr u g Safet y De part me nt, Merc k K Ga A, Dar msta dt, Ger ma n y, or t heir desi g nate d 
re prese ntati ves will s u per vise dr u g safety a n d t he ti mel y re p orti n g of a d verse e ve nts ( A Es) a n d 
seri o us a d verse e ve nts (S A Es ).
Q ualit y  ass ura nce of t he trial c o n d uct will be perf or me d b y t he Researc h & De vel o p me nt Q ualit y 
De part me nt , Merc k K Ga A, Dar msta dt, Ger ma n y.
T he de part me nt of Gl o bal Bi ostatistics will s u per vise t he statistical a nal yses ( wit h t he e xce pti o n 
of t he 
 data a nal yses), w hic h will be o uts o urce d t o a C R O.   T he trial will a p pear i n t he f oll o wi n g 
cli nical trial re gistr y: Cli nical Trials.g o v
2. 3
Re vie w C o m mittees
2. 3. 1
I n de pe n de nt D at a M o nit ori n g C o m mittee
A n I n de pe n de nt Data M o nit ori n g 
C o m mittee (I D M C) will be c o m p ose d of a mi ni m u m of 
3 me m bers w h o d o n ot ha ve a n y  c o nflict of i nterests wit h t he trial S p o ns or, i ncl u di n g 2 cli nicia ns 
a n d a bi ostatisticia n.  The I D M C will peri o dicall y  re vie w safety data.  The f ull me m bers hi p, 
ma n date, a n d pr ocesses of t he I D M C will be detaile d i n t he I D M C c harter.
2. 3. 2
I n de pe n de nt R a di ol o gist
A n i n de pe n de nt ra di ol o gist verifies a n d c o nfir m s eli gi bilit y t o e nter t he Mai nte na nce P hase.
3
B ac k gr o u n d I nf or m ati o n
3. 1
G astric C a ncer
Gl o ball y , gastric ca ncer is t he fift h m ost c o m m o n ca ncer a n d t he t hir d lea di n g ca use of ca ncer 
deat h .  I n 2 0 1 2, t here were a p pr o xi matel y 95 0, 0 0 0 ne w cases a n d 7 2 3, 0 0 0 deat hs w orl d wi de 
(Ste wart 2 0 1 4 ). Of t hese ca ncers, a p pr o xi matel y 9 0 % t o 9 5 % were a de n ocarci n o mas wit h t he 
re mai ni n g 5 % t o 1 0 % c o m prisi n g of ne ur oe n d ocri ne t u m ors, l ym p h o mas, s q ua m o us cell ca ncer, 
a n d sarc o mas.
T he i nci de nce of gastric ca ncer varies wi del y  by c o u ntr y, wit h n o tr ue gl o bal sta n dar d treat me nt 
esta blis he d. Hi g her i nci de nce rates are o bser ve d i n Asia, C osta Rica, Per u, a n d Easter n E ur o pe, 
w hile Wester n E ur o pe a n d t he U S A ha ve l o wer i nci de nce rates (Gl o b oca n 2 0 1 2 ).
C he m ot hera p y is r o uti nel y use d t o treat metastatic gastric ca ncer; h o we ver, t here is n o si n gle 
sta n dar d re gi me n t hat is use d gl o ball y . C o m m o n che m ot hera p y a ge nts use d t o treat gastric ca ncer, 
eit her as m o n ot hera p y  or i n c o m bi nati o n, i ncl u de t he f oll o wi n g: fl u or o uracil ( 5-F U) a n d ot her 
fl u or o p yrimi di nes (e g, ca pecita bi ne, S 1), car m usti ne, se m usti ne a n d d o x or u bici n, mit o m y ci n C, 
cis plati n, o xali plati n, ta xa nes, a n d iri n oteca n. T he relati ve be nefits of t hese differe nt dr u gs, al o ne 
a n d i n c o m bi nati o n, are u nclear (N C C N 2 0 1 5 ). Rece ntl y , trast uz u ma b has bec o me a vaila ble f or 
use wit h c he m ot hera p y f or t he treat me nt of patie nts w h ose t u m ors o vere x press t he h u ma n 
e pi der mal gr o wt h fact or rece pt or 2 ge ne (H u dis 2 0 0 7 ). Des pite t he a vaila bilit y of t hese a ge nts,
ad va nce d, u nresecta ble, a n d/ or metastatic gastric ca ncer re mai ns a si g nifica nt u n met me dical nee d.
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 2 / 1 5 0
3. 2
Pr o gr a m me d De at h Rece pt or a n d Li g a n ds
T he pr o gra m me d deat h 1 ( P D -1) rece pt or a n d P D -1 li ga n ds 1 a n d 2 ( P D -L 1 , P D-L 2 ) pla y i nte gral 
r oles i n i m m u ne re g ulati o n.  E x presse d o n acti vate d T- cells, P D - 1 is acti vate d b y  PD- L 1 a n d 
P D -L 2  ex presse d b y  str o mal cells, t u m or cells, or b ot h, i nitiati n g T- cell deat h a n d l ocalize d 
i m m u ne s u p pressi o n (D o n g 1 9 9 9 ; D o n g 2 0 0 2 ; Free ma n 2 0 0 0 ; T o palia n 2 0 1 2a ), p ote ntiall y 
pr o vi di n g a n i m m u ne-t olera nt e n vir o n me nt f or t u m or de vel o p me nt a n d gr o wt h. 
 
 
I n t he cli nical setti n g, treat me nt wit h a nti b o dies t hat bl oc k t he P D- 1 – a nti-P D -L 1  interacti o n ha ve 
bee n re p orte d t o pr o d uce o bjecti ve res p o nse rates ( O R R) of 7 % t o 3 8 % i n patie nts wit h a d va nce d 
or metastatic s oli d t u m ors, wit h t olera ble safety pr ofiles (Ha mi d 2 0 1 3 ; Bra h mer 2 0 1 2 ; T o palia n 
2 0 1 2 b ). N ota bl y , res p o nses a p peare d pr ol o n ge d, wit h d urati o ns of 1 year or m ore f or t he maj ority 
of patie nts. Rece nt st u dies ha ve d oc u me nte d t he acti vit y of a nti-P D -L 1 a nti b o dies i n s u bjects wit h 
a d va nc e d gastric ca ncer (M ur o 2 0 1 4 ; L u tz k y 2 0 1 4).
3. 3
A vel u m a b
T he i n vesti gati o nal me dici nal pr o d uct (I M P) f or t he prese nt trial is a vel u ma b.  Avel u ma b is a f ull y 
h u ma n m o n ocl o nal a nti b o d y of t he i m m u n o gl o b uli n (I g) G 1 is ot y pe.  A vel u ma b selecti vel y bi n ds 
t o P D -L 1  an d c o m petiti vel y bl oc ks its i nteracti o n wit h P D - 1.  C o m pare d wit h a nti-P D -1 a nti b o dies 
t hat tar get T- cells, a vel u ma b tar gets t u m or cells a n d is t heref ore e x pecte d t o ha ve fe wer si de 
effects, i ncl u di n g a l o wer ris k of a ut oi m m u ne -relate d safety iss ues, as bl oc ka de of P D -L 1  lea ves 
t he P D -L 2 / P D-1 pat h wa y  intact t o pr o m ote peri p heral self-t olera nce (Latc h ma n 2 0 0 1 ).  For 
c o m plete details of t he i n vitr o a n d n o ncli nical trials, please refer t o t he I n vesti gat or’s Br oc h ure 
(I B).
I n li g ht of t he rece nt data de m o nstrati n g t he cli nical efficac y of a n a nti-P D -L 1  anti b o d y  in 
a d va nce d gastric ca ncer, a n d gi ve n t he cli nical i m p orta nce of P D-L 1 e x pressi o n i n gastric ca ncer 
t u m or cells ( O ki 2 0 1 4) a n d t he m o de of acti o n of a vel u ma b, a vel u ma b is bei n g de vel o pe d as a 
p ote ntial t hera py f or patie nts wit h vari o us a d va nce d s oli d t u m ors, i ncl u di n g gastric ca ncer.  T his 
a nti-P D -L 1 t hera pe utic a ntib o d y  co nce pt is i nte n de d t o be de vel o pe d i n o nc ol o gical setti n gs b y  
Merc k K Ga A, Dar msta dt, Ger ma n y, a n d b y its s u bsi diar y, E M D Ser o n o R & D.
T he o n g oi n g trials f or a vel u ma b are descri be d i n t he I B.  A vel u ma b is c urre ntl y in cli nical 
de vel o p me nt wit h 2 o n g oi n g P hase I trials i n s u bjects wit h s oli d t u m ors, o ne o n g oi n g P hase II trial 
i n Mer kel cell carci n o ma ( M C C), a n d 2 P hase III trials i n n o n- s mall cell l u n g ca ncer ( N S C L C).  
Of t he o n g oi n g st u dies, 2 of t hese st u dies ha ve c o h orts of patie nts wit h a d va nce d gast ric ca ncer:

Trial E M R 1 0 0 0 7 0 - 0 0 1 is “a P hase I, o pe n -la bel, m ulti ple -asce n di n g d ose trial t o i n vesti gate t he 
safety, t olera bilit y, P K, bi ol o gical, a n d cli nical acti vit y of a vel u ma b i n s u bjects wit h metastatic 
or l ocall y  a d va nce d s oli d t u m ors.”

Trial E M R 1 0 0 0 7 0- 0 0 2 is “a P hase I trial t o i n vesti gate t he t olera bilit y, safet y, P K, bi ol o gical, 
a n d cli nical acti vit y of a vel u ma b i n Ja pa nese s u bjects wit h metastatic or l ocall y a d va nce d s oli d 
t u m ors, wit h e x pa nsi o n part i n Asia n s u bjects wit h gastric ca ncer.”
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 3 / 1 5 0
I n a d diti o n t o t he trial descri be d i n t his pr ot oc ol, E M R 1 0 0 0 7 0 - 0 0 7, a n ot her P hase III st u d y in 
patie nts wit h a d va nce d gastric ca ncer ( E M R 1 0 0 0 7 0 - 0 0 8) is o n g oi n g f or t hir d-li ne treat me nt.  
3. 3. 1
S afet y
A vaila ble safet y a n d efficac y data f or t he a vel u ma b pr o gra m are disc usse d i n t he I B a n d esta blis h 
a p ositi ve be nefit ris k f or c o n d ucti n g P hase III st u dies wit h 1 0 m g/ k g (t he d osi n g use d i n t his trial).  
T he safety pr ofile of a vel u ma b has bee n e val uate d fro m data of m ore t ha n 1, 7 5 0 s u bjects, i ncl u di n g 
all
s u bjects treate d wit h 
1 0 m g/ k g 
fr o m st u dies E M R 1 0 0 0 7 0 - 0 0 1 ( 1, 6 5 0 s u bjects) a n d 
E M R 1 0 0 0 7 0 -0 0 3 Part A ( 8 8 s u bjects as p o ole d safet y dataset wit h a data c ut -off of 0 9 J u ne 2 0 1 6) 
a n d s u bjects i n t he o n g oi n g l ocal Ja pa nese P hase I E M R 1 0 0 0 7 0 - 0 0 2.  T he se safety data fr o m 
s u bjects wit h differe nt t u m or t ypes treate d wit h a vel u ma b s u g gests a n acce pta ble safet y pr ofile of 
t he c o m p o u n d.  M ost of t he o bser ve d e ve nts were eit her i n li ne wit h t h ose e x pecte d i n s u bjects 
wi t h a d va nce d s oli d t u m ors or wit h si milar class effects of m o n ocl o nal a nti b o dies bl oc ki n g t he 
P D -1/ P D -L 1  axis .  I nf usi o n-relate d reacti o ns i ncl u di n g dr u g h y perse nsiti vit y  reacti o ns, a n d 
i m m u ne-me diate d 
a d verse reacti o ns (i m m u ne-relate d p ne u m o nitis, i m m u ne-relate d c olitis, 
i m m u ne-relate d he patitis, 
i m m u ne-relate d e n d ocri n o pat hies 
[t h yr oi d dis or ders, 
a dre nal 
i ns ufficie nc y, ne w o nset T y pe I dia betes mellit us, pit uitar y  dis or ders], i m m u ne-relate d ne p hritis, 
a n d re nal d y sf u ncti o n a n d ot her i m m u ne-relate d A Es [ m yo sitis, m y ocar ditis, G uillai n -Barre 
s yn dr o me, u veitis] ) ha ve bee n i de ntifie d as i m p orta nt ris ks f or a vel u ma b ( please see c urre nt I B f or 
details).  Detaile d g ui deli nes f or t he ma na ge me nt of i m m u ne-relate d A Es a n d i nf usi o n-relate d 
reacti o ns ha ve bee n i m ple me nte d i n t he st u d y pr ot oc ols, i ncl u di n g t his o ne ( please see Secti o n 3. 5 , 
Secti o n 5. 1. 2. 2. 1,  Secti o n 5. 1. 3. 2,  Secti o n 6. 2. 1,  Secti o n 6. 4,  Secti o n 6. 5. 4 , Secti o n 6. 5. 5,  a n d 
Secti o n 6. 1 2 ).
3. 3. 2
P h ar m ac o k i netic Res ults
Draft 
P K 
assess me nts ha ve bee n perf or me d i n o n g oi n g Trials 
E M R 1 0 0 0 7 0 - 0 0 1 a n d 
E M R 1 0 0 0 7 0- 0 0 2. T he preli mi nar y  res ults base d o n t he data a vaila ble as of 1 9 Dece m ber 2 0 1 4 
are prese nte d u n der t he i n di vi d ual trial hea di n gs.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 4 / 1 5 0
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 5 / 1 5 0
3. 4
R ati o n ale f or t he C urre nt Cli nic al Tri al
T he safet y an d cli nical efficac y of a vel u ma b ha ve bee n deter mi n e d i n m ulti ple t u m or t ypes 
(N S C L C, o varia n ca ncer, mes ot heli o ma, mela n o ma, t h ym o ma, a n d a dre n oc ortic ocarci n o ma) 
(Disis 2 0 1 5 , G ulle y  2 0 1 5).  T he rati o nale t o e nr oll s u bjects wit h u nresecta ble l ocall y  ad va nce d or 
metastatic a de n ocarci n o ma of t he st o mac h or gastr oes o p ha geal j u ncti o n ( G EJ) is s u p p orte d b y  data 
re p orte d fr o m ot her P D -1/ P D -L 1  age nts a n d fr o m 2 e x pa nsi o n c o h orts i n 2 a vel u ma b P hase I 
st u dies.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 6 / 1 5 0
3. 4. 1
D at a fr o m A nti -P D -1/ P D -L 1 T her a pies i n G astric C a ncer
Data fr o m ot her a nti -P D -1/ P D -L 1  t hera pies i n gastric ca ncer are as f oll o ws:

Data prese nte d at t he A merica n S ociet y f or Cli nical O nc ol o g y  An n ual Meeti n g 2 0 1 4 fr o m a 
P hase I e x pa nsi o n c o h ort of 1 6 s u bjects wit h gastr oes o p ha geal ca ncer treate d wit h M E DI 4 7 3 6 
(a nti-P D -L 1), w hic h re p orte d 4 o u t of 1 6 res p o n ders (L utz k y  2 0 1 4).

Data prese nte d at t he E ur o pea n S ociet y f or Me dical O nc ol o g y  An n ual Meeti n g 2 0 1 4 fr o m a 
P hase I c o h ort of 3 9 P D -L 1 + s u bjects wit h a d va nce d gastric ca ncer treate d wit h a nti-P D -1 
( Ke yn ote 0 1 2), w hic h re p orte d 1 2 o ut of 3 9 res p o n ders (M ur o 2 0 1 4 ).
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 7 / 1 5 0
3. 5
S u m m ar y of t he O ver all Be nefit a n d Ris k
Base d o n t he n o ncli nical a n d P hase I data a vaila ble t o date, t he c o n d uct of t he trial is c o nsi dere d 
j ustifia ble usi n g t he d ose a n d d ose re gi me n of t he a vel u ma b as s pecifie d i n t his cli nical trial 
pr ot oc ol. A n I D M C ( see Secti o n  2. 3. 1) will assess t he ris k-be nefit rati o o n a n o n g oi n g basis. T he 
trial will be disc o nti n ue d i n t he e ve nt of a n y ne w fi n di n gs t hat i n dicate a rele va nt deteri orati o n of 
t he ris k-be nefit relati o ns hi p t hat w o ul d re n der c o nti n uati o n of t he trial u nj ustifia ble.
T he pri mar y  k n o w n i de ntifie d ris ks of e x p os ure t o a vel u ma b i ncl u de:

I nf usi o n-relate d reacti o ns

I m m u ne-relate d a d verse e ve nts (ir A Es).
T o miti gate t he ris k of i nf usi o n-relate d reacti o ns, p re me dicate patie nts wit h a n a nti hista mi ne a n d 
wit h paraceta m ol (aceta mi n o p he n) pri or t o t he first 4 i nf usi o ns of a vel u ma b. Pre me dicati o n s h o ul d 
be 
a d mi nistere d f or s u bse q ue nt a vel u ma b d oses 
base d 
u p o n 
cli nical j u d g me nt a n d 
pre se nce/se verit y of pri or i nf usi o n reacti o ns.  T his re gi me n m a y  be m o difie d base d o n l ocal 
treat me nt sta n dar ds a n d g ui deli nes as a p pr o priate pr o vi de d it d oes n ot i ncl u de s yste mic 
c ortic oster oi ds .
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 8 / 1 5 0
I n a d diti o n, si nce a vel u ma b ca n i n d uce a nti b o d y-de pe n de nt cell-me diate d c yt ot o xicit y ( A D C C), 
t here is a p ote ntial ris k of t u m or l ysis s yn dr o me (see Secti o n  6. 5. 4. 3) .  
As n ote d i n Secti o n  3. 2 , trials wit h a nti b o dies t hat bl oc k t he P D- 1 – P D -L 1 i nteracti o n ha ve bee n 
re p orte d t o pr o d uce O R R of 7 % t o 3 8 % i n patie nts wit h a d va nce d or metastatic s oli d t u m o rs, wit h 
res p o nse d urati o ns of 1 year or m ore f or t he maj orit y of patie nts.
T his cli nical trial will be c o n d ucte d i n c o m plia nce wit h t he cli nical trial pr ot oc ol, I CH G C P, a n d 
t he a p plica ble nati o nal re g ulat or y re q uire me nts.
4
Tri al O bjecti ves
4. 1
Pri m ar y O bjecti ves

T he pri mar y  o bjecti ves of t his trial are t o de m o nstrate s u peri orit y of mai nte na nce t hera p y wit h 
a vel u ma b vers us c o nti n uati o n of first -li ne c he m ot hera p y wit h re gar d t o O verall S ur vi val (O S )
i n all ra n d o mize d s u bjects or i n P D -L 1 + s u bjects w h o ha ve n ot pr o gresse d o n first-li ne 
c he m ot hera p y.
4. 2
Sec o n d ar y O bjecti ves
Sec o n dar y  o bjecti ves are as f oll o ws:

T o de m o nstrate s u peri orit y of mai nte na nce t hera p y wit h a vel u ma b vers us c o nti n uati o n of 
first-li ne c he m ot hera p y wit h re gar d t o P F S as per R E CI S T v 1. 1 acc or di n g t o I n vesti gat or 
assess me nt.

T o de m o nstrate s u peri orit y of mai nte na nce t hera p y wit h a vel u ma b vers us c o nti n uati o n of 
first-li ne c he m ot hera p y wit h re gar d t o t he O R R as per R E CI S T v 1. 1 a n d per I nvesti gat or 
assess me nt

T o c o m pare t he s u bject-re p orte d o utc o mes / q ualit y of life ( Q o L) of s u bjects w he n treate d wit h 
a vel u ma b vers us c o nti n uati o n of first-li ne c he m ot hera p y as assesse d b y  t he E ur o pea n Q o L
5- di me nsi o ns 5 Le vel Q uesti o n naire (E Q - 5 D-5 L ), a n d t he E ur o pea n Or ga nizati o n f or Researc h 
a n d Treat me nt of Ca ncer ( E O R T C) Q L Q -C 3 0 a n d m o d ule Q L Q -S T O 2 2

T o deter mi ne t he safe t y a n d t olera bilit y of a vel u ma b.
D oc u me nt N o. 
O bject N o.
C CI
C CIC CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
4 9 / 1 5 0
5
I n vesti g ati o n al Pl a n
5. 1
O ver all Tri al Desi g n a n d Pl a n
T his is a m ultice nter, i nter nati o nal, ra n d o mize d, o pe n -la bel P hase III trial c o m pari n g mai nte na nce 
t hera py wit h a vel u ma b wit h c o nti n uati o n of first -li ne c he m ot hera py i n s u bjects wit h u nresecta ble, 
l ocall y ad va nce d or met astatic, a de n ocarci n o ma of t he st o mac h, or of t he G EJ ( See Secti o ns 5. 1. 2. 1
a n d 5. 1. 2. 2 f or details).
T he me dici nal pr o d ucts o xali plati n, 5- F U a n d ca pecita bi ne are use d as c he m ot hera p y age nts i n t he 
I n d ucti o n P hase a n d t he Mai nte na nce P hase of t his trial.  All t hree s u bsta nces are acce pte d as 
sta n dar d of treat me nt f or t he i n dicati o n u n der st u d y. Bef ore a d mi nisteri n g a n y of t hese s u bsta nces, 
t he In vesti gat or is re q uire d t o refer t o w hat is state d i n t he c urre nt pr o d uct i nf or mati o n (l ocal la bel, 
S u m mar y  of Pr o d uct C haracteristics [ S m P C]), partic ularl y i n re gar d t o c o ntrai n dicati o ns, war ni n gs 
a n d preca uti o ns f or use, d osa ge a dj ust me nts i n t he e ve nt of t o xicit y, pat ie nt m o nit ori n g pr o visi o ns, 
t he d urati o n of t he nee d f or c o ntrace pti o n, a n d me dici nal pr o d ucts t hat are pr o hi bite d or t hat m ust 
be use d wit h ca uti o n.  In case of a p ote ntial c o ntra dicti o n bet wee n t he s pecificati o ns o utli ne d i n 
t his cli nical trial pr ot oc ol a n d t he i nf or mati o n c o ntai ne d i n t he pr o d uct i nf or mati o n (l ocal la bel, 
S m P C) of o xali plati n, 5 -F U, or ca pecita bi ne, t he l ocal la bel al wa ys pre vails.  I n vesti gat ors s h o ul d 
c hec k u p date d la beli n g via rele va nt we bsites bef ore e nr oll me nt, ra n d o mizati o n, a n d c h e m ot hera p y 
a d mi nistrati o n i n t he In d ucti o n P hase a n d t he Mai nte na nce P hase.  
T his st u d y  is c o n d ucte d wit h a S cree ni n g peri o d a n d a n I n d ucti o n P hase, Mai nte na nce P hase, a n d 
F oll o w -u p P hase.
5. 1. 1
O ver all Desi g n
A p pr o xi matel y  46 6 s u bjects are pla n ne d t o be e nr olle d i n t he M ai nte na nce P hase. T he act ual 
n u m ber of s u bjects e nr olle d i n t he I n d ucti o n P hase will be dri ve n b y  obser ve d i n d ucti o n fail ure 
rates a n d will be s uc h t o all o w f or a p pr o xi matel y 4 6 6 patie nts t o be ra n d o mize d i n t he M ai nte na nce 
P hase.   At t he ti me of t his pr ot oc ol a me n d me nt, s u bject e nr oll me nt i n t he Mai nte na nce P hase is 
c o m plete, wit h 4 9 9 s u bjects ra n d o mize d i nt o t he Mai nte na nce P hase.
S u bjects e nr olle d i n t he 
In d ucti o n P hase will recei ve a first-li ne t hera p y c o m prise d of o xali plati n a n d eit her 5- F U or 
ca pecita bi ne (I n d ucti o n P hase) f or 1 2 wee ks (see Secti o n 5. 1. 2. 1). 
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 0 / 1 5 0
F oll o wi n g t he I n d ucti o n P hase, s u bjects w h o e x perie nce a C R, P R, or S D after 1 2 wee ks 
(a p pr o xi matel y 4 6 6 s u bjects) will be ra n d o ml y assi g ne d ( Mai nte na nce P hase) t o recei ve eit her 
avel u ma b (see Secti o n  5. 1. 2. 2. 1) or c o nti n uati o n of t he sa me re gi me n of c he m othera p y fr o m t he 
I n d ucti o n P hase (see Secti o n  5. 1. 2. 2. 2 ). S u bjects w h o are n ot dee me d eli gi ble t o recei ve f urt her 
c he m ot hera p y will recei ve best s u p p orti ve care ( B S C) al o ne wit h n o acti ve t hera p y.
Pri or t o ra n d o mizati o n, In vesti gat ors m ust s pecif y w hic h of treat me nts (c o nti n uati o n of t he sa me 
re gi me n of c he m ot hera p y fr o m the I n d ucti o n P hase vers us B S C) will be selecte d f or s u bjects i n 
c he m ot hera p y c o ntr ol ar m.  
 
 
 
 
After t he I n d ucti o n P hase, all s u bjects will b e 
e val uate d f or eli gi bilit y i nt o t he Mai nte na nce P hase b y an i n d e pe n de nt ra di ol o gist usi n g R E CI S T 
v 1. 1.  
St u d y  treat me nt will c o nti n ue u ntil:

Disease pr o gressi o n (see Secti o n 5. 5. 1)

Si g nifica nt cli nical deteri orati o n (cli nical pr o gressi o n) b y  In vesti gat or’s o pi ni o n

U nacce pta ble t o xicit y per I n vesti gat or o pi ni o n, or

A n y  criteri o n f or wit h dra wal fr o m t he trial or trial treat me nt is f ulfille d (see Secti o n 5. 5).
S u bjects recei vi n g a vel u ma b ma y  co nti n ue treat me nt past t he i nitial deter mi nati o n of disease 
pr o gressi o n per R E CI S T v 1. 1 as l o n g t he f oll o wi n g criteria are met:

I n vesti gat or-assesse d cli nical be nefit, wit h o ut a n y ra pi d disease pr o gressi o n

T olera nce of trial treat me nt

Sta ble Easter n C o o perati ve O nc ol o g y  Gr o u p (E C O G ) perf or ma nce stat us (P S ) ( P S = 0 or 1)

Treat me nt b e y o n d pr o gressi o n will n ot dela y a n i m mi ne nt i nter ve nti o n t o pre ve nt seri o us 
c o m plicati o ns of disease pr o gressi o n (f or e xa m ple, ce ntral ner v o us s ys te m metastases).
T he decisi o n t o c o nti n ue a vel u ma b treat me nt be y o n d pr o gressi o n s h o ul d be disc usse d wit h t he 
M e dical M o nit or a n d d oc u me nte d i n t he st u d y rec or ds.
F or s u bjects c o nti n ui n g a vel u ma b after i nitial pr o gressi ve disease (P D ), a ra di o gra p hic assess me nt 
s h o ul d be perf or me d wit hi n 6 wee ks of ori gi nal P D t o deter mi ne w het her t here has bee n a decrease 
i n t he t u m or size, or c o nti n ue d P D.  The assess me nt of cli nical be nefit s h o ul d be bala nce d b y  
cli nical j u d g me nt as t o w het her t he s u bject is cli nicall y deteri orati n g a n d u nli kel y  to recei ve a n y 
be nefit fr o m c o nti n ue d treat me nt wit h a vel u ma b.
F or s u bjects recei vi n g a vel u mab, if disc o nti n uati o n occ urs d ue t o pr o gressi o n a n d a defi niti ve 
dia g n osis/ra di o gra p hic c o nfir mati o n is n ot ma de at t he ti me of disc o nti n uati o n, a sec o n d i ma gi n g 
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 1 / 1 5 0
sca n m a y  be all o we d f or c o nfir mati o n of pr o gressi o n.  If pr o gressi o n at t he sec o n d i ma gi n g scan 
is n ot c o nfir me d a n d t he s u bject wis hes t o restart, t he s u bject will be all o we d t o c o nti n ue recei vi n g 
a vel u ma b as l o n g as t he y meet t he criteria f or c o nti n uati o n of treat me nt be y o n d pr o gressi o n. 
If t he I n vesti gat or feels t hat t he s u bject c o nti n ues t o achie ve cli nical be nefit b y  co nti n ui n g 
treat me nt, t he s u bject s h o ul d re mai n o n t he trial a n d c o nti n ue t o recei ve m o nit ori n g acc or di n g t o 
t he Sc he d ule of Assess me nts (Ta ble 3 ).
A n y  a d diti o nal c o nti n uati o n of a vel u ma b pl us B S C be y o n d f urt her pr o gressi o n m ust be disc usse d 
a n d a gree d u p o n wit h t he M e dical M o nit or.  Furt her disease pr o gressi o n is defi ne d as a n a d diti o nal 
i ncrease i n t u m or b ur de n of 2 0 % a n d ≥ 5 m m a bs ol ute i ncrease i n t u m or b ur de n fr o m ti me of i nitial 
P D.   T his i ncl u des a n i ncrease i n t he s u m of all tar get lesi o ns a n d/ or t he de vel o p me nt of ne w 
meas ura ble lesi o ns.
S u bjects recei vi n g a vel u ma b w h o ha ve e x perie nce d a C R s h o ul d be treate d f or a mi ni m u m of 
1 2 m o nt hs or u ntil disease pr o gressi o n or u nacce pta ble t o xicit y, after c o nfir mati o n of res p o nse. I n 
case a s u bject wit h a c o nfir me d C R rela pses after st o p pi n g treat me nt, b ut pri or t o t he e n d of t he 
trial, 1 re-i nitiati o n of treat me nt is all o we d at t he discreti o n of t he I n vesti gat or a n d after a gree me nt 
wit h t he Me dical M o nit or. 
T o be eli gi ble f or retreat me nt, t he s u bject m ust n ot ha ve e x perie nce d 
a n y to xicit y  that le d t o treat me nt disc o nti n uati o n of t he i nitial a vel u ma b t hera py. S u bjects w h o 
re-i nitiate treat me nt will sta y o n trial a n d will be treate d a n d m o nit ore d acc or di n g t o t he pr ot oc ol 
a n d f oll o w t he Sc he d ule of Assess me nts u ntil disease pr o gressi o n (see Ta ble 3 ).
S u bjects recei vi n g mai nte na nce
c he m ot hera p y will recei ve trial treat me nt u ntil P D per R E CI S T 
v ersi o n 1. 1, f or t he acce pte d ma xi mal d urati o n of t he a ge nt(s) selecte d, si g nifica nt cli nical 
deteri orati o n (cli nical pr o gressi o n), u nac ce pta ble t o xicit y, wit h dra wal of c o nse nt, or if a n y 
criteri o n f or wit h dra wal fr o m t he trial or trial treat me nt is f ulfille d.   
O n -st u d y su bject ma na ge me nt a n d st u d y en d p oi nt e val uati o n will be base d o n I n vesti gat or 
assess me nts (see Secti o n 7. 3).
S u bjects will atte n d cli nic visits at re g ular i nter vals t o recei ve trial treat me nt a n d f or efficac y  an d 
safety assess me nts (see Secti o n  7. 1 ).
T he pri mar y e n d p oi nt of t he trial is O S , defi ne d as t he ti me (i n m o nt hs) fr o m ra n d o mizati o n t o t he 
date of deat h, re gar dless of t he act ual ca use of t he s u bject’s deat h. T he pri mar y  e n d p oi nt O S will 
be teste d i n all ra n d o mize d s u bjects (i nte nt-t o-treat [I T T] A nal y sis Set ) a n d i n P D -L 1 + s u bjects 
( P D-L 1 + A nal y sis Set) .
T he P D -L 1 e x pressi o n stat us will be deter mi ne d acc or di n g t o t he 
c o n ve nti o nal t u m or-cell (cell n u m ber -base d perce nta ge) sc ori n g met h o d w here s u bjects wit h 
P D -L 1  t u m or e x pressi o n ≥1 % are c o nsi dere d t o be P D -L 1 +.
Safet y  e n d p oi nts i ncl u de A Es, assesse d t hr o u g h o ut t he trial a n d e val uate d usi n g t he N CI-C T C A E 
v 4. 0 3; p h y sical e xa mi nati o ns; cli nical la b orat or y assess me nts; c o nc o mita nt me dicati o ns ; vital 
si g ns; electr ocar di o gra m ( E C G) para meters; a n d E C O G P S .
T he trial desi g n sc he matic is prese nte d i n  Fi g ure 1.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 2 / 1 5 0
Fi g ure 1 
Sc he m atic of Tri al Desi g n
All s u bjects i n b ot h ar ms will recei ve B S C as bac k gr o u n d t hera p y as s pecifie d i n Secti o n  6. 1. 4 .
B S C = best s u p p orti ve care; 5- F U = 5-f l u or o uracil; n = n u m ber of s u bjects; P D = pr o gressi ve disease .
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 3 / 1 5 0
5. 1. 2
Tri al tre at me nt A d mi nistr ati o n a n d Sc he d ule
T he trial Sc he d ule of Assess me nts are prese nte d i n Ta ble 1 t o Ta ble 7.
5. 1. 2. 1
I n d ucti o n C he m ot her a p y
S u bjects e nr olle d i n t his trial will start wit h a 1 2 -wee k c he m ot hera p y I n d ucti o n P hase c o m prise d 
of o xali plati n a n d eit her 5- F U or ca pecita bi ne (acc or di n g t o t he d osi n g sc he d ule i n S ecti o n 6. 2. 2
a n d Ta ble 1 a n d Ta ble 2 or i n acc or da nce t o t he la bel i nstr ucti o ns a n d per l ocal g ui deli nes ).

O xali plati n at 8 5 m g/ m 2 I V on D a y  1 wit h le uc o v ori n 2 0 0 m g/ m 2 I V o n Da y  1 ( or e q ui vale nt 
le v ole uc o v ori n d ose ) f oll o we d b y  5-F U at 2 6 0 0 m g/ m 2 I V c o nti n u o us i nf usi o n o ver 2 4 h o urs 
o n Da y  1, gi ve n e ver y 2 wee ks (f or u p t o 1 2 wee ks, Ta ble 2) .
O R
O xali plati n at 8 5 m g/ m 2 I V on D a y  1 wit h le uc o v ori n 4 0 0 m g / m2 I V on Da y 1 ( or e q ui vale nt 
le v ole uc o v ori n d ose) f oll o we d b y  5-F U at 4 0 0 m g/ m 2 I V pus h o n Da y  1 an d 2 4 0 0 m g/ m 2 I V 
c o nti n u o us i nf usi o n o ver 4 6- 4 8 h o urs ( Da ys 1 a n d 2) gi ve n e ver y 2 wee ks (f or u p t o 1 2 wee ks)
O R

O xali plati n at 1 3 0 m g/ m 2 IV o n D a y 1 wit h ca pecita bi ne at 1 0 0 0 m g / m2, t wice dail y  for 2 wee ks 
f oll o we d by a 1 -wee k rest peri o d gi ve n e ver y  3 wee ks (f or u p t o 1 2 wee ks, Ta ble 1 ).
L ocal la bel a n d g ui deli nes s h o ul d be f oll o we d f or s pecific starti n g d oses d ue t o re nal or he patic 
i m pair me nts a n d f or s u bse q ue nt d ose m o dificati o ns d ue t o differe nt t o xicities.
S u bjects w h o e x perie nce a C R, P R , or S D after 1 2 wee ks will be ra n d o ml y assi g ne d t o eit her 
avel u ma b or c o nti n ue t he sa me re gi me n of c he m ot hera p y fr o m t he I n d ucti o n P hase .  S u bjects w h o 
de m o nstrate a res p o nse d uri n g t he I n d ucti o n P hase t hat re n ders t heir meas ura ble disease n o l o n ger 
meas ura ble at t he ti me of t he Mai nte na nce P ha se ca n be ra n d o mize d .
5. 1. 2. 2
M ai nte n a nce T her a p y
5. 1. 2. 2. 1
A vel u m a b Ar m
S u bjects ra n d o ml y  assi g ne d t o t he a vel u ma b ar m will recei ve I V i nf usi o n of a vel u ma b ( 1 0 m g/ k g 
o ver 1 h o ur) o nce e ver y  2 wee ks (see Ta ble 6) . 
T o miti gate i nf usi o n-relate d reacti o ns, pre me dicate patie nts wit h a n a nti hista mi ne a n d wit h 
paraceta m ol (aceta mi n o p he n) pri or t o t he first 4 i nf usi o ns of a vel u ma b. Pre me dicati o n s h o ul d be 
a d mi nistere d f or s u bse q ue nt a vel u ma b d oses base d u p o n cli nical j u d g me nt a n d prese nce/se verit y 
of pri or i nf usi o n reacti o ns.  T his re gi me n ma y be m o difie d base d o n l ocal treat me nt sta n dar ds a n d 
g ui deli nes as a p pr o priate pr o vi de d it d o es n ot i ncl u de s yste mic c ortic oster oi ds.
T he f or m ulati o n a n d pac ka gi n g i nf or mati o n of a vel u ma b is pr o vi de d i n Secti o n  6. 1. 2, Secti o n 6. 1. 1
a n d Secti o n 6. 6, res pecti vel y.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 4 / 1 5 0
5. 1. 2. 2. 2
C he m ot her a p y Ar m
S u bjects ra n d o ml y assi g ne d t o t he m ai nte na nce c he m ot hera p y ar m will recei ve first-li ne 
c he m ot hera p y acc or di n g t o t he d osi n g sc he d ule (see Secti o n 6. 2 a n d Ta ble 3 t o Ta ble 4) or i n 
acc or da nce t o t he la bel i nstr ucti o ns a n d p er l ocal g ui deli nes ) u ntil disease pr o gressi o n, 
u nacce pta ble t o xicit y, f or t he acce pte d ma xi mal d urati o n of t he a ge nt(s) selecte d, or a n y of t he 
criteria f or wit h dra wal fr o m trial treat me nt is f ulfille d ( Secti o n  5. 5 ).
T he d ose a n d sc he d ule d uri n g t he Mai nte na nce P hase are as f oll o ws:
S u bjects 
ra n d o ml y 
assi g ne d t o c he m ot hera p y 
will c o nti n ue 
t he sa me re gi me n of 
o xali plati n -fl u or o p yri mi di ne d o u blet as t he y recei ve d d uri n g t he I n d ucti o n P hase u ntil disease 
pr o gressi o n.

S u bjects w h o are n ot dee me d eli gi ble t o recei ve f urt her c he m ot hera p y will recei ve B S C 
al o ne wit h n o acti ve t hera p y.  Pri or t o ra n d o mizati o n, I n vesti gat ors m ust s pecif y BS C 
treat me nt f or t hese s u bjects (see Ta ble 5)

F or s u bjects recei vi n g c he m ot hera p y ( o xali plati n + 5- F U or o xali plati n + ca pecita bi ne), 
d ose m o dificati o ns after t he starti n g d ose are all o we d if t he c o nti n uati o n of t he o xali plati n -
fl u or o p yri mi di ne d o u blet , or a c o m p o ne nt t here of, is pr o hi bite d b y  to xicit y .  F or s u bjects 
i nt olera nt t o f urt her o xali plati n, si n gle-a ge nt ca pecita bi ne or 5 -F U + le uc o v ori n will be a n 
o pti o n f or d ose m o dificati o n.
A d diti o nall y , i n or der t o re d uce t he i nci de nce a n d se verity of na usea a n d v o miti n g as well as t he 
se verity of h y perse nsiti vit y  reacti o ns, s u bjects will be a d mi nistere d pretreat me nt pri or t o eac h 
t hera py i nf usi o n per l ocal i nstit uti o nal practice.
5. 1. 3
D ose M o dific ati o n 
a n d A d verse Dr u g Re acti o ns Re q uiri n g 
Tre at me nt Disc o nti n u ati o n
5. 1. 3. 1
D ose M o dific ati o n f or A vel u m a b
T he d ose of a vel u ma b will be calc ulate d base d o n t he wei g ht of t he s u bject deter mi ne d wit hi n 
7 2 h o urs pri or t o t he da y of dr u g a d mi nis trati o n. T he d ose of a vel u ma b use d f or t he pre vi o us 
a d mi nistrati o n ca n be re peate d if t he c ha n ge i n t he s u bject’s wei g ht is 1 0 % or less t ha n t he wei g ht 
use d f or t he last d ose calc ulati o n.
Eac h s u bject will sta y on t he a vel u ma b-assi g ne d d ose of 1 0 m g/ k g u n less treat me nt nee ds t o be 
st o p pe d. D osi n g m o dificati o ns (c ha n ges i n i nf usi o n rate) a n d d ose dela y s are descri be d i n 
Secti o n 5. 1. 3. 2 a n d Secti o n  6. 5. 4. 1. T here will be n o d ose re d ucti o ns.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 5 / 1 5 0
5. 1. 3. 2
A d verse 
Dr u g 
Re acti o ns 
Re q uiri n g 
A vel u m a b 
Disc o nti n u ati o n or M o dific ati o ns
T he f oll o wi n g a d verse dr u g reacti o ns ( A D Rs, see Secti o n 7. 4. 1. 1 ) re q uire per ma ne nt treat me nt 
disc o nti n uati o n of a vel u ma b:

A n y  Gra de 4 A D Rs re q uire treat me nt disc o nti n uati o n wit h a vel u ma b e xce pt f or si n gle 
la b orat or y val ues o ut of n or mal ra n ge t hat are u nli kel y relate d t o trial treat me nt as assesse d b y 
t he I nvesti gat or, d o n ot ha ve a n y cli nical c orrelate, a n d res ol ve wit hi n 7 da y s wit h a de q uate 
me dica l ma na ge me nt.

A n y  Gra de 3 A D Rs re q uire treat me nt disc o nti n uati o n wit h a vel u ma b e xce pt f or a n y of t he 
f oll o wi n g: 

Tra nsie nt (≤ 6 h o urs) Gra de 3 fl u-li ke s ym pt o ms or fe ver, w hic h are c o ntr olle d wit h me dical 
ma na ge me nt

Tra nsie nt (≤ 2 4 h o urs) Gra de 3 fati g ue, l ocal reacti o ns, hea dac he, na usea, or e mesis t hat 
res ol ve t o Gra de ≤ 1 

Si n gle la b orat or y val ues o ut of n or mal ra n ge (e xcl u di n g Gra de ≥ 3 li ver f u ncti o n test 
i ncrease) t hat are u nli kel y  relate d t o trial treat me nt acc or di n g t o t he I n vesti gat or, d o n ot ha ve 
a n y cli nical c orrelate

Gra de 3 s ki n t o xicit y

T u m or flare p he n o me n o n defi ne d as l ocal pai n, irritati o n, or ras h l ocalize d at sites of k n o w n 
or s us pecte d t u m or

C ha n ge i n E C O G P S t o ≥ 3 t hat res ol ves t o ≤ 2 wit hi n 1 4 da y s (i nf usi o ns s h o ul d n ot be gi ve n 
o n t he f oll o wi n g c ycle, if t he E C O G P S is ≥ 3 o n t he da y  of trial treat me nt a d mi nistrati o n).

As y m pt o matic 
Gra de 
≥ 3 li pase or a m ylase ele vati o n n ot ass ociate d wit h 
cli nical 
ma nifestati o ns of pa ncreatitis. Me dical M o nit or m ust be c o ns ulte d f or s uc h li pase a n d 
a m yl ase a b n or malities .

A n y  Gra de 2 A D R s h o ul d be ma na ge d as f oll o ws:

If a Gra de 2 A D R res ol ves t o Gra de ≤ 1 b y  t he last da y of t he c urre nt c ycle, treat me nt ma y 
c o nti n ue.

If a Gra de 2 A D R d oes n ot res ol ve t o Gra de ≤ 1 b y  the last d a y  of t he c urre nt c ycle, i nf usi o ns 
s h o ul d n ot be gi ve n o n t he f oll o wi n g c ycle.  If at t he e n d of t he f oll o wi n g c ycle t he e ve nt 
has n ot res ol ve d t o Gra de 1, t he s u bject s h o ul d per ma ne ntl y disc o nti n ue treat me nt wit h a n 
a vel u ma b A D R (e xce pt f or h or m o ne i ns ufficie ncies, t hat ca n be ma na ge d b y  re place me nt 
t hera py;  f or t hese h or m o ne i ns ufficie ncies, u p t o 2 s u bse q ue nt d oses ma y be o mitte d).

U p o n t he sec o n d occ urre nce of t he sa me Gra de 2 A D R (e xce pt f or h or m o ne i ns ufficie ncies 
t hat ca n be ma na ge d b y re place me nt t hera p y) i n t he sa me s u bject, treat me nt wit h a vel u ma b 
has t o be per ma ne ntl y  disc o nti n ue d.
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 6 / 1 5 0
I nf usi o n-relate d reacti o ns, h y perse nsiti vit y  reacti o ns , a n d fl u-li ke s ym pt o ms ( Gra des 1 t o 4), t u m or 
l ysis s yn dr o me, a n d ir A Es s h o ul d be ha n dle d acc or di n g t o g ui deli nes i n Secti o n  6. 5. 4. 1, Secti o n
6. 5. 4. 2,  Secti o n 6. 5. 4. 3, a n d Secti o n  6. 5. 4. 4.
5. 1. 3. 3
D ose M o dific ati o n f or C he m ot her a p y
D uri n g t he I n d ucti o n P hase, d ose m o dificati o ns ( d ose dela y s a n d d ose c ha n ges) f or t o xicit y after 
t he starti n g d ose are all o we d a n d s h o ul d be ma de i n acc or da nce wit h la beli n g i nstr ucti o ns a n d l ocal 
i nstit uti o nal g ui deli nes.  Su bjects o n c he m ot hera p y i n t he Mai nte na nce P hase will c o nti n ue wit h 
t he sa me d ose t he y ha d at t he e n d of t he I n d ucti o n P hase (starti n g d ose or re d uce d d ose).  D uri n g 
t he Mai nte na nce P hase, d ose m o dificati o ns are als o all o we d f or t o xicit y.
T he d ose of c he m ot hera p y will be calc ulate d base d o n t he wei g ht or b o d y  surface area, as 
a p plica ble, of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or t o t he d a y  of dr u g a d mi nistrati o n (see 
Ta ble 9 ).  
D ose m o dificati o n g ui deli nes 
( d ose dela y s a n d d ose c ha n ges) after t he starti n g d ose f or 
c he m ot hera py are pr o vi de d i n Ta ble 8.   F or s pecific starti n g d oses d ue t o re nal or he patic 
i m pair me nt a n d f or s u bse q ue nt d ose m o dificati o ns d ue t o differe nt t o xicities, please f oll o w t he 
l ocal la bel a n d g ui deli nes.
F or s u bjects i nt olera nt t o f urt her o xali plati n, si n gle-a ge nt ca pecita bi ne or 5- F U + le uc o v ori n will 
be a n o pti o n f or d ose m o dificati o n.
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 7 / 1 5 0
T a ble 8
D ose M o dific ati o n Ge ner al G ui deli nes f or C he m ot her a p y
M ai nt e n a n c e T h er a p y
Fir st D o s e R e d u cti o n
S e c o n d D o s e R e d u cti o n
T hir d D o s e R e d u cti o n
5- F U ( 2 6 0 0 m g/ m2 d o s e
o v er 2 4 h o ur s )
1 9 5 0 m g/ m 2 - 2 0 8 0 m g/ m
2
o v er 2 4 h o ur s
1 3 0 0 m g/ m 2 (1 5 6 0 m g/ m 2
o v er 2 4 h o ur s )
Di s c o nti n u e
5- F U ( 2 4 0 0 m g/ m 2 d o s e)
o v er 4 6 -4 8 h o ur s
1 8 0 0 m g/ m 2 - 1 9 2 0 m g/ m 2
o v er 4 6 -4 8 h o ur s
1 2 0 0 m g/ m 2 -1 4 4 0 m g/ m 2
o v er 4 6 -4 8 h o ur s
Di s c o nti n u e
C a p e cit a bi n e
7 5 % of st arti n g d o s e 
5 0 % of st arti n g d o s e
Di s c o nti n u e
O x ali pl ati n ( 8 5 m g/ m
2
d o s e)
6 4 t o 6 8 m g/ m
2 i n 
a c c or d a n c e wit h l o c al 
l a b el/i n stit uti o n al 
g ui d eli n e s
4 2. 5 m g/ m 2 i n a c c or d a n c e 
wit h l o c al l a b el/i n stit uti o n al 
g ui d eli n e s
Di s c o nti n u e
O x ali pl ati n ( 1 3 0 m g/ m 2
d o s e)
9 8 t o 1 0 4 m g/ m 2 i n 
a c c or d a n c e wit h l o c al 
l a b el/i n stit uti o n al 
g ui d eli n e s
6 5
m g/ m 2 i n a c c or d a n c e 
wit h l o c al l a b el/i n stit uti o n al 
g ui d eli n e s
Di s c o nti n u e
5- F U = 5 -fl u or o ur a cil
5. 2
Disc ussi o n of Tri al Desi g n
5. 2. 1
R ati o n ale 
S u p p ort i n g 
t he 
C h oice 
of 
t he 
F irst-li ne 
C he m ot her a p y
T here is n o c o nse ns us o n w hat s h o ul d be t he o pti mal first -li ne c he m ot hera p y f or t he ma na ge me nt 
of a d va nce d gastric ca ncer. A plati n u m fl u or o pyri mi di ne d o u blet is c o nsi dere d as a n acce pta ble 
o pti o n b y  the Nati o nal C o m pre he nsi ve Ca ncer Net w or k (N C C N ), E S M O , a n d Ja pa nese g ui deli nes 
f or t he ma na ge me nt of t hat disease (Wa d dell
2 0 1 3 ). I n the pr o p ose d st u d y, all s u bjects will recei ve 
a plati n u m fl u or o p yri mi di ne d o u blet c o nsisti n g of ca pecita bi ne or 5 -F U a n d o xali plati n .  S u bjects
w h ose disease is at least sta ble will be ra n d o mly assi g ne d t o recei ve eit her a vel u ma b (acti ve ar m) 
or will, per t he j u d g me nt of t he In vesti gat or, recei ve s u bse q ue nt c ycles of t he i nitial c he m ot hera p y 
re gi me n u ntil u nacce pta ble t o xicities or disease pr o gressi o n.
T he a d mi nistrati o n of o xali plati n a n d ca pecita bi ne or 5- F U as a first-li ne re gi me n f or t he treat me nt 
of a d va nce d gastric ca ncer is acce pta ble f or t he f oll o wi n g reas o ns: 

St u d y  RE A L - 2 (C u n ni n g ha m 2 0 0 8 ) de m o nstrate d t hat ca pecita bi ne a n d o xali plati n are as 
effecti ve as fl u or o uracil a n d cis plati n, res pecti vel y i n patie nts wit h pre vi o usl y u ntreate d gastric 
ca ncer. I n ter ms of safet y, o xali plati n a d mi nistrati o n res ulte d i n l o wer i nci de nce of Gra de 3 
a n d 4 ne utr o pe nia, re nal t o xicit y an d t hr o m b oe m b olis m b ut t o sli g htl y hi g her i nci de nce of 
Gra de 3 a n d 4 diarr hea a n d ne ur o pat h y . T he safet y pr ofiles of 5- F U a n d ca pecitabi ne were 
si milar.

Ca pecita bi ne or 5- F U i n c o m bi nati o n wit h a plati n u m -base d a nti ne o plastic a ge nt (cis plati n) was 
t he c he m ot hera p y bac k b o ne use d i n t he T O G A st u d y that s u p p orte d t he a p pr o val of trast uz u ma b 
f or patie nts wit h gastric ca ncer w it h h u ma n e pi der mal gr o wt h fact or rece pt or 2 p ositi ve 
( HE R 2 +) disease .
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 8 / 1 5 0

O xali plati n tri g gers a partic ular t y pe of a p o pt otic deat hs t hat is c o nsi dere d t o be i m m u n o ge nic 
a n d was preferre d t o cis plati n f or t he plati n u m c o m p o ne nt of t he re q uire d c he m ot hera p y d o u blet
(Tes niere 2 0 1 0 ).

T o ha ve o nl y o xali plati n as t he plati n u m salt will li mit t he ris k of ha vi n g a c o nf o u n di n g fact or 
o n t he pri mar y  en d p oi nt s as R E A L - 2 di d n ot c o m pletel y  rule -o ut t hat cis plati n a n d o xali plati n 
ha d e xactl y t he sa me cli nical efficac y.
5. 2. 2
R ati o n ale f or E xcl usi o n of H E R 2 P ositi ve P o p ul ati o n 
S u bjects wit h h u ma n e pi der mal gr o wt h fact or rece pt or 2- p ositi ve disease are e xcl u de d fr o m t his 
trial.  This rati o nale f or e xcl u di n g t hese s u bjects is t hat t he c urre nt sta n dar d of care (S O C ) f or 
H E R 2 p ositi ve s u bjects is differe nt t ha n H E R 2 ne gati ve s u bjects a n d w o ul d re q uire a d diti o n of
trast uz u ma b t o t he i n d ucti o n c he m ot hera p y c h oices.  I ncl usi o n of H E R 2 p ositi ve s u bjects w o ul d 
als o res ult i n a n a d diti o nal o pti o n f or m ai nte na nce t hera py a n d t h us res ult i n greater s u bject 
heter o ge neit y .  
5. 2. 3
R ati o n ale f or S witc hi n g S u bjects
fr o m C he m ot her a p y t o 
A vel u m a b
T he pr o p osal t o s witc h s u bjects assi g ne d t o t he e x peri me ntal ar m after t he y ha ve c o m plete d 
1 2 wee ks of c he m ot hera p y  is a ppr o priate f or t he f oll o wi n g reas o ns:

T here is n o data s u p p orti n g t hat a d diti o nal c he m ot hera p y b e yo n d 4 t o 6 c yc les ( u p t o 1 2 wee ks 
of treat me nt) will res ult i n i m pr o ve d s ur vi val i n t he c o nte xt of a disease w here it is c o m m o n 
practice t o re-i n d uce patie nts at t he ti me of disease pr o gressi o n. 
Patie nts w h o ha ve n ot 
res p o n de d t o or w h o will cease t o res p o n d t o a vel u ma b will be re-i n d uce d eit her wit h 
plati n u m -base d d o u blets or wit h dr u gs t hat ha ve s h o w n cli nical be nefit as a sec o n d-li ne t hera p y. 
S u bjects will be m o nit ore d e ver y 6 wee ks a n d resc ue t hera p y m a y be a d mi nistere d o nce disease 
pr o gressi o n is esta blis he d .

Treat me nt of patie nts wit h a vel u ma b has res ulte d i n a n O R R of 1 5 % i n patie nts wit h gastric 
ca ncer fr o m Asia n a n d n o n -Asia n re gi o ns.  So me of t hese res p o nses were l o n g lasti n g a n d a 
n u m ber of s u bjects wit h pr ol o n ge d S D were als o o bser ve d.  Base d o n t hese data , it is reas o na ble 
t o i nterr u pt c he m ot hera p y after 1 2 wee ks t o i nitiate a n i m m u n ot hera p y that has bee n re p orte d 
t o i n d uce pr ol o n ge d res p o nses i n a d va nce d gastric ca ncer patie nts w h o will ulti matel y pr o gress 
after i nitial c he m ot hera p y re gi me ns. 

F or s u bjects ra n d o mly assi g ne d t o recei ve a d diti o nal c he m ot hera p y i n t he Mai nte na nce P hase, 
it is rec o m me n de d t hat t he c he m ot hera p y re gi me n d o es n ot t o e xcee d 6 c ycles.  This is 
s u p p orte d b y  the pre vi o usl y  esta blis he d re gi me n i n t he re gistrati o n st u d y for trast uz u ma b 
( T O G A).  In c o ncl usi o n, s witc hi n g s u bjects after 1 2 wee ks
of c he m ot hera p y t o recei ve 
a vel u ma b treat me nt is c o nsi dere d a p pr o priate.
5. 2. 4
J ustific ati o n of O pe n -l a bel St u d y Desi g n
T he o pe n -la bel st u d y desi g n is j ustifie d base d o n t he f oll o wi n g:
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
5 9 / 1 5 0
D o u ble- bli n d c o ntr olle d st u d y wo ul d be i m p ossi ble d ue t o differe nces i n treat me nt sc he d ule a n d 
t o xicit y pr ofile t hat w o ul d u n mas k treat me nt assi g n me nt.
5. 2. 5
R ati o n ale f or t he Pri m ar y E n d p oi nt
O verall s ur vi val was c h ose n as t he pri mar y  e n d p oi nt beca use t his is a n u ne q ui v ocal meas ure me nt 
of cli nical be nefit t hat will n ot be c o nf o u n de d b y t he o pe n -la bel nat ure of t he st u d y.
O verall s ur vi val i n P D -L 1 + s u bjects was c h ose n as o ne of t he pri mar y  o bjecti ves base d o n res ults 
fr o m t he E M R 1 0 0 0 7 0 -0 0 1, P hase I b, gastric pri mar y  co h ort. I n t he gr o u p of G C/ G EJ C s u bjects 
w h o di d n ot pr o gress o n or after first-li ne c he m ot hera py, a differe nce i n me dia n O S of 4. 3 m o nt hs 
was o bser ve d i n s u bjects wit h P D -L 1  t u m or cells ≥1 % c o m pare d t o t he o verall s u bjects.
5. 2. 6
Tri al Peri o ds
T he st u d y will c o nsist of (i) Scree ni n g / baseli ne e val uati o n, (ii) i n d ucti o n, (iii) mai nte na nce , a n d 
(i v) p ost -treat me nt f oll o w-u p peri o d.
i) D uri n g Scree ni n g / baseli ne ( Da y - 2 8 t o D a y 1), i nf or me d c o nse nt will be o btai ne d a n d s u bject 
c o m plia nce wit h t he i ncl usi o n/e xcl usi o n criteria will be ascertai ne d.
ii) D uri n g t he I n d ucti o n P hase, s u bjects will recei ve 4 c ycles of c he m ot hera p y c o m prise d of
o xali plati n a n d ca pecita bi ne e ver y 3 wee ks O R 6 c ycles of c he m ot hera p y c o m prise d of o xali plati n 
a n d 5-F U e ver y 2 wee ks.  
I n d ucti o n C he m ot hera py:
S u bjects e nr olle d i n t his trial will recei ve c he m ot hera p y c o m prise d of o xali plati n a n d eit her 
5- F U or ca pecita bi ne.  Su bjects w h o e x perie nce a C R, P R, or S D after 1 2 wee ks will be 
ra n d o ml y assi g ne d t o eit her a vel u ma b or c o nti n uati o n of t he sa me first-li ne c he m ot hera p y t he y 
recei ve d d uri n g t he I n d ucti o n P hase.   S u bjects w h o de m o nstrate a res p o nse d uri n g t he 
I n d ucti o n P hase t hat re n ders t heir meas ura ble disease n o l o n ger meas ura ble at t he ti me of t he 
Mai nte na nce P hase ca n be ra n d o miz e d.
iii) D uri n g t he Mai nte na nce P hase , s u bjects will be ra n d o ml y assi g ne d t o recei ve eit her avel u ma b 
or c o nti n uati o n of t he sa me c he m ot hera p y re gi me n fr o m t he I nd ucti o n P hase, u ntil disease 
pr o gressi o n , u nacce pta ble t o xicit y , or f or t he acce pte d ma xi mal d urati o n of t he a ge nt(s) selecte d.
Mai nte na nce A vel u ma b A r m:
S u bjects recei vi n g avel u ma b will 
c o nti n ue o n -treat me nt u ntil disease pr o gressi o n or 
u nacce pta ble t o xicit y. S u bjects recei vi n g a vel u ma b d uri n g t he Mai nte na nce 
P hase ma y 
c o nti n ue treat me nt past t he i nitial deter mi nati o n of disease pr o gressi o n acc or di n g t o 
R E CI S T v 1. 1 if t h e y meet t he criteria prese nte d i n Secti o n  6. 2. 1 (I n vesti gat or-assesse d be nefit; 
t olera nce of treat me nt; sta ble E C O G P S; a n d d oes n ot dela y ot her i m mi ne nt i nter ve nti o n).
S u bjects recei vi n g a vel u ma b w h o ha ve e x perie nce d a C R s h o ul d be treate d f or a mi ni m u m of 
1 2 m o nt hs or u ntil disease pr o gressi o n or u nacce pta ble t o xicit y, after c o nfir mati o n of res p o nse.  
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 0 / 1 5 0
I n case a s u bject wit h a c o nfir me d C R rela pses after st o p pi n g treat me nt, b ut pri or t o t he e n d of 
t he trial, 1 re-i nitiati o n of treat me nt is all o we d at t he discreti o n of t he I nvesti gat or a n d after 
a gree me nt wit h t he Me dical M o nit or.  I n or der t o be eli gi ble f or retreat me nt, t he s u bject m ust 
n ot ha ve e x perie nce d a n y t o xicit y  t hat le d t o treat me nt disc o nti n uati o n of t he i nitial a vel u ma b 
t hera py.  S u bjects w h o re -i nitiate treat me nt will sta y o n trial a n d will be t reate d a n d m o nit ore d 
acc or di n g t o t he pr ot oc ol.
Mai nte na nce C he m o t hera p y A r m:
Mai nte na nce c he m ot hera p y will c o nti n ue u ntil disease pr o gressi o n or u nacce pta ble t o xicit y or 
u ntil t he ma xi m u m acce pta ble d osi n g is ac hie ve d at t he discreti o n of t he I nvesti gat or.
S u bjects w h o are n ot dee me d eli gi ble t o recei ve f urt her c he m ot hera p y will recei ve B S C al o ne 
wit h n o acti ve t hera p y until disease pr o gressi o n.   Pri or t o ra n d o mizati o n, I n vesti gat ors m ust 
s pecif y B S C treat me nt f or t hese s u bjects.
i v) T he F oll o w - u p P hase will i ncl u de a p ost -treatme nt peri o d a n d l o n g-ter m f oll o w- u p visits. 
D uri n g t he p ost -treat me nt peri o d (fr o m treat me nt disc o nti n uati o n t o S afet y F oll o w -u p), a S afet y
F oll o w -u p visit will be sc he d ule d 3 0 da y s after last treat me nt a n d a p h o ne call will occ ur 9 0 da ys 
after treat me nt disc o nti n uati o n.
A l o n g-ter m f oll o w- u p visit will occ ur e ver y 1 2 wee ks f or 5 years after t he last s u bject recei ves 
t he last d ose of st u d y dr u g (see Secti o n 7. 1. 7 f or details).
D uri n g Scree ni n g , i n d ucti o n, mai nte na nce a n d p ost-treat me nt peri o ds, s u bject will u n der g o visits 
a n d assess me nt pr oce d ures as per descri be d i n t he Sc he d ule of Assess me nts (Ta ble 1 t o Ta ble 7) .
5. 2. 7
I ncl usi o n of S peci al P o p ul ati o ns
N ot a p plica ble.
5. 3
Selecti o n of Tri al P o p ul ati o n
O nl y  pers o ns meeti n g all i ncl usi o n criteria a n d n o e xcl usi o n criteria ma y be e nr olle d i nt o t he trial 
as s u bjects. Pri or t o perf or mi n g a n y trial assess me nts n ot part of t he s u bject’s r o uti ne me dical 
care, t he I n vesti gat or will e ns ure t hat t he s u bject or t he s u bject’s le gal re prese ntati ve has pr o vi de d 
writte n i nf or me d c o nse nt f oll o wi n g t he pr oce d ure descri be d i n Secti o n  9. 2.
5. 3. 1
I ncl usi o n Criteri a
F or i ncl usi o n i n t he trial, all of t he f oll o wi n g i ncl usi o n criteria m ust be f ulfille d:
1.
Has rea d, u n derst o o d a n d si g ne d writte n i nf or me d c o nse nt bef ore a n y trial-relate d pr oce d ure 
is u n derta ke n t hat is n ot part of t he sta n dar d s u bject ma na ge me nt
2.
Male or fe male s u bjects a ge d ≥1 8 y ears
3.
A vaila bilit y  of a rece ntl y-o btai ne d ( wit hi n 6 m o nt hs)
bi o ps y  fr o m a n o n -irra diate d area, 
f or mali n-fi xe d, paraffi n -e m be d de d ( F F P E) bl oc k c o ntai ni n g t u m or tiss ue or a mi ni m u m 
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 1 / 1 5 0
n u m ber of 1 0 ( prefera bly 2 5) u nstai ne d t u m or sli des (c ut wit hi n 1 wee k) s uita ble f or P D -L 1  
e x pressi o n assess me nt . 
4.
Disease m ust be meas ura ble per R E CI S T v 1. 1
5.
S u bjects 
wit h 
hist ol o gicall y  co nfir me d u nresecta ble l ocall y ad va nce d or metastatic 
a de n ocarci n o ma of t he st o mac h or G EJ
6.
E C O G P S of 0 t o 1 at trial e ntr y
7.
Esti mate d life e x pecta nc y  of m ore t ha n 1 2 wee ks
8.
A de q uate he mat ol o gical f u ncti o n defi ne d b y  w hite bl o o d cell (W B C ) c o u nt ≥ 2. 5 × 1 0 9/ L wit h 
a bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1. 5 × 1 0 9/ L, l ym p h oc y te c o u nt ≥ 0. 5 × 1 0 9/ L, platelet c o u nt 
≥1 0 0 × 1 0 9/ L, a n d he m o gl o bi n ≥9 g/ d L ( ma y  ha ve bee n tra nsf use d). 
9.
A de q uate he patic f u ncti o n defi ne d b y a t otal bilir u bi n le vel ≤ 1. 5 × t he u p per li mit of n or mal 
( U L N) ra n ge a n d as partate a mi n otra nsferase (A S T ) a n d ala ni ne a mi n otra nsferase ( AL T) le vels 
≤ 2. 5 × U L N f or all s u bjects
1 0. A de q uate re nal f u ncti o n defi ne d b y  a n esti mate d creati ni ne cleara nce ≥3 0 m L / mi n acc or di n g 
t o t he C oc kcr oft-Ga ult f or m ula ( or l ocal i nstit uti o nal sta n dar d met h o d)
1 1. Ne gati ve bl o o d pre g na nc y  test at Scree ni n g f or w o me n of c hil d beari n g p ote ntial .  F or t he 
p ur p oses of t his trial, w o me n of c hil d beari n g p ote ntial are defi ne d as: “ All fe male s u bjects 
after p u bert y  unless t he y are p ost me n o pa usal f or at least 2 years, are s ur gicall y sterile, or are 
se x uall y i nacti ve.”
1 2. Hi g hl y effecti ve c o ntrace pti o n (ie, met h o ds wit h a fail ure rate of less t ha n 1 % per ye ar) f or 
b ot h male a n d fe male s u bjects if t he ris k of c o nce pti o n e xists ( N ote: T he effects of t he trial 
treat me nt o n the de vel o pi n g h u ma n fet us are u n k n o w n; t h us, w o me n of c hil d beari n g p ote ntial 
a n d me n m ust a gree t o use hi g hl y effecti ve c o ntrace pti o n, defi ne d i n  A p pe n di x II
G ui da nce 
o n C o ntrace pti o n
or as sti p ulate d i n nati o nal or l ocal g ui deli nes.  
Hi g hly effecti ve 
c o ntrace pti o n m ust be use d 1 5 d a y s pri or t o first trial treat me nt a d mi nistrati o n, a n d f or t he 
d urati o n of trial treat me nt for all s u bjects.  Hi g hl y effecti ve c o ntrace pti o n m ust be use d at least 
f or 6 0 d a y s after st o p pi n g a vel u ma b treat me nt a n d as i n dicate d i n t he res pecti ve la bel [ S m P C] 
f or o xali plati n, 5- F U or ca pecita bi ne f or s u bjects recei vi n g c he m ot hera p y [i n t he I nd ucti o n
P hase a n d t he Mai nte na nce P hase], or as per la bel of a n y  ot her t hera p y use d as B S C .  S h o ul d 
a w o ma n bec o me pre g na nt or s us pect s he is pre g na nt w hile s he or her part ner is partici pati n g 
i n t his trial, t he treati n g p h ysicia n s h o ul d be i nf or me d i m me diatel y).
5. 3. 2
E xcl usi o n Criteri a
S u bjects are n ot eli gi ble f or t his trial if t he y  f ulfill a n y of t he f oll o wi n g e xcl usi o n criteria:
1.
Pri or t hera py wit h a n y a nti b o d y or dr u g tar geti n g T- cell c ore g ulat or y pr otei ns (i m m u ne 
c hec k p oi nts) s uc h as P D- 1, P D -L 1 , or c yt ot o xic T-ly m p h oc y te a nti ge n-4 ( C T L A -4)  
2.
C o nc urre nt a ntica ncer treat me nt (f or e xa m ple, c yt ore d ucti ve t hera p y, ra di ot hera py [ wit h t he 
e xce pti o n of palliati ve b o ne - directe d ra di ot hera p y], i m m u ne t hera p y, or c yt o ki ne t hera py,  
e xce pt f or er yt hr o p oieti n)
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 2 / 1 5 0
3.
Pri or c he m ot hera p y  for u nresecta ble l ocally a d va nce d or metastatic a de n ocarci n o ma of t he 
st o mac h or G EJ
4.
T u m or s h o w n t o be H E R 2 + b y  im m u n o hist oc he mistr y  (I H C > 3 +) a n d/ or b y  fl u oresce nce i n 
sit u h ybri dizati o n ( FI S H) (I H C 2 +, FI S H + )
5.
Maj or s ur ger y f or a n y reas o n, e xce pt dia g n ostic bi o ps y , wit hi n 4 wee ks of e nr ollme nt a n d/ or 
if t he s u bject has n ot f ull y rec o vere d fr o m t he s ur ger y wit hi n 4 wee ks of e nr ollme nt
6.
S u bjects recei vi n g i m m u n os u p pressi ve a ge nts (s uc h as ster oi ds) f or a n y reas o n s h o ul d be 
ta pere d off t hese dr u gs bef ore i nitiati o n of t he trial treat me nt ( wit h t he e xce pti o n of s u bjects 
wit h a dre nal i ns ufficie nc y, w h o m a y  co nti n ue c ortic oster oi ds at p h y si ol o gic re place me nt d ose, 
e q ui vale nt t o ≤1 0 m g pre d nis o ne dail y ).  N ote: Pre vi o us or o n g oi n g a d mi nistrati o n of s yste mic 
ster oi ds f or t he ma na ge me nt of a n ac ute aller gic p he n o me n o n is acce pta ble as l o n g as it is 
a ntici pate d t hat t he a d mi nistrati o n of ster oi ds will be c o m plete d i n 1 4 d a y s, or t hat t he daily 
d ose after 1 4 da y s will be ≤ 1 0 m g per da y  of e q ui vale nt pre d nis o ne
7.
All s u bjects wit h brai n metastases, e xce pt t h ose meeti n g t he f oll o wi n g criteria:
a.
Brai n metastases ha ve bee n treate d l ocally, ha ve n ot bee n pr o gressi n g at least 2 m o nt hs 
after c o m pleti o n of t hera p y, a n d n o ster oi d mai nte na nce t hera p y is re q uire d, a n d
b.
N o o n g oi n g ne ur ol o gical s y m pt o ms t hat are relate d t o t he brai n l ocalizati o n of t he disease 
(se q uelae t hat are a c o nse q ue nce of t he treat me nt of t he brai n metastases are acce pta ble)
8.
Pre vi o us mali g na nt disease ( ot her t ha n gastric ca ncer) wit hi n t he last 5 ye ars wit h t he 
e xce pti o n of basal or s q ua m o us cell carci n o ma of t he s ki n or carci n o ma i n sit u (e g, bla d der, 
cer vical, c ol orectal, breast)
9.
Pri or or ga n tra ns pla ntati o n, i ncl u di n g all o ge neic ste m -cell tra ns pla ntati o n
1 0. Si g nifica nt ac ute or c hr o ni c i nfecti o ns i ncl u di n g, a m o n g ot hers:
a.
K n o w n hist or y  of testi n g p ositi ve f or h u ma n i m m u n o deficie nc y vir us ( HIV) or k n o w n 
ac q uire d i m m u n o deficie nc y  sy n dr o me ( AI D S)
b.
P ositi ve test f or H B V s urface a nti ge n a n d / or c o nfir mat or y HC V ri b o n ucleic aci d (R N A ) 
test if t he a nti-H C V a nti b o d y  test is p ositi ve.
c.
Acti ve t u berc ul osis ( T B) ( hist or y of e x p os ure or hist or y of p ositi ve T B test; pl us prese nce 
of cli nical s y m pt o ms, p h y sical or ra di o gra p hic fi n di n gs)
1 1. Acti ve a ut oi m m u ne disease t hat mi g ht deteri orate w he n recei vi n g a n i m m u n osti m ulat or y 
a ge nt:
a.
S u bjects wit h dia betes t ype I, vitili g o, ps oriasis, h y p o- or h y pert h yr oi d disease n ot 
re q uiri n g i m m u n os u p pressi ve treat me nt are eli gi ble
b.
S u bjects re q uiri n g h or m o ne re place me nt wit h c ortic oster oi ds are eli gi ble if t he ster oi ds are 
a d mi nistere d o nl y f or t he p ur p ose of h or m o nal re place me nt a n d at d oses ≤1 0 m g or 1 0 m g 
e q ui vale nt pre d nis o ne per da y
c.
A d mi nistrati o n of ster oi ds t hr o u g h a r o ute k n o w n t o res ult i n a mi ni mal s ys te mic e x p os ure 
(t o pical, i ntra nasal, i ntr o- oc ular, or i n halati o n) are acce pta ble
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 3 / 1 5 0
1 2. K n o w n se vere h y perse nsiti vit y  reacti o ns t o m o n ocl o nal a nti b o dies ( Gra de ≥3 N CI -C T C A E 
v 4. 0 3), a n y hist or y of a na p h yla xis, or u nc o ntr olle d ast h ma (t hat is, 3 or m ore feat ures of 
partiall y  c o ntr olle d ast h ma)
1 3. Persisti n g t o xicit y  relate d t o pri or t hera p y of Gra de > 2 N CI -C T C A E v 4. 0 3 e xce pt al o pecia
1 4. Ne ur o pat h y Gra de > 3.
1 5. Pre g na nc y  or lactati o n
1 6. K n o w n alc o h ol or dr u g a b use
1 7. Hist or y  of u nc o ntr olle d i nterc urre nt ill ness i ncl u di n g b ut n ot li mite d t o:
a.
H y perte nsi o n u nc o ntr olle d b y  sta n dar d t hera pies ( n ot sta bilize d t o 1 5 0/ 9 0 m m H g or l o wer), 
or
b.
U nc o ntr olle d acti ve i nfecti o n, or 
c.
U nc o ntr olle d dia betes (e g, he m o gl o bi n A 1c ≥ 8 %)
1 8. Cli nicall y  si gnifica nt (ie, acti ve) car di o vasc ular disease: cere bral vasc ular acci de nt / str o ke 
( < 6 m o nt hs pri or t o e nr ollme nt ), m y ocar dial i nfarcti o n ( < 6 m o nt hs pri or t o e nr ollme nt ), 
u nsta ble a n gi na pect oris, c o n gesti ve heart fail ure ( Ne w Y or k Heart Ass ociati o n Classificati o n 
Class ≥ II), or seri o us car diac arr h yt h mia re q uiri n g me dicati o n (i ncl u di n g c orrecte d Q T 
i nter val [Q Tc ] pr ol o n gati o n of > 4 7 0 ms a n d/ or pace ma ker) or pri or dia g n osis of c o n ge nital 
l o n g Q T sy n dr o me
1 9. All ot her si g nifica nt diseases (f or e xa m ple, i nfla m mat or y bo wel disease), w hic h, i n t he 
o pi ni o n of t he I n vesti gat or, mi g ht i m pair t he s u bject’s t olera nce of trial treat me nt
2 0. A n y  ps yc hiatric c o n diti o n t hat w o ul d pr o hi bit t he u n dersta n di n g or re n deri n g of i nf or me d 
c o nse nt a n d t hat w o ul d li mit c o m plia nce wit h st u d y re q uire me nts
2 1. Vacci nati o n wit h li ve or li ve/atte n uate d vir uses wit hi n 5 5 da y s ( 5 half -li ves x 1 2 7 h o urs 
+ 3 0 d a y s) of first d ose of a vel u ma b a n d w hile o n trial is pr o hi bite d e xce pt f or a d mi nistrati o n
of i nacti vate d vacci nes (f or e xa m ple, i nacti vate d i nfl ue nza vacci nes)
2 2. Le gal i nca pacit y or li mite d le gal ca pacit y
2 3. Patie nts will 
be e xcl u de d fr o m t he I n d ucti o n P hase a n d t he Mai nte na nce 
P hase if 
a d mi nistrati o n of t heir c he m ot hera p y w o ul d be i nc o nsiste nt wit h t he c urre nt l ocal la beli n g 
( S m P C) (e g, i n re gar d t o c o ntrai n dicati o ns, war ni n gs/ preca uti o ns or s pecial pr o visi o ns) f or 
t hat c he m ot hera p y.  In vesti gat ors s h o ul d c hec k u p date d la beli n g via rele va nt we bsites at t he 
ti me of e ntr y i nt o t he I n d ucti o n P hase a n d t he Mai nte na nce P hase.
5. 4
Criteri a f or I niti ati o n of Tri al Tre at me nt
T he i ncl usi o n a n d e xcl usi o n criteria will be c hec ke d at t he Scree ni n g visit .  Eli gi ble s u bjects will 
be e nr olle d bef ore treat me nt start after verificati o n of f ulfilli n g all i ncl usi o n criteria wit h o ut 
matc hi n g a n y e xcl usi o n criteri o n.
D oc u me nt N o.
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 4 / 1 5 0
5. 5
Criteri a f or S u bject Wit h dr a w al
5. 5. 1
Wit h dr a w al fr o m Tri al T her a p y
S u bjects will be wit h dra w n fr o m trial treat me nt d uri n g t he I n d ucti o n a n d/ or Mai nte na nce P hase 
f or a ny of t he f oll o wi n g reas o ns:

S u bjects meeti n g t he defi niti o n of P D w hile o n -treat me nt base d o n R E CI S T v 1. 1 . Su bjects i n 
t he Mai nte na nce P hase recei vi n g a vel u ma b w h o e x perie nce disease pr o gressi o n ma y  co nti n ue 
treat me nt wit h a vel u ma b if t hey meet t he criteria prese nte d i n Secti o n 6. 2. 1 (In vesti gat or 
belie ves t he s u bject will e x perie nce cli nical be nefit fr o m t he treat me nt a n d t here is n o 
u nacce pta ble t o xicity res ulti n g fr o m t he treat me nt [ See Secti o n  6. 2. 1]. S uc h s u bjects will be 
wit h dra w n fr o m t he treat me nt if t here is a s u bse q ue nt sca n/assess me nt of P D base d o n R E CI S T 
v 1. 1).

Si g nifica nt cli nical deteri orati o n (cli nical pr o gressi o n), defi ne d as ne w s ym pt o ms t hat are 
dee me d b y  the I n vesti gat or t o be cli nicall y si g nifica nt or si g nifica nt w orse ni n g of e xisti n g 
s ym pt o ms

U nacce pta ble t o xicit y

Wit h dra wal of c o nse nt

Occ urre nce of a n e xcl usi o n criteri o n, w hic h is cli nicall y rele va nt a n d affects t he s u bject’s 
safety, if disc o nti n uati o n is c o nsi dere d necessar y  b y t he I n vesti gat or a n d / or S p o ns or

T hera pe utic fail ure re q uiri n g ur ge nt a d diti o nal dr u g (if a p plica ble )

Occ urre nce of a n y Gra de ≥ 3 A D Rs or re petiti ve Gra de 2 A D Rs as defi ne d i n Secti o n  5. 1. 3. 2
f or s u bjects recei vi n g a vel u ma b.

Occ urre nce of A Es, res ulti n g i n t he disc o nti n uati o n of t he trial dr u g bei n g d e sire d or c o nsi dere d 
necessar y  b y t he I n vesti gat or a n d / or t he s u bject 

Occ urre nce of pre g na nc y 

Use of a n o n per mitte d c o nc o mita nt dr u g, as defi ne d i n Secti o n 6. 5. 2,  w here t he pre defi ne d 
c o nse q ue nce is wit h dra wal fr o m t he trial dr u g

N o nc o m plia nce (see Secti o n 6. 9) .
F or s u bjects recei vi n g a vel u ma b, if disc o nti n uati o n occ urs d ue t o pr o gressi o n a n d a defi niti ve 
dia g n osis/ra di o gra p hic c o nfir mati o n is n ot ma de at t he ti me of disc o nti n uati o n, a sec o n d i ma gi n g 
sca n m a y  be all o we d f or c o nfir mati o n of pr o gressi o n.  If pr o gressi o n at t he sec o n d i ma gi n g sca n 
is n ot c o nfir me d a n d t he s u bject wis hes t o restart, t he s u bject will be all o we d t o c o nti n ue recei vi n g
a vel u ma b as l o n g as t he y meet t he criteria f or c o nti n uati o n of treat me nt be y o n d pr o gressi o n.   F or 
m ore i nf or mati o n, see Secti o n  6. 2. 1.  
S u bjects w h o wit h dra w fr o m trial t hera p y  will c o nti n ue t o be f oll o we d f or s ur vi val a n d ne w a nti-
ca ncer t hera pies.  The s ur vi val f oll o w- u p of all s u bjects wil l c o nti n ue u ntil 5 ye ars after t he last 
s u bject recei ves t he last d ose of a vel u ma b.  Un der s o me circ u msta nces, t he s u bjects ma y  not be 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 5 / 1 5 0
f oll o we d f or 5 years f or s ur vi val i n t his st u d y, e g, t he s u bjects ma y be offere d t o e nr oll i nt o a r oll-
o ver st u d y , or t he S p o ns or ma y  ter mi nate t he st u d y early.
5. 5. 2
Wit h dr a w al fr o m t he Tri al
S u bjects ma y wit h dra w fr o m t he trial at a n y ti me wit h o ut gi vi n g a reas o n .  Wit h dra wal of c o nse nt 
will be c o nsi dere d wit h dra wal fr o m t he trial.  I n case of wit h dra wal fr o m t he trial, t he assess me nts 
sc he d ule d f or t he last visit ( E n d of Treat me nt visit) s h o ul d be perf or me d (see Secti o n 7. 1. 5 ), if 
p ossi ble, wit h f oc us o n t he m ost rele va nt assess me nts.  I n a n y  case, t he a p pr o priate E n d of Safety 
F oll o w - u p e C R F pa ge m ust be c o m plete d.  In case of wit h dra wal, s u bjects will be as ke d to 
c o nti n ue safety a n d s ur vi val f oll o w- u p, w hic h i ncl u des t he c ollecti o n of data o n s ur vi val, 
s u bject-re p orte d o utc o mes/ Q o L q uesti o n naires, a n d s u bse q ue nt a ntica ncer t hera p y.
A s u bject m ust be wit h dra w n if a n y of t he f oll o wi n g occ ur d uri n g t he trial:

Wit h dr a wal of t he s u bject’s c o nse nt

Partici pati o n i n a n y ot her t hera pe utic trial d uri n g t he treat me nt d urati o n of t his trial; h o we ver, 
s u bjects will c o nti n ue t o be f oll o we d f or s ur vi val (see Secti o n 7. 1. 7).
If a s u bject fails t o atte n d sc he d ule d trial assess me nts, t he In vesti gat or m ust deter mi ne t he reas o ns 
a n d t he circ u msta nces as c o m pletel y a n d acc uratel y as p ossi ble .
If a s u bject is wit h dra w n pri or t o pro gressi o n f or a n y  reas o n, t he s u bject will n ot be re place d.
5. 6
Pre m at ure Ter mi n ati o n of t he Tri al
T he w h ole trial ma y  be disc o nti n ue d pre mat urely i n t he e ve nt of a n y of t he f oll o wi n g:

Ne w i nf or mati o n lea di n g t o u nfa v ora ble ris k-be nefit j u d g me nt of t he trial dr u g, f or e xa m ple, 
d ue t o:

E vi de nce of i nefficac y  of t he trial dr u g

Occ urre nce of si g nifica nt pre vi o usl y  un k n o w n a d verse reacti o ns or u ne x pecte dl y  hi gh 
i nte nsit y or i nci de nce of k n o w n a d verse reacti o ns

Ot her u nfa v ora ble safet y fi n di n gs.
( N ote: Evi de nce of i neffic acy m ay arise fr o m t his tri al or fr o m ot her tri als; u nf av or a ble s afety 
fi n di n gs m ay arise fr o m cli nic al or  
 ex a mi n ati o ns, f or ex a m ple, t oxic ol o gy.)

S p o ns or’s decisi o n t hat c o nti n uati o n of t he trial is u nj ustifia ble f or me dical or et hical reas o ns

P o or e nr ollme nt
of s u bjects ma ki n g c o m pleti o n of t he trial wit hi n a n acce pta ble ti me fra me 
u nli kel y

Disc o nti n uati o n of de vel o p me nt of t he S p o ns or’s I M P

After t he i nteri m a nal y sis, t he ID M C declares s u peri or efficac y  i n t he a vel u ma b treat me nt ar m 
c om pare d 
wit h 
t h ose ra n d o ml y assi g ne d t o c o nti n ue o n first-li ne c he m ot hera p y a n d 
rec o m me n ds t hat t he trial be st o p pe d earl y.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 6 / 1 5 0
Healt h A ut h orities a n d I nde pe n de nt Et hics C o m mittees (I E Cs)/I nstit uti o nal Re vie w B oar ds (I R Bs) 
will be i nf or me d a b o ut t he disc o nti n ua ti o n of t he trial i n acc or da nce wit h a p plica ble re g ulati o ns.
T he w h ole trial ma y  be ter mi nate d or s us pe n de d u p o n re q uest of Healt h A ut h orities.
5. 7
Defi niti o n of E n d of Tri al
If t he trial is n ot ter mi nate d f or a reas o n gi ve n i n Secti o n  5. 6, t he s ur vi val f oll o w-u p will c o nti n ue 
u ntil 5 y ears after t he last s u bject recei ves t he last d ose of a vel u ma b.
6
I n vesti g ati o n al Me dici n al Pr o d uct a n d Ot her Dr u gs Use d i n 
t he Tri al
T he ter m I MP refers t o t he i n vesti gati o nal dr u g u n der g oi n g a cli nical trial, as well as t o a n y 
c o m parat or dr u g or place b o (as a p plica ble).  I n t his trial, t he i n vesti gati o nal dr u g is a vel u ma b a n d 
t he c o m parat or is a c he m ot hera p y re gi me n a d mi nistere d after ra n d o mizati o n.  
6. 1
Descri pti o n of t he I n vesti g ati o n al Me dici n al Pr o d uct
6. 1. 1
I n d ucti o n C he m ot her a p y
S u bjects will recei ve a n o xali plati n -fl u or o p yri mi di ne d o u blet c o m prise d of o xali plati n a n d eit her 
5- F U or ca pecita bi ne d uri n g t he I n d ucti o n P hase , w hic he ver is a p pr o ve d a n d us e d as t he S O C at 
t he In vesti gat or’s i nstit uti o n.

O xali plati n is a sterile l y o p hilize d p o w der or c o nce ntrate f or s ol uti o n f or i nf usi o n i nte n de d f or 
i nf usi o n, a n d is sli g htl y sol u ble i n water .  T he m olec ular wei g ht of o xali plati n is 3 9 7. 2 8 5 8 g/ m o l

5- F U is a sterile s ol uti o n i nte n de d f or I V ad mi nistrati o n.  It is a w hite t o practicall y w hite 
cr ys talli ne p o w der w hic h is s pari n gl y s ol u ble i n water.  T he m olec ular wei g ht of fl u or o uracil is 
1 3 0. 0 8 k Da.

Ca pecita bi ne is a w hite t o off -w hite cr ys talli ne p o w der s u p plie d as a ta blet f or m ulati o n i nte n de d 
f or oral a d mi nistrati o n .  Ta blets s h o ul d be s wall o we d wit h water wit hi n 3 0 mi n utes after a meal .  
T he m olec ular wei g ht of ca pecita bi ne is 3 5 9. 3 5 g/ m ol.
6. 1. 2
A vel u m a b
A vel u ma b is a sterile, clear, a n d c ol orless s ol uti o n i nte n d e d f or I V a d mi nistrati o n .  It is prese nte d 
at a c o nce ntrati o n of 2 0 m g/ m L  in si n gle-use glass vials cl ose d wit h a r u b ber st o p per a n d seale d 
wit h a n al u mi n u m p ol y pr o p y le ne fli p-off seal.
6. 1. 3
M ai nte n a nce C he m ot her a p y
S u bjects will c o nti n ue t he sa me re gi me n of o x ali plati n-fl u or o p yri mi di ne d o u blet as i n t he 
I n d ucti o n P hase (see Secti o n 6. 1. 1) .
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 7 / 1 5 0
6. 1. 4
Best S u p p orti ve C are
All s u bjects i n b ot h ar ms will recei ve B S C as bac k gr o u n d t hera p y .  S u bjects w h o are n ot dee me d 
eli gi ble t o recei ve f urt her c he m ot hera p y will recei ve B S C al o ne wit h n o acti ve t hera p y .  T here is 
n o u ni versal defi niti o n of B S C t hat ca n be a p plie d acr oss i nstit uti o ns, c o u ntries, or re gi o ns 
(Zafar 2 0 0 8 ).  Best s u p p orti ve care is defi ne d as “treat me nt a d mi nistere d wit h t he i nte nt t o 
ma xi mize Q o L wit h o ut a s pecific a nti ne o plastic re gi me n, w hic h i ncl u de a nti bi otics, a nal gesics, 
a ntie metics, t h orace ntesis, parace ntesis, bl o o d tra nsf usi o ns, n utriti o nal s u p p ort (i ncl u di n g 
jej u n ost o m y), ste nts f or d y s p ha gia, a n d f ocal e xter nal-bea m ra diati o n f or c o ntr ol of pai n, c o u g h, 
d y s p nea, or blee di n g” (Jasse m 2 0 0 8 ).  Best s u p p orti ve care will be a d mi nistere d per i nstit uti o nal 
g ui deli nes a n d ca n be a d mi nistere d wit h o ut a n y  a d diti o nal t hera p y.
6. 2
D os a ge a n d A d mi nistr ati o n
6. 2. 1
A vel u m a b D os a ge a n d A d mi nistr ati o n
S u bjects will recei ve a n I V i nf usi o n of a vel u ma b at a d ose of 1 0 m g / k g ( o ver t he d urati o n of 
1 h o ur) f oll o wi n g pretreat me nt as descri be d i n Secti o n 5. 1. 2. 2. 1 (Ta ble 3 ). M o dificati o ns of t he 
i nf usi o n rate d ue t o i nf usi o n-relate d reacti o ns are descri be d i n Secti o n 6. 5. 4. 1.  T he d ose of 
a vel u ma b will be calc ulate d base d o n t he wei g ht of t he s u bject deter mi ne d wit hi n 7 2 h o urs pri or 
t o t he da y  of dr u g a d mi nistrati o n. T he d ose of a vel u ma b use d f or t he pre vi o us a d mi nistrati o n ca n 
be re peate d if t he c ha n ge i n t he s u bject’s wei g ht is 1 0 % or less t ha n t he wei g ht use d f or t he last 
d ose calc ulati o n.  S u bjects will recei ve a vel u ma b o nce e ver y 2 wee ks u ntil t he criteria i n 
Secti o ns 5. 5 t hr o u g h 5. 7 are met.
S u bjects recei vi n g a vel u ma b ma y  co nti n ue treat me nt past t he i nitial deter mi nati o n of disease 
pr o gressi o n per R E CI S T v 1. 1 as l o n g t he f oll o wi n g criteria are met:

I n vesti gat or-assesse d cli nical be nefit, wit h o ut a n y r a pi d disease pr o gressi o n

T olera nce of a vel u ma b

Sta ble E C O G P S

Treat me nt b e y o n d pr o gressi o n will n ot dela y  an i m mi ne nt i nter ve nti o n t o pre ve nt seri o us 
c o m plicati o ns of disease pr o gressi o n (f or e xa m ple, ce ntral ner v o us s ys te m metastases).
T he decisi o n t o c o nti n ue a vel u ma b treat me nt be y o n d pr o gressi o n s h o ul d be disc usse d wit h t he 
M e dical M o nit or a n d d oc u me nte d i n t he trial rec or ds.
F or s u bjects c o nti n ui n g a vel u ma b after i nitial P D, a ra di o gra p hic assess me nt s h o ul d be perf or me d 
wit hi n 6 wee ks of ori gi nal P D t o deter mi ne w het her t here has bee n a decrease i n t he t u m or size, 
or c o nti n ue d P D. T he assess me nt of cli nical be nefit s h o ul d be bala nce d b y c li nical j u d g me nt as t o 
w het her t he s u bject is cli nicall y deteri orati n g a n d u nli kel y  to recei ve a n y be nefit fr o m c o ntin ue d 
treat me nt wit h a vel u ma b.
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 8 / 1 5 0
F or s u bjects recei vi n g a vel u ma b, if disc o nti n uati o n occ urs d ue t o pr o gressi o n a n d a defi niti ve 
dia g n osis/ra di o gra p hic c o nfir mati o n is n ot ma de at t he ti me of disc o nti n uati o n, a sec o n d i ma gi n g 
sca n m a y  be all o we d f or c o nfir mati o n of pr o gressi o n.  If pr o gressi o n at t he sec o n d i ma gi n g sca n 
is n ot c o nfir me d a n d t he s u bject wis hes t o restart, t he s u bject will be all o we d t o c o nti n ue recei vi n g 
a vel u ma b as l o n g as t he y meet t he criteria f or c o nti n uati o n of treat me nt be y o n d pr o gressi o n.
If t he I n vesti gat or feels t hat t he s u bject c o nti n ues t o ac hie ve cli nical be nefit b y  co nti n ui n g 
treat me nt, t he s u bject s h o ul d re mai n o n t he trial a n d c o nti n ue t o recei ve m o nit ori n g acc or di n g t o 
t he Sc he d ule of Assess me nts (Ta ble 3 ).
A n y  a d diti o nal c o nti n uati o n of a vel u ma b pl us B SC be y o n d f urt her pr o gressi o n m ust be disc usse d 
a n d a gree d u p o n wit h t he Me dical M o nit or. F urt her disease pr o gressi o n is defi ne d as a n a d diti o nal 
i ncrease i n t u m or b ur de n of 2 0 % a n d ≥ 5 m m a bs ol ute i ncrease i n t u m or b ur de n fr o m ti me of i nitial 
P D . T his i ncl u des a n i ncrease i n t he s u m of all tar get lesi o ns or t he de vel o p me nt of ne w 
meas ura ble lesi o ns.
Ne w lesio ns are c o nsi dere d meas urea ble at t he ti me of i nitial pr o gressi o n if t he l o n gest dia meter 
is at least 1 0 m m (e xce pt f or pat h ol o gical l ym p h n o des, w hic h m ust ha ve a s h ort a xis of at least 
1 5 m m). A n y  ne w lesi o n c o nsi dere d n o n meas ura ble at t he ti me of i nitial pr o gressi o n ma y  bec o me 
meas urea ble a n d t heref ore i ncl u de d i n t he t u m or b ur de n v ol u me if t he l o n gest dia meter i ncreases 
t o at least 1 0 m m (e xce pt f or pat h ol o gical l ym p h n o des, w hic h m ust ha ve a s h ort a xis of at least 
1 5 m m).
A d diti o nall y , s u bjects recei vi n g a vel u ma b w h o ha ve e x perie nce d a C R s h o ul d be treate d f or a 
mi ni m u m 
of 1 2 m o nt hs a n d/ or 
u ntil disease pr o gressi o n or u nacce pta ble t o xicit y, after 
c o nfir mati o n of res p o nse. I n case a s u bject wit h a c o nfir me d C R rela pses after st o p pi n g treat me nt, 
b ut pri or t o t he e n d of t he trial, 1 re-i nitiati o n of treat me nt is all o we d at t he discreti o n of t he 
I n vesti gat or a n d after a gree me nt wit h t he Me dical M o nit or. 
T o be eli gi ble f or retreat me nt, t he 
s u bject m ust n ot ha ve e x perie nce d a n y t o xicit y that le d t o treat me nt disc o nti n uati o n of t he i nitial 
a vel u ma b t hera py. S u bjects w h o re-i nitiate treat me nt will sta y on trial a n d will be treate d a n d 
m o nit ore d acc or di n g t o t he pr ot oc ol a n d f oll o w t he Sc he d ule of Assess me nts
u ntil disease 
pr o gressi o n (see Ta ble 3 ).
6. 2. 2
C he m ot her a p y D os a ge a n d A d mi nistr ati o n
I n d ucti o n c he m ot her a p y will be a d mi nistere d acc or di n g t o t he f oll o wi n g r ules.
T hera p y will be a d mi nistere d at t he d ose a n d sc he d ule s h o w n i n Ta ble 1 a n d Ta ble 2 or i n 
acc or da nce t o t he la bel i nstr ucti o ns a n d per l ocal g ui deli nes.  T he d osi n g fre q ue nc y is s u m marize d 
bel o w:

O xali plati n at 8 5 m g/ m 2 I V on D a y 1 wit h le uc o v ori n 2 0 0 m g/ m 2 I V o n Da y  1 ( or e q ui vale nt 
le v ole uc o v ori n d ose ) f oll o we d b y  5-F U at 2 6 0 0 m g/ m 2 I V c o nti n u o us i nf usi o n o ver 2 4 h o urs 
o n Da y  1, give n e ver y  2 wee ks (f or u p t o 1 2 wee ks) ,
O R
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
6 9 / 1 5 0
O xali plati n at 8 5 m g/ m 2 I V on D a y  1 wit h le uc o v ori n 4 0 0 m g / m2 I V on Da y 1 ( or e q ui vale nt 
le v ole uc o v ori n d ose) f oll o we d b y  5-F U at 4 0 0 m g/ m 2 I V pus h o n Da y  1 an d 2 4 0 0 m g/ m 2 I V 
c o nti n u o us i nf usi o n o ver 4 6- 4 8 h o urs ( Da ys 1 a n d 2) gi ve n e ver y 2 wee ks (f or u p t o 1 2 wee ks)
O R

O xali plati n at 1 3 0 m g/ m 2 I V on D a y 1 wit h ca pecita bi ne at 1 0 0 0 m g/ m 2 t wice dail y  for 2 wee ks 
f oll o we d by a 1 -wee k rest peri o d gi ve n e ver y  3 wee ks (f or u p t o 1 2 wee ks).  
L ocal la bel a n d g ui deli nes s h o ul d be f oll o we d f or s pecific starti n g d oses d ue t o re nal or he patic 
i m pair me nts a n d f or s u bse q ue nt d ose m o dificati o ns d ue t o differe nt t o xicities .
C he m ot hera p y d uri n g Mai nte na nce P hase will be a d mi nistere d acc or di n g t o t he f oll o wi n g r ules:

S u bjects will recei ve c o nti n uati o n of t he sa me re gi me n of o xali plati n -fl u or o p yri mi di ne 
d o u blet as i n t he I n d ucti o n P hase .

S u bjects w h o are n ot dee me d eli gi ble t o recei ve f urt her c he m ot hera p y will recei ve B S C 
al o ne wit h n o acti ve t hera p y.  Pri or t o ra n d o mizati o n, I n vesti gat ors m ust s pecif y BS C 
treat me nt f or t hese s u bjects.  

F or s u bjects recei vi n g c he m ot hera p y ( o xali plati n + 5- F U or o xali plati n + ca pecita bi ne) ,
d ose m o dificati o ns after t he starti n g d ose are all o we d if t he c o nti n uati o n of t he o xali plati n -
fl u or o p yri mi di ne d o u blet , or a c o m p o ne nt t here of, is pr o hi bite d b y  to xicit y .  F or s u bjects 
i nt olera nt t o f urt her o xali plati n, si n gle-a ge nt ca pecita bi ne or 5 -F U + le uc o v ori n will be a n 
o pti o n f or d ose m o dificati o n.
T hera p y will be a d mi nistere d u ntil disease pr o gressi o n, or u nacce pta ble t o xicit y, or f or t he 
acce pte d ma xi mal d urati o n of t he a ge nt(s) selecte d.
T hera p y  will be st o p pe d after t he first o n -treat me nt ra di ol o gical e val uati o n of disease pr o gressi o n.
S u bjects will recei ve trial treat me nt u ntil P D per R E CI S T v 1. 1, si g nifica nt cli nical deteri orati o n 
(cli nical pr o gressi o n), u nacce pta ble t o xicit y, f or t he acce pte d ma xi mal d urati o n of t he a ge nt(s) 
selecte d, wit h dra wal of c o nse nt, or if a n y  criteri o n f or wit h dra wal fr o m t he trial or trial treat me nt 
is f ulfille d.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 0 / 1 5 0
T a ble 9
All o we d T her a p y Re gi me ns
Pr o d u ct 
D e s cri pti o n
D o s a g e 
F or m
D o s e
D o si n g Fr e q u e n c y
5- fl u or o ur a cil 
( 5-F U )
I ntr a v e n o u s
(I V)
L e u c o v ori n 2 0 0 m g/ m 2 f oll o w e d b y 
5- F U 2 6 0 0 m g/ m
2
L e u c o v ori n 4 0 0 m g/ m 2 f oll o w e d b y 
5- F U 4 0 0 m g/ m
2 i ntr a v e n o u s p u s h 
(I V P) f oll o w e d b y 2 4 0 0 m g/ m
2 I V
O n D a y 1 e v er y 2 w e e k s.
L e u c o v ori n o n D a y 1 
5- F U I V P o n D a y 1
5- F U I V o v er 4 6 -4 8 h o ur s o n D a y 1 a n d 
D a y 2
C a p e cit a bi n e 
T a bl et
1 0 0 0 m g/ m 2
T wi c e d ail y f or 2 w e e k s f oll o w e d b y a 1 -w e e k 
r e st p eri o d, gi v e n i n 3-w e e k c y cl e s
O x ali pl ati n
I ntr a v e n o u s
(I V)
8 5 m g/ m 2 wit h 5 -F U
1 3 0 m g/ m
2 wit h c a p e cit a bi n e
O n D a y 1 e v er y 2 w e e k s 
O n D a y 1 e v er y 3 w e e k s .  C a p e cit a bi n e 
t a bl et s s h o ul d b e s w all o w e d wit h w at er wit hi n 
3 0 mi n ut e s aft er a m e al .
6. 3
Assi g n me nt t o Tre at me nt Gr o u ps
O nce t he s u bject has pr o vi de d a si g ne d i nf or me d c o nse nt f or m (IC F) a n d meets i ncl usi o n a n d
e xcl usi o n criteria, a n d has c o m plete d t he In d ucti o n P hase as s pecifie d i n t his pr ot oc ol, t he 
I n vesti gat or or dele gate will re q uest t he trial treat me nt assi g n me nt usi n g t he I WR S. 
Q uali fie d 
s u bjects will be ra n d o ml y assi g ne d i n a 1: 1 rati o t o recei ve eit her a vel u ma b or mai nte na nce 
c he m ot hera py. T he trial is f ull y co ntr olle d b y  the I WR S, w hic h assi g ns treat me nt i n di vi d ual 
( u ni q ue) kit n u m bers f or eac h s u bject. T he kit n u m ber is li n ke d via t he G o o d Ma n ufact uri n g 
Practice q ual ifie d sys te m t o t he c orres p o n di n g treat me nt as well as t o t he s u bject.
S u bject i de ntifiers will c o m prise 1 7 di gits, t he first 1 0 di gits re prese nti n g t he trial n u m ber, t he 
f oll o wi n g 3 di gits re prese nti n g t he site n u m ber, a n d t he last 4 di gits re prese nti n g the s u bject 
n u m ber, w hic h is all ocate d s e q ue ntiall y starti n g wit h 0 0 0 1.
6. 4
N o n- i n vesti g ati o n al Me dici n al Pr o d ucts t o be Use d
S u bjects ra n d o ml y assi g ne d t o recei ve a vel u ma b will recei ve pretreat me nt as descri be d i n 
Secti o n 5. 1. 2. 2. 1.
S u bjects ra n d o ml y  assi g ne d t o recei ve mai nte na nce c he m o t hera p y will recei ve pretreat me nt pri or 
t o eac h i nf usi o n per l ocal i nstit uti o nal practice.
I m me diate access t o a n i nte nsi ve care u nit or e q ui vale nt e n vir o n me nt a n d a p pr o priate me dical 
t hera py (i ncl u di n g e pi ne p hri ne, c ortic oster oi ds, I V a nti hista mi nes, br o nc h o dilat ors, a n d o x y ge n) 
m ust be a vaila ble f or use i n t he treat me nt of i nf usi o n -relate d reacti o ns. I nf usi o n of a vel u mab will 
be st o p pe d i n case of Gra de ≥ 2 i nf usi o n -relate d, aller gic, or a na p h ylactic reacti o ns.
As wit h all m o n ocl o n al a nti b o d y t her a pies, t here is a ris k of aller gic re acti o n .  A vel u m a b 
s h o ul d be a d mi nistere d i n a setti n g t h at all o ws f or i m me di ate access a n d a d mi nistr ati o n of 
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 1 / 1 5 0
t her a p y f or se vere aller gic/ h y perse nsiti vit y re acti o ns, s uc h as t he a bilit y t o i m ple me nt 
i m me di ate res uscit ati o n me as ures .  Ster oi ds ( de x a met h as o ne 1 0 m g), e pi ne p hri ne ( 1: 1 0 0 0 
dil uti o n), aller g y me dic ati o ns 
( a nti hist a mi nes), or e q ui v ale nts s h o ul d be a v ail a ble f or 
i m me di ate access.
If h y perse nsiti vit y  reacti o n occ urs, t he s u bject m ust be treate d acc or di n g t o t he best a vaila ble 
me dical 
practice. 
G ui deli nes 
f or ma na ge me nt 
of i nf usi o n-relate d reacti o ns a n d se vere 
h y perse nsiti vit y  an d fl u-li ke s ym pt o ms acc or di n g t o t he N CI are f o u n d i n Secti o ns 6. 5. 4. 1 a n d 
6. 5. 4. 2 , res pecti vel y.  A c o m plete g ui deli ne f or t he e mer ge nc y treat me nt of a na p h yl actic reacti o ns 
acc or di n g t o t he W or ki n g Gr o u p of t he Res uscitati on C o u ncil ( U nite d Ki n g d o m) ca n be f o u n d at 
htt ps:// w w w.res us. or g. u k/ pa ges/reacti o n. p df .  S u bjects s h o ul d be i nstr ucte d t o re p ort a n y  dela ye d 
reacti o ns t o t he I n vesti gat or i m me diatel y.
6. 5
C o nc o mit a nt Me dic ati o ns a n d T her a pies
All c o nc o mita nt me dicati o ns ta ke n b y  the s u bject d uri n g t he trial, fr o m t he date of si g nat ure of 
i nf or me d c o nse nt are t o be rec or de d i n t he a p pr o priate secti o n of t he eC R F, n oti n g t he na me, d ose, 
d urati o n, a n d i n dicati o n of eac h dr u g. N o n dr u g i nter ve nti o ns a n d a n y c ha n ges t o a c o nc o mita nt 
me dicati o n or ot her i nter ve nti o n s h o ul d als o be rec or de d i n t he e C R F.
6. 5. 1
Per mitte d Me dici nes
A n y  me dicati o ns ( ot her t ha n t h ose e xcl u de d b y  the cli nical trial pr ot oc ol) t hat are c o nsi dere d 
necessar y  t o pr otect s u bject welfare a n d will n ot i nterfere wit h t he trial treat me nt ma y be gi ve n at 
t he In vesti gat or’s discreti o n.
Ot her dr u gs t o be use d f or pr o p h yl a xis, treat me nt of h y perse nsiti vit y  reacti o ns, a n d treat me nt of 
fe ver or fl u-li ke sy m pt o ms are descri be d i n Secti o n  6. 5. 4. 2.
T he I n vesti gat or will rec or d all c o nc o mita nt me dicati o ns ta ke n b y  the s u bject d uri n g t he trial, fr o m 
t he date of si g nat ure of i nf or me d c o nse nt, i n t he a p pr o priate secti o n of t he e C R F.
A n y  ad diti o nal c o nc o mita nt t hera py t hat bec o mes necessar y  duri n g t he trial a n d a n y cha n ge t o 
c o nc o mita nt dr u gs m ust be rec or de d i n t he c orres p o n di n g secti o n of t he e C R F, n oti n g t he na me, 
d ose, d urati o n, a n d i n dicati o n of eac h dr u g.
Palliati ve b o ne -directe d ra di ot hera p y m a y be a d mi nistere d d uri n g t he trial.  T he assess me nt of P D 
will be ma de acc or di n g 
t o R E CI S T v 1. 1 a n d n ot base d o n t he necessit y f or palliati ve 
b o ne- directe d- ra di ot hera p y. Resc ue me dica ti o ns m a y  be a d mi nistere d t o a d dress i neffecti ve 
treat me nt, a ntici pate d a d verse reacti o ns, or a ntici pate d e mer ge nc y sit uati o ns.
Me dici nal pr o d ucts k n o w n t o pr ol o n g t he Q Tc m ust be use d wit h ca uti o n i n s u bjects recei vi n g 
o xali plati n.  
Bis p h os p h o nate or de n os u ma b treat me nt is all o we d d uri n g t he st u d y pr o vi de d t hat t he y are 
a d mi nistere d as c o nc o mita nt palliati ve a n d s u p p orti ve care f or disease -relate d s ym pt o ms.  Disease 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 2 / 1 5 0
pr o gressi o n s h o ul d be c o m pletel y rule d o ut a n d t he e xact reas o n f or t he use of t hese t herapies m ust 
clearl y be d oc u me nt e d.  
6. 5. 2
Pr o hi bite d Me dici nes
As state d f or t he e xcl usi o n criteria i n Secti o n  5. 3. 2 , s u bjects m ust n ot ha ve ha d pri or t hera p y wit h 
a n y anti b o d y  or dr u g tar geti n g T- cell c ore g ulat or y pr otei ns (i m m u ne c hec k p oi nts) s uc h as 
a nti-P D - 1, a nti-P D -L 1, or a nti-c yt ot o xic T -l ym p h oc y te a nti ge n -4 a nti b o d y or c o nc urre nt 
a ntica ncer treat me nt (f or e xa m ple, c yt ore d ucti ve t hera py, ra di ot hera p y [ wit h t he e xce pti o n of 
palliati ve b o ne- directe d ra di ot hera py, * or ra di ot hera py a d mi nistere d o n s u perficial lesi o ns], 
i m m u ne t hera py, or c yt o ki ne t hera py e xce pt f or er yt hr o p oieti n), maj or s ur ger y (e xcl u di n g pri or 
dia g n ostic bi o ps y ), or c o nc urre nt s yste mic t hera p y wit h ster oi ds or ot her i m m u n os u p pressi ve 
a ge nts or use of a n y i n vesti gati o nal dr u g wit hi n 2 8 da y s bef ore starti n g st u d y treat me nt.
* Palliati ve b o ne -directe d ra di ot hera p y s h o ul d be w it hi n a li mite d fiel d of ra diati o n a n d f or palliati o n o nl y.  It s h o ul d 
be a s h ort c o urse, acc or di n g t o l ocal i nstit uti o nal rec o m me n dati o n, a n d s h o ul d be c o m plete d at least 7 da ys pri or t o 
t he first a d mi nistrati o n of a vel u ma b.
I n a d diti o n, t he f oll o wi n g treat me nts m ust n ot be a d mi nistere d d uri n g t he trial:

I m m u n ot hera py, i m m u n os u p pressi ve dr u gs (t hat is, c he m ot hera p y or s yste mic c ortic oster oi ds 
e xce pt f or s h ort-ter m treat me nt of aller gic reacti o ns or f or t he treat me nt of ir A Es), or ot her 
e x peri me ntal p har mace utical pr o d ucts. S h ort -ter m a d mi nistrati o n of s yste mic ster oids (t hat is, 
f or aller gic reacti o ns or t he ma na ge me nt of ir A Es is all o we d)

Gr o wt h
fact ors f or s u bjects ra n d o ml y assi g ne d t o recei ve a vel u ma b ( gra n ul oc yte c ol o n y 
sti m ulati n g fact or or gra n ul oc y te macr o p ha ge 
c ol o n y sti m ulati n g fact or). 
E xce pti o n: 
er yt hr o p oieti n a n d dar be p oeti n al p ha ma y be prescri be d at t he I n vesti gat or’s discreti o n.
If t he a d mi nistrati o n of a n o n-per mitte d c o nc o mita nt dr u g bec o mes necessar y  d uri n g t he trial, t he 
s u bject will be wit h dra w n fr o m trial treat me nt (t he S p o ns or ma y  be c o ntacte d t o disc uss w het her 
t he trial treat me nt m ust be disc o nti n ue d). T he s u bject s h o ul d c o m plete t he E n d of Treat me nt visit 
( Secti o n 7. 1. 5)  a n d be f oll o we d f or s ur vi val acc or di n g t o Secti o n 7. 1. 6.
Me dicati o ns ot her t ha n th ose s pecifically e xcl u de d i n t his trial (see a b o ve) ma y  be a d mi nistere d 
f or t he ma na ge me nt of s ym pt o ms ass ociate d wit h t he a d mi nistrati o n of a vel u ma b or mai nte na nce
c he m ot hera py as re q uire d. 
T hese 
mi g ht 
i ncl u de a nal gesics, a nti-na usea me dicati o ns, 
a nti hista mi nes, di uretics, a ntia n xiet y me dicati o ns, a n d me dicati o n f or pai n ma na ge me nt, i ncl u di n g 
narc otic a ge nts.
A n y  ad diti o nal c o nc o mita nt t hera py t hat bec o mes necessar y  duri n g t he trial a n d a n y cha n ge t o 
c o nc o mita nt dr u gs m ust be rec or de d i n t he c orres p o n di n g secti o n of t he e C R F, n oti n g t he na me, 
d ose, d urati o n, a n d i n dicati o n of eac h dr u g.
6. 5. 3
Ot her I nter ve nti o ns
T he f oll o wi n g n o n dr u g t hera pies m ust n ot be a d mi nistere d d uri n g t he trial ( or wit hi n 2 8 da y s 
bef ore ra n d o mizati o n):
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 3 / 1 5 0

Maj or s ur ger y  (e xcl u di n g pri or dia gn ostic bi o ps y )

Her bal re me dies wit h i m m u n osti m ulati n g pr o perties (f or e xa m ple, mistlet oe e xtract) or k n o w n 
t o p ote ntiall y i nterfere wit h maj or or ga n f u ncti o n (f or e xa m ple, h yperici n)

S u bjects s h o ul d n ot a b use alc o h ol or ot her dr u gs d uri n g t he trial.
6. 5. 4
S peci al Prec a uti o ns
As a r o uti ne preca uti o n, s u bjects ra n d o ml y assi g ne d t o t he a vel u ma b ar m m ust be o bser ve d i n a n 
area wit h res uscitati o n e q ui p me nt a n d e mer ge nc y age nts. 
At all ti mes d uri n g a vel u ma b or 
mai nte na nce
c he m ot hera p y treat me nt, i m me diate e mer gen c y  treat me nt of a n i nf usi o n-relate d 
reacti o n or a se vere hy perse nsiti vit y  reacti o n acc or di n g t o i nstit uti o nal sta n dar ds m ust be ass ure d. 
I n or der t o treat p ossi ble h y perse nsiti vit y  reacti o ns, f or i nsta nce, de xa met has o ne 1 0 m g  an d 
e pi ne p hri ne i n a 1: 1 0 0 0 dil uti o n or e q ui vale nts s h o ul d al wa y s be a vaila ble al o n g wit h e q ui p me nt 
f or assiste d ve ntilati o n.
I nf usi o n of a vel u ma b will be st o p pe d i n case of Gra de ≥ 2 h y perse nsiti vit y , i nfla m mat or y res p o nse, 
or i nf usi o n-relate d reacti o n. T he treat me nt rec o m me n dati o ns f or i nf usi o n-relate d reacti o ns, se vere 
h y perse nsiti vit y  reacti o ns, a n d t u m or l ysis s yn dr o me acc or di n g t o t he N CI  are as o utli ne d i n 
Secti o n  6. 5. 4. 1, Secti o n 6. 5. 4. 2, a n d Secti o n  6. 5. 4. 3, res pecti vely.
I n vesti gat ors s h o ul d als o m o nit or s u bjects cl osel y f or p ote ntial ir A Es, w hic h m a y  first ma nifest 
after wee ks of treat me nt. S uc h e ve nts m a y  co nsist of persiste nt ras h, diarr hea a n d c olitis, 
a ut oi m m u ne he patitis, art hritis, gl o mer ul o ne p hritis, car di o m yo pat h y, or u veitis a n d ot her 
i nfla m mat or y eye  co n diti o ns. T he s pectr u m of h y p ot hetical ir A Es als o i ncl u des f or mati o n of a ut o-
a nti b o dies li ke a nti n uclear a nti b o dies or a nti ne utr o p hil c yt o plas mic a nti b o dies.  See Secti o n 
6. 5. 4. 4 f or details o n t he ma na ge me nt of ir A Es.
6. 5. 4. 1
I nf usi o n-rel ate d Re acti o ns
S y m pt o ms of i nf usi o n -relate d reacti o ns are fe ver, c hills, ri g ors, dia p h oresis, a n d hea dac he.  T hese 
s ym pt o ms ca n be ma na ge d acc or di n g t o  Ta ble 1 0.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 4 / 1 5 0
T a ble 1 0
Tre at me nt M o dific ati o n 
f or S y m pt o ms of I nf usi o n-rel ate d Re acti o ns 
Ass oci ate d wit h A vel u m a b
N CI - C T C A E Gr a d e v 4. 0 3
Tr e at m e nt M o difi c ati o n f or A v el u m a b
Gr a d e 1 – mil d

Mil d tr a n si e nt r e a cti o n; i nf u si o n i nt err u pti o n n ot 
i n di c at e d; i nt er v e nti o n n ot i n di c at e d.

D e cr e a s e t h e a v el u m a b i nf u si o n r at e b y 5 0 % 
a n d m o nit or cl o s el y f or a n y w or s e ni n g.
Gr a d e 2 – m o d er at e

T h er a p y or i nf u si o n i nt err u pti o n i n di c at e d b ut 
r e s p o n d s pr o m ptl y t o s y m pt o m ati c tr e at m e nt 
(f or e x a m pl e, a nti hi st a mi n e s, N S AI D s, 
n ar c oti c s, I V fl ui d s); pr o p h yl a cti c m e di c ati o n s 
i n di c at e d f or 2 4 h o ur s.

St o p a v el u m a b i nf u si o n.

R e s u m e i nf u si o n at 5 0 % of pr e vi o u s r at e o n c e 
i nf u si o n-r el at e d r e a cti o n h a s r e s ol v e d or 
d e cr e a s e d t o at l e a st Gr a d e 1 i n s e v erit y, a n d 
m o nit or cl o s el y f or a n y w or s e ni n g.
Gr a d e 3 or Gr a d e 4 – s e v er e or lif e- t hr e at e ni n g

Gr a d e 3: Pr ol o n g e d (f or e x a m pl e, n ot r a pi dl y 
r e s p o n si v e t o s y m pt o m ati c m e di c ati o n a n d/ or 
bri ef i nt err u pti o n of i nf u si o n); r e c urr e n c e of 
s y m pt o m s f oll o wi n g i niti al i m pr o v e m e nt; 
h o s pit ali z ati o n i n di c at e d f or cli ni c al s e q u el a e.

Gr a d e 4: Lif e -t hr e at e ni n g c o n s e q u e n c e s; 
ur g e nt i nt er v e nti o n i n di c at e d.

St o p t h e a v el u m a b i nf u si o n i m m e di at el y a n d 
di s c o n n e ct i nf u si o n t u bi n g fr o m t h e s u bj e ct.

S u bj e ct s h a v e t o b e wit h dr a w n i m m e di at el y 
fr o m a v el u m a b tr e at m e nt a n d m u st n ot r e c ei v e 
a n y f urt h er a v el u m a b tr e at m e nt.
I V =i ntr a v e n o u s, N CI-C T C A E = N ati o n al C a n c er I n stit ut e -C o m m o n T er mi n ol o g y Cri t eri a f or A d v er s e E v e nt, 
N S AI D s = n o n st er oi d al a nti -i nfl a m m at or y dr u g s.
O nce t he a vel u ma b i nf usi o n rate has bee n decrease d b y  50 % or i nterr u pte d d ue t o a n 
i nf usi o n-relate d reacti o n, it m ust re mai n decrease d f or all s u bse q ue nt i nf usi o ns. If t he s u bject has 
a sec o n d i nf usi o n-relate d reacti o n Gra de ≥ 2 o n t he sl o wer i nf usi o n rate, t he i nf usi o n s h o ul d b e 
st o p pe d, a n d t he s u bject s h o ul d disc o nti n ue a vel u ma b treat me nt. If a s u bject e x perie nces a Gra de 3 
or 4 i nf usi o n-relate d reacti o n at a n y time, t he s u bject m ust disc o nti n ue a vel u ma b. If a n i nf usi o n 
reacti o n occ urs, all details a b o ut dr u g pre parati o n a n d i nf usi o n m ust be rec or de d.
6. 5. 4. 2
Se vere H y perse nsiti vit y Re acti o ns a n d Fl u -li ke S y m pt o ms
If h y perse nsiti vit y  reacti o n occ urs, t he s u bject m ust be treate d acc or di n g t o t he best a vaila ble 
me dical practice. A c o m plete g ui deli ne f or t he e mer ge nc y treat me nt of a na p h ylactic reacti o ns 
acc or di n g t o t he W or ki n g Gr o u p of t he Res uscitati o n C o u ncil ( U nite d Ki n g d o m) ca n be f o u n d at 
htt ps:// w w w.res us. or g. u k/ pa ges/reacti o n. p df. S u bjects s h o ul d be i nstr ucte d t o re p ort a n y  dela ye d 
reacti o ns t o t he I n vesti gat or i m me diatel y.
S y m pt o ms i ncl u de i m paire d air wa y, decrease d o x y ge n sat urati o n ( < 9 2 %), c o nf usi o n, let har g y, 
h y p ote nsi o n, pale or cla m m y ski n, a n d c ya n osis. 
T hese s ym pt o ms ca n be ma na ge d wit h 
e pi ne p hri ne i njecti o n a n d de xa met has o ne. S u bjects s h o ul d be place d o n m o nit or i m me diatel y, a n d 
t he i nte nsi ve care u nit s h o ul d be alerte d f or p ossi ble tra nsfer if re q uire d.
F or pr o p h y la xis of fl u-li ke s ym pt o ms, 2 5 m g i n d o met haci n or c o m para ble n o nster oi dal a nti-
i nfla m mat or y dr u g d ose (e g, 6 0 0 m g i b u pr ofe n, 5 0 0 m g na pr o xe n s o di u m) ma y be a d mi nistere d 2 
h o urs bef ore a n d 8 h o urs after t he start of eac h d ose of a vel u ma b I V i nf usi o n. Alter nati ve 
treat me nts f or fe ver (e g, paraceta m ol/aceta mi n o p he n) may b e gi ve n t o s u bjects at t he discreti o n of 
t he In vesti gat or.
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 5 / 1 5 0
6. 5. 4. 3
T u m or L ysis S y n dr o me
I n a d diti o n, beca use a vel u ma b ca n i n d uce A D C C , t here is a p ote ntial ris k of t u m or l ysis s yn dr o m e. 
S h o ul d t his occ ur, s u bjects s h o ul d be treate d per t he l ocal g ui deli nes a n d t he ma na ge me nt 
al g orit h m (Fi g ure 2 ) p u blis he d b y H o war d ( 2 0 1 1).
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 -0 0 7
7 6 /1 5 0
Fi g ure 2
Assess me nt a n d I niti al M a n a ge me nt of T u m or L ysis S y n dr o me
T L S =t u m or l ysis s y n dr o me.
D oc u me nt N o. 
O bject N o.
M e a s ur e s er u m p ot a s s iu m, p h o s p h or u s , c al c iu m , cr e ati ni n e, ur i c a ci d , a n d ur in e o ut p ut 
J 
! 
L a b or at or y T L S 
Cli ni c a iT L S 
N o T L S at d i a g n o si s 
2: 2 a b n or m a l l a b or at or y 
A c ut e ki d n e y i nj ur y 
t e st v a lu e s 
S y m pt o m ati c h y p o -
! 
N o s y m pt o m s 
c a lc e mi a 
D y sr h yt h m i a 
A s s e s s c a n c er m a s s 
I 
1 
1 
S m a ll or r e s e ct e d 
M e d iu m- s iz e 
L ar g e c a n c er m a s s 
l o c aliz e d t u m or 
c a n c er m a s s 
B ul k y t u m or or or g a n 
i nfiltr atio n 
B o n e m arr o w r e pl a c e d 
w it h c a n c er 
+ 
A s s e s s c ell- ly s i s p ot e nt i al 
A s s e s s c ell- ly s i s p ot e nti al 
I 
I 
! 
! 
! 
r 
L o w II M e di u m or I 
u n k n o w n 
Hi g h 
L o w II M e d iu m or II 
u n k n o w n 
Hi g h I 
! 
A s s e s s p at ie nt 
pr e s e nt at io n 
Pr e e x isti n g n e p hr o p at h y 
D e h y dr at io n 
H y p ot e n s io n 
N e p h r ot o x i n e x p o s ur e 
I 
j_ c p 
j_ c: p 
N e g ligi bl e Ri s k 
L o w Ri s k or 
Hi g h Ri s k of 
Hi g h Ri s k of 
E st a b lis h e d 
of C lin i c a l T L S 
of Cl i ni c al T L S 
C lini c ai T L S 
Cli n ic a iT L S 
Cli n ic a iT L S 
N o pr o p h y la xi s 
lntr a v e n o u s fl uid s 
l ntr a v e n o u s fl uid s 
Intr a v e n o u s fl uid s 
Intr a v e n o u s fl ui d s 
N o m o n it orin g 
All o p ur in o l 
A llo p ur in o l or r a s-
R a s b ur ic a s e 
R a s b ur ic a s e 
D a ily la b or at or y t e st s 
b uri c a s e 
C ar d ia c m o n it orin g 
C ar d ia c m o n it orin g 
I n p ati e nt m o n it orin g 
L a b or at or y t e st s e v er y 
Int e n s iv e c ar e u n it 
L a b or at or y t e st s e v er y 
6- 8 hr 
L a b or at or y t e st s e v er y 
8- 1 2 h r 
4- 6 hr 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 7 / 1 5 0
6. 5. 4. 4
I m m u ne-rel ate d A d verse E ve nts
Beca use i n hi biti o n of P D -L 1  sti m ulates t he i m m u ne s yste m, ir A Es m a y  occ ur. Treat me nt of ir A Es 
is mai nl y de pe n de nt u p o n se verity ( N CI -C T C A E gra de):

Gra des 1 t o 2: treat s y m pt o maticall y  or wit h m o derate d ose ster oi ds, m ore fre q ue nt m o nit ori n g

Gra des 1 t o 2 ( persiste nt): ma na ge si milar t o hi g h gra de A E ( Gra des 3 t o 4)

Gra des 3 t o 4 : treat wit h hi g h d ose c ortic oster oi ds.
Treat me nt of ir A Es s h o ul d f oll o w t he g ui deli nes i n  Ta ble 1 1.
T a ble 1 1
M a n a ge me nt of I m m u ne -rel ate d A d verse E ve nts
G a str oi nt e sti n al ir A E s
S e v erit y of Di arr h e a / C oliti s
( N CI-C T C A E v 4)
I niti al M a n a g e m e nt
F oll o w -u p M a n a g e m e nt
Gr a d e 1
Di arr h e a: < 4 st o ol s/ d a y o v er 
B a s eli n e
C oliti s: a s y m pt o m ati c
C o nti n u e a v el u m a b t h er a p y .
S y m pt o m ati c tr e at m e nt ( e g, 
l o p er a mi d e)
Cl o s e m o nit ori n g f or w or s e ni n g 
s y m pt o m s
E d u c at e s u bj e ct t o r e p ort 
w or s e ni n g i m m e di at el y
If w or s e n s:
Tr e at a s Gr a d e 2 , 3 or 4
Gr a d e 2
Di arr h e a: 4 t o 6 st o ol s p er d a y o v er 
B a s eli n e; I V fl ui d s i n di c at e d 
< 2 4 h o ur s; n ot i nt erf eri n g wit h 
a cti viti e s of d ail y li vi n g (A D L )
C oliti s: a b d o mi n al p ai n; bl o o d i n 
st o ol
Wi t h h ol d a v el u m a b t h er a p y .
S y m pt o m ati c tr e at m e nt
If i m pr o v e s t o Gr a d e ≤1: 
R e s u m e a v el u m a b t h er a p y
If p er si st s > 5-7 d a y s or r e c ur s:
Tr e at a s Gr a d e 3 o r 4
Gr a d e 3 t o 4
Di arr h e a ( Gr a d e 3): ≥ 7 st o ol s p er 
d a y o v er B a s eli n e; i n c o nti n e n c e; I V 
fl ui d s ≥2 4 h; i nt erf eri n g wit h A D L
C oliti s ( Gr a d e 3): s e v er e a b d o mi n al 
p ai n, m e di c al i nt er v e nti o n i n di c at e d, 
p erit o n e al si g n s
Gr a d e 4: lif e -t hr e at e ni n g, p erf or ati o n
Wi t h h ol d a v el u m a b f or Gr a de 3 .
P er m a n e ntl y di s c o nti n u e a v el u m a b f or 
Gr a d e 4 or r e c urr e nt Gr a d e 3.
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e I V or 
e q ui v al e nt .
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s .
C o n si d er l o w er e n d o s c o p y
If i m pr o v e s: 
C o nti n u e st er oi d s u ntil Gr a d e ≤1, 
t h e n t a p er o v er at l e a st 1 m o nt h; 
r e s u m e a v el u m a b t h er a p y 
f oll o wi n g st er oi d s t a p er (f or i niti al 
Gr a d e 3).
If w or s e n s, p er si st s > 3 t o 5 d a y s, 
or r e c ur s aft er i m pr o v e m e nt :
A d d i nfli xi m a b 5 m g/ k g (if n o 
c o ntr ai n di c ati o n).
N ot e: I nfli xi m a b s h o ul d n ot b e 
u s e d i n c a s e s of p erf or ati o n or 
s e p si s
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 8 / 1 5 0
D er m at ol o gi c al ir A E s
Gr a d e of R a s h
( N CI-C T C A E v 4)
I niti al M a n a g e m e nt
F oll o w -u p M a n a g e m e nt
Gr a d e 1 t o 2 
C o v eri n g ≤ 3 0 % b o d y s urf a c e ar e a 
C o nti n u e a v el u m a b t h er a p y .
S y m pt o m ati c t h er a p y (f or e x a m pl e, 
a nti hi st a mi n e s, t o pi c al st er oi d s).
If Gr a d e 2 p er si st s > 1 t o 2 w e e k s 
or r e c ur s: 
Wi t h h ol d a v el u m a b t h er a p y
C o n si d er s ki n bi o p s y 
C o n si d er 0. 5 t o 1. 0 m g/ k g/ d a y 
pr e d ni s o n e or e q ui v al e nt . O n c e 
i m pr o vi n g, t a p er st er oi d s o v er at 
l e a st 1 m o nt h, c o n si d er 
pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s, a n d 
r e s u m e a v el u m a b t h er a p y
f oll o wi n g st er oi d s t a p er.
If w or s e n s: 
Tr e at a s Gr a d e s 3 t o 4 
Gr a d e s 3 t o 4
Gr a d e 3: C o v eri n g > 3 0 % b o d y 
s urf a c e ar e a 
Gr a d e 4: Lif e -t hr e at e ni n g 
c o n s e q u e n c e s
Wi t h h ol d a v el u m a b f or Gr a d e 3.
P er m a n e ntl y di s c o nti n u e f or Gr a d e 4 or 
r e c urr e nt Gr a d e 3.
C o n si d er s ki n bi o p s y .
D er m at ol o g y c o n s ult .
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt .
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s
If i m pr o v e s t o Gr a d e ≤1: 
T a p er st er o i d s o v er at l e a st 1 
m o nt h ; r e s u m e a v el u m a b t h er a p y 
f oll o wi n g st er oi d s t a p er (f or i niti al 
Gr a d e 3)
P ul m o n ar y  ir A E s
Gr a d e of P n e u m o niti s
( N CI-C T C A E v 4)
I niti al M a n a g e m e nt
F oll o w -u p M a n a g e m e nt
Gr a d e 1
R a di o gr a p hi c c h a n g e s o nl y 
C o n si d er wit h h ol di n g a v el u m a b 
t h er a p y 
M o nit or f or s y m pt o m s e v er y 2
t o 3 
d a y s 
C o n si d er P ul m o n ar y a n d I nf e cti o u s 
Di s e a s e c o n s ult s 
R e -a s s e s s at l e a st e v er y 3 w e e k s
If w or s e n s: 
Tr e at a s Gr a d e 2 or Gr a d e 3 t o 4 
Gr a d e 2
Mil d t o m o d er at e n e w s y m pt o m s 
Wi t hh ol d a v el u m a b t h er a p y
P ul m o n ar y a n d I nf e cti o u s Di s e a s e 
c o n s ult s
M o nit or s y m pt o m s d ail y, c o n si d er 
h o s pit ali z ati o n 
R e -a s s e s s e v er y 1 t o 3 d a y s 
If i m pr o v e s: 
W h e n s y m pt o m s r et ur n t o 
Gr a d e ≤1, t a p er st er oi d s o v er at 
l e a st 1 m o nt h, a n d t h e n r e s u m e 
a v el u m a b t h er a p y f oll o wi n g 
st er oi d s t a p er
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
7 9 / 1 5 0
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt 
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s
C o n si d er br o n c h o s c o p y, l u n g bi o p s y 
If n ot i m pr o vi n g aft er 2 w e e k s or 
w or s e ni n g or f or r e c urr e nt 
Gr a d e 2 : 
Tr e at a s Gr a d e 3 t o 4 
Gr a d e 3 t o 4
Gr a d e 3: S e v er e n e w s y m pt o m s; 
N e w/ w or s e ni n g h y p o xi a;
Gr a d e 4: Lif e -t hr e at e ni n g 
P er m a n e ntl y di s c o nti n u e a v el u m a b 
t h er a p y
H o s pit ali z e
P ul m o n ar y a n d I nf e cti o u s Di s e a s e 
c o n s ult s
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt 
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s 
C o n si d er br o n c h o s c o p y, l u n g bi o p s y 
If i m pr o v e s t o Gr a d e ≤ 1: 
T a p er st er oi d s o v er at l e a st 1 
m o nt h 
If n ot i m pr o vi n g aft er 4 8 h o ur s or 
w or s e ni n g: 
A d d a d diti o n al 
i m m u n o s u p pr e s si o n (f or e x a m pl e, 
i nfli xi m a b, c y cl o p h o s p h a mi d e, I V 
i m m u n o gl o b uli n, or 
m y c o p h e n ol at e m of etil) 
H e p ati c ir A E s
Gr a d e of Li v er T e st El e v ati o n
( N CI-C T C A E v 4)
I niti al M a n a g e m e nt
F oll o w -u p M a n a g e m e nt
Gr a d e 1
Gr a d e 1 A S T or A L T > U L N t o 3. 0 ×
U L N a n d/ or t ot al bilir u bi n > U L N t o 
1. 5 × U L N 
C o nti n u e a v el u m a b t h er a p y
C o nti n u e li v er f u n cti o n m o nit ori n g 
If w or s e n s: 
Tr e at a s Gr a d e s 2 or 3 t o 4 
Gr a d e 2
A S T or A L T > 3. 0 t o ≤ 5 × U L N 
a n d/ or t ot al bilir u bi n > 1. 5 t o ≤ 3 ×
U L N 
Wi t h h ol d a v el u m a b t h er a p y .
I n cr e a s e fr e q u e n c y of m o nit ori n g t o 
e v er y 3 d a y s 
If r et ur n s t o Gr a d e ≤1 : 
R e s u m e r o uti n e m o nit ori n g, 
r e s u m e a v el u m a b t h er a p y
If el e v ati o n p er si sts > 5 t o 7 d a y s 
or w or s e n s : Tr e at a s Gr a d e 3 t o 4
Gr a d e 3 t o 4
A S T or A L T > 5 × U L N a n d/ or t ot al 
bilir u bi n > 3 × U L N 
P er m a n e ntl y d i s c o nti n u e a v el u m a b 
t h er a p y 
I n cr e a s e fr e q u e n c y of m o nit ori n g t o 
e v er y 1 t o 2 d a y s .
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt .
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s .
C o n s ult g a st r o e nt er ol o gi st/ 
h e p at ol o gi st.
C o n si d er o bt ai ni n g M RI/ C T s c a n of 
li v er a n d li v er bi o p s y if cli ni c all y 
w arr a nt e d .
If r et ur n s t o Gr a d e ≤1 : 
T a p er st er oi d s o v er at l e a st 1 
m o nt h 
If d o e s n ot i m pr o v e i n > 3 t o 5 
d a y s, w or s e n s or r e b o u n d s: 
A d d m y c o p h e n ol at e m of etil 1 
gr a m ( g) t wi c e d ail y 
If n o r e s p o n s e wit hi n a n a d diti o n al 
3 t o 5 d a y s, c o n si d er ot h er 
i m m u n o s u p pr e s s a nt s p er l o c al 
g ui d eli n e s
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 0 / 1 5 0
R e n al ir A E s
Gr a d e of Cr e ati ni n e I n cr e a s e d 
( N CI-C T C A E v 4)
I niti al M a n a g e m e nt
F oll o w - u p M a n a g e m e nt
Gr a d e 1
Cr e ati ni n e i n cr e a s e 1. 5 x b a s eli n e or 
Cr e ati ni n e i n cr e a s e d > U L N t o 1. 5 ×
U L N
C o nti n u e a v el u m a b t h er a p y
C o nti n u e r e n al f u n cti o n m o nit ori n g
If w or s e n s:
Tr e at a s Gr a d e 2 t o 3 or 4
Gr a d e 2 t o 3
Cr e ati ni n e i n cr e a s e d > 1. 5 x 
b a s eli n e a n d ≤ 6 × U L N or 
Cr e ati ni n e > 1. 5 a n d ≤6 x U L N
Wi t h h ol d a v el u m a b t h er a p y
I n cr e a s e fr e q u e n c y of m o nit ori n g t o 
e v er y 3 d a y s
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s
C o n si d er r e n al bi o p s y
If r et ur n s t o G r a d e ≤1:
T a p er st er oi d s o v er at l e a st 1 
m o nt h, a n d r e s u m e a v el u m a b 
t h er a p y f oll o wi n g st er oi d s t a p er
If w or s e n s: 
Tr e at a s Gr a d e 4
Gr a d e 4
Cr e ati ni n e i n cr e a s e d > 6 × U L N
P er m a n e ntl y di s c o nti n u e a v el u m a b 
t h er a p y
M o nit or cr e ati ni n e d ail y
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt.
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s
C o n si d er r e n al bi o p s y
N e p hr ol o g y c o n s ult
If r et ur n s t o Gr a d e ≤1:
T a p er st er oi d s o v er at l e a st 1 
m o nt h
C ar di a c ir A E s
M y o c ar diti s
I niti al M a n a g e m e nt
F oll o w -u p M a n a g e m e nt
N e w o n s et of c ar di a c si g n s or 
s y m pt o m s a n d / or n e w l a b or at or y 
c ar di a c bi o m ar k er el e v ati o n s ( e g,
tr o p o ni n, C K-m u s cl e/ br ai n , B N P) or 
c ar di a c i m a gi n g a b n or m aliti e s 
s u g g e sti v e of m y o c ar diti s
Wi t h h ol d a v el u m a b t h er a p y.
H o s pit ali z e .
I n t h e pr e s e n c e of lif e- t hr e at e ni n g 
c ar di a c d e c o m p e n s ati o n, c o n si d er 
tr a n sf er t o a f a cilit y e x p eri e n c e d i n 
a d v a n c e d h e art f ail ur e a n d arr h yt h mi a 
m a n a g e m e nt .
C ar di ol o g y c o n s ult t o e st a bli s h eti ol o g y 
a n d r ul e -o ut i m m u n e -r el at e d m y o c ar diti s.
G ui d eli n e b a s e d s u p p ort i v e tr e at m e nt a s 
p er c ar di ol o g y c o n s ult. *
C o n si d er m y o c ar di al bi o p s y if 
r e c o m m e n d e d p er c ar di ol o g y c o n s ult.
If s y m pt o m s i m pr o v e a n d i m m u n e-
r el at e d eti ol o g y i s r ul e d o ut, r e st art 
a v el u m a b t h er a p y.
If s y m pt o m s d o n ot i m pr o v e/ w or s e n, 
vir al m y o c ar diti s i s e x cl u d e d, a n d 
i m m u n e-r el at e d eti ol o g y i s 
s u s p e ct e d or c o nfir m e d f oll o wi n g 
c ar di ol o g y c o n s ult, m a n a g e a s 
i m m u n e-m e di at e d m y o c ar diti s.
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 1 / 1 5 0
I m m u n e-r el at e d m y o c ar diti s
P er m a n e ntl y di s c o nti n u e a v el u m a b.
G ui d eli n e b a s e d s u p p orti v e tr e at m e nt a s 
a p pr o pri at e a s p er c ar di ol o g y c o n s ult. *
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s.
O n c e i m pr o vi n g, t a p er st er oi d s o v er 
at l e a st 1 m o nt h.
If n o i m pr o v e m e nt or w or s e ni n g, 
c o n si d er a d diti o n al 
i m m u n o s u p pr e s s a nt s ( e g,
a z at hi o pri n e, c y cl o s p ori n e A)
* L o c al g ui d eli n e s, or e g , E ur o p e a n S o ci et y of C ar di ol o g y or A m eri c a n H e art A s s o ci ati o n g ui d eli n e s
E ur o p e a n S o ci et y of C ar di ol o g y g ui d eli n e s w e b sit e: htt p s:// w w w. e s c ar di o. or g/ G ui d eli n e s/ Cli ni c al- Pr a cti c e -
G ui d eli n e s
A m eri c a n H e art A s s o ci ati o n g ui d eli n e s w e b sit e:
htt p:// pr of e s si o n al. h e art. or g/ pr of e s si o n al/ G ui d eli n e s St at e m e nt s/ s e ar c hr e s ult s.j s p ? q = & y = &t = 1 0 0 1
E n d o cri n e ir A E s
E n d o cri n e Di s or d er
I niti al M a n a g e m e nt
F oll o w -u p M a n a g e m e nt
Gr a d e 1 or Gr a d e 2 
e n d o cri n o p at hi e s ( h y p ot h yr oi di s m, 
h y p ert h yr oi di s m, a dr e n al 
i n s uffi ci e n c y, T y p e I di a b et e s 
m ellit u s)
C o nti n u e a v el u m a b t h er a p y
E n d o cri n ol o g y c o n s ult if n e e d e d
St art t h yr oi d h or m o n e r e pl a c e m e nt 
t h er a p y (f or h y p ot h yr oi di s m), 
a nti -t h yr oi d tr e at m e nt (f or 
h y p ert h yr oi di s m), c orti c o st er oi d s (f or 
a dr e n al i n s uffi ci e n c y) or i n s uli n (f or 
T y p e I di a b et e s m ellit u s) a s 
a p pr o pri at e.  
R ul e -o ut s e c o n d ar y e n d o cri n o p at hi e s 
(i e, h y p o pit uit ari s m / h y p o p h y siti s)
C o nti n u e h or m o n e 
r e pl a c e m e nt/ s u p pr e s si o n a n d 
m o nit ori n g of e n d o cri n e f u n cti o n a s 
a p pr o pri at e.
Gr a d e 3 or Gr a d e 4 
e n d o cri n o p at hi e s ( h y p ot h yr oi di s m, 
h y p ert h yr oi di s m, a dr e n al 
i n s uffi ci e n c y, T y p e I di a b et e s 
m ellit u s)
Wi t h h ol d a v el u m a b t h er a p y
C o n si d er h o s pit ali z ati o n
E n d o cri n ol o g y c o n s ult
St art t h yr oi d h or m o n e r e pl a c e m e nt 
t h er a p y (f or h y p ot h yr oi di s m), 
a nti -t h yr oi d tr e at m e nt (f or 
h y p ert h yr oi di s m), c orti c o st er oi d s (f or 
a dr e n al i n s uffi ci e n c y) or i n s uli n (f or 
T y p e I di a b et e s m ellit u s) a s 
a p pr o pri at e.  
R ul e -o ut s e c o n d ar y e n d o cri n o p at hi e s 
(i e, h y p o pit uit ari s m / h y p o p h y siti s)
R e s u m e a v el u m a b o n c e 
s y m pt o m s a n d/ or l a b or at or y t e st s 
i m pr o v e t o Gr a d e ≤ 1 ( wit h or 
wit h o ut h or m o n e 
r e pl a c e m e nt/ s u p pr e s si o n).
C o nti n u e h or m o n e 
r e pl a c e m e nt/ s u p pr e s si o n a n d 
m o nit ori n g of e n d o cri n e f u n cti o n 
a s a p pr o pri at e. 
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 2 / 1 5 0
H y p o pit uit ari s m/ H y p o p h y siti s 
( s e c o n d ar y e n d o cri n o p at hi e s)
If s e c o n d ar y t h yr oi d a n d/ or a dr e n al 
i n s uffi ci e n c y i s c o nfir m e d (i e,
s u b n or m al s er u m t h yr o xi n e wit h 
i n a p pr o pri at el y l o w t h yr oi d-sti m ul ati n g 
h or m o n e a n d/ or l o w s er u m c orti s ol wit h 
i n a p pr o pri at el y l o w a dr e n o c orti c otr o pi c
h or m o n e ):

R ef er t o e n d o cri n ol o gi st f or 
d y n a mi c t e sti n g a s i n di c at e d a n d 
m e a s ur e m e nt of ot h er h or m o n e s 
( F S H, L H, G H/I G F-1, P R L, 
t e st o st er o n e i n m e n, e str o g e n s i n 
w o m e n) 

H or m o n e 
r e pl a c e m e nt/ s u p pr e s si v e t h er a p y 
a s a p pr o pri at e 

P erf or m pit uit ar y M RI a n d vi s u al 
fi el d e x a mi n ati o n a s i n di c at e d
If h yp o p h y siti s c o nfir m e d:

C o nti n u e a v el u m a b if mil d 
s y m pt o m s wit h n or m al M RI. 
R e p e at t h e M RI i n 1 m o nt h

Wi t h h ol d a v el um a b if m o d er at e, 
s e v er e or lif e -t hr e at e ni n g 
s y m pt o m s of h y p o p h y siti s a n d/ or 
a b n or m al M RI. C o n si d er 
h o s pit ali z ati o n. Initi at e 
c orti c o st er oi d s ( 1 t o 2 m g/ k g/ d a y 
pr e d ni s o n e or e q ui v al e nt) f oll o w e d 
b y c orti c o st er oi d s t a p er d uri n g at 
l e a st 1 m o nt h. 
•
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u n i sti c i nf e cti o n s.
R e s u m e a v el u m a b o n c e s y m pt o m s 
a n d h or m o n e t e st s i m pr o v e t o 
Gr a d e ≤ 1 ( wit h or wit h o ut h or m o n e 
r e pl a c e m e nt).
I n a d diti o n, f or h y p o p h y siti s wit h 
a b n or m al M RI, r e s u m e a v el u m a b 
o nl y o n c e s hri n k a g e of t h e pit uit ar y 
gl a n d o n M RI/ C T s c a n i s 
d o c u m e nt e d. 
C o nti n u e h or m o n e 
r e pl a c e m e nt/ s u p pr e s si o n t h er a p y a s 
a p pr o pri at e.
Ot h er ir A E s ( n ot d e s cri b e d a b o v e)
Gr a d e of ot h er ir A E s
( N CI-C T C A E v 4)
I niti al M a n a g e m e nt
F oll o w - u p M a n a g e m e nt
Gr a d e 2 or Gr a d e 3 cli ni c al si g n s or 
s y m pt o m s s u g g e sti v e of a p ot e nti al 
ir A E
Wi t h h ol d a v el u m a b t h er a p y p e n di n g 
cli ni c al i n v e sti g ati o n
If ir A E i s r ul e d o ut, m a n a g e a s 
a p pr o pri at e a c c or di n g t o t h e
di a g n o si s a n d c o n si d er r e st arti n g 
a v el u m a b t h er a p y
If ir A E i s c o nfir m e d, tr e at a s 
Gr a d e 2 or 3 ir A E
Gr a d e 2 ir A E or fir st o c c urr e n c e of 
Gr a d e 3 ir A E
Wi t h h ol d a v el u m a b t h er a p y
1. 0 t o 2. 0 m g/ k g/ d a y pr e d ni s o n e or 
e q ui v al e nt  
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s 
S p e ci alt y c o n s ult a s a p pr o pri at e
If i m pr o v e s t o Gr a d e ≤ 1: 
T a p er st er oi d s o v er at l e a st 1 m o nt h 
a n d r e s u m e a v el u m a b t h er a p y 
f oll o wi n g st er oi d s t a p er.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 3 / 1 5 0
R e c urr e n c e of s a m e Gr a d e 3 ir A E s
P er m a n e ntl y di s c o nti n u e a v el u m a b 
t h er a p y
1. 0 t o 2. 0 m g/ k g/ d a y
pr e d ni s o n e or e q ui v al e nt
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s 
S p e ci alt y c o n s ult a s a p pr o pri at e
If i m pr o v e s t o Gr a d e ≤ 1: 
T a p er st er oi d s o v er at l e a st 1 m o nt h
Gr a d e 4 
P er m a n e ntl y di s c o nti n u e a v el u m a b 
t h er a p y
1. 0 t o 2. 0 m g/ k g/ d a y
pr e d ni s o n e or e q ui v al e nt a n d/ or ot h er 
i m m u n o s u p pr e s s a nt a s n e e d e d
A d d pr o p h yl a cti c a nti bi oti c s f or 
o p p ort u ni sti c i nf e cti o n s 
S p e ci alt y c o n s ult
If i m pr o v e s t o Gr a d e ≤ 1: 
T a p er st er oi d s o v er at l e a st 1 m o nt h
R e q uir e m e nt f or 1 0 m g p er d a y or 
gr e at er pr e d ni s o n e or e q ui v al e nt f or 
m or e t h a n 1 2 w e e k s f or r e a s o n s 
ot h er t h a n h or m o n al r e pl a c e m e nt f or 
a dr e n al i n s uffi ci e n c y
P er si st e nt Gr a d e 2 or 3 ir A E l a sti n g 
1 2 w e e k s or l o n g er
P er m a n e ntl y di s c o nti n u e a v el u m a b 
t h er a p y
S p e ci alt y c o n s ult
A D L = a cti viti e s of d ail y li vi n g , A L T = al a ni n e a mi n otr a n sf er a s e, A S T = a s p art at e a mi n otr a n sf er a s e, B N P = B- t y p e 
n atri ur eti c p e pti d e , C K = cr e ati n e ki n a s e , C T = c o m p ut e d t o m o gr a p h y , F S H =f olli cl e-sti m ul ati n g h or m o n e, G H = gr o wt h 
h or m o n e, I G F -1 =i n s uli n -li k e gr o wt h f a ct or 1, ir A E =i m m u n e-r el at e d a d v er s e e v e nt, I V =i ntr a v e n o u s, L H =l ut ei ni zi n g 
h or m o n e , M RI = m a g n eti c r e s o n a n c e i m a gi n g, N CI-C T C A E = N ati o n al C a n c er I n stit ut e -C o m m o n T er mi n ol o g y Crit eri a 
f or A d v er s e E v e nt, P R L = pr ol a cti n, U L N = u p p er li mit of n or m al.
6. 5. 5
M a n a ge me nt 
of S pecific A d verse E ve nts or A d verse Dr u g 
Re acti o ns
T he ma na ge me nt of ir A Es is descri be d i n Secti o n 6. 5. 4. 4.
6. 6
P ac k a gi n g a n d L a beli n g
of t he I n vesti g ati o n al Me dici n al 
Pr o d uct
A vel u ma b is f or m ulate d as a 2 0 m g/ m L s ol uti o n a n d is s u p plie d b y  the S p o ns or i n si n gle-use glass 
vials, st o p pere d wit h a r u b be r se pt u m a n d seale d wit h a n al u mi n u m p ol ypr o p y le ne fli p-off seal.
All I MPs will be pac ka ge d a n d la bele d i n acc or da nce wit h all a p plica ble re g ulat or y  re q uire me nts 
a n d G o o d Ma n ufact uri n g Practice G ui deli nes. A vel u ma b will be pac ke d i n b o xes eac h c o ntai ni n g 
1 vial. T he i nf or mati o n o n t he trial treat me nt will be i n acc or da nce wit h a p pr o ve d s u b missi o n 
d oc u me nts .  
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 4 / 1 5 0
O xali plati n, 5 -F U, a n d ca pecita bi ne, will be s u p plie d b y  the st u d y ce nter or b y  the S p o ns or, 
acc or di n g t o l ocal la ws a n d re g ulati o ns.
6. 7
Pre p ar ati o n, H a n dli n g , a n d St or a ge of t he I n vesti g ati o n al 
Me dici n al Pr o d uct
T he c o nte nts of t he a vel u ma b vials are sterile a n d n o n p yr o ge nic, a n d d o n ot c o ntai n bacteri ostatic 
preser vati ves. A n y s pills t hat occ ur s h o ul d be clea ne d u p usi n g t he facilit y’s sta n dar d clea n u p 
pr oce d ures f or bi ol o gic pr o d ucts.
A vel u ma b m ust be st ore d at 
 t o 
 u ntil use, wit h a te m perat ure l o g mai ntai ne d dail y . All 
me dicati o n b o xes s u p plie d t o eac h trial site m ust be st ore d caref ull y, safel y, a n d se parately fr o m 
ot her dr u gs.
A vel u ma b st ore d at r o o m te m perat ure 
 or at ele vate d te m perat ures 
 
f or e xte n de d peri o ds is s u bject t o de gra dati o n. A vel u ma b m ust n ot be fr oze n. R o u g h s ha ki n g of 
a vel u ma b m ust be a v oi de d.
F or a p plicati o n i n t his trial, a vel u ma b m ust be dil ute d wit h 0. 9 % sali ne s ol uti o n (s o di u m c hl ori de 
i njecti o n). Detaile d i nf or mati o n o n i nf usi o n ba gs a n d me dical de vices t o be use d f or t he 
pre parati o n of t he dil uti o ns a n d s u bse q ue nt a d mi nistrati o n will be pr o vi de d i n t he I P M P.
A vel u ma b m ust n ot be use d f or a n y  p ur p ose ot her t ha n t he trial. T he a d mi nistrati o n of a vel u ma b 
t o s u bjects w h o ha ve n ot bee n e nr olle d i nt o t he trial is n ot c o vere d by t he trial i ns ura nce.
A n y  un use d p orti o n of t he s ol uti o n s h o ul d be discar de d i n bi o hazar d waste dis p osal wit h fi nal 
dis p osal b y  acce pte d l ocal a n d nati o nal sta n dar ds of i nci nerati o n.
St ora ge, ha n dli n g, pre parati o n, a n d dis p osal of I M P s h o ul d be acc ordi n g t o l ocal i nstit uti o nal 
g ui deli nes.
6. 8
I n vesti g ati o n al Me dici n al Pr o d uct Acc o u nt a bilit y
T he I n vesti gat or is res p o nsi ble f or e ns uri n g acc o u nta bilit y for a vel u ma b a n d mai nte na nce 
c he m ot hera p y, i ncl u di n g rec o nciliati o n a n d mai nte na nce of dr u g rec or ds.

U p o n recei pt of trial treat me nt, t he I nvesti gat or ( or desi g nee) will c hec k f or acc urate deli ver y 
a n d ac k n o wle d ge recei pt b y  si gni n g ( or i nitiali n g) a n d dati n g t he d oc u me ntati o n pr o vi de d b y  
t he S p o ns or a n d ret ur ni n g it t o t he S p o ns or. A c o p y will be retai ne d f or t he I nvesti gat or Site 
File.

T he dis pe nsi n g of t he trial treat me nt will be caref ull y rec or de d o n t he a p pr o priate dr u g 
acc o u nta bilit y for ms pr o vi de d b y  t he S p o ns or a n d a n acc urate acc o u nti n g will be a vaila ble f or 
verificati o n b y t he cli nical researc h ass oci ate ( C R A) at eac h m o nit ori n g visit.

Trial treat me nt acc o u nta bilit y  rec or ds will i ncl u de:
1.
C o nfir mati o n of trial treat me nt deli ver y  t o t he trial site
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 5 / 1 5 0
2.
T he i n ve nt or y at t he site of trial treat me nt pr o vi de d b y  the S p o ns or a n d pre pare d at 
t he site
3.
T he use of eac h d ose b y  eac h s u bject
4.
T he dis p ositi o n of u n use d trial treat me nt
5.
Dates, q ua ntities, batc h n u m bers, e x pir y  dates a n d (f or trial treat me nt pre pare d at t he 
site) f or m ulati o n, as well as t he s u bjects’ trial n u m bers.

T he I n vesti gat or s h o ul d mai ntai n rec or ds t ha t a de q uatel y d oc u me nt:
1.
T hat t he s u bjects were 
pr o vi de d t he d oses s pecifie d b y  the cli nical trial 
pr ot oc ol/a me n d me nt(s)
2.
T hat all trial treat me nt pr o vi de d b y  t he S p o ns or was f ull y rec o ncile d.
U n use d trial treat me nt m ust n ot be discar de d or use d f or a n y p ur p ose ot her t ha n t he prese nt trial. 
A n y  trial treat me nt t hat has bee n dis pe nse d t o a s u bject m ust n ot be re-dis pe nse d t o a differe nt 
s u bject.
T he C R A will peri o dicall y  collect t he trial treat me nt acc o u nta bilit y for ms a n d will c hec k all ret ur ns 
( b ot h u n use d an d use d c o ntai ners) bef ore a ut h orizi n g t heir destr ucti o n b y  t he trial site.
At t he c o ncl usi o n or ter mi nati o n of t his trial, trial site pers o n nel a n d t he C R A will c o n d uct a fi nal 
pr o d uct s u p pl y in ve nt or y  on t he i n vesti gati o nal dr u g acc o u nta bilit y for ms a n d all u n use d 
c o ntai ners will be destr o y e d. I nstr ucti o ns f or destr ucti o n of pr o d uct will be pr o vi de d t o t he site. 
T he C li nical T rial M o nit or will be s u p plie d wit h a c o p y f or fili n g of t he i n vesti gati o nal dr u g 
acc o u nta bilit y f or ms. T his d oc u me ntati o n m ust c o ntai n a rec or d of cli nical s u p plies use d, u n use d, 
a n d destr o ye d a n d s hall i ncl u de i nf or mati o n o n:

All a d mi nistere d u nits

All u n use d u nits

All destr o y e d u nits ( d uri n g t he trial)

All destr o y e d u nits at t he e n d of t he trial

Date of destr ucti o n(s)

Na me a n d si g nat ure of t he I n vesti gat or/ p har macist.
It m ust be e ns ure d at eac h trial site t hat t he trial treat me nt is n ot use d:

After t he e x pir y  date

After t he retest date u nless t he trial treat me nt is re- a nal yz e d a n d its retest date e xte n de d.
T his is t o be cl osel y  m o nit ore d b y t he Cli nical Trial M o nit or.
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 6 / 1 5 0
6. 9
Assess me nt of I n vesti g ati o n al Me di ci n al Pr o d uct C o m pli a nce
I n t his trial, s u bjects will recei ve trial treat me nt at t he i n vesti gati o nal site. Well -trai ne d me dical 
staff will m o nit or a n d perf or m t he trial treat me nt a d mi nistrati o n. T he i nf or mati o n of eac h trial 
treat me nt a d mi nistrati o n i nclu di n g t he date, ti me, a n d d ose of trial treat me nt will be rec or de d o n 
t he e C R F. T he I nvesti gat or will ma ke s ure t hat t he i nf or mati o n e ntere d i nt o t he e C R F re gar di n g 
dr u g a d mi nistrati o n is acc urate f or eac h s u bject. A n y  reas o n f or n o nc o m plia nce s h o ul d be 
d oc u me nte d.
N o nc o m plia nce is defi ne d as a s u bject missi n g > 1 st u d y treat me nt a d mi nistrati o n f or n o n me dical 
reas o ns (see Secti o n 5. 5. 1 ). If 1 st u d y treat me nt a d mi nistrati o n is misse d a n d t he i nter val bet wee n 
t he s u bse q ue nt treat me nt a n d t he last st u d y treat me nt visit is l o n ger t ha n 4 wee ks f or n o n me dical 
reas o ns, t he criteria of i ns ufficie nt c o m plia nce are met as well.
6. 1 0
Bli n di n g
T his is a n o pe n -la bel trial; t h us, trial treat me nt is n ot bli n de d.
6. 1 1
E mer ge nc y U n bli n di n g
N ot a p plica ble.
6. 1 2
Tre at me nt of O ver d ose
A n o ver d ose is defi ne d as a n y dose ≥ 1 0 % 
o ver t he calc ulate d d ose f or t hat partic ular 
a d mi nistrati o n as descri be d i n t his cli nical trial pr ot oc ol. A n y  o ver d ose m ust be rec or de d i n t he 
trial treat me nt secti o n of t he e C R F.
F or m o nit ori n g p ur p oses, a n y  case of o ver d ose, w het her or n ot ass ociate d wit h a n A E (seri o us or 
n o nseri o us), m ust be re p orte d t o t he S p o ns or’s Gl o bal Dr u g Safet y D e part me nt i n a n e x pe dite d 
ma n ner usi n g t he a p pr o priate re p orti n g f or m (see Secti o n 7. 4. 1. 4 ).
T here are n o k n o w n s y m pt o ms of a vel u ma b o ver d ose t o date. T he I nvesti gat or sh o ul d use his or 
her cli nical j u d g me nt w he n treati n g a n o ver d ose of t he trial treat me nt.
F or all mai nte na nce
c he m ot hera py, I n vesti gat ors m ust f oll o w l ocal i nstit uti o nal g ui deli nes f or 
o ver d ose treat me nt.
6. 1 3
Me dic al C are of S u bjects after E n d of Tri al
After a s u bject has st o p pe d trial treat me nt, us ual treat me nt will be a d mi nistere d, if re q uire d, i n 
acc or da nce wit h t he trial site’s S O C a n d ge nerall y acce pte d me dical practice a n d de pe n di n g o n t he 
s u bject’s i n di vi d ual me dical nee ds.
U p o n wit h dra wal fr o m trial treat me nt, s u bjects ma y  recei ve t he t ype of care t he y an d t heir 
p h y sicia ns a gree u p o n. 
S u bjects will be f oll o we d f or s ur vi val a n d A Es as s pecifie d i n 
Secti o n 7. 1. 6.   
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 7 / 1 5 0
7
Tri al Pr oce d ures a n d Assess me nts
7. 1
Sc he d ule of Assess me nts
A c o m plete Sc he d ule of Assess me nts f or t he Scree ni n g peri o d a n d t he I n d ucti o n P hase is pr o vi de d 
i n Ta ble 1 a n d Ta ble 2,  f or t he Mai nte na nce a n d F oll o w - u p P hase i n Ta ble 3 t o Ta ble 6,  a n d f or 
Pri or t o perf or mi n g a n y trial assess me nts n ot part of t he s u bject’s r o uti ne me dical care, t he 
I n vesti gat or will e ns ure t hat t he s u bject or t he s u bject’s le gal re prese ntati ve has pr o vi de d writte n 
i nf or me d c o nse nt acc or di n g t o t he pr oce d ure descri be d i n Secti o n 9. 2.
7. 1. 1
Scree ni n g a n d B aseli ne P r oce d ures a n d Assess me nts
T he Scree ni n g pr oce d ures a n d B aseli ne assess me nts will be c o m plete d wit hi n 2 8 da ys bef ore trial 
treat me nt starts.
D uri n g t he Scree ni n g peri o d a n d bef ore a n y trial-relate d i n vesti gati o ns a n d assess me nts are starte d, 
s u bjects will be as ke d t o si g n t he I C F. T he Scree ni n g pr oce d ures a n d Baseli ne assess me nts will 
be c o m plete d wit hi n 2 8 da y s of si g ni n g t he I CF. Fail ure t o esta blis h eli gi bilit y wit hi n 2 8 d a y s 
w o ul d res ult i n scree ni n g fail ure a n d t he s u bject will be e xcl u de d fr o m t he trial; h o we ver, s u bjects 
ca n be re-e ntere d i n t he trial base d o n t he I nvesti gat or’s j u d g me nt a n d f oll o wi n g S p o ns or a p pr o val .  
I n t his case, a ne w I C F will be re q uire d t o be si g ne d b y t he s u bject.
T he s u bjects’ i nf or mati o n t hat will be d oc u me nte d d uri n g Scree ni n g i ncl u des t he de m o gra p hic 
i nf or mati o n ( birt h date, se x, a n d et h nicit y) a n d t he c o m plete me dical hist or y, i ncl u di n g t he hist or y 
of gastric ca ncer, pre vi o us a n d o n g oi n g me dicati o ns, a n d baseli ne me dical c o n diti o n (t he 
i nf or mati o n of c o nc o mita nt me dicati o ns a n d A Es a n d S A Es will be m o nit ore d t hr o u g h o ut t he trial 
treat me nt peri o d). M ore o ver, a n E mer ge nc y  Me dical S u p p ort car d will be ha n de d o ut at t he 
Baseli ne as sess me nts visit.
D uri n g Scree ni n g , s u bjects will u n der g o a c o m plete p h y sical e xa mi nati o n, i ncl u di n g rec or di n g 
b o d y  hei g ht a n d wei g ht, vital si g ns, 1 2 -lea d E C G, a n d a deter mi nati o n of t he E C O G P S (Ta ble 1
a n d Ta ble 2) . T he Q o L q uesti o n naires will be a d mi nistere d a n d c o m plete d b y  the s u bjects at 
baseli ne t o c ollect baseli ne data a b o ut t heir healt h -relate d Q o L.
T he Scree ni n g
la b orat or y exa mi nati o n i ncl u des he mat ol o g y , he m ostase ol o g y , f ull ser u m 
c he mistr y, a n d f ull uri nal y sis ( di pstic k pl us micr osc o pic e val uati o n). F ree t h yr o xi ne ( T4) a n d 
t h yr oi d-sti m ulati n g h or m o ne ( T S H) will als o be assesse d at Scree ni n g f or all s u bjects. T he 
baseli ne
 
D uri n g Scree ni n g, a ser u m β- h u ma n c h ori o nic g o na d otr o pi n ( β-h C G ) pre g na nc y  test will be 
perf or me d f or fe males of c hil d beari n g p ote ntial ( ma y be a nal yz e d l ocall y). H E R 2 testi n g ( per 
l ocal g ui deli nes) , bl o o d H B V a n d H C V m a y  be a nal yze d l ocally f or all Scree ni n g s u bjects as t hese 
c o n diti o ns are trial e ntr y excl usi o n criteria (see Secti o n 5. 3. 2) .  H B V s urface a nti ge n a n d a nti-H C V 
tests m ust be perf or me d at Scree ni n g t o e xcl u de s u bjects wit h he patitis i nfecti o n.  If t he a nti-H C V 
D oc u me nt N o.
O bject N o.
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 8 / 1 5 0
test is p ositi ve, t he i nfecti o n m ust be c o nfir me d b y  an H C V R N A test.  Fe males w h o are 
p ost me n o pa usal (a ge-relate d a me n orr hea ≥ 1 2 c o nsec uti ve m o nt hs 
a n d i ncrease d f ollicle-
sti m ulati n g h or m o ne [ F S H] > 4 0 mI U/ m L), or w h o ha ve u n der g o ne h ysterect o m y or bilateral 
o o p h orect o m y a re e xe m pt fr o m pre g na nc y  testi n g.  If necessar y  to c o nfir m p ost me n o pa usal stat us, 
F S H will be dra w n at Scree ni n g.
T he t u m or e val uati o n (t y pe a n d sta gi n g, etc .) will be perf or me d usi n g C T sca n or M RI (if M RI is 
use d, C T of c hest is ma n dat or y ) as well as t u m or mar kers or an y  ot her esta blis he d met h o ds (see
Secti o n  7. 2. 5 f or details). A brai n C T/ M RI  sca n is re q uire d at Scree ni n g if n ot perf or me d wit hi n 
6 wee ks pri or t o e nteri n g t he I n d ucti o n P hase .  A b o ne sca n s h o ul d be d o ne at Scree ni n g as 
cli nicall y i n dicate d.
S u bjects are re q uire d t o pr o vi de t u m or tiss ue sa m ples; see Secti o n  7. 6. 1 f or details. T u m or tiss ue 
collecti o n will be d o ne of a rece ntl y -o btai ne d bi o ps y  wit hi n 6 m o nt hs fr o m a n o n- irra diate d area, 
F F P E bl oc k c o ntai ni n g t u m or tiss ue or a mi ni m u m n u m ber of 1 0 ( prefera bl y  2 5) u nstai ne d t u m or 
sli des s uita ble f or P D-L 1  e x pressi o n assess me nt (c ut wit hi n 1 wee k). Criteria f or deter mi ni n g t he 
a de q uac y of t u m or tiss ue are descri be d i n t he St u d y Ma n ual. 
S u bjects w h o u n der g o a bi o ps y  s pecifically as part of t he Scree ni n g assess me nts f or t his pr ot oc ol 
s hall be per mitte d t o part ici pate i n t he pr ot oc ol pr o vi de d t he y meet all ot her i ncl usi o n criteria a n d 
n o e xcl usi o n criteria.  It is rec o m me n de d t hat m ulti ple bi o ps y  sa m ples s h o ul d be c ollecte d, as 
feasi ble, f or bi o mar ker assess me nt t o mi ni mize 
i nacc uracies i n assess me nt d ue t o t u m or 
heter o ge neit y . T he site pat h ol o gist s hall re vie w t he H e mat o x yl i n a n d E osi n stai ns w he n m ore t ha n 
o ne F F P E bl oc k fr o m a s u bject has bee n recei ve d. If fr o m a resecti o n s peci me n, t he bl oc k t hat 
ma xi mizes t u m or c o nte nt a n d t u m or cell preser vati o n s h o ul d be teste d b y  the ce ntral la b orat or y.
If fr o m bi o ps y s peci me n(s), all a vaila ble t u m or-c o ntai ni n g bl oc ks re prese nti n g u p t o a ma xi m u m 
of 6 disti nct bi o psies, s h o ul d be se nt t o t he ce ntral la b orat or y  as feasi ble.  
T he bl o o d sa m ples f or baseli ne 
, a n d 
 as well as f or 
 
assess me nts ( o pti o nal) will be c ollecte d bef ore or o n Da y  1 bef ore trial treat me nt starts f or s u bjects 
ra n d o ml y assi g ne d t o recei ve a vel u ma b. 
7. 1. 2
I n d ucti o n P h ase Tre at me nt Peri o d
I n t his trial, t he treat me nt will be gi ve n u ntil P D, si g nifica nt cli nical deteri orati o n (cli nical 
pr o gressi o n), u nacce pta ble t o xicit y, or a n y c riteri o n f or wit h dra wal fr o m t he trial or trial treat me nt 
is f ulfille d (see Secti o n 5. 5. 1 ). 
Treat me nt d uri n g t he I n d ucti o n P hase will c o nsist of: 

6 c y cles of o xali plati n ( 8 5 m g/ m2 I V o n Da y 1 e ver y 2 wee ks) + le uc o v ori n ( 2 0 0 m g/ m2 I V o n 
D a y  1 ev er y  2 wee ks or e q ui vale nt le v ole uc o v ori n d ose ) f oll o we d b y  5-F U ( 2 6 0 0 m g/ m 2 I V 
c o nti n u o us i nf usi o n o ver 2 4 h o urs o n Da y 1 e ver y  2 wee ks,
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
8 9 / 1 5 0
O R
O xali plati n at 8 5 m g/ m 2 I V on D a y  1 wit h le uc o v ori n 4 0 0 m g / m2 I V on Da y 1 ( or e q ui vale nt 
le v ole uc o v ori n d ose) f oll o we d b y  5-F U at 4 0 0 m g/ m 2 I V pus h o n Da y  1 an d 2 4 0 0 m g/ m 2 I V 
c o nti n u o us i nf usi o n o ver 4 6- 4 8 h o urs ( Da ys  1 a n d 2) gi ve n e very 2 wee ks (f or u p t o 1 2 wee ks) .
O R

4 c ycles of O xali plati n ( 1 3 0 m g/ m 2 I V on Da y  1 ever y  3 wee ks ) + Ca pecita bi ne ( 1 0 0 0 m g / m2
P O t wice daily o n Da y s 1-1 4). Ca pecita bi ne ta blets s h o ul d be s wall o we d wit h water wit hi n 3 0 
mi n utes after a meal.
All t he l a b or at or y s a m ples a n d vit al si g ns will be c ollecte d pri or t o e ac h dr u g a d mi ni str ati o n.  
A d mi nistr ati o n of c he m ot her a p y will t a ke pl ace o nl y after rele v a nt res ults h a ve bee n 
c hec ke d b y a me dic all y q u alifie d pers o n a n d criteri a f or d osi n g h a ve bee n met.  
D uri n g t he treat me nt peri o d, t he f oll o wi n g assess me nts a n d pr oce d ures will be perf or me d (see 
Ta ble 1 a n d Ta ble 2 f or t he detaile d sc he d ule):

S A Es, A Es a n d c o nc o mita nt me dicati o ns a n d pr oce d ures will be d oc u me nte d at eac h trial visit.

E C O G P S will be assesse d at Da y  1 of eac h treat me nt c ycle (Scree ni n g E C O G P S ma y  be use d 
f or C ycle 1 Da y 1 if it was perf or me d wit hi n 3 da ys pri or t o Da y 1).

P h y sical e xa mi nati o ns will be perf or me d o n D a y  1 of eac h treat me nt c ycle.  S uc h e xa mi nati o ns 
will i ncl u de a c o m pre he nsi ve s ki n e xa mi nati o n f or t u m or.

Vital si g ns a n d b o d y  wei g ht will be assesse d at eac h visit.

B o d y wei g ht will be assesse d at Da y 1 of eac h c ycle.

T he la b orat or y he mat ol o g y a n d he m ostase ol o g y , will be assesse d o n Da y  1 of eac h c ycle.  C ore 
ser u m c he mistr y tests will be assesse d at Da y  1 of eac h c ycle.  A f ull uri nal y sis will be 
perf or me d at Scree ni n g a n d t he E n d - of-treat me nt visit.  S u bjects s h o ul d als o ret ur n t o t he site 
as per l ocal i nstit uti o nal practice f or a n y a d diti o nal r o uti ne assess me nts d uri n g c he m ot hera p y.

A uri ne or ser u m β - hC G pre g na nc y test will be perf or me d e ver y 4 wee ks d uri n g t he treat me nt 
c ycle ( bef ore c he m ot hera p y a d mi nistrati o n) f or fe males of c hil d beari n g p ote ntial.
D oc u me nt N o.
O bject N o.
C CI
C CIC CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 0 / 1 5 0
7. 1. 3
R a n d o miz ati o n/ Re -b aseli ne
At t he e n d of 1 2 wee ks of I nd ucti o n P hase, s u bjects e nter a 1 0- d a y  Re-baseli ne peri o d a n d t he 
f oll o wi n g assess me nts a n d pr oce d ures will be perf or me d (see Ta ble 3 t o Ta ble 6 f or detaile d 
sc he d ule):

Re vie w of eli gi bilit y  criteria

T he s u bject-re p orte d o utc o mes / Q o L assess me nts will be c o m plete d b y  su bjects pri or t o 
a n y ot her trial-relate d pr oce d ures.

A Es a n d c o nc o mita nt me dicati o ns a n d pr oce d ures

E C O G P S

1 2- lea d E C G

P h y sical e xa mi nati o n, i ncl u di n g a c o m pre he nsi ve s ki n e xa mi nati o n f or t u m or

Vital si g ns a n d b o d y wei g ht

La b orat or y  he mat ol o g y, he m ostase ol o g y, f ull ser u m c he mistr y (i ncl u di n g c ore c he mistr y) 
a n d f ull uri nalys is

Uri ne or ser u m β - hC G pre g na nc y  test f or fe males of c hil d beari n g p ote ntial

Free T 4 a n d T S H

Car diac tr o p o ni n le vels will be c ollecte d fr om Re- baseli ne u p t o 1 2 wee ks i n t he 
M ai nte na nce P hase.  
Car diac tr o p o ni n le vels will be e val uate d ce ntrall y.  Local la b orat ories ma y  be use d at t he 
discreti o n of t he I n vesti gat or as cli nicall y nee de d f or safet y m a na ge me nt/treat me nt decisi o n of t he 
s u bject. Meas ure me nt of car diac tr o p o ni n T (c T n T) is preferre d, h o we ver car diac tr o p o ni n I (c T nI) 
ma y  be s u bstit ute d w here c T n T is n ot a vaila ble at t he l ocal la b orat or y.  The sa me s u b u nit (c T n T 
or c T nI) meas ure d at t he R e-baseli ne visit s h o ul d be meas ure d c o nsiste ntl y thr o u g h o ut t he st u d y 
i n eac h patie nt.  At t he R e-baseli ne visit , cli nicall y si gnifica nt p ositi ve res ults s h o ul d be f urt her 
assesse d as per l ocal S O C t o r ule-o ut c o nc urre nt car diac c o n diti o ns w hic h w o ul d ma ke t he patie nt 
i neli gi ble f or t he st u d y as p er e xcl usi o n criteria.  Duri n g t he st u d y, cli nicall y si gnifica nt ne w 
ele vati o ns s u g gesti ve of m y ocar ditis s h o ul d be assesse d as per  Ta ble 1 1 .  Ad diti o nal tests s h o ul d 
als o be perf or me d w he n cli nicall y i n dicate d.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 1 / 1 5 0
S u bjects w h o pr o gress d uri n g t he I n d ucti o n P hase or w h o are deter mi ne d t o ha ve P D d uri n g t he 
Re - baseli ne peri o d will be disc o nti n ue d fr o m t he trial.
S u bjec ts wit h o ut P D will be ra n d o mly assi g ne d t o recei ve mai nte na nce treat me nt wit h eit her 
a vel u ma b or c o nti n uati o n of t he sa me re gi me n of c he m ot hera p y fr o m t he I nd ucti o n P hase .  
S u bjects w h o de m o nstrate a res p o nse d uri n g t he I n d ucti o n P hase t hat re n ders t heir meas ura ble 
disease n o l o n ger meas ura ble at t he ti me of t he Mai nte na nce P hase ca n be ra n d o mize d.
S u bjects w h o disc o nti n ue treat me nt d ue t o a n y reas o n d uri n g t he Re -baseli ne peri o d a n d bef ore 
ra n d o mizati o n will ha ve a n e n d o f treat me nt (E O T ) visit wit hi n 7 da y s of t he decisi o n t o 
disc o nti n ue c he m ot hera p y an d a 3 0- d a y  Safet y Foll o w - u p visit i n acc or da nce wit h t he I n d uctio n 
P hase S c he d ule of A ssess me nts.
7. 1. 4
M ai nte n a nce P h ase Tre at me nt Peri o d
I n t he Mai nte na nce P hase, s u bjects will recei ve trial treat me nt (a vel u ma b or c o nti n uati o n of t he 
re gi me n of c he m ot hera p y fr o m t he I n d ucti o n P hase ) u ntil P D, f or t he acce pte d ma xi mal d urati o n 
of t he a ge nt(s) selecte d, u nacce pta ble t o xicit y, or a n y criteri o n f or wit h dra wal fr o m trial dr u g is 
f ulfille d (see Secti o n 5. 5).
T he C T/ M RI  sca ns will be c ollecte d u ntil P D is assesse d b y  the In vesti gat or acc or di n g t o 
R E CI S T v 1. 1.  S u bjects recei vi n g a vel u ma b ma y c o nti n ue treat me nt past t he i nitial deter mi nati o n 
of disease pr o gressi o n acc or di n g t o R E CI S T v 1. 1 if t he y 
meet t he criteria prese nte d i n 
Secti o n 6. 2. 1 (I n vesti gat or-assesse d be nefit; t olera nce of treat me nt; sta ble E C O G P S; a n d d oes n ot 
dela y  ot her i m mi ne nt i nter ve nti o n).
T he decisi o n t o c o nti n ue a vel u ma b treat me nt be y o n d pr o gressi o n s h o ul d be disc usse d wit h t he 
M e dical M o nit or a n d d oc u me nte d i n t he st u d y rec or ds.
F or s u bjects c o nti n ui n g a vel u ma b after i nitial P D, a ra di o gra p hic assess me nt s h o ul d be perf or me d 
wit hi n 6 wee ks of ori gi nal P D t o deter mi ne w het her t here has bee n a decrease i n t he t u m or size, 
or c o nti n ue d P D.  T he assess me nt of cli nical be nefit s h o ul d be bala nce d b y c li nical j u d g me nt as t o 
w het her t he s u bject is cli nicall y deteri orati n g a n d u nli kel y  to recei ve a n y be nefit fr o m c o nti n ue d 
treat me nt wit h a vel u ma b.
F or s u bjects recei vi ng a vel u ma b, if disc o nti n uati o n occ urs d ue t o pr o gressi o n a n d a defi niti ve 
dia g n osis/ra di o gra p hic c o nfir mati o n is n ot ma de at t he ti me of disc o nti n uati o n, a sec o n d i ma gi n g 
sca n m a y  be all o we d f or c o nfir mati o n of pr o gressi o n.  If pr o gressi o n at t he sec o n d i ma gi n g sca n 
is n ot c o nfir me d a n d t he s u bject wis hes t o restart, t he s u bject will be all o we d t o c o nti n ue recei vi n g 
a vel u ma b as l o n g as t he y meet t he criteria f or c o nti n uati o n of treat me nt be y o n d pr o gressi o n. 
If t he I n vesti gat or feels t hat t he s u bject c o nti nues t o ac hie ve cli nical be nefit b y  co nti n ui n g 
treat me nt, t he s u bject s h o ul d re mai n o n t he trial a n d c o nti n ue t o recei ve m o nit ori n g acc or di n g t o 
t he Sc he d ule of Assess me nts (Ta ble 3 ).
A n y  a d diti o nal c o nti n uati o n of a vel u ma b pl us B S C be y o n d f urt her pr o gressi o n m ust be disc usse d 
a n d a gree d u p o n wit h t he M e dical M o nit or.  Furt her disease pr o gressi o n is defi ne d as a n a d diti o nal 
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 2 / 1 5 0
i ncrease i n t u m or b ur de n of 2 0 % a n d ≥ 5 m m a bs ol ute i ncrease i n t u m or b ur de n fr o m ti me of i nitial 
P D.   T his i ncl u des a n i ncrease i n t he s u m of all tar get lesi o ns or t he de vel o p me nt of ne w 
meas ura ble lesi o ns.  
A d diti o nall y , s u bjects recei vi n g a vel u ma b w h o ha ve e x perie nce d a C R s h o ul d be treate d f or a 
mi ni m u m of 1 2 m o nt hs or u ntil disease pr o gressi o n or u nacce pta ble t o xicit y, after c o nfir mati o n of 
res p o nse. I n case a s u bject wit h a c o nfir me d C R rela pses after st o p pi n g treat me nt, b ut pri or t o t he 
e n d of t he trial, 1 re-i nitiati o n of tr eat me nt is all o we d at t he discreti o n of t he I n vesti gat or a n d after 
a gree me nt wit h t he Me dical M o nit or. I n or der t o be eli gi ble f or retreat me nt, t he s u bject m ust n ot 
ha ve e x perie nce d a n y t o xicit y  that le d t o treat me nt disc o nti n uati o n of t he i nitial a vel u mab t hera py.  
S u bjects w h o re -i nitiate treat me nt will sta y o n trial a n d will be treate d a n d m o nit ore d acc or di n g t o 
t he pr ot oc ol a n d f oll o w t he Sc he d ule of Assess me nts u ntil disease pr o gressi o n (see Ta ble 3 ).
T he treat me nt s h o ul d start wit hi n 4 d a y s after ra n d o mizati o n.  W hile o n trial treat me nt, s u bjects 
will be as ke d t o visit t he trial site as s pecifie d i n t he S c he d ule of A ssess me nts (see Ta ble 3, Ta ble 
4, Ta ble 5 , a n d Ta ble 6) .
F or b ot h a vel u ma b a n d mai nte na nce c he m o t hera py, a ti me wi n d o w of u p t o 4 d a y s bef ore or 2 d a y  
after t he sc he d ule d visit da y  (-4/ + 2 da y s) will be per mitte d f or all trial pr oce d ures . Su bjec ts s h o ul d 
ret ur n t o t he tar get date e ve n if t he pre vi o us visit was off sc he d ule.
T he t u m or e val uati o n (see Secti o n  7. 3) will be perf or me d e ver y 6 wee ks (f or t he first 1 2 m o nt hs 
a n d e ver y 1 2 wee ks t hereafter ) wit h a ti me wi n d o w of -5 da y s f or b ot h a vel u ma b a n d mai nte na nce
c he m ot hera py.
S u bjects will recei ve eit her:

A vel u ma b b y  IV i nf usi o n f oll o wi n g pretreat me nt (see Secti o n 5. 1. 2. 2. 1) o nce e ver y 2 wee ks 
(see Secti o n 6. 2. 1 ), or

Mai nte na nce c he m ot hera p y foll o wi n g pretreat me nt as a p plica ble pri or t o eac h i nf usi o n (see 
Secti o n  6. 2. 2).
Assess me nts t o be perf or me d d uri n g t he M a i nte na nce P hase are prese nte d i n Ta ble 3 t o Ta ble 6.
D uri n g t he treat me nt peri o d, t he f oll o wi n g assess me nts a n d pr oce d ures will be perf or me d (see 
Ta ble 3 t o Ta ble 6 f or t he detaile d sc he d ule):

T he s u bject-re p orte d o utc o mes/ Q o L  assess me nts will be c o m plete d b y  su bjects pri or t o 
a n y trial-relate d pr oce d ures (ti me p oi nts o utli ne d i n Ta ble 3 t o Ta ble 6) a n d t he n e ver y 
6 wee ks t hereafter.

A Es a n d c o nc o mita nt me dicati o ns a n d pr o ce d ures will be d oc u me nte d at eac h visit.

E C O G P S will be assesse d at eac h treat me nt visit.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 3 / 1 5 0

P h y sical e xa mi nati o ns will be perf or me d t hr o u g h Wee k 
1 3 or w hile t he s u bject is 
o n- treat me nt.
After Wee k 1 3, t he p h y sical e xa mi nati o n will occ ur e ver y 6 wee ks.  Su c h 
e xa mi nati o ns will i ncl u de a c o m pre he nsi ve s ki n e xa mi nati o n f or t u m or .

Vital si g ns a n d b o d y wei g ht will be assesse d i n eac h treat me nt visit.

T he la b orat or y  he mat ol o g y, he m ostase ol o g y will be assesse d at eac h visit.

S er u m c he mistr y tests will be assesse d as f oll o ws:
o
F ull ser u m c he mistr y  at Re-baseli ne f or all s u bjects
o
C ore ser u m c he mistr y :

S u bjects o n t he a vel u ma b ar m: Wee k 1, Wee k 3, Wee k 5, W ee k 7, W ee k 9, 
W ee k 1 1, Wee k 1 3, a n d e ver y 2 wee ks t hereafter.

S u bjects o n B S C -o nl y  wit h n o acti ve t hera p y: W ee k 1 , Wee k 4, Wee k
7, 
W ee k 1 0, Wee k 1 3, a n d e ver y 3 wee ks t hereafter.

S u bjects o n t he c he m ot hera p y d o u blet ar m recei vi n g o xali plati n + 
ca pecita bi ne o n W ee k 1, Wee k 4, Wee k 7, W ee k 1 0, W ee k 1 3 a n d e ver y 
3 wee ks t hereafter.

S u bjects o n t he c he m ot hera p y d o u blet ar m recei vi n g o xali plati n + 5 -F U o n 
W ee k 1, W ee k 3, Wee k 5, Wee k 7, W ee k 9, W ee k 1 1, W ee k 1 3, a n d e ver y 
2 wee ks t hereafter.

A basic uri nal y sis ( di pstic k) will be at Wee k 1, Wee k 7, Wee k 1 3, a n d e ver y 1 2 wee ks 
t hereafter.  If t he basic uri nal ysis is a b n or mal, a f ull uri nal ysis s h o ul d be perf or me d.

A uri ne or ser u m β - hC G pre g na nc y  test will be perf or me d at t he visits i n dicate d i n t he 
Assess me nt Sc he d ules (f or fe males of c hil d beari n g p ote ntial).  

Bl o o d sa m ples f or P K deter mi nati o ns will be c ollecte d fr o m all s u bjects i n t he a vel u ma b 
ar m o n or bef ore D a y 1 ( Wee k 1) pri or t o t he first a d mi nistrati o n of st u d y dr u g, wit hi n 
2 h o urs pri or t o eac h trial dr u g a d mi nistrati o n at Wee ks 
3, 5, 7 (e ver y 2 wee ks), at 
Wee ks
1 3, 1 9, a n d 2 5 (e ver y 6 wee ks), a n d t he n at 1 2- wee k i nter vals w hile o n- treat me nt
u p t o Wee k 1 0 9 ( 2 years fr o m ra n d o mizati o n) .  P ost-trial dr u g a d mi nistrati o n sa m ples will 
be c ollecte d at t he e n d of i nf usi o n ( wit hi n 1 5 mi n utes) at Wee ks 1, 7, a n d 2 5.  Sa m ples will 
be c ollecte d at t he E n d -of -Treat me nt visit a n d t he 3 0- d a y  Safet y F oll o w -u p visit , e x ce pt 
f or s u bjects still o n trial treat me nt be yo n d Wee k 1 0 9 .
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 4 / 1 5 0

T rial dr u g i nf usi o n at eac h trial visit ( o nce e ver y 2 or 3 wee ks).  

Pre me dicati o n as descri be d i n Secti o n 5. 1. 2. 2. 1

Car diac tr o p o ni n le vels will be c ollecte d fr o m Re- baseli ne u p t o 1 2 wee ks i n t he 
M ai nte na nce P hase.  
Car diac tr o p o ni n le vels will be e va l uate d ce ntrall y.  Local la b orat ories ma y  be use d at t he 
discreti o n of t he I n vesti gat or as cli nicall y nee de d f or safet y m a na ge me nt/treat me nt decisi o n of t he 
s u bject. Meas ure me nt of c T n T is preferre d, h o we ver c T nI ma y  be s u bstit ute d w here c T n T is n ot 
a vaila ble at t he l ocal la b orat or y. T he sa me s u b u nit (c T n T or c T nI) meas ure d at t he Re- baseli ne
visit s h o ul d be meas ure d c o nsiste ntl y thr o u g h o ut t he st u d y in eac h patie nt.
At t he Re- baseli ne
visit , cli nicall y si g nifica nt p ositi ve res ults s h o ul d be f urt her assesse d as per l ocal S O C t o r ule-o ut 
c o nc urre nt car diac c o n diti o ns w hic h w o ul d ma ke t he patie nt i neli gi ble f or t he st u d y as per 
e xcl usi o n criteria.
D uri n g 
t he st u d y, cli nicall y si g nifica nt ne w ele vati o ns s u g gesti ve of 
m y ocar ditis s h o ul d be assesse d as per  Ta ble 1 1. A d diti o nal tests s h o ul d als o be perf or me d w he n 
cli nicall y i n dicate d.
7. 1. 5
E n d of T re at me nt
S u bjects m ust u n der g o a n E n d - of-Treat me nt visit after disc o nti n uati o n of I MP f or a n y reas o n.  
T his visit s h o ul d be perf or me d wit hi n 7 da y s of t he decisi o n t o disc o nti n ue treat me nt b ut bef ore 
a n y ne w a nti ne o plastic t hera py is starte d (if p ossi ble), w hic he ver occ urs earlier.  See Ta ble 1
t hr o u g h Ta ble 7 f or t he assess me nts t o be perf or me d.
All A Es will be c ollecte d u p u nt il t he 3 0-Da y  Safet y F oll o w- up visit. 
At t he E n d - of-Treat me nt visit, t he f oll o wi n g assess me nts will be perf or me d:
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 5 / 1 5 0

D oc u me ntati o n of A Es a n d c o nc o mita nt me dicati o n a n d pr oce d ures

P h y sical e xa mi nati o n, i ncl u di n g vital si g ns, a n d b o d y wei g ht

1 2- lea d E C Gs

La b o rat or y he mat ol o g y, he m ostase ol o g y , f ull ser u m c he mistr y, pre g na nc y  test, a n d f ull
uri nal y sis.

T 4 a n d T S H

E C O G P S
7. 1. 6
S afet y F oll o w -u p Visit
A ll s u bjects will ha ve a s u bse q ue nt visit sc he d ule d 3 0 da y s ( ± 5 d a y s) after t he last a d mi nistrati o n 
of trial dr u g, a n d will be c o ntacte d b y  ph o ne 9 0 da y s ( ± 1 wee k) after t he last a d mi nistrati o n of 
trial dr u g.  
T he visit will i ncl u de t he f oll o wi n g f ull assess me nt of safet y para meters ( see Ta ble 3 t o Ta ble 6 ):

T he s u bject-re p orte d o utc o mes / Q o L assess me nts will be c o m plete d b y  su bjects pri or t o a n y 
trial-relate d pr oce d ures

D oc u me ntati o n of A Es a n d c o nc o mita nt me dicati o n a n d pr oce d ures

E C O G P S

P h y sical e xa mi nati o n i ncl u di n g vital si g ns, b o dy wei g ht, a n d s ki n t u m or e xte nt

T he la b orat or y he mat ol o g y, he m ostase ol o g y , f ull ser u m c he mistr y, a n d basic uri nal y sis 
( di pstic k pl us micr osc o pic e val uati o n) .  If t he basic uri nal y sis is a b n or mal, a f ull uri nal y sis 
s h o ul d be perf or me d.

A uri ne β - hC G pre g na nc y test (i n fe males of c hil d beari n g p ote ntial) will be c o n d ucte d.

T 4 a n d T S H le vels
All A Es will be d oc u me nte d u ntil t he 3 0- d a y  Safet y Foll o w -u p visit. S u bjects wit h a n o n g oi n g 
S A E at t he 3 0 -d a y  Safet y F oll o w-u p visit m ust be m o nit ore d a n d f oll o we d u p b y  t he I n vesti gat or 
u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is d oc u me nte d as “l ost t o 
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 6 / 1 5 0
f oll o w- u p”.
After t his vi sit, all S A Es a n d all treat me nt-relate d n o n-seri o us A Es nee d t o be 
d oc u me nte d u ntil t he 9 0- da y  Safet y F oll o w - u p P h o ne Call.   All s u bjects will be c o ntacte d b y  ph o ne 
9 0 da y s after t he last a d mi nistrati o n of trial dr u g t o c ollect i nf or mati o n o n ne w or o n g oi n g S A Es 
a n d treat me nt-relate d n o n-seri o us A Es.  
If a n ot her a nti ne o plastic t hera py is a d mi nistere d bef ore t he e n d of t his 3 0- d a y  p eri o d, t he 3 0- da y 
Safet y  F oll o w-u p visit s h o ul d be c o n d ucte d, if p ossi ble, pri or t o t he start of t his ne w t hera p y .
7. 1. 7
L o n g -ter m F oll o w-u p
All S A E s o n g oi n g at t he Safet y  Foll o w - u p Ph o ne C all m ust be m o nit ore d a n d f oll o we d u p b y  t he 
I n vesti gat or u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is d oc u me nte d as 
“l ost t o f oll o w -u p.”
A n y  S A E assesse d as relate d t o I M P m ust be re p orte d w he ne ver it occ urs, irres pecti ve of t he ti me 
ela pse d si nce t he last a d mi nistrati o n of t he I M Ps.
S u bjects wit h o ut P D acc or di n g t o R E CIS T v 1. 1 at t he E n d- of-Treat me nt visit will be f oll o we d u p 
f or disease pr o gressi o n ( C T / M RI  sca ns e ver y 6 wee ks [ ± 1 wee k ], a n d after 1 2 m o nt hs, e ver y 
1 2 wee ks [± 1 wee k ] usi n g t he sa me pr oce d ures a n d re vie w as w hile o n-treat me nt) u ntil P D.  
S u bjects will be f oll o we d q uarterl y (t hat is, e ver y 1 2 w ee ks, ± 2 wee ks) f or s ur vi val (i ncl u di n g 
assess me nt of a n y ne w t u m or t hera py) .  The s ur vi val f oll o w- u p of s u bjects will c o nti n ue u ntil 5 
ye ars after t he last s u bject recei ves t he last d ose of a vel u ma b.  U n der s o me circ u msta nces, t he 
s u bjects ma y n ot be f oll o we d f or 5 years f or s ur vi val i n t his st u d y, e g, t he s u bjects ma y be offere d 
t o e nr oll i nt o a r oll-o ver st u d y , or t he S p o ns or ma y  ter mi nate t he st u d y earl y.
7. 1. 8
Bl o o d Dr a ws f or Cli nic al Assess me nts
T he o verall a m o u nt of bl o o d t o be dra w n fr o m a si n gle s u bject wit h a b o d y  wei g ht ≥7 0 k g ( 1 5 4 l bs) 
m ust n ot e xcee d 6 0 m L/ da y a n d 2 0 0 m L  in a n 8- wee k peri o d f or safet y la b orat or y testi n g, 
pre g na nc y  testi n g, 
7. 2
De m o gr a p hic a n d Ot her B aseli ne C h ar acteristics
7. 2. 1
De m o gr a p hic D at a
At Scree ni n g , t he f oll o wi n g de m o gra p hic data will be c ollecte d: date of birt h, se x ( ge n der), race, 
a n d et h nicit y.
7. 2. 2
Di a g n osis of G astric C a ncer
T he t u m or disease i nf or mati o n t hat will be d oc u me nte d a n d verifie d at t he Scree ni n g visit f or eac h 
s u bject i ncl u des
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 7 / 1 5 0

Detaile d hist or y  of t he t u m or, i ncl u din g hist o pat h ol o gical dia g n osis, gra di n g, a n d sta gi n g i n 
acc or da nce wit h t he I nter nati o nal U ni o n A gai nst Ca ncer T u m or N o de Metastasis Classificati o n 
of Mali g na nt T u m ors at dia g n osis;

All t hera py use d f or pri or treat me nt of t he t u m or (i ncl u di n g s ur ger y, ra diot hera p y  an d 
c he m ot hera p y, i m m u n ot hera p y);

A n y  ot her c o n diti o ns t hat were 
treate d wit h 
c he m ot hera p y, ra diati o n t hera py, or 
i m m u n ot hera p y;

S m o ki n g hist or y ;

C urre nt ca ncer si g ns a n d s ym pt o ms a n d si de effects fr o m c urre nt a n d pre vi o us a ntica ncer 
treat me nts; an d

C urre nt ca ncer disease stat us.
7. 2. 3
Me dic al Hist or y
I n or der t o deter mi ne t he s u bject’s eli gi bilit y to t he trial, a c o m plete me dical hist or y  of eac h s u bject 
will be c ollecte d a n d d oc u me nte d d uri n g Scree ni n g , w hic h will i ncl u de, b ut ma y n ot be li mite d t o, 
t he f oll o wi n g:

Past a n d c o nc o mita nt n o n mali g na nt diseases a n d treat me nts

All me dicati o ns (i ncl u di n g her bal me dicati o ns) ta ke n a n d pr oce d ures carrie d o ut wit hi n 2 8 da y s 
pri or t o Scree ni n g .
F or t he trial e ntr y, all of t he s u bjects m ust f ulfill all i ncl usi o n criteria descri be d i n Secti o n 5. 3. 1 , 
a n d n o ne of t he s u bjects s h o ul d ha ve a n y e xcl usi o n criteri o n fr o m t he list descri be d i n 
Secti o n 5. 3. 2.
7. 2. 4
Vit al Si g ns a n d P h ysic al E x a mi n ati o n
Vital si g ns i ncl u di n g b o d y  te m perat ure, res pirat or y rate, heart rate (after 5- mi n ute rest), a n d arterial 
bl o o d press u re (after 5- mi n ute rest) will be rec or de d at trial e ntr y .
A c o m plete p h y sical e xa mi nati o n (i ncl u di n g, i n ge neral, a p peara nce, der mat ol o gical, hea d/ nec k, 
p ul m o nar y , car di o vasc ular, gastr oi ntesti nal, ge nit o uri nar y , l ym p hatic, m usc ul os keletal s yste m, 
e xtre mities, e yes [i ns pecti o n a n d visi o n c o ntr ol], n ose, t hr oat, a n d ne ur ol o gic stat us) will be 
perf or me d a n d t he res ults d oc u me nte d.
T he E C O G P S will be d oc u me nte d d uri n g t he Scree ni n g P hase a n d at eac h sc he d ule d visit (if t he 
Scree ni n g E C O G P S was perf or me d wit hi n 3 da y s pri or t o Da y 1, it d oes n ot ha ve t o be re peate d 
at Da y 1).
B o d y wei g ht a n d hei g ht will be rec or de d.
D oc u me nt N o.
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 8 / 1 5 0
7. 2. 6
Ot her B aseli ne Assess me nts
All ot her baseli ne meas ure me nts, s uc h as vital si g ns, a c o m plete p h ysical e xa mi nati o n, E C O G P S, 
cli nical la b orat or y para meters, a n d 1 2-lea d E C G, will be assesse d.
7. 3
Effic ac y Assess me nts
Ra di o gra p hic i ma ges a n d p h y sical fi n di n gs ( p hys ical assess me nts) use d f or t he deter mi nati o n of 
disease pr o gressi o n will be e val uate d per I n vesti gat or assess me nt, w hic h will deter mi ne w het her 
t he criteria f or t u m or res p o nse or pr o gressi o n acc or di n g t o R E CI S T v 1. 1 ha ve bee n met , as well 
as deter mi ne t he ti me p oi nt o verall res p o nse a n d date of disease pr o gressi o n acc or di n g t o R E CI S T 
v 1. 1 f or eac h s u bject .
F or eac h s u bject, t u m or res p o nse assess me nt will be perf or me d b y  CT sca n or M RI  (if M RI is 
use d, c hest C T is ma n dat or y ) i ma gi n g of t he c hest/a b d o me n/ pel vis ( pl us ot her re gi o ns as 
s pecifically re q uire d) a n d ot her esta blis he d assess me nts of t u m or b ur de n if C T / M RI i ma gi n g is 
i ns ufficie nt f or t he i n di vi d ual s u bject. A ll t he sca ns perf or me d at baseli ne a n d ot her i ma gi n g 
perf or me d as cli nicall y re q uire d ( ot her s u p p orti ve i ma gi n g) nee d t o be re peate d at s u bse q ue nt visits 
(e xce pt f or brai n sca ns, u nless cli nicall y in dicate d). I n ge neral, lesi o ns detecte d at baseli ne nee d 
t o be f oll o we d usi n g t he sa me i ma gi n g met h o d ol o g y an d prefera bl y t he sa me i ma gi n g e q ui p me nt 
at s u bse q ue nt t u m or e val uati o n visits.
A brai n C T/ M RI sca n is re q uire d at Scree ni n g if n ot perf or me d wit hi n 6 wee ks pri or t o e nteri n g 
t he I n d ucti o n P hase . Brai n C T / M RI  sca ns s h o ul d be perf or me d after Scree ni n g , if cli nicall y 
i n dicate d b y  de vel o p me nt of ne w s pecific s ym pt o ms. 
A b o ne sca n s h o ul d be d o ne as cli nicall y 
i n dicate d at Scree ni n g a n d be yo n d. F or eac h s u bject, t he I n vesti gat or will desi g nate 1 or m ore of 
t he f oll o wi n g meas ures of t u m or stat us t o f oll o w f or deter mi ni n g res p o nse: C T or M RI i ma ges of 
pri mar y  an d/ or metastatic t u m or masses, p h y sical e xa mi nati o n fi n di n gs, a n d t he res ults of ot her 
assess me nts. All a vaila ble i ma ges c ollecte d d uri n g t he trial per i o d will be c o nsi dere d. T he m ost 
a p pr o priate meas ures t o e val uate t he t u m or stat us of a s u bject s h o ul d be use d .  T he meas ure(s) t o 
be c h ose n f or se q ue ntial e val uati o n d uri n g t he trial m ust c orres p o n d t o t he meas ures use d t o 
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
9 9 / 1 5 0
d oc u me nt t he pr o gressi ve t u m or stat us t hat q ualifies t he s u bject f or e nr ollme nt . T he t u m or 
res p o nse assess me nt will be assesse d a n d liste d acc or di n g t o t he Sc he d ule of Assess me nts (see
Ta ble 1 ).
Treat me nt decisi o ns will be ma de b y  the I n vesti gat or base d o n t he I nvesti gat or’s assess me nt of 
t u m or stat us.
T he C T/ M RI  sca ns will be c ollecte d u ntil P D is assesse d b y  the In vesti gat or acc or di n g t o 
R E CI S T v 1. 1.  
F or efficac y deter mi nati o n, t u m or res p o nses t o treat me nt will be base d o n t he e val uati o n of t he 
res p o nse of tar get, n o n- tar get, a n d ne w lesi o ns acc or di n g t o R E CI S T v 1. 1 (all meas ure me nts 
s h o ul d be rec or de d i n metric n otati o n, as descri be d i n R E CI S T v 1. 1) as per I n vesti gat or 
assess me n t.

T o assess O R R , t he t u m or b ur de n at baseli ne will be esti mate d a n d use d f or c o m paris o n 
wit h s u bse q ue nt meas ure me nts. 
At baseli ne, t u m or lesi o ns will be cate g orize d i n tar get 
a n d n o n -tar get lesi o ns as descri be d i n R E CIS T v 1. 1.
Res ults f or t hese e val uati ons will be rec or de d wit h as m uc h s pecificit y as p ossi ble s o t hat pre - a n d 
p ost -treat me nt res ults will pr o vi de t he best o p p ort u nit y f or e val uati n g t u m or res p o nse.
A n y  CR or P R s h o ul d be c o nfir me d, prefera bl y at t he sc he d ule d 6- wee k i nter val, b ut n o s o o ner 
tha n 4 wee ks after t he i nitial d oc u me ntati o n of C R or P R. C o nfir mati o n of P R ca n be c o nfir me d 
at a n assess me nt later t ha n t he ne xt assess me nt after t he i nitial d oc u me ntati o n of P R.
T he I n vesti gat or ma y perf or m sca ns i n a d diti o n t o a sc he d ule d trial sca n f or me dical reas o ns or if 
t he I n vesti gat or s us pects P D. S u bjects w h o wit h dra w fr o m t he trial f or cli nical or s ym pt o matic 
deteri orati o n bef ore o bjecti ve d oc u me ntati o n of P D will be re q ueste d t o u n der g o a p pr o priate 
i ma gi n g t o c o nfir m P D. E ver y  eff ort s h o ul d be ma de t o c o nfir m a cli nical dia g n osis of P D b y  
i ma gi n g.  If disc o nti n uati o n occ urs d ue t o pr o gressi o n a n d a defi niti ve dia g n osis/ra di o gra p hic 
c o nfir mati o n is n ot ma de at t he ti me of disc o nti n uati o n, a sec o n d i ma gi n g sca n m a y  be all o we d 
f or c o nfir mati o n o f pr o gressi o n.  If pr o gressi o n at t he sec o n d i ma gi n g sca n is n ot c o nfir me d a n d 
t he s u bject wis hes t o restart, t he s u bject will be all o we d t o c o nti n ue recei vi n g a vel u ma b as l o n g as 
t he y meet t he criteria f or c o nti n uati o n of treat me nt be y o n d pr o gressi o n.
7. 4
Ass ess me nt of S afet y
T he safet y pr ofile of t he trial treat me nts will be assesse d t hr o u g h t he rec or di n g, re p orti n g, a n d 
a nal yz i n g of baseli ne me dical c o n diti o ns, A Es, p h y sical e xa mi nati o n fi n di n gs, i ncl u di n g vital 
si g ns, a n d la b orat or y tests.
C o m pre he nsi ve assess me nt of a n y a p pare nt t o xicit y  e x perie nce d b y t he s u bject will be perf or me d 
t hr o u g h o ut t he c o urse of t he trial, fr o m t he ti me of t he s u bject’s si g nat ure of i nf or me d c o nse nt. 
Trial site pers o n nel will re p ort a n y A E, w het her o bser ve d b y  the I n vesti gat or or re p orte d b y  th e 
s u bject (see Secti o n 7. 4. 1. 2 ). Gi ve n t he i nte n de d mec ha nis m of acti o n of a vel u ma b, partic ular 
atte nti o n will be gi ve n t o A Es t hat ma y  f oll o w t he e n ha nce d T-cell acti vati o n, s uc h as der matitis, 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 0 / 1 5 0
c olitis, he patitis, u veitis, or ot her i m m u ne-relate d reacti o ns. O p ht hal m ol o gic e xa mi nati o ns s h o ul d 
be c o nsi dere d, w he n cli nicall y  i n dicate d, f or si g ns or s ym pt o ms of u veitis .
T he re p orti n g peri o d f or A Es is descri be d i n Secti o n  7. 4. 1. 3.
T he safet y assess me nts will be perf or me d acc or di n g t o t he Sc he d ule of Assess me nts (Ta ble 1 a n d 
Ta ble 5 ).
7. 4. 1
A d verse E ve nts
7. 4. 1. 1
A d verse E ve nt Defi niti o ns
A d verse E ve nt
A n A E is a n y u nt o war d me dical occ urre nce i n a s u bject or cli nical i n vesti gati o n s u bject 
a d mi nistere d a p har mace utical pr o d uct, re gar dless of ca usal relati o ns hi p wit h t his treat me nt. A n 
A E ca n t heref ore be a n y unfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), sy m pt o m, or disease te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her 
or n ot c o nsi dere d relate d t o t he me dici nal pr o d uct.
F or s ur gical or dia g n ostic pr oce d ures, t he c o n diti o n/ill ness lea di n g t o s uc h a pr oce d ure is 
c o nsi dere d as t he A E rat her t ha n t he pr oce d ure itself.
T he I n vesti gat or is re q uire d t o gra de t he se verit y or t o xicit y  of eac h A E.
I n vesti gat ors will refere nce t he N CI-C T C A E v 4. 0 3 ( p u blicati o n date: 1 4 J u ne 2 0 1 0), a descri pti ve 
ter mi n ol o g y t hat ca n be use d f or A E re p orti n g.
A ge neral gra di n g (se verit y/i nte nsit y; hereafter referre d t o as se verity) scale is pr o vi de d at t he 
be gi n ni n g of t he a b o ve refere nce d d oc u me nt, a n d s pecific e ve nt gra des are als o pr o vi de d.
If a partic ular A E’s se verit y is n ot s pecifically gra de d b y t he g ui da nce d oc u me nt, t he I n vesti gat or 
is t o use t he ge neral N CI -C T C A E defi niti o ns of Gra de 1 t hr o u g h Gra de 5 f oll o wi n g his or her best 
me dical j u d g me nt.
T he 5 ge neral gra des are:

Gra de 1 or Mil d

Gra de 2 or M o derate

Gra de 3 or Se vere 

Gra de 4 or L ife-t hreate ni n g

Gra de 5 or Deat h
Acc or di n g t o S p o ns or c o n ve nti o n, a n y cli nical A E wit h se verity of Gra de 4 or 5 m ust als o be 
re p orte d as a n S A E. H o we ver, a la b orat or y ab n or malit y  of Gra de 4, s uc h as a ne mia or ne utr o pe nia, 
is c o nsi dere d seri o us o nl y if t he c o n diti o n meets o ne of t he seri o us criteria descri be d bel o w.
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 1 / 1 5 0
If deat h occ urs, t he pri mar y  ca use of deat h or e ve nt lea di n g t o deat h s h o ul d be rec or de d a n d 
re p orte d as a n S A E. “ Fatal” will be rec or de d as t he o utc o me of t his s pecific e ve nt a n d deat h will 
n ot be rec or de d as se parate e ve nt. O nl y , if n o ca use of deat h ca n be re p orte d (f or e xa m ple, s u d de n 
deat h, u ne x plai ne d de at h), t he deat h per se mi g ht t he n be re p orte d as a n S A E.
I n vesti gat ors m ust als o s yste maticall y assess t he ca usal relati o ns hi p of A Es t o trial treat me nt usi n g 
t he f oll o wi n g defi niti o ns. Decisi ve fact ors f or t he assess me nt of ca usal relati o ns hi p of a n A E t o 
t he trial treat me nt i ncl u de, b ut m a y  not be li mite d t o, te m p oral relati o ns hi p bet wee n t he A E a n d 
t he trial treat me nt, k n o w n si de effects of trial treat me nt, me dical hist or y, c o nc o mita nt me dicati o n, 
c o urse of t he u n derl yi n g disease, trial pr oce d ures.
U nrel ate d:
N ot 
reas o na bly 
relate d t o t he I M P.  T he 
A E 
c o ul d 
n ot 
me dicall y 
( p har mac ol o gically/ cli nicall y) be attri b ute d t o t he trial treat me nt u n der st u d y i n t his 
cli nical trial pr ot oc ol.  A reas o na ble alter nati ve e x pla nati o n m ust be a vaila ble.
Rel ate d:
Reas o na bl y 
relate d 
t o 
t he 
I MP.  
 
T he  
A E 
c o ul d 
me dicall y  
( p har mac ol o gically/ cli nicall y) be attri b ute d t o t he trial treat me nt u n der st u d y i n t his 
cli nical trial pr ot oc ol.
A b n or m al L a b or at or y Fi n di n gs a n d Ot her A b n or m al I n vesti g ati o n al Fi n di n gs
A b n or mal la b orat or y fi n di n gs a n d ot her a b n or mal i n vesti gati o nal fi n di n gs (f or e xa m ple, o n a n 
E C G trace) s h o ul d n ot be re p orte d as A Es u nless t he y are ass ociate d wit h cli nical si g ns a n d 
s ym pt o ms, lea d t o treatme nt disc o nti n uati o n or are c o nsi dere d ot her wise me dicall y  im p orta nt b y  
t he I n vesti gat or. If a la b orat or y a b n or malit y f ulfills t hese criteria, t he i de ntifie d me dical c o n diti o n 
(f or e xa m ple, a ne mia, i ncrease d A L T) m ust be re p orte d as t he A E rat her t ha n t he a b n or mal val ue 
itself.
A d verse Dr u g Re acti o n 
A d verse Dr u g Reacti o ns are defi ne d i n t his st u d y as a n y A E s us pecte d t o be relate d t o st u d y 
treat me nt b y t he I n vesti gat or a n d/ or S p o ns or.
S eri o us A d verse E ve nts
A n S A E is a n y  u nt o war d me dical occ urre nce t hat at a ny d ose:

Res ults i n deat h.

Is life-t hreate ni n g.  ( N ote: T he ter m “life-t hreate ni n g” refers t o a n e ve nt i n w hic h t he s u bject is 
at ris k of deat h at t he ti me of t he e ve nt, n ot a n e ve nt t hat h y p ot heticall y  mi g ht ha ve ca use d deat h 
if it was m ore se vere).

Re q uires i n patie nt h os pitalizati o n or pr ol o n gs a n e xisti n g h os pitalizati o n.

Res ults i n persiste nt or si g nifica nt disa bilit y  or i nca pacity.

Is a c o n ge nital a n o maly or birt h defect.

Is ot her wise c o nsi dere d t o be me dicall y i m p orta nt.
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 2 / 1 5 0
N ote: 
I m p orta nt me dical e ve nts t hat m a y  not res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n ma y  be c o nsi dere d as S A Es w he n, base d u p o n a p pr o priate me dical j u d g me nt, t he y 
ma y  je o par dize t he s u bject or m a y  re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he 
o utc o mes liste d a b o ve. 
E xa m ples of s uc h e ve nts i ncl u de aller gic br o nc h os pas m re q uiri n g 
i nte nsi ve treat me nt i n a n e mer ge nc y r o o m or at h o me, bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot 
res ult i n i n patie nt h os pitalizati o n, or t he de vel o p me nt of dr u g de pe n de nc y  or dr u g a b use.
F or t he p ur p oses of re p orti n g, a n y s us pecte d tra ns missi o n of a n i nfecti o us a ge nt via a n I M P  is als o 
c o nsi dere d a n S A E, as descri be d i n Secti o n  7. 4. 1. 4.
E ve nts t h at D o N ot Meet t he Defi niti o n of a n S A E
Electi ve h os pitalizati o ns t o a d mi nister, or t o si m plif y trial treat me nt or trial pr oce d ures (f or 
e xa m ple, a n o ver ni g ht sta y t o facilitate t hera p y an d relate d h y drati o n t hera p y  ap plicati o n) are n ot 
c o nsi dere d S A Es. 
H o we ver, all e ve nts lea di n g t o u n pla n ne d h os pitalizati o ns or u n pla n ne d 
pr ol o n gati o n of a n electi ve h os pitalizati o n (f or e xa m ple, u n desira ble effects of a n y ad mi nistere d 
treat me nt) m ust be d oc u me nte d a n d re p orte d as S A Es.
Pr o gressi o n of t he disease/ dis or der bei n g st u die d assesse d b y  
meas ure me nt of lesi o ns o n 
ra di o gra p hs or ot her met h o ds as well as ass ociate d cli nical si g ns or s ym pt o ms (i ncl u di n g 
la b orat or y ab n or malities) s h o ul d n ot be re p orte d as a n (S) A E, u nless t he patie nt’s ge neral 
c o n diti o n is m ore se vere t ha n e x pecte d a n d/ or u nless t he o utc o me is fatal wit hi n t he a d verse e ve nt 
re p orti n g peri o d (as defi ne d i n Secti o n 7. 4. 1. 3 ).
E ve nts N ot t o Be C o nsi dere d as A Es/ S A Es
Me dical c o n diti o ns prese nt at t he i nitial trial visit t hat d o n ot w orse n i n se verit y or fre q ue nc y duri n g 
t he trial are defi ne d as b aseli ne m e dical co n diti o ns, a n d are n ot t o be c o nsi dere d A Es.   H o we ver, 
if a d verse si g ns or s ym pt o ms occ ur i n ass ociati o n wit h disease pr o gressi o n, t he n t hese s h o ul d b e 
rec or de d as A Es.
A E/ S A Es O bser ve d i n Ass oci ati o n wit h Dise ase Pr o gressi o n
Disease pr o gressi o n rec or de d i n t he c o urse of efficac y  assess me nts o nl y, b ut wit h o ut a n y a d verse 
si g ns or sy m pt o ms s h o ul d n ot be re p orte d as A Es.
H o we ver, if a d verse si g ns or s ym pt o ms occ ur i n ass ociati o n wit h disease pr o gressi o n t he n t hese 
s h o ul d be rec or de d as A Es or re p orte d as S A Es, if t he y meet criteria f or seri o us ness.
A d verse E ve nts of S peci al I nterest
A n y  AE t hat is s us pecte d t o be a p ote ntial ir A E a n d i nf usi o n -relate d reacti o ns will be c o nsi dere d 
a n a d verse e ve nt of s pecial i nterest ( A E SI). 
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 3 / 1 5 0
7. 4. 1. 2
Met h o ds of Rec or di n g a n d Assessi n g A d verse E ve nts
At eac h trial v isit, t he s u bject will be q uerie d o n c ha n ges i n his or her c o n diti o n. D uri n g t he 
re p orti n g peri o d, a n y u nfa v ora ble c ha n ges i n t he s u bject’s c o n diti o n will be rec or de d as A Es, 
w het her re p orte d b y t he s u bject o r o bser ve d b y t he In vesti gat or.
C o m plete, acc ur ate, a n d c o nsiste nt data o n all A Es e x perie nce d f or t he d urati o n of t he re p orti n g 
peri o d ( defi ne d i n Secti o n 7. 4. 1. 3 ) will be re p orte d o n a n o n g oi n g basis i n t he a p pr o priate secti o n 
of t he e C R F. All S A Es m ust be a d diti o nall y doc u me nte d a n d re p orte d usi n g t he a p pr o priate re p ort
f or m as descri be d i n Secti o n 7. 4. 1. 4.
It is i m p orta nt t hat eac h A E re p ort i ncl u de a descri pti o n of t he e ve nt, its d urati o n ( o nset a n d 
res ol uti o n dates [a n d ti mes w he n it is i m p orta nt t o assess t he ti me of A E o nset relati ve t o t he 
rec or de d treat me nt a d mi nistrati o n ti me]), its se verit y, its ca usal relati o ns hi p wit h t he trial 
treat me nt, a n y ot her p ote ntial ca usal fact ors, a n y treat me nt gi ve n or ot her acti o n ta ke n, i ncl u di n g 
d ose m o dificati o n or disc o nti n uati o n of t he trial treat me nt, a n d its o utc o me. I n ad diti o n, seri o us 
cases s h o ul d be i de ntifie d a n d t he a p pr o priate s eri o us ness criteria d oc u me nte d.
S pecific g ui da nce ca n be f o u n d i n t he e C R F C o m pleti o n a n d M o nit ori n g C o n ve nti o ns.
7. 4. 1. 3
Defi niti o n of t he A d verse E ve nt Re p orti n g Peri o d
T he A E re p orti n g peri o d f or safet y s ur veilla nce be gi ns w he n t he s u bject is i nitiall y  incl u de d i n t he 
trial ( date of first si g nat ure of i nf or me d c o nse nt) a n d c o nti n ues f or all S A Es a n d treat me nt-relate d 
n o n- seri o us A Es t hr o u g h t he st u d y’s Safet y F oll o w -u p P h o ne Call, defi ne d as 9 0 da y s ( ± 1 wee k) 
after t he last IM P .
A n y  SA E assesse d as relate d t o t he trial treat me nt m ust be re p orte d w he ne ver it occ urs, irres pecti ve 
of t he ti me ela pse d si nce t he last a d mi nistrati o n.
7. 4. 1. 4
Pr oce d ure f or Re p orti n g Seri o us A d verse E ve nts, A d verse 
E ve nts of S peci al I nterest a n d D ose -L i miti n g T o xicities
I n t he e ve nt of a n y ne w S A E occ urri n g d uri n g t he re p orti n g peri o d, t he I n vesti gat or m ust 
i m me diatel y ( wit hi n a ma xi m u m 2 4 h o urs after bec o mi n g a ware of t he e ve nt) i nf or m t he S p o ns or 
or its des i g nee usi n g t he S A E Re p ort F or m f oll o wi n g s pecific c o m pleti o n i nstr ucti o ns .
I n e xce pti o nal circ u msta nces, a n S A E ( or f oll o w- u p i nf or mati o n) m a y  be re p orte d b y  tele p h o ne; 
i n t hese cases, a S A E R e p ort F or m m ust be pr o vi de d i m me diatel y  t hereafter.  
Rele va nt pa ges fr o m t he eC R F m a y  be pr o vi de d i n parallel (f or e xa m ple, me dical hist or y , 
c o nc o mita nt dr u gs). A d diti o nal d oc u me nts ma y  be pr o vi de d b y  t he I n vesti gat or, if a vaila ble (f or 
e xa m ple, la b orat or y res ults, h os pital re p ort, a ut o ps y re p ort). I n all cases, t he i nf or mati o n pr o vi de d 
o n t he S A E Re p ort F or m m ust be c o nsiste nt wit h t he data a b o ut t he e ve nt rec or de d i n t he e C R F.
T he I n vesti gat or m ust res p o n d t o a n y re q uest f or f oll o w- u p i nf or mati o n (f or e xa m ple, a d diti o nal 
i nf or mati o n, o utc o me, fi nal e val uati o n, ot her rec or ds w here nee de d) or t o a n y questi o n t he 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 4 / 1 5 0
S p o ns or/ desi g nee m a y  h ave o n t he A E wit hi n t he sa me ti meli nes as t h ose n ote d a b o ve f or i nitial 
re p orts. T his is necessar y  to e ns ure pr o m pt assess me nt of t he e ve nt b y  the S p o ns or or desi g nee 
a n d (as a p plica ble) t o all o w t he S p o ns or t o meet strict re g ulat or y ti meli nes ass ociate d wit h 
e x pe dite d safet y re p orti n g o bli gati o ns.
Re q uests f or f oll o w -u p will us uall y  be ma de via t he res p o nsi ble m o nit or, alt h o u g h i n e xce pti o nal 
circ u msta nces t he Gl o bal Dr u g Safe t y De part me nt of t he S p o ns or m a y  co ntact t he I n vesti gat or 
directl y  t o o btai n clarificati o n or t o o btai n f urt her i nf or mati o n or t o disc uss t he e ve nt.
7. 4. 1. 5
S afet y Re p orti n g t o He alt h A ut h orities, I n de pe n de nt Et hics 
C o m mittees/ I nstit uti o n al Re vie w B o ar ds a n d I n ve sti g at ors
T he S p o ns or will se n d a p pr o priate safety n otificati o ns t o Healt h A ut h orities i n acc or da nce wit h 
a p plica ble la ws a n d re g ulati o ns.
T he I n vesti gat or m ust c o m pl y wit h a n y a p plica ble site-s pecific re q uire me nts relate d t o t he 
re p orti n g of S A Es ( partic ularly deat hs) i n v ol vi n g trial s u bjects t o t he I EC/I R B t hat a p pr o ve d t he 
trial.
I n acc or da nce wit h I C H G C P, t he S p o ns or/ desi g nee will i nf or m t he I n vesti gat or of “fi n di n gs t hat 
c o ul d a d versel y affect t he safety o f s u bjects, i m pact t he c o n d uct of t he trial or alter t he I EC’s/I R B’s 
a p pr o val/fa v ora ble o pi ni o n t o c o nti n ue t he trial”.
I n partic ular a n d i n li ne wit h res pecti ve 
re g ulati o ns, t he S p o ns or/ desi g nee will i nf or m t he I nvesti gat or of A Es t hat are b ot h seri o us a n d 
u ne x pecte d a n d are c o nsi dere d t o be relate d t o t he a d mi nistere d pr o d uct (sus pecte d u ne x pecte d 
seri o us ad verse reacti o ns [S U S A Rs ]). T he I nvesti gat or s h o ul d place c o pies of Safet y  Re p orts i n 
t he I n vesti gat or Site File .  Nati o nal re g ulati o ns wit h re gar d t o Safet y Re p ort n otificati o ns t o 
I n vesti gat ors will be ta ke n i nt o acc o u nt.
W he n 
s pecificall y re q uire d b y  re g ulati o ns a n d g ui deli nes, t he S p o ns or/ desi g nee will pr o vi de 
a p pr o priate Safet y Re p orts directl y  to t he c o ncer ne d lea d I E C/IR B a n d will mai ntai n rec or ds of 
t hese n otificati o ns. 
W he n 
direct re p orti n g is n ot clearl y defi ne d b y  nati o nal or site-s pecific 
re g ulati o ns, t he I n vesti gat or will be res p o nsi ble f or pr o m ptl y n otif yi n g t he c o ncer ne d I E C/IR B of 
a n y Safet y Re p orts pr o vi de d b y  the S p o ns or/ desi g nee a n d of fili n g c o pies of all relate d 
c orres p o n de nce i n t he I n vesti gat or Site File.
F or trials c o vere d b y t he E ur o pea n Directi ve 2 0 0 1/ 2 0/ E C, t he S p o ns or’s res p o nsi bilities re gar di n g 
t he re p orti n g of S A Es/ S U S A Rs/ Safet y Iss ues will be carrie d o ut i n acc or da nce wit h t hat Directi ve 
a n d wit h t he relate d Detaile d G ui da nce d oc u me nts.
7. 4. 1. 6
M o nit ori n g of S u bjects wit h A d verse E ve nts
A d verse e ve nts are rec or de d a n d assesse d c o nti n u o usl y thr o u g h o ut t he trial (see Secti o n 7. 4. 1. 3 ) 
a n d are assesse d f or fi nal o utc o me at t he 3 0- da y  Safet y F oll o w- u p visit. After t h is visit, S A Es a n d 
treat me nt-relate d n o n-seri o us A Es are rec or de d a n d assesse d c o nti n u o usl y u ntil t he 9 0-d a y Safet y 
F oll o w -u p P h o ne Call . 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 5 / 1 5 0
All S A Es o n g oi n g at t he 9 0 -d a y  Safet y F oll o w - u p Ph o ne C all m ust be m o nit ore d a n d f oll o we d u p 
b y  the I n vesti gat or u ntil sta bilizati o n or u ntil t he o utc o me is k n o w n, u nless t he s u bject is 
d oc u me nte d as “l ost t o f oll o w -u p”. Re as o na ble atte m pts t o o btai n t his i nf or mati o n m ust be ma de 
a n d d oc u me nte d. It is als o t he res p o nsi bilit y of t he I nvesti gat or t o e ns ure t hat a n y necessar y 
a d diti o nal t hera pe utic meas ures a n d f oll o w- u p pr oce d ures are perf or me d.
7. 4. 2
Pre g n a nc y a n d I n Uter o Dr u g E x p os ure
O nl y  pre g na ncies c o nsi dere d by t he I n vesti gat or t o be relate d t o trial treat me nt ( e g, res ulti n g fr o m 
a dr u g i nteracti o n wit h a c o ntrace pti ve me dicati o n) are c o nsi dere d t o be A Es. 
H o we ver, all 
pre g na ncies wit h a n esti mate d c o nce pti o n date d uri n g t he peri o d defi ne d i n Secti o n 7. 4. 1. 3 m ust 
be rec or de d b y  co n ve nti o n i n t he A E pa ge/secti o n of t he e C R F. 
T he sa me r ule a p plies t o 
pre g na ncies i n fe male s u bjects a n d t o pre g na ncies i n fe male part ners of male s u bjects. T he 
I n vesti gat or m ust n otif y t he S p o ns or/ desi g nee i n a n e x pe dite d ma n ner of a n y pre g na nc y usi n g t he 
Pre g na nc y  Re p ort F or m , w hic h m ust be tra ns mitte d acc or di n g t o t he sa me pr ocess as descri be d 
f or S A E re p orti n g i n Secti o n 7. 4. 1. 4.
I n vesti gat ors m ust 
acti vel y foll o w - u p, d oc u me nt, a n d re p ort o n t he o utc o me of all t hese 
pre g na ncies, e ve n if t he s u bjects are wit h dra w n fr o m t he trial.
T he I nvesti gat or m ust n otif y  the S p o ns or/ desi g nee of t hese o utc o mes usi n g t he Pre g na nc y  For m. 
If a n a b n or mal o utc o me occ urs, t he S A E Re p ort F or m will be use d if t h e s u bject s ustai ns a n e ve nt 
a n d t he Pare nt -C hil d/ Fet us A E Re p ort F or m if t he c hil d/fet us s ustai ns a n e ve nt.
A n y  ab n or mal o utc o me m ust be re p orte d i n a n e x pe dite d ma n ner as descri be d i n Secti o n  7. 4. 1. 4,  
w hile n or mal o utc o mes m ust be re p orte d wit hi n 4 5 da y s after deli ver y.
I n the e ve nt of a pre g na nc y  in a s u bject occ urri n g d uri n g t he c o urse of t he trial, t he s u bject m ust 
be disc o nti n ue d fr o m trial treat me nt i m me diatel y . T he S p o ns or/ desi g nee m ust be n otifie d wit h o ut 
dela y  a n d t he s u bject m ust be f oll o we d as me nti o ne d a b o ve.
7. 4. 3
Cli nic al L a b or at or y Assess me nts
All la b orat or y sa m ples t hat are detaile d i n t he Sc he d ule of Assess me nts (see Ta ble 1 t o Ta ble 7 ) 
m ust be c ollecte d, a n d se nt t o t he ce ntral la b orat or y for a nal ys is.  Ser u m β- h C G pre g na nc y  tests 
ma y  be a nalyz e d l ocall y.
Sa m ple f or c o m plete bl o o d c o u nt a n d c ore c he mistr y m ust be a vaila ble a n d re vie we d pri or t o d ose 
a d mi nistrati o n.  Res ults of all ce ntral la b orat or y testi n g will be tra nsferre d t o t he cli nical data base.
Uri nal y sis a n d u ri ne p re g na nc y testi n g will be d o ne l ocall y.
L ocal la b orat or y  sa m ples ma y be dra w n a n d if c ollecte d are re q uire d t o be rec or de d i n t he e C R Fs.
I n t he case of li ver f u ncti o n test (L F T ) ele vati o ns ( A S T, A L T a n d/ or t otal bilir u bi n) re q uiri n g 
a d diti o nal la b dra ws (acc or di n g t o g ui deli nes set f ort h i n Ta ble 1 1 Ma na ge me nt of ir A Es), a n 
u nsc he d ule d la b dra w s h o ul d be se nt t o t he ce ntral la b orat or y  f or a nalys is.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 6 / 1 5 0
Car diac tr o p o ni n le vels will be c ollecte d fr o m R e- baseli ne u p t o 1 2 wee ks i n t he M ai nte na nce 
P hase.  Car diac tr o p o ni n le vels will be e val uate d ce ntrall y .  Local la b orat ories ma y  be use d at t he 
discreti o n of t he I n vesti gat or as cli nicall y nee de d f or safet y m a na ge me nt/treat me nt decisi o n of t he 
s u bject. Meas ure me nt of c T n T is preferre d, h o we ver c T nI m a y  be s u bstit ute d w here c T n T is n ot 
a vaila ble at t he l ocal la b orat or y. T he sa me s u b u nit (c T n T or c T nI) meas ure d at t he Re- baseli ne
visit s h o ul d be meas ure d c o nsiste ntl y thr o u g h o ut t he st u d y in eac h patie nt . 
At t he Re -baseli ne 
visit , cli nicall y si g nifica nt p ositi ve res ults s h o ul d be f urt her assesse d as per l ocal S O C t o r ule-o ut 
c o nc urre nt car diac c o n diti o ns w hic h w o ul d ma ke t he patie nt i neli gi ble f or t he st u d y as per 
e xcl usi o n criteria.
D uri n g 
t he st u d y, cli nicall y si g nifica nt ne w ele vati o ns s u g gesti ve of 
m y ocar ditis s h o ul d be assesse d as per  Ta ble 1 1. A d diti o nal tests s h o ul d als o be perf or me d w he n 
cli nicall y i n dicate d.
T he re p ort of t he res ults m ust be retai ne d as a part of t he s u bject’s me dical rec or d or s o urce 
d oc u me nts.  Bl o o d sa m ples f or t he f ull safet y t ests liste d i n Ta ble 1 2 will be ta ke n fr o m n o nfaste d 
s u bjects d uri n g t he Scree ni n g P hase ( 2 8 d a y s pri or t o e nteri n g t he I n d ucti o n P hase ); d uri n g t he 
T reat me nt P hase as s pecifie d i n Ta ble 1,  Ta ble 2,  Ta ble 3,  Ta ble 4,  Ta ble 5, Ta ble 6 ; at t he 
E n d - of-Treat me nt visit ; a n d at t he Safet y  Foll o w - u p visit.  T he T 4, T S H, a n d uri nal y sis will o nl y  
be assesse d at t he ti me p oi nts defi ne d i n Ta ble 1, Ta ble 2, Ta ble 3, Ta ble 4, Ta ble 5 , a n d Ta ble 6.   
If c o nfir mati o n of a s u bject’s p ost me n o pa usal stat us is necessar y , a n F S H le vel will als o be 
perf or me d at Scree ni n g , see Secti o n 7. 1.
T a ble 1 2
Cli nic al L a b or at or y Assess me nts
F ull C h e mi str y
C or e C h e mi str y a
H e m at ol o g y
Al b u mi n
Al k ali n e p h o s p h at a s e
A b s ol ut e l y m p h o c yt e c o u nt
Al k ali n e p h o s p h at a s e
A L T
A b s ol ut e n e utr o p hil c o u nt
A L T
A m yl a s e
H e m at o crit
A m yl a s e
A S T
H e m o gl o bi n
A S T
B U N/t ot al ur e a
Pl at el et c o u nt
G G T
C al ci u m
R B C c o u nt
B U N/t ot al ur e a
C hl ori d e
W h it e bl o o d c ell c o u nt a n d diff er e nti al c o u nt
C al ci u m
Cr e ati n e ki n a s e
R eti c ul o c yt e s
C hl ori d e
Cr e ati ni n e
M C H
C h ol e st er ol
Gl u c o s e
M e a n c or p u s c ul ar v ol u m e
Cr e ati n e ki n a s e
L D H
M C H C
Cr e ati ni n e
Li p a s e
C R P
P h o s p h or u s/ P h o s p h at e s
Gl u c o s e
M a g n e si u m
H e m o st a s e ol o g y
L D H
P ot a s si u m
a P T T
Li p a s e
S o di u m
Pr ot hr o m bi n ti m e/I N R
P h o s p h or u s/ P h o s p h at e s
T ot al bilir u bi n
M a g n e si u m
B a si c Uri n al y si s ( di p sti c k, i n cl u di n g m a cr o s c o pi c 
a p p e ar a n c e, bilir u bi n, bl o o d, c ol or, gl u c o s e, 
k et o n e s, l e u k o c yt e e st er a s e, nitrit e, p H, pr ot ei n, 
s p e cifi c gr a vit y, ur o bili n o g e n)
P ot a s si u m
S o di u m
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 7 / 1 5 0
F ull C h e mi str y
C or e C h e mi str y a
H e m at ol o g y
T ot al bilir u bi n
F ull uri n al y si s ( di p sti c k pl u s mi cr o s c o pi c e v al u ati o n) 
t o b e p erf or m e d o nl y at t h e S cr e e ni n g, 
R e -b a s eli n e, a n d E n d of Tr e at m e nt vi sit s a n d a 
b a si c uri n al y si s pri or t o e a c h a d mi ni str ati o n of t h e 
tri al tr e at m e nt at We e k 1, W e e k 7, W e e k 1 3, e v er y 
1 2 w e e k s t h er e aft er, a n d at 3 0 -d a y S af et y 
F oll o w -u p vi sit.
T ot al pr ot ei n
Uri c a ci d
T ot alit y of bi n di n g 
Tri gl y c eri d e s
T S H a n d T 4
H or m o n e
F S H ( y e s/ n o if a p pli c a bl e)
, A L T = al a ni n e a mi n otr a n sf er a s e, a P T T = a cti v at e d p arti al t hr o m b o pl a sti n ti m e, 
A S T = a s p art at e a mi n otr a n sf er a s e, B U N = bl o o d ur e a nitr o g e n, C R P = C-r e a cti v e pr ot ei n, F S H =f olli cl e- sti m ul ati n g 
h or m o n e, G G T = g a m m a -gl ut a m yltr a n sf er a s e, I N R =i nt er n ati o n al n or m ali z e d r ati o, L D H =l a ct at e d e h y dr o g e n a s e, 
M C H = m e a n c or p u s c ul ar h e m o gl o bi n, M C H C = m e a n c or p u s c ul ar h e m o gl o bi n c o n c e ntr ati o n, R B C =r e d bl o o d c ell, 
T S H =t h yr oi d -sti m ul ati n g h or m o n e, T 4 =fr e e t h yr o xi n e.
a.
C or e s er u m c h e mi stri e s.
If a s u bject has a cli nicall y si gnifica nt a b n or mal la b orat or y test val ue t hat is n ot prese nt at baseli ne, 
t he test will be re peate d wee kl y a n d t he s u bject will be f oll o we d u ntil t he test val ue has ret ur ne d 
t o t he n or mal ra n ge or t he I n vesti gat or has deter mi ne d t hat t he a b n or mality is c hr o nic or sta ble.
7. 4. 4
Vit al Si g ns, P h ysic al E x a mi n ati o ns, a n d Ot her Assess me nts
Vital si g ns i ncl udi n g b o d y  te m perat ure, res pirat or y rate, heart rate (after 5- mi n ute rest), a n d arterial 
bl o o d press ure (after 5 -mi n ute rest) w ill be rec or de d at trial e ntr y.
A c o m plete p h y sical e xa mi nati o n (i ncl u di n g ge neral a p peara nce, der mat ol o gical, hea d/ nec k, 
p ul m o nar y , car di o vasc ular, gastr oi ntesti nal, ge nit o uri nar y , l ym p hatic, m usc ul os keletal s yste m, 
e xtre mities, e yes [i ns pecti o n a n d visi o n c o ntr ol], n ose, t hr oat, a n d ne ur ol o gic stat us) will be 
perf or me d at Scree ni n g a n d at s u bse q ue nt visits as d oc u me nte d i n t he Sc he d ule of Assess me nts 
a n d t he res ults d oc u me nte d i n t he e C R F.  A b n or mal fi n di n gs are t o be reassesse d at s u bse q ue nt 
visits.
T he E C O G P S will be d oc u me nte d d uri n g t he Scree ni n g P hase a n d at eac h sc he d ule d visit (if t he 
Scree ni n g E C O G P S was perf or me d wit hi n 3 da y s pri or t o Da y 1, it d oes n ot ha ve t o be re peate d 
at Da y 1) a n d d oc u me nte d i n t he e C R F.
B o d y wei g ht will be rec or de d at Scree ni n g a n d at s u bse q ue nt visits as i n dicate d i n t he Sc he d ule of 
Assess me nts a n d d oc u me nte d i n t he e C R F. Hei g ht will be meas ure d at Scree ni n g o nl y .
A 1 2 -lea d E C G will be rec or de d as i n dicate d i n t he Sc he d ule of Assess me nts.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 8 / 1 5 0
All ne wl y  dia g n ose d or w orse ni n g c o n diti o ns, si g ns, a n d s ym pt o m s o bser ve d fr o m Scree ni n g , 
w het her relate d t o trial treat me nt or n ot, are t o be re p orte d as A Es.
F or fe male s u bjects of c hil d beari n g p ote ntial, a ser u m β- h C G pre g na nc y  test will be carrie d o ut 
d uri n g t he Scree ni n g P hase . A uri ne or ser u m β- h C G test will b e perf or me d at t he visits as 
i n dicate d i n t he Sc he d ules of Assess me nts . Res ults of t he m ost rece nt pre g na nc y  test has t o be 
a vaila ble pri or t o t he ne xt d osi n g of trial treat me nt. S u bjects w h o are p ost me n o pa usal (a ge-relate d 
a me n orr hea ≥ 1 2 c o nsec uti ve m o nt hs a n d F S H > 4 0 mI U/ m L), or w h o ha ve u n der g o ne 
h y sterect o my or bilateral o o p h orect o m y are e xe m pt fr o m pre g na nc y testi n g.
7. 5. 1
B o d y Fl ui d(s)
W h ole bl o o d s ufficie nt t o pr o vi de 0. 2 m L  of ser u m will be c ollecte d f or 
.  F urt her 
details will be s u m marize d i n t he La b orat or y  Ma n ual.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 0 9 / 1 5 0
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 0 / 1 5 0
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 1 / 1 5 0
7. 7
Ot her Assess me nts
7. 7. 1
S u bject- re p orte d O utc o mes / Q u alit y of Life
S u bject -re p orte d o utc o mes / Q o L  will be assesse d b y t he E Q- 5 D-5 L , a n d E O R T C Q LQ- C 3 0, a n d  
m o d ule Q L Q -S T O 2 2. 
Q uesti o n naires will be c o m plete d b y  the s u bject at Scree ni n g a n d as 
i n dicate d w hile o n trial treat me nt (see Ta ble 1 t o Ta ble 6 f or detaile d sc he d ule f or eac h re gi me n). 
S u bject -re p orte d o utc o mes will als o be assesse d at t he Disc o nti n uati o n/ E n d of Treat me nt visit a n d 
t he Safety F oll o w -u p visit ( details will be pr o vi de d i n t he St u d y  Ma n ual).  
T he s u bject-re p orte d o utc o mes / Q o L q uesti o n naires s h o ul d be c o m plete d b y  the s u bject pri or t o 
a n y of t he ot her trial-relate d assess me nts bei n g perf or me d, t hat is, p h y sical e xa mi nati o ns, bl o o d 
dra ws, trial treat me nt a d mi nistrati o n, etc.  S u bjects will use a vali date d electr o nic ta blet or 
vali date d site pa d t o rec or d t heir res p o nses t o t hese q uesti o n naires.  In rare a nd e xte n uati n g 
circ u msta nces w he n a n electr o nic ta blet or site pa d is n ot a vaila ble or n ot w or ki n g pr o perl y, 
c ollecti o n o n vali date d pa per q uesti o n naires m a y  be all o we d t o e ns ure data are c ollecte d a n d n ot 
l ost.
Data will be c ollecte d b y t he C R O a n d h o use d i n a data base. A nal ys is of t he q uesti o n naires will 
be descri be d i n t he statistical a nal ys is pla n (S A P ).
8
St atistics
8. 1
S a m ple Size
T he sa m ple size of t his st u d y is base d o n c o m pari n g mai nte na nce t hera p y a vel u ma b vers us 
c o nti n uati o n of first-li ne c he m ot hera p y i n ter ms of t he t w o pri mar y  h yp ot heses (for hierarc h y  of 
m ulti ple testi n g pr oce d ure, see Secti o n 8. 5. 1 ) of O S i n all ra n d o mize d s u bjects a n d i n P D -L 1 + 
s u bjects.
T he st u d y  will be c o nsi dere d s uccessf ul if at least o ne of t he t w o n ull h y p ot heses f or O S i n eit her 
all ra n d o mize d s u bjects or i n P D -L 1 + s u bjects, c o ul d be rejecte d as statisticall y si g nifica nt. A n 
i m bala nce d t ype I err or all ocati o n will be use d f or t he t w o pri mar y h y p ot heses a n d c o ntr ol o verall 
fa mil y wise t ype I err or rate at 2. 5 % ( 1-si de d) wit h 0. 5 % ( 1-si de d) all ocate d t o P D -L 1 + s u bjects
a n d 2 % (1- si de d) all ocate d t o all ra n d o mize d s u bjects . T he sa m ple size f or t his st u d y is dri ve n b y 
t he f oll o wi n g ass u m pti o ns f or t he pri mar y e n d p oi nt of O S:

E x p o ne ntial distri b uti o n of O S ;

1: 1 ra n d o mizati o n;

Dr o p -o ut rate = 5 %;

U nif or m accr ual o ver a peri o d of 1 8 m o nt hs;

A f oll o w - u p ti me of 1 8 m o nt hs after ra n d o mizati o n of t he last s u bject;
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 2 / 1 5 0

F or all ra n d o mize d s u bjects recei vi n g a vel u ma b, me dia n O S is 1 5 m o nt hs;

F or P D -L 1 + s u bjects recei vi n g a vel u ma b, t he me dia n O S is 1 9. 3 m o nt hs;

F or all ra n d o mize d s u bjects a n d P D -L 1 + s u bjects recei vi n g first-li ne c he m ot hera p y, t he 
me dia n O S is 1 0. 5 m o nt hs.
T his c orres p o n ds t o a h azar d rati o ( H R) of 0. 7 f or O S i n all ra n d o mize d s u bjects a n d 0. 5 4 f or O S 
i n P D-L 1 + s u bjects. At pla n ni n g sta ge, it wa s ass u me d t hat t he pre vale nce of P D-L 1 + s u bjects i n 
all ra n d o mize d s u bjects is 3 5 %.  D ue t o a l o wer pre vale nce of P D-L 1 + s u bjects i n t he st u d y t ha n 
i nitiall y e xpecte d, t he tar gete d 1 1 2 O S e ve nts i n P D -L 1 + s u bjects f or t he pri mar y a nal ys is will n ot 
be reac he d d uri n g t he st u d y.  T he pri mar y a nal ys is of O S i n P D-L 1 + s u bjects will be c o n d ucte d at 
t he ti me of t he pri mar y a nal ysis of O S i n all ra n d o mize d s u bjects wit h p o wer less t ha n 8 0 %.
T he ass u me d dr o p - o ut rate f or O S is base d o n res pecti ve e x perie nce i n pre vi o us cli nical st u dies.
T he act ual n u m ber of s u bjects e nr olle d i n t he I nd ucti o n P hase will be dr i ve n b y  the o bser ve d 
i n d ucti o n fail ure rates, a n d will be s uc h t o all o w f or a p pr o xi matel y 4 6 6 s u bjects t o be ra n d o mize d 
i nt o t he treat me nt ar m i n t he Mai nte na nce P hase.  At t he ti me of t his pr ot oc ol a me n d me nt, s u bject 
e nr oll me nt i nt o t he Mai nte na nce P hase is c o m plete, wit h a t otal of 4 9 9 s u bjects ra n d o mize d i nt o 
t he Mai nte na nce P hase .
T he data c ut -off f or t he pri mar y a nal ysis wil l ta ke place o n a pr os pecti vely -deter mi ne d date, u p o n 
w hic h t he tar get n u m ber of 3 5 6 O S e ve nts i n all ra n d o mize d s u bjects are pr ojecte d t o ha ve bee n 
reac he d, a n d t he last s u bject ra n d o mize d i n t he Mai nte na nce P hase has bee n f oll o we d f or at least 
1 8 m o nt hs fr o m ra n d o mizati o n.
F or O S
i n all ra n d o mize d s u bjects, 3 5 6 O S e ve nts are re q uire d t o ac hie ve 9 0 % p o wer of t he 
l o g-ra n k test at a 1- si de d o verall 2 % al p ha le vel. T his calc ulati o n i ncl u des o ne i nteri m efficac y 
a nal ys is a n d ass u mes it will be perf or me d after 7 5 % of e ve nts ha ve bee n o bser ve d. T he i nteri m 
a n d pri mar y  a nal ys es will f oll o w a se q ue ntial al p ha s pe n di n g f u ncti o n a p pr oac h de vel o pe d b y  Lan 
a n d De Mets, usi n g a n O’ Brie n a n d Fle mi n g b o u n dar y  fu ncti o n. A p pl y i n g t his a p pr oac h wit h a n 
ass u me d 2 6 7 a n d 3 5 6 o bser ve d e ve nts res pecti vel y, a 1- si de d si g nifica nce le vel of 0. 0 0 7 2 f or t he 
i nteri m a nal ysis a n d 0. 0 1 7 8 f or t he fi nal a nal ys is w ill preser ve a n o verall t ype I err or rate of 2 % 
f or t he O S i n all ra n d o mize d s u bjects.
T he si m ulati o ns wit h t he a b o ve ass u m pti o ns ha ve bee n perf or me d t o assess t he o verall p o wer f or 
t he tar get n u m ber of O S e ve nts a n d ti mi n g of i nteri m a n d pri mar y  anal yses. T he c orrelati o n 
bet wee n test statistics f or O S i n all ra n d o mize d s u bjects a n d O S i n P D -L 1 + s u bjects (s q uare r o ot 
of pre vale nce = √0. 3 5 ) has bee n c o nsi dere d. T he c o m plete m ulti ple testi n g pr oce d ure f or t he t w o 
O S h y p ot heses ( details of m ulti ple testi n g pr oce d ure are i n Secti o n 8. 5. 1 ) usi n g t he i nteri m test 
statistics f or all ra n d o mize d s u bjects a n d test statistics f or all ra n d o mize d s u bjects a n d P D -L 1 + 
s u bjects at pri mar y anal ysis ha ve bee n a p plie d i n t he si m ulati o ns. If e xactl y 3 5 6 O S e ve nts i n all 
ra n d o mize d s u bjects a n d 1 1 2 O S e ve nts i n P D -L 1 + s u bjects are reac he d, the si m ulati o ns s h o we d 
a pr o ba bilit y  of rejecti o n at least o ne h y p ot hesis of 9 3. 5 %. 
T he n ull h y p ot hesis of O S i n all 
ra n d o mize d s u bjects is rejecte d i n ar o u n d 9 0. 9 % of t he si m ulati o ns, t he n ull h y p ot hesis of O S i n 
P D -L 1 + s u bjects is rejecte d i n ar o u n d 8 0. 3 % of t he si m ulati o ns.
Calc ulati o ns were perf or me d usi n g E A S T ® versi o n 6. 3, C y tel I nc a n d R s oft ware .
D oc u me nt N o.
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 3 / 1 5 0
8. 2
R a n d o miz ati o n
T he st u d y is a ra n d o mize d, acti ve -c o ntr olle d, a n d o pe n -la bel st u d y.  Eli gi ble s u bjects will be 
ra n d o ml y assi g ne d i nt o eit her t he a vel u ma b ar m or c o ntr ol gr o u p i n a 1: 1 rati o after 1 2- wee k
c he m ot hera p y i n t he In d ucti o n P hase. T he ra n d o mizati o n will be stratifie d b y re gi o n (Asia vers us 
n o n- Asia) . T he p ur p ose of t he stratificati o n is t o e ns ure a bala nce of t he treat me nt ar ms wit hi n 
eac h re gi o n. Ra n d o mizati o n will occ ur usi n g t he I WR S as descri be d i n Secti o n  2 u p o n c o m pleti o n 
of t he I n d ucti o n P hase a n d deter mi nati o n of s u bject eli gi bilit y .  
8. 3
E n d p oi nts
8. 3. 1
Pri m ar y E n d p oi nt
T he pri mar y  e n d p oi nt of t he trial is O S, defi ne d as t he ti me (i n m o nt hs) fr o m ra n d o mizati o n t o t he 
date of deat h, re gar dless of t he act ual ca use of t he s u bject’s deat h .
T he s ur vi val f oll o w- u p will c o nti n ue u ntil 5 ye ars after t he last s u bject recei ves t he last d ose of 
a vel u ma b.  F or s u bjects w h o are still ali ve at t he ti me of data a nal ys is or w h o are l ost t o f oll o w-u p, 
O S will be ce ns ore d at t he last rec or de d date t hat t he s u bject is k n o w n t o be ali ve ( date of last 
c o ntact, last visit date, date of last ra n d o mize d treat me nt a d mi nistrati o n, or date of last sca n, 
w hic he ver is t he latest) as of t he data c ut -off date f or t he a nal y sis.  
8. 3. 2
Sec o n d ar y E n d p oi nts
T he sec o n dar y e n d p oi nts , w hic h c orres p o n d t o t he Mai nte na nce 
P hase i n t his trial, are t he 
f oll o wi n g:

P F S i n all ra n d o mize d s u bjects accor di n g t o R E CI S T v 1. 1, per I n vesti gat or assess me nt

B O R i n all ra n d o mize d s u bjects acc or di n g t o R E CIS T v 1. 1 , per I n vesti gat or assess me nt

S u bject -re p orte d o utc o mes / Q o L

Safet y  a n d t olera bilit y i n all s u bjects.
8. 3. 2. 1
Pr o gressi o n -Free S ur vi v al
Pr o gressi o n -Free S ur v i val, defi ne d as t he ti me (i n m o nt hs) fr o m ra n d o mizati o n t o t he date of t he 
first d oc u me ntati o n of o bjecti ve P D or deat h d ue t o a n y ca use ( w hic he ver occ urs first), is t he first 
ke y  sec o n dar y en d p oi nt of t he st u d y. T he date of t he first d oc u me nte d o bjecti ve P D will be 
deter mi ne d acc or di n g t o R E CI S T v 1. 1 base d o n In vesti gat or res p o nse assess me nt.
T he P F S data will be ce ns ore d o n t he date of t he last a de q uate t u m or assess me nt f or s u bjects w h o 
d o n ot ha ve a n e ve nt ( P D or deat h), f or s u bjects w h o start ne w a ntica ncer treat me nt pri or t o a n 
e ve nt, or f or s u bjects wit h a n e ve nt after 2 or m ore missi n g t u m or assess me nts.  S u bjects w h o d o 
n ot ha ve a baseli ne t u m or assess me nt or w h o d o n ot ha ve a n y p ost -baseli ne t u m or assess ments 
will be ce ns ore d o n t he date of ra n d o mizati o n u nless deat h occ urre d o n or bef ore t he ti me of t he 
sec o n d pla n ne d t u m or assess me nt, i n w hic h case t he deat h will be c o nsi dere d a n e ve nt.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 4 / 1 5 0
8. 3. 2. 2
Best O ver all Res p o nse
Best O verall Res p o nse i n Mai nte na nce P hase is t he ke y sec o n dar y en d p oi nt f or t he st u d y.  T he 
c o nfir me d B O R will be deter mi ne d acc or di n g t o R E CI S T v 1. 1, per I n vesti gat or assess me nt, a n d 
statisticall y e val uate d as t he O R R.  B O R is defi ne d as t he best res p o nse o btai ne d a m o n g all t u m or 
assess me nt visits after t he date of ra n d o mizati o n u ntil d oc u me nte d disease pr o gressi o n.
F or a B O R of P R or C R, c o nfir mati o n of t he res p o nse acc or di n g t o R E CI S T v 1. 1 will be re q uire d, 
prefera bl y at t he re g ularl y sc he d ule d 6 -wee k assess me nt i nter val b ut n o s o o ner t ha n 4 wee ks a fter 
t he i nitial d oc u me ntati o n of C R or P R.  Co nfir mati o n of P R ca n be c o nfir me d at a n assess me nt 
later t ha n t he ne xt assess me nt after t he i nitial d oc u me ntati o n of P R.  A BO R of S D re q uires t hat 
a n o verall res p o nse of S D has bee n deter m i ne d at a ti me p oi nt at least 6 wee ks after ra n d o mizati o n.
T he O R R is defi ne d as t he pr o p orti o n of all ra n d o mize d s u bjects wit h a c o nfir me d B O R of P R or 
C R acc or di n g t o R E CI S T v 1. 1 , as per I n vesti gat or assess me nt.
8. 3. 2. 3
S u bject- Re p orte d O utc o mes / Q u alit y of Life
T he f oll o wi n g s u bject-re p orte d o utc o mes are f urt her sec o n dar y en d p oi nts f or m ai nte na nce 
t hera py :

E Q - 5 D-5 L

E O R T C Q L Q- C 3 0

E O R T C Gastric Ca ncer M o d ule Q L Q- S T O 2 2 .
8. 3. 3
S afet y E n d p oi nts
Safet y  en d p oi nts i ncl u de A Es, 
p h y sical e xa mi nati o ns, cli nical la b orat or y assess me nts, 
c o nc o mita nt me dicati o ns, vital si g ns, E C G para meters, a n d E C O G P S .
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 5 / 1 5 0
8. 4
A n al ysis Sets
Scree ni n g A n al ysis Set
T he Scree ni n g A nal ys is Set i ncl u des all s u bjects w h o si g ne d t he I C F.
I nte nti o n-t o-Tre at (I T T) A n al ysis Set
T he I T T A nal ys is Set will i ncl u de all s u bjects w h o were ra n d o ml y assi g ne d t o Mai nte na nce P hase 
st u d y treat me nt. A nal ys es perf or me d o n t he I TT A nal y sis Set will be perf or me d acc or di n g t o
s u bjects’ treat me nt ar ms, as ra n d o mize d. T he I TT A nal ys is Set will be t he pri mar y  an al y sis set 
f or all pri mar y a n d sec o n dar y efficac y e n d p oi nts.
Per -Pr ot oc ol A n al ysis Set
T he Per- Pr ot oc ol ( P P) A nal y sis Set will i ncl u de all I TT s u bjects w h o di d n ot ha ve cli nicall y 
i m p orta nt pr ot oc ol de viati o ns . Cli nicall y  i m p orta nt pr ot oc ol de viati o ns will be s pecifie d i n t he 
trial S A P.  
P D -L 1 + A n al ysis Set
T he P D -L 1 + A nal ys is Set is a s u bset of t he I TT A nal y sis Set c o nsisti n g of all P D -L 1 + s u bjects 
deter mi ne d b y t he P D -L 1  I H C 7 3-1 0 p har m D x c o m pa ni o n dia g n ostic assa y.  A nal yses perf or me d 
o n t he P D -L 1 +
A nal ys is Set will be perf or me d acc or di n g t o s u bjects’ treat me nt ar ms as 
ra n d o mize d.  One of t w o pri mar y  hy p ot heses f or O S s u bjects will be teste d i n t he P D -L 1 + A nal ys is 
Set.
He alt h -Rel ate d Q u alit y of Life A n al ysis Set 
T he H R Q o L A nal ys is Set is a s u bset o f t he I T T A nal y sis Set a n d i ncl u des all I T T s u bjects w h o 
meet b ot h of t he f oll o wi n g criteria:

Re -baseli ne H R Q o L assess me nt c o m plete d

At least o ne M ai nte na nce P hase H R Q o L assess me nt c o m plete d .
Re -baseli ne H R Q o L assess me nt occ urs f oll o wi n g c o m pleti o n of I n d ucti o n P hase c he m ot hera p y 
treat me nt at t he Re-baseli ne visit, w hic h s h o ul d occ ur wit hi n t he 1 0 -d a y  Re- baseli ne peri o d. 
Mai nte na nce P hase H R Q o L assess me nt is defi ne d as H R Q o L q uesti o n naires c o mplete d after t he 
first d ose of Mai nte na nce 
P hase st u d y treat me nt f or s u bjects w h o recei ve d a vel u ma b or 
c o nti n uati o n of I n d ucti o n P hase c he m ot hera p y treat me nt, a n d H R Q o L q uesti o n naires c o m plete d 
after date of ra n d o mizati o n f or s u bjects o n B S C- o nl y . 
S afet y f or I n d ucti o n P h ase ( S afet y-I n d ucti o n) A n al ysis Set
D oc u me nt N o.
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 6 / 1 5 0
T he Safet y- I n d ucti o n A nal y sis Set will i ncl u de all s u bjects w h o were e nr olle d i nt o t he st u d y (ie, 
si g ne d i nf or me d c o nse nt) a n d recei ve d at least 1 d ose of I n d ucti o n P hase c he m ot hera p y.  A n al ysis 
f or t he Safet y- I n d ucti o n A nal ysis Set will be s u m marize d f or all s u bjects as o ne si n gle gr o u p.
S afet y f or M ai nte n a nce P h ase ( S afet y -M ai nte n a nce) A n al ysis Set
T he Safet y- Mai nte na nce A nal ys is Set will i ncl u de all s u bjects w h o recei ve d at least 1 d ose of 
ra n d o mize d treat me nt or w h o were assi g ne d t o recei ve B S C - o nl y i n t he Mai nte na nce P hase .  
A nal y ses perf or me d o n t he Safet y- Mai nte na nce A nal y sis Set will c o nsi der s u bjects as treate d.
8. 5
Descri pti o n of St atistic al A n al yses
8. 5. 1
Ge ner al C o nsi der ati o ns
F ull details of all pla n ne d a nal yses will be descri be d i n t he trial S A P.   T he S A P ma y  mo dif y  the 
pla ns o utli ne d i n t he pr ot oc ol; h o we ver, a n y maj or m o dificati o ns of pla n ne d a nal ys es will be 
reflecte d i n a pr ot oc ol a me n d me nt if it is m o difie d bef ore data u n bli n di n g.  If, after t he trial is 
u n bli n de d, c ha n ges are ma de t o t he S A P, t he n t hese de viati o ns t o t he pla n will be d oc u me nte d i n 
t he Cli nical Trial Re p ort.
All safety a n d efficac y en d p oi nts will be s u m marize d b y  treat me nt ar m wit h t he e xce pti o n of 
e n d p oi nts c orres p o n di n g t o t he I n d ucti o n P hase w hic h will be s u m marize d b y  total n u m ber of 
s u bjects.  
I n or der t o pr o vi de o verall esti mates of treat me nt effects, data will be p o ole d acr oss trial ce nters.  
T he “ce nter” fact or will n ot be c o nsi dere d i n statistical m o dels or f or s u b gr o u p a nal ys es d ue t o t he 
hi g h n u m ber of partici pati n g ce nters i n c o ntrast t o t he a ntici pate d s mall n u m ber of s u bjects 
ra n d o mize d at eac h ce nter.
I n ge neral, c o nti n u o us varia bles will be s u m marize d usi n g n u m ber ( n), mea n, me dia n, sta n dar d 
de viati o n, mi ni m u m, a n d ma x i m u m. Cate g orical varia bles will be s u m marize d usi n g fre q ue nc y 
c o u nts a n d perce nta ges.
T he calc ulati o n of pr o p orti o ns will be base d o n t he n u m ber of s u bjects i n t he A nal y sis S et of 
i nterest, u nless ot her wise s pecifie d i n t he trial S A P.
B aseli ne
F or t he I n d ucti o n P hase, baseli ne is defi ne d as t he last meas ure me nt ta ke n pri or t o t he first d ose of 
treat me nt d uri n g t he I n d ucti o n P hase. F or t he Mai nte na nce P hase , baseli ne is defi ne d as t he last 
meas ure me nt ta ke n pri or t o t he first d ose of ra n d o mize d treat me nt f or safet y e n d p oi nts a n d t he last 
meas ure me nt ta ke n pri or t o ra n d o mizati o n f or efficac y en d p oi nts .  If s uc h a val ue is missi n g, t he 
last meas ure me nt pri or t o t he first d ose of ra n d o mize d treat me nt will be use d as t he baseli ne 
meas ure me nt
f or t he efficac y anal ys is e xce pt f or a nal ys es of t u m or assess me nts data w here t he 
B aseli ne assess me nt w o ul d be c o nsi dere d missi n g . F or s u bjects w h o recei ve d B S C -o nl y , baseli ne 
is defi ne d as t he last meas ure me nt ta ke n pri or t o ra n d o mizati o n f or b ot h safety a n d efficac y 
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 7 / 1 5 0
e n d p oi nts. B aseli ne f or heart rate a n d Q Tc assess me nts will be deri ve d fr o m t he visit w here b ot h
heart rate a n d Q T are n ot missi n g.
O n -Tre at me nt
F or t he I n d ucti o n P hase, t he o n- treat me nt peri o d is defi ne d as t he ti me fr o m t he first a d mi nistrati o n 
of c he m ot hera p y t o t he last a d mi nistrati o n of c he m ot hera p y + 3 0 d a y s, t he earliest date of 
s u bse q ue nt a ntica ncer dr u g t hera p y - 1 d a y , or t he date of ra n do mizati o n i nt o t he Mai nte na nce 
P hase - 1 da y , w hic he ver occ urs first.
F or s u bjects ra n d o mize d t o acti ve Mai nte na nce P hase st u d y me dicati o n, the o n- treat me nt peri o d 
is defi ne d as t he ti me fr o m t he first st u d y treat me nt a d mi nistrati o n t o t he last st u d y treatme nt 
a d mi nistrati o n date + 3 0 da y s or t he earliest date of s u bse q ue nt a ntica ncer dr u g t hera py mi n us 1 
da y, w hic he ver occ urs first, u nless ot her wise state d. F or s u bjects w h o recei ve d B S C -o nl y , st u d y 
treat me nt is c o nsi dere d t o start o n t he da y  of ra n d o mizati o n a n d e n d o n t he earliest date fr o m 
a m o n g t he f oll o wi n g: t he date gi ve n o n t he E n d of Assess me nt a n d St u d y  Ter mi nati o n e C R F pa ges, 
date of deat h .
M ulti ple C o m p aris o n Str ate g y
A hierarc h ical test strate g y will be use d t o c o ntr ol t he o verall t ype I err or rate f or t he pri mar y 
e n d p oi nt O S a n d ke y sec o n dar y e n d p oi nts of P F S a n d B O R i n t he f oll o wi n g hierarc hical or der:
1: O S i n t he IT T A nal y sis Set a n d t he P D -L 1 + A nal y sis Set i n t he Mai nte na nce P hase
2: P F S i n t he IT T A nal ysis Set i n t he Mai nte na nce P hase
3 : B O R i n t he I T T A nal ysis Set i n t he Mai nte na nce P hase
T he o verall 2. 5 % ( 1-si de d) t ype I err or will be s plit bet wee n O S i n all ra n d o mize d s u bjects a n d 
P D -L 1 + s u bjects wit h 2. 0 % ( 1-si de d) a n d 0. 5 % ( 1-si de d), res pecti vely.
O ne i nteri m a nal ysis is 
pla n ne d f or O S i n all ra n d o mize d s u bjects.  OS i n P D -L 1 + s u bjects will be teste d at t he pri mar y 
a nal ys is o nl y .  A La n -De Mets al p ha s pe n di n g f u ncti o n f or O’ Brie n -Fle mi n g b o u n daries will b e 
us e d t o c o ntr ol t he o verall t ype I err or rate of O S i n all ra n d o mize d s u bjects at 2 % bet wee n t he 
i nteri m a n d pri mar y a nal ysis (see Secti o n 8. 6 ).
F or t he pri mar y e n d p oi nt, a cl ose d testi n g pr oce d ure wit h wei g hte d B o nferr o ni tests , descri be d by 
H o m mel 2 0 0 7 will be use d f or deter mi ni n g si g nifica nce of t he d ual h y p ot hesis pri mar y  testi n g.
T he s u m mar y  is briefly descri b e d as f oll o ws (detaile d pr ocess is i n t he st u d y S A P ).
If a n y of t he t w o n ull h y p ot heses of O S (e val uate d i n all ra n d o mize d s u bjects a n d i n P D -L 1 + 
s u bjects) is rejecte d, t he c orres p o n di n g al p ha le vel will be rec ycle d bet wee n b ot h p o p ulati o ns. T he 
al p ha re c ycli n g a p pr oac h is as f oll o ws :
1.
If t he n ull hy p ot hesis of O S i n all ra n d o mize d s u bjects is rejecte d at eit her t he i nteri m or 
t he pri mar y  anal ys is, t he 2 % ( 1-si de d) al p ha all ocate d t o O S i n all ra n d o mize d s u bjects 
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 8 / 15 0
will be rec y cle d t o O S i n P D-L 1 + s u bjects, t he n 2. 5 % ( 1 -si de d) al p ha le vel will be use d 
f or O S i n P D-L 1 + s u bjects.
2.
If t he n ull h y p ot hesis of O S i n P D -L 1 + s u bjects at t he pri mar y  anal ys is is rejecte d, t he 
0. 5 % al p ha all ocate d t o O S i n P D -L 1 + s u bjects will be rec ycle d t o O S i n all ra n d o mize d 
s u bjects. I n this case, t he si g nifica nce will be base d o n a l ocal 2. 5 % ( 1-si de d) al p ha le vel 
f or O S i n all ra n d o mize d s u bjects. Ass u mi n g t he pla n ne d n u m ber of e ve nts are o bser ve d 
at eac h a nal ys is, t he 1-si de d b o u n daries w o ul d t he n be 0. 0 2 3 3 f or O S i n all ra n d o mize d 
s u bjects at pri mar y  anal ysis.  This has bee n recalc ulate d b y  kee pi n g t he al p ha le vel of 
0. 0 0 7 2 at i nteri m a nal ys is u nc ha n ge d.
P F S , f oll o we d b y B O R, will be teste d if a n d o nl y  if b ot h n ull h yp ot heses f or O S i n all ra n d o mize d 
s u bjects a n d P D -L 1 + s u bjects are rejecte d. I n t hat case, P F S will be teste d wit h f ull 2. 5 % ( 1-si de d) 
t ype I err or at t he pri mar y a nal ys is. B O R will be teste d wit h f ull 2. 5 % ( 1 -si de d) t y pe I err or at t he 
pri mar y  anal ys is after t he n ull h y p ot hesis of P F S is rejecte d. All a nal ys es i ncl u di n g O S i n P D -L 1 + 
s u bjects, P F S a n d B O R will be e x pl orat or y if t he st u d y is st o p pe d at i nteri m base d o n rejecti o n of 
n ull h y p ot hesis of O S i n all ra n d o mize d s u bjects.
N o f or mal a dj ust me nt f or m ulti plicit y  will be u n derta ke n f or n o n- ke y sec o n dar y en d p oi nts, 
se nsiti vit y a nalys es, or e x pl orat or y a nalys es.
Statistical a nal y ses will be perf or me d usi n g S A S ® versi o n 9.4 or hi g her.
8. 5. 2
A n al ysis of Pri m ar y E n d p oi nt
Pri m ar y A n al ysis
T he pri mar y  en d p oi nt f or mai nte na nce t hera py is O S . T he t w o pri mar y  anal y sis sets will be t he 
I T T A nal ys is Set a n d t he P D -L 1 + A nal y sis Set.
T he f oll o wi n g a nal ys is will be c o n d ucte d i n t he 
sa me ma n ner f or b ot h I TT a n d P D -L 1 + A nal y sis sets.
T he differe nce bet wee n t he t w o treat me nt 
ar ms will be c o m pare d usi n g a stratifie d, 1- si de d, l o g-ra n k test. T he stratificati o n fact or will be 
re gi o n ( Asia vers us n o n- Asia).
C o ntr ol of t ype I err or a n d statistical si g nifica nce is disc usse d i n 
S ecti o n 8. 5. 1. T he f oll o wi n g n ull h y p ot hes is will be teste d:
H 0: A (t)/ B (t) ≥ 1, vers us H 1: A (t)/ B (t) < 1
w here (t) re prese nts t he hazar d rate (c orres p o n di n g t o eac h e n d p oi nt) at ti me t f or treat me nt ar ms 
A ( a vel u ma b ) a n d B (c o nti n uati o n of t he sa me c he m ot hera p y re gi me n / B S C).
A stratifie d C o x pr o p orti o nal hazar ds m o del will be use d t o assess treat me nt effect bet wee n t he 
t w o treat me nt ar ms a n d t o e x pl ore t he r o b ust ness of t he pri mar y  en d p oi nt c o nfir mat or y anal ys is.  
T he nat ural para meter of t his m o del is t he l o g hazar d rati o.  Eac h strat u m will defi ne a se parate 
baseli ne hazar d f u ncti o n.  Ties will be ha n dle d b y re placi n g t he pr o p orti o nal hazar ds m o del b y t he 
discrete l o gistic m o del.   T he hazar d rati o of a vel u ma b vers us mai nte na nce c he m ot hera p y/ B S C
( with mai nte na nce c he m ot hera p y / B S C as refere nce) t o get her wit h t he c orres p o n di n g Wal d 2- si de d 
9 5 % CI s will be prese nte d. 
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 1 9 / 1 5 0
Ka pla n -Meier (ie, pr o d uct -li mit) esti mates of me dia n O S
will be prese nte d b y  treat me nt ar m 
t o get her wit h 2-si de d 9 5 % CIs calc ulate d acc or di n g t o  Br o o k me y er a n d Cr o wle y ( 1 9 8 2). Fi nall y,  
t he n u m ber of s u bjects at ris k vs. faile d al o n g wit h Ka pla n-Meier esti mates of s ur vi val pr o ba bilit y 
( ofte n referre d t o as “s ur vi val rate”) at 3, 6, 9 a n d 1 2 m o nt hs will be esti mate d wit h c orres p o n di n g 
2- si de d 9 5 % CI s deri ve d usi n g t he l o g-l o g tra nsf or mati o n acc or di n g t o Kal bfleisc h a n d Pre ntice 
( 1 9 8 0).
T he n u m ber a n d perce nta ge of s u bjects wit h o bser ve d O S e ve nts will be prese nte d b y  treat me nt 
ar m (a vel u ma b or mai nte na nce c he m ot hera p y/ B S C). I n a d diti o n, fre q ue nc y c o u nts f or ce ns ori n g 
reas o n will be prese nte d b y treat me nt gr o u p.
Se nsiti vit y A n al yses
T he f oll o wi n g se nsiti vit y anal ys es f or O S will be perf or me d t o e x pl ore t he r o b ust ness of t he 
pri mar y  c o nfir mat or y a nal yses. T hese se nsiti vit y  anal ys es will be perf or me d i n t he sa me ma n ner 
f or b ot h I TT a n d P D -L 1 + a nal ys is sets. A d diti o nal se nsiti vit y anal y ses ma y  be s pecifie d i n t he 
trial S A P.

T he pri ma r y e n d p oi nt a nal ysis will be re peate d base d o n t he P P A nalys is Set if t his a nalys is set 
i ncl u des less t ha n 9 0 % of s u bjects i n t he I T T A nal ysis Set.

A n u nstrati fie d a nalys is will be perf or me d c o m pari n g O S bet wee n t he treat me nt ar ms.

If t he act ual n u m ber of e ve nts is 1 0 % m ore t ha n t he pla n ne d n u m ber at t he pri mar y  anal ys is, 
t he pri mar y a nalys is of O S will be re peate d b y usi n g t he date at w hic h e xactl y  3 5 6 e ve nts i n all 
ra n d o mize d s u bjects were o bser ve d, or after a mi ni m u m f oll o w-u p of at least 1 8 m o nt hs after
ra n d o mizati o n, w hic he ver occ urs last.
T he f oll o wi n g a nal ys es will als o be perf or me d:

T he vali dit y  of t he pr o p orti o nal hazar ds ass u m pti o n will be assesse d vis uall y  by pl otti n g 
l o g(-l o g(s ur vi val)) vers us l o g(ti me) b y treat me nt ar m.

A Ka pla n -Meier pl ot f or O S f oll o w-u p d urati o n will als o be ge nerate d t o assess t he f oll o w-u p 
ti me i n t he treat me nt ar ms b y re versi n g t he O S ce ns ori n g a n d e ve nt i n dicat ors.
8. 5. 3
A n al ysis of Sec o n d ar y E n d p oi nts
Base d o n t he hierarc hical testi n g strate g y  descri be d i n Secti o n 8. 5. 1,  P F S a n d B O R will be teste d 
at t he pri mar y  an al y sis, if, a n d o nl y  if, b ot h of h y p ot hes es testi n g O S (i n all ra n d o mize d s u bjects 
a n d P D-L 1 + s u bjects ) reach statistical si g nifica nce.
8. 5. 3. 1
Ke y Sec o n d ar y E n d p oi nt – Pr o gressi o n -Free S ur vi v al
T he statistical a nal ysis of P F S per In vesti gat or assess me nt will be t he sa me as descri be d f or t he 
pri mar y  a nalys is of O S. 
I n a d diti o n, t he f oll o wi n g se nsiti vit y a nalys es of P F S will be perf or me d:
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 0 / 1 5 0

E ve nts ( P Ds/ deat hs) after t he start of ne w a ntica ncer treat me nt will be c o nsi dere d as e ve nts

Cli nical pr o gressi o n will be c o nsi dere d as a n e ve nt

C o u nti n g all P D a n d deat hs as e ve nts re gar dless of missi n g assess me nts or ti mi n g of t he 
e ve nt.
8. 5. 3. 2
Ke y Sec o n d ar y E n d p oi nt – Best O ver all Res p o nse
F or t he a nal ys is of B O R i n t he Mai nte na nce P hase (see Secti o n 8. 5. 3 ) acc or di n g t o R E CI S T v 1. 1 
a n d per I n vesti gat or assess me nt, t he O R R ( defi ne d as ha vi n g a c o nfir me d B O R of C R or P R ) will 
be calc ulate d al o n g wit h
c orres p o n di n g 2- si de d e xact Cl o p per -Pears o n 9 5 % CI s f or t he t w o
treat me nt ar ms. T he C oc hra n -Ma ntel -Hae nszel test will be stratifie d b y re gi o n ( Asia vers us 
n o n- Asia) t o c o m pare t he O R R bet wee n t he t w o treat me nt ar ms. I n case t he ass u m pti o ns of t he 
C oc hra n -Ma ntel -Hae nszel test are vi olate d d ue t o a s mall n u m ber of s u bjects i n s o me strata, a 
Fis her’s e xact test will be use d.  T his a nal ys is will be base d o n t he I T T A nal ysis Set.
8. 5. 3. 3
Ot her Sec o n d ar y E n d p oi nts
8. 5. 3. 3. 1
E ur o pe a n Q u alit y of Li fe - 5 Di me nsi o ns - 5 Le vels 
O bser ve d a n d c ha n ge fr o m baseli ne val ues f or t he E Q -5 D- 5 L  in de x sc ore will be s u m marize d 
descri pti vel y at pla n ne d visits d uri n g t he Mai nte na nce 
P hase, t he Disc o nti n uati o n Visit, a n d 
E n d - of-Treat me nt Visit b y  treat me nt ar m. T his a nal ys is will be base d o n t he H R Q o L A nal ys is 
Set. T he E Q - 5 D-5 L  Vis ual A nal o g Scale sc ores will be prese nte d by data listi n g o nl y .
8. 5. 3. 3. 2
E ur o pe a n 
Or g a niz ati o n 
f or Re se arc h a n d Tre at me nt 
of 
C a ncer Q L Q -C 3 0
O bser ve d a n d c ha n ge fr o m baseli ne val ues f or t he Gl o bal healt h stat us / Q o L scale a n d eac h of t he 
fi ve Q L Q -C 3 0 f u ncti o nal scales (ie, P h y sical, R ole, E m oti o nal, C o g niti ve, a n d S ocial) will be 
s u m marize d descri pti vel y at pla n ne d visits d uri n g t he Mai nte na nce P hase, t he Disc o nti n uati o n 
Visit, a n d E n d - of-Treat me nt Visit b y  treat me nt ar m. I n a d diti o n, t he best (lar gest p ositi ve c ha n ge), 
w orst (lar gest ne gati ve c ha n ge), a n d last-o bser ve d o n -treat me nt c ha n ge fr o m baseli ne val ues will 
be s u m marize d. 
Eac h meas ure will be c o m pare d bet wee n t he t w o treat me nt ar ms usi n g a 
mi xe d -effect s m o del re peate d meas ures ( M M R M) a nal ys is t o e val uate l o n git u di nal c ha n ge fr o m 
baseli ne usi n g re gi o n a n d baseli ne val ue as c o variates. T his a nal y sis will be base d o n t he H R Q o L
A nal y sis Set.
8. 5. 3. 3. 3
E ur o pe a n 
Or g a niz ati o n 
f or Re se arc h a n d Tre at me nt 
of 
C a ncer G astric C a ncer M o d ule Q L Q -S T O 2 2
O bser ve d a n d c ha n ge fr o m baseli ne val ues f or eac h of t he fi ve Q L Q -S T O 2 2 gastric ca ncer m o d ule 
s ym pt o m scales (ie, d ys p ha gi a, pai n, refl u x , eati n g, a n d an xiet y ) will be s u m marize d descri pti vel y 
at pla n ne d visits d uri n g t he Mai nte na nce P hase, t he Disc o nti n uati o n Visit, a n d E n d - of-Treat me nt 
Visit b y  treat me nt ar m. I n a d diti o n, t he best (lar gest ne gati ve c ha n ge), w orst (lar gest p ositi ve 
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 1 / 1 5 0
c ha n ge), a n d last- o bser ve d o n-treat me nt c ha n ge fr o m baseli ne val ues will be s u m marize d. Eac h 
meas ure will be c o m pare d bet wee n t he t w o treat me nt ar ms usi n g a M M R M a nal ysis t o e val uate 
l o n git u di nal c ha n ge fr o m baseli ne usi n g re gi o n a n d baseli ne val ue as c o variates. T his a nal ysis 
will be base d o n t he H R Q o L A nal ys is Set.
D oc u me nt N o.
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 2 / 1 5 0
8. 5. 5
A n al ysis of S afet y E n d p oi nts
All Safet y  anal ys es will be perf or me d o n t he Safet y -Mai nte na nce A nal ys is Set u nless ot her wise 
n ote d. Safet y e n d p oi nts will be ta b ulate d usi n g descri pti ve statistics o nl y.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 3 / 1 5 0
Safet y  assess me nts will be base d o n re vie w of A Es , c o nc o mita nt me dicati o ns, l ocal la b orat or y 
meas ure me nts (ser u m c he mistr y, he mat ol o g y, a n d uri nal ysis), E C O G P S , p h ysical e xa mi nati o ns, 
b o d y  wei g ht, vital si g ns, a n d 1 2-lea d E C Gs.
A d verse E ve nts
All A Es will be c o de d acc or di n g t o t he Me dical Dicti o nar y  for Re g ulat or y  Acti vities (Me d D R A )
dicti o nar y ( Versi o n 2 0. 1) .  Se verit y  of A Es will be gra de d usi n g t he N CI -C T C A E v 4. 0 3 t o xicit y 
gra di n g s cale. 
T reat me nt- e mer ge nt A Es ( T E A Es) are defi ne d as e ve nts wit h o nset dates occ urri n g o n -treat me nt 
or e ve nts w hic h w orse n o n -treat me nt (see Secti o n 7. 4. 1. 2 ).  T E A Es are defi ne d se paratel y f or t he 
I n d ucti o n a n d Mai nte na nce P hases. U nless ot her wise s pecifie d, s u m maries will be perf or me d o n 
Mai nte na nce
P hase T E A Es.
T he i nci de nce of T E A Es, re gar dless of relate d ness t o treat me nt, will be s u m marize d b y  Sys te m 
Or ga n Class a n d Preferre d Ter m f or eac h treat me nt ar m. Si milar s u m maries will als o be pr o vi de d 
f or treat me nt- e mer ge nt seri o us a d verse e ve nts ( T E S A Es), T E A Es lea din g t o per ma ne nt 
disc o nti n uati o n of treat me nt, T E A Es b y  ma xi m u m se verit y, T E A Es b y  hi g hest relati o ns hi p t o 
treat me nt, T E A Es wit h fatal o utc o me, a n d T E A Es of s pecial i nterest ( A E SIs) s uc h as ir A Es.
T he i nci de nce of T E A Es a n d T E S A Es d uri n g t he I n d ucti o n P hase will be s u m marize d b y  s yste m 
or ga n class/ preferre d ter m b y  t otal n u m ber of s u bjects.
C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures
C o nc o mita nt me dicati o ns (ie, me dicati o ns ot her t ha n trial treat me nt ta ke n at a n y ti me o n-
treat me nt) will be s u m marize d f or t he Mai n te na nce P hase usi n g fre q ue ncies a n d perce nta ges 
wit hi n a gi ve n dr u g class a n d preferre d na me b y  treat me nt ar m a n d o verall. 
C o nc o mita nt 
pr oce d ures (ie , pr oce d ures u n derta ke n at a n y  ti me o n-treat me nt) will be liste d o nl y.
L a b or at or y V al ues
O bser ve d a n d c ha n ge fr o m baseli ne val ues d uri n g t he Mai nte na nce P hase will be s u m marize d b y 
visit, test, a n d treat me nt ar m f or c he mistr y  an d he mat ol o g y  la b orat or y res ults.  La b orat or y res ults 
will be classifie d b y  gra de acc or di n g t o N CI -C T C A E .  T he w orst o n- treat me nt gra de s d uri n g t he 
Mai nte na nce P hase f or c he mistr y an d he mat ol o g y  la b orat or y res ults b y treat me nt ar m will be 
s u m marize d. S hifts i n t o xicit y gra di n g fr o m baseli ne t o hi g hest gra de d uri n g t he Mai nte na nce 
P hase b y  treat me nt ar m will be dis pla y e d. Res ults d uri n g t he Mai nte na nce P hase f or la b orat or y 
tests t hat are n ot part of N CI-C T C A E will be prese nte d cate g oricall y (e g, bel o w, wit hi n, or a b o ve 
n or mal li mits) b y  treat me nt ar m. O nl y  su bjects wit h p ost -baseli ne la b orat or y val ues will be 
i ncl u de d i n t hese a nal yses. Uri nal y sis res ults will be liste d o nl y . F urt her details of a nal yses f or 
t he la b orat or y para meters will be pr o vi de d i n t he trial S A P.
E C O G Perf or m a nce St at us
D oc u me nt N o.
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 4 / 1 5 0
S hifts fr o m Re- baseli ne (e n d of I n d ucti o n P hase) i n E C O G P S sc ore will be prese nte d at pla n ne d 
visits d uri n g t he Mai nte na nce P hase, t he Disc o nti n uati o n Visit, a n d E n d - of-Treat me nt Visit b y  
n u m ber a n d perce nta ge f or eac h treat me nt ar m. S hifts fr o m Re- baseli ne t o hi g hest o n- treat me nt 
E C O G P S sc ore will be s u m marize d i n a si milar fas hi o n.
P h ysic al E x a mi n ati o ns
Cli nicall y  si gnifica nt, a b n or mal fi n di n gs fr o m p h y sical e xa mi nati o ns bef ore I CF si g nat ure are t o 
be re p orte d as pre -e xisti n g me dical c o n diti o ns a n d will be i ncl u de d i n s u m maries of me dical 
hist or y . O n t he ot her ha n d, cli nicall y si gnifica nt, a b n or mal fi n di n gs fr o m p h y sical e xa mi nati o ns 
after I C F si g nat ure are t o be re p orte d as A Es a n d will b e i ncl u de d i n s u m maries of A Es.
Vit al Si g ns
Ma xi m u m o n- treat me nt i ncrease a n d ma xi m u m o n- treat me nt decrease fr o m baseli ne val ues d uri n g 
t he Mai nte na nce P hase will be s u m marize d b y  para meter (e g, b o d y te m perat ure, res pirat or y rate, 
heart rate, a n d bl o o d press ure) usi n g descri pti ve statistics b y  treatme nt ar m. A si milar s u m mar y 
will be pr o vi de d f or t he I n d ucti o n P hase b y t otal n u m ber of s u bjects.
1 2- Le a d E C Gs
O bser ve d a n d c ha n ge fr o m baseli ne val ues d uri n g t he Mai nte na nce P hase base d o n 1 2 -lea d E C Gs 
will be s u m marize d at t he Disc o nti n uati o n Visit a n d E n d - of-Treat me nt Visit b y  para meter (e g, 
Heart Rate, P R I nter val, Q R S I nter val, R R I nter val, Q T I nter val, Q T c orrecte d b y  Bazzett’s 
f or m ula [Q Tc B ] I nter val, or Q T c orrecte d b y  Fri dericia’s f or m ula [Q Tc F ] I nter val) a n d treat me nt 
ar m. I n ad diti o n, s hifts fr o m baseli ne i n E C G res ults (e g , n or mal, a b n or mal) will be prese nte d at 
t he Disc o nti n uati o n Visit a n d E n d-of- Treat me nt Visit b y  para meter a n d treat me nt ar m.
F urt her details of safet y a nal yses will be pr o vi de d i n t he trial S A P.
8. 5. 6
Re p orti n g of Ot her Cli nic al D a t a of I nterest
S u bject C h ar acteristics
Pre -i n d ucti o n s u bject c haracteristics will be o btai ne d d uri n g t he Scree ni n g / Baseli ne pr oce d ures 
a n d will be s u m marize d b y  total n u m ber of s u bjects f or t he I T T A nal y sis Set. 
S u bject 
c haracteristics m a y  incl u de, b ut are n ot li mite d t o, a ge, se x, race/et h nicity,  hei g ht, wei g ht, b o d y 
mass i n de x, re gi o n c orres p o n di n g t o t he site at w hic h t he s u bject is e nr olle d, a n d E C O G P S.  A 
si milar s u m mar y of pre -mai nte na nce Re- baseli ne c haracteristics will be pr o vi de d b y  treat me nt ar m
a n d o verall f or t he I T T A nal y sis Set.
Dise ase C h ar acteristics
I nf or mati o n o n baseli ne disease c haracteristics c ollecte d o n t he e C R F will be s u m marize d b y 
treat me nt ar m a n d o verall f or t he I T T A nal ys is Set. Disease c haracteristics ma y  incl u de, b ut are 
n ot li mite d t o, site of pri mar y  tu m or (ie , st o mac h, G EJ), o verall t u m or res p o nse stat us (ie, C R, P R, 
or S D) f oll o wi n g t he I n d ucti o n P hase, a n d P D -L 1  assa y stat us (ie, p ositi ve, ne gati ve).
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 5 / 1 5 0
E nr ol lme nt a n d Dis p ositi o n
T he n u m ber a n d perce nta ge of s u bjects scree ne d ( n u m ber o nl y), scree n-faile d ( n u m ber o nl y) , 
disc o nti n ue d d uri n g t he I n d ucti o n P hase ( n u m ber o nl y ), ra n d o mize d, ra n d o mize d b ut n ot treate d 
d uri n g t he Mai nte na nce 
P hase, treate d d uri n g t he Mai nte na nce 
P hase, a n d pre mat urel y 
disc o nti n ue d d uri n g t he Mai nte n a nce P hase will be s u m marize d b y  treat me nt ar m a n d o verall.
Pri mar y  reas o ns f or scree n-fail ure, ra n d o mizati o n fail ure, a n d pre mat ure wit h dra wal d uri n g t he 
Mai nte na nce P hase will be s u m marize d. T he n u m ber a n d perce nta ge of s u bjects i n t he A nal ys is 
Set wit h maj or pr ot oc ol de viati o ns lea di n g t o e xcl usi o n fr o m t he P P A nal y sis Set will be prese nte d 
b y  treat me nt ar m a n d reas o n f or e xcl usi o n. All maj or pr ot oc ol de viati o ns will be liste d.
Me dic al Hist or y
Pre -e xisti n g me dical c o n diti o ns re p orte d at t he ti me of t h e Scree ni n g / Baseli ne pr oce d ures will be 
s u m marize d usi n g fre q ue nc y ta bles b y  treat me nt ar m a n d o verall f or t he Safet y- Mai nte na nce 
A nal y sis Set.   A si milar s u m mar y will be pr o vi de d b y  total s u bjects f or t he Safet y- I n d ucti o n 
A nal y sis Set.
Tre at me nt E x p os ure a n d C o m pli a nce
T he e xte nt of e x p os ure t o treat me nt d uri n g t he I n d ucti o n P hase will be s u m marize d f or t otal 
n u m ber of s u bjects i n t he Safet y -I n d ucti o n A nal y sis Set.
T he e xte nt of e x p os ure t o ra n d o mize d treat me nt (ie, a vel u ma b or mai nte na nce c he m ot hera py) wi ll 
be c haracterize d b y  durati o n ( wee ks), n u m ber of a d mi nistrati o ns, c u m ulati ve d ose (e g, m g / k g or 
m g/ m 2), d ose i nte nsity ( m g/ k g/ wee k or m g / m2/ wee k), relati ve d ose i nte nsit y (act ual d ose gi ve n / 
pla n ne d d ose), n u m ber of d ose dela y s, a n d n u m ber of i nf usi o n rate re d ucti o ns (a vel u ma b ar m 
o nl y ), f or t he Safet y- Mai nte na nce A nal ys is Set. T he n u m ber a n d perce nta ge of n o n- c o m plia nt 
s u bjects (see Secti o n 6. 9 ) wit h re gar d t o ra n d o mize d treat me nt will be prese nte d b y treat me nt ar m 
base d o n t he Safet y -Mai nte na nce A nal ys is Set.
Pri or A nti -C a ncer T her a pies a n d Pr oce d ures
Pri or a nti -ca ncer t hera pies (ie, a nti -ca ncer me dicati o ns ot her t ha n trial tr eat me nt ta ke n at a n y ti me 
pri or t o I CF si g nat ure) will be s u m marize d usi n g fre q ue ncies a n d perce nta ges b y  dr u g class a n d 
preferre d na me wit hi n treat me nt ar m a n d o verall f or t he Safet y -I n d ucti o n A nal y sis S et a n d 
Safet y -Mai nte na nce A nal y sis Set. A si milar su m mar y  will be pr o vi de d b y  dr u g class, preferre d 
na me, a n d t otal s u bjects f or t he Safet y- I n d ucti o n A nal y sis Set.  Pri or a nti-ca ncer pr oce d ures (ie, 
pr oce d ures u n derta ke n at a n y  ti me pri or t o IC F si g nat ure) will be liste d o nl y .
8. 6
I nteri m a n d A d diti o n al Pl a n ned A n al yses
N o i nteri m a nal ysis is pla n ne d f or O S i n P D -L 1 + s u bjects. T here is o ne i nteri m a nal ys is pla n ne d 
f or o ver w hel mi n g efficac y of O S i n all ra n d o mize d s u bjects w he n a p pr o xi matel y 7 5 % of O S
e ve nts, ie, 2 6 7 O S e ve nts ha ve bee n o bser ve d. 
A La n -De Mets al p ha s pe n di n g f u ncti o n f or 
O’ Brie n -Fle mi n g b o u n daries will be use d t o c o ntr ol t he o verall t ype I err or rate of 2 % ( 1-si de d) 
f or O S. T he b o u n dar ies f or declari n g s u peri orit y for t he i nteri m a nal y sis a n d t he fi nal a nal ysis of 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 6 / 1 5 0
O S i n all ra n d o mize d s u bjects will be u p date d base d o n t he act ual n u m ber of e ve nts o bser ve d at 
t he ti me of t he data c ut f or eac h a nal ys is.  If t he pla n ne d n u m ber of e ve nts are o bser ve d at eac h 
a nal ys is, 1- si de d b o u n daries of 0. 0 0 7 2 a n d 0. 0 1 7 8, res pecti vely will be use d f or e val uati n g 
statistical si g nifica nce. Si nce f or mal efficac y bo u n daries will be use d at t he i nteri m a nal ysis f or 
t he statistical testi n g of O S i n all ra n d o mize d s u bjects, a statisticall y si g nifica nt fi n di n g at t he 
i nteri m will be i nte n de d t o clai m t he s u peri ority. If O S i n all ra n d o mize d s u bjects is statisticall y 
si g nifica nt at t he i nteri m a nal ys is, o nl y  descri pti ve a nal ys is of O S i n P D -L 1 + s u bjects will be 
perf or me d at t his i nteri m a nal ys is ti me p oi nt. If t he st u d y pr ocee ds t o t he fi nal a nal ys is a n d n ull 
h y p ot hesi s of O S i n P D -L 1 + is rejecte d at al p ha le vel 0. 0 0 5 t he n t he b o u n dar y  for t he fi nal 
h y p ot hesis of O S i n ra n d o mize d s u bjects will be base d o n a l ocal si g nifica nce le vel of 0. 0 2 5. 
Ass u mi n g t he pla n ne d n u m ber of e ve nts are o bser ve d at eac h a nal ys is, t he 1- si de d b o u n daries 
w o ul d t he n be 0. 0 2 3 3 f or O S i n all ra n d o mize d s u bjects at pri mar y  anal y sis. T his has bee n 
recalc ulate d by kee pi n g t he al p ha le vel of 0. 0 0 7 2 at i nteri m a nal ys is u nc ha n ge d.
T he Ta ble 1 3 s u m marizes t he o perati n g c haracteristics a n d efficac y bo u n daries, i n t he case t hat 
pla n ne d n u m ber of e ve nts are o bser ve d f or O S i n ra n d o mize d s u bjects i n b ot h a nal yses.  T he
O’ Brie n -Fle mi n g efficac y bo u n daries b ase d o n a La n -De Mets s pe n di n g f u ncti o n will be u p date d 
pri or t o t he ti me of a nal ysis of O S base d o n t he act ual n u m ber of e ve nts a n d t he i nf or mati o n 
fracti o n f or t ype I err or c o ntr ol.  I nf or mati o n fracti o n at t he i nteri m a nal ysis will be calc ulate d 
ass u mi n g t he pla n ne d 3 5 6 e ve nts will be o bser ve d at t he ti me of t he pri mar y a nal ys is. At t he 
pri mar y  a nalys is, t he b o u n daries will be u p date d base d o n t he tr ue n u m ber of e ve nts o bser ve d a n d 
i nf or mati o n fracti o n use d at eac h a nalys is.
T a ble 1 3
Pl a n ne d L a n -De Mets ( O’ Brie n-Fl e mi n g) Effic ac y B o u n d aries of O S
i n 
All R a n d o mize d S u bjects
L o o k
I nf o 
Fr acti o n 
A p pr o x. 
C u m. E ve nts 
of O S
C u m ul ati ve T y pe 
I Err or 
( 1-si de d)
Effic ac y B o u n d aries
Z- sc ale
P- sc ale
( 1-si de d)
I nteri m
~ 7 5 %
2 6 7
0. 0 0 7 2
2. 4 5
0. 0 0 7 2
Fi nal
1 0 0 % 
3 5 6
0. 0 2 0 0
2. 1 0
0. 0 1 7 8
O S = O verall S ur vi val.
La n -De Mets al p ha s pe n di n g f u ncti o n f or O’ Brie n -Fle mi n g b o u n daries
T he o verall t y pe I err or rate = 0. 0 2 0 ( 1 -si de d) f or pri mar y e n d p oi nt of O S i n all ra n d o mize d s u bjects.
T he e xact efficac y b o u n daries ma y be u p date d pri or t o t he ti me of a nal ysis base d o n t he act ual n u m ber of 
e ve nts a n d t he i nf or mati o n fracti o n.
F urt her details re gar di n g t he i nteri m a nal ys is will be pr o vi de d i n t he trial S A P.
A n I D M C will be f or me d a n d will be res p o nsi ble f or peri o dic e val uati o ns of t he trial as well as t he 
e val uati o n of t he i nteri m a nal ysis. T he I D M C (see Secti o n 2. 3. 1 ) will c o n ve ne t o perf or m t he 
e val uati o n at t he i nteri m a nal ys is i n or der t o safe g uar d t he S p o ns or’s pers o n nel fr o m u n bli n de d 
trial res ults. T he pri mar y  en d p oi nt of O S , t he ke y  sec o n dar y en d p oi nt s of P F S, B O R , a n d ot her 
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 7 / 1 5 0
sec o n dar y efficac y e n d p oi nt (re p orte d o utc o mes / Q o L
assesse d b y  th e E Q - 5 D-5 L , E O R T C 
Q L Q -C 3 0, a n d E O R T C m o d ule Q L Q- S T O 2 2 q uesti o n naires) a nal ys es will be c o n d ucte d i n t his 
i nteri m a nal ys is. See Secti o n s 8. 5. 1 a n d 8. 5. 3 f or details re gar di n g t he hierarc hical testi n g strate g y 
t o be use d. If at t he ti me of t his i nteri m a nal ysis, t he a nal ys is is perf or me d wit h e xactl y 2 6 7 deat h s 
o bser ve d ( 7 5 % pla n ne d i nf or mati o n fracti o n), t he O S i n all ra n d o mize d s u bjects of a vel u ma b-
assi g ne d s u bjects is s h o w n t o be s u peri or t o t hat of s u bjects ra n d o ml y assi g ned t o t he mai nte na nce 
c he m ot hera p y / B S C ar m wit h a p- val ue of < 0. 0 0 7 2 t he I D M C ma y  declare s u peri or efficac y in t he 
a vel u ma b treat me nt ar m c o m pare d wit h t he mai nte na nce c he m ot hera p y / B S C ar m a n d rec o m me n d 
t hat t he trial be st o p pe d earl y. 
T he I D M C will als o be prese nte d wit h s u bject dis p ositi o n, 
de m o gra p hic i nf or mati o n, baseli ne disease c haracteristics, a n d safet y inf or mati o n. 
A n 
i n de pe n de nt statistical pr o vi der will perf or m t he i nteri m a nal yses t o s u p p ort t he I DM C. 
Details 
will be d oc u me n te d i n a se parate S A P or I D M C c harter.  Res ults fr o m t he i nteri m a nalys es will be 
tra ns mitte d fr o m t his gr o u p t o t he I DM C 
o nl y . Trial staff i n v ol ve d wit h t he da y  to d a y  
ma na ge me nt of t he trial as well as a n y Sp o ns or staff will n ot ha ve access t o t his i nteri m 
i nf or mati o n. Details of t he I D M C missi o n, c o m p ositi o n, a n d o perati o ns will be pr o vi de d i n t he 
I D M C c harter.
9
Et hic al a n d Re g ul at or y As pects
9. 1
Res p o nsi bilities of t he I n vesti g at or
T he I n vesti gat or is res p o nsi ble f or t he c o n d uct of t he trial at his / her site.  He / s he will e ns ure t hat 
t he trial is perf or me d i n acc or da nce wit h t he cli nical trial pr ot oc ol a n d wit h t he et hical pri nci ples 
t hat ha ve t heir ori gi n i n t he Declarati o n of Helsi n ki, as well as wit h t he I C H N ote f or G ui da nce o n 
G C P (IC H T o pic E 6, 1 9 9 6) a n d a p plica ble re g ulat or y re q uire me nts.  I n partic ular, t he I n vesti gat or 
m ust e ns ure t hat o nl y  s u bjects w h o ha ve gi ve n t heir i nf or me d c o nse nt are i ncl u de d i n t he trial.
Acc or di n g t o U nite d States C o de of Fe deral Re g ulati o ns Part 5 4. 2 (e), f or trials c o n d ucte d i n a n y 
c o u ntr y that c o ul d res ult i n a pr o d uct s u b missi o n t o t he U nite d States F D A f or mar keti n g a p pr o val 
a n d c o ul d c o ntri b ute si g nifica ntl y to t he de m o nstrati o n of efficac y an d safet y of a n I M P ( w hic h 
are c o nsi dere d “c o vere d cli nical trials” b y  t he F D A), t he I n vesti gat or a n d all s u bi n vesti gat ors are 
o bli ge d t o discl ose a n y f i na ncial i nterest w hic h t he y, t heir s p o uses or t heir de pe n de nt c hil dre n m a y  
ha ve i n t he S p o ns or or t he S p o ns or’s pr o d uct u n der st u d y. T his i nf or mati o n is re q uire d d uri n g t he 
trial a n d f or 1 2 m o nt hs f oll o wi n g c o m pleti o n of t he trial.
9. 2
S u bject I nf or m ati o n a n d I nf or me d C o nse nt
A n u nc o n diti o nal prere q uisite f or a s u bject’s partici pati o n i n t he trial is his / her writte n i nf or me d 
c o nse nt.  The s u bject’s writte n i nf or me d c o nse nt t o partici pate i n t he trial m ust be gi ve n bef ore 
a n y trial-relate d acti vities are carrie d o ut.   
 
 
A de q uate i nf or mati o n m ust t heref ore be gi ve n t o t he s u bject b y  the I n vesti gat or bef ore i nf or me d 
c o nse nt is o btai ne d (a pers o n desi g nate d b y  the I n vesti gat or m a y  gi ve the i nf or mati o n, if per mitte d 
b y  local re g ulati o ns).  A su bject i nf or mati o n s heet i n t he l ocal la n g ua ge a n d pre pare d i n acc or da nce 
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 8 / 1 5 0
wit h t he N ote f or G ui da nce o n G C P (I C H T o pic E 6, 1 9 9 6) will be pr o vi de d b y t he S p o ns or f or t he 
p ur p ose of o btai ni n g i nf or me d co nse nt.  In a d diti o n t o pr o vi di n g t his writte n i nf or mati o n t o a 
p ote ntial s u bject, t he I nvesti gat or or his / her desi g nate will i nf or m t he s u bject ver ball y  of all 
perti ne nt as pects of t he trial.  The la n g ua ge use d i n d oi n g s o m ust be c h ose n s o t hat t he i nfor mati o n 
ca n be f ull y a n d rea dil y  u n derst o o d b y l a y pers o ns.
De pe n di n g o n nati o nal re g ulati o ns, a pers o n ot her t ha n t he I n vesti gat or m a y  inf or m t he s u bject 
a n d si g n t he I CF, as a b o ve.
W here t he i nf or mati o n is pr o vi de d b y  the I n vesti gat or, t he I C F m ust be si g ne d a n d pers o nall y 
date d b y t h e s u bject a n d t he I n vesti gat or.
T he si g ne d a n d date d declarati o n of i nf or me d c o nse nt will re mai n at t he I n vesti gat or’s site, a n d 
m ust be safel y arc hi ve d b y  the I n vesti gat or s o t hat t he f or ms ca n be retrie ve d at a n y ti me f or
m o nit ori n g, a u diti n g, a n d i ns pecti o n p ur p oses.  A co p y  of t he si g ne d a n d date d i nf or mati o n a n d 
I CF s h o ul d be pr o vi de d t o t he s u bject pri or t o partici pati o n.  Whe ne ver i m p orta nt ne w i nf or mati o n 
bec o mes a vaila ble t hat ma y  be rele va nt t o t he s u bject’s c o nse nt, t he writte n s u bject i nf or mati o n 
s heet a n d a n y ot her writte n i nf or mati o n pr o vi de d t o s u bjects will be re vise d b y  the S p o ns or or 
desi g nee a n d be s u b mitte d a gai n t o t he I E C / I RB f or re vie w a n d fa v ora ble o pi ni o n.  T he a gree d, 
re vise d i nf or mati o n will be pro vi de d t o eac h s u bject i n t he trial f or si g ni n g a n d dati n g , w hic h will 
be d oc u me nte d .  S ufficie nt ti me will be pr o vi de d t o s u bjects t o rea d t he i nf or mati o n a n d t he 
o p p ort u nit y  to as k q uesti o ns a n d t o re q uest a d diti o nal i nf or mati o n a n d clarificati o n a b o ut the 
c ha n ges.  T he I n vesti gat or will e x plai n t he c ha n ges t o t he pre vi o us versi o n .
9. 3
S u bject I de ntific ati o n a n d Pri v ac y
A u ni q ue s u bject n u m ber will be assi g ne d t o eac h s u bject at i ncl usi o n b y  the I WR S s yste m, 
i m me diatel y after i nf or me d c o nse nt has bee n o btai ne d.  This n u m ber will ser ve as t he s u bject’s 
i de ntifier i n t he trial as well as i n t he cli nical trial data base.
T he s u bject’s data c ollecte d i n t he trial will be st ore d u n der t his n u m ber.  Onl y  the I n vesti gat or 
will be a ble t o li n k t he s u bject’s trial data t o t he s u bject via a n i de ntificati o n list ke pt at t he site.  
T he s u bject’s ori gi nal me dical data t hat are re vie we d at t he site d uri n g s o urce data verificati o n b y 
t he Cli nical Trial M o nit or, 
a u dits, a n d Healt h A ut h orit y  ins pecti o ns will be ke pt strictly 
c o nfi de ntial.
Data pr otecti o n a n d pri vac y  re g ulati o ns will be o bser ve d i n ca pt uri n g, f or war di n g, pr ocessi n g, a n d 
st ori n g s u bject data.  Su bjects will be i nf or me d acc or di n gl y a n d will be re q ueste d t o gi ve t heir 
c o nse nt o n data ha n dli n g pr oce d ures i n acc or da nce wit h nati o nal re g ulati o ns (see Secti o n 7. 6) .  
Details re gar di n g s u bjects’ ri g ht t o pri vac y  will be descri be d i n t he I C F.
9. 4
E mer ge nc y Me dic al S u p p ort a n d S u bject C ar d
S u bjects e nr olle d i n t his cli nical trial will be pr o vi de d wit h E mer ge nc y  Me dical S u p p ort car ds 
d uri n g t heir trial partici pati o n, w hic h will be f ur nis he d b y  the S p o ns or or desi g nee.  Th e 
E mer ge nc y  Me dical S u p p ort car d is base d o n t he nee d t o pr o vi de cli nical trial s u bjects wit h a wa y 
of i de ntif yi n g t he msel ves as partici pati n g i n a cli nical trial, a n d s u bse q ue ntl y to gi ve healt h care 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 2 9 / 1 5 0
pr o vi ders access t o t he i nf or mati o n a b o ut t his partici pati o n t hat m a y  be nee de d t o deter mi ne t he 
c o urse of t h e s u bject’s me dical treat me nt.
T his ser vice is desi g ne d t o pr o vi de i nf or mati o n t o healt h care pr o vi ders w h o are n ot part of t he 
cli nical trial.
Cli nical trial In vesti gat ors, w h o are alrea d y a ware of t he cli nical trial pr ot oc ol a n d treat me nt, ha ve 
ot her mea ns of accessi n g t he necessar y  me dical i nf or mati o n f or t he ma na ge me nt of e mer ge ncies 
occ urri n g i n t heir s u bjects.
T he first p oi nt of c o ntact f or all e mer ge ncies will be t he cli nical trial I n vesti gat or cari n g f or t he 
affecte d s u bject.  The I nvesti gat or a grees t o pr o vi de his or her e mer ge nc y co ntact i nf or mati o n o n 
t he car d f or t his p ur p ose.  If t he I n vesti gat or is a vaila ble w he n a n e ve nt occ urs, s he or he will 
a ns wer a n y q uesti o ns.  An y  su bse q ue nt acti o n will f oll o w t he sta n dar d pr ocesses esta blis he d f or 
t he In vesti gat ors.
I n cases w here t he I n vesti gat or is n ot a vaila ble, Merc k K Ga A / E M D Ser o n o R & D or desi g nee 
will pr o vi de t he a p pr o priate mea ns t o c o ntact a S p o ns or p h ys icia n. T his i ncl u des t he pr o visi o n of 
a 2 4- h o ur c o ntact n u m ber at a call ce nter, w here b y  t he healt h care pr o vi ders will be gi ve n access 
t o t he a p pr o priate S p o ns or p h ysicia n t o assist wit h t he me dical e mer ge nc y a n d t o pr o vi de s u p p ort 
f or t he s u bject c o ncer ne d.
9. 5
Cli nic al Tri al I ns ur a nce a n d C o m pe ns ati o n t o S u bjects
I ns ura nce c o vera ge wi ll be pr o v i de d f or eac h c o u ntr y partici pati n g t o t he trial.  I ns ura nce 
c o n diti o ns s hall meet g o o d l ocal sta n dar ds, as a p plica ble.
9. 6
I n de pe n de nt Et hics C o m mittee or I nstit uti o n al Re vie w B o ar d
Pri or t o c o m me nce me nt of t he trial at a gi ve n site, t his cli nical trial pr ot o c ol will be s u b mitte d 
t o get her wit h its ass ociate d d oc u me nts (s uc h as t he I CF) t o t he res p o nsi ble I EC or I RB f or its 
fa v ora ble o pi ni o n or a p pr o val, w hic h will be file d i n t he I n vesti gat or Site File. A c o p y will be 
file d i n t he S p o ns or Trial Master File at t he C R O.
T he I E C or I R B will be as ke d t o d oc u me nt t he date of t he meeti n g at w hic h t he fa v ora ble o pi ni o n 
or a p pr o val was gi ve n a n d t he me m bers a n d v oti n g me m bers prese nt. 
Writte n 
e vi de nce of 
fa v ora ble o pi ni o n or a p pr o val t hat clearly i de ntifies t he trial, t he cli nical trial pr ot oc ol versi o n a n d 
t he S u bject I nf or mati o n a n d I CF versi o n re vie we d s h o ul d be pr o vi de d. 
W here p ossi ble, c o pies of 
t he meeti n g mi n utes s h o ul d be o btaine d.
A me n d me nts t o t his cli nical trial pr ot oc ol will als o be s u b mitte d t o t he c o ncer ne d I E C or I R B, 
bef ore i m ple me ntati o n of s u bsta ntial c ha n ges (see Secti o n 1 0. 5 ). Rele va nt safety i nf or mati o n will 
be s u b mitte d t o t he I EC or I RB d uri n g t he c o urse of t he trial i n acc or da nce wit h nati o nal 
re g ulati o ns a n d re q uire me nts.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 0 / 1 5 0
9. 7
He alt h A ut h orities
T he cli nical trial pr ot oc ol a n d a n y a p plica ble d oc u me ntati o n (e g, I M P D ossier, 
S u bject 
I nf or mati o n, a n d t he I C F) will be s u b mitte d or n otifie d t o t he Healt h A ut h orities i n acc or da nce 
wit h all l ocal a n d nati o nal re g ulati o ns f or eac h site.
1 0
Tri al M a n a ge me nt
1 0. 1
C ase Re p ort F or m H a n dli n g
T he I n vesti gat or or desi g nee will be res p o nsi ble f or e nteri n g trial data i n t he e C R F pr o vi de d b y  
t he C R O a n d f oll o w t he data e ntr y gui deli nes.  It is t he I nvesti gat or’s res p o nsi bilit y  t o e ns ure t he 
acc urac y of t he data e ntere d i n t he e C R Fs a n d t o si g n t he case re p ort f or ms.  Please refer t o the 
Ma n ual of O perati o ns f or e C R F ha n dli n g g ui deli nes.
T he data will be e ntere d i nt o a vali date d data base.  The C R O will f oll o w t he sta n dar ds of t he 
S p o ns or i n t he data base desi g n a n d data str uct ure.  The C R O will be res p o nsi ble f or data re vie w 
a n d pr ocessi n g, i n acc or da nce wit h t he C R O’s data ma na ge me nt pr oce d ures.  Data base l oc k will 
occ ur o nce q ualit y  co ntr ol pr oce d ures a n d q ualit y ass ura nce pr oce d ures (if a p plica ble) ha ve bee n 
c o m plete d.  Co pies of t he e C R Fs will be pr o vi de d t o t he I n vesti gat ors at t he co m pleti o n of t he 
trial.
1 0. 2
S o urce D at a a n d S u bject Files
T he I n vesti gat or m ust kee p a file ( me dical file, ori gi nal me dical rec or ds) o n pa per or electr o nicall y 
f or e ver y s u bject i n t he trial.  It m ust be p ossi ble t o i de ntif y eac h s u bject b y usi n g t his s u bject file.  
T his file will c o ntai n t he de m o gra p hic a n d me dical i nf or mati o n f or t he s u bject liste d bel o w a n d 
s h o ul d be as c o m plete as p ossi ble. 

S u bject’s f ull na me, date of birt h, se x, hei g ht, wei g ht

Me dical hist or y  a n d c o nc o mita nt diseases

Pri or a n d c o nc o mita n t t hera pies (i ncl u di n g c ha n ges d uri n g t he trial)

Trial i de ntificati o n, ie, t he S p o ns or trial n u m ber f or t his cli nical trial, a n d s u bject n u m ber

Dates f or e ntr y  i nt o t he trial (i nf or me d c o nse nt) a n d visits t o t he site

A n y  me dical e xa mi nati o ns a n d cli nical fi n di n gs pre defi ne d i n t his cli nical trial pr ot oc ol

All A Es

Date t hat t he s u bject left t he trial i ncl u di n g a n y reas o n f or earl y wit h dra wal fr o m t he trial or 
I M P (if a p plica ble).

It m ust be p ossi ble t o i de ntif y eac h s u bject b y usi n g t his s u bject file.
A d diti o nall y , a n y ot her d oc u me nts c o ntai ni n g s o urce data m ust be file d.  This i ncl u des ori gi nal 
pri nt o uts of data rec or de d or ge nerate d b y  aut o mate d i nstr u me nts, p h ot o gra p hic ne gati ves, X- ra ys, 
C T or M RI  sca n i ma ges, E C G rec or di n gs, la b orat or y val ue listi n gs, etc.  Suc h d oc u me nts m ust 
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 1 / 1 5 0
i ncl u de at least t he s u bject n u m ber a n d t he date w he n t he pr oce d ure was perf or me d.  I nf or mati o n 
s h o ul d be pri nte d b y  the i nstr u me nt use d t o perf or m t he assess me nt or meas ure me nt, if p ossi ble.  
I nf or mati o n t hat ca n n ot be pri nte d by a n a ut o mate d i nstr u me nt will be e ntere d ma n uall y.  Me dical 
e val uati o n of s uc h rec or ds s h o ul d be d oc u me nte d as necessar y  a n d t he d oc u me ntati o n si g ne d a n d 
date d b y t he I n vesti gat or.
1 0. 3
I n vesti g at or Site File a n d Arc hi vi n g
T he I n vesti gat or will be pr o vi de d wit h a n I n vesti gat or Site File u p o n i nitiati o n of t he trial.  This 
file will c o ntai n all d oc u me nts necessar y  for t he c o n d uct of t he trial a n d will be u p date d a n d 
c o m plete d t hr o u g h o ut t he trial.  It m ust be a vaila ble f or re vie w by t he M o nit or, a n d m ust be rea d y 
for S p o ns or a u dit as well as f or i ns pecti o n b y  Healt h A ut h orities d uri n g a n d after t he trial, a n d 
m ust be safel y arc hi ve d f or at least 1 5 y ears ( or per l ocal re q uire me nts or as ot her wise n otifie d b y 
t he S p o ns or) after t he e n d of t he trial.  The d oc u me nts t o be arc hi ve d i ncl u de t he S u bject 
I de ntificati o n Li st a n d t he si g ne d s u bject I C Fs.  If arc hi vi n g of t he I n vesti gat or Site File is n o 
l o n ger p ossi ble at t he site, t he In vesti gat or m ust n otif y  t he S p o ns or.
All ori gi nal s u bject files ( me dical rec or ds) m ust be st ore d at t he site ( h os pital, researc h i nstit ute, 
or practice) f or t he l o n gest p ossi ble ti me per mitte d b y  the a p plica ble re g ulati o ns, a n d / or as per 
I C H G C P g ui deli nes, w hic he ver is l o n ger.  In a n y case, t he I n vesti gat or s h o ul d e ns ure t hat n o 
destr ucti o n of me dical rec or ds is perf or me d wit h o ut t he writte n a p pr o val of t he S p o ns or.
1 0. 4
M o nit ori n g, 
Q u alit y Ass ur a nce 
a n d I ns pecti o n b y He alt h 
A ut h orities
T his trial will be m o nit ore d i n acc or da nce wit h t he I CH N ote f or G ui da nce o n G C P (IC H T o pic 
E 6, 1 9 9 6).  T he Cli nical Trial M o nit or will perf or m visits t o t he trial site at re g ular i nter vals.
Re prese ntati ves of t he S p o ns or’s Q ualit y  Ass ura nce u nit or a desi g nate d or ga nizati o n, as well as 
Healt h A ut h orities, m ust be per mitte d t o i ns pect all trial -relate d d oc u me nts a n d ot her materials at 
t he site, i ncl u di n g t he I n vesti gat or Site File, t he c o m plete d e C R Fs, t he trial dr u g, a n d t he s u bjects’ 
ori gi nal me dical rec or ds / files.
T he cli nical trial pr ot oc ol, eac h ste p of t he data ca pt ure pr oce d ure, a n d t he ha n dli n g of t he d ata, 
i ncl u di n g t he fi nal C li nical T rial R e p ort, will be s u bject t o i n de pe n de nt q ualit y  ass ura nce acti vities.  
A u dits ma y  be c o n d ucte d at a n y t i me d uri n g or after t he trial t o e ns ure t he vali dit y a n d i nte grit y of 
t he trial data.
1 0. 5
C h a n ges t o t he Cli nic al Tri al Pr ot oc ol
C ha n ges t o t he cli nical trial pr ot oc ol will be d oc u me nte d i n writte n pr ot oc ol a me n d me nts.  Maj or 
(s u bsta ntial, si g nifica nt) a me n d me nts will us uall y  re q uire s u b missi o n t o t he Healt h A ut h orities a n d 
t o t he rele va nt IE C / I R B f or a p pr o val or fa v ora ble o pi ni o n.  I n s uc h cases, t he a me n d me nt will be 
i m ple me nte d o nl y after a p pr o val or fa v ora ble o pi ni o n has bee n o btai ne d.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 2 / 1 5 0
Mi n or ( n o ns u bsta ntial) pr ot oc ol a me n d me nts, i ncl u di n g a d mi nistrati ve c ha n ges, will be file d b y  
t he S p o ns or a n d at t he site.  The y will be s u b mitte d t o t he rele va nt I E C / I RB or t o Healt h 
A ut h orities o nl y  w here re q ueste d by perti ne nt re g ulati o ns .
A n y  ame n d me nt t hat c o ul d affect t he s u bject’s a gree me nt t o partici pate i n t he trial re q uires
a d diti o nal i nf or me d c o nse nt pri or t o i m ple me ntati o n (see Secti o n  9. 2).
1 0. 6
Cli nic al Tri al Re p ort a n d P u blic ati o n P olic y
1 0. 6. 1
Cli nic al Tri al Re p ort
After c o m pleti o n of t he trial, a C li nical T rial R e p ort w ill be writte n b y t he S p o ns or i n c o ns ultati o n 
wit h t he C o or di nati n g I n vesti gat or f oll o wi n g t he g ui da nce i n I C H T o pic E 3.
1 0. 6. 2 
P u blic ati o n
T he first p u blicati o n will be a p u blicati o n of t he res ults of t he a nal ys is of t he pri mar y  en d p oi nts 
t hat will i ncl u de data fr o m all trial sites.
T he I n vesti gat or will i nf or m t he S p o ns or i n a d va nce a b o ut a n y pla ns t o p u blis h or prese nt data 
fr o m t he trial.  An y  pu blicati o ns a n d prese ntati o ns of t he res ults (a bstracts i n j o ur nals or 
ne ws pa pers, oral prese ntati o ns, etc.), eit her i n w h ole or i n part, b y  In vesti gat ors or t heir 
re prese ntati ves will re q uire pres u b missi o n re vie w b y t he S p o ns or.
T he S p o ns or will n ot s u p press or vet o p u blicati o ns, b ut mai ntai ns t he ri g ht t o dela y p u blicati o n i n 
or der t o pr otect i ntellect ual pr o pert y ri g h ts.
1 1
Refere nces Cite d i n t he Te xt
Br o o k me y er R, Cr o wle y J. A C o nfi de nce I nter val f or t he Me dia n S ur vi val Ti me. Bi o metrics. 
1 9 8 2; 3 8: 2 9 - 4 1.
C u n ni n g ha m 
D, 
Starli n g N, 
Ra o 
S , et al. Ca pecita bi ne 
a n d o xali plati n f or a d va nce d 
es o p ha g o gas tric ca ncer. N E n gl J Me d 2 0 0 8; 3 5 8:3 6 – 4 6.
D o n g H, Z h u G, Ta ma da K, C he n L.  B7- H 1, A t hir d me m ber of t he B 7 fa mil y, c o -sti m ulates T-
cell pr oliferati o n a n d i nterle u ki n- 1 0 secreti o n. Nat ure Me d. 1 9 9 9; 5( 1 2): 1 3 6 5 - 9.
D o n g H, Str o me S E, Sal o ma o D R, et al. T u m or -ass ociate d B 7 -H 1 pr o m otes T- cell a p o pt osis: a 
p ote ntial mec ha nis m of i m m u ne e vasi o n. Nat ure Me d. 2 0 0 2; 8( 8): 7 9 3- 8 0 0.
Eise n ha uer E A, T herasse P, B o gaerts J, et al. Ne w res p o nse e val uati o n criteria i n s oli d t u m o urs: 
re vise d R E CIS T g ui deli ne ( versi o n 1. 1). E ur J Ca ncer . 2 0 0 9; 4 5( 2): 2 2 8- 4 7.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 3 / 1 5 0
Free ma n GJ, L o n g AJ, I wai Y, et al. E n ga ge me nt of t he P D - 1 i m m u n oi n hi bit or y rece pt or b y  a 
n o vel B 7 fa mily me m ber lea ds t o ne gati ve re g ulati o n of l ym p h oc y te acti vati o n. J E x p Me d. 
2 0 0 0; 1 9 2( 7): 1 0 2 7 - 3 4.
H o m mel G, Bretz F a n d Ma urer
W. 
P o werf ul s h ort-c uts f or m ulti ple testi n g pr oce d ures wit h 
s pecial refere nce t o gate kee pi n g strate gies. Statist Me d. 2 0 0 7; 2 6 ; 4 0 6 3- 7 3.
H o war d S C, J o nes D P, P ui C H. T he t u m or l ysis s y n dr o me. N E n gl J Me d. 2 0 1 1; 3 6 4( 1 9): 1 8 4 4 - 5 4.
H u dis C A. Trast uz u ma b -mec ha nis m of acti o n a n d use i n cli nical practice. N E n gl J Me d. 
2 0 0 7; 3 5 7( 1): 3 9 - 5 1.
I nter nati o nal A ge nc y  for Researc h o n Ca ncer W H O. 
G L O B O C A N 2 0 1 2: Esti mate d Ca ncer 
I nci de nce, M ortalit y , an d Pre vale nce W orl d wi de 
i n 2 0 1 2 [ 0 6 A pril 2 0 1 5]. A vaila ble fr o m: 
htt p:// gl o b oca n.iarc.fr/ Defa ult.as p x.
Jasse m J, Ra mla u R, Sa nt or o A, et al. P hase III trial of pe metre xe d pl us best s u p p orti ve care 
c o m pare d wit h best s u p p orti ve care i n pre vi o usl y t reate d patie nts wit h a d va nce d mali g na nt ple ural 
mes ot heli o ma. J Cli n O nc ol. 2 0 0 8; 2 6( 1 0): 1 6 9 8 -7 0 4.
Kal bfleisc h J D, Pre ntice R L . T he Statistical A nal ysis of Fail ure Ti me Data. Ne w Y or k: J o h n Wile y 
& S o ns; 1 9 8 0.
Latc h ma n Y, W o o d C R, C her n o va T, et al. P D -L 2  is a sec o n d li ga n d f or P D -1 a n d i n hi bits T cell 
acti vati o n. Nat ure I m m u n ol. 2 0 0 1; 2( 3): 2 6 1- 8.
L utz k y  J, A nt o nia SJ, Bla ke -Has ki ns A, et al. A p hase 1 st u d y of M E DI 4 7 3 6, a n a nti– P D L 1 
a nti b o d y, i n patie nts wit h a d va nce d s oli d t u m ors [ A S C O a bstract 3 0 0 1 ^]. J Cli n O nc ol. 
2 0 1 4; 3 2( 5s) :a bstr 3 0 0 1.
M ur o K, Ba n g Y, S ha n kara n V, et al. A P hase 1 B St u d y  of pe m br oliz u ma b ( pe m br o; M K -3 4 7 5) 
i n patie nts wit h a d va nce d gastric ca ncer. A n n O nc ol . 2 0 1 4; 2 5(s u p pl 5): v 1- v 4 1.
Nati o nal C o m pre he nsi ve Ca ncer Net w or k G ui deli nes f or Gastric Ca ncer. 2 0 1 5; Ver si o n 3 . 2 0 1 5.
O ki E, O ka n o S, A n d o K, et al. H E R 2 a n d pr o gra m me d deat h - 1 li ga n d-1 ( P D-L 1 ) e x pressi o n i n 
gastric carci n o ma. J Cli n O nc ol. 2 0 1 4; 3 2( N o 1 5 _s u p pl ( Ma y  2 0 S u p ple me nt)):e 1 5 0 4 1.
Ste wart B W, Wil d C P, e dit ors. W orl d Ca ncer Re p ort 2 0 1 4: I nter nati o nal A ge nc y  f or Researc h o n 
Ca ncer, W orl d Healt h Or ga nizati o n; 2 0 1 4.
Tes niere A 1, Sc hle m mer F, B oi ge V, et al. I m m u n o ge nic deat h of c ol o n ca ncer cells treate d wit h 
o xali plati n. O nc o ge ne. 2 0 1 0 Ja n 2 8; 2 9( 4): 4 8 2 - 9 1.
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 4 / 1 5 0
T o palia n S L , Dra ke C G, Par d oll D M. Tar geti n g t he P D -1/ B 7 -H 1( P D -L 1) pat h wa y  to acti vate a nti-
t u m or i m m u nit y. C urr O pi n I m m u n ol . 2 0 1 2; 2 4( 2): 2 0 7- 1 2.
T o palia n S L , H o di F S, Bra h mer J R, et al. Safet y, acti vit y, a n d i m m u ne c orrelates of a nti-P D -1 
a nti b o d y i n ca ncer. N E n gl J Me d . 2 0 1 2; 3 6 6( 2 6): 2 4 4 3-5 4.
Wa d dell T, Ver heij M, All u m W, et al. Gastric ca ncer: E S M O -E S S O -E S T R O cli nical practice 
g ui deli nes f or dia g n osis, treat me nt a n d f oll o w -u p. A n n O nc ol 2 0 1 3; 2 4 (s u p pl 6): vi 5 7 -vi 6 3.
Zafar 
S Y, C urr o w 
D, 
A ber net h y A P. 
Defi ni n g 
best s u p p orti ve care. J Cli n 
O nc ol.
2 0 0 8; 2 6( 3 1): 5 1 3 9 - 4 0.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 5 / 1 5 0
1 2
A p pe n dices
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 6 / 1 5 0
A p pe n di x I
Si g n at ure P a ges a n d Res p o nsi ble Pers o ns f or t he Tri al
D oc u me nt N o. 
O bject N o.
C CI
C CI

A v el u m a b 
E M R 1 0 0 0 7 0- 0 0 7 
A v el u m a b i n First-li n e G astri c C a n c er 
Si g n at ur e P a g e - Pr ot o c ol L e a d 
Tri al Titl e: 
I N D N u m b er: 
E u dr a C T N u m b er: 
A 
P h as e 
ill o p e n- la bel, m ulti c e nt er 
trial of 
m ai nt e n a n c e t h er a p y wit h a v el u m a b ( M S B 0 0 1 0 71 8 C) 
v ers us c o nti n u ati o n of first-li ne c he m ot hera p y i n 
s u bj e cts wit h 
u nr es e ct a bl e, l ocally a d v a n c e d or 
m et ast ati c, a d e n o c ar ci n o m a of t h e st o m a c h, or of t h e 
g astr o- es o p h a g e al j u n cti o n 
 
 
2 0 1 5- 0 0 3 3 0 0- 2 3 
Cli ni c al 
Tri al 
Pr ot o c ol 
D at e 
I 1 7 J ul y 2 0 1 9 N ersi o n 7. 0 
V ersi o n: 
Pr ot o c ol L e a d r es p o nsi bl e f or d esi g ni n g t h e cli ni c al tri al: 
I a p pr o ve t he desi g n of ;;;teal trial: 
Si g n at ur e 
N a m e, a c a d e mi c d e gr e e: 
 
F u n cti o n I Titl e: 
 
I nstit uti o n: 
E M D S er o n o R es e ar c h & D e v el o p m e nt I nstit ute, I nc. 
A d dr ess: 
T el e p h o n e n u m b er: 
E- m ail a d dr ess: 
4 5 A Mi d dl es e x T ur n pi ke, Bill eri c a, M A 0 1 8 2 1- 3 9 3 6, U S A 
 
 
D oc u m e nt N o.
 
O bject N o. 
 
 
 
1 3 7/1 5 0 
C CI
C CI
C CI
P P D
P P D
P P D
P P D
P P D
P P D

A vel u ma b 
E M R 1 0 0 0 7 0- 0 0 7 
A v el u m a b i n First-li n e G astri c C a n c er 
Si g n at ur e P a g e - C o or di n ati n g I n v esti g at or 
Tri al Titl e 
I N D N u m b er 
E u dr a C T N u m b er 
A P h as e ill o pe n-la bel , m ultice nter trial of mai nte na nce 
t he r a p y wit h 
a vel u ma b 
( M S B O O 1 0 7 1 8 C) 
v e rs us 
c o nti n uati o n offrr st-li ne c he m ot hera p y i n su bjects wit h 
u nresecta ble , 
l ocally 
a dv a nce d 
or 
metastatic , 
a de n ocarci n o ma 
of 
t h e 
st o mac h, 
or 
of 
t he 
gastr o -es o p ha geal j u n cti o n 
... 
 
2 0 1 5- 0 0 3 3 0 0- 2 3 
Cli ni c al 
Tri al 
Pr ot o c ol 
D at e 
I 1 7 J ul y 2 0 1 9 N ersi o n 7. 0 
V ersi o n 
I a p pr o ve t he d esi g n of t h e cli nical trial a n d I u n dersta n d a n d will c o n d u ct t he trial acc or di n g t o 
t h e cli ni c al tri al pr ot o c ol , a n y a p pr o v e d pr ot o c ol a me n d me nts , I nter nati o nal C o u ncil f or 
Har m o nisati o n 
G o o d 
Cli nical 
Pr a cti ce ( T o pic E 6) a n d all a p plica ble Healt h 
A ut h orit y 
re q uire me nts a n d n ati o n al la ws. 
Si g nat ure 
D at e of Si g nat ure 
N a me, aca de mic d e gr e e : 
 
I nstit uti o n: 
 
A d dre ss: 
 
E- mail a d dre ss: 
 
D o c u m e nt N o. 
 
O bj e ct N o . 
 
 
 
13 8/ 1 5 0 
C CI
C CI
C CI
P P D
P P D
P P D
P P D
P P D
P P D

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 3 9 / 1 5 0
Si g n at ure P a ge – Pri nci p al I n vesti g at or
Tri al Title
A 
P hase 
III o pe n -la bel, m ultice nter 
trial of 
mai nte na nce t hera p y wit h a vel u ma b ( M S B 0 0 1 0 7 1 8 C) 
vers us c o nti n uati o n of first-li ne c he m ot hera p y in 
s u bjects wit h 
u nresecta ble, l ocally a d va nce d or 
metastatic, a de n ocarci n o ma of t he st o mac h, or of t he 
gastr o -es o p ha geal j u ncti o n
I N D N u m ber
E u dr a C T N u m ber
2 0 1 5- 0 0 3 3 0 0- 2 3
Cli nic al 
Tri al 
Pr ot oc ol 
D ate 
/ 
Versi o n
1 7 J ul y 2 0 1 9/Versi o n 7. 0
Ce nter N u m ber
Pri nci p al I n vesti g at or
I, t he u n dersi g ne d, a m res p o nsi ble f or t he c o n d uct of t he trial at t his site a n d affir m t hat I 
u n dersta n d a n d will c o n d uct t he trial acc or di n g t o t he cli nical trial pr ot oc ol, a n y a p pr o ve d pr ot oc ol 
a me n d me nts, I nter nati o nal C o u ncil f or Har m o nisati o n G o o d Cl i nical Practice ( T o pic E 6) a n d all 
a p plica ble Healt h A ut h orit y re q uire me nts a n d nati o nal la ws.
I als o affir m t hat I u n dersta n d t hat Healt h A ut h orities ma y re q uire t he S p o ns ors of cli nical trials t o 
o btai n a n d s u p pl y details a b o ut o w ners hi p i nterests i n t he S p o ns or or I nvesti gati o nal Me dici nal 
Pr o d uct a n d a n y ot her fi na ncial ties wit h t he S p o ns or .  T he S p o ns or will use a n y s uc h i nf or mati o n 
s olel y for t he p ur p ose of c o m pl y i n g wit h t he re g ulat or y re q uire me nts.  I t heref ore a gree t o s u p pl y 
t he S p o ns or wit h a n y necessar y  inf or mati o n re gar di n g o w ners hi p i nterest a n d fi na ncial ties 
i ncl u di n g t h ose of my s p o use a n d de pe n de nt c hil dre n, a n d t o pr o vi de u p dates as necessar y t o meet 
Healt h A ut h orit y  re q uire me nts.
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Si g nat ure
Date of Si g nat ure
Na me, aca de mic de gree:
F u ncti o n / Title:
I nstit uti o n:
A d dress:
Tele p h o ne n u m ber:
Fa x n u m ber:
E- mail a d dress:
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 0 / 1 5 0
S p o ns or Res p o nsi ble Pers o ns n ot N a me d o n t he C o ver P a ge
Na me, aca de mic de gree:
F u ncti o n / Title:
I nstit uti o n:
E M D Ser o n o Researc h & De vel o p me nt I nstit ute, I nc.
A d dress:
4 5 A Mi d dlese x T ur n pi ke, Billerica, M A 0 1 8 2 1, U S A
Tele p h o ne n u m ber:
E- mail a d dress:
Na me, aca de mic de gree:
F u ncti o n / Title:
I nstit uti o n:
Merc k Healt hcare K Ga A Dar msta dt, Ger ma n y, a n affiliate of Merc k 
K Ga A, Dar msta dt, Ger ma n y .
A d dress:
Fra n kf urter Str. 2 5 0, 6 4 2 9 3 Dar msta dt, Ger ma n y
Tele p h o ne n u m ber:
 
Fa x n u m ber:
E- mail a d dress:
Na me, aca de mic de gree:
F u ncti o n / Title:
I nstit uti o n:
E M D Ser o n o Researc h & De vel o p me nt I nstit ute, Inc.
A d dress:
4 5 A Mi d dlese x T ur n pi ke, Billerica, M A 0 1 8 2 1, U S A
Tele p h o ne n u m ber:
E- mail a d dress:
D oc u me nt N o. 
O bject N o. 
C CI
C CI
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

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 1 / 1 5 0
A p pe n di x II
G ui d a nce o n C o ntr ace pti o n
BI R T H C O N T R O L M E T H O D S C O N SI D E R E D A S HI G H L Y E F F E C TI V E
Acc or di n g t o t he C T F G “ Rec o m me n dati o ns relate d t o c o ntrace pti o n a n d pre g na nc y  testi n g i n cli nical trials” met h o ds t hat ca n ac hie ve a fail ure rate of 
less t ha n 1 % per ye ar w he n use d c o nsiste ntl y a n d c orrectl y are c o nsi dere d as hi g hly effecti ve birt h c o ntr ol met h o ds, s uc h as:
o
c o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 1 ( oral, i ntra va gi nal, tra ns der mal)
o
pr o gester o ne - o nly h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n 1 ( oral, i njecta ble, i m pla nta ble2)
o
i ntra uteri ne de vice (I U D)2
o
i ntra uteri ne h or m o ne -releasi n g sys te m (I U S)2
o
bilateral t u bal occl usi o n 2
o
vasect o mize d part ner 2, 3
o
se x ual a bsti ne nce. 4
1 H or m o nal c o ntrace pti o n ma y be s usce pti ble t o i nteracti o n wit h t he I M P, w hic h ma y re d uce t he efficac y of t he c o ntrace pti o n met h o d.
2 C o ntrace pti o n met h o ds i n t he c o nte xt of t his g ui da nce are c o nsi dere d t o ha ve l o w  user de pe n de nc y.
3 Vasect o mise d part ner is a hi g hl y effecti ve birt h c o ntr ol met h o d pr o vi de d t hat t he part ner is t he s ole se x ual part ner of t he w o m a n of c hil d beari n g p ote ntial trial partici pa nt a n d t hat 
t he vasect o mize d part ner has recei ve d me dical assess me nt of t he s ur gical s uccess.
4 I n t he c o nte xt of t his g ui da nce se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y if defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e nt ire peri o d of ris k 
ass ociate d wit h t he st u d y treat me nts. T he relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d i n relati o n t o t he d urati o n of t he cli nical trial a n d t he preferre d a n d us ual lifest yle of 
t he s u bject.
D oc u me nt N o. 
O bject N o.
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 2 / 1 5 0
A p pe n di x III
Pr ot oc ol A me n d me nts a n d List of C h a n ges
Pr ot oc ol Versi o n 1. 0 ( 1 4 A u g ust 2 0 1 5) was t he ori gi nal pr ot oc ol.  The pr ot oc ol was re vise d t o i ncl u de fee d bac k fr o m t he F D A, P M D A, a n d E M A, 
a n d Versi o n 2. 0 ( A me n d me nt 1) was iss ue d o n 2 3 Se pte m ber 2 0 1 5.  Versi o n 3. 0 ( A me n d me nt 2) was iss ue d o n 0 6 Ja n uar y 20 1 6 a n d i ncl u de d fee d bac k 
fr o m V ol u ntar y  Har m o nisati o n Pr oce d ure (V H P ).  Versi o n 3. 1 (Ja pa n O nl y A d de n d u m) was iss ue d o n 0 6 A pril 2 0 1 6 a n d i ncl u de d m o dificati o ns f or 
t he P har mace uticals a n d Me dical De vices A ge nc y.  Versi o n 3. 2 ( Fra nce O nl y  Ad de n d u m) was iss ue d o n 0 1 A pril 2 0 1 6 a n d i ncl u de d m o dificati o ns 
f or t he Fre nc h Nati o nal A ge nc y  for Me dici nes a n d Healt hcare Pr o d ucts Safet y  (A N S M) a n d Fre nc h Ce ntral Et hics C o m mittee re q uests.  Pr ot oc ol 
Versi o n 4. 0 ( A me n d me nt 3) was iss ue d o n 2 5 Ja n uar y 2 0 1 7 a n d i ncl u des pr o gra m -wi de c ha n ges a n d c orrecte d a n a d mi nistrati ve err or i n t he versi o n 
n u m beri n g of t he pr ot oc ol . Pr ot oc ol Versi o n 5 . 0 ( A me n d me nt 4 ) was iss ue d o n 2 8 A u g ust 2 0 1 7 a n d i ncl u des pr o gra m- wi de c ha n ges c o nsi dere d as 
n o n- s u bsta ntial as o nl y a d mi nistrati ve c h a n ges were ma de . Pr ot oc ol Versi o n 6. 0 ( A me n d me nt 5) was iss ue d o n 2 1 J u ne 2 0 1 8 a n d i ncl u de d c ha n ges 
t o t he st u d y pri mar y an d sec o n dar y en d p oi nts/ o bjecti ves c o nsi dere d as s u bsta ntial.  Versi o n 6. 1 (Ja pa n o nl y  ad de n d u m) was iss ue d o n 1 1 J ul y 2 0 1 8 
a n d Versi o n 6. 2 ( Fra nce o nl y  a d de n d u m) was iss ue d o n 0 7 A u g ust 2 0 1 8 a n d i ncl u de d A me n d me nt 5 .
Pr ot oc ol Versi o n 7 . 0 S u m m ar y of C h a n ges
T he ke y  reas o ns f or A me n d me nt 6, Pr ot oc ol versi o n 7. 0, are s u m marize d bel o w:
R ati o n ale f or C h a n ges
St u d y  EM R 1 0 0 0 7 0 - 0 0 7 was a me n de d i n J u ne 2 0 1 8 t o c ha n ge t he pri mar y  objecti ve t o i ncl u de O S i n P D -L 1 + s u bjects, i n a d diti o n t o O S i n all 
ra n d o mize d s u bjects, w here P D -L 1 stat us was defi ne d base d o n a 1 % c ut-off f or t u m or cells (refere nce pr ot oc ol E M R 1 0 0 0 7 0 - 0 0 7 A me n d me nt 5, 
V ersi o n 6).  At t hat ti me, t he pre vale nce of P D -L 1 + s u bjects was ass u me d t o be 3 5 % ( base d o n t he pre vale nce of P D -L 1 + t u m ors i n patie nts wit h 
gastric ca ncer ( G C) i n t he n o n- pr o gresse d G C c o h ort of st u d y EM R 1 0 0 0 7 0 -0 0 1).  As s uc h, 1 1 2 e ve nts i n t he P D -L 1 + s u b gr o u p were pr ojecte d t o 
occ ur t o t he 3 5 6 O S e ve nts re q uire d f or t he pri mar y a nal ys is i n all ra n d o mize d s u bjects, a n d t he pri mar y a nalys is i n b ot h a nal ysis sets was pla n ne d at 
a c o m m o n ti me p oi nt w he n b ot h c o n diti o ns are met. 
At t he ti me o f release of P r ot oc ol V ersi o n 6, t he P D -L 1 assa y utilize d was a n i n vesti gati o nal use o nl y  (I UO) assa y for
 testi n g.  Beca use 
t he a me n de d pri mar y e n d p oi nt of O S i n t he P D -L 1 + a nal ysis set w o ul d re q uire testi n g b y  vali date d assa y, vali dati o n of t he pr o p ose d P D -L 1 I H C 7 3-
1 0 p har m D x kit f or testi n g of G C sa m ples at 1 % c ut- off f or t u m or cells was i nitiate d i n Se pte m ber 2 0 1 8.
Res ults of t he P D -L 1  sc ori n g wit h vali date d assa y beca me a vaila ble i n J une 2 0 1 9.  Fr o m 4 9 9 ra n d o mize d s u bjects, 4 3 8 sa m ples we re a vaila ble f or 
P D -L 1  sc ori n g wit h t he vali date d assa y .  Less t ha n 1 5 % of t he sa m ples were sc ore d as P D-L 1 p ositi ve, w hic h is c o nsi dera bl y less t ha n t he pre vi o usl y 
ass u me d pre vale nce d uri n g Pr ot oc ol V ersi o ns 1- 6.  Base d o n t his pre vale nce, t he n u m ber of p re vi o usl y pr ojecte d e ve nts ( Pr ot oc ol V ersi o n 6) i n t he 
P D -L 1 + s u bjects will n ot be reac he d.  Th us, t he c o n diti o n of meeti n g t he pre -s pecifie d n u m ber of P D-L 1 + e ve nts f or t he Fi nal A nal y sis data c ut-off 
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 3 / 1 5 0
has bee n re m o ve d as a tri g ger f or t he Fi nal A nal ys is i n t he P r ot oc ol V ersi o n 7. T he Fi nal A nal ys is will be tri g gere d b y  the e ve nts i n t he I TT p o p ulati o n 
as well as a mi ni m u m f oll o w- u p ti me of 1 8 m o nt hs
f or pri mar y  anal ys is w hic h is e x pecte d t o e ns ure s ufficie ntly mat ure data f or O S i n P D -L 1 + 
s u bjects.  T he p ri mar y anal y sis of O S i n P D -L 1 + s u bjects will be c o n d ucte d at t he sa me ti me as O S i n all ra n d o mize d s u bjects wit h s u bsta ntiall y 
re d uce d p o wer, acc or di n g t o t he e n d p oi nt defi niti o n as i n P r ot oc ol V ersi o n 6.
T he sa m pli n g f or P K a n d 
a nal ys is was li mite d t o 2 ye ars fr o m ra n d o mizati o n, as f urt her sa m pli n g will n ot a d d val ue t o p har mac o ki netic a n d 
 e val uati o n. T heref ore, t he last sa m pli n g p oi nt will be at Wee k 1 0 9. T his will a v oi d u n necessar y b ur de n t o t he s u bjects.
T he a b o ve -me nti o ne d c ha n ges are c o nsi dere d s u bsta ntial base d o n t he ‘ Detaile d g ui da nce o n t he re q uest t o t he c o m pete nt a ut h orities f or a ut h orizati o n 
of a cli nical trial o n a me dici nal pr o d uct f or h u ma n use, t he n otificati o n of s u bsta ntial a me n d me nts a n d t he declarati o n of t he e n d of t he trial ( C T -1)’.
Pr ot oc ol Versi o n 7 . 0 Det aile d List of C h a n ges
C ha n ges t o t he cli nical trial pr ot oc ol te xt wit h t he e xce pti o n of mi n or e dit orial c ha n ges t o t he cli nical trial pr ot oc ol te xt are prese nte d i n t he ta ble 
bel o w. A d diti o ns a n d a me n de d te xt are s h o w n i n b ol d.
Deleti o ns are mar ke d usi n g stri ke t hr o u g h.
C o m p aris o n wit h Cli nic al Tri al Pr ot oc ol Versi o n 6. 0, 2 1 J u ne 2 0 1 8 ( A me n d me nt 5)
C h a n ge
Secti o n
P a ge
Pre vi o us W or di n g
Ne w W or di n g
R ati o n ale
S p o ns or 
Me dical 
res p o nsi ble pers o n 
c ha n ge d fr o m Ilaria 
C o nti
t o 
H o n g 
Z ha n g
Title Pa ge a n d 
Si g nat ure 
Pa ge - Pr ot oc ol 
Lea d
1, 
1 3 5
St u d y Pers o n nel 
u p date d
Last s u bject o ut date 
c ha n ge d fr o m Q 4 t o 
Q 3
S y n o psis 
Pla n ne d Trial 
Peri o d
1 1
La st s u bject o ut: Q 4, 2 0 1 9
La st s u bject o ut: Q3 , 2 0 1 9
U p date d as t he date 
o n w hic h data 
c ollecti o n is 
c o m plete d f or all 
t he pri mar y a nal ysis
is 1 3 Se p 2 0 1 9
A s t he pre vale nce 
of P D -L 1 + s u bjects 
S y n o psis
1 8
T he data c ut -off f or t he pri mar y a nal ysis will 
ta ke place o n a pr os pecti vel y-deter mi ne d date, 
T he data c ut -off f or t he pri mar y a nal ysis will ta ke 
place o n a pr os pecti vel y -deter mi ne d date, u p o n 
As per t he res ults of 
t he P D-L 1 sc ori n g 
D oc u me nt N o. 
O bject N o.
C CI
C CI
P P D P P D
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 4 / 1 5 0
is l o wer t ha n i nitial 
f orecaste d 3 5 %. 
Fr o m  c urre nt 
e nr olle d n u m ber of 
s u bjects, it is 
i mp ossi ble t o e ver 
reac h 1 1 2 e ve nts 
a ntici pate d f or 
pri mar y a nal ysis i n 
P D -L 1 p ositi ve 
s u bjects.
u p o n w hic h t he tar get n u m ber of 3 5 6 O S e ve nts 
i n all ra n d o mize d s u bjects a n d 1 1 2 O S e ve nts i n 
P D -L 1 + s u bjects are pr ojecte d t o ha ve bee n 
reac he d, a n d t he last s u bject ra n d o mize d i n t he 
st u d y has bee n f oll o we d f or at least 1 8 m o nt hs 
fr o m ra n d o mizati o n.
[ ….]
F or O S i n P D -L 1 + s u bjects, a pre vale nce rate of 
3 5 % i n all ra n d o mize d s u bjects is ass u me d, a n d 
a me dia n O S of 1 9. 3 m o nt hs i n t he a vel u ma b 
ar m c orres p o n di n g t o a hazar d rati o of 0. 5 4.
w hic h t he tar get n u m ber of 3 5 6 O S e ve nts i n all 
ra n d o mize d s u bjects a n d 1 1 2 O S e ve nts i n P D - L 1 + 
s u bjects are pr ojecte d t o ha ve bee n reac he d, a n d t he 
last s u bject ra n d o mize d i n t he st u d y has bee n 
f oll o we d f or at least 1 8 m o nt hs fro m  ra n d o mizati o n.
[ ….]
F or O S i n P D -L 1 + s u bjects, at pl a n ni n g st a ge a
pre vale nce rate of 3 5 % i n all ra n d o mize d s u bjects 
w a s is ass u me d, a n d a me dia n O S of 1 9. 3 m o nt hs i n 
t he a vel u ma b ar m c orres p o n di n g t o a hazar d rati o of 
0. 5 4.
wit h vali date d assa y 
a vaila ble i n J u ne 
2 0 1 9 , t he n u m ber of 
pre vi o usl y 
pr ojecte d e ve nts 
( Pr ot oc ol V ersi o n 
6) i n t he P D - L 1 + 
s u bjects will not be 
reac he d.  T h us, t he 
c o n diti o n of 
meeti n g t he pre -
s pecifie d n u m ber of 
P D -L 1 + e ve nts f or 
t he Fi nal A nal ysis 
data c ut -of f has 
bee n re m o ve d as a 
tri g ger f or t he Fi nal 
A nal ysis .  T he Fi nal 
A nal ysis will be 
tri g gere d b y t he 
e ve nts i n t he I T T 
p o p ulati o n as we ll 
as a mi ni m u m 
f oll o w-u p ti me of 
1 8 m o nt hs f or 
pri mar y a nal ysis 
w hic h is e x pecte d 
t o e ns ure 
s ufficie ntl y mat ure 
data f or O S i n P D -
L 1 + s u bjects .  T he 
pri mar y a nal ysis of 
O S i n P D - L 1 + 
s u bjects will be 
c o n d ucte d at t he 
sa me ti me as O S i n 
all ra n d o mize d 
s u bjects wit h 
s u bsta ntiall y 
re d uce d p o wer.
D oc u me nt N o. 
O bject N o. 
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 5 / 1 5 0
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 6 / 1 5 0
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 7 / 1 5 0
be at Wee k 1 0 9 t o 
a v oi d u n necessar y 
b ur de n t o t he 
s u bjects, e xce pt f or 
s u bjects still o n 
treat me nt be y o n d 
Wee k 1 0 9.
D oc u me nt N o. 
O bject N o. 
C CI
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 8 / 1 5 0
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI
C CIC CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 4 9 / 1 5 0
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI

A vel u m a b
A vel u m a b i n First -li ne G astric C a ncer
E M R 1 0 0 0 7 0 - 0 0 7
1 5 0 / 1 5 0
D oc u me nt N o. 
O bject N o.
C CI
C CI
C CI