TRASTUZUMAB BS for Intravenous Infusion 60 mg [Pfizer], TRASTUZUMAB BS for Intravenous Infusion 150 mg [Pfizer] General Investigation (Unresectable Advanced/Recurrent HER2-Overexpressing Gastric Cancer)
Conditions: Gastric Cancer
Sponsor: Pfizer

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 of 3 0 
( A n ne x) 
 
 
 
T R A S T U Z U M A B B S f or I ntr a ve n o us I nf usi o n 6 0 m g [ Pfizer] 
T R A S T U Z U M A B B S f or I ntr a ve n o u s I nf usi o n 1 5 0 m g [ Pfizer] 
 
 
 Ge ner al
 
I n vesti g ati o n
 
( U nresect a ble A d v a nce d/ Rec urre nt H E R 2- O vere x pressi n g G astric C a ncer) 
F ull Pr ot oc ol 
 
 
 
 
 
 
 
 
 
 
 
 
Pfizer Ja pa n I nc.  
 
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer. E xce pt as ot her wise a gree d t o i n writi n g, 
b y acce pti n g or re vie wi n g t his d oc u me nt, y o u a gree t o h ol d t his i nf or mati o n i n c o nfi de nce a n d n ot c o p y or 
discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or use it f or u na ut h orize d p ur p oses. I n t he e ve nt 
of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be pr o m ptl y n otifie d. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 of 3 0  
  
S T U D Y I N F O R M A TI O N  
Title 
T R A S T U Z U M A B B S f or I ntra ve n o us 
I nf usi o n 6 0 m g [ Pfizer]/ T R A S T U Z U M A B 
B S f or I ntra ve n o us I nf usi o n 1 5 0 m g [ Pfizer] 
Ge neral I n vesti gati o n ( U nresecta ble 
A d va nce d/ Rec urre nt H E R 2- O vere x pressi n g 
Gastric Ca ncer) 
Pr ot oc ol n u m ber 
B 3 2 7 1 0 0 7 
Pr ot o versi o n i de ntifier  
 
Versi o n 5 
D ate 
2 2 Dece m ber 2 0 2 2 
Ge neric na me  
Trast uz u ma b ( Ge netical Rec o m bi nati o n) 
[ Trast uz u ma b Bi osi milar 3] 
Pr o d uct na me  
T R A S T U Z U M A B B S f or I ntra ve n o us 
I nf usi o n 6 0 m g [ Pfizer]/ T R A S T U Z U M A B 
B S f or I ntra ve n o us I nf usi o n 1 5 0 m g [ Pfizer] 
Rese arc h q uesti o n a n d o bjecti ves 
T o c o nfir m t he safet y a n d efficac y of t his 
dr u g u n der t he act ual use. 
A ut h or 
 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)
P P D

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 3 of 3 0  
 
T A B L E O F C O N T E N T S 
1. LI S T O F A B B R E VI A TI O N S ...................................................................................................... .............. 6 
2. R E S P O N SI B L E P A R TI E S ........................................................................................................ ................ 6 
3. A M E N D M E N T S A N D U P D A T E S ..................................................................................................... ...... 6 
4. MI L E S T O N E S ................................................................................................................. .......................... 9 
5. R A TI O N A L E A N D B A C K G R O U N D ................................................................................................... ... 9 
6. R E S E A R C H Q U E S TI O N A N D O BJ E C TI V E S ...................................................................................... 1 0  
6. 1. Safet y S pecificati o ns .................................................................................................... .................. 1 0 
7. R E S E A R C H M E T H O D S ........................................................................................................... ............. 1 0 
7. 1. St u d y Desi g n ............................................................................................................. ...................... 1 0 
7. 2. Setti n g .................................................................................................................. ........................... 1 0 
7. 2. 1. Re gistrati o n criteria .................................................................................................. .......... 1 0 
7. 2. 2. E xcl usi o n criteria...................................................................................................... .......... 1 1 
7. 2. 3. St u d y sites ............................................................................................................ .............. 1 1 
7. 2. 4. Pla n ne d st u d y peri o d ................................................................................................... ....... 1 1 
7. 2. 5. St u d y pr oce d ures ....................................................................................................... ......... 1 1 
7. 2. 5. 1. St u d y met h o d ...................................................................................................... 1 1  
7. 2. 6. O bser vati o n peri o d ..................................................................................................... ........ 1 1 
7. 3. Varia bles ................................................................................................................ ......................... 1 1 
7. 3. 1. Patie nt c haracteristics ................................................................................................ ......... 1 2 
7. 3. 2. A d mi nistrati o n rec or d of tar gete d dr u g .............................................................................. 1 3  
7. 3. 3. Pri or t hera p y ( dr u g t hera p y) ........................................................................................... .... 1 3 
7. 3. 4. C o nc o mita nt t hera p y ( dr u g t hera p y) .................................................................................. 1 4  
7. 3. 5. C o nc o mita nt t hera p y ( n o n- dr u g t hera p y) ........................................................................... 1 4  
7. 3. 6. Dr u gs use d f or pre ve nti o n of i nf usi o n reacti o ns ................................................................ 1 4  
7. 3. 7. Tests .................................................................................................................. ................. 1 4 
7. 3. 7. 1. Cli nical la b orat or y tests ...................................................................................... 1 4  
7. 3. 8. 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) ............................ 1 4  
7. 3. 9. Pre g na nc y (fe male o nl y) ................................................................................................ .... 1 5 
7. 3. 1 0. E n d- of-st u d y ( disc o nti n uati o n rec or d) ............................................................................. 1 5  
7. 3. 1 1. Effecti ve ness e val uati o n .............................................................................................. ..... 1 5 
7. 3. 1 2. A d verse e ve nts ........................................................................................................ ......... 1 6 
7. 4. Data S o urces ............................................................................................................. ...................... 1 6 
7. 5. St u d y Size ............................................................................................................... ........................ 1 6 
7. 5. 1. Pla n ne d sa m ple size .................................................................................................... ....... 1 6 
7. 5. 2. Rati o nale f or sa m ple size .............................................................................................. ..... 1 7 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 4 of 3 0  
7. 6. Data Ma na ge me nt .......................................................................................................... ................. 1 7 
7. 6. 1. Case re p ort f or m ( C R F)/ Electr o nic da ta rec or d ................................................................. 1 7 
7. 6. 2. Rec or d rete nti o n ....................................................................................................... .......... 1 7 
7. 6. 3. Data c ollecti o n met h o d ( E D C) ...........................................................................................  1 7 
7. 6. 4. Patie nt re gistrati o n ( E D C) ............................................................................................. ..... 1 7 
7. 6. 5. P oi nts t o c o nsi der f or e ntr y, re visi o n, a n d s u b missi o n of case re p ort f or m ( E D C) ............ 1 8  
7. 6. 5. 1. Data e ntr y ...........................................................................................................  1 8 
7. 6. 5. 2. Data Re visi o n ..................................................................................................... 1 8  
7. 6. 5. 3. S u b missi o n ......................................................................................................... 1 8  
7. 7. Data A nal ysis ............................................................................................................ ...................... 1 8 
7. 8. Q ualit y C o ntr ol .......................................................................................................... ..................... 1 9 
7. 9. Li mitati o ns of t he Researc h Met h o ds ...................................................................................... ....... 1 9 
7. 1 0. Ot her As pects ........................................................................................................... ..................... 1 9 
8. P R O T E C TI O N O F H U M A N S U BJ E C T S ...............................................................................................  1 9 
8. 1. Patie nt I nf or mati o n ...................................................................................................... ................... 1 9 
8. 2. Patie nts C o nse nt ......................................................................................................... ..................... 2 0 
8. 3. I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m m ittee (I E C) ...................................... 2 0 
8. 4. Et hical C o n d uct of t he St u d y .... ...................................................................................................... 2 1 
9. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E D R U G 
R E A C TI O N S ..................................................................................................................... .................... 2 1 
9. 1. Re q uire me nts f or Rec or ds a n d Re p orti n g ................................................................................... .... 2 1 
9. 2. Re p orti n g Peri o d ......................................................................................................... .................... 2 2 
9. 3. Ca usalit y Assess me n t ..................................................................................................................... 2 2 
9. 4. Defi niti o n of Safet y E ve nts .. ........................................................................................................... 2 2 
9. 4. 1. A d verse e ve nts ......................................................................................................... .......... 2 2 
9. 4. 2. Seri o us a d verse e ve nts ................................................................................................. ...... 2 4 
9. 5. Sce nari os Necessitati n g Re p orti n g t o Pfizer Safet y wit hi n 2 4 H o urs ............................................. 2 5  
1 0. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S ............................ 2 8  
1 1. N A M E A N D A D D R E S S O F C O N T R A C T O R A S W E L L A S S C O P E O F W O R K 
C O N T R A C T E D .................................................................................................................... ................ 2 8 
1 2. A D DI TI O N A L M E A S U R E S T H A T M A Y B E I M P L E M E N T E D B A S E D O N T H E S T U D Y 
R E S U L T S A N D C RI T E RI A F O R D E T E R MI N A TI O N  O F T H E I NI TI A TI O N ................................. 2 9 
1 3 . S C H E D U L E D TI MI N G O F MI L E S T ON E S A N D T H EI R R A TI O N A L E S F O R 
E V A L U A TI O N O F S T U D Y I M P L E M E N T A TI O N S T A T U S A N D R E S U L T S A N D 
R E P O R TI N G T O T H E P M D A ......................................................................................................... .... 2 9 
1 4. O T H E R N E C E S S A R Y M A T T E R S ................... ................................................................................... 2 9 
1 5. C O N T A C T I N F O R M A TI O N ....................................................................................................... ......... 3 0 
1 5. 1. C o ntact I nf or mati o n f or I n q uiries a b o ut t he St u d y ....................................................................... 3 0 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 5 of 3 0  
1 5. 2. C o ntact I nf or mati o n f or I n q uiries a b o ut P ost- mar keti n g S ur veilla nce Data C ollecti o n 
S yste m ........................................................................................................................ .................. 3 0 
1 6. R E F E R E N C E S ................................................................................................................ ...................... 3 0 
1 7. LI S T O F T A B L E S ............................................................................................................ ..................... 3 0 
1 8. LI S T O F FI G U R E S ........................................................................................................... .................... 3 0 
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S .............................................................................. 3 0  
A N N E X 2. A D DI TI O N A L I N F O R M A TI O N .......... ................................................................................... 30  
 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 6 of 3 0  
 
1.  LI S T O F A B B R E VI A TI O N S 
A b bre vi ati o n
 Defi niti o n
 
C A 1 9- 9
 Car b o h y drate
 
a nti ge n 1 9- 9
 
C E A
 Carci n oe m br y o nic a nti g e n 
C R
 C o m plete
 
Res p o nse
 
C T C A E  
C o m m o n Ter mi n ol o g y Crit eria f or A d verse E ve nts 
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 D C  
Electr o nic Data Ca pt ure 
H E R 2  
H u ma n E pi der mal gr o wt h fact or Rece pt or T y pe 2 
I E C
 I n de pe n de nt
 
Et hics C o m mittee 
I R B
 I nstit uti o nal
 
Re vie w
 
B oar d
 
L V E F  
Left ve ntric ular ejecti o n fracti o n 
M U G A
 M ulti p le-g ate d ac q uisiti o n tec h ni q ue 
N E
 N ot
 
E val ua ble
 
P D
 Pr o gressi ve
 
Disease
 
P R
 Percial
 
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 
S D
 Sta ble
 
Disease
 
S A P  
Statistical A nal ysis Pla n 
2.  R E S P O N SI B L E P A R TI E S 
T he Ja pa n G o o d P ost mar keti n g St u d y Practice officer 
3.  A M E N D M E N T S A N D U P D A T E S 
A me n d me nt 
n u m ber 
D ate 
Pr ot oc ol 
secti o n(s) 
c h a n ge d 
S u m m ar y of 
a me n d me nt(s) 
Re as o n 
A me n de d 4 
2 2 Dece m ber 
2 0 2 2 
C o ver pa ge 
C ha n ge of t he 
c o m pa n y l o g o 
C ha n ge of t he 
l o g o 
S T U D Y 
I N F O R M A TI O N 
C ha n ge of t he 
de part me nt of t he 
a ut h or 
Or ga nizati o nal 
c ha n ge 
4., 7. 6. 1., 7. 6. 5., 
7. 9., 8. 4. 
A d diti o n of ite ms 
a n d u p dates of 
descri pti o ns 
A dj ust me nt of 
descri pti o n 
5 
U p dates of 
mi nisterial 
or di na nce, 
n otificati o n, etc. 
Partial 
a me n d me nt t o t he 
mi nisterial 
or di na nce 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 7 of 3 0  
9. ，9. 4. 1. ，9. 5. 
C ha n ges of 
Ja pa nese tra nslati o n 
a n d a dj ust me nt of 
descri pti o n 
C ha n ges 
ass ociate d wit h 
re visi o n of t he 
i nter nal f or mat 
F or mer 1 1 
Deleti o n ( m o vi n g 
u p t he f oll o wi n g 
n u m bers) 
A dj ust me nt of 
descri pti o n 
ass ociate d wit h 
t he n otificati o n of 
“ Esta blis h me nt 
a n d P u blicati o n of 
Ris k Ma na ge me nt 
Pla n” date d 
Marc h 1 8, 2 0 2 2 
1 1. 
U p dates of t he 
sc o pe of c o ntracte d 
w or k a n d 
a dj ust me nt of 
descri pti o n 
E x pa nsi o n of t he 
sc o pe of 
c o ntracte d w or k 
1 5. 1. 
C ha n ge of t he 
de part me nt na me i n 
c o ntact i nf or mati o n 
a n d a dj ust me nt of 
descri pti o n 
Or ga nizati o nal 
c ha n ge 
1 5. 2. 
C ha n ge of t he 
tele p h o ne n u m ber 
i n c o ntact 
i nf or mati o n a n d 
a dj ust me nt of 
descri pti o n 
C ha n ge of t he 
p h o ne n u m ber i n 
c o ntact 
i nf or mati o n 
1 7 
U p date of t he 
rele va nt pa ge 
A dj ust me nt of 
descri pti o n 
A me n de d 3  
3 1 Ma y 2 0 2 1 
S T U D Y 
I N F O R M A TI O N 
C ha n ges of versi o n 
i de ntifier, date of 
pre parati o n, a n d 
a ut h or 
C ha n ge of versi o n 
i de ntifier a n d 
pers o n i n c har ge 
4. 
MI L E S T O N E S 
Clarificati o n of t he 
date of start of t he 
st u d y 
C ha n ge of t he date 
of st u d y 
c o m pleti o n/ date of 
pre parati o n of fi nal 
Beca use t he 
ti mi n g of t he start 
of t he st u d y 
beca me clear 
Pr ol o n gati o n of 
t he i n vesti gati o n 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 8 of 3 0  
re p ort
 peri o d
 
7. 2. 4. Pla n ne d 
st u d y peri o d 
C ha n ge of t he 
i n vesti gati o n 
peri o d/re gistrati o n 
peri o d 
Pr ol o n gati o n of 
t he i n vesti gati o n 
peri o d/re gistrati o
n peri o d 
A me n de d 2  
2 4 J u ne 2 0 1 9 
7. 6. 4. Patie nt 
Re gistrati o n 
( E D C) 
Descri pti o n of t he 
peri o d of patie nt 
re gistrati o n 
Setti n g of t he 
re gistrati o n peri o d 
as a ma n dat or y 
pr oce d ure 
A me n de d 1  
2 4 Ma y 2 0 1 9  
S T U D Y 
I N F O R M A TI O N 
C ha n ge of 
res p o nsi ble 
pers o n nel 
A dj ust me nt of 
descri pti o n 
ass ociate d wit h 
re visi o n of 
i nter nal sta n dar d 
f or ms 
9
 A d diti o n
 
of
 
t he
 
secti o n f or 
ma na ge me nt a n d 
re p orti n g of a d verse 
e ve nts/a d verse 
reacti o ns  
C o ver pa ge, etc.  
C orrecti o n of ter ms 
I nitial 
2 8 Marc h 
2 0 1 9 
N/ A
 N/ A
  
N/ A
 
 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 9 of 3 0  
 
4.  MI L E S T O N E S 
Milest o ne
 Pl a n ne d
 
d ate
Start of t he st u d y  
A u g ust 2 0 1 9 
Start of data c ollecti o n (re gistrati o n of t he first 
patie nt)  
Ar o u n d A u g ust 2 0 2 3 
C o m pleti o n of t he st u d y 
Fe br uar y 2 0 2 5 
E n d of data c ollecti o n (release of t he data base)  
Ar ou n d Se pte m ber 2 0 2 5 
Fi nal st u d y re p ort 
Wit hi n 7 years after t he start of 
mar keti n g 
 
5.  R A TI O N A L E A N D B A C K G R O U N D 
T R A S T U Z U M A B B S f or I n tra ve n o us I nf usi o n 6 0 m g [ Pfizer] a n d T R A S T U Z U M A B B S f or 
I ntra ve n o us I nf usi o n 1 5 0 m g [ Pfizer] ( ge neric na me: trast uz u ma b [ ge netical rec o m bi nati o n] 
[ Trast uz u ma b Bi osi milar 3]) ( herei nafter referre d t o as t his dr u g) are bi osi milar pr o d ucts of 
t he bi ol o gic pr o d uct Herce pti n (t he ge neric na me of t he pr o d uct a p pr o ve d i n Ja pa n: 
trast uz u ma b [ ge netical rec o m bi nati o n], a n d t he pr o d uct na me: H E R C E P TI N f or I njecti o n 6 0 
a n d H E R C E P TI N f or I njecti o n 1 5 0). 
T his ge neral i n vesti gati o n ( herei nafter, t his st u d y) is i nte n de d t o i n vesti gate t he safet y a n d 
efficac y of t his dr u g u n der t he act ual use i n patie nts wit h u nresecta ble a d va nce d/rec urre nt 
gastric ca ncer wit h H E R 2 o vere x pressi o n. 
T his St u d y s hall be c o n d ucte d i n strict c o m plia nce wit h t he " M H L W Or di na nce o n t he 
Sta n dar d f or P ost- Mar keti n g St u dies a n d Cli nical Trials of Me dical Pr o d ucts" ( M H L W 
Or di na nce N o. 1 7 1, date d Dece m ber 2 0, 2 0 0 4) , t he " E nf orce me nt of t he M H L W Or di na nce 
o n t he Sta n dar d f or P ost- mar keti n g St u dies a n d Cli nical Trials of Me dical Pr o d ucts" ( P F S B 
N otificati o n N o. 1 2 2 0 0 0 8, date d Dece m ber 2 0 , 2 0 0 4), t he " M H L W Or di na nce o n Sta n dar ds 
f or P ost- mar keti n g Safet y C o ntr ol of Me diccal Pr o d ucts, Q uasi- me dical Pr o d ucts, C os metics, 
Me dical De vices a n d Re ge nerati ve Me dica l Pr o d ucts" ( M H L W Or di na nce N o. 1 3 5, date d 
Se pte m ber 2 2, 2 0 0 4), t he " E nf orce me nt of t he M H L W Or di na nce o n Sta n dar ds f or P ost-
mar keti n g Safet y C o ntr ol of Me dical Pr o d ucts , Q uasi- me dical Pr o d ucts, C os metics, Me dical 
De vices, a n d Re ge nerati ve Me dical Pr o d ucts " ( P F S B N otificati o n N o. 0 8 1 2- 4, date d A u g ust 
1 2, 2 0 1 4), t he " M H L W Or di na nce t o Partiall y A me n d t he M H L W Or di na nce o n t he Sta n dar d 
f or P ost- mar keti n g St u dies a n d Cli nical Trials of Me dical Pr o d ucts" ( M H L W Or di na nce N o. 
1 1 6, date d Oct o ber 2 6, 2 0 1 7), a n d " A n n o u nce me n t of t he M H L W Or di na nce t o Partiall y 
A me n d t he M H L W Or di na nce o n t he Sta n dar d f or P ost- mar keti n g St u dies a n d Cli nical Trials 
of Me dical Pr o d ucts ( Re gar di n g t he M H L W Or di na nce o n t he Sta n dar d f or P ost- Mar keti n g 
St u dies a n d Cli nical Trials of Me dical Pr o d uc ts)" ( P S E H B N otificati o n N o. 1 0 2 6- 1, date d 
Oct o ber 2 6, 2 0 1 7). 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 0 of 3 0  
6.  R E S E A R C H Q U E S TI O N A N D O B J E C TI V E S 
T o c o nfir m t he safet y a n d efficac y of t his dr u g u n der t he act ual use. 
6. 1.  S afet y S pecific ati o ns 
[I m p ort a nt I de ntifie d Ris ks] 
•  Car diac dis or der 
•  I nf usi o n reacti o ns 
•  Hae mat ot o xicit y 
•  I nterstitial p ne u m o nia/l u n g dis or der 
•  He patic fail ure/li ver dis or der 
•  C o ma, cere br o vasc ular dis or der, brai n oe de ma 
•  Re nal dis or der 
•  I nfecti o n 
•  T u m o ur l ysis s y n dr o me 
7.  R E S E A R C H M E T H O D S 
7. 1.  St u d y Desi g n 
T his st u d y is a n o pe n-la bel, m ultice nter, o ne  ar m pr os pecti ve o bser vati o nal c o h ort st u d y i n 
patie nts wit h u nresecta ble a d va nce d/rec urre nt gastric ca ncer w h o ha ve bee n c o nfir me d t o 
ha ve H E R 2 o vere x pressi o n  recei vi n g t his dr u g. T he i n vesti gat ors c o m plete t he case re p ort 
f or m ( C R F) base d o n t he i nf or mati o n e xtracte d fr o m t he me dical rec or d create d i n dail y 
me dical practice. 
7. 2.  Setti n g 
Patie nts w h o satisf y all of t he re gistrati o n criteria are s u bject t o t his st u d y. 
7. 2. 1.  Re gistr ati o n criteri a 
Patie nts w h o meet all of t he f oll o wi n g re gistrati o n criteria t o be eli gi ble f or i ncl usi o n i n t his 
st u d y. 
1.  Patie nts wit h u nresecta ble a d va nce d/rec urre nt gastric ca ncer w h o are c o nfir me d t o ha ve 
H E R 2 o vere x pressi o n a n d starte d treat me nt wit h t his dr u g * 
2.  Patie nts w h o recei ve t his dr u g * f or t he first ti me after t his dr u g* is la u nc he d 
Refer t o t he latest pac ka ge i nsert of t his dr u g w he n t his dr u g is a d mi nistere d. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 1 of 3 0  
* N ot i ncl u di n g t he bi ol o gical pr o d uct, H E R C E P TI N, a n d bi osi milars of H E R C E P TI N ot her 
t ha n t his dr u g 
7. 2. 2.  E xcl usi o n criteri a 
E xcl usi o n criteria are n ot s pecifie d i n t his st u d y. 
7. 2. 3.  St u d y sites 
T he s ur ve y will be c o n d ucte d at a p pr o xi matel y 5 0 me dical i nstit uti o ns i ncl u di n g t he 
de part me nt of me dical o nc ol o g y, t he de part me nt  of s ur gical o nc ol o g y, t he de part me nt of 
gastr oi ntesti nal s ur ger y, a n d t he de pa rt me nt of gastr oi ntesti nal me dici ne. 
7. 2. 4.  Pl a n ne d st u d y peri o d 
T he pla n ne d peri o d of c o vere d b y t his st u d y is as f oll o ws. 
I n vesti gati o n peri o d: A u g ust 2 0 1 9 t o Fe br uar y 2 0 2 5 (fr o m t he start of t he re gistrati o n peri o d 
t o t he c o m pleti o n of t he o bser vati o n peri o d of t he last patie nt) 
Re gistrati o n peri o d: A u g ust 2 0 1 9 t o A u g ust 2 0 2 4 
7. 2. 5.  St u d y pr oce d ures 
7. 2. 5. 1.  St u d y met h o d 
Ce ntral re gistrati o n s yste m: Patie nts meeti n g t he re gistrati o n criteria will be re gistere d u ntil 
data are c ollecte d o n a tar g et n u m ber of patie nts. 
7. 2. 6.  O bser v ati o n peri o d 
T he start of o bser vati o n is defi ne d as t he first da te of t he a d mi nistrati o n of t his dr u g ( Da y 1), 
a n d t he o bser vati o n peri o d lasts u ntil 2 8 da ys after t he last d ose wit hi n 2 4 wee ks fr o m t he 
start of a d mi nistrati o n, t he first d ose of t his dr u g a d mi nistere d m ore t ha n 2 4 wee ks after t he 
start of a d mi nistrati o n, or t he start of t he ne xt treat me nt, w hic he ver c o mes first. 
H o we ver, if a d mi nistrati o n of t his dr u g is  disc o nti n ue d i n earlier t ha n 2 4 wee ks, t he 
o bser vati o n peri o d will be u ntil 2 8 da ys after t he date of disc o nti n uati o n of t his dr u g or t he 
start of t he ne xt treat me nt, w hic he ver c o mes first. 
7. 3.  V ari a bles 
T his st u d y will be c o n d ucte d acc or di n g t o  t he o bser vati o n sc he d ule i n Ta ble 1. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 2 of 3 0  
T a ble 1.  
V ari a bles a n d sc he d ule of o bser v ati o n 
 
Varia ble  
Re gistrati o n 
f or m 
Case re p ort f or m  
At re gistrati o n 
O bser vati o n peri o d 
U ntil 2 4 wee ks fr o m t he 
start of a d mi nistrati o n * 
I D n u m ber 
● 
○ 
Ge n de r 
● 
○ 
Year of birt h 
● 
○ 
Date of t he start of a d mi nistrati o n of t his dr u g  
● 
○ 
C o nfir mati o n of eli g i bility  
● 
 
I nf or me d c o nse nt 
 
● 
B o d y  weig h t 
 
● 
Disease, disease sta ge, lesi o n site, date of i nitial dia g n osis of 
g astric ca ncer 
 
● 
Fa mil y  hist ory  of malig na nc y  
 
● 
Me dical hist or y  
 
● 
Prese nce/a bse nce of hist or y of trast uz u ma b pr o d ucts use, dr u g 
na me, tar g et disease 
 
● 
P re vi o us treat me nt dr u g s/c o nc o mita nt me dicati o ns 
 
● 
N o n- dr u g  t hera py  
 
● 
Tar g ete d dr ug  use rec ord  
 
● 
Tests 
 
● 
E C O G P S 
 
● 
Effecti ve ness e val uati o n 
 
● 
Pre g na nc y  ( Fe male O nly ) 
 
● 
Rec or ds of c o nti n uati o n/ disc o nti n uati o n (c o m pleti o n) of st u d y 
a n d c o m pleti o n of o bser vati o n 
 
● 
A d verse e ve nts 
 
● 
○: S o me ele me nts i n t he Re gistrati o n F or m are a ut o mati call y refl ecte d i n t he C R F. I n ve sti gat ors s h o ul d c h ec k a n d u p date t he C R F as 
nee de d.
 
 
*: If a d mi nistrati o n of t his dr u g is disc o nti n ue d i n earlier t ha n  2 4 wee ks, t he o bser v ati o n p erio d will be u ntil 2 8 da ys after t he dat e of 
disc o nti n uati o n of t his dr u g or t h e start of t he ne xt treat me nt, w hic h e ver c o mes first. I nf or mati o n bef ore t he start of a d mi nis trati o n is 
i ncl u d e d de pe n di n g o n t h e varia bles. 
7. 3. 1.  P atie nt c h ar acteristics 
E nter t he i nf or mati o n i n t he re gistrati o n f or m at t he start of a d mi nistrati o n of t his dr u g. 
1.  I D n u m ber 
2.  Ge n der 
3.  Year of birt h 
4.  Date of t he start of a d mi nistrati o n of t his dr u g 
5.  C o nfir mati o n of eli gi bilit y 
T he f oll o wi n g i nf or mati o n will be rec or de d i n C R F at t he start of a d mi nistrati o n of t his dr u g. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 3 of 3 0  
1.  I D n u m ber 
2.  Ge n der 
3.  Year of birt h 
4.  I nf or me d c o nse nt 
5.  B o d y wei g ht 
6.  Disease ( u nresecta ble a d va nce d/rec urre nt H E R 2- o vere x pressi n g gastric ca ncer), disease 
sta ge ( T N M), lesi o n site ( perit o ne u m, l y m p h n o de, li ver, ot hers), a n d date of i nitial 
dia g n osis of gastric ca ncer 
7.  Fa mil y hist or y of mali g na nc y 
8.  Me dical hist or y ( past hist or y a n d c o nc urre nt ill ness) (i ncl u di n g hist or y of aller g y a n d 
prese nce or a bse nce of he patic f u ncti o n dis or der) 
9.  Prese nce/a bse nce of hist or y of trast uz u ma b pr o d ucts use, * dr u g na me, tar get disease 
(a d va nce d/rec urre nt gastric ca ncer, breast ca ncer, a n d ot hers) 
* T he bi ol o gical pr o d uct, H E R C E P TI N, a n d bi osi milars of H E R C E P TI N ot her t ha n t his dr u g 
7. 3. 2.  A d mi nistr ati o n rec or d of t ar gete d dr u g 
T he f oll o wi n g i nf or mati o n will be rec or de d re gar di n g t he stat us of use of t his dr u g fr o m t he 
date of t he start of a d mi nistrati o n of t his dr u g t o t he date of t he e n d of t he o bser vati o n peri o d. 
1.  D ose per a d mi nistrati o n 
2.  Date of a d mi nistrati o n 
3.  Reas o n f or use (first-li ne t hera p y, sec o n d-li ne t hera p y, a n d ot hers) 
4.  Reas o n f or c ha n ge (a d verse e ve nts [ A Es], c ha n ge t o mai nte na nce d ose, a n d ot hers) 
7. 3. 3.  Pri or t her a p y ( dr u g t her a p y) 
E nter t he i nf or mati o n o n pre vi o us treat me nt dr u gs use d f or t he treat me nt of u nresecta ble 
a d va nce d/rec urre nt H E R 2- o vere x pressi n g gastric ca ncer bef ore t he start of a d mi nistrati o n of 
t his dr u g. H o we ver, t he dr u gs t hat are c o nti n u o usl y use d e ve n after t he start of a d mi nistrati o n 
of t his dr u g s h o ul d be e ntere d i n c o nc o mita nt t hera p y ( dr u g t hera p y). 
1.  Dr u g na me 
2.  R o ute of a d mi nistrati o n 
3.  Reas o n f or disc o nti n uati o n (i n t he case of di sc o nti n uati o n) (i na de q uate res p o nse, A Es, 
a n d ot hers) 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 4 of 3 0  
7. 3. 4.  C o nc o mit a nt t her a p y ( dr u g t her a p y) 
E nter t he f oll o wi n g i nf or mati o n o n t he dr u gs  use d f or t he treat me nt of u nresecta ble 
a d va nce d/rec urre nt H E R 2- o vere x pressi n g gastri c ca ncer fr o m t he date of t he start of 
treat me nt wit h t his dr u g t o t he date of t he e n d of t he o bser vati o n peri o d. 
1.  Dr u g na me 
2.  R o ute of a d mi nistrati o n 
3.  Date of t he start of a d mi nistrati o n a n d date of t he e n d of a d mi nistrati o n 
7. 3. 5.  C o nc o mit a nt t her a p y ( n o n- dr u g t her a p y) 
E nter t he f oll o wi n g i nf or mati o n o n t he n o n- dr u g t hera pies c o n d ucte d f or t he treat me nt of 
u nresecta ble a d va nce d/rec urre nt H E R 2- o vere x p ressi n g gastric ca ncer bet wee n 6 m o nt hs 
bef ore t he date of t he start of a d mi nistrati o n of t his dr u g a n d t he date of t he e n d of t he 
o bser vati o n peri o d. 
1.  Na me of t hera p y ( na me of s ur gical pr oce d ure f or s ur ger y, etc.) 
2.  Start date a n d e n d date 
7. 3. 6.  Dr u gs use d f or pre ve nti o n of i nf usi o n re acti o ns 
E nter t he f oll o wi n g i nf or mati o n o n dr u gs use d f or pre ve nti o n of i nf usi o n reacti o ns ca use d b y 
a d mi nistrati o n of t his dr u g. 
1.  Dr u g na me 
2.  R o ute of a d mi nistrati o n 
3.  Date of a d mi nistrati o n 
7. 3. 7.  Tests 
7. 3. 7. 1.  Cli nic al l a b or at or y tests 
E nter all of t he res ults of tests perf or me d at baseli ne (t he m ost rece nt data fr o m 3 m o nt hs 
bef ore t he date of t he start of a d mi nistrati o n of t his dr u g t o t he da y bef ore t he start of 
a d mi nistrati o n of t his dr u g) a n d d uri n g t he o bser vati o n peri o d. 
Cli nical la b orat or y tests: C E A, C A 1 9- 9, Q T, Q Tc, L V E F (ec h ocar di o gra m or M U G A 
sca n) 
7. 3. 8.  E C O G P S ( E aster n C o o per ati ve O n c ol o g y Gr o u p Perf or m a nce St at us) 
E nter t he data at baseli ne (t he m ost rece nt data  fr o m 3 m o nt hs bef ore t he date of t he start of 
a d mi nistrati o n of t his dr u g t o t he da y bef ore t he start of a d mi nistrati o n of t his dr u g) a n d at 
t he e n d of a d mi nistrati o n (t he m ost rece nt data bef ore t he e n d of t he o bser vati o n peri o d). 
1.  Date of e val uati o n 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 5 of 3 0  
2.  E val uati o n res ults 
7. 3. 9.  Pre g n a nc y (fe m ale o nl y) 
E nter t he pre g na nc y stat us fr o m t he date of t he start of a d mi nistrati o n of t his dr u g t o t he date 
of t he e n d of t he o bser vati o n peri o d. 
7. 3. 1 0.  E n d- of-st u d y ( disc o nti n u ati o n rec or d) 
E nter t he f oll o wi n g i nf or mati o n re gar di n g w het her or n ot treat me nt wit h t his dr u g is 
c o nti n ue d at t he e n d of t he o bser vati o n peri o d. 
1.  Date of t he e n d of t he o bser vati o n peri o d/ disc o nti n uati o n 
2.  Reas o n f or disc o nti n uati o n (c o m pleti o n) ( Select fr o m t he f oll o wi n g.) 
a. C o m plete d (treat me nt c o nti n ue d) 
b.  I ns ufficie nt cli nical effecti ve ness 
c. A d verse e ve nt ( E nter necessar y i nf or mati o n i n t he c ol u m n of A Es.) 
d.  Deat h ( E nter necessar y i nf or mati o n i n t he c ol u m n of A Es.) 
e. N o ret ur n visit 
f. Tra nsfer t o a n ot her h os pital/ de part me nt 
g.  Ot hers ( E nter reas o n f or disc o nti n uati o n.) 
7. 3. 1 1.  Effecti ve ness e v al u ati o n 
E nter t he f oll o wi n g ite ms fr o m baseli ne t o t he date of t he e n d of t he o bser vati o n peri o d. 
E nter t he i nf or mati o n as of t he ti me of disc o nti n uati o n if t he a d mi nistrati o n of t his dr u g is 
disc o nti n ue d. 
E val uate t he effecti ve ness of t his dr u g usi n g t he effecti ve ness assess me nt ite ms i n 
" G ui deli nes o n Ne w Res p o nse E val uati o n Criteria i n S oli d T u m ors, versi o n 1. 1" a n d e nter 
t he res ults. 
Assess me nt of t u m or res p o nse: Assess t he t u m o r res p o nse acc or di n g t o R E CI S T Ver. 1. 1. 
I de ntif y tar get lesi o ns a n d n o n-tar get lesi o ns i n t he classificati o n of t u m or lesi o ns at t he start 
of a d mi nistrati o n of t his dr u g, a n d c o nfir m t he prese nce or a bse nce of ne w lesi o ns i n a d diti o n 
t o t he res ults of assess me nt of t u m or res p o nse i n eac h t u m or lesi o n d uri n g t he o bser vati o n 
peri o d, a n d t he n e val uate o verall res p o nse. 
1.  Prese nce or a bse nce of tar get lesi o ns at t he start of a d mi nistrati o n of t his dr u g 
2.  Prese nce or a bse nce of effecti ve ness e val uati o n 
•  Date of assess me nt of best o verall res p o nse 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 6 of 3 0  
•  Best o verall res p o nse ( C R, P R, S D, P D, N E, N o n- C R/ N o n- P D) 
7. 3. 1 2.  A d verse e ve nts 
Occ urre nce of A Es fr o m t he start date of a d mi ni strati o n of t his dr u g t o t he e n d date of t he 
o bser vati o n peri o d s h o ul d be c o nfir me d a n d t he f oll o wi n g i nf or mati o n s ho ul d be rec or de d.  
Als o, f urt her i n vesti gati o n s h o ul d be se paratel y c o n d ucte d, if dee me d necessar y b y S p o ns or 
f or patie nts w h o e x perie nce d a seri o us a d verse reacti o n, a n u ne x pecte d a d verse reacti o n or 
ot her a d verse reacti o ns n ot liste d i n t he pac ka ge i nsert. 
•  Prese nce/a bse nce of A E 
•  Na me of A E 
•  Classificati o n of A E ( prese nce/a bse nce of i nf usi o n reacti o ns) 
•  Date of occ urre nce 
•  Se verit y of A E ( C T C A E Gra de ver. 5. 0) 
•  I nter ve nti o n 
•  C ha n ge i n a d mi nistrati o n of t his dr u g 
•  Seri o us ness 
•  O utc o me 
•  Date of res ol uti o n or rec o ver y/ date of deat h 
•  Date of o utc o me c o nfir mati o n 
•  Ca usal relati o ns hi p t o t his dr u g 
•  M ost li kel y ca use of A E 
7. 4.  D at a S o urces  
I n t his st u d y, t he i n vesti gat ors tra nscri be t he necessar y i nf or mati o n fr o m t he me dical rec or d 
u n der dail y me dical practice i n acc or da nce wit h t he F ull Pr ot oc ol. 
7. 5.  St u d y Size 
7. 5. 1.  Pl a n ne d s a m ple size 
1 0 0 patie nts as t he safet y a nal ysis set ( S A S) * 1 
* 1: T he safet y a nal ysis set is defi ne d as t he f ull a nal ysis set t hat is as cl ose as p ossi ble t o all 
patie nts treate d wit h t his dr u g. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 7 of 3 0  
7. 5. 2.  R ati o n ale f or s a m ple size 
B y acc u m ulati n g data fr o m 1 0 0 patie nts, it is p o ssi ble t o detect A Es wit h a tr ue i nci de nce of 
3 % or hi g her i n at least 1 patie nt wit h a pr o ba bilit y of a p pr o xi mat el y 9 5 % i n a ge neral 
i n vesti gati o n. 
7. 6.  D at a M a n a ge me nt 
7. 6. 1.  C ase re p ort f or m ( C R F)/ Electr o nic d at a rec or d 
As use d i n t his F ull Pr ot oc ol, t he ter m C R F s h o ul d be u n derst o o d t o refer t o a n electr o nic 
data rec or d, de pe n di n g o n t he data c ollecti o n met h o d use d i n t his st u d y. 
A C R F is re q uire d a n d s h o ul d be c o m plete d f or eac h i ncl u de d patie nt. T he c o m plete d 
ori gi nal C R Fs are t he s ole pr o pert y of Pfizer a n d s h o ul d n ot be ma de a vaila ble i n a n y f or m t o 
t hir d parties, e xce pt f or a ut h orize d re prese ntati ves of Pfizer or a p pr o priate re g ulat or y 
a ut h orities, wit h o ut writte n pe r missi o n fr o m Pfizer. T he i n vesti gat or s hall e ns ure t hat t he 
C R Fs are sec urel y st ore d at t he st u d y site i n e ncr y pte d electr o nic f or m a n d will be pass w or d 
pr otecte d or sec ure d i n a l oc ke d r o o m t o pr e ve nt access b y u na ut h orize d t hir d parties. 
T he i n vesti gat or has ulti mate res p o nsi bilit y f o r t he c ollecti o n a n d re p orti n g of all cli nical, 
safet y, a n d la b orat or y data e ntere d o n t he C R Fs a n d a n y ot her data c ollecti o n f or ms (s o urce 
d oc u me nts) a n d e ns uri n g t hat t he y are acc urate, a ut he ntic/ ori gi nal, attri b uta ble, c o m plete, 
c o nsiste nt, le gi ble, ti mel y (c o nte m p ora ne o us), e n d uri n g, a n d a vaila ble w he n re q uire d. T he 
C R Fs m ust be si g ne d b y t he i n vesti gat or or b y a n  a ut h orize d staff me m ber t o attest t hat t he 
data c o ntai ne d i n t he C R Fs are tr ue. A n y c orrec ti o ns t o e ntries ma de i n t he C R Fs or s o urce 
d oc u me nts m ust be date d, i n itiale d ( or sta m pe d "c orrecti on seal"), a n d e x plai ne d (if 
necessar y) a n d s h o ul d n ot o bsc ure t he ori gi nal e ntr y.  
T he s o urce d oc u me nts are t he h os pital or p h ysici a n's me dical rec or ds. I n t hese cases, data 
c ollecte d o n t he C R Fs m ust matc h t h ose rec or ds. 
7. 6. 2.  Rec or d rete nti o n 
T he rec or ds relate d t o t his st u d y s h o ul d be retai ne d at t he st u d y site u ntil t he E n d of St u d y 
Letter b y Pfizer is recei ve d or d uri n g t he peri o d defi ne d b y t he st u d y site, w hic he ver is l o n ger. 
7. 6. 3.  D at a c ollecti o n met h o d ( E D C) 
T he data f or t his st u d y will be c ollecte d a n d c o nfir me d b y usi n g t he electr o nic s yste m o n t he 
i nter net desi g ne d f or c ollecti n g p ost- mar keti n g s ur ve y data ( Electr o nic Data Ca pt ure, 
herei nafter referre d t o as E D C). 
7. 6. 4.  P atie nt re gistr ati o n ( E D C) 
T he i n vesti gat or will e nter i nf or mati o n o n t he patie nt re gistrati o n scree n of E D C (t he 
re gistrati o n f or m) a n d sa ve t he data. Patie nt re gistrati o n will be perf or me d wit hi n 2 7 da ys 
after t he first a d mi nistrati o n of t his dr u g. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 8 of 3 0  
If i nf or mati o n i n t he re gistrati o n f or m re q uire c o nfir mati o n, t he i n vesti gat or ma y be 
re q ueste d t o perf or m f oll o w- u p s ur ve y a n d res p o n d t o t he q uer y. Re gistrati o n will be fi xe d 
after t he q uer y is res ol ve d. 
7. 6. 5.  P oi nts t o c o nsi der f or e ntr y, re visi o n, a n d s u b missi o n of c ase re p ort f or m ( E D C) 
7. 6. 5. 1.  D at a e ntr y 
T he i n vesti gat or s h o ul d c o nfir m t he s ur ve y ite ms a n d e nter t he data i nt o E D C base d o n 
me dical rec or ds. 
7. 6. 5. 2.  D at a Re visi o n 
U p o n recei vi n g q uer y fr o m S p o ns or o n t he c o nte nts of t he C R F (f oll o w- u p s ur ve y), t he 
i n vesti gat or will a gai n c o nfir m t he c o nte nts of me dical rec or ds, a n d as re q uire d, c orrect 
rele va nt secti o ns a n d sa ve t he data. 
7. 6. 5. 3.  S u b missi o n 
After data e ntr y a n d re visi o n are c o m plete d, C R Fs s h o ul d be  si g ne d electr o nicall y b y t he 
i n vesti gat or f oll o wi n g c o nfir mati o n of e ntr y a n d f oll o w- u p s ur ve y. 
7. 7.  D at a A n al ysis 
1.  Defi niti o n of a nal ysis set 
T he S A S c o nsists of a f ull a nal ysis set t hat is as cl oser as p ossi ble t o all patie nts w h o 
recei ve d t his dr u g. T he efficac y a nal ysis set c o nsists of patie nts i ncl u de d i n t he S A S 
c o nsi dere d e val ua ble f or efficac y acc or di n g t o t he se paratel y prescri be d Statistical 
A nal ysis Pla n ( S A P). 
2.  Met h o d of a nal ysis 
•  
A nal ysis f or safet y e val uati o n 
E ve nts p ossi bl y relate d t o t his dr u g are c o nsi dere d as a d verse dr u g reacti o ns ( A D Rs). T he 
n u m ber of patie nts wit h A D Rs a n d t he pr o p o rti o n ([ %]: n u m ber of patie nts wit h A D Rs/ 
n u m ber of patie nts i ncl u de d i n t he S A S) will be calc ulate d. 
•  
A nal ysis f or effecti ve ness e val uati o n 
A nal yses f or effecti ve ness e val uati o n base d o n R E CI S T e val uati o n will be perf or me d. 
Detaile d met h o d ol o g y f or s u m mar y a n d statistical a nal yses of data c ollecte d i n t his st u d y will 
be d oc u me nte d i n t he S A P, w hic h will be date d, file d a n d mai ntai ne d b y t he S p o ns or.  T he 
S A P ma y m o dif y t he pla n o utli ne d i n t he pr ot oc ol; a n y maj or m o dificati o ns of pri mar y 
e n d p oi nt defi niti o ns or t heir a nal yses w o ul d be reflecte d i n a pr ot oc ol a me n d me nt. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 1 9 of 3 0  
7. 8.  Q u alit y C o ntr ol 
Pri or t o c o n d ucti n g  t he st u d y, t he pers o n nel i n c har ge of t he st u d y site will e x plai n t o t he 
i n vesti gat or a b o ut t he c o nte nts of t he F ull Pr ot oc ol, etc. a n d as k t he i n vesti gat or f or 
c o m pleti o n of a C R F base d o n me dical rec or ds. 
7. 9.  Li mit ati o ns of t he Rese arc h Met h o ds 
T here ma y be p ote ntial li mitati o n i n t his st u d y: 
1.  Si nce n o c o ntr ol gr o u p is i ncl u de d i n t he st u d y, t here is a li mitati o n i n deter mi ni n g 
w het her or n ot a ris k of de vel o pi n g A Es a n d a d verse reacti o ns i ncreases wit h 
a d mi nistrati o n of t his dr u g. 
2.  D ue c o nsi derati o n ma y n ot be gi ve n t o c o nf o u n di n g fact ors d ue t o i ns ufficie nt 
bac k gr o u n d i nf or mati o n c ollecte d. 
3.  Si nce t his st u d y c ollects i nf or mati o n descri be d i n me dical rec or ds, s pecifie d data ma y n ot 
be c ollecte d or ma y be missi n g. 
7. 1 0.  Ot her As pects 
N ot a p plica ble 
8.  P R O T E C TI O N O F H U M A N S U B J E C T S 
8. 1.  P atie nt I nf or m ati o n 
All parties will c o m pl y wit h all a p plica ble la ws, i ncl u di n g la ws re ga r di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical me as ures t o e ns ure pr otecti o n of data of patie nts pers o nal 
data. S uc h meas ures will i ncl u de o mitti n g patie nt  na mes or ot her directl y i de ntifia ble data i n 
a n y re p orts, p u blicati o ns, or ot her discl os ures e xce pt w here re q uire d b y a p plica ble la ws. T he 
pers o nal data will be st ore d at t he st u d y site  i n e ncr y pte d electr o nic a n d/ or pa per f or m a n d 
will be pass w or d pr otecte d or sec ure d i n a l oc k e d r o o m t o e ns ure t hat o nl y a ut h orize d st u d y 
staff ha ve access. T he st u d y sites will i m ple me nt a p pr o priate tec h nical a n d or ga nizati o nal 
meas ures t o e ns ure t hat t he pers o nal data ca n be  rec o vere d i n t he e ve nt of a disaster. I n t he 
e ve nt of a p ote ntial pers o nal data breac h, t he st u d y site s hall be res p o nsi ble f or deter mi ni n g 
w het her a pers o nal data breac h ha s i n fact occ urre d a n d, if s o, pr o vi di n g breac h n otificati o ns 
as re q uire d b y la w. 
 
T o pr otect t he ri g hts a n d free d o ms of nat ural pers o ns wit h re gar d t o t he pr ocessi n g of 
pers o nal data, w he n st u d y data are c o m pile d f o r tra nsfer t o Pfizer a n d ot her a ut h orize d 
parties, patie nt na mes will be re m o ve d a n d will be re place d b y a si n gle, s pecific, n u merical 
c o de, base d o n a n u m beri n g s yste m defi ne d b y Pf izer. All ot her i de ntifia ble data tra nsferre d 
t o Pfizer or ot her a ut h orize d parties will be i de ntifie d b y t his si n gle, patie nt-s pecific c o de. 
T he st u d y site will mai ntai n a c o nfi de ntial lis t of patie nts w h o partici pate d i n t he st u d y, 
li n ki n g eac h patie nt's n u merical c o de t o his/ her act ual i de ntit y. I n case of data tra nsfer, Pfizer 
will mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr otecti o n of patie nt's pers o nal data 
c o nsiste nt wit h t he cli nical st u d y a gree m e nt a n d a p plica ble pri vac y la ws ( Pers o nal 
I nf or mati o n Pr otecti o n La w). 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 0 of 3 0  
8. 2.  P atie nts C o nse nt 
I n pri nci ple, t he i nf or mati o n pr o vi de d t o Pfizer i n t his st u d y d oes n ot c orres p o n d t o t he 
pers o nal i nf or mati o n s pecifie d i n  t he Pers o nal I nf or mati o n Pr otecti o n La w or is pr o vi de d 
base d o n t he la ws a n d re g ulati o ns  (e ve n if it c orres p o n ds t o pers o nal i nf or mati o n u n der t he 
Pers o nal I nf or mati o n Pr otecti o n La w). T heref ore, it is n ot necessar y t o o btai n t he patie nt's 
c o nse nt t o t he pr o visi o n of pers o nal i nf or mati o n fr o m t he st u d y site t o Pfizer. Si milarl y, it is 
n ot necessar y t o o btai n i nf or me d c o nse nt fr o m patie nts beca use re p orti n g or s u b missi o n of 
i nf or mati o n a n d res ults o btai ne d i n t his st u d y fr o m Pfizer t o Ja pa nese re g ulat or y a ut h orities 
or pr o visi o n of i nf or mati o n t o healt hcare pr ofessi o nals as necessar y is base d o n t he 
a p plica ble la ws a n d re g ulati o ns. 
I n t his st u d y, Pfizer will c ollect i nf or mati o n t hat ca n n ot i de ntif y s pecific patie nts fr o m t he 
st u d y sites. T he res ults of t his st u d y, w hic h are pre pare d n ot t o i de ntif y s pecific patie nts, ma y 
be re p orte d t o Pfizer I nc. or Gr o u p c o m pa nies, or re g ulat or y a ut h orities i n ot her c o u ntries, as 
nee de d, or p u blis he d it as a prese ntati o n at aca de mic c o nfere nces or ma n uscri pt f or t he 
p ur p ose of pr o vi di n g pr o per use i nf or mati o n f o r t his dr u g. If t hese i nf or mati o n falls u n der 
pers o nal i nf or mati o n of t he Pers o nal I nf or mati o n Pr otecti o n La w, t hese acti o ns ma y n ot be 
base d o n t he la ws or re g ulati o ns , a n d t heref ore, ma y c orres p o n d t o pr o visi o n t o t he t hir d 
part y a n d usi n g t he i nf or mati o n f or p ur p oses ot her t ha n b usi ness t hat re q uire c o nse nt fr o m 
t he patie nt. T heref ore, t he st u d y sites will o btai n writte n or ver bal c o nse nt fr o m t he patie nts 
t o be i ncl u de d i n  t his st u d y s o t hat Pfizer ca n use t he res ults of t his st u d y t o re p ort t o Pfizer 
I nc., gr o u p c o m pa nies or re g ulat or y a ut h orities i n ot her c o u ntries, or t o prese nt it at aca de mic 
c o nfere nces or p u blis h ma n uscri pt, etc. W het her c o nse nt is o btai ne d fr o m patie nts or n ot is 
descri be d i n t he C R F. T he ori gi nal of t he writte n  i nf or me d c o nse nt f or m s h o ul d be retai ne d 
b y t he st u d y i n vesti gat or.  
I n ge neral, t he i n vesti gat or m ust o btai n c o nse nt fr o m a patie nt pers o na ll y. H o we ver, if t he 
i n vesti gat or deter mi nes t hat a patie nt’s decisi o nal ca pacit y is s o li mite d t hat he/s he ca n n ot 
reas o na bl y be c o ns ulte d or he/s he is a mi n or, c o nse nt is o btai ne d fr o m le gall y acce pta ble 
re prese ntati ve or pare nt(s). I n t his case, e very eff ort s h o ul d be ma de t o o btai n t he patie nt’s 
asse nt as far as p ossi ble after o btai ni n g c o ns e nt fr o m le gall y acce pta ble re prese ntati ve or 
pare nt(s) if a mi n or. If t he st u d y patie nt d oes n ot pr o vi de his/ her o w n c o nse nt, t he s o urce 
d oc u me nts m ust rec or d t he relati o ns hi p of t h e pers o n si g ni n g t he c o nse nt t o t he patie nt  (e. g., 
pare nt(s), s p o use). If a mi n or re gistere d i n t he st u d y reac hes a d ult h o o d d uri n g t he st u d y, t he 
c o nse nt will be ac q uire d as far as p ossi ble fr o m t he patie nt at t he ti me of a d ult h o o d acc or di n g 
t o Ja pa nese la w. 
At t he ti me of o btai ni n g i nf or me d c o nse nt, t h e i n vesti gat or m ust use i nf or me d c o nse nt f or m 
a n d ot her materials a n d e ns ure t hat eac h st u d y patie nt, or his/ her le gall y acce pta ble 
re prese ntati ve, or pare nt(s) if a mi n or, is f ull y i nf or me d a b o ut t he i nf or mati o n pr o vi de d t o 
Pfizer a n d t he o bjecti ves of use a n d p ossi ble ris ks ass ociate d wit h c o nse nt. 
8. 3.  I nstit uti o n al Re vie w B o ar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) 
I n t his st u d y, re vie w b y t he I nstit uti o nal Revie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee 
(I E C) is n ot re q uire d. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 1 of 3 0  
8. 4.  Et hic al C o n d uct of t he St u d y 
T his st u d y will be c o n d ucte d i n c o m plia nce wit h t he mi nisterial or di na nces, etc. i n " 5. 
R A TI O N A L E A N D B A C K G R O U N D," a n d will als o be  c o n d ucte d i n acc or da nce wit h le gal 
a n d re g ulat or y re q uire me nts, as well as wit h scie ntific p ur p ose, val ue a n d ri g or. 
9.  M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E D R U G 
R E A C TI O N S 
9. 1.  Re q uire me nts f or Rec or ds a n d Re p orti n g 
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g safet y e ve nts i n t he C R Fs a n d f or 
re p orti n g safet y e ve nts o n t he N o n-I nter ve nti o nal St u d y ( NI S) A d verse E ve nt M o nit ori n g 
( A E M) Re p ort F or m t o Pfizer Safet y. T hese re q uire me nts are deli neate d f or 3 t y pes of 
e ve nts: ( 1) seri o us A Es ( S A Es); ( 2) n o n-seri o us A Es (as a p plica ble); a n d ( 3) sce nari os 
i n v ol vi n g dr u g e x p os ure, i ncl u di n g dr u g e x p os ure d uri n g pre g na nc y, e x p os ure d uri n g 
breastfee di n g, me dicati o n err or, o ver d ose, mi s use, e xtra vasati o n, lac k of efficac y, a n d 
occ u pati o nal e x p os ure.  T hese e ve nts are defi ne d i n t he secti o n of “ Defi niti o n of Safet y 
E ve nts.” 
S afet y E ve nt 
Rec or d o n t he C R F 
Re p ort e ve nts t o Pfizer 
S afet y wit hi n 2 4 H o urs 
of A w are ness usi n g t he 
NI S A E Re p ort F or m 
Seri o us A Es 
All 
All 
N o n-seri o us A Es 
All 
N o ne  
Sce nari os i n v ol vi n g e x p os ure 
t o a dr u g u n der st u d y, 
i ncl u di n g e x p os ure d uri n g 
pre g na nc y, e x p os ure d uri n g 
breastfee di n g, me dicati o n 
err or, o ver d ose, mis use, 
e xtra vasati o n, lac k of efficac y, 
a n d occ u pati o nal e x p os ure 
All (re gar dless of w het her 
ass ociate d wit h a n A E) e xce pt 
occ u p ati o n al e x p os ure  
All (re gar dless of 
w het her ass ociate d wit h 
a n A E) 
N ote: A n y ass ociate d 
A E is re p orte d t o get her 
wit h t he e x p os ure 
sce nari o. 
 
F or eac h A E, t he i n vesti gat or m ust p urs ue a n d o btai n a de q uate i nf or mati o n b ot h t o deter mi ne 
t he o utc o me a n d t o assess w het her it meets t he criteria f or classificati o n as a n S A E ( See t he 
secti o n of " Seri o us A d verse E ve nts" bel o w). 
T he safet y e ve nts f or w hic h re p orti n g t o Pfizer Safet y is re q uire d i n t he ta ble a b o ve m ust be 
re p orte d t o Pfizer Safet y wit hi n 2 4 h o urs of a ware ness of t he e ve nt b y t he i n vesti gat or, 
w het her or n ot t he i n vesti g at or deter mi nes t h at t he e ve nt is rel ate d t o t his dr u g.  I n 
partic ular, if t he S A E is fatal or life-t hreate ni n g, n otificati o n t o Pfizer  Safet y m ust be ma de 
i m me diatel y, irres pecti ve of t he e xte nt of a vaila ble i nf or mati o n. T his ti mefra me als o a p plies 
t o a d diti o nal ne w (f oll o w- u p) i nf or mati o n o n a pre vi o usl y f or war de d re p orts. I n t he rare 
sit uati o n t hat t he i n vesti gat or d oes n ot bec ome i m me diatel y a ware of t he occ urre nce of a 
safet y e ve nt, t he i n vesti gat or m ust re p ort t he e ve nt wit hi n 2 4 h o urs after lear ni n g of it a n d 
d oc u me nt t he ti me of his/ her fi rst a ware ness of t he e ve nt. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 2 of 3 0  
F or safet y e ve nts t hat are c o nsi dere d seri o us or are s pecifie d i n t he far ri g ht c ol u m n of t he 
ta ble a b o ve as re q uiri n g re p orti ng t o Pfizer Safet y wit hi n 2 4 h o urs of a ware ness, t he 
i n vesti gat or m ust c o n d uct f oll o w- u p a n d re p ort a ny a d diti o nal i nf or mati o n t o Pfizer Safet y i n 
acc or da nce wit h t he 2 4 h o ur ti mefra me. I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y 
Pfizer Safet y t o o btai n s pecific f oll o w- u p i nf or mati o n i n a n e x pe dite d fas hi o n. T his 
i nf or mati o n is re q uire d t o be m ore detaile d t ha n t he i nf or mati o n rec or de d i n t he C R F. I n 
ge neral, t his i nf or mati o n will i ncl u de a descri pt i o n of t he e ve nt i n s ufficie nt detail t o all o w 
f or a c o m plete me dical assess me nt of t he A E a n d e na bli n g i n de pe n de nt deter mi nati o n of 
p ossi ble ca usalit y. I nf or mati o n o n t he e ve nt (c o nc o mita nt dr u gs, c o m plicati o ns, etc.) m ust 
als o be pr o vi de d. I n t he e ve nt of a patie nt’s deat h, a s u m mar y of a vaila ble a ut o ps y fi n di n gs 
m ust be pr o m ptl y pr o vi de d t o Pfizer Safet y or pers o ns t o w h o m Pfizer o uts o urces s uc h 
o perati o ns.  
9. 2.  Re p orti n g Peri o d 
T he re p orti n g peri o d f or eac h patie nt's safet y e ve nt (see t he ta ble a b o ve) t o Pfizer Safet y 
be gi ns wit h t he first a d mi nistrati o n of t his dr u g t o t he patie nt a n d e n ds at t he e n d of t he 
o bser vati o n peri o d f or t he s ur ve y, b ut is at least 2 8 da ys (cale n dar da y) after t he last d ose of 
t his dr u g. If safet y e ve nts of t he t y pes liste d i n t he ta ble a b o ve occ ur d uri n g t his re p orti n g 
peri o d, t he i n vesti gat or s h o ul d s u b mit a re p ort t o Pfizer Safet y u nit of Pfizer ( or pers o ns t o 
w h o m Pfizer o uts o urces s uc h o perati o ns). If a patie nt is recei vi n g t his dr u g o n t he last da y of 
t he o bser vati o n peri o d, t he re p orti n g peri o d s h o ul d be e xte n de d t o 2 8 da ys (cale n dar da y) 
after t he e n d of t he o bser vati o n peri o d.  
If t he i n vesti gat or lear ns of a n y S A E occ urri n g at a n y ti me after c o m pleti o n of t he s ur ve y a n d 
he/s he c o nsi ders t he S A E t o be re late d t o t his dr u g, t he S A E s h o ul d als o be re p orte d t o Pfizer 
Safet y. 
9. 3.  C a us alit y Assess me nt 
T he i n vesti gat or m ust assess a n d rec or d ca usalit y. I n a d diti o n, t he i n vesti gat or s h o ul d o btai n 
s ufficie nt i nf or mati o n t o deter mi ne t he ca usal relati o ns hi p of eac h A E. F or A Es relate d t o 
t his dr u g, f oll o w- u p b y t he i n vesti gat or is re q uire d u ntil t he e ve nt or its se q uelae res ol ves, or 
sta bilizes at a le vel acce pta ble t o t he i n vesti gat or, a n d Pfizer a grees wit h t hat assess me nt. 
T he i n vesti gat or's ca usalit y assess me nt will be base d o n w het her t here is a reas o na ble 
p ossi bilit y t hat t he dr u g ca use d or c o ntri b ute d t o t he A E. If t he i n vesti gat or's fi nal 
deter mi nati o n of ca usalit y is  " u n k n o w n" a n d he/s he ca n n ot deter mi ne w het her t his dr u g 
ca use d t he e ve nt, t he safet y e ve nt m ust be re p orte d wit hi n 2 4 h o urs. 
If t he i n vesti gat or ca n n ot i de ntif y t he ca use of t he e ve nt, b ut deter mi nes t hat t his dr u g d oes 
n ot ca use t he e ve nt, t his s h o ul d be clearl y d oc u me nte d i n t he C R F a n d NI S A E Re p ort F or m. 
9. 4.  Defi niti o n of S afet y E ve nts 
9. 4. 1.  A d verse e ve nts 
A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt a d mi nistere d a me dici nal pr o d uct. 
T he e ve nt d oes n ot necessaril y ha ve a ca usal relati o ns hi p wit h t he a d mi nistrati o n or use of 
t he pr o d uct. E xa m ples of A Es i ncl u de, b ut are n ot li mite d t o:  
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 3 of 3 0  
•  A b n or mal test fi n di n gs ( See bel o w f or c o n diti o ns u n der w hic h a b n or mal la b orat or y 
fi n di n gs c o nstit ute a n A E.); 
•  Cli nicall y si g nifica nt s y m pt o ms a n d si g ns; 
•  C ha n ges i n p h ysical e xa mi nati o n fi n di n gs; 
•  H y perse nsiti vit y; 
•  Lac k of efficac y; 
•  Dr u g a b use; 
•  Dr u g de pe n de nc y. 
I n a d diti o n, A Es ma y i ncl u de si g ns a n d s y m pt o ms res ulti n g fr o m: 
•  Dr u g o ver d ose; 
•  Dr u g wit h dra wal; 
•  Dr u g mis use; 
•  Off-la bel use; 
•  Dr u g i nteracti o ns; 
•  E xtra vasati o n; 
•  E x p os ure d uri n g pre g na nc y; 
•  E x p os ure d uri n g breastfee di n g; 
•  Me dicati o n err or; 
•  Occ u pati o nal e x p os ure. 
A b n or mal test fi n di n gs 
T he criteria f or deter mi ni n g w het her a n a b n or mal  test fi n di n g s h o ul d be re p orte d as a n A E 
are as f oll o ws: 
•  Test res ult is ass ociate d wit h acc o m pa n yi n g a n y relate d s y m pt o ms; 
•  Test res ult re q uires a d diti o nal dia g n ostic te sti n g or me dical/s ur gical i nter ve nti o n; 
•  Test res ult lea ds t o a c ha n ge i n d osi n g of t his dr u g, disc o nti n uati o n of t he st u d y, or 
a d diti o n of c o nc o mita nt dr u g treat me nt or ot her treat me nt; 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 4 of 3 0  
•  T he i n vesti gat or or Pfizer j u d ges it t o be a n A E. 
C o nti n uati o n of a n a b n or mal val ue t hat d oes n o t meet a n y of t he a b o ve criteria is n ot a n A E. 
A b n or mal val ues d ue t o la b orat or y err ors d o n ot nee d t o be re p orte d as A Es. 
9. 4. 2.  Seri 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 i n a patie nt w h o recei ve d a me dici nal or 
n utriti o nal pr o d uct (i ncl u di n g pe diatric pre parati o ns) at a n y d ose t hat: 
•  Res ults i n deat h; 
•  Is life-t hreate ni n g; 
•  Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n ( See bel o w 
f or circ u msta nces t hat d o n ot q ualif y as a n A E); 
•  Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y (s u bsta ntial disr u pti o n of t he 
a bilit y t o c o n d uct n or mal life f u ncti o ns); 
•  Res ults i n c o n ge nital a n o mal y/ birt h defect. 
Pr o gressi o n of t he mali g na nc y (i ncl u di n g si g ns a n d s y m pt o ms of pr o gressi o n) i n vesti gate d i n 
t his st u d y s hall n ot be re p orte d as a n S A E u nless t he o utc o me d uri n g t he re p orti n g peri o d is 
deat h. H os pitalizati o n f or si g ns a n d s y m pt o ms of disease pr o gressi o n will n ot be re p orte d as 
a n S A E. H o we ver, if t he o utc o me of t he mali g na nc y d uri n g t he st u d y or d uri n g t he re p orti n g 
peri o d is deat h, t he e ve nt lea di n g t o deat h m ust be rec or de d as a n A E a n d m ust be re p orte d as 
a Gra de 5 S A E.  
Me dical a n d scie ntific j u d g me nt is e xercise d i n  deci di n g w het her a n e ve nt is a si g nifica nt 
me dical e ve nt. A si g nifica nt me dical e ve nt ma y n ot be i m me diatel y life-t hreate ni n g a n d/ or 
res ult i n deat h or h os pitalizati o n. H o we ver, if it is deter mi ne d t hat t he e ve nt ma y je o par dize 
t he patie nt or ma y re q uire 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, t he 
si g nifica nt e ve nt s h o ul d be re p orte d as a n S A E. 
E xa m ples of s uc h e ve nts are 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 f or 
aller gic br o nc h os pas m; bl o o d d yscrasia or c o n v ulsi o n t hat d o n ot res ult i n h os pitalizati o n; or 
de vel o p me nt of dr u g de pe n de nc y or dr u g a b use. 
I n a d diti o n, s us pecte d tra ns missi o n of a n i nfecti o us a ge nt via a Pfizer pr o d uct is c o nsi dere d 
seri o us, w het her pat h o ge nic or n o n- pat h o ge nic. T he e ve nt ma y be s us pecte d base d o n cli nical 
si g ns or la b orat or y fi n di n gs s u g gesti ve of i nfecti o n i n patie nts e x p ose d t o a Pfizer pr o d uct. 
T he ter m "s us pecte d tra ns missi o n of i nfecti o n" is c o nsi dere d s y n o n y m o us wit h "i nfecti o n 
tra ns missi o n." T hese cases will be c o nsi dere d u ne x pecte d a n d will be ha n dle d as seri o us 
e x pe dite d cases b y Pfizer Safet y. S uc h cases s h o ul d als o be c o nsi dere d f or re p orti n g as 
pr o d uct defects, if a p pr o priate. 
H os pitalizati o n 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 5 of 3 0  
H os pitalizati o n is defi ne d as a n y i nitial a d missi o n (e ve n if less t ha n 2 4 h o urs) i n a h os pital or 
e q ui vale nt healt hcare facilit y or a n y pr ol o n gati o n t o a n e xisti n g a d missi o n. H os pitalizati o n 
als o i ncl u des tra nsfer wit hi n t he h os pital t o ot her de part me nt or t he ac ute/i nte nsi ve care u nit  
(e. g., tra nsfer fr o m t he ps yc hiatric war d t o a me dical fl o or, fr o m t he me dical fl o or t o a 
c or o nar y care u nit, or fr o m ne ur ol o gical fl o or t o a t u berc ul os is u nit, etc.). A n e mer ge nc y 
r o o m visit d oes n ot necessaril y c o nstit ute a h ospitalizati o n; h o we ver, e ve nts lea di n g t o t he 
e mer ge nc y r o o m visit is asse sse d f or me dical si g nifica nce. 
H os pitalizati o n wit h o ut a me dical A E is n ot i n  itself a n A E, a n d re p orti n g is n ot re q uire d. 
F oll o wi n gs are e xa m ples of h os pitalizati o n wi t h o ut me dical A Es t hat d oes n ot nee d t o be 
re p orte d. 
•  S ocial h os pitalizati o n (e. g., n o ac c o m m o dati o n f or patie nts/s u bjects) 
•  A d mi nistrati ve h os pitalizati o n (e. g ., f or a n n ual me dical c hec k u p) 
•  O pti o nal h os pitalizati o n n ot ass ociate d wit h a preci pitati n g cli nical deteri orati o n (e. g., 
o pti o nal c os metic s ur ger y) 
•  H os pitalizati o n f or o bser vati o n wit h o ut a me dical A E 
•  H os pitalizati o n f or treat me nt of a pree xisti n g c o n diti o n n ot ass ociate d wit h t he 
de vel o p me nt of a ne w A E or wit h a w orse ni n g of t he pree xisti n g c o n diti o n (e. g., cl ose 
e xa mi nati o n f or a persiste nt pretreat me nt la b orat or y a b n or malit y) 
9. 5.  Sce n ari os Necessit ati n g Re p orti n g t o Pfizer S afe t y wit hi n 2 4 H o urs  
Sce nari os i n v ol vi n g e x p os ure d uri n g pre g na nc y, e x p os ure d uri n g brea stfee di n g, me dicati o n 
err or, o ver d ose, mis use, e xtra vasati o n, lac k  of efficac y, a n d occ u pati o nal e x p os ure are 
descri be d bel o w.  
E x p os ure d uri n g pre g na nc y 
A n e x p os ure d uri n g pre g na nc y ( E D P) occ urs if: 
1.  A fe male bec o mes, or is f o u n d t o be, pre g na nt eit her w hile recei vi n g or ha vi n g bee n 
directl y e x p ose d (e. g., e n vir o n me ntal e x p os ure ) t o t his dr u g. A fe male bec o mes, or is 
f o u n d t o be, pre g na nt after disc o nti n ui n g or ha vi n g bee n directl y e x p ose d t o t his dr u g 
( mater nal e x p os ure). 
E n vir o n me ntal e x p os ure i ncl u des direct c o ntac t wit h a Pfizer pr o d uct i n a pre g na nt 
w o ma n (f or e xa m ple, a n urse re p orts a pre g na nc y a n d has bee n e x p ose d t o 
c he m ot hera pe utic pr o d ucts). 
2.  A male has bee n e x p ose d t o t his dr u g pri or t o or ar o u n d t he ti me of c o nce pti o n b y 
treat me nt or e n vir o n me ntal e x p os ure. A male has bee n e x p ose d d uri n g his part ner's 
pre g na nc y ( pater nal e x p os ure). 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 6 of 3 0  
F or e x p os ure d uri n g pre g na nc y i n st u dies of pre g na nt w o me n, data o n t he e x p os ure t o t his 
dr u g d uri n g pre g na nc y are n ot re p orta ble u nle ss ass ociate d wit h seri o us or n o n-seri o us 
a d verse e ve nts.  
As a ge neral r ule, pr os pecti ve a n d retr os pec ti ve e x p os ure d uri n g pre g na nc y re p orts fr o m a n y 
s o urce are re p orta ble irres pecti ve of t he prese nce of a n ass ociate d A E a n d t he pr oce d ures f or 
S A E re p orti n g s h o ul d be f oll o we d, wit h t he e xce pti o n of t h ose st u dies c o n d ucte d i n pre g na nt 
w o me n (as descri be d i n a b o ve), f or w hic h data  o n t he e x p os ure are n ot re p orta ble u nless 
ass ociate d wit h seri o us or n o n-seri o us a d verse e ve nts 
If a s u bject or a s u bject's part ner bec o mes, or is f o u n d t o be, pre g na nt d uri n g t he c o urse of 
treat me nt wit h t his dr u g, t his i nf or mati o n m ust be s u b mitte d t o Pfizer o n t he NI S A E Re p ort 
F or m a n d t he E D P S u p ple me ntal  F or m, re gar dless of w het her a n A E has occ urre d.  
I n a d diti o n, i nf or mati o n re gar di n g e n vir o n me ntal e x p os ure of a pre g na nt w o ma n t o t his dr u g 
(e. g., acci de ntal as pirati o n of a c yt ot o xic a ge nt b y a pre g na nt s u bject or e x p os ure t o t he 
s pille d a ge nt) m ust be s u b mitte d usi n g t he NI S A E Re p ort F or m a n d t he E D P S u p ple me ntal 
F or m. T hese re p orts m ust be ma de irres pect i ve of w het her a n A E has occ urre d.   
T he i nf or mati o n s u b mitte d s h o ul d i ncl u de t he es ti mate d date of deli ver y ( See bel o w f or 
i nf or mati o n o n ter mi nati o n of pre g na nc y). 
Ge neral i nf or mati o n o n pre g na nc y will be f oll o we d u p. I n a d diti o n, all E D P re p orts wit h 
u n k n o w n pre g na nc y o utc o me wi ll be f oll o we d u p f or E D P o utc o me i nf or mati o n. T he 
pre g na nc y will be f oll o we d u ntil birt h or te r mi nati o n of t he pre g na nc y (i n d uce d a b orti o n, 
etc.) a n d t he o utc o me will be re p orte d t o Pfizer. T his i nf or mati o n is pr o vi de d as a f oll o w- u p 
t o t he i nitial E D P re p ort. I n t he case of a ne w b or n, t he a bse nce of e xter nal malf or mati o n i n 
t he ne w b or n s hall be e val uate d at birt h. I n t he e ve nt of a ter mi nati o n, t he reas o n (s) f or 
ter mi nati o n s h o ul d be s pecifie d a n d, if cli nicall y p ossi ble, t h e str uct ural i nte grit y of t he 
ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual i ns pecti o n ( u nless t he test c o nfir ms a 
c o n ge nital a n o mal y a n d is re p orte d). 
If t he o utc o me of t he pre g na nc y meets t he criteria f or a n S A E (i.e. ect o pic pre g na nc y, 
s p o nta ne o us a b orti o n, i ntra uteri ne fetal deat h, ne o natal deat h, c o n ge nital a n o mal y (i n a  li ve 
b or n, a ter mi nate d fet us, a n i ntra uteri ne fetal de mise, or a ne o natal deat h)], t he pr oce d ures f or 
re p orti n g S A Es s h o ul d be f oll o we d. 
A d diti o nal i nf or mati o n re gar di n g pre g na nc y o ut c o mes t o be re p orte d as S A E is pr o vi de d 
bel o w. 
•  S p o nta ne o us a b orti o n i ncl u des miscarria ge a n d misse d a b orti o n. 
•  Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d as S A Es re gar dless 
of ca usalit y. I n a d diti o n, i nfa nt deat hs afte r 1 m o nt h s h o ul d be re p orte d as S A Es w he n t he 
i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y related t o dr u g e x p os ure t o 
i n vesti gati o nal pr o d uct. 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 7 of 3 0  
A d diti o nal i nf or mati o n re gar di n g t he e x p os ure d uri n g pre g na nc y ma y be  re q ueste d. F urt her 
f oll o w- u p of birt h o utc o mes will be ha n dle d o n a case- b y-case basis (e. g., f oll o w- u p o n 
preter m i nfa nts t o i de ntif y de vel o p me ntal dela ys).   
I n t he case of pater nal e x p os ure, t he st u d y partici pa nt will be pr o vi de d wit h t he Pre g na nt 
Part ner Release of I nf or mati o n F or m t o deli ver t o  his part ner. It m ust be rec or de d t hat t his 
d oc u me nt was pr o vi de d t o t he st u d y partici pa nt,  w hic h was t o be pr o vi de d t o t he part ner. 
E x p os ure d uri n g breastfee di n g 
Sce nari os of e x p os ure d uri n g breastfee di n g m ust be re p orte d, irres pecti ve of t he prese nce of 
a n ass ociate d A E. A n e x p os ure d uri n g breastfee d i n g re p ort is n ot create d w he n a Pfizer dr u g 
s pecificall y a p pr o ve d f or use i n breastfee di n g w o me n (e. g., vita mi ns) is a d mi nistere d i n 
acc or d wit h a ut h orize d use. H o we ver, if t he i nfa nt e x perie nces a n A E ass ociate d wit h s uc h a 
dr u g's a d mi nistrati o n, t he A E is re p orte d t o ge t her wit h dr u g e x p os ure d uri n g breastfee di n g. 
Me dicati o n err or 
A me dicati o n err or is a n y pre ve nta ble e ve nt, w h ic h ma y lea d t o i na p pr o priate use of a dr u g 
u n der t he ma na ge me nt of a healt hcare pr ofes si o nal, patie nt, or c o ns u mer, or ma y e xert 
a d verse effects o n patie nts. S uc h e ve nts ma y be relate d t o me dical practices, pr o d ucts, 
pr oce d ures, a n d s yste ms, i ncl u di n g prescri bi n g,  prescri pti o n tra ns missi o n, pr o d uct la beli n g, 
pac ka gi n g a n d n o me nclat ure, c o m p o u n di n g, di s pe nsi n g, distri b uti o n, a d mi nistrati o n, 
e d ucati o n, m o nit ori n g, a n d use. 
E xa m ples of me dicati o n err ors are as f oll o ws: 
•  A n y me dicati o n err ors pre ve nte d i n a d va nce re gar dless of w het her ha vi n g direct i m pacts 
o n patie nts (e. g., i na d verte nt/i nc orrect a d mi ni strati o n w here t he healt hcare pr ofessi o nal or 
patie nt/c o ns u mer uses t he pr o d uct i nc orrectl y at a d ose or a d mi nistrati o n met h o d n ot 
liste d i n t he pr o d uct la bel or prescri pti o n) 
•  Mi x- u p of na me (e. g., pr o d uct na me) 
T he i n vesti gat or m ust s u b mit re p orts o n t he f oll o wi n g me dicati o n err ors wit h or wit h o ut 
ass ociate d A Es/ S A Es: 
•  Me dicati o n err ors i n v ol vi n g patie nt e x p os ur e t o t he pr o d uct, w het her or n ot t he 
me dicati o n err or is acc o m pa nie d b y a n A E. 
•  Me dicati o n err ors t hat d o n ot directl y i n v ol ve t he patie nt ( p ote ntial me dicati o n err ors or 
err ors nearl y misse d, i ncl u di n g t he o nes w hic h are late nt or pre ve nte d i n a d va nce). If t he 
me dicati o n err or d oes n ot i n v ol ve patie nt e x p os ure t o t he pr o d uct, a me dicati o n err or 
re p ort will be ge nerate d base d o n t he f oll o wi n g mi ni m u m criteria: 
•  I de ntifia ble re p orter 
•  S us pecte d pr o d uct 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 8 of 3 0  
•  E ve nt of me dicati o n err or 
O ver d ose, mis use, e xtra vasati o n 
Re p orts of o ver d ose, mis use, a n d e xtra vasati o n ass ociate d wit h t he use of a Pfizer pr o d uct are 
re p orte d t o Pfizer b y t he i n vesti gat or, irres pecti ve of t he prese nce of a n ass ociate d A E/ S A E.  
Lac k of efficac y 
Re p orts of lac k of efficac y t o a Pfizer pr o d uct are re p orte d t o Pfizer b y t he i n vesti gat or, 
irres pecti ve of t he prese nce of a n acc osiate d A E/ S A E or t he i n dicati o n f or use of t he Pfizer 
pr o d uct. 
Occ u pati o nal e x p os ure 
Re p orts of occ u pati o nal e x p os ure t o a Pfizer pr o d uct are re p orte d t o Pfizer b y t he i n vesti gat or, 
irres pecti ve of t he prese nce of a n acc osiate d A E/ S A E. 
1 0.  P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S 
I nf or mati o n c ollecte d i n t his stu d y will be use d f or re p orti n g t o t he M H L W, P har mace uticals 
a n d Me dical De vices A ge nc y ( P M D A), Pfizer I nc. w hic h is t he c or p orate pare nt of t he 
S p o ns or of t his st u d y, a n d t he gr o u p c o m pa nie s, or re g ulat or y a ge nc y i n ot her c o u ntries. 
Als o, it will be use d f or s u b mitti n g a p plicati o n of ree xa mi nati o n (i ncl u di n g Peri o dic Safet y 
U p date Re p ort), re-e val uati o n, pre parati o n of material f or pr o per use i nf or mati o n of t his 
dr u g, p u blicati o ns a n d acti vities f or i nf or mati o n pr o visi o n. I n a d diti o n, Pfizer ma y discl ose 
t he st u d y res ults t o pr o vi de i nf or mati o n f or pr o per use, as nee de d, o n w w w.cli nicaltrials. g o v 
( Cli nical Trials. g o v), as prese ntati o ns at aca de mic c o nfere nces, or as ma n uscri pts, etc. 
 
Data o btai ne d fr o m t he patie nts re gistere d i n t his st u d y will be re p orte d t o t he M H L W 
p urs ua nt t o t he P har mace utical a n d Me dical De vice Act. I n t his case, t he data ma y be 
p u blicl y p oste d i n M H L W's " P har mace utical a n d Me dical De vice Safet y I nf or mati o n" a n d 
" P har mace uticals a n d Me dical De vices I nf or mati o n We bsite ( htt p:// w w w.i nf o. p m da. g o.j p)" 
as a listi n g of patie nts, w hic h will i ncl u de t he na mes of dr u gs, a d verse reacti o ns, ge n der, a ge 
(i ncre me nt of 1 0 years), a n d ot her rele va nt i nf or mati o n. F urt her m ore, data c ollecte d ma y als o 
be discl ose d if t he M H L W is re q uire d t o disc l ose s uc h i nf or mati o n i n acc or da nce wit h t he 
" Act o n Access t o I nf or mati o n Hel d b y A d ministrati ve Or ga ns" ( Act N o. 4 2 date d Ma y 1 4, 
1 9 9 9); pr o vi de d t hat i n n o e ve nt will t he na mes of p h ysicia ns, me dical i nstit uti o ns, a n d ot her 
pers o nal i nf or mati o n be s u bject t o s uc h discl o s ure, n or will it be p oste d or discl ose d. 
I n t he e ve nt of a n y pr o hi biti o n or restricti o n i m p ose d (e. g., cli nical h ol d) b y a n a p plica ble 
C o m pete nt A ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n w hic h mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris k s of a Pfizer pr o d uct, 
Pfizer s h o ul d be i nf or me d i m me diatel y.  
1 1.  N A M E A N D A D D R E S S O F C O N T R A C T O R A S W E L L A S S C O P E O F W O R K 
C O N T R A C T E D 
C o m pa n y na me: Pfizer R & D Ja pa n G. K. 
A d dress: 3- 2 2- 7, Y o y o gi, S hi b u ya- k u, T o k y o 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 2 9 of 3 0  
Sc o pe of w or k c o ntracte d: W or ks relate d t o pl a n ni n g a n d drafti n g of st u d y, o perati o n of t he 
st u d y, a n d m o nit ori n g etc. 
C o m pa n y na me: Me di data S ol uti o ns, I nc. 
A d dress: 2- 7- 2, Mar u n o uc hi, C hi y o da- k u, T o k y o 
Sc o pe of w or k c o ntracte d: Esta blis h me nt, o pera ti o n a n d mai nte na nce of t he E D C s yste m, etc. 
C o m pa n y na me: E P S C or p orati o n 
A d dress: 2- 2 3, S hi m o mi ya bic h o, S hi nj u k u- k u, T o k y o 
Sc o pe of w or k c o ntracte d: Re gistrati o n, esta bl is h me nt of t he E D C s yste m, data ma na ge me nt, 
statistical a nal ysis etc. 
1 2.  A D DI TI O N A L M E A S U R E S T H A T M A Y B E I M P L E M E N T E D B A S E D O N T H E 
S T U D Y R E S U L T S A N D C RI T E RI A F O R D E T E R MI N A TI O N O F T H E I NI TI A TI O N 
Re vie w t he ris k ma na ge me nt pla n i ncl u di n g t he f oll o wi n g c o nte nts at t he sc he d ule d ti mi n g of 
milest o nes. 
1.  Re vie w t he necessit y f or c ha n gi n g t he c o nte n ts of ris k mi ni mizati o n acti vities f or t he 
c urre nt safet y s pecificati o ns. 
2.  Re vie w t he necessit y f or c ha n gi n g t he c o nte nts of t his st u d y pla n i ncl u di n g t he prese nce 
or a bse nce of ne w safet y s pecificati o ns (c o nti n uati o n of t he st u d y, i m ple me ntati o n of 
a d diti o nal st u d y, etc.). 
3.  Re vie w t he necessit y f or f or m ulati n g ris k  mi ni mizati o n meas ures f or ne w safet y 
s pecificati o ns. 
1 3.  S C H E D U L E D TI MI N G O F MI L E S T O N E S A N D T H EI R R A TI O N A L E S F O R 
E V A L U A TI O N O F S T U D Y I M P L E M E N T A TI O N S T A T U S A N D R E S U L T S A N D 
R E P O R TI N G T O T H E P M D A 
Safet y re vie w a n d re p orti n g at t he ti me of e val uati o n re p ort a n d c o m pleti o n of t he st u d y. 
1 4.  O T H E R N E C E S S A R Y M A T T E R S 
1.  A me n d me nt of t he F ull Pr ot oc ol 
Base d o n t he ne w k n o wle d ge t o be o btai ne d acc or di n g t o t he pr o gress of t his st u d y, t he nee d 
f or a me n d me nt of t he F ull Pr ot oc ol will be e xa mi ne d a n d t he F ull Pr ot oc ol will be a me n de d 
if necessar y.  Als o, t he nee d f or a me n d me nt of t he F ull Pr ot oc ol will be e xa mi ne d a n d t he 
F ull Pr ot oc ol will be a me n de d w he n t he partia l c ha n ge i n t he d osa ge a n d a d mi nistrati o n or 
i n dicati o n is a p pr o ve d d uri n g t he ree xa mi nati o n peri o d (e xce pt w he n t he ree xa mi nati o n 
peri o d is ne wl y desi g nate d), etc. 
2.  Acti o ns t o be ta ke n i n t he case of a n y pr o ble m or iss ue 
Re visi o n of t he pac ka ge i nsert a n d c o n d uct of a ne w P ost- mar keti n g s ur veilla nce or ne w 
P ost- mar keti n g Cli nical Trial s h o ul d be c o nsi dere d f or t he f o ll o wi n g cases: a n y seri o us a n d 
u n k n o w n a d verse reacti o n is s u g geste d; a si g nif ica nt i ncrease i n t he fre q ue nc y of a d verse 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)

Trast uz u ma b B S 
B 3 2 7 1 0 0 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
A me n de d 4, 2 2 Dece m ber 2 0 2 2 
P FI Z E R C O N FI D E N TI A L 
C T 2 4- WI-J P N- G P S P 0 1- R F 0 9 7. 0 N o n-I nter ve nti o nal St u d y Pr ot oc ol Te m plate f or Sec o n dar y Data C ollecti o n 
St u d y 1 5- Se p- 2 0 2 2 
Pa ge 3 0 of 3 0  
reacti o ns; a n y effecti ve ness or safet y c o ncern c o m pare d t o pre-a p pr o val; rare a d verse 
reacti o n is s u g geste d. 
1 5.  C O N T A C T I N F O R M A TI O N 
1 5. 1.  C o nt act I nf or m ati o n f or I n q uiries a b o ut t he St u d y 
Na me 
P M S Affairs, Pfizer R & D Ja pa n G. K. 
A d dress 
3- 2 2- 7, Y o y o gi, S hi b u ya- k u, T o k y o, 1 5 1- 8 5 8 9 
Fa x n u m ber  
0 3- 5 3 0 9- 9 1 8 6 
E- mail a d dress  
T S X _ D R P M S @ pfizer.c o m 
 
1 5. 2.  C o nt act I nf or m ati o n f or I n q uiries a b o ut P ost- m ar keti n g S ur veill a nce D at a 
C ollecti o n S yste m 
Na me
 Me di data
 
Hel p des k
 
B usi ness H o urs 
Wee k da ys: 9: 0 0 t o 2 0: 0 0 (e xcl u di n g Sat ur da ys, S u n da ys, nati o nal h oli da ys a n d year-e n d 
a n d be gi n ni n g) 
T E L
 
 (e xcl usi ve n u m ber f or Pfizer) 
E- mail a d dress 
ja pa n hel p des k @ m ds ol.c o m 
 
1 6.  R E F E R E N C E S 
N ot a p plica ble 
1 7.  LI S T O F T A B L E S 
Pa ge 1 2.  T a ble 1.  
V ari a bles a n d sc he d ule of o bser v ati o n 
1 8.  LI S T O F FI G U R E S 
N ot a p plica ble 
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S 
N ot a p plica ble 
A N N E X 2. A D DI TI O N A L I N F O R M A TI O N 
N ot a p plica ble 
 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)
P P D

 
T R A N S L A TI O N R E C O R D 
( F O R P O S T- M A R K E TI N G S U R V EI L L A N C E S T U D Y I N J A P A N) 
1 0- J a n- 2 0 1 9 
 
P FI Z E R C O N FI D E N TI A L 
Pa ge 1 of 1 
 
D oc u me nt T y pe 
（Pr ot oc ol ） 
D oc u me nt D ate 
( Ori gi n al) 
2 2 Dec 2 0 2 2 
Pr o gr a m  
B 3 2 7 
St u d y 
B 3 2 7 1 0 0 7 
Ori gi n al L a n g u a ge 
Site 
N A 
Tr a nsl ati o n L a n g u a ge 
Is a b ac k 
tr a nsl ati o n 
re q uire d ? 
 
N O 
 
 
F U L L T R A N S L A TI O N A N D R E VI E W I N F O R M A TI O N 
 
Tr a nsl at or Q u alific ati o n 
T y pe 
Tra nslati o n Ve n der 
Tr a nsl ati o n Ve n d or  
H o n ya k u Ce nter I nc. 
Tr a nsl at or N a me 
H o n ya k u Ce nter I nc. 
D ate of Tr a nsl ati o n 
1 6 J u n 2 0 2 4 
Re vie wer N a me 
 
D ate of Re vie w 
1 8 J u n 2 0 2 4 
 
 
0 9 0 1 7 7 e 1 a 4 0 9 8 5 d 7\ A p pr o v e d\ A p pr o v e d O n: 1 8- J ul- 2 0 2 5 0 3: 3 0 ( G M T)
P P D
N o n- E n gli s h t e xt 
N o n- E n gli s h t e xt