A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07062119 IN PATIENTS WITH ADVANCED GASTROINTESTINAL TUMORS
Phase: PHASE1
Conditions: Gastrointestinal Tumors, Colorectal Adenocarcinomas, Gastric Adenocarcinomas, Esophageal Adenocarcinomas
Sponsor: Pfizer

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1
  
A P H A S E 1 D O S E E S C A L A TI O N A N D E X P A N SI O N S T U D Y E V A L U A TI N G T H E
S A F E T Y, T O L E R A BI LI T Y , P H A R M A C O KI N E TI C S, P H A R M A C O D Y N A MI C S 
A N D A N TI T U M O R A C TI V I T Y O F P F-0 7 0 6 2 1 1 9 I N P A TI E N T S WI T H A D V A N C E D 
G A S T R OI N T E S TI N A L T U M O R S
I n vesti g ati o n al Pr o d uct N u m ber:
P F -0 7 0 6 2 1 1 9
I n vesti g ati o n al Pr o d uct N a me:
N ot A p plica ble ( N/ A)
U nite d St ates ( U S) I n vesti g ati o n al Ne w 
Dr u g (I N D) N u m ber:
1 4 3 4 1 6
E ur o pe a n Cli nic al Tri als D at a b ase 
( E u dr a C T) N u m ber:
N ot A p plica ble ( N/ A)
Pr ot oc ol N u m ber:
C 3 8 6 1 0 0 1
P h ase:
1
S h ort Title: A P hase 1, o pe n -la bel, d ose escalati o n a n d e x pa nsi o n st u d y of 
P F -0 7 0 6 2 1 1 9 i n pati ents wit h selecte d a d va nce d or metastatic gastr oi ntesti nal t u m ors.
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n 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 hese d oc u me nts, 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 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2
D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 7
1 9 N o ve m ber 2 0 2 1
A me n d me nt 6
0 8 Oct o ber 2 0 2 1
A me n d me nt 5
1 6 Marc h 2 0 2 1
A me n d me nt 4
0 5 Oct o ber 2 0 2 0
A me n d me nt 3
1 7 A u g ust 2 0 2 0
A me n d me nt 2
1 0 Oct o ber 2 0 1 9
A me n d me nt 1
0 8 Oct o ber 2 0 1 9
Ori gi nal pr ot oc ol
2 0 A u g ust 2 0 1 9
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d I R Bs/ E Cs a n d a n y pr ot oc ol a d mi nistrati ve 
clarificati o n letter.
Pr ot oc ol A me n d me nts S u m m ar y of C h a n ges T a bl e
A m e n d me nt 7 ( 1 9 N o ve m ber 2 0 2 1)
O ver all R ati o n ale f or t he A me n d me nt: T he pri mar y  p ur p ose of t he a me n d me nt is t o 
i nc or p orate fee d bac k recei ve d fr o m t he U nite d States ( U S) F o o d a n d Dr u g A d mi nistrati o n 
( F D A). I n a d diti o n, clarificati o ns, a d mi nistrati ve a n d t yp o gra p hical m o dificati o ns were 
ma de.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n al e
Secti o n 5. 1 
I ncl usi o n Criteria
I ncl usi o n criteri o n # 1 2 was 
a da pte d t o re m o ve t he f oll o wi n g 
la n g ua ge, “< U L N if t here is 
li ver i n v ol ve me nt sec o n dar y t o 
t u m or”
T o re q uire all partici pa nts 
(i ncl u di n g t h ose wit h li ver 
metastases) t o ha ve A S T a n d A L T 
≤ 2. 5 x U L N at st u d y e ntr y.
Secti o n 6. 7. 3 
Ta ble 1 2
D ose m o dificati o n g ui deli nes f or 
s pecific i m m u ne relate d t o xicit y 
attri b ute d t o i n vesti gati o nal 
pr o d uct were u p date d t o pr o vi de 
a d diti o nal detail ar o u n d Li ver 
( He patitis) a n d C R S e ve nts. 
T o pr o vi de s pecific d ose 
i nterr u pti o n a n d m o dificati o n 
g ui deli nes base d o n gra des f or 
patie nts w h o e x perie nce li ver a n d 
C R S e ve nts.
Secti o n 1 0. 1 1
A p pe n di x 1 1
C R S ma na ge me nt g ui deli nes 
were a d de d t o acc o m pa n y t he 
C R S ma na ge me nt al g orit h m
T o pr o vi de s u g geste d ma na ge me nt 
g ui deli nes f or C R S
Secti o n 1 0. 1 3
A p pe n di x 1 3
D osi n g m o dificati o ns a n d d ose 
i nterr u pti o ns f or Gra de 2 
he patitis a d verse e ve nts t hat last 
T o pr o vi de m ore detaile d f oll o w 
u p i nstr ucti o ns f or He patitis 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n al e
l o n ger t ha n 7 da ys ha ve bee n 
pr o vi de d i n Ta ble 1 2, 
ma na ge me nt g ui deli nes ha ve 
bee n ali g ne d i n Ta ble 2 0 a n d 
t hr o u g h o ut the pr ot oc ol .
(ir A Es) ma na ge me nt of Gra de 2 
e ve nts.  
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4
T A B L E O F C O N T E N T S
LI S T O F T A B L E S ...................................................................................................................1 1
LI S T O F FI G U R E S .................................................................................................................1 2
1. S C H E D U L E O F A C TI V I TI E S ( S O A)................................................................................1 3
2. I N T R O D U C TI O N ...............................................................................................................3 5
2. 1. St u d y  Rati o nale.......................................................................................................3 5
2. 2. Bac k gr o u n d .............................................................................................................3 6
2. 2. 1. A d va nce d Ga str oi ntesti nal A de n ocarci n o mas ............................................3 6
2. 2. 2. G U C Y 2c E x pressi o n i n H u ma n Ca ncers ....................................................3 7
2. 2. 3. Bis pecific Re directe d T -cell E n ga gi n g T hera pies...................................... 3 7
2. 2. 4. P F - 0 7 0 6 2 1 1 9...............................................................................................3 7
2. 2. 5. N o ncli n ical P har mac ol o g y..........................................................................3 8
2. 2. 5. 1. I n Vitr o P har mac o d y na mics ......................................................3 8
2. 2. 6. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 4 2
2. 2. 7. N o ncli nical Safet y ...................................................................................... 4 3
2. 2. 8. S u m mar y  of C urre nt Cli nical Data fr o m St u d y C 3 8 6 1 0 0 1........................4 4
2. 2. 8. 1. Safet y Data U p date ....................................................................4 4
2. 2. 8. 2. P har mac o ki netics ................................ ......................................4 4
2. 3. A nti- Pr o gra m me d Cell Deat h Pr otei n -1 ( A nti -P D - 1)............................................. 4 5
2. 3. 1. P F -0 6 8 0 1 5 9 1, a n A nti -P D -1 A nti b o d y : Cli nical E x perie nce i n 
St u d y B 8 0 1 1 0 0 1 ( N C T 0 2 5 7 3 2 5 9)................................................................... 4 5
2. 4. O ver vie w of Be vaciz u ma b- Pfizer ( Zira be v ™)................................ .......................4 6
2. 5. Be nefit/ Ris k Assess me nt................................ .........................................................4 6
3. O BJ E C TI V E S A N D E N D P OI N T S .....................................................................................4 7
4. S T U D Y D E SI G N .................................................................................................................5 0
4. 1. O verall Desi g n................................ .........................................................................5 0
4. 1. 1. Part 1 A........................................................................................................ 5 2
4. 1. 1. 1. P F -0 7 0 6 2 1 1 9 Treat me nt Wit h o ut a Pri mi n g D ose ....................5 2
4. 1. 1. 2. P F -0 7 0 6 2 1 1 9 Treat me nt Wit h a Pri mi n g D ose .........................5 2
4. 1. 2. Part 1 B ( C o m bi nati o n C o h orts) ..................................................................5 3
4. 1. 3. Part 2........................................................................................................... 5 4
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................5 5
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5
4. 3. J ustificati o n f or D ose ..............................................................................................5 5
4. 3. 1. Starti n g D ose f or M o n ot hera p y D ose Escalati o n Wit h o ut a Pri mi n g 
D ose ( Part 1 A) .................................................................................................5 5
4. 3. 2. Starti n g D ose f or M o n ot hera p y D ose Escalati o n Wit h a Pri mi n g 
D ose ( Part 1 A) .................................................................................................5 6
4. 3. 3. S u bc uta ne o us R o ute.................................................................................... 5 7
4. 3. 4. Fi xe d D osi n g A p pr oac h ..............................................................................5 7
4. 3. 5. D osi n g I nter val ( Q 2 W) ...............................................................................5 7
4. 3. 6. Starti n g D ose f or C o m bi nati o n D ose Fi n di n g ( Part 1 B) ............................5 7
4. 3. 7. Criteria f or D o se Escalati o n........................................................................5 8
4. 3. 8. D ose L i miti n g T o xicit y Defi niti o n.............................................................5 9
4. 3. 9. L ate O nset T o xicit y ....................................................................................6 1
4. 3. 1 0 . Ma xi m u m T olerate d D ose Defi niti o n.......................................................6 1
4. 3. 1 1. Rec o m me n de d P hase 2 D ose Defi niti o n ..................................................6 1
4. 3. 1 2. Part 2 Res pecti ve Starti n g D oses f or P F- 0 7 0 6 2 1 1 9 as a Si n gle 
A ge nt a n d C o m bi nati o n D ose E x pa nsi o n C o h orts ..........................................6 1
4. 3. 1 3. Part 2 P F -0 7 0 6 2 1 1 9 as a Si n gle A ge nt i n A d va nce d or Metastatic 
C ol orectal A de n ocarci n o ma................................ .............................................6 2
4. 3. 1 4. Part 2 P F -0 7 0 6 2 1 1 9 i n C o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 i n 
A d va nce d or Metastatic C ol orectal A de n ocarci n o ma................................ .....6 2
4. 3. 1 5. Part 2 P F -0 7 0 6 2 1 1 9 i n C o m bi nati o n wit h Be vaciz u ma b -Pfizer i n 
A d va nce d or Metastatic C ol orectal A de n ocarci n o ma................................ .....6 2
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................6 2
5. S T U D Y P O P U L A T I ON................................ ......................................................................6 2
5. 1. I ncl usi o n Criteria .....................................................................................................6 3
5. 2. E xcl usi o n Criteria ....................................................................................................6 4
5. 3. L ifest yle C o nsi derati o ns..........................................................................................6 7
5. 3. 1. C o ntrace pti o n ..............................................................................................6 7
5. 4. Scree n Fail ures ........................................................................................................6 8
6. S T U D Y I N T E R V E N TI O N ..................................................................................................6 8
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................6 8
6. 1. 1. A d mi nistrati o n ............................................................................................6 9
6. 1. 1. 1. P F - 0 7 0 6 2 1 1 9.............................................................................6 9
6. 1. 1. 2. P F - 0 6 8 0 1 5 9 1.............................................................................7 0
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6
6. 1. 1. 3. Be vaciz u ma b -Pfizer ..................................................................7 0
6. 2. Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y ........................................................7 1
6. 3. Pre parati o n a n d Dis pe nsi n g .....................................................................................7 2
6. 4. Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g .....................................7 2
6. 4. 1. All ocati o n t o I n vesti gati o nal Pr o d uct/ St u d y  Inter ve nti o n ..........................7 2
6. 5. St u d y I nter ve nti o n C o m plia nce...............................................................................7 3
6. 6. C o nc o mita nt T hera p y ..............................................................................................7 3
6. 6. 1. Ot her A nti -t u m or/ A nti-ca ncer Treat me nt ...................................................7 4
6. 6. 2. S u p p orti ve Care ..........................................................................................7 4
6. 6. 2. 1. S u p p orti ve Care f or C y t o ki ne Release Sy n dr o me .....................7 4
6. 6. 2. 2. S u p p orti ve Care f or I nf usi o n -Relate d Reacti o ns ......................7 5
6. 6. 2. 3. S u p p orti ve Care f or H y perse nsiti vit y  Reacti o ns T ypes 1 
a n d 3 ..................................................................................................7 5
6. 6. 2. 4. S u p p orti ve Care f or I m m u ne - Relate d A d verse E ve nts............. 7 5
6. 6. 3. He mat o p oietic Gr o wt h Fact ors ...................................................................7 5
6. 6. 4. A nti- Diarr heal, A nti -E metic T hera p y......................................................... 7 6
6. 6. 5. A nti- I nfla m mat or y T hera p y................................ ........................................ 7 6
6. 6. 6. C ortic oster oi ds............................................................................................ 7 6
6. 6. 7. S ur ger y ........................................................................................................7 7
6. 6. 8. Resc ue Me dici ne .........................................................................................7 7
6. 7. D ose M o dificati o n ...................................................................................................7 7
6. 7. 1. D osi n g I nterr u pti o ns ...................................................................................7 7
6. 7. 1. 1. D ose I nterr u pti o n of Partici pa nts wit h Pres u me d or Acti ve 
C O VI D -1 9/ S A R S -C o V 2 I nfecti o n ....................................................7 8
6. 7. 2. D ose Dela y s................................................................................................ 7 9
6. 7. 3. D ose Re d uct i o ns.........................................................................................7 9
6. 8. I nter ve nti o n After t he E n d of t he St u d y ..................................................................8 6
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ...........................................................................8 6
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................8 6
7. 1. 1. Re q uest t o C o nti n ue Treat me nt ..................................................................8 6
7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y .......................................8 7
7. 3. L ost t o F oll o w - u p....................................................................................................8 8
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ...............................................................8 9
8. 1. Safet y Assess me nts .................................................................................................9 0
8. 1. 1. P h y sical E xa mi nati o ns ................................................................................9 0
8. 1. 2. C O VI D ‑ 1 9: Use of Alter nati ve Met h o ds f or I n-Pers o n Visits ...................9 0
8. 1. 3. Vital Si g ns ..................................................................................................9 0
8. 1. 4. Electr ocar di o gra ms..................................................................................... 9 0
8. 1. 5. Cli nical Safet y  La b orat or y Assess me nts....................................................9 1
8. 1. 6. Pre g na nc y  Testi n g ......................................................................................9 2
8. 1. 7. I njecti o n Site T olera bilit y  Assess me nt.......................................................9 2
8. 2. A d verse E ve nts a n d Seri o us A d verse E ve nts................................ ..........................9 2
8. 2. 1. Ti me Peri o d a n d Fre q ue nc y  f or C ollecti n g A E a n d S A E I nf or mati o n.......9 3
8. 2. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ...............................................9 3
8. 2. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F................... 9 4
8. 2. 2. Met h o d of Detecti n g A Es a n d S A Es ..........................................................9 4
8. 2. 3. F oll o w -u p of A Es a n d S A Es .......................................................................9 4
8. 2. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es ...........................................9 4
8. 2. 5. E x p os ure D uri n g Pre g na nc y  or Breastfee di n g, a n d Occ u pati o nal 
E x p os ure ..........................................................................................................9 5
8. 2. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................9 5
8. 2. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................9 5
8. 2. 5. 3. Occ u pati o nal E x p os ure .............................................................9 5
8. 2. 6. Me dicati o n Err ors .......................................................................................9 6
8. 3. Tre at me nt of O ver d ose ............................................................................................9 6
8. 4. P har mac o ki netics a n d I m m u n o ge nicit y.................................................................. 9 7
8. 4. 1. P har mac o ki netic Assess me nts.................................................................... 9 7
8. 4. 2. A nal y sis of A nti-Dr u g A nti b o dies a n d Ne utralizi n g A nti -A nti b o dies 
( P F-0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1, or be vaciz u ma b -Pfizer) ...................................9 8
8. 5. P har mac o d y na mics ..................................................................................................9 8
8. 6. Bi o mar ker a n d P har mac o d y na mic Assess me nts .....................................................9 9
8. 7. Ge netics ...................................................................................................................9 9
8. 7. 1. S pecifie d Ge netics ......................................................................................9 9
8. 7. 2. Ba n ke d Bi os peci me ns f or Ge netics ............................................................9 9
8. 8. Bi o mar kers ............................................................................................................1 0 0
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8
8. 8. 1. Arc hi val Pre -treat me nt a n d O pti o nal De N o v o Pre- a n d O n -
Treat me nt T u m or Bi o psies f or Part 1 A a n d Pa rt 1 B......................................1 0 0
8. 8. 2. Ma n dat or y  De N o v o Pre- a n d O n -Treat me nt T u m or Bi o psies at 
R P 2 D i n Part 1 A, Part 1 B, a n d Part 2 ............................................................1 0 1
8. 8. 3. Peri p heral Bl o o d Sa m ple Assess me nts .....................................................1 0 2
8. 8. 4. C y t o ki ne Assess me nts ..............................................................................1 0 2
8. 8. 5. T Cell I m m u n o p he n ot y pi n g ......................................................................1 0 2
8. 9. T u m or Res p o nse Assess me nts ..............................................................................1 0 3
8. 1 0. Healt h Ec o n o mics ...............................................................................................1 0 3
9. S T A TI S T I C A L C O N SID E R A TI O N S ................................ ..............................................1 0 3
9. 1. Statistical H y p ot heses ...........................................................................................1 0 3
9. 2. Sa m ple Size Deter mi nati o n ...................................................................................1 0 3
9. 2. 1. Part 1 D ose Escalati o n ..............................................................................1 0 3
9. 2. 2. Part 2 D ose E x pa nsi o n ..............................................................................1 0 4
9. 3. P o p ulati o ns f or A nal ysis .......................................................................................1 0 4
9. 4. Statistical A nal y ses ...............................................................................................1 0 5
9. 4. 1. Ma xi m u m T olerate d D ose Deter mi nati o n ................................................1 0 5
9. 4. 2. Efficac y  A nalys es .....................................................................................1 0 7
9. 4. 3. Safet y A nal ys es ........................................................................................1 0 7
9. 4. 3. 1. Electr ocar di o gra m A nal y ses....................................................1 0 8
9. 4. 3. 2. A d verse E ve nts ........................................................................1 0 9
9. 4. 3. 3. La b orat or y  Test A b n or malities ...............................................1 0 9
9. 4. 4. Ot her A nal ys es ..........................................................................................1 0 9
9. 4. 4. 1. P har mac o ki netic A nal y ses ......................................................1 0 9
9. 4. 4. 2. P har mac o d y na m ic A nalys es ...................................................1 1 0
9. 5. I nteri m A nalys es ...................................................................................................1 1 1
9. 5. 1. Dat a M o nit ori n g C o m mittee .....................................................................1 1 1
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S................................ ........................................................................1 1 2
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns.............1 1 2
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns ..................................................1 1 2
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P .......................................................................1 1 2
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9
1 0. 1. 2. Fi na ncial Discl os ure ...............................................................................1 1 3
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ......................................................................1 1 3
1 0. 1. 4. Data Pr otecti o n .......................................................................................1 1 4
1 0. 1. 5. Disse mi nati o n of Cli nical St u d y  Data ....................................................1 1 4
1 0. 1. 6. Data Q ualit y Ass ura nce ..........................................................................1 1 5
1 0. 1. 7. S o urce D oc u me nts ..................................................................................1 1 7
1 0. 1. 8. St u d y  a n d Site Cl os ure............................................................................1 1 7
1 0. 1. 9. P u blicati o n P olic y................................................................................... 1 1 7
1 0. 1. 1 0. S p o ns or’s Q ualifie d Me dical Pers o n nel ...............................................1 1 8
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests...............................................................1 1 9
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -u p, a n d Re p orti n g ....................................................................1 2 1
1 0. 3. 1. Defi niti o n of A E .....................................................................................1 2 1
1 0. 3. 2. Defi niti o n of S A E................................................................................... 1 2 2
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w- u p of A Es a n d/ or S A Es .....................1 2 4
1 0. 3. 4. Re p orti n g of S A Es.................................................................................. 1 2 7
1 0. 4. A p pe n di x 4: C o ntrace pti ve G ui da nce a n d C ollecti o n of Pre g na nc y 
I nf or mati o n ..............................................................................................................1 2 8
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criter ia..................................1 2 8
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria ...............................1 2 8
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial ( W O C B P) ........................................1 2 9
1 0. 4. 4. C o ntrace pti o n Met h o ds ...........................................................................1 3 0
1 0 . 5. A p pe n di x 5: Ge netics..........................................................................................1 3 3
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-u p Assess me nts ......1 3 4
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n .................................1 3 6
1 0. 8. A p pe n di x 8: C o u ntr y -S pecific Re q uire me nts .....................................................1 3 8
1 0. 9. A p pe n di x 9: Preli mi nar y  Cli nical S u m mar y f or St u d y B 8 0 1 1 0 0 1 P hase 1 
FI H ( P F - 0 6 8 0 1 5 9 1).................................................................................................1 3 9
1 0. 1 0. A p pe n di x 1 0: Detaile d D ose Escalati o n/ Fi n di n g Sc he me f or B L R M ..............1 4 1
1 0. 1 0. 1. Statistical M o del ...................................................................................1 4 1
1 0. 1 0. 2. Pri or S pecificati o ns f or M o n ot hera p y Wit h o ut Pri mi n g ...................... 1 4 1
1 0. 1 0. 3. Pri or S pecificati o ns f or M o n ot hera p y wit h Pri mi n g ............................1 4 2
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0
1 0. 1 1. A p pe n di x 1 1: S u g geste d C yt o ki ne R elease S yn dr o me Ma na ge me nt 
Al g orit h m a n d Re vise d C R S Gra di n g S y ste m ........................................................1 4 4
1 0. 1 2. A p pe n di x 1 2: E C O G Perf or ma nce Stat us .........................................................1 4 6
1 0. 1 3. A p pe n di x 1 3: S u p p orti ve Care f or I m m u ne- Relate d A d verse E ve nts 
(ir A Es) .....................................................................................................................1 4 7
1 0. 1 4. A p pe n di x 1 4: R E CI S T ( Res p o nse E val uati o n Criteria i n S oli d T u m ors) 
Versi o n 1. 1 G ui deli nes ............................................................................................1 5 1
1 0. 1 5. A p pe n di x 1 5: I m m u ne -Relate d Res p o nse Criteria Deri ve d fr o m R E CI S T 
1. 1 (ir R E CI S T) ........................................................................................................1 5 6
1 0. 1 6. A p pe n di x 1 6: A b bre viati o ns .............................................................................1 5 8
1 0. 1 7. A p pe n di x 1 7: Ja pa n S pecific Matters................................ ................................1 6 4
1 0. 1 8. A p pe n di x 1 8: Alter nati ve Meas ures D uri n g P u blic E mer ge ncies .....................1 6 5
1 0. 1 9. P E T I ma gi n g S u bst u d y  wit h 8 9Zr -Df -I AB 2 2 M 2 C ............................................1 7 0
1 0. 1 9. 1. O verall desi g n a n d Scie ntific Rati o nal f or S u bst u d y ............................1 7 0
1 0. 1 9. 2. Be nefit/ Ris k Assess me nt...................................................................... 1 7 1
1 0. 1 9. 3. P E T I ma gi n g S u bst u d y  O bjecti ves.......................................................1 7 2
1 0. 1 9. 4. P E T I ma gi n g S u bst u d y  Desi g n.............................................................1 7 2
1 0. 1 9. 5. C D 8 P E T Tracer I ma gi n g Pr oce d ures: .................................................1 7 4
1 0. 2 0. S u bc uta ne o us I njecti o n Site L ocati o ns .............................................................1 7 9
1 0. 2 1. Pr ot oc ol A me n d me nt S u m mar y of C ha n ges Ta ble T hr o u g h A me n d me nt 6 ....1 8 0
1 1. R E F E R E N C E S ................................................................................................................2 0 2
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1
LI S T O F T A B L E S
Ta ble 1.
Sc he d ule of Acti vities f or Part 1 A, Part 1 B, a n d Part 2 Wit h o ut 
Pri mi n g D ose ............................................................................................1 3
Ta ble 2.
Sc he d ule of Acti vities f or Part 1 A, Part 1 B, a n d Part 2 Wit h 
Pri mi n g D ose ............................................................................................1 9
Ta ble 3.
Sc he d ule of P har mac o ki netic, P har mac o d y na mic, a n d 
I m m u n o ge nicity Assess me nts f or Part 1 A a n d Part 1 B Wit h o ut 
Pri mi n g D ose ............................................................................................2 4
Ta ble 4.
Sc he d ule of P har mac o ki netic, P har mac o d y n a mic, a n d 
I m m u n o ge nicity Assess me nts f or Part 1 A a n d Part 1 B Wit h 
Pri mi n g D ose ............................................................................................2 7
Ta ble 5.
Sc he d ule of P har mac o ki netic, P har mac o d y na mic, a n d 
I m m u n o ge nicity Assess me nts f or Part 2 Wit h o ut Pri mi n g D ose .............3 0
Ta ble 6.
Sc he d ule of P har mac o ki n etic, P har mac o d y n a mic, a n d 
I m m u n o ge nicity Assess me nts f or Part 2 Wit h Pri mi n g D ose ..................3 2
Ta ble 7.
Mea n ( % C V) P K Para meters F oll o wi n g S i n gle S C D oses of 
P F - 0 7 0 6 2 1 1 9 i n Partici pa nts wit h A d va nce d GI T u m ors 
( St u d y C 3 8 6 1 0 0 1) .....................................................................................4 5
Ta ble 8.
Mi ni m u m I n patie nt O bser vati o n Sta ys .....................................................5 1
Ta ble 9.
S C D ose Escalati o n Le vels f or A d mi nistrati o n Wit h o ut Pri mi n g 
D ose ..........................................................................................................5 9
Ta ble 1 0.
A d mi nistere d St u d y  Inter ve nti o ns ............................................................6 8
Ta ble 1 1.
D ose M o dificati o ns f or T o xicit y  Attri b ute d t o I n vesti gati o nal 
Pr o d uct or I n vesti gati o nal C o m bi nati o n T hera p y  f or N o n-I m m u ne-
Relate d A Es c .............................................................................................8 1
Ta ble 1 2.
D ose M o dificati o ns f or S pecific I m m u ne Relate d T o xicit y  
Attri b ute d t o I n vesti gati o nal Pr o d uct or C o m bi nati o n 
I n vesti gati o nal T hera py............................................................................ 8 3
Ta ble 1 3.  
D osa ge M o dificati o ns f or A d verse Reacti o ns ..........................................8 5
Ta ble 1 4.
Bi o mar ker C ollecti o ns a n d A nal y ses........................................................9 9
Ta ble 1 5.
Safet y  La b orat or y Tests..........................................................................1 1 9
Ta ble 1 6.
Pri or Distri b uti o n f or t he M o del Para meters ..........................................1 4 2
Ta ble 1 7.
S u m mar y  of Pri or Distri b uti o n of D ose Li miti n g T o xicit y Rates f or 
P F - 0 7 0 6 2 1 1 9...........................................................................................1 4 2
Ta ble 1 8.
Pri or Distri b uti o n f or t he M o del Para meters ( Wit h Pri mi n g)................. 1 4 3
Ta ble 1 9.
S u m mar y  of Pri or Distri b uti o n of D ose Li miti n g T o xicit y Rates f or 
P F - 0 7 0 6 2 1 1 9 ( Wit h Pri mi n g D ose of 4 0 0 µ g).......................................1 4 3
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2
Ta ble 2 0.
Ma na ge me nt of I mm u ne Relate d A d verse E ve nts (ir A Es) ....................1 4 7
Ta ble 2 1.
O bjecti ve Res p o nse Stat us at Eac h E val uati o n ...................................... 1 5 4
Ta ble 2 2.
O bjecti ve Res p o nse Stat us at Eac h E val uati o n f or Patie nts wit h N o n 
Tar get Disease O nl y ............................................................................... 1 5 5
Ta ble 2 3.
O verall Res p o nse Deri ve d fr o m C ha n ges i n I n de x, N o n i n de x a n d 
Ne w Lesi o ns ...........................................................................................1 5 7
Ta ble 2 4.
O ver vie w of P E T I ma gi n g S u bst u d y  Visits............................................1 7 4
Ta ble 2 5.
Sc he d ule of Assess me nts f or 8 9Zr -Df -I AB 2 2 M 2 C I m m u n o -P E T 
C D 8 Mi ni -b o d y  Ima gi n g S u bst u d y ........................................................1 7 8
LI S T O F FI G U R E S
Fi g ure 1.
Si n gle A ge nt P F -0 7 0 6 2 1 1 9 Efficac y  i n Esta blis he d T u m or M o dels 
wit h A d o pti ve H u ma n T Cell Tra nsfer .....................................................4 0
Fi g ure 2.
A nti- t u m or Efficac y f oll o wi n g P F-0 7 0 6 2 1 1 9 i n C o m bi nati o n wit h 
A nti P D - 1, A nti-P D -L 1 , or A nti-V E G F -A i n C ol orectal T u m or 
M o dels ......................................................................................................4 2
Fi g ure 3.
C 3 8 6 1 0 0 1 St u d y  Sc he ma..........................................................................5 0
Fi g ure 4.
S u m mar y  of D L T Rates f or P F- 0 7 0 6 2 1 1 9 ............................................. 1 4 2
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3
1. S C H E D U L E O F A C TI VI TI E S ( S O A)  
T he S o A ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures. Refer t o t he S T U D Y A S S E S S M E N T S A N D 
P R O C E D U R E S secti o n of t he pr ot oc ol f or detaile d i nf or mati o n o n eac h assess me nt re q uire d f or c o m plia nce wit h t he pr ot oc ol.
T he i n vesti gat or ma y  sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d i n t he S o A ta ble, i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he wel l-bei n g of t he partici pa nt.
A p pe n di x 1 8 prese nts alter nati ve meas ures t hat ma y be use d d uri n g t he c o urse of t he st u d y i n li g ht of t he C O VI D -1 9 pa n de mic.
T a ble 1 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h o ut Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase - O ne C ycle = 2 8 d a ys
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
C ycle 1
C ycles ≥2 
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
3
D a y 
5 2 3
D a y
8
D a y
1 5
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 1
d a y
± 2 
d a ys
± 2
d a ys
± 2
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
I nf or me d C o nse nt2
X
Me dical/ O nc ol o gical Hist or y
X
Baseli ne Si g ns/ S y m pt o ms 3
X
P h ysical E xa mi nati o n 3
X
( X)
X
Brief P h ysical E xa mi nati o n 3
X
X  
X  
X  
X
X
X
Vital Si g ns 4
X  
X
X  
X  
X  
X
X  
X
X
E C O G Perf or ma nce Stat us 5
X  
X
X
X
C o ntrace pti o n C hec k
X  
X
X
X
X
1 2 -Lea d E C G 6
X  
X  
X
X 6
X
X
X 6
X ( C 4 
o nl y)
X ( C 4 
o nl y)
X ( C 4 
o nl y)
X ( C 4 
o nl y)
X
L a b or at ory St u dies
Viral disease scree ni n g 7
X
He mat ol o g y 8
X  
X
X  
X  
X  
X
X ( C 2 
& C 3 
o nl y)
X
( X)
Bl o o d C he mistr y 9
X  
X
X  
X  
X  
X
X ( C 2 
& C 3 
o nl y)
X
( X)
C oa g ulati o n 1 0
X  
X
X
( X)
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4
T a ble 1 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h o ut Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase - O ne C ycle = 2 8 d a ys
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
C ycle 1
C ycles ≥2 
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
3
D a y 
5 2 3
D a y
8
D a y
1 5
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 1
d a y
± 2 
d a ys
± 2
d a ys
± 2
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
Uri nal ysis 1 1
X
X 1 1
X 1 1
X 1 1
X 1 1
X
( X)
Pre g na nc y test 1 2
X  
X
X 1 2
X
X 1 2
C y t o ki ne e val uati o n (l ocal la b) 
C y t o ki nes s h o ul d be assesse d wit h la b orat or y st u dies i n t he e ve nt of C R S.
P K, P D, a n d I m m u n o ge nicit y 
Assess me nts
Refer t o Ta ble 3 a n d Ta ble 5
St u dy Tre at me nt
Re gistrati o n 1 3
X
Pre me dicati o n 2 4
X
P F -0 7 0 6 2 1 1 9 a d mi nistrati o n 1 4
X
X
X
X
P F -0 6 8 0 1 5 9 1 a d mi nistrati o n 1 4
X
X
Be vaciz u ma b - Pf izer a d mi nistrati o n 1 4
X
X
X
X
I njecti o n Site T olera bilit y 
Assess me nt 1 5
X  
X ( C 1 
o nl y)
X
A s cli nic ally i n dic ate d
I n patie nt M o nit ori n g1 6
◄--►
◄--►
X
X
Ot her Cli nic al Assess me nts
A d verse E ve nt Re p orti n g 1 7
◄----------------------------------------------------------------------------------------------------------------------------- ----------------------------------►
C o nc o mita nt Me dicati o ns/ Treat me nts 1 8
◄------------------------------------------------------------------------------------------------------------------------------ ►
Dise ase Assess me nts 2 1
C T/ M RI Sca ns of C hest, A b d o me n, 
Pel vis, a n y cli nicall y i n dicate d sites of 
disease, a n d of b o ne lesi o ns; Cli nical 
e val uati o n of s u perficial disease 
X
Perf or me d e ver y 8 wee ks fr o m C 1 D 1 ( ± 7 da ys) f or t he first 6 m o nt hs, e ver y 1 2 wee ks 
( ± 7 da ys) f or t he ne xt 1 8 m o nt hs, a n d e ver y 4 m o nt hs t hereafter.
X
Carci n oe m br y o nic A nti ge n ( C E A) 
Assess me nt 2 2
X  
X
X
X
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5
T a ble 1 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h o ut Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase - O ne C ycle = 2 8 d a ys
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
C ycle 1
C ycles ≥2 
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
3
D a y 
5 2 3
D a y
8
D a y
1 5
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 1
d a y
± 2 
d a ys
± 2
d a ys
± 2
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
N otes: Visit wi n d o ws are calc ulate d fr o m t he first da y of eac h c ycle. Assess me nts t hat a p pear as ( X) are o pti o nal.
1 Scree ni n g : t o be o btai ne d wit hi n 2 8 da ys pri or t o re gistrati o n.
2 I nf or me d C o nse nt: m ust be o btai ne d pri or t o u n der g oi n g a n y st u d y s pecific pr oce d ures. Ma y be o btai ne d m ore t ha n 2 8 da ys pri or t o re gistrati o n. I n Ja pa n, after c o m pleti o n of 
C y cle 1, partici pa nts will be as ke d t o si g n a n a d diti o nal c o nse nt d oc u me nt i n at least Part 1 A f or c o nfir mati o n of t he partici pa nt’ s willi n g ness t o c o nti n ue partici pati o n i n t his st u d y 
bef ore starti n g C ycle 2.
3 C o m plete P h ysic al E x a m i n ati o n: N o nee d t o re peat o n C 1 D 1 if scree ni n g assess me nt is perf or me d wit hi n 3 da ys of d osi n g, i ncl u di n g assess me nt of wei g ht . Brief P h ysic al 
E x a m i n ati o n i ncl u di n g Baseli ne Si g ns a n d S y m pt o ms: A s y m pt o m directe d e xa m a n d assess me nt f or e mer ge nt t o xicities or c ha n ges fr o m pri or vis its ( See Secti o n 8. 1. 1 ), d oes n ot 
nee d t o be re peate d if d o ne wit hi n 2 4 h o urs of C 1 D 1.
4 Vit al Si g ns: I ncl u des te m perat ure ( oral, t y m pa nic, te m p oral or a xillar y), b o d y wei g ht, bl o o d press ure ( B P), a n d p ulse rate t o be rec or de d i n a se mis u pi ne or seate d p ositi o n. O n 
eac h d osi n g da y, vitals s h o ul d be meas ure d pri or t o t he P F -0 7 0 6 2 1 1 9 i njecti o n or i nf usi o n. I n a d diti o n, p ulse o xi metr y is t o be rec or de d o n d osi n g da ys pri or t o t he P F -0 7 0 6 2 1 1 9 
i njecti o n or i nf usi o n as part of t he vital si g n e val uati o n.
5 Perf or m a nce St at us: Use Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G).
6 Tri plic ate 1 2 -Le a d E C G: Tri plicate E C Gs t o be c ollecte d i n C ycle 1 o n Da y 1, 2, 3 ( partici pa nts i n Part 1 A a n d 1 B o nl y), 5, a n d 1 5 a n d o n Da y 1 of C y cles 2, 3, 4 a n d 5.
A d diti o nall y, i n C ycle 4 o nl y, E C Gs will be c ollecte d o n Da y 2, 5, 8, a n d 1 5, c oi nci di n g wit h t he P K sa m ple c ollecti o n . F oll o wi n g C ycle 5, E C Gs will be ta ke n o n Da y 1 of e ver y 
3r d c ycle o nl y (ie, C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc). A d diti o nal E C Gs s h o ul d be c ollecte d as cli nicall y i n dicate d, at t he discreti o n of t he i n vesti gat or. At eac h 
ti me p oi nt 3 c o nsec uti ve 1 2 -lea d E C Gs will be perf or me d a p pr o xi matel y 2 mi n utes a part t o deter mi ne mea n Q Tc F ( Q T usi n g Fri dericia's f or m ula). W he n c oi nci di n g wit h bl o o d 
sa m ple c ollecti o ns f or p har mac o ki netics ( P K), E C G assess me nt s h o ul d be perf or me d pri or t o bl o o d sa m ple c ollecti o n, s uc h t hat t he bl o o d sa m ple is c ollecte d at t he n o mi nal ti me. 
If t he mea n Q Tc F is pr ol o n ge d ( > 5 0 0 msec), t he E C Gs s h o ul d be re -e val uate d b y a q ualifie d pers o n at t he i nstit uti o n f or c o nfir mati o n.
7 U ni q ue Scree ni n g/ Vir al Dise ase L a b or at or y Tests: He patitis B s urface a nti ge n, he patitis B c ore a nti b o d y, he patitis C a nti b o d y a n d HI V or AI D S as well as f ollicle sti m ulati n g 
h or m o ne ( F S H) f or p ost me n o pa usal w o me n w h o are a me n orr h oeic f or at least 1 2 c o nsec uti ve m o nt hs o nl y. Sa m ples will be a nal yze d l ocall y.
8 He m at ol o g y: N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys of d osi n g. Assess me nts perf or me d at all s u bse q ue nt d osi n g visits s h o ul d be o btai ne d 
wit hi n 4 8 h o urs pri or t o d osi n g. He mat ol o g y assess me nt f oll o wi n g c ycle 1 (e g, C 1 D 2 9 or C 1 D 3 0) s h o u l d be c ollecte d a n d re vie we d pri or t o d osi n g o n C 2 D 1. Sa m ples will be 
a nal yze d l ocall y. A c o m plete list of he mat ol o g y la bs ca n be f o u n d i n A p pe n di x 2 .
9 Bl o o d C he mistr y: A c o m plete list of bl o o d c he mistr y la bs ca n b e f o u n d i n A p pe n di x 2 . Meas ure me nt of C -reacti ve pr otei n ( C R P) n ot re q uire d after C 2 D 1 if wit hi n n or mal 
ra n ge or si milar t o baseli ne le vels; h o we ver, C R P s h o ul d be meas ure d a n yti me c yt o ki ne release s y n dr o me is s us pecte d a n d n ot alrea d y sc he d ule d t o be meas ure d (e g, C ycle 2). N o 
nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys pri or t o d osi n g. Assess me nts perf or me d at all s u bse q ue nt d osi n g visits s h o ul d be o btai ne d wit hi n 4 8 h o urs 
pri or t o d osi n g. Bl o o d c he mistr y assess me nt f oll o wi n g C ycle 1 (e g, C 1 D 2 9 or C 1 D 3 0) s h o ul d be c ollecte d a n d re vie we d pri or t o d osi n g o n C 2 D 1. Sa m ples will be a nal yze d 
l ocall y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6
T a ble 1 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h o ut Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase - O ne C ycle = 2 8 d a ys
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
C ycle 1
C ycles ≥2 
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
3
D a y 
5 2 3
D a y
8
D a y
1 5
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 1
d a y
± 2 
d a ys
± 2
d a ys
± 2
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
1 0 C o a g ul ati o n: A c o m plete list of c oa g ulati o n la bs ca n be f o u n d i n A p pe n di x 2 . N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys of d osi n g. Sa m ples 
will be a nal yze d l ocall y.
1 1 Uri n al ysis: Di pstic k is acce pta ble. Micr osc o pic a nal yses if di pstic k a b n or mal. N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys of d osi n g, wit h t he 
e xce pti o n of partici pa nts w h o are recei vi n g be vaciz u ma b -Pf izer w h o will re q uire uri nal ysis ( di pstic k is acce pta ble) pri or t o e ver y d ose of be vaciz u ma b-Pf izer. Sa m ples will be 
a nal yze d l ocall y. Ur i nal ysis ( di pstic k is acce pta ble) assess me nt is re q uire d pri or t o e ver y be vaciz u ma b-Pf izer d ose t hr o u g h o ut t he c o urse of t he st u d y. If uri nal ysis de m o nstrates 
pr otei n greater t ha n or e q ual t o 2 +, t he n a 2 4 -h o ur ur i ne pr otei n c ollecti o n s h o ul d f oll o w. I n pa rtici pa nts wit h pr otei n uria greater t ha n or e q ual t o 2 gra ms per 2 4 h o urs, 
be vaciz u ma b -Pf izer s h o ul d be hel d u ntil rec o ver y (less t ha n 2 gra ms per 2 4 h o urs). Disc o nti n ue be vaciz u ma b-Pf izer i n partici pa nts t hat de vel o p ne p hr otic s y n dr o me.
1 2 Pre g n a nc y Test: F or fe male partici pa nts of c hil d beari n g p ote ntial, a ser u m or uri ne pre g na nc y test, wit h se nsiti vit y of at least 2 5 mI U/ m L will be perf or me d o n 2 occasi o ns 
pri or t o starti n g st u d y treat me nt – o nce at t he start of scree ni n g a n d o nce o n C 1 D 1 i m me diatel y bef ore a d mi nistrati o n of st u d y i nter ve nti o n ( wit hi n 2 4 h o urs pri or t o C 1 D 1 d osi n g). 
Pre g na nc y tests will als o be r o uti nel y re peate d at e ver y ot her c ycle d uri n g t he acti ve treat me nt peri o d f oll o wi n g C 1 D 1 a n d C 2 D 1, at t he e n d of st u d y treat me nt a n d a d diti o nal 
w he ne ver o ne me nstr ual c ycle is misse d or w he n p ote ntial pre g na nc y is ot her wise s us pecte d. D uri n g f oll o w -u p, a pre g na nc y test is o nl y re q uire d 3 0, 9 0, a n d 1 8 0  da ys after E O T 
f or partici pa nts w h o recei ve P F- 0 6 8 0 1 5 9 1. A d diti o nal pre g na nc y tests ma y als o be u n derta ke n if re q ueste d b y I R B or if re q uire d b y l ocal re g ulati o ns.
1 3 Re gistr ati o n: Partici pa nt e nr oll me nt n u m ber a n d d ose le vel all ocati o n pr o vi de d b y Pfizer I nc. Re gistrati o n s h o ul d occ ur bef ore a n y ot her Da y 1 acti vities are perf or me d.
1 4 St u d y Tre at me nt: P F -0 7 0 6 2 1 1 9 will be a d mi nistere d o nce e ver y 1 4 da ys as a n S C i njecti o n. P F -0 6 8 0 1 5 9 1 will be a d mi nistere d o nce e ver y 2 8 -d a y  c ycle as a n S C i njecti o n 
be gi n ni n g o n C 1 D 1 of Part 1 B. Be vaciz u ma b -Pf izer or t he bi osi milar versi o n of A vasti n® , ma n ufact ure d b y Pfizer a n d hereafter referre d t o as be vaciz u ma b -Pf izer will be use d f or 
t his st u d y a n d a d mi nistere d o nce e ver y 1 4 da ys as I V i nf usi o n be gi n ni n g o n C 1 D 1 of Part 1 B. See Secti o n 6. 1. 1 of t he pr ot oc ol f or a d mi nistrati o n i nf or mati o n. Partici pa nts pla n ne d 
t o recei ve P F-0 7 0 6 2 1 1 9 i n c o m bi nati o n wit h be vaciz u ma b -Pf izer s h o ul d be wei g he d wit hi n 7 2 h o urs pri or t o d osi n g f or e ver y c ycle t o e ns ure t he y di d n ot e x perie nce eit her a 
wei g ht l oss or gai n > 1 0 % fr o m t he pri or wei g ht use d t o calc ulate t he a m o u nt of be vaciz u ma b -Pf izer re q uire d f or d ose pre parati o n. Decisi o n t o recalc ulate be vaciz u ma b-Pf izer d ose 
base d o n t he wei g ht o bta i ne d at eac h c ycle ca n be i n acc or da nce wit h i nstit uti o nal practice, h o we ver if t he partici pa nt e x perie nce d eit her a wei g ht loss or gai n > 1 0 % c o m pare d t o 
t he wei g ht use d t o calc ulate eit her t he i nitial or pre vi o us d ose, t he a m o u nt of be vaciz u ma b-Pf izer re quire d f or pre parati o n a n d a d mi nistrati o n f or t he c urre nt c ycle m ust be 
recalc ulate d usi n g t his m ost rece nt wei g ht o btai ne d. Partici pa nts i n Part 2 will be o bser ve d f or at least 2 4 h o urs after t he first S C d ose. Partici pa nts ma y o nl y be release d after t he 
in vesti gat or has c o nfir me d t he partici pa nt has n ot e x hi bite d si g ns of c yt o ki ne release s y n dr o me.
1 5 I njecti o n Site T oler a bilit y Assess me nt: Assess me nt of eac h i njecti o n s h o ul d be c o n d ucte d f or at least 1 h o ur f oll o wi n g eac h treat me nt a d mi nistrati o n i n C ycle 1. I n a d diti o n, 
a n assess me nt s h o ul d be perf or me d 2 4 h o urs ( ± 1 h o ur) after t he C 1 D 1 d ose. I njecti o n site t olera bilit y assess me nts s h o ul d c o nt i n ue after eac h d osi n g visit i n C ycle 2 a n d be y o n d, 
o nl y if i njecti o n site pai n or I S R c haracteristics c o nti n ue t o persist. T he assess me nts s h o ul d c o nti n ue at re g ularl y sc he d ule d visits u ntil t he s y m pt o ms res ol ve. All fi n di n gs s h o ul d 
be rec or de d o n t he i njecti o n site reacti o n C R F. See Secti o n 8. 1. 7 f or m ore details.
1 6 I n p atie nt M o nit ori n g: Partici pa nts recei vi n g P F -0 7 0 6 2 1 1 9 S C will be a d mitte d f or i n patie nt m o nit ori n g f or at least 4 8 h o urs f oll o wi n g t he first a d mi nistrati o n of st u d y 
treat me nt ( C 1 D 1) a n d f or at least 8 h o urs f oll o wi n g t he sec o n d a d mi nistrati o n of st u d y treat me nt ( C 1 D 1 5). Partici pa nts s h o ul d re mai n i n h o use f or o bser vati o n f or at least 1-h o ur 
p ost d ose f or all visits after C 1 f or Parts 1 A a n d 1 B; i n patie nt m o nit ori n g after C 1 f or Part 2 is at t he i n vesti gat or’s discreti o n. Partici pa nts ma y be release d o nl y after t he 
i n vesti gator has c o nfir me d t he partici pa nt has n ot e x hi bite d si g ns of a c yt o ki ne reacti o n. Partici pa nts s h o ul d c o m plete t he re q uire d st u d y s pecific la b orat or y assess me nts as detaile d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7
T a ble 1 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h o ut Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase - O ne C ycle = 2 8 d a ys
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
C ycle 1
C ycles ≥2 
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
3
D a y 
5 2 3
D a y
8
D a y
1 5
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 1
d a y
± 2 
d a ys
± 2
d a ys
± 2
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
i n t he Sc he d ule of P har mac o ki netic, P har mac o d y na mic, a n d I m m u n o ge nicit y Assess me nts f or Parts 1 A a n d 1 B w here P F- 0 7 0 6 2 1 1 9 will be a d mi nistere d S C a n d s h o ul d be 
m o nit ore d per l ocal sta n dar d practice f or i n patie nt m o nit ori n g.
1 7 A d verse E ve nt ( A E) Assess me nts: A Es s h o ul d be d oc u me nte d a n d rec or de d at eac h visit usi n g t he Nati o nal Ca ncer I n stit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse 
E ve nts ( N CI C T C A E) versi o n 5. 0. Partici pa nts m ust be f oll o we d f or A Es f or 2 8 da ys after t he last st u d y treat me nt a d mi nistrati o n or u ntil all dr u g -relate d t o xicities ha ve res ol ve d, 
w hic he ver is later; or earli er t ha n 2 8 da ys s h o ul d t he partici pa nt c o m me nce a n ot her a ntica ncer t hera p y i n t he mea nti me. F or seri o us a d verse e ve nts ( S A Es) , t he acti ve re p orti n g 
peri o d t o Pfizer or its desi g nate d re prese ntati ve be gi ns fr o m t he ti me t hat t he partici pa nt pr o vi des i nf or me d c o nse nt, w hic h is o btai ne d pri or t o t he partici pa nt’s partici pati o n i n t he 
st u d y, ie, pri or t o u n der g oi n g a n y st u d y-relate d pr oce d ure a n d/ or recei vi n g st u d y i nter ve nti o n, t hr o u g h a n d i ncl u di n g 2 8 cale n dar da ys after t he last st u d y treat me nt a d mi nistrati on. 
S A Es occ urri n g t o a partici pa nt after t he acti ve re p orti n g peri o d has e n de d s h o ul d be re p orte d t o t he s p o ns or if t he i n vesti g at or bec o mes a ware of t he m; at a mi ni m u m, all S A Es 
t hat t he i n vesti gat or belie ves ha ve at least a reas o na ble p ossi bilit y of bei ng relate d t o st u d y i nter ve nti o n are t o be re p orte d t o t he s p o ns or.
1 8 C o nc o mit a nt Tre at me nts: Al l c o nc o mita nt me dicati o ns s h o ul d be rec or de d i n t he case re p ort f or m ( C R F) i ncl u di n g s u p p orti ve care dr u gs (e g, a nti-e metic treat me nt a n d 
pr o p h yla xis), a n d t he dr u gs use d t o treat a d verse e ve nts or c hr o nic diseases, a n d n o n- dr u g s u p p orti ve i nter ve nti o ns (e g, tra nsf usi o ns).
1 9 E n d of Tre at me nt Visit/ Wit h dr a w al ( E O T): O btai n t hese assess me nts if n ot c o m plete d i n t he last wee k (last 6 wee ks f or t u m or assess me nts).
2 0 F oll o w -U p: At least 2 8 da ys, a n d n o m ore t ha n 3 5 da ys, after disc o nti n uati o n of treat me nt, all partici pa nts will ret ur n t o o btai n t hese assess me nts as well as a n e val uate t he
res ol uti o n of a n y treat me nt-relate d t o xicit y. Partici pa nts w h o recei ve P F- 0 6 8 0 15 9 1 will als o ret ur n f or f oll o w -u p assess me nts 3 0, 9 0, a n d 1 8 0 da ys after treat me nt disc o nti n uati o n. 
Partici pa nts c o nti n ui n g t o e x perie nce t o xicit y at t his p oi nt f oll o wi n g disc o nti n uati o n of treat me nt will c o nti n ue t o be f oll o we d at least e ver y 4 wee ks u nt il res ol uti o n or 
deter mi nati o n, i n t he cli nical j u d g me nt of t he i n vesti gat or, t hat n o f urt her i m pr o ve me nt is e x pecte d. Partici pa nts wit h a n u n res ol ve d A E p ossi bl y relate d t o a nti-dr u g a nti b o dies 
( A D A) will be as ke d t o ret ur n t o t he cli nic f or A D A/ ne utralizi n g a nti b o dies ( NA b) a n d dr u g c o nce ntrati o n assess me nts at a p pr o xi matel y 3- m o nt h i nter vals u ntil t he A E or its 
se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or u p t o a ma xi m u m of 9 m o nt hs. S u bse q ue nt t o t he F oll o w- U p visi t, partici pa nts s h o ul d be c o ntacte d 
b y tele p h o ne e ver y 8 wee ks ( ± 7 d a y s) t o o btai n i nf or mati o n o n s u bse q ue nt a nti-ca ncer treat me nt a n d o verall s ur vi val f or u p t o t w o years fr o m t he date of ra n d o mizati o n.
2 1 T u m or Assess me nts: T u m or assess me nts will i ncl u de all k n o w n or s us pecte d disease sites. I ma gi n g ma y i ncl u de c hest, a b d o me n a n d pel vis C T or M RI sca ns or e q ui vale nt. 
T he sa me m o dalit y s h o ul d be c o m plete d, if p ossi ble t hr o u g h o ut t he st u d y. B o ne sca ns will be perf or me d at baseli ne if disease is s us pecte d a nd o n st u d y as a p pr o priate t o f oll o w 
disease. Baseli ne ce ntral ner v o us s yste m ( C N S) i ma gi n g is n ot re q uire d wit h t he e xce pti o n of s y m pt o matic partici pa nts t o r ule o ut C N S metastases; partici pa nt i neli gi ble if p ositi ve 
f or ne w C N S metastases, pre vi o usl y treate d C N S metastases are all o we d as o utli ne d e xcl usi o n criteria. C T or M RI sca ns t o be d o ne as o utli ne d i n t he Sc he d ule of Acti vities ( S O A ) 
u ntil disease pr o gressi o n b y ir R E CI S T or deat h, or u ntil per ma ne nt disc o nti n uati o n of st u d y treat me nt. Res p o nse (c o m plete res p o nse ( C R)/ partial res p o nse ( P R)) a n d disease 
pr o gressi o n will be c o nfir me d wit h 2 c o nsec uti ve ti me p oi nts at least 4 wee ks a part (i n t he a bse nce of ra pi d cli nical deter i orati o n f or pr o gressi o n). T u m or assess me nts s h o ul d be 
fi xe d acc or di n g t o t he cale n dar, re gar dless of treat me nt dela ys. T u m or assess me nts s h o ul d be re peate d at t he E n d of Treat me nt visit if m ore t ha n 6 wee ks ha ve passe d si nce t he last 
e val uati o n.
2 2 C E A As sess me nts: Perf or me d o n Da y 1 of eac h C ycle f or u p t o 1 year. After 1 year, perf or m e ver y 4 m o nt hs t hereafter.
2 3 T he Da y 5 visit wi n d o w is e x pa n de d ( ± 1 da y) f or partici pa nts i n Part 2 o nl y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8
T a ble 1 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h o ut Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase - O ne C ycle = 2 8 d a ys
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
C ycle 1
C ycles ≥2 
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
3
D a y 
5 2 3
D a y
8
D a y
1 5
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 1
d a y
± 2 
d a ys
± 2
d a ys
± 2
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
2 4 Pre m e dic ati o n: A p pr o xi matel y 1 h o ur pri or t o P F -0 7 0 6 2 1 1 9 d osi n g o n C 1 D 1 o nl y, a d mi nister pre me dicati o n as f oll o ws: aceta mi n o p he n 6 5 0 m g ( or e q ui vale nt), oral; 
di p he n h y dra mi ne 2 5 m g, oral or I V; de xa met has o ne 1 2 m g ( or e q ui vale nt), oral or I V. I n a d diti o n, pre me dicati o n be y o n d t he 1st f ull d ose a n d m o dificati o ns t o t he pre me dicati o n 
re gi me n (e g, fre q ue nc y of pre me dicati o n, d oses of i n di vi d ual a ge nts, re m o val or a d diti o n of a ge nts) ma y be i m ple me nte d b y t he s p o ns or base d o n e mer gi n g data. A n y e xce pti o ns 
t o pre me dicati o n re q uire disc ussi o n a n d a gree me nt bet wee n t he s p o nsor a n d i n vesti gat or.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9
T a ble 2 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase ( 1 C ycle = 2 8 d a ys)
C ycle 1
C ycles ≥2
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
8
D a y 
1 5
D a y
1 6
D a y
1 9
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 2 
d a ys
± 1 
d a ys
± 2
d a ys
± 2 
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
I nf or me d C o nse nt2
X
Me dical/ O nc ol o gical Hist or y
X
Baseli ne Si g ns/ S y m pt o ms 3
X
P h ysical E xa mi nati o n 3
X
( X)
X
X
Brief P h ysical E xa mi nati o n 3
X  
X
X  
X
X
X
Vital Si g ns 4
X  
X  
X  
X
X  
X
X  
X
X
E C O G Perf or ma nce Stat us 5
X  
X
X
X
C o ntrace pti o n C hec k
X  
X
X
X
X
1 2 -Lea d E C G 6
X  
X  
X
X 6
X
X 6
X ( C 4 
o nl y)
X ( C 4 
o nl y)
X ( C 4 
o nl y)
X ( C 4 
o nl y)
X
L a b or at ory St u dies
Viral disease scree ni n g 7
X
He mat ol o g y 8
X  
X  
X  
X
X  
X
X ( C 2 
& C 3 
o nl y)
X
( X)
Bl o o d C he mistr y 9
X  
X  
X  
X
X  
X
X ( C 2
& C 3 
o nl y)
X
( X)
C oa g ulati o n 1 0
X  
X
X
( X)
Uri nal ysis 1 1
X
X 1 1
X 1 1
X 1 1
X 1 1
X
( X)
Pre g na nc y test 1 2
X  
X
X 1 2
X
X 1 2
C y t o ki ne e val uati o n (l ocal la b) 
C y t o ki nes s h o ul d be assesse d wit h la b orat or y st u dies i n t he e ve nt of C R S.
P K, P D, a n d I m m u n o ge nicit y 
Assess me nts
See Ta ble 4 a n d Ta ble 6
St u dy Tre at me nt
Re gistrati o n 1 3
X
Pre me dicati o n 2 3
X
X
P F -0 7 0 6 2 1 1 9 a d mi nistrati o n 1 4
X
X
X
X
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0
T a ble 2 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase ( 1 C ycle = 2 8 d a ys)
C ycle 1
C ycles ≥2
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
8
D a y 
1 5
D a y
1 6
D a y
1 9
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 2 
d a ys
± 1 
d a ys
± 2
d a ys
± 2 
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
P F -0 6 8 0 1 5 9 1 a d mi nistrati o n 1 4
X
X
Be vaciz u ma b - Pf izer a d mi nistrati o n1 4
X
X
X
I njecti o n Site T olera bilit y 
Assess me nt 1 5
X  
X ( C 1 
o nl y)
X
A s cli nic ally i n dic ate d
I n patie nt M o nit ori n g1 6
◄--► 
◄--►
X
X
Ot her Cli nic al Assess me nts
A d verse E ve nt Re p orti n g 1 7
◄---------------------------------------------------------------------------------------------------------------------------------------------------------------►
C o nc o mita nt Me dicati o ns/ Treat me nts 1 8
◄----------------------------------------------------------------------------------------------- -------------------------------►
Dise ase Assess me nts 2 1
C T/ M RI Sca ns of C hest, A b d o me n, 
Pel vis, a n y cli nicall y i n dicate d sites of 
disease, a n d of b o ne lesi o ns; Cli nical 
e val uati o n of s u perficial disease 
X
Perf or me d e ver y 8 wee ks fr o m C 1 D 1 ( ± 7 da ys) f or t he first 6 m o nt hs, e ver y 1 2 wee ks 
( ± 7 da ys) f or t he ne xt 1 8 m o nt hs, a n d e ver y 4 m o nt hs t hereafter.
X
C E A Assess me nt 2 2
X  
X
X
X
N otes: Visit wi n d o ws are calc ulate d fr o m t he first da y of  eac h c ycle. Assess me nts t hat a p pear as ( X) are o pti o nal.
1 Scree ni n g : t o be o btai ne d wit hi n 2 8 da ys pri or t o re gistrati o n.
2 I nf or me d C o nse nt: m ust be o btai ne d pri or t o u n der g oi n g a n y st u d y s pecific pr oce d ures. Ma y be o btai ne d m ore t ha n 2 8 da ys pri or t o re gistrati o n.
3 C o m plete P h ysic al E x a m i n ati o n: N o nee d t o re peat o n C 1 D 1 if scree ni n g assess me nt is perf or me d wit hi n 3 da ys of d osi n g, i ncl u di n g assess me nt of wei g ht . Brief P h ysic al 
E x a m i n ati o n i ncl u di n g Baseli ne Si g ns a n d S y m pt o ms: A s y m pt o m directe d e xa m a n d assess me nt f or e mer ge nt t o xicities or c ha n ges fr o m pri or visits ( See Secti o n 8. 1. 1 ), d oes n ot 
nee d t o be re peate d if d o ne wit hi n 2 4 h o urs of C 1 D 1.
4 Vit al Si g ns: I ncl u des te m perat ure ( oral, t y m pa nic, te m p oral or a xillar y), b o d y wei g ht, B P, a n d p ulse rate to be rec or de d i n a se mis u pi ne or seate d p ositi o n. O n eac h d osi n g da y, 
vitals s h o ul d be meas ure d pri or t o t he P F - 0 7 0 6 2 1 1 9 i njecti o n or i nf usi o n. I n a d diti o n, p ulse o xi metr y is t o be rec or de d o n d osi n g da ys pri or t o t he P F-0 7 0 6 2 1 1 9 i njecti o n or 
i nf usi o n as p art of t he vital si g n e val uati o n.
5 Perf or m a nce St at us: Use E C O G.
6 Tri plic ate 1 2 -Le a d E C G: Tri plicate E C Gs t o be c ollecte d i n C ycle 1 o n Da y 1, 2 ( partici pa nts i n Part 1 A a n d 1 B o nl y), 8, a n d 1 5 a n d o n Da y 1 of C ycle s 2, 3, 4 a n d 5.
A d diti o nall y, i n C ycle 4 o nl y, E C Gs will be c ollecte d o n Da y 2, 5, 8, a n d 1 5, c oi nci di n g wit h t he P K sa m ple c ollecti o n. F oll o wi n g C ycle 5, E C Gs will be ta ke n o n Da y 1 of e ver y 
3r d c ycle o nl y (ie, C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc). A d diti o nal E C Gs s h o ul d be c ollecte d as cli nicall y i n dicate d, at t he discreti o n of t he i n vesti gat or. At eac h 
ti me p oi nt 3 c o nsec uti ve 1 2 -lea d E C Gs will be perf or me d a p pr o xi matel y 2 mi n utes a part t o deter mi ne mea n Q Tc F. W he n c oi nci di n g wit h bl o o d sa m ple c ollecti o ns f or P K, E C G 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1
T a ble 2 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase ( 1 C ycle = 2 8 d a ys)
C ycle 1
C ycles ≥2
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
8
D a y 
1 5
D a y
1 6
D a y
1 9
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 2 
d a ys
± 1 
d a ys
± 2
d a ys
± 2 
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
assess me nt s h o ul d be perf or me d pri or t o bl o o d sa m ple c ollecti o n, s uc h t hat t he bl o o d sa m ple is c ollecte d at t he n o mi nal ti me. If t he mea n Q Tc F is pr ol o n ge d ( > 5 0 0 msec), t he 
E C Gs s h o ul d be re -e val uate d b y a q ualifie d pers o n at t he i nstit uti o n f o r c o nfir mati o n.
7 U ni q ue Scree ni n g/ Vir al Dise ase L a b or at or y Tests: He patitis B s urface a nti ge n, he patitis B c ore a nti b o d y, he patitis C a nti b o d y a n d HI V or AI D S as well as F S H f or 
p ost me n o pa usal w o me n w h o are a me n orr h oeic f or at least 1 2 c o nsec uti ve m o nt hs o nl y. Sa m ples will be a nal yze d l ocall y.
8 He m at ol o g y: N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys of d osi n g. Assess me nts perf or me d at all s u bse q ue nt d osi n g visits s h o ul d be o btai ne d 
wit hi n 4 8 h o urs pri or t o d osi n g. He mat ol o g y assess me nt f oll o wi n g c ycle 1 (e g, C 1 D 2 9 or C 1 D 3 0) s h o ul d be c ollecte d a n d re vie we d pri or t o d osi n g o n C 2 D 1. Sa m ples will be 
a nal yze d l ocall y. A c o m plete list of he mat ol o g y la bs ca n be f o u n d i n A p pe n di x 2 .
9 Bl o o d C he mistr y:
A c o m plete list of bl o o d c he mistr y la bs ca n be f o u n d i n A p pe n di x 2 . Meas ure me nt of C R P n ot re q uire d after C 2 D 1 if wit hi n n or mal ra n ge or si milar t o 
baseli ne le vels; h o we ver, C R P s h o ul d be meas ure d a n yti me c yt o ki ne release s y n dr o me is s us pecte d a n d n ot alrea d y sc he d ule d t o be meas ure d (e g, C ycle 2). N o nee d t o re peat o n 
C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys pri or t o d osi n g. Assess me nts perf or me d at all s u bse q ue nt d osi n g visits s h o ul d be o btai ne d wit hi n 4 8 h o urs pri or t o d osi n g. 
Bl o o d c he mistr y assess me nt f oll o wi n g C ycle 1 (e g, C 1 D 2 9 or C 1 D 3 0) s h o ul d be c ollecte d a n d re vie we d pri or t o d osi n g o n C 2 D 1. Sa m ples will be a nal yze d l ocall y.
1 0 C o a g ul ati o n: A c o m plete list of c oa g ulati o n la bs ca n be f o u n d i n A p pe n di x 2 . N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys of d osi n g. Sa m ples 
will be a nal yze d l ocall y.
1 1 Uri n al ysis: Di pstic k is acce pta ble. Micr osc o pic a nal yses if di pstic k a b n or mal. N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 7 da ys of d osi n g, wit h t he 
e xce pti o n of partici pa nts w h o are recei vi n g be vaciz u ma b -Pf izer w h o will re q uire uri nal ysis ( di pstic k is acce pta ble) pri or t o e ver y d ose of be vaciz u ma b-Pf izer. Sa m p les will be 
a nal yze d l ocall y. Uri nal ysis ( di pstic k is acce pta ble) assess me nt is re q uire d pri or t o e ver y be vaciz u ma b-Pf izer d ose t hr o u g h o ut t he c o urse of t he st u d y. If uri nal ysis de m o nstrates 
pr otei n greater t ha n or e q ual t o 2 +, t he n a 2 4 -h o ur ur i ne pr otei n c ollecti o n s h o ul d f oll o w. I n partici pa nts wit h pr otei n uria greater t ha n or e q ual t o 2 gra ms per 2 4 h o urs, 
be vaciz u ma b -Pf izer s h o ul d be hel d u ntil rec o ver y (less t ha n 2 gra ms per 2 4 h o urs). Disc o nti n ue be vaciz u ma b-Pf izer i n partici pa nts t hat de vel o p ne p hr otic s y n dr o me.
1 2 Pre g n a nc y Test: F or fe male partici pa nts of c hil d beari n g p ote ntial, a ser u m or uri ne pre g na nc y test, wit h se nsiti vit y of at least 2 5 mI U/ m L will be perf or me d o n 2 occasi o ns 
pri or t o starti n g st u d y treat me nt – o nce at t he start of scree ni n g a n d o nce o n C 1 D 1 i m me diatel y bef ore a d mi nistrati o n of st u d y i nter ve nti o n ( wit hi n 2 4 h o urs pri or t o C 1 D 1 d osi n g). 
Pre g na nc y tests will als o be r o uti nel y re peate d at e ver y ot her c ycle d uri n g t he acti ve treat me nt peri o d f oll o wi n g C 1 D 1 a n d C 2 D 1, at t he e n d of st u d y treat me nt a n d a d diti o nal 
w he ne ver o ne me nstr ual c ycle is misse d or w he n p ote ntial pre g na nc y is ot her wise s us pecte d. D uri n g f oll o w -u p, a pre g na nc y test is o nl y re q uire d 3 0, 9 0 a n d 1 8 0 da ys after E O T f or 
partici pa nts w h o recei ve P F -0 6 8 0 1 5 9 1. A d diti o nal pre g na nc y tests ma y als o be u n derta ke n if re q ueste d b y I R B or if re q uire d b y l ocal re g ulati o ns.
1 3 Re gistr ati o n: Partici pa nt e nr oll me nt n u m ber a n d d ose le vel all ocati o n pr o vi de d b y Pfizer I nc. Re gistrati o n s h o ul d occ ur bef ore a n y ot her Da y 1 acti vities ar e perf or me d.
1 4 St u d y Tre at me nt: P F -0 7 0 6 2 1 1 9 will be a d mi nistere d o nce e ver y 1 4 da ys as a n S C i njecti o n. A pri mi n g d ose will be a d mi nistere d o n C 1 D 1 f oll o we d b y a f ull d ose o n C 1 D 1 5 
a n d Q 2 W t hereafter.  See Secti o n 4. 1. 1. 2 f or p ote ntial c ha n ges t o t he pri mi n g d ose re gi me n (e g, ste p-u p d osi n g strate g y).  P F - 0 6 8 0 1 5 9 1 will be a d mi nistere d o nce e ver y 2 8-da y 
c ycle as a n S C i njecti o n be gi n ni n g o n C 1 D 1 5 of Part 1 B. Be vaciz u m a b -Pf izer or t he bi osi milar versi o n of A vasti n® , ma n ufact ure d b y Pfizer a n d hereafter referre d t o as 
be vaciz u ma b -Pf izer will be use d f or t his st u d y a n d a d mi nistere d o nce e ver y 1 4 da ys as I V i nf usi o n be gi n ni n g o n C 1 D 1 5 of Part 1 B. See Secti o n 6. 1. 1 of t he pr ot oc ol f or 
a d mi nistrati o n i nf or mati o n. Partici pa nts pla n ne d t o recei ve P F -0 7 0 6 2 1 1 9 i n c o m bi nat i o n wit h be vaciz u ma b-Pf izer s h o ul d be wei g he d wit hi n 7 2 h o urs pri or t o d osi n g f or e ver y 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2
T a ble 2 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase ( 1 C ycle = 2 8 d a ys)
C ycle 1
C ycles ≥2
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
8
D a y 
1 5
D a y
1 6
D a y
1 9
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 2 
d a ys
± 1 
d a ys
± 2
d a ys
± 2 
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
c ycle t o e ns ure t he y di d n ot e x perie nce eit her a wei g ht l oss or gai n > 1 0 % fr o m t he pri or wei g ht use d t o calc ulate t he a m o u nt of be vaciz u ma b -Pf izer re q uire d f or d ose preparati o n. 
Decisi o n t o recalc ulate be vaciz u ma b -Pf izer d ose base d o n t he wei g ht o btai ne d at eac h c ycle ca n be i n acc or da nce wit h i nstit uti o nal practice, h o we ver if t he partici pa nt e x perie nce d 
eit her a wei g ht l oss or gai n > 1 0 % c o m pare d t o t he wei g ht use d t o c alc ulate eit her t he i nitial or pre vi o us d ose, t he a m o u nt of be vaciz u ma b -Pf izer re q uire d f or pre parati o n a n d 
a d mi nistrati o n f or t he c urre nt c ycle m ust be recalc ulate d usi n g t his m ost rece nt wei g ht o btai ne d. Partici pa nts i n Part 2 will be o bser ve d f or at lea st 2 4 h o urs after t he first S C d ose. 
Partici pa nts ma y o nl y be release d after t he i n vesti gat or has c o nfir me d t he partici pa nt has n ot e x hi bite d si g ns of c yt o ki ne re lease s y n dr o me.
1 5 I njecti o n Site T oler a bilit y Assess me nt: Assess me nt of eac h i njecti o n s h o ul d be c o n d ucte d f or at least 1 h o ur f oll o wi n g eac h treat me nt a d mi nistrati o n i n C ycle 1. I n a d diti o n, 
a n assess me nt s h o ul d be perf or me d 2 4 h o urs ( ± 1 h o ur) after t he C 1 D 1 d ose. I njecti o n site t olera bilit y assess me nts s h o ul d c o nt i n ue after eac h d osi n g visit i n C ycle 2 a n d be y o n d, 
o nl y if i njecti o n site pai n or I S R c haracteristics c o nti n ue t o persist. T he assess me nts s h o ul d c o nti n ue at re g ularl y sc he d ule d visits u ntil t he s y m pt o ms res ol ve. All fi n di n gs s h o ul d 
be rec or de d o n t he i njecti o n site reacti o n C R F. See Se cti o n 8. 1. 7 f or m ore details.
1 6 I n p atie nt M o nit ori n g: Partici pa nts recei vi n g P F -0 7 0 6 2 1 1 9 S C will be a d mitte d f or i n patie nt m o nit ori n g f or at least 2 4 h o urs f oll o wi n g t he first a d mi nistrati o n of st u d y 
treat me nt ( C 1 D 1) a n d f or at least 2 4 h o urs f oll o wi n g t he sec o n d a d mi nistrati o n of st u d y treat me nt ( C 1 D 1 5). Partici pa nts s h o uld re mai n i n h o use f or o bser vati o n f or at least 1- h o ur 
p ost d ose f or all visits after C 1 D 1 f or Pa rts 1 A a n d 1 B; i n patie nt m o nit ori n g after C 1 f or Part 2 is at t he i n vesti gat or’s discreti o n. Partici pa nts ma y be release d o nly after t he 
i n vesti gat or has c o nfir me d t he partici pa nt has n ot e x hi bite d si g ns of a c yt o ki ne reacti o n. Partici pa nts s h o ul d c o m plete t he re q uire d st u d y s pecific la b orat or y assess me nts as detaile d 
i n t he Sc he d ule of P har mac o ki netic, P har mac o d y na mic, a n d I m m u n o ge nicit y Assess me nts f or Parts 1 A a n d 1 B w here P F- 0 7 0 6 2 1 1 9 will be a d mi nistere d S C a n d s h o ul d be 
m o nit ore d per l ocal sta n dar d pra ctice f or i n patie nt  m o nit ori n g.
1 7 A E Assess me nts: A Es s h o ul d be d oc u me nte d a n d rec or de d at eac h visit usi n g t he N CI C T C A E versi o n 5. 0. Partici pa nts m ust be f oll o we d f or A Es f o r 2 8 da ys after t he last 
st u d y treat me nt a d mi nistrati o n or u ntil all dr u g-relate d t o xicities ha ve res ol ve d, w hic he ver is later; or earlier t ha n 2 8 da ys s h o ul d t he partici pa nt c o m me nce a n ot her a ntica ncer 
t hera p y i n t he mea nti me. F or S A Es, t he acti ve re p orti n g peri o d t o Pfizer or its desi g nate d re prese ntati ve be gi ns fr o m t he ti me t hat t he partici pa nt pr o vi des i nf or me d c o nse nt, w hic h 
is o btai ne d pri or t o t he partici pa nt’s partici pati o n i n t he st u d y, ie, pri or t o u n der g oi n g a n y st u d y-relate d pr oce d ure a n d/ or recei vi n g st u d y i nter ve nti o n, t hr o u g h a n d i ncl u di n g 2 8 
cale n dar da ys after t he last st u d y treat me nt a d mi nistrati o n. S A Es occ urri n g t o a partici pa nt after t he acti ve re p orti n g peri o d has e n de d s h o ul d be re p orte d t o t he s p o ns or if t he 
i n vesti gat or bec o mes a ware of t he m; at a mi ni m u m, all S A Es t hat t he i n vesti gat or belie ves ha ve at least a reas o na ble p ossi bilit y of bei n g relate d t o st u d y i nter ve nti o n are t o be 
re p orte d t o t he s p o ns or.
1 8 C o nc o mit a nt Tre at me nts: All c o nc o mita nt me dicati o ns s h o ul d be rec or de d i n t he C R F i ncl u di n g s u p p orti ve care dr u gs (e g, a nti -e metic treat me nt a n d pr o ph yla xis), a n d t he 
dr u gs use d t o treat a d verse e ve nts or c hr o nic diseases, a n d n o n- dr u g s u p p orti ve i nter ve nti o ns (e g, tra nsf usi o ns).
1 9 E O T / Wit h dr a w al: O btai n t hese assess me nts if n ot c o m plete d i n t he last wee k (last 6 wee ks f or t u m or assess me nts).
2 0 F oll o w -U p: At least 2 8 da ys, a n d n o m ore t ha n 3 5 da ys, after disc o nti n uati o n of treat me nt, all partici pa nts will ret ur n t o o btai n t hese assess me nts as well as a n e val uate t he
res ol uti o n of a n y treat me nt-relate d t o xicit y. Partici pa nts w h o recei ve P F-0 6 8 0 1 5 9 1 wi ll als o ret ur n f or f oll o w-u p assess me nts 3 0, 9 0 a n d 1 8 0 da ys after treat me nt disc o nti n uati o n. 
Partici pa nts c o nti n ui n g t o e x perie nce t o xicit y at t his p oi nt f oll o wi n g disc o nti n uati o n of treat me nt will c o nti n ue t o be f oll o we d at least e ver y 4 wee ks u ntil res o l uti o n or 
deter mi nati o n, i n t he cli nical j u d g me nt of t he i n vesti gat or, t hat n o f urt her i m pr o ve me nt is e x pecte d. Partici pa nts wit h a n u n res ol ve d A E p ossi bl y relate d t o A D A will be as ke d t o 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3
T a ble 2 . 
Sc he d ule of Acti vities f or P art 1 A, P art 1 B, a n d P art 2 Wit h Pri mi n g D ose
Pr ot oc ol Acti vit y
Scree ni n g 1
Acti ve Tre at me nt P h ase ( 1 C ycle = 2 8 d a ys)
C ycle 1
C ycles ≥2
E n d of 
Tre at me nt/ 
Wit h dr a w al
1 9
P ost -Tre at me nt 
F oll o w -U p 2 0
St u d y D a y
Wit hi n 2 8 d a ys 
pri or t o 
re gistr ati o n
D a y 
1
D a y 2
D a y 
8
D a y 
1 5
D a y
1 6
D a y
1 9
D a y
2 2
D a y 
1
D a y 
2
D a y 
5
D a y 
8
D a y
1 5
Visit Wi n d o w
± 1 
d a y
± 2 
d a ys
± 1 
d a ys
± 2
d a ys
± 2 
d a ys
± 1 
d a y
± 1 
d a y 
± 2
d a ys
± 7
d a ys
ret ur n t o t he cli nic f or A D A/ NA b a n d dr u g c o nce ntrati o n assess me nts at a p pr o xi matel y 3 - m o nt h i nter vals u ntil t he A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o 
t he i n vesti gat or a n d s p o ns or u p t o a ma xi m u m of 9 m o nt hs. S u bse q ue nt t o t he F oll o w-U p visit, partici pa nts s h o ul d be c o ntacte d b y tele p h o ne e ver y 8 wee ks ( ± 7 d a y s) t o o btai n 
i nf or mati o n o n s u bse q ue nt a nti-ca ncer treat me nt a n d o verall s ur vi val f or u p t o t w o years fr o m t he date of ra n d o mizati o n.
2 1 T u m or Assess me nts: T u m or assess me nts will i ncl u de all k n o w n or s us pecte d disease sites. I ma gi n g ma y i ncl u de c hest, a b d o me n a n d pel vis C T or M RI sca ns or e q ui vale nt. 
T he sa me m o dalit y s h o ul d be c o m plete d, if p ossi ble t hr o u g h o ut t he st u d y. B o ne sca ns will be perf or me d at baseli ne if disease is s us pecte d a n d o n st u d y as a p pr o priate t o f oll o w 
disease. Baseli ne C N S i ma gi n g is n ot re q uire d wit h t he e xce pti o n of s y m pt o matic partici pa nts t o r ule o ut C N S metastases; partici pa nt i neli gi ble if p ositi ve f or ne w C N S 
metastases, pre vi o usl y treate d C N S metastases are all o we d as o utli ne d e xcl usi o n criteria. C T or M RI sca ns t o be d o ne as o utli ne d i n t he Sc he d ule of Acti vities ( S O A ) u ntil disease 
pr o gressi o n b y ir R E CI S T or deat h, or u ntil per ma ne nt disc o nti n uati o n of st u d y treat me nt. Res p o nse ( C R , P R) a n d disease pr o gressi o n will be c o nfir me d wit h 2 c o nse c uti ve 
ti me p oi nts at least 4 wee ks a part (i n t he a bse nce of ra pi d cli nical deteri orati o n f or pr o gressi o n). T u m or assess me nts s h o ul d be fi xe d acc or di n g t o t he cale n dar, re gar dless of 
treat me nt dela ys. T u m or assess me nts s h o ul d be re peate d at t he E n d of Treatme nt visit if m ore t ha n 6 wee ks ha ve passe d si nce t he last e val uati o n.
2 2 C E A Assess me nts : Perf or me d o n Da y 1 of eac h C ycle f or u p t o 1 year. After 1 year, perf or m e ver y 4 m o nt hs t hereafter.
2 3 Pre m e dic ati o n: A p pr o xi matel y 1 h o ur pri or t o P F-0 7 0 6 2 1 1 9 d osi n g d uri n g C ycle 1 o nl y, a d mi nister pre me dicati o n as f oll o ws: aceta mi n o p he n 6 5 0 m g ( or e q ui vale nt), oral; 
di p he n h y dra mi ne 2 5 m g, oral or I V; de xa met has o ne 1 2 m g ( or e q ui vale nt), oral or I V. I n a d diti o n, pre me dicati o n be y o n d t he 1st f ull d ose a n d m o dificati o ns t o t he pre me dicati o n 
re gi me n (e g, fre q ue nc y of pre me dicati o n, d oses of i n di vi d ual a ge nts, re m o val or a d diti o n of a ge nts) ma y be i m ple me nte d b y t he s p o ns or base d o n e mer gi n g data. A n y e xce pti o ns 
t o pre me dicati o n re q uire disc ussi o n a n d a gree me nt bet wee n t he s p o ns or a n d i n vesti gat or. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 4
T a ble 3 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 1 A a n d P art 1 B 
Wit h o ut Pri mi n g D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
2
3
5
8
1 5
2 2
1
2
5
8
1 5
E n d of 
Tre at me nt/
Wit h dr a w al
H o urs Pre -/ P ost-D ose 1
0 2
4
8
2 4
4 8
9 6
1 6 8
0
8 
( P art 
1 B 
o nl y)
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 0. 5 hr ± 1 hr
± 3 hrs
± 6 hrs
± 2 4 hrs ± 2 4 hrs
± 1 hr ± 4 8 hrs
± 3 hrs
± 2 4 
hrs
± 2 4 hrs
P har mac o ki netic sa m ples
Bl o o d sa m ples f or 
P F - 0 7 0 6 2 1 1 9 
c o nce ntrati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
( C 4 o nl y)
X 1
( C 4 
o nl y)
X
( C 4 
o nl y)
X
X
Bl o o d sa m ples f or 
A D A/ N A b a gai nst 
P F -0 7 0 6 2 1 1 9 3
X
X
X 3
X
Bl o o d sa m ples f or 
P K/ A D A/ N A b a gai nst 
P F -0 6 8 0 1 5 9 1 3
X
X
X 3
X
Bl o o d sa m ples f or 
P K/ A D A/ N A b a gai nst 
be vaciz u ma b -Pf izer3
X
X
X 3
X
P har mac o d y na mic sa m ples
Pf izer Pre p D 1 ba n ke d 
sa m ple4
X
Arc hi val T u m or 
Sa m ple 5
X
O pti o nal or Ma n dat or y 
De N o v o Pre -treat me nt 
bi o ps y 5 ,6
X
O pti o nal or Ma n dat or y 
O n -Treat me nt T u m or 
Bi o ps y 6
X 
C 3 o nl y
( ± 7 
da ys)
X                
( or 2n d o n 
treat me nt)
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 5
T a ble 3 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 1 A a n d P art 1 B 
Wit h o ut Pri mi n g D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
2
3
5
8
1 5
2 2
1
2
5
8
1 5
E n d of 
Tre at me nt/
Wit h dr a w al
H o urs Pre -/ P ost-D ose 1
0 2
4
8
2 4
4 8
9 6
1 6 8
0
8 
( P art 
1 B 
o nl y)
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 0. 5 hr ± 1 hr
± 3 hrs
± 6 hrs
± 2 4 hrs ± 2 4 hrs
± 1 hr ± 4 8 hrs
± 3 hrs
± 2 4 
hrs
± 2 4 hrs
Bl o o d sa m ple f or T cell 
I m m u n o p he n ot y pi n g7
X
X  
X  
X  
X  
X  
X  
X 7
X ( C 2 a n d C 3 
o nl y)
Bl o o d (ser u m) sa m ple 
f or C yt o ki nes & 
Circ ulati n g Mar kers 8
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 7
X ( C 2 a n d C 3 
o nl y)
1 Sa m pli n g ti mes i n dicate d are relate d t o t he e n d of t he S C i njecti o n. All eff orts s h o ul d be ma de t o o btai n t he P K sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. H o we ver, 
sa m ples o btai ne d wit hi n t he wi n d o w s pecifie d will be c o nsi dere d acce pta ble. Starti n g C ycle 5, pre d ose P K sa m ples will be c ollecte d o nl y o n Da y 1 of e ver y 3 r d c ycle ( C ycle 5 
Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.). A d di ti o n al P K/ P D s a m ples s h o ul d als o be t a ke n if C R S is s us pecte d, a n d P K/ P D s a m ples are n ot alre a d y sc he d ule d t o be 
t a ke n. 
2 T he 0 -h o ur P K a n d A D A/ N A b sa m ples s h o ul d be ta ke n wit hi n 6 h o urs pri or t o P F - 0 7 0 6 2 1 1 9 a d mi nistrati o n.
3 Bl o o d s a m ples f or P F -0 7 0 6 2 1 1 9 , P F-0 6 8 0 1 5 9 1, a n d be v aciz u m a b -Pfizer i m m u n o ge nicit y testi n g a n d P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b -Pfizer P K: Bl o o d sa m ples f or 
P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer will o nl y be c ollecte d i n partici pa nts recei vi n g c o m bi nati o n t hera p y (ie, P art 1 B): Refer t o Secti o n 8. 4 f or details. A bl o o d sa m ple f or 
P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer P K a nal yses s h o ul d be dra w n wit h eac h i m m u n o ge nicit y sa m ple f or P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer, res pecti vel y. All sa m ples s h o ul d 
be c ollecte d o n Da y 1 of a c ycle ( als o o n D a y 1 5, i n C ycle 1 o nl y ) a n d will be dra w n pre d ose - wit hi n 6 h o urs pri or t o a n y of t he dr u gs bei n g a d mi nistere d. Starti n g at C ycle 5, 
bl o o d sa m ples f or P K a n d A D A/ N A b a gai nst P F -0 7 0 6 2 1 1 9 (a n d P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer i n Part 1 B) will be c ollecte d e ver y 3r d c ycle pre d ose (ie, C ycle 5 Da y 1, 
C y cle 8 Da y 1, C ycle 1 1 Da y 1, etc.). Partici pa nts wit h a n u nres ol ve d A E p ossi bl y relate d t o A D A will be as ke d t o r et ur n t o t he cli nic f or A D A a n d dr u g c o nce ntrati o n 
assess me nts at a p pr o xi matel y 3 - m o nt h i nter vals u ntil t he A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or u p t o a ma xi m u m of 9 m o nt hs.
4 Pfizer Pre p D 1 B a n ke d S a m ple: If n ot c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect at t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g c ollecte d i n c o nj u ncti o n 
wit h a partici pa nt visit.
5 T u m or Tiss ue S a m ples: Partici pa nts e nr olle d i n Part 1 A, a n d Part 1 B of t his st u d y will pr o vi de eit her a n arc hi val f or mali n-fi xe d paraffi n e m be d de d material c o ntai ni n g t u m or 
t hat is of dia g n ostic q ualit y a n d re prese ntati ve of t heir dia g n ose d mali g na nc y or prefera bl y a de n o v o pre-treat me nt bi o ps y. If t he arc hi val t u m or is n ot a vaila ble, partici pa nts m ust 
pr o vi de a de n o v o  pre -treat me nt bi o ps y f or e val uati o n of baseli ne tiss ue bi o mar kers ( prefera bl y c ollecte d wit hi n 2 8 da ys of st u d y start). O n-treat me nt bi o ps y sa m ples c ollecte d 
prefera bl y after t he t hir d d ose a n d wit hi n 7 da ys of C 3 D 1 are o pti o nal f or partici pa nts e nr olle d i n eac h c o h ort i n Part 1 A a n d Part 1 B f or e val uati o n of tiss ue bi o mar ker 
m o d ulati o ns d uri n g treat me nt . If o n tre at me nt t u m or c ollecti o n t a kes pl ace gre ater t h a n ± 3 d a ys fr o m C 3 D 1, a d diti o n al u nsc he d ule d bl o o d s a m ple f or c yt o ki ne a n d 
circ ul ati n g m ar kers a n d a n u nsc he d ule d bl o o d s a m ple f or T cell i m m u n o p he n ot y pi n g s a m ple s h o ul d be c ollecte d t o m atc h t he d a y of bi o ps y c ollecti o n. S pecific tiss ue 
re q uire me nts a n d i nstr ucti o ns are liste d i n Bi o mar ker Secti o n 8. 8 .
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 6
T a ble 3 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 1 A a n d P art 1 B 
Wit h o ut Pri mi n g D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
2
3
5
8
1 5
2 2
1
2
5
8
1 5
E n d of 
Tre at me nt/
Wit h dr a w al
H o urs Pre -/ P ost-D ose 1
0 2
4
8
2 4
4 8
9 6
1 6 8
0
8 
( P art 
1 B 
o nl y)
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 0. 5 hr ± 1 hr
± 3 hrs
± 6 hrs
± 2 4 hrs ± 2 4 hrs
± 1 hr ± 4 8 hrs
± 3 hrs
± 2 4 
hrs
± 2 4 hrs
6 P aire d T u m or S a m ples : As t he R P 2 D/ M T D is a p pr oac he d or t he R P 2 D/ M T D of P F-0 7 0 6 2 1 1 9 has bee n deter mi ne d, a n o pti o nal s u bset of partici pa nts ma y be e nr olle d 
(a p pr o xi matel y 6-1 2 partici pa nts) wit h t he re q uire me nt of pr o vi di n g ma n dat or y paire d de n o v o pretreat me nt a n d o n treat me nt bi o ps y sa m ples i n P arts 1 A a n d 1 B t o e na ble 
e val uati o n of tiss ue bi o mar ker P D acti vit y. T he o pti o n t o e nr oll t he s u bset of partici pa nts f or ma n dat or y paire d t u m or sa m ples will be base d o n e val uati o n of e mer gi n g cli nical 
data (i ncl u di n g a vaila ble safet y/t olera bilit y, P K, a n d P D fi n di n gs) b y t he s p o ns or. De n o v o pre -treat me nt a n d o n-treat me nt bi o psies s h o ul d be ta ke n fr o m t he sa me lesi o n, n ot 
pre vi o usl y irra diate d, if p ossi ble. De n o v o pre -treat me nt bi o psies s h o ul d be prefera bl y c ollecte d wit hi n 2 8 da ys of st u d y start after all eli gi bilit y criteria ha ve bee n verifie d. 
O n -treat me nt bi o ps y sa m ples are t o be collecte d prefera bl y after t he 3r d d ose a n d wit hi n 7 da ys of C 3 D 1. If o n tre at me nt t u m or c ollecti o n t a kes pl ace gre ater t h a n ± 3 d a ys 
fr o m C 3 D 1, a d diti o n al u nsc he d ule d bl o o d s a m ple f or c yt o ki ne a n d circ ul ati n g m ar kers a n d a n u nsc he d ule d bl o o d s a m ple f or T cell i m m u n o p he n ot y pi n g s h o ul d be 
c ollecte d t o m atc h t he d a y of bi o ps y c ollecti o n. A d diti o nal u nsc he d ule d o n -treat me nt bi o psies, after C 4 D 1 5 ( > 6 wee ks after i nitial o n treat me nt bi o ps y) ma y be c ollecte d, if 
i n dicate d t o e val uate p ote ntial res p o nses t o treat ment or s us pecte d ac q uire d resista nce t o t hera p y a n d a gree d u p o n b y t he s p o ns or a n d i n vesti gat or a n d a gree d t o b y t he partici pa nt. 
If t he partici pa nt disc o nti n ues t he st u d y bef ore t he sc he d ule d o n-treat me nt bi o ps y ( C 3 D 1), t he partici pa nt will be as ke d t o pr o vi de a bi o ps y at t he E n d of Treat me nt visit. S pecific 
tiss ue re q uire me nts a n d i nstr ucti o ns are liste d i n Bi o mar ker Secti o n 8. 8 .
7 Bl o o d s a m ple f or T cell I m m u n o p he n ot y pi n g : O ne 5 m L bl o o d sa m ple will be c ollecte d f or i m m u n o p he n ot y pe circ ulati n g l y m p h oc ytes at baseli ne ( pre d ose C ycle 1 Da y 1), 
a n d d uri n g treat me nt as descri be d a b o ve t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples s h o ul d be 
c ollecte d. If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or meas ure me nt t his sa m ple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d 
will be c ollecte d e ver y 3 r d c ycle pre d ose ( ie., C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.) (Secti o n 8. 8. 5 ).
8 Bl o o d S a m ple f or C yt o ki nes a n d Circ ul ati n g M ar kers (ce ntr al l a b): F or ce ntral la b orat or y testi n g, o ne 5 m L bl o o d sa m ple will be c ollecte d t o is olate ser u m f or c yt o ki ne a n d 
circ ulati n g mar ker meas ure me nt. Baseli ne c ollecti o n is re q uire d pre d ose o n C ycle 1 Da y 1. O n -treat me nt sa m ples f or c yt o ki ne a n d circ ulati n g mar ker meas ure me nt will be 
c ollecte d as descri be d a b o ve. T hese sa m ples will be use d t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n d r o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples 
s h o ul d be c ollecte d t o matc h cli nicall y i n dicate d safet y c yt o ki ne sa m ples. If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or 
meas ure me nt t his sa m ple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d sa m ples f or c yt o ki ne a n d circ ulati n g mar kers will be c ollecte d e ver y 3 r d c ycle pre d ose (ie., C ycle 5 
Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.) ( Secti o n 8. 8. 4 ).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 7
T a ble 4 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 1 A a n d P art 1 B Wit h 
Pri mi n g D ose
Visit I de ntifier
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
2
8
1 5
1 6
1 9
2 2
1
2
5
8
1 5
E O T/
Wit h dr a w al
H o urs Pre -/ P ost-D ose 1
0 2
8
2 4
1 6 8
0
4
8 
2 4
9 6
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr
± 3 hrs
± 2 4 hrs
± 0. 5 hr ± 1 hr ± 3 hrs ± 2 4 hrs ± 4 8 hrs
± 3 hrs
± 2 4 hrs ± 2 4 hrs
P har mac o ki netic sa m ples
Bl o o d sa m ples f or 
P F - 0 7 0 6 2 1 1 9 
c o nce ntrati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
( C 4 
o nl y)
X 1
( C 4 
o nl y)
X
(C 4 
o nl y)
X  
X
Bl o o d sa m ples f or 
A D A/ N A b a gai nst 
P F -0 7 0 6 2 1 1 9 3
X
X
X 3
X
Bl o o d sa m ples f or 
P K/ A D A/ N A b a gai nst 
P F -0 6 8 0 1 5 9 1 3
X
X 3
X
Bl o o d sa m ples f or 
P K/ A D A/ N A b a gai nst 
be vaciz u ma b -Pf izer3
X
X 3
X
P har mac o d y na mic sa m ples
Pf izer Pre p D 1 ba n ke d 
sa m ple4
X
Arc hi val T u m or Sa m ple 5
X
O pti o nal or Ma n dat or y De 
N o v o Pre -treat me nt 
bi o ps y 5 ,6
X
O pti o nal or Ma n dat or y 
O n -Treat me nt T u m or 
Bi o ps y 6
X C 3 
o nl y
( ± 7 da ys)
X ( or 2 n d o n 
treat me nt)
Bl o o d sa m ple f or T cell 
I m m u n o p he n ot y pi n g7
X
X  
X  
X
X  
X  
X  
X 7
X ( C 2 a n d 
C 3 o nl y)
Bl o o d (ser u m) sa m ple f or 
C y t o ki nes & Circ ulati n g 
Mar kers
8
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 7
X ( C 2 a n d 
C 3 o nl y)
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 8
T a ble 4 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 1 A a n d P art 1 B Wit h 
Pri mi n g D ose
Visit I de ntifier
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
2
8
1 5
1 6
1 9
2 2
1
2
5
8
1 5
E O T/
Wit h dr a w al
H o urs Pre -/ P ost-D ose 1
0 2
8
2 4
1 6 8
0
4
8 
2 4
9 6
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr
± 3 hrs
± 2 4 hrs
± 0. 5 hr ± 1 hr ± 3 hrs ± 2 4 hrs ± 4 8 hrs
± 3 hrs
± 2 4 hrs ± 2 4 hrs
1 Sa m pli n g ti mes i n dicate d are relate d t o t he e n d of t he S C i njecti o n. All eff orts s h o ul d be ma de t o o btai n t he P K sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. H o we ver, 
sa m ples o btai ne d wit hi n t he wi n d o w s pecifie d will be c o nsi dere d acce pta ble. Starti n g C ycle 5, pre d ose P K sa m ples will be c ollecte d o nl y o n Da y 1 of e ver y 3 r d c ycle ( C ycle 5 Da y 
1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.). A d diti o n al P K/ P D s a m ples s h o ul d als o be t a ke n if C R S is s us pec te d, a n d P K/ P D s a m ples are n ot alre a d y sc he d ule d t o be t a ke n. 
2 T he 0 -h o ur P K a n d A D A/ N A b sa m ples s h o ul d be ta ke n wit hi n 6 h o urs pri or t o P F - 0 7 0 6 2 1 1 9 a d mi nistrati o n.
3 Bl o o d s a m ples f or P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b -Pfizer i m m u n o ge nicit y testi n g a n d P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b -Pfizer P K: Bl o o d sa m ples f or P F -
0 7 0 6 2 1 1 9 will be c ollecte d i n partici pa nts recei vi n g m o n ot hera p y ( ie, P art 1 A D ose Pri mi n g). Bl o o d sa m ples f or P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer will be 
c ollecte d i n partici pants recei vi n g c o m bi nati o n t hera p y ( ie, P art 1 B D ose Pri mi n g): Refer t o Secti o n 8. 4 f or details. A bl o o d sa m ple f or P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer P K  
a nal yses s h o ul d be dra w n wit h eac h i m m u n o ge nicit y sa m ple f or P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer, res pecti vel y. All sa m ples f or be vaciz u ma b-Pf izer s h o ul d be c ollecte d o n 
Da y 1 of a c ycle ( e xce pt o n Da y 1 5, i n C ycle 1 o nl y) a n d f or P F-0 6 8 0 1 5 9 1 o n Da y 1 5 of eac h c ycle. Sa m ples will be dra w n pre d ose - wit hi n 6 h o urs pri or t o a n y of t he dr u gs bei n g 
a d mi nistere d. Starti n g at C ycle 5, bl o o d sa m ples f or P K a n d A D A/ N A b a gai nst P F -0 7 0 6 2 1 1 9 (a n d P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer i n Part 1 B) will be c ollecte d e ver y 3r d c ycle 
pre d ose (ie, C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc. f or P F-0 7 0 6 2 1 1 9/ be vaciz u ma b -Pf izer a n d C ycle 5 Da y 1 5, C ycle 8 Da y 1 5, C ycle 1 1 Da y 1 5 f or P F- 0 6 8 0 1 5 9 1 ). 
Partici pa nts wit h a n u nres ol ve d A E p ossi bl y relate d t o A D A will be as ke d t o re t ur n t o t he cli nic f or A D A a n d dr u g c o nce ntrati o n assess me nts at a p pr o xi matel y 3-m o nt h i nter vals 
u ntil t he A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or u p t o a ma xi m u m of 9 m o nt hs.
4 Pfizer Pre p D 1 B a n ke d S a m ple: If n ot c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect at t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g c ollecte d i n c o nj u ncti o n 
wit h a partici pa nt visit.
5 T u m or Tiss ue S a m ples: Partici pa nts e nr olle d i n Part 1 A, a n d Part 1 B of t his s t u d y will pr o vi de eit her a n arc hi val f or mali n-fi xe d paraffi n e m be d de d material c o ntai ni n g t u m or 
t hat is of dia g n ostic q ualit y a n d re prese ntati ve of t heir dia g n ose d mali g na nc y or prefera bl y a de n o v o pre-treat me nt bi o ps y. If t he arc hi val t u m or is n ot a vailable, partici pa nts m ust 
pr o vi de a de n o v o  pre -treat me nt bi o ps y f or e val uati o n of baseli ne tiss ue bi o mar kers ( prefera bl y c ollecte d wit hi n 2 8 da ys of st u d y start). O n-treat me nt bi o ps y sa m ples c ollecte d 
prefera bl y after t he t hir d d ose a n d wit hi n 7 da ys of C 3 D 1 are o pti o nal f or partici pa nts e nr olle d i n eac h c o h ort i n Part 1 A a n d Part 1 B f or e val uati o n of tiss ue bi o mar ker m o d ulati o ns
d uri n g treat me nt . If o n tre atme nt t u m or c ollecti o n t a kes pl ace gre ater t h a n ± 3 d a ys fr o m C 3 D 1, a d diti o n al u nsc he d ule d bl o o d s a m ple f or c yt o ki ne a n d circ ul ati n g m ar kers 
a n d a n u nsc he d ule d bl o o d s a m ple f or T cell i m m u n o p he n ot y pi n g s a m ple s h o ul d be c ollecte d t o m atc h t he d a y of bi o ps y c ollecti o n. S pecific tiss ue re q uire me nts a n d 
i nstr ucti o ns are liste d i n Bi o mar ker Secti o n 8. 8 .
6 P aire d T u m or S a m ples : As t he R P 2 D/ M T D is a p pr oac he d or t he R P 2 D/ M T D of P F- 0 7 0 6 2 1 1 9 has bee n deter mi ne d, a n o pti o nal s u bset of partici pa nts ma y be e nr olle d 
(a p pr o xi matel y 6-1 2 partici pa nts) wit h t he re q uire me nt of pr o vi di n g ma n dat or y paire d de n o v o pretreat me nt a n d o n treat me nt bi o ps y sa m ples i n P arts 1 A a n d 1 B t o e na ble 
e val uati o n of tiss ue bi o mar ker P D acti vit y. T he o pti o n t o e nr oll t he s u bset of partici pa nts f or ma n dat or y paire d t u m or sa m ples will be base d o n e val uati o n of e mer gi n g cli nical data 
(i ncl u di n g a vaila ble safet y/t olera bilit y, P K, a n d P D fi n di n gs) b y t he s p o ns or. De n o v o pre-treat me nt a n d o n-treat me nt bi o psies s h o ul d be ta ke n fr o m t he sa me lesi o n, n ot pre vi o usl y 
irra diate d, if p ossi ble. De n o v o pre-treat me nt bi o psies s h o ul d be prefera bl y c ollecte d wit hi n 2 8 da ys of st u d y start after all eli gi bilit y criteria ha ve bee n verifie d. O n-treat me nt bi o ps y 
sa m ples are t o be c ollecte d prefera bl y after t he 3r d d ose a n d wit hi n 7 da ys of C 3 D 1. If o n tre atme nt t u m or c ollecti o n t a kes pl ace gre ater t h a n ± 3 d a ys fr o m C 3 D 1, a d diti o n al 
u nsc he d ule d bl o o d s a m ple f or c yt o ki ne a n d circ ul ati n g m ar kers a n d a n u nsc he d ule d bl o o d s a m ple f or T cell i m m u n o p he n ot y pi n g s h o ul d be c ollecte d t o m atc h t he d a y of 
bi o ps y c ollecti o n. A d diti o nal u nsc he d ule d o n -treat me nt bi o psies, after C 4 D 1 5 ( > 6 wee ks after i nitial o n treat me nt bi o ps y) ma y be c ollecte d, if i n dicate d t o e val uate p ote ntial 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 9
T a ble 4 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 1 A a n d P art 1 B Wit h 
Pri mi n g D ose
Visit I de ntifier
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
2
8
1 5
1 6
1 9
2 2
1
2
5
8
1 5
E O T/
Wit h dr a w al
H o urs Pre -/ P ost-D ose 1
0 2
8
2 4
1 6 8
0
4
8 
2 4
9 6
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr
± 3 hrs
± 2 4 hrs
± 0. 5 hr ± 1 hr ± 3 hrs ± 2 4 hrs ± 4 8 hrs
± 3 hrs
± 2 4 hrs ± 2 4 hrs
res p o nses t o treat me nt or s us pecte d ac q uire d resista nce t o t hera p y a n d a gree d u p o n b y t he s p o ns or a n d i n vesti gat or a n d a gree d t o b y t he partici pa nt. If t he partici pa nt disc o nti n ues 
t he st u d y bef ore t he sc he d ule d o n-treat me nt bi o ps y ( C 3 D 1), t he partici pa nt will be as ke d t o pr o vi de a bi o ps y at t he E n d of Treat me nt visit. S pecific tiss ue re quire me nts a n d 
i nstr ucti o ns are liste d i n Bi o mar ker Secti o n 8. 8 .
7 Bl o o d s a m ple f or T cell I m m u n o p he n ot y pi n g: O ne 5 m L bl o o d sa m ple will be c ollecte d f or i m m u n o p he n ot y pe circ ulati n g l y m p h oc ytes at baseli ne ( pre d ose C ycle 1 Da y 1), 
a n d d uri n g treat me nt as descri be d a b o ve t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples s h o ul d be c ollecte d. 
If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or meas ure me nt t his sa m ple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d will be 
c ollecte d e ver y 3 r d c ycle pre d ose ( ie., C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.) (Secti o n 8. 8. 5 ).
8 Bl o o d S a m ple f or C yt o ki nes a n d Circ ul ati n g M ar kers (ce ntr al l a b): F or ce ntral la b orat or y testi n g, o ne 5 m L bl o o d sa m ple will be c ollecte d t o is olate ser u m f or c yt o ki ne a n d 
circ ulati n g mar ker meas ure me nt. Baseli ne c ollecti o n is re q uire d pre d ose o n C ycle 1 Da y 1. O n -treat me nt sa m ples f or c yt o ki ne a n d circ ulati n g mar ker meas ure me nt will be c ollecte d 
as descri be d a b o ve. T hese sa m ples will be use d t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples s h o ul d be 
c ollecte d t o matc h cli nicall y i n dicate d safet y c yt o ki ne sa m ples. If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or meas ure me nt t his 
sa mple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d sa m ples f or c yt o ki ne a n d circ ulati n g mar kers will be c ollecte d e ver y 3 r d c ycle pre d ose (ie., C ycle 5 Da y 1, C ycle 8 Da y 1, 
C y cle 1 1 Da y 1, etc.) ( Secti o n 8. 8. 4 ).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 0
T a ble 5 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 2 Wit h o ut Pri mi n g 
D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
5
8
1 5
2 2
1
2
5
8
1 5
E O T/
wit h dr a w al
P ost 
tre atme nt 
f oll o w u p
H o urs Pre -/ P ost-D ose 1
0 2
8
9 6
1 6 8
0
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr ± 2 4 hrs
± 2 4 hrs
± 4 8 hrs
± 3 hrs
± 2 4 hrs
± 2 4 hrs
± 7 d a ys
P har mac o ki netic sa m ples
Bl o o d sa m ples f or P F - 0 7 0 6 2 1 1 9 
c o nce ntrati o ns
X  
X  
X  
X  
X  
X  
X
X 
( C 4 o nl y)
X 1
( C 4 o nl y)
X 
( C 4 o nl y)
X  
X  
X
Bl o o d sa m ples f or A D A/ N A b a gai nst 
P F -0 7 0 6 2 1 1 9 3
X
X
X 3
X  
X
Bl o o d sa m ples f or P K/ A D A/ N A b a gai nst 
P F -0 6 8 0 1 5 9 1 3
X
X
X 3
X
Bl o o d sa m ples f or P K/ A D A/ N A b a gai nst 
be vaciz u ma b -Pf izer3
X
X
X 3
X
P har mac o d y na mic sa m ples
Pf izer Pre p D 1 ba n ke d sa m ple4
X
Arc hi val T u m or sa m ple 5
X
De N o v o Pre -treat me nt T u m or Bi o ps y5 ,6
X
O pti o nal or Ma n dat or y O n -Treat me nt 
T u m or Bi o ps y 6
X 
C 2 o nl y 
( ± 7 da ys)
X
( or 2n d o n 
treat me nt)
Bl o o d sa m ple f or C yt o ki nes a n d 
Circ ulati n g Mar kers 7
X  
X  
X  
X  
X  
X  
X 7
X 
( C 2 o nl y)
Bl o o d sa m ple f or T cell 
I m m u n o p he n ot y pi n g8
X
X  
X  
X  
X 7
X 
( C 2 o nl y)
1 Sa m pli n g ti mes i n dicate d are relate d t o t he e n d of t he S C i njecti o n. All eff orts s h o ul d be ma de t o o btai n t he P K sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. H o we ver, 
sa m ples o btai ne d wit hi n t he wi n d o w s pecifie d will be c o nsi dere d acce pta ble. Starti n g C ycle 5, pre d ose P K sa m ples will be c ollecte d o nl y o n Da y 1 of e ver y 3 r d c ycle ( C ycle 5 Da y 
1, C ycle 8 Da y 1 , C ycle 1 1 Da y 1, etc.). A d diti o nal P K/ P D sa m ples s h o ul d als o be ta ke n if C R S is s us pecte d, a n d P K/ P D sa m ples are n ot alrea d y sc he d ul e d t o be ta ke n.
2 T he 0 -h o ur P K a n d A D A/ N A b sa m ples s h o ul d be ta ke n wit hi n 6 h o urs pri or t o P F - 0 7 0 6 2 1 1 9 a d mi nistrati o n.
3 B l o o d s a m ples f or P F-0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b -Pfizer i m m u n o ge nicit y testi n g a n d P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b - Pfizer P K: Bl o o d sa m ples f or P F -
0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer will o nl y be c ollecte d i n partici pa nts recei vi n g c o m bi nati o n t hera p y : Refer t o Secti o n 8. 4 f or details. A bl o od sa m ple f or P F -0 6 8 0 1 5 9 1 or 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 1
T a ble 5 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 2 Wit h o ut Pri mi n g 
D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
5
8
1 5
2 2
1
2
5
8
1 5
E O T/
wit h dr a w al
P ost 
tre atme nt 
f oll o w u p
H o urs Pre -/ P ost-D ose 1
0 2
8
9 6
1 6 8
0
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr ± 2 4 hrs
± 2 4 hrs
± 4 8 hrs
± 3 hrs
± 2 4 hrs
± 2 4 hrs
± 7 d a ys
be vaciz u ma b -Pf izer P K a nal yses s h o ul d be dra w n wit h eac h i m m u n o ge nicit y sa m ple f or P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer, res pecti vel y. All sa m ples s h o ul d be c ollecte d o n 
Da y 1 of a c ycle (als o o n Da y 1 5, i n C ycle 1 o nl y) a n d will b e dra w n pre d ose wit hi n 6 h o urs pri or t o a n y of t he dr u gs bei n g a d mi nistere d. Starti n g C ycle 5, bl o o d sa m ples f or P K 
a n d A D A/ N A b a gai nst P F -0 7 0 6 2 1 1 9 (a n d P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer i n c o m bi nati o n) will be c ollecte d e ver y 3r d c ycle pre d ose (ie, C ycle 5 Da y 1, C ycle 8 Da y 1, 
C y cle 1 1 Da y 1, etc.). Partici pa nts wit h a n u nres ol ve d A E p ossi bl y relate d t o A D A will be as ke d t o ret ur n t o t he cli nic f or A D A a n d dr u g c o nce ntrati o n assess me nts at 
a p pr o xi matel y 3 -m o nt h i nter vals u ntil t he A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or u p t o a ma xi m u m of 9 m o nt hs.
4 Pfizer Pre p D 1 B a n ke d S a m ple: If n ot c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect at t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g c ollecte d i n c o nj u ncti o n 
wit h a partici pa nt visit.
5 Pretre at me nt T u m or Tiss ue S a m ples: Partici pa nts s h o ul d pr o vi de a de n o v o pre -treat me nt bi o ps y f or e val uati o n of baseli ne tiss ue bi o mar kers, u nless n ot me dicall y feasi ble, 
f or e val uati o n of baseli ne tiss ue bi omar kers. De n o v o pretreat me nt bi o psies are prefera bl y c ollecte d wit hi n 2 8 da ys of st u d y start after all eli gi bilit y criteria ha ve bee n verifie d. I n 
a d diti o n, s u b missi o n of arc hi val sa m ples if a vaila ble is als o e nc o ura ge d, b ut n ot ma n dat or y, t o c o m pare p oss i ble c ha n ges i n baseli ne tiss ue bi o mar kers d ue t o pri or t hera pies. 
S pecific tiss ue re q uire me nts, i nstr ucti o ns, a n d c o n diti o ns f or s u b mitti n g arc hi val sa m ples w he n c ollecti o n of de n o v o sa m ples is n ot me dicall y feasi ble are liste d i n Bi o mar ker 
Secti o n 8. 8 .
6 P aire d T u m or S a m ples : Paire d de n o v o pretreat me nt a n d o n-treat me nt bi o ps y sa m ples will be ma n dat or y f or a p pr o xi matel y 1 0 partici pa nts i n eac h of t he d ose e x pa nsi o n ar ms 
a n d o pti o nal b ut e nc o ura ge d f or all ot her partici pa nts t o e na ble e val uati o n of tiss ue bi o mar ker P D acti vit y. O n -treat me nt bi o psies s h o ul d be ta ke n fr o m t he sa me lesi o n, n ot 
pre vi o usl y irra dia te d, if p ossi ble. O n-treat me nt bi o ps y sa m ples are t o be c ollecte d prefera bl y after t he 3r d d ose a n d wit hi n 7 da ys of C 2 D 1 5. If o n tre atme nt t u m or c ollecti o n 
t a kes pl ace gre ater t h a n ± 3 d a y s fr o m C 2 D 1 5, a d diti o n al u nsc he d ule d bl o o d s a m ple f or c yt o ki ne a n d circ ul ati n g m ar kers a n d a n u nsc he d ule d bl o o d s a m ple f or T cell 
i m m u n o p he n ot y pi n g s a m ple s h o ul d be c ollecte d t o m atc h t he d a y of bi o ps y c ollecti o n. A d diti o nal u nsc he d ule d o n -treat me nt bi o psies, after C 4 D 1 5 ( > 6 wee ks after i nitial o n 
treat me nt bi o ps y) ma y be c ollecte d, if i n dicate d t o e val uate p ote ntial res p o nses t o treat me nt or s us pecte d ac q uire d resista nce t o t hera p y a n d a gree d u p o n b y t he s p o ns or a n d 
i n vesti gat or a n d a gree d t o b y t he partici pa nt. If t he partici pa nt disc o nti n ues t he st u d y bef ore t he sc he d uled o n -treat me nt bi o ps y ( C 2 D 1 5), t he partici pa nt will be as ke d t o pr o vi de a 
bi o ps y at t he E n d of Treat me nt visit. S pecific tiss ue re q uire me nts a n d i nstr ucti o ns are liste d i n Bi o mar ker Secti o n 8. 8 .
7 Bl o o d S a m ple f or C yt o ki nes a n d Circ ul ati n g M ar kers (ce ntr al l a b) : F or ce ntral la b orat or y testi n g, o ne 5 m L bl o o d sa m ple will be c ollecte d t o is olate ser u m f or c yt o ki ne a n d 
circ ulati n g mar ker meas ure me nt. Baseli ne c ollecti o n is re q uire d pre d ose o n C ycle 1 Da y 1. O n -treat me nt sa m ples f or c yt o ki ne a n d circ ulati n g mar kers meas ure me nt will be 
c ollecte d as descr i be d a b o ve. T hese sa m ples will be use d t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples 
s h o ul d be c ollecte d t o matc h cli nicall y i n dicate d safet y c yt o ki ne sa m ples. If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or 
meas ure me nt t his sa m ple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d sa m ples f or c yt o ki ne a n d circ ulati n g mar kers will b e c ollecte d e ver y 3 r d c ycle pre d ose (i.e., C ycle 5 Da y 
1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.).
8 Bl o o d s a m ple f or T cell I m m u n o p he n ot y pi n g: O ne 5 m L bl o o d sa m ple will be c ollecte d t o i m m u n o p he n ot y pe circ ulati n g l y m p h oc ytes at baseli ne, pre d ose C ycle 1 Da y 1, a n d 
d uri n g treat me nt as descri be d a b o ve t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples s h o ul d be c ollecte d. If 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 2
T a ble 5 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 2 Wit h o ut Pri mi n g 
D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys 
pri or t o 
re gistr ati o n
1
5
8
1 5
2 2
1
2
5
8
1 5
E O T/
wit h dr a w al
P ost 
tre atme nt 
f oll o w u p
H o urs Pre -/ P ost-D ose 1
0 2
8
9 6
1 6 8
0
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr ± 2 4 hrs
± 2 4 hrs
± 4 8 hrs
± 3 hrs
± 2 4 hrs
± 2 4 hrs
± 7 d a ys
Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or meas ure me nt t his sa m ple s h o ul d be c ollecte d. S tarti n g wit h C ycle 5, bl o o d sa m ples f or 
c yt o ki ne a n d circ ulati n g mar kers a n d bl o o d sa m ple will be c ollecte d e ver y 3r d c ycle pre d ose (i.e., C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc).
T a ble 6 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 2 Wit h Pri mi n g D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys pri or 
t o 
re gistr ati o n
1
8
1 5
1 9
2 2
1
2
5
8
1 5
E O T/
Wit h dr a w al
P ost tre at me nt 
f oll o w u p
H o urs Pre -/ P ost-D ose 1
0 2
8
1 6 8
0
8
9 6
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr
± 2 4 hrs
± 1 hr
± 2 4 hrs ± 4 8 hrs
± 3 hrs
± 2 4 hrs
± 2 4 hrs
± 7 d a ys
P har mac o ki netic sa m ples
Bl o o d sa m ples f or 
P F - 0 7 0 6 2 1 1 9 
c o nce ntrati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X
( C 4 
o nl y)
X 1
( C 4 o nl y)
X
( C 4 o nl y)
X  
X
X
Bl o o d sa m ples f or 
A D A/ N A b a gai nst 
P F -0 7 0 6 2 1 1 9 3
X
X
X 3
X
X
Bl o o d sa m ples f or 
P K/ A D A/ N A b a gai nst 
P F -0 6 8 0 1 5 9 1 3
X
X 3
X
Bl o o d sa m ples f or 
P K/ A D A/ N A b a gai nst 
be vaciz u ma b -Pf izer3
X
X 3
X
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 3
T a ble 6 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 2 Wit h Pri mi n g D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys pri or 
t o 
re gistr ati o n
1
8
1 5
1 9
2 2
1
2
5
8
1 5
E O T/
Wit h dr a w al
P ost tre at me nt 
f oll o w u p
H o urs Pre -/ P ost-D ose 1
0 2
8
1 6 8
0
8
9 6
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr
± 2 4 hrs
± 1 hr
± 2 4 hrs ± 4 8 hrs
± 3 hrs
± 2 4 hrs
± 2 4 hrs
± 7 d a ys
P har mac o d y na mic 
sa m ples
Pf izer Pre p D 1 ba n ke d 
sa m ple4
X
Arc hi val T u m or sa m ple 5
X
De N o v o Pre -treat me nt 
T u m or Bi o ps y 5 ,6
X
O pti o nal or Ma n dat or y 
O n -Treat me nt T u m or 
Bi o ps y 6
X 
C 2 o nl y 
( ± 7 da ys)
X
( or 2n d o n 
treat me nt)
Bl o o d sa m ple f or 
C y t o ki nes a n d 
Circ ulati n g Mar kers 7
X  
X  
X  
X  
X  
X  
X  
X 7
X 
( C 2 o nl y)
Bl o o d sa m ple f or T cell 
I m m u n o p he n ot y pi n g8
X
X  
X
X  
X  
X 7
X 
( C 2 o nl y)
1 Sa m pli n g ti mes i n dicate d are relate d t o t he e n d of t he S C i njecti o n. All eff orts s h o ul d be ma de t o o btai n t he P K sa m ples at t he e xact n o mi nal ti me relati ve t o d osi n g. H o we ver, 
sa m ples o btai ne d wit hi n t he wi n d o w s pecifie d will be c o nsi dere d acce pta ble. Starti n g C ycle 5, pre d ose P K sa m ples will be c ollecte d o nl y o n Da y 1 of e ver y 3 r d c ycle ( C ycle 5 
Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.). A d diti o nal P K/ P D sa m ples s h o ul d als o be ta ke n if C R S is s us pecte d, a n d P K/ P D sa m ples are n ot alrea d y sc he d ule d t o be ta ke n.
2 T he 0 -h o ur P K a n d A D A/ N A b sa m ples s h o ul d be ta ke n wit hi n 6 h o urs pri or t o P F - 0 7 0 6 2 1 1 9 a d mi nistrati o n.
3 Bl o o d s a m ples f or P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b -Pfizer i m m u n o ge nicit y testi n g a n d P F -0 6 8 0 1 5 9 1, a n d be v aciz u m a b - Pfizer P K: Bl o o d sa m ples f or P F -
0 7 0 6 2 1 1 9 will be c ollecte d i n partici pa nts recei vi n g m o n ot hera p y. Bl o o d sa m ples f or P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer will be c ollecte d i n partici pa nts 
recei vi n g c o m bi nati o n t hera py : Refer t o Secti o n 8. 4 f or details. A bl o o d sa m ple f or P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer P K a nal yses s h o ul d be dra w n wit h eac h i m m u n o ge nicit y 
sa m ple f or P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer, res pecti vel y. All sa m ples f or be vaciz u ma b-Pf izer s h o ul d be c ollecte d o n Da y 1 of a c ycle (e xce pt o n Da y 1 5, i n C ycle 1 o nl y) 
a n d f or P F-0 6 8 0 1 5 9 1 o n Da y 1 5 of a c ycle. Sa m ples will be dra w n pre d ose wit hi n 6 h o urs pri or t o a n y of t he dr u gs bei n g a d mi nistere d. Starti n g C ycle 5, bl o o d sa m ples f or P K 
a n d A D A/ N A b a gai nst P F -0 7 0 6 2 1 1 9 (a n d P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pf izer i n c o m bi nati o n) will be c ollecte d e ver y 3r d c ycle pre d ose (ie, C ycle 5 Da y 1, C ycle 8 Da y 1, 
C y cle 1 1 Da y 1, etc. f or P F-0 7 0 6 2 1 1 9/ be vaciz u ma b -Pf izer a n d C ycle 5 Da y 1 5, C ycle 8 Da y 1 5, C ycle 1 1 Da y 1 5 f or P F- 0 6 8 0 1 5 9 1 ). Partici pa nts wit h a n u nres ol ve d A E p ossi bl y 
relate d t o A D A will be as ke d t o ret ur n t o t he cli nic f or A D A a n d dr u g c o nce ntrati o n assess me nts at a p pr o xi matel y 3-m o nt h i nter vals u ntil t he A E or its se q uelae r es ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or u p t o a ma xi m u m of 9 m o nt hs.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 4
T a ble 6 .
Sc he d ule of P h ar m ac o ki netic, P h ar m ac o d y n a mic, a n d I m m u n o ge nicit y Assess me nts f or P art 2 Wit h Pri mi n g D ose
Visit I de ntifier 
Scree ni n g
C ycle 1
C ycle ≥2
St u d y D a y
Wit hi n 
2 8 d a ys pri or 
t o 
re gistr ati o n
1
8
1 5
1 9
2 2
1
2
5
8
1 5
E O T/
Wit h dr a w al
P ost tre at me nt 
f oll o w u p
H o urs Pre -/ P ost-D ose 1
0 2
8
1 6 8
0
8
9 6
1 6 8
0
2 4
9 6
1 6 8
0
Visit wi n d o w 
± 1 hr
± 2 4 hrs
± 1 hr
± 2 4 hrs ± 4 8 hrs
± 3 hrs
± 2 4 hrs
± 2 4 hrs
± 7 d a ys
4 Pfizer Pre p D 1 B a n ke d S a m ple: If n ot c ollecte d o n t he desi g nate d c ollecti o n da y, c ollect at t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g collecte d i n c o nj u ncti o n 
wit h a partici pa nt visit.
5 Pretre at me nt T u m or Tiss ue S a m ples: Partici pa nts s h o ul d pr o vi de a de n o v o pre -treat me nt bi o ps y f or e val uati o n of baseli ne tiss ue bi o mar kers, u nless n ot me dicall y feasi ble, 
f or e val uati o n of baseli ne tiss ue bi o mar kers. De n o v o pretreat me nt bi o psies are prefera bl y c ollecte d wit hi n 2 8 da ys of st u d y start after all eli gi bilit y criteria ha ve bee n verifie d. I n 
a d diti o n, s u b missi o n of arc hi val sa m ples if a vaila ble is als o e nc o ura ge d, b ut n ot ma n dat or y, t o c o m pare p ossi ble c ha n ges i n b aseli ne tiss ue bi o mar kers d ue t o pri or t hera pies. 
S pecific tiss ue re q uire me nts, i nstr ucti o ns, a n d c o n diti o ns f or s u b mitti n g arc hi val sa m ples w he n c ollecti o n of de n o v o sa m ples is n ot me dicall y feasi ble are liste d i n Bi o mar ker 
Secti o n 8. 8 .
6 P aire d T u m or S a m ples : Paire d de n o v o pretreat me nt a n d o n-treat me nt bi o ps y sa m ples will be ma n dat or y f or a p pr o xi matel y 1 0 partici pa nts i n eac h of t he d ose e x pa nsi o n ar ms 
a n d o pti o nal b ut e nc o ura ge d f or all ot her partici pa nts t o e na ble e val uati o n of tiss ue bi o mar ker P D acti vit y. O n -treat me nt bi o psies s h o ul d be ta ke n fr o m t he sa me lesi o n, n ot 
pre vi o usl y irra diate d, if p ossi ble. O n- treat me nt bi o ps y sa m ples are t o be c ollecte d prefera bl y after t he 3r d d os e a n d wit hi n 7 da ys of C 2 D 1 5. If o n tre atme nt t u m or c ollecti o n 
t a kes pl ace gre ater t h a n ± 3 d a y s fr o m C 2 D 1 5, a d diti o n al u nsc he d ule d bl o o d s a m ple f or c yt o ki ne a n d circ ul ati n g m ar kers a n d a n u nsc he d ule d bl o o d s a m ple f or T cell 
i m m u n o p he n ot y pi n g s a m ple s h o ul d be c ollecte d t o m atc h t he d a y of bi o ps y c ollecti o n. A d diti o nal u nsc he d ule d o n -treat me nt bi o psies, after C 4 D 1 5 ( > 6 wee ks after i nitial o n 
treat me nt bi o ps y) ma y be c ollecte d, if i n dicate d t o e val uate p ote ntial res p o nses t o treat me nt or s us pecte d ac q uire d resista nce t o t hera p y a n d a gree d u p o n b y t he s p o ns or a n d 
i n vesti gat or a n d a gree d t o b y t he partici pa nt. If t he partici pa nt disc o nti n ues t he st u d y bef ore t he sc he d ule d o n-treat me nt bi o ps y ( C 2 D 1 5), t he partici pa nt will be as ke d t o pr o vi de a 
bi o ps y at t he E n d of Treat me nt visit. S pecific tiss ue re q uire me nts a n d i nstr ucti o ns are liste d i n Bi o mar ker Secti o n 8. 8 .
7 Bl o o d S a m ple f or C yt o ki nes a n d Circ ul ati n g M ar k ers (ce ntr al l a b) : F or ce ntral la b orat or y testi n g, o ne 5 m L bl o o d sa m ple will be c ollecte d t o is olate ser u m f or c yt o ki ne 
a n d circ ulati n g mar ker meas ure me nt. Baseli ne c ollecti o n is re q uire d pre d ose o n C ycle 1 Da y 1. O n -treat ment sa m ples f or c yt o ki ne a n d circ ulati n g mar kers meas ure me nt will be 
c ollecte d as descri be d a b o ve. T hese sa m ples will be use d t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples 
s h o ul d be c ollecte d t o matc h cli nicall y i n dicate d safet y c yt o ki ne sa m ples. If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or 
meas ure me nt t his sa m ple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d sa m ples f or c yt o ki ne a n d circ ulati n g mar kers will b e c o llecte d e ver y 3r d c ycle pre d ose (ie, C ycle 5 
Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc.).
8 Bl o o d s a m ple f or T -cell I m m u n o p he n ot y pi n g : O ne 5 m L bl o o d sa m ple will be c ollecte d t o i m m u n o p he n ot y pe circ ulati n g l y m p h oc ytes at baseli ne, pre d ose C ycle 1 Da y 1, 
a n d d uri n g treat me nt as descri be d a b o ve t o e val uate c ha n ges fr o m baseli ne. If Gra de ≥1 c yt o ki ne release s y n dr o me is s us pecte d, a d diti o nal u nsc he d ule d sa m ples s h o ul d be 
c ollecte d. If Gra de ≥2 diarr hea is o bser ve d or s us pecte d a n d P D sa m ples are n ot alrea d y sc he d ule d f or meas ure me nt t his sa m ple s h o ul d be c ollecte d. Starti n g wit h C ycle 5, bl o o d 
sa m ples f or c yt o ki ne a n d circ ulati n g mar kers a n d bl o o d sa m ple will be c ollecte d e ver y 3r d c ycle pre d ose (ie, C ycle 5 Da y 1, C ycle 8 Da y 1, C ycle 1 1 Da y 1, etc).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 5
2. I N T R O D U C TI O N
P F -0 7 0 6 2 1 1 9 is a n a nti -G ua n yl yl  Cyclase 2 C ( G U C Y 2c)/a nti-C D 3 bis pecific Fc dia b o d y 
tar geti n g C D 3 o n T cells wit h o ne bi n di n g d o mai n a n d G U C Y 2c wit h t he ot her bi n di n g 
d o mai n. P F - 0 7 0 6 2 1 1 9 acts as a T cell re directi n g bis pecific f or t he treat me nt of 
gastr oi ntesti nal t u m ors i ncl u di n g c ol orectal, gastr ic a n d es o p ha geal a de n ocarci n o mas.
2. 1. St u d y R ati o n ale
I n t he d ose-escalati o n/fi n di n g p hase ( Part 1), P F -0 7 0 6 2 1 1 9 will be e val uate d wit h or wit h o ut 
a pri mi n g d ose f or t he treat me nt of a d ult partici pa nts wit h a d va nce d gastr oi ntesti nal 
a de n ocarci n o mas (c ol orecta l, gastric, a n d es o p ha geal) k n o w n t o e x press G U C Y 2c a n d f or 
w h o m n o sta n dar d t hera p y  is a vaila ble. T he pri mi n g d ose has bee n i m ple me nte d t o miti gate 
c yt o ki ne release sy n dr o me ( C R S) wit h t he i nitial f ull d ose. Base d o n a vaila ble data fr o m 
partici pa nts e nr ol le d acr oss d ose escalati o n wit h o ut pri mi n g, c yt o ki ne pr o d ucti o n a n d C R S 
occ ur pri maril y wit h t he i nitial d ose of P F -0 7 0 6 2 1 1 9, s u p p orti n g t he h y p ot hesis t hat 
i n d ucti o n of i m m u ne acti vati o n wit h a l o wer pri mi n g d ose ma y atte n uate C R S ass ociate d 
wit h t he i nit ial f ull d ose. T he use of a pri mi n g a p pr oac h t o miti gate C R S is als o s u p p orte d by 
data fr o m cli nical st u dies wit h ot her T- cell e n ga gi n g a ge nts a n d will be e val uate d i n t his 
cli nical st u d y. 
I n t he d ose-e x pa nsi o n p hase ( Part 2), P F -0 7 0 6 2 1 1 9 will be e val uate d wit h or wit h o ut a 
pri mi n g d ose i n se parate d ose- e x pa nsi o n ar ms as m o n ot hera p y a n d i n c o m bi nati o n wit h 
a n ot her a ge nt (e g, i m m u ne c hec k p oi nt i n hi bit or a n d a nti- V E G F, se paratel y ) i n c ol orectal 
ca ncer ( C R C) a n d t he n p ossi bl y be e val uate d i n ot her gastr oi ntesti nal a de n ocarci n o mas, C R C 
s u bt ypes, or c o m bi nati o n o pti o ns, as i n dicate d.
A n u m ber of cli nical trials ha ve s h o w n a c orrelati o n bet wee n certai n t u m or m utati o ns 
(e g, K R A S or B R A F) a n d t he lac k of res p o nse t o tar gete d t hera p y , s uc h as a nti-E G F R 
a nti b o dies i n partici pa nts wit h t u m ors t hat are K R A S p ositi ve ( Alle gra et al, 2 0 0 9; Di 
Nic ola nt o ni o et al, 2 0 0 8; Pratilas et al, 2 0 0 8; S olit et al, 2 0 0 6). 2 ,1 4 ,3 5 ,4 2  Pfizer’s i n vi v o 
p har mac ol o g y  st u dies de m o nstrate d a nti-t u m or efficac y wit h P F-0 7 0 6 2 1 1 9 i n cell li ne 
xe n o graft ( C L X) a n d partici pa nt- deri ve d xe n o graft ( P D X) m o dels of c ol orectal ca ncer, m ost 
of w hic h are m uta nt f or K R A S or B R A F o nc o ge nes. A d diti o nall y , P F-0 7 0 6 2 1 1 9 has t he 
p ote ntial t o be use d i n t he setti n gs of eit her micr osatellite sta ble ( M S S) or hi g h micr osatellite 
i nsta bilit y ( M SI- H) disease gastr oi ntesti nal a de n ocarci n o mas as G U C Y 2 C is e x presse d 
acr oss b ot h s u bt ypes ( Bas hir et al, 2 0 1 9). 5
A d diti o nall y , i m m u ne c hec k p oi nt i n hi biti o n mec ha nis ms ( Sal ma ni neja d, 2 0 1 9),3 9 s uc h as 
u pre g ulati o n of P D -L 1 ( Pr o gra m me d deat h li ga n d 1) i n res p o nse t o treat me nt c o ul d lea d t o 
resista nce t o P F-0 7 0 6 2 1 1 9 acti vit y , w hic h is de pe n de nt o n T-cell acti vati o n. T o a d dress t his 
iss ue, P F-0 7 0 6 2 1 1 9 c o m bi nati o ns wit h i m m u ne c hec k p oi nt i n hi bit ors were e val uate d a n d 
s h o we d e n ha nce d efficac y c o m pare d t o si n gle a ge nts. F urt her m ore, c o m bi nati o ns of 
P F -0 7 0 6 2 1 1 9 were e val uate d wit h a nti -a n gi o ge nesis a ge nts, w hic h ha ve bee n re p orte d t o 
e n ha nc e T-cell i nfiltrati o n i nt o t u m ors ( Alle n et al 2 0 1 7). 3 Acc or di n gl y, c o m bi nati o ns of 
P F - 0 7 0 6 2 1 1 9 wit h eit her a n a nti-V E G F -A a nti b o d y , or a xiti ni b, a small m olec ule 
a nti-a n gi o ge nic a ge nt, s h o we d c o m plete t u m or re gressi o ns c o m pare d t o si n gle a ge nts, w hic h 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 6
ha d mi ni mal t o m o derate efficac y  i n t he c ol orectal t u m or m o del teste d. T hese st u dies 
c ollecti vel y s u g gest t hat si n gle a ge nt efficac y  o bser ve d wit h P F- 0 70 6 2 1 1 9 ca n be e n ha nce d 
wit h i m m u ne c hec k p oi nt bl oc ka de a ge nts, w hic h pre ve nt T -cell e x ha usti o n, as well as wit h 
a nti-a n gi o ge nesis a ge nts w hic h c o ul d i ncrease t u m or i nfiltrati n g l y m p h oc y tes ( TI Ls).
2. 2. B ac k gr o u n d
2. 2. 1. A d v a nce d G astr oi ntesti n al A de n oc arci n o m as
Certai n gastr oi ntesti nal t u m ors, i ncl u di n g c ol orectal ca ncer ( C R C), gastric ca ncer, a n d 
gastr oes o p ha geal ca ncer, c o nti n ue t o be a n area of u n met me dical nee d des pite a d va nces i n 
c yt ot o xic c he m ot hera pies a n d ne wer tar gete d a ge nts.
C R C gl o ball y  ra n ks t hir d i n ter ms of i nci de nce wit h o ver 1. 8 milli o n ne w C R C cases a n d 
8 8 1, 0 0 0 deat hs are esti mate d t o occ ur ( Bra y  et al, 2 0 1 8).1 0 I n t he U S, nearl y 1 5 0, 0 0 0 ne w 
cases of C R C are dia g n ose d eac h year, res ulti n g i n t he deat hs of nearl y 5 0, 0 0 0 pe o ple 
a n n uall y ( A h me di n et al, 2 0 0 9).1  C urre ntl y , treat me nt o pti o ns i nclu de c o m bi nati o ns of a 
fl u or o p yri mi di ne wit h eit her o xali plati n or iri n oteca n as a bac k b o ne. Tar gete d a ge nts ha ve 
s h o w n a d de d be nefit w he n a d de d t o t hese re gi me ns, i ncl u di n g m o n ocl o nal a nti b o dies 
directe d a gai nst t he E pi der mal Gr o wt h Fact or Rece pt or ( E G F R; cet u xi ma b a n d 
pa nit u m u ma b) a n d vasc ular e n d ot helial gr o wt h fact or ( V E G F; be vaciz u ma b, afli berce pt) 
( H ur witz HI et al, 2 0 0 9; Saltz L B et al, 2 0 0 8, C ha u I a n d C u n ni n g ha m D, 2 0 0 9). 2 0 ,3 8 ,1 2 Als o , 
t h o u g h t he cli nical be nefit is ver y li mite d, treat me nt f or a d va nce d refract or y C R C has bee n 
de vel o pe d, i ncl u di n g re g orafe ni b, a n oral m ulti ki nase i n hi bit or, a n d trifl uri di ne/ti piracil 
( Lo ns urf ® ), a D N A s y nt hesis m o d ulat or t hat i n hi bits cell pr oliferati o n ( Gr ot he y A et al, 2 0 1 3, 
L o ns urf ® U S PI ).1 7  H o we ver, des pite a d va nces i n t he treat me nt of C R C, pr o gressi o n of 
disease will occ ur i n a si g nifica nt pr o p orti o n of partici pa nts lea di n g t o m or bi dit y  a n d 
m ortalit y .
Gastric ca ncer is als o pre vale nt wit h a n esti mate d 2 0 0, 0 0 0 ne w cases i n t he U S, E U 5, a n d 
Ja pa n a n d is t he fift h m ost fre q ue ntly dia g n ose d ca ncer w orl d wi de ( Bra y  F et al, 2 0 1 8).1 0 T he 
dia g n osis of gastric ca ncer occ urs w he n alrea d y i n a d va nce d sta ge disease a n d ma y prese nt i n 
differe nt areas of t he st o mac h i ncl u di n g t he gastr oes o p ha geal j u ncti o n. S yste mic 
c he m ot hera p y is t he m ost c o m m o n treat me nt a p pr oac h f or rec urre nt/ metastatic disease t hat 
ma y  i ncl u de t he use of F O L F O X a n d e pir u bici n-base d plati n u m c o m bi nati o n c he m ot hera p y 
al o n g wit h trast uz u ma b a d diti o n t o t h ose o vere x pressi n g H E R 2 as c o m m o n fr o ntli ne 
re gi me ns. Ra m ucir u ma b ( C yra mza® ) wit h or wit h o ut paclita xel or paclita xel wit h iri n oteca n 
a n d ge mcita bi ne or ot her m o n o a n d c o m b o c he m ot hera pies are use d i n m ore a d va nce d li nes 
( Na gaic h N a n d S har ma R, 2 0 1 8).3 3  Als o, i m m u n o -o nc ol o g y  c o m p o u n ds, s uc h as 
pe m br oliz u ma b, ha ve de m o nstrate d li mite d cli nical be nefit a n d ma y  be c o nsi dere d 
( Ki yoz u mi Y et al, 2 0 1 8). 2 3
Eac h ye ar, o ver 5 0 0, 0 0 0 ne w cases of es o p ha geal ca ncer are dia g n ose d w orl d wi de wit h o ver 
1 7, 0 0 0 cases dia g n ose d i n t he U S, of w hic h a de n ocarci n o ma c o m prises a n est i mate d 2 0 % of 
cases ( Bra y et al, 2 0 1 8).1 0 Treat me nt o pti o ns f or es o p ha geal a de n ocarci n o ma are ge nerall y 
si milar t o t h ose use d i n gastric a de n ocarci n o ma. C he m ot hera p y, p ossi bl y al o n g wit h tar gete d 
dr u g t hera p y has bee n use d. Si milar t o C R C patie nts, o utc o mes f or patie nts wit h rec urre nt 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 7
metastatic gastric a n d es o p ha geal ca ncer disease are p o or. T h us, effecti ve t hera pies t o 
a d dress c ol o n, gastric a n d es o p h a geal a de n ocarci n o mas are nee de d.
2. 2. 2. G U C Y 2c E x pressi o n i n H u m a n C a ncers 
G U C Y 2c is a ca n di date tar get f or bis pecific a nti b o d y -base d i m m u n ot hera p y  d ue t o its hi g h 
e x pressi o n acr oss gastr oi ntesti nal t u m ors i ncl u di n g c ol o n ca ncer (e x presse d i n > 9 0 % of cases 
acr oss all sta ges), a n d gastric or gastr oes o p ha geal j u ncti o n ca ncer (e x presse d i n > 5 0 % of 
a de n ocarci n o ma cases of t he es o p ha g us a n d st o mac h) ( Bir be et al, 2 0 0 5; Da naee et al, 
2 0 1 7). 9 ,1 3  Tar get e x pressi o n i n n or mal tiss ues is lar gel y restricte d t o t he a pical si de of 
i ntesti nal e pit helial ti g ht j u ncti ons, w hic h c o ul d all o w f or prefere ntial u pta ke of G U C Y 2 C 
tar gete d bi ol o gics b y t u m ors t hat ha ve disr u pte d ti g ht j u ncti o n arc hitect ure ma ki n g it a n 
a p pr o priate a nti ge n t o tar gete d t hera p y a p pr oac hes. T hese c o nsi derati o ns hi g hli g ht t he 
p ote ntial of P F - 0 7 0 6 2 1 19 as a treat me nt o pti o n f or c ol o n, gastric a n d es o p ha geal 
a de n ocarci n o mas.
2. 2. 3. Bis pecific Re directe d T -cell E n g a gi n g T her a pies
T he p ote ntial of re directe d T -cell t hera pe utics i n ca ncer treat me nt has bee n de m o nstrate d b y 
t he U nite d States F o o d a n d Dr u g A d mi nistrati o n’s a p pr o val of t he bis pecific T-cell e n ga ger, 
bli nat u m o ma b f or t he treat me nt of rela pse d or refract or y  B-cell prec urs or ac ute 
l ym p h o blastic le u ke mia. 4 2 Bis pecifics wit h a re directe d T -cell e n ga gi n g m o dalit y ha ve als o 
s h o w n pr o mise f or t he treat me nt of s oli d t u m ors, i ncl u di n g C R C, wit h se veral bis pecific 
a ge nts i n earl y cli nical st u dies ( Ta ber ner o et al, 2 0 1 7; M o ore P A et al, 2 0 1 8). 4 5 ,2 7
C y t ot o xic T l ym p h oc y tes ( C T Ls) c o n ve nti o nally rec o g nize cell pr otei n a nti ge ns prese nte d i n 
c o m ple x wit h Maj or Hist oc o m pati bilit y C o m ple x ( M H C) Class I m olec ules o n t he cell 
s urface via t heir T- cell rece pt ors ( T C Rs). 3 8 C D 3 bis pecifics circ u m ve nt t he nee d f or T C R 
e n ga ge me nt t hr o u g h M H C Class I  i n c o m ple x wit h a nti ge nic pe pti de, a n d i nstea d recr uit 
T cells t o tar get cells e x pressi n g cell s urface tar get pr otei n (a nti ge n). O ne ar m of t he 
bis pecific bi n ds t o a t u m or ass ociate d cell s urface a nti ge n, a n d t he ot her ar m bi n ds t o t he 
C D 3ε pr otei n, w hic h is a part of t he T C R c o m ple x o n T cells. C o-e n ga ge me nt of C D 3ε o n 
T cells a n d tar get a nti ge n o n t u m or cells via a bis pecific m olec ule lea ds t o a c y t ot o xic 
res p o nse. Cyt ot o xicit y  is me diate d b y release a n d tra nsfer of gra nz yme B a n d perf ori n fr o m 
t he T cell t o t he tar get cell. Usi n g t his C D 3 -bis pecific mec ha nis m of acti o n, P F - 0 7 0 6 2 1 1 9 
re directs T cells t o tar get G U C Y 2c e x pressi n g t u m or cells t hr o u g h c o-e n ga ge me nt of C D 3ε
o n t he T cell, a n d G U C Y 2c o n t he t u m or cell s urface, t here b y br oa de ni n g t he re pert oire of 
T cells t hat ca n rec o g nize t u m ors a n d act as effect or cells.
2. 2. 4. P F -0 7 0 6 2 1 1 9
P F -0 7 0 6 2 1 1 9 is a f ull y h u ma nize d a n d o pti mize d a nti - G U C Y 2c bis pecific t hera pe utic dr u g 
ca n di date t hat is a heter o di meric dia b o d y Fc f usi o n pr otei n c o m prise d of t w o rec o m bi na nt 
sc F v d o mai ns, o ne f ull y h u ma n d o mai n directe d a gai nst G U C Y 2c a n d t he ot her a gai nst t he 
C D 3ε c hai n ( h u ma nize d), f use d t o t he h u ma n Fc d o mai n of i m m u n o gl o b uli n 1 (I g G 1). 
P F - 0 7 0 6 2 1 1 9 bi n di n g of C D 3ε o n T cells a n d G U C Y 2c o n t u m or cells re directs T cells t o 
tar get G U C Y 2c-e x pressi n g t u m or cells w hic h i nitiates killi n g of t he G U C Y 2c e x pressi n g 
t u m or cell. P F-0 7 0 6 2 1 1 9 all o ws t he T -cell t o circ u m ve nt t he nee d f or t he i nteracti o n of t he 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 8
T C R a n d M H C class I  i n c o m ple x wit h a nti ge n, a n d i nstea d re directs T-cells t o tar get cells 
t hr o u g h direct c o-e n ga ge me nt of C D 3ε e x presse d o n T -cells.
2. 2. 5. N o ncli nic al P h ar m ac ol o g y
F urt her details of t he n o ncli nical p har mac ol o g y  of P F-0 7 0 6 2 1 1 9 are pr o vi de d i n t he I B.
2. 2. 5. 1. I n Vitr o P h ar m ac o d y n a mics
P F -0 7 0 6 2 1 1 9 de m o nstrate d l o w -n M bi n di n g t o h u ma n G U C Y 2c ( K D = 7. 4 7 n M) a n d h u ma n 
C D 3 ( K D = 2 3. 9 7 n M) b y  s urface plas m o n res o na nce ( S P R, 2 5° C), a n d l o w-n M bi n di n g t o 
b ot h tar gets si m ulta ne o usl y  ( E C5 0 = 8. 7 8 n M) b y  rec o m bi na nt pr otei n e nzy me li n ke d 
i m m u n os or be nt assa y ( E LI S A). P F-0 7 0 6 2 1 1 9 bi n di n g t o c y n o m ol g us m o n ke y  G U C Y 2c a n d 
m o use G U C Y 2c de m o nstrate d K D val ues of 3. 0 1 n M a n d 1 7. 2 7 n M, res pecti vel y .
2. 2. 5. 1. 1. Cell S urf ace Bi n di n g a n d C yt ot o xicit y of P F- 0 7 0 6 2 1 1 9 i n G U C Y 2c E x pressi n g 
T u m or Cell Li nes
P F -0 7 0 6 2 1 1 9 s h o we d d ose de pe n de nt bi n di n g b y fl o w c yt o metr y t o cell li ne 
3 0 0. 1 9 e n gi neere d t o e x press h u ma n G U C Y 2c, w h ile n o bi n di n g was o bser ve d i n pare ntal 
n o n -G U C Y 2c e x pressi n g 3 0 0. 1 9 cells, t here b y de m o nstrati n g s pecificit y  of P F-0 7 0 6 2 1 1 9 t o 
G U C Y 2c. G U C Y 2c cell s urface e x pressi o n was q ua ntifie d o ver a pa nel of ca ncer cell li nes 
usi n g a fl o w c y t o metr y-base d assa y  wit h a n a nti-h u ma n G U C Y 2c m o n ocl o nal a nti b o d y  
( m A b). H C T 1 1 6 cells were verifie d as ne gati ve f or G U C Y 2c e x pressi o n a n d were use d as 
t he ne gati ve c o ntr ol cell li ne i n s u bse q ue nt C T L assa ys.
P F - 0 7 0 6 2 1 1 9- me diate d cell killi n g was assesse d i n t hese cell li nes i n a 4 8- h o ur C T L  assa y 
at a 5: 1 or 1: 1 effect or ( T cell) t o tar get (t u m or cell) rati o. T he o bser ve d c y t ot o xicit y was 
T cell de pe n de nt si nce n o acti vit y  was o bser ve d wit h P F-0 7 0 6 2 1 1 9 i n t he a bse nce of T cells. 
P F - 0 7 0 6 2 1 1 9 de m o nstrate d cell killi n g i n all G U C Y 2c e x pressi n g cell li nes b ut n ot i n 
G U C Y 2c ne gati ve H C T 1 1 6 cells. C y t o ki ne release was als o assesse d i n t hese i n vitr o C T L 
assa ys as a s urr o gate meas ure of P F-0 7 0 6 2 1 1 9 a bilit y  t o acti vate h u ma n T cells. F oll o wi n g 
t he a d diti o n of P F-0 7 0 6 2 1 1 9 a n d T cells, c y t o ki nes were detecte d i n t he s u per nata nts of all 
G U C Y 2c -e x pressi n g ca ncer cell li nes, b ut n ot i n G U C Y 2c -ne gati ve H C T 1 1 6 cells.
A d diti o nall y , P F-0 7 0 6 2 1 1 9 was assesse d f or its p ote ntial t o a g o nize G U C Y 2c pat h wa y  
acti vit y b y meas uri n g t he pr o d ucti o n of t he d o w nstrea m effect or c yclic g ua n osi ne 
m o n o p h os p hate (c G M P) i n G U C Y 2c e x pressi n g T 8 4 t u m or cells. W hile t he G U C Y 2c 
pat h wa y  a g o nist, bacterial e nter ot o xi n S T p, i ncrease d c G M P i n a d ose- de pe n de nt ma n ner, 
c G M P pr o d ucti o n was n ot e n ha nce d b y t he a d diti o n of i ncreasi n g c o nce ntrati o ns of 
P F -0 7 0 6 2 1 1 9. A d diti o nall y , P F-0 7 0 6 2 1 1 9 di d n ot affect c G M P pr o d ucti o n i n d uce d b y S T p, 
i n dicati n g t hat P F-0 7 0 6 2 1 1 9 is neit her a G U C Y 2c pat h wa y  a g o nist, n or d oes it ne utralize 
G U C Y 2c pat h wa y  f u ncti o n i n t he prese nce of li ga n d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 3 9
2. 2. 5. 1. 2. I n Vi v o P h ar m ac o d y n a mics
Si n gle A ge nt P F -0 7 0 6 2 1 1 9 St u dies: A nti -t u m or Effic ac y of P F-0 7 0 6 2 1 1 9 i n C ol orect al 
T u m or M o dels wit h V ar yi n g G U C Y 2c E x pressi o n
I n vi v o st u dies wit h P F-0 7 0 6 2 1 1 9 were c o n d ucte d i n C L X a n d P D X m o dels of c ol orectal 
ca ncer wit h var yi n g le vels of G U C Y 2c e x pressi o n. Fi g ure 1 hi g hli g hts d ose -de pe n de nt si n gle 
a ge nt a nti -t u m or acti vit y o bser ve d i n t he L S 1 0 3 4 C LX m o del a n d t he P D X -C R X - 1 1 2 0 1 
P D X m o del, b ot h of w hic h ha d relati vel y  hi g h e x pressi o n of G U C Y 2c a n d were m uta nt f or 
B R A F a n d K R A S.
Fe male N O D -sci d I L- 2 Rn ull ( N S G) mice were i m pla nte d s u bc uta ne o usl y wit h t he 
L S 1 0 3 4 cell li ne or fra g me nts of P D X -C R X -1 1 2 0 1, usi n g a d o pti ve h u ma n T -cell tra nsfer. I n 
t he LS 1 0 3 4 m o del, P F -0 7 0 6 2 1 1 9 treat me nt res ulte d i n si g nifica nt ef ficac y ( p 0. 0 0 0 1 vers us 
ve hicle) wit h c o m plete t u m or re gressi o ns i n 1 0/ 1 0 mice d ose d as l o w as 0. 1 m g/ k g 
(Fi g ure 1 - A). T he a nti-t u m or acti vit y was d ose-de pe n de nt, si nce l o wer efficac y  was o bser ve d 
at 0. 0 3 m g/ k g of P F -0 7 0 6 2 1 1 9. P D X -C R X - 1 1 2 0 1 t u m or beari n g mice treate d wit h 
P F -0 7 0 6 2 1 1 9 als o s h o we d si g nifica nt efficac y  ( p 0. 0 0 0 1 vers us ve hicle) wit h 9/ 1 0 c o m plete 
t u m or re gressi o ns at 0. 1 5 m g/ k g ( Fi g ure 1 - B). A l o wer d ose of 0. 0 5 m g/ k g res ulte d i n 
re d uce d efficac y ( p 0. 0 5 vers us ve hicle), w hereas 0. 0 1 m g/ k g di d n ot s h o w a n y t u m or 
i n hi biti o n. Neit her t he P BS ve hicle c o ntr ol, n or t he ne gati ve c o ntr ol bis pecific, P F - 0 7 0 6 9 6 9 9, 
i n hi bite d t u m or gr o wt h i n a n y m o del. All treat me nts were well t olerate d wit h n o o verall 
effect o n b o d y wei g ht.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 0
Fi g ure 1.
Si n gle A ge nt P F -0 7 0 6 2 1 1 9 Effic ac y i n Est a bl is he d T u m or M o dels wit h 
A d o pti ve H u m a n T Cell Tr a nsfer
N S G mice beari n g A. L S 1 0 3 4, B. P D X -C R X -1 1 2 0 1 t u m ors were d ose d I V w it h P F-0 7 0 6 2 1 1 9, P F -0 7 0 6 9 6 9 9 or 
P B S w it h wee kl y I V d oses ( 3 d oses f or L S 1 0 3 4 a n d 4 d oses f or P D X-C R X -1 1 2 0 1), a n d h u ma n T cells were 
a d mi nistere d o ne da y after t he first d ose. T u m ors were meas ure d t w ice wee kl y. Data are re p orte d as mea n 
t u m or v ol u me ± S E M.
I V =i ntra ve n o us; N S G = N O D-sci d I L-2 Rγ n ull; P F-0 7 0 6 2 1 1 9 = G U C Y 2c -C D 3 bis pecific; P F -0 7 0 6 9 6 9 9 = ne gati ve 
c o ntr ol C D 3 bis pecific; S E M =sta n dar d err or of t he mea n.
2. 2. 5. 1. 2. 1. E v al u ati o n of I ntr a ve n o us vers us S u bc ut a ne o us D osi n g F oll o wi n g Si n gle 
A ge nt P F -0 7 0 6 2 1 1 9 i n a C ol orect al T u m or M o del
T he r o ute of a d mi nistrati o n of d osi n g P F -0 7 0 6 2 1 1 9 was c o m pare d i n efficac y  st u dies usi n g 
t he hi g h G U C Y 2c-e x pressi n g LS 1 0 3 4 S C C L X m o del, w here t he bis pecific was d ose d 
Q 7 D x 3 I V or S C 0. 1 m g/ k g, 0. 0 6 m g/ k g a n d 0. 0 3 m g/ k g. T here was n o statisticall y  
si g nifica nt differe nce i n t he efficac y o bser ve d wit h I V or S C a d mi nistrati o n of P F-0 7 0 6 2 1 1 9 
at eac h d ose le vel teste d ( p -val ues 0. 0 5).
2. 2. 5. 1. 2. 2. C o m bi n ati o n St u dies wit h P F -0 7 0 6 2 1 1 9 a n d A nti -P D -L 1, A nti -P D -1, or 
A nti -V E G F - A
T he L S 1 0 3 4 C L X m o del de m o nstrate d P F -0 7 0 6 2 1 1 9 treat me nt de pe n de nt i ncrease i n TI Ls 
wit h e x pressi o n of gra nz y me B t hat was p olarize d t o war ds t u m or cells, s u g g esti n g t hat t hese 
TI Ls were p oise d t o f or m i m m u ne s y na pses a n d kill t u m or cells. A d diti o nall y , t u m ors treate d 
wit h P F -0 7 0 6 2 1 1 9 als o s h o we d u pre g ulati o n of P D -L 1 (a vel u ma b m o use re verse c hi meric 
a nti b o d y) at b ot h 1 m g/ k g a n d 0. 0 3 m g/ k g d oses, i n dicati n g t hat c hec k p oi nt mec ha nis ms t hat 
c o ul d da m pe n C T L acti vit y were bei n g i n d uce d wit h treat me nt. T heref ore, P F-0 7 0 6 2 1 1 9 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 1
c o m bi nati o ns wit h P D - 1 ( pe m br oliz u ma b a nti b o d y wit h h u ma n I g G 2 Fc effect or f u ncti o n 
m uta nt bac k b o ne [ D 2 6 5 A hl g G 2 d A Fc effect or f u ncti o n m uta nt] )/ P D-L 1  c hec k p oi nt 
i n hi bit ors were e val uate d i n t his m o del. T u m or-beari n g mice were treate d wit h a mi ni mall y  
efficaci o us d ose of 0. 0 3 m g/ k g of P F -0 7 0 6 2 1 1 9 as a si n gle a ge nt, i n c o m bi nati o n wit h eit her 
1 0 m g/ k g a nti -P D -L 1 or 5 m g/ k g a nti -P D -1. I n b ot h a nti -P D -L 1  a n d a nti-P D -1 c o m bi nati o ns 
wit h P F -0 7 0 6 2 1 1 9, a si g nifica nt c o m bi nati o n be nefit was o bser ve d ( p -val ues of < 0. 0 0 0 1 a n d 
0. 0 0 0 4 res pecti vel y), w hereas mi ni mal t o n o efficac y  was o bser ve d wit h si n gle a ge nts 
(Fi g ure 2 ).
I n a d diti o n, a nti-V E G F bl oc ka de, a mec ha nis m k n o w n t o i ncrease T -cell i nfiltrati o n i n 
t u m ors was c o m bi ne d wit h P F-0 7 0 6 2 1 1 9. T he P D X -C R X -1 1 2 0 1 m o del, w hic h is partiall y  
res p o nsi ve t o a nti- VE G F - A m A b treat me nt, was use d t o e val uate t he be nefit of c o m bi ni n g 
P F - 0 7 0 6 2 1 1 9 wit h a nti-V E G F -A t hera p y. T he c o m bi nati o n of t he a nti -V E G F -A treat me nt 
wit h a mi ni mall y  efficaci o us si n gle a ge nt d ose of P F-0 7 0 6 2 1 1 9 at 0. 0 5 m g / k g le d t o 
c o m plete t u m or re gressi o ns i n 1 0/ 1 0 mice. I n all c o m bi nati o n st u dies, all treat me nts were 
well t olerate d a n d t here was n o o verall effect o n b o d y  wei g ht.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 2
Fi g ure 2.
A nti -t u m or Effic ac y f oll o wi n g P F-0 7 0 6 2 1 1 9 i n C o m bi n ati o n wit h A nti P D -1, 
A nti -P D -L 1, or A nt i-V E G F -A i n C ol orect al T u m or M o dels
A . N S G mice beari n g S C L S 1 0 3 4 t u m ors were d ose d I V wit h P F-0 7 0 6 2 1 1 9 (as si n gle a ge nt or i n c o m bi nati o n 
wit h a nti -P D -L 1/ a nti -P D -1 m A bs), P F -0 7 0 6 9 6 9 9 or P B S o n Da ys -1, 6 a n d 1 3 ( Q 7 D x 3) I V. A nti -P D -L 1 m A b 
wa s a d mi nistere d I V o n da ys -1, 2, 5, 8, 1 1 a n d 1 4 ( Q 3 D x 6) eit her as a si n gle a ge nt or c o m bi nati o n wit h 
P F -0 7 0 6 2 1 1 9. A nti -P D - 1 m A b w as d ose d I V o n da ys -1, 6 a n d 1 3 ( Q 7 D x 1 3) eit her as si n gle a ge nt or i n 
c o m bi nati o n wit h P F-0 7 0 6 2 1 1 9. All mice were d ose d I V wit h T cells o n Da y 0 t o e val uate c o m bi nati o n be nefits 
of a d mi nisteri n g P F -0 7 0 6 2 1 1 9 w it h a nti-P D -L 1/a nti -P D -1 vs si n gle a ge nt treat me nt. 
B. N S G mice beari n g S C P D X -C R X -1 1 2 0 1 t u m ors were d ose d I V w it h P F-0 7 0 6 2 1 1 9 (as si n gle a ge nt or i n 
c o m bi nati o n wit h a nti -V E G F -A m A b), P F -0 7 0 6 9 6 9 9 or P B S o n Da ys 0, 7 a n d 1 4 ( Q 7 D x 3) I V. A nti -V E G F -A 
m A b was a d mi nistere d I V o n da ys 0, 3, 6, 9 ( Q 3 D x 4) eit her as a si n gle a ge nt or c o m bi nati o n wit h 
P F -0 7 0 6 2 1 1 9. All mice were d ose d I V w it h T cells o n Da y 1 t o e val uate c o m bi nati o n be nefit of a d mi nisteri n g 
P F -0 7 0 6 2 1 1 9 wit h V E G F bl oc ka de. T u m or were meas ure d t w ice wee kl y. Data are re p orte d as mea n t u m or 
v ol u me ± S E M.
I V =i ntra ve n o us; N S G = N O D-sci d I L-2 R n ull; P F-0 7 0 6 2 1 1 9 = G U C Y 2c -C D 3 bis pecific; P F -0 7 0 6 9 6 9 9 = ne gati ve 
c o ntr ol C D 3 bis pecific; m A b = m o n ocl o nal a nti b o d y; Q 7 D x 3 = d osi n g e ver y 7 d a y s f or a t otal of 3 d oses; 
Q 3 D x 6 = d osi n g e ver y 3 da ys f or a t otal of 6 d oses; Q 3 D x 4 = d osi n g e ver y 3 da ys f or a t otal of 4 d oses; 
S E M =sta n dar d err or of t he mea n.
F or a d diti o nal details of t he i n vitr o a n d i n vi v o acti vit y  of P F -0 7 0 6 2 1 1 9 refer t o t he I B.
2. 2. 6. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m
P K of P F -0 7 0 6 2 1 1 9 was e val uate d i n c y n o m ol g us m o n ke y s f oll o wi n g I V i njecti o ns of P F-
0 7 0 6 2 1 1 9 at d oses fr o m 1 µ g/ k g t o 1 8 0 µ g / k g a n d S C a d mi nistrati o n at 3 µ g/ k g t o 6 0 µ g/ k g. 
P F -0 7 0 6 2 1 1 9 mea n s ys te mic e x p os ure i ncrease d wit h d ose i n a ge nerall y d ose-pr o p orti o nal 
ma n ner s u g gesti n g n o e vi de nce of tar get -me diate d dr u g dis p ositi o n ( T M D D) acr oss t he 
teste d d ose ra n ge. Base d o n p o p ulati o n P K a nal ysis, t he mea n dr u g cleara nce fr o m t he ce ntral 
c o m part me nt ( C L) i n c yn o m ol g us m o n ke y s was 0. 2 2 m L / h/ k g, t he mea n stea d y state v ol u me 
of distri b uti o n ( V ss) was 7 3 m L / k g, a n d t he mea n ter mi nal eli mi nati o n half-life (t½ ) was 1 0 
da y s. F oll o wi n g s u bc uta ne o us ( S C) a d mi nistrati o n, bi oa vaila bilit y was m o derate ( ~ 6 0 %) [as 
assesse d b y area u n der t he c ur ve wit hi n t he first d osi n g i nter val ( A U Cta u)]. T he mea n P F-
0 7 0 6 2 1 1 9 ma xi m u m o bser ve d c o nce ntrati o n ( Cma x ) after t he first d ose a d mi nistrati o n of 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 3
6 0 µ g/ k g S C was ~ 7 0 % l o wer c o m pare d t o 6 0 µ g / k g I V a d mi nistrati o n. T he i nci de nce of 
A D A i n d ucti o n i n t he pi v otal t o xicit y  st u d y was a p pr o xi matel y 1/ 2 7 ( 3. 7 %), t h us n o f or mal 
assess me nt of t he i m pact o n A D A o n P F- 0 7 0 6 2 1 1 9 e x p os ure was c o n d ucte d. N o a p pare nt 
i m pact of ge n der o n t he s yste mic e x p os ure of P F-0 7 0 6 2 1 1 9 was o bse r ve d. Base d o n t he P K 
o bser ve d i n c y n o m ol g us m o n ke y s, t he P K of P F- 0 7 0 6 2 1 1 9 i n h u ma ns is e x pecte d t o be 
li near acr oss t he d ose ra n ge t o be teste d wit h a t½ of a p pr o xi matel y  2 1 da ys.
2. 2. 7. N o ncli nic al S afet y
I n n o ncli nical I V or S C st u dies wit h P F-0 7 0 6 2 1 1 9 i n c y n o m ol g us m o n ke y s of u p t o 1-m o nt h 
i n d urati o n, se verely t o xic fi n di n gs were o bser ve d at t he hi g h n o n -t olerate d d ose of 6 0 µ g/ k g 
( o nce wee kly I V or S C) i n t he 1-m o nt h G L P t o xicit y  st u d y. T his d ose was n ot t olerate d d ue 
t o decli ni n g c o n diti o n relate d t o e xte nsi ve a n d persiste nt cli nical o bser vati o ns of 
gastr oi ntesti nal distress (i ncl u di n g diarr hea, de h y d rati o n, h yp oacti vit y , re d uce d a p petite, etc.) 
a n d b o d y wei g ht l oss t hat res ulte d i n u nsc he d ule d e ut ha nasia of 4 a ni mals ( 2 a ni mals i n t he 
I V gr o u p a n d 2 a ni mals i n t he S C gr o u p) a n d disc o nti n uati o n of dr u g treat me nt f or 
3 a d diti o nal a ni mals at t he hi g h d ose ( 1 a n d 2 a ni mals i n t he I V a n d S C gr o u ps, res pecti vel y). 
Cli nical si g ns of gastr oi ntesti nal distress, partic ularl y  diarr hea a n d de hy d rati o n, were als o 
o bser v e d at a l o wer d ose of 3 0 µ g/ k g I V d uri n g 1 0 -d a y  n o n-G L P t o xic ol o g y  st u dies b ut were 
t olerate d wit h s u p p orti ve care ( oral a n d S C fl ui ds). T he d ose of 3 µ g / k g S C was t olerate d i n 
t he 1-m o nt h G L P t o xicit y  st u d y wit h o nl y mi n or occasi o nal cli nical o bser vati o ns of e mesis 
or l o ose st o ol. A d diti o nall y , cli nical o bser vati o ns of c yt o ki ne release sy n dr o me (i ncl u di n g 
e mesis, h yp oacti vit y , c ha n ges i n b o d y te m perat ure, h u nc he d p ost ure, etc) were o bser ve d after 
t he first d ose of P F-0 7 0 6 2 1 1 9 a n d were ass ociate d wit h ele va te d ser u m c yt o ki nes a n d 
mar kers of T -cell acti vati o n. T hese o bser vati o ns were li mite d t o 1/ 1 0 a ni mals wit h tra nsie nt 
e mesis o n Da y 1 at 3 µ g / k g S C. T he i nci de nce of cli nical o bser vati o ns relate d t o c yt o ki ne 
release as well as t he ma g nit u de of ser u m c yt o ki ne ele vati o ns were si g nifica ntl y  l o wer a n d 
was ass ociate d wit h a decrease d C ma x of a p pr o xi matel y 7 0 % i n a ni mals d ose d via t he S C 
r o ute c o m pare d wit h t he I V r o ute.
Test article -relate d, b ut n o na d verse, tar get or ga ns i de ntifie d i ncl u de d t he gastr oi ntesti nal tract 
(cry pt cell h y per plasia, vill o us atr o p h y , mi xe d cell i nfla m mati o n, gastric gla n d h ypertr o p h y ), 
he mat ol y m p h o p oietic s yste m ( decrease d cell ularit y of b o ne marr o w, s plee n a n d t h y m us), 
pa ncreas ( m o n o n uclear cell i nfiltrates of islet cells), testis (se mi nifer o us t u b ular de ge nerati o n 
a n d re d uce d s per m), e pi di d y mis (cell ular de bris a n d e pit helial vac u olati o n), a n d ki d ne y  
(t u b ular dilatati o n of pr o xi mal a n d distal t u b ules a n d c ollecti n g d uct) a n d all fin di n gs 
c o m pletel y rec o vere d or were o nly see n i n a ni mals e ut ha nize d earl y ( ki d ne y, testis, 
e pi di d ymis).
T he N o A d verse Effect Le vel ( N O A E L)/ Hi g hest N o n- Se verel y  T o xic D ose ( H N S T D) i n t he 
pi v otal 1 -m o nt h g o o d la b orat or y  practice ( G LP) st u d y  was 3 µ g/ k g S C. T he mea n C ma x a n d 
A U C 1 6 8 after a d mi nistrati o n of o ne d ose of 3 µ g / k g S C were 2 4. 7 n g/ m L  a n d 3 7 1 0 n g· h/ m L, 
res pecti vely. T he mea n C ma x a n d A U C 1 6 8 after a d mi nistrati o n of 5 wee kl y d oses of 3 µ g/ k g 
S C were 8 9. 7 n g/ m L  a n d 1 3, 6 0 0 n g· h/ m L, res pecti vel y . 
T he sta rti n g d ose of 4 5 µ g Q 2 W is pre dicte d t o ha ve a h u ma n Cma x of 4. 2 n g/ m L a n d 
A U C 1 6 8 of 5 6 6 n g• hr/ m L. T he mar gi n of safet y base d o n C ma x a n d A U C 1 6 8 was calc ulate d as 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 4
a p pr o xi matel y 2 1 × a n d 2 4 ×, res pecti vely base d o n t he c o m paris o n of H N S T D e x p os ure i n 
t he 1-m o nt h re peat -d ose G L P t o xicit y  st u d y i n m o n ke ys t o t he pre dicte d h u ma n e x p os ure at 
t he rec o m me n de d starti n g d ose.
F urt her details of t he n o ncli nical safet y pr o gra m are pr o vi de d i n t he c urre nt I B.
2. 2. 8. S u m m ar y of C urre nt Cli nic al D at a fr o m St u d y C 3 8 6 1 0 0 1
T he c urre nt s u m mar y  of cli nical data is base d o n Part 1 A, d ose escalati o n of t he 
P F -0 7 0 6 2 1 1 9 m o n ot hera p y  wit h o ut pri mi n g d ose, of St u d y C 3 8 6 1 0 0 1. As of 
2 8 Dece m ber 2 0 2 0, 2 2 partici pa nts ha ve bee n d ose d acr oss 5 d ose le vels ( 4 5 µ g, 1 3 5 µ g, 
4 0 0 µ g, 8 0 0 µ g, a n d 1 6 0 0 µ g) of P F -0 7 0 6 2 1 1 9 a d mi nistere d S C Q 2 W. 
2. 2. 8. 1. S afet y D at a U p d ate
T he m ost c o m m o n treat me nt -e mer ge nt a d verse e ve nts occ urri n g i n ≥1 0 % of partici pa nts a n d 
p ossi bl y  relate d t o P F-0 7 0 6 2 1 1 9 i ncl u de d fe ver, diarr hea, v o miti n g, C R S, na usea, pr urit us, 
fati g ue, i njecti o n site reacti o n, decrease d a p petite, h yp ote nsi o n, li pase i ncrease, ala ni ne 
a mi n otra nsferase i ncrease d, a m yl ase i ncrease d, as partate a mi n otra nsferase i ncrease d, c hills, 
c o nsti pati o n, hea dac he, a n d h y p o kale mia. A D L T of Gra de 3 diarr hea (lasti n g > 3 da ys)
occ u rre d i n b ot h partici pa nts treate d at t he hi g hest d ose le vel ( 1 6 0 0 µ g) wit h o ut pri mi n g, a n d 
D L T of Gra de 3 diarr hea (lasti n g > 3 da y s) a n d Gra de 3 C R S occ urre d res pecti vel y i n 2 of 9 
partici pa nts treate d at t he d ose le vel ( 8 0 0 µ g) esta blis he d as t he si n gle -age nt ma xi m u m 
t olerate d d ose ( M T D) wit h o ut pri mi n g.
2. 2. 8. 2. P h ar m ac o ki netics
Preli mi nar y  P K para meters f or partici pa nts esti mate d usi n g n o mi nal c ollecti o n ti mes a n d 
q ualit y -c o ntr olle d, n ot q ualit y-ass ure d bi oa nal ytical data are prese nte d i n Ta ble 7 . Data are 
s u m marize d f or all c o h orts ( 4 5 µ g, 1 3 5 µ g, 4 0 0 µ g, 8 0 0 µ g, a n d 1 6 0 0 µ g) treate d wit h a 
si n gle S C d ose of P F-0 7 0 6 2 1 1 9. 
F oll o wi n g S C a d mi nistrati o n, P F -0 7 0 6 2 1 1 9 was a bs or be d sl o wl y wit h a me dia n T ma x f or 
m ost c o h orts ra n gi n g fr o m 4 t o 7 da y s p ost si n gle- d ose a d mi nistrati o n. O verall, e x p os ures 
i ncrease d i n a n a p pr o xi matel y d ose-pr o p orti o nal ma n ner wit h i ncreasi n g d oses. 
F oll o wi n g re peate d d osi n g Q 2 W, t he pre d ose c o nce ntrati o ns i ncrease d wit h eac h s uccessi ve 
d ose i n dicati n g p ote ntial acc u m ulati o n of t he dr u g. Li mite d data are a vaila ble f or m ulti ple 
d ose P K i n C y cle 4, d ue t o m ost partici pa nts c o mi n g off st u d y  pri or t o t he assess me nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 5
T a ble 7 .  
Me a n ( % C V) P K P ar a meters F oll o wi n g Si n gle S C D oses of P F-0 7 0 6 2 1 1 9 
i n P artici p a nts wit h A d v a nce d GI T u m ors ( St u d y C 3 8 6 1 0 0 1)
D ose ( µ g) S C/ # of 
p artici p a nts
St u d y D a y
T m a x 2
( hr)
C m a x 1
( n g/ m L)
A U C 1 6 8 1, 3
( n g * hr/ m L)
A U C 3 3 6 1, 3 ( n g * hr/ m L)
4 5 ( n = 2)
C 1 D 1
8- 3 3 6 
2. 9 7 
3 3 9 
8 0 3 
1 3 5 ( n = 3)
C 1 D 1
1 6 8 
( 9 6-1 6 8)
9. 0 3 ( 9. 8)
1 2 0 5 ( 4. 4)
2 6 0 0 ( 8. 0)
4 0 0 ( n = 6)
C 1 D 1
9 6 
( 9 6-3 3 6)
4 3. 7 ( 4 0)
5 5 8 2 ( 5 4)
1 2 0 6 8 ( 4 2)
8 0 0 ( n = 9)
C 1 D 1
9 6
( 2 4-1 6 8)
6 6. 8 ( 3 9)
9 0 4 1 ( 3 9)
1 8 9 4 3 ( 3 5)
1 6 0 0 ( n = 2) 4
C 1 D 1
2 4 
1 1 5 
1 6 4 5 1
--
1 C ma x , A U C 1 6 8 a n d A U C 3 3 6: mea n ( % C V). O nl y mea n prese nte d f or N = 2. O nl y i n di vi d ual val ue prese nte d if 
N = 1.
2 T ma x : Me dia n ( Ra n ge). O nl y ra n ge prese nte d f or N = 2. O nl y i n di vi d ual val ue prese nte d if N = 1.
3 8 0 0 µ g: n = 8 f or A U C1 6 8 a n d A U C 3 3 6
4 1 6 0 0 µ g: n = 1 f or T ma x , Cma x a n d A U C 1 6 8. O ne of t he 2 partici pa nts at t his d ose le vel pr o vi de d P K o nl y u p t o 
4 8 h o urs.
2. 3. A nti - Pr o gr a m me d Cell De at h Pr otei n-1 ( A nti -P D -1)  
Bi n di n g of t he pr o gra m me d cell deat h pr otei n -1 li ga n ds, P D -L 1 a n d P D -L 2 , t o t he P D- 1 
rece pt or f o u n d o n T cells i n hi bits T -cell pr oliferati o n, c yt o ki ne pr o d ucti o n, a n d its c yt ot o xic 
f u ncti o ns. U pre g ulati o n of P D-1 li ga n ds occ ur i n certai n t u m or t y pes a n d si g nali n g t hr o u g h 
t his pat h wa y ca n c o ntri b ute t o t he i n hi biti o n of acti ve T-cell i m m u ne s ur veilla nce of t u m ors. 
I n sy n ge neic m o use t u m or m o dels, bl oc ki n g P D -1 acti vit y  res ulte d i n decrease d t u m or 
gr o wt h. A p pr o val of ni v ol u ma b/ O p di v o ® (a f ully h u ma n i m m u n o gl o b uli n G 4 [I g G 4] 
a nti-P D -1 a nti b o d y  [ A b]), pe m br oliz u ma b/ Ke ytr u da® (a h u ma nize d I g G 4 a nti-P D -1 A b), 
Atez oliz u ma b/ Tece ntri q ® (a h u ma nize d I g G 1 a nti-P D -L 1  A b), d ur val u ma b/I mfizi®
(a h u ma nize I g G 1 a nti -P D - 1 A b), a n d a vel u ma b/ Ba ve nci o® (a f ully h u ma n I g G 1 a nti -P D -L 1 
A b) f or t he treat me nt of m ulti ple t u m or i n dicati o ns pr o vi de c o m pelli n g e vi de n ce t hat 
bl oc ka ge of t he P D -1 pat h wa y  is a vali date d i m m u n ot hera pe utic a p pr oac h ( O p di v o® U nite d 
States Pac ka ge I nsert ( U S PI ), 2 0 1 9; Tece ntri q® U S PI , 2 0 1 9; Ke ytr u da® U S PI , 2 0 1 9; 
I mfi nzi™U S PI , 2 0 1 8; Ba ve nci o® U S PI, 2 0 1 9).
2. 3. 1. P F -0 6 8 0 1 5 9 1, a n A nti -P D -1 A nti b o d y: Cli nic al E x perie nce i n St u d y B 8 0 1 1 0 0 1 
( N C T 0 2 5 7 3 2 5 9)
B 8 0 1 1 0 0 1 is a n o n g oi n g P hase 1, o pe n -la bel, m ulti-ce nter, m ulti ple-d ose, d ose escalati o n 
a n d e x pa nsi o n, safet y, P K, a n d P D st u d y of P F -0 6 8 0 1 5 9 1. T he pri mar y  p ur p ose of t his st u d y 
is t o e val uate safet y a n d earl y si g ns of efficac y . T his cli nical st u d y was di vi de d i nt o a d ose 
escalati o n ( Part 1) p hase a n d a d ose e x pa nsi o n ( Part 2) p hase. As of 1 0 Fe br uar y  2 0 2 1, 
e nr oll me nt has bee n c o m plete d i n t his st u d y  a n d 1 4 6 partici pa nts ha ve bee n d ose d o n t he 
st u d y ra n gin g fr o m 0. 5 m g/ k g I V u p t o 3 0 0 m g S C. Refere nce Secti o n 1 0. 9 f or Preli mi nar y 
Cli nical S u m mar y . M ore detaile d i nf or matio n a b o ut t he k n o w n a n d e x pecte d be nefits a n d 
ris ks a n d reas o na bly e x pecte d A Es of P F -0 6 8 0 1 5 9 1 ma y  be f o u n d i n t he res pecti ve I B, w hic h 
is t he si n gle refere nce safet y d oc u me nt ( S R S D).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 6
2. 4. O ver vie w of Be v aciz u m a b -Pfizer ( Zir a be v ™)
Be vaciz u ma b is a vasc ular e n d ot heli n gr o wt h fact or ( V E G F) i n hi bit or a n d a p pr o ve d f or 
treat me nt of metastatic c ol orectal ca ncer, i n c o m bi nati o n wit h i ntra ve n o us fl u or o uracil-base d 
c he m ot hera p y f or first- or sec o n d-li ne treat me nt a n d als o i n c o m bi nati o n wit h 
fl u or o p yri mi di ne-, iri n oteca n- or fl u or o p y ri mi di ne-o xali plati n base d c he m ot hera p y  f or 
sec o n d-li ne treat me nt i n partici pa nts w h o ha ve pr o gresse d o n a first-li ne be vaciz u ma b 
pr o d uct -c o ntai ni n g re gi me n. Cli nicall y si g nifica nt a d verse reacti o ns i ncl u de gastr oi ntesti nal 
perf orati o ns a n d fis t ulae, s ur ger y a n d w o u n d heali n g c o m plicati o ns, he m orr ha ge, arterial a n d 
ve n o us t hr o m b oe m b olic e ve nts, h y perte nsi o n, p osteri or re versi ble e nce p hal o pat h y s y n dr o me, 
re nal i nj ur y a n d pr otei n uria, i nf usi o n-relate d reacti o ns, o varia n fail ure, a n d c o n gesti ve heart 
fail ure ( Pfizer, U nite d States Pac ka ge I nsert ( U S PI), 2 0 1 9). T he bi osi milar versi o n of 
A vasti n ® will be use d i n t his st u d y , ma n ufact ure d b y Pfizer a n d hereafter referre d t o as 
be vaciz u ma b -Pfizer. Be vaciz u ma b -Pfizer is c o m merciall y a vaila ble a n d will be use d i n 
acc or da nce wit h its l ocal la bel. T he S R S D f or be vaciz u ma b- Pfizer is its c ore data s heet 
( C D S).
2. 5. Be nefit/ Ris k Assess me nt
T here c o nti n ues t o be si g nifica nt u n met me dical nee d f or m ore effecti ve t hera pies f or 
a d va nce d or metastatic gastr oi ntesti nal a de n ocarci n o mas t hat ha ve rela pse d or are refract or y  
t o c urre nt t hera pies. C urre ntl y a vaila ble t hera pies f or a d va nce d or metastatic c ol orectal a n d 
gastric a de n ocarci n o mas ha ve ver y  li mite d cli nical be nefit b ot h i n ter ms of res p o nse a n d 
d urati o n of res p o nse. A lt h o u g h t here is li mite d cli nical e x perie nce wit h P F-0 7 0 6 2 1 1 9, w hic h 
is a n a nti-G U C Y 2c/a nti -C D 3 -bis pecific bei n g de vel o pe d f or a d va nce d gastr oi ntesti nal 
mali g na ncies i ncl u di n g c ol orectal a n d gastric a de n ocarci n o mas, si g nifica nt t u m or re d ucti o n 
was o bser ve d i n precli nical p har mac ol o g y st u dies wit h P F- 0 7 0 6 2 1 1 9 i n a n u m ber of m o dels 
wit h c ol orectal a de n ocarci n o mas, i ncl u di n g t h ose t hat are es peciall y resista nt s uc h as t h ose 
wit h K R A S a n d B R A F p ositi vit y . A d diti o nall y, P F-0 7 0 6 2 1 1 9 has t he p ote ntial t o be use d i n 
t he setti n gs of eit her micr osatellite sta ble ( M S S) or hi g h micr osatellite i nsta bilit y hi g h 
( M SI-H) disease gastr oi ntesti nal a de n ocarci n o mas si nce G U C Y 2c is e x presse d acr oss b ot h 
s u bt ypes ( Bas hir et al, 2 0 1 9). 5
T he safet y pr ofile of P F -0 7 0 6 2 1 1 9 has bee n c haracterize d i n e x pl orat or y  a n d pi v otal 
t o xic ol o g y st u dies a n d is descri be d i n Secti o n 2. 2. 8 . T he pri mar y t o xicities ass ociate d wit h 
P F -0 7 0 6 2 1 1 9 i n n o n -h u ma n pri mates i ncl u de diarr hea a n d C R S at d oses c o nsi dere d t o n ot be 
t olera ble. H o we ver, t hese t o xicities were of li mite d fre q ue nc y a n d gra de a n d t heref ore 
c o nsi dere d n o n -a d verse at t olera ble d oses. C R S a n d diarr hea ha ve bee n o bser ve d i n t he 
cli nical st u d y. Cl ose me dical m o nit ori n g, i ncl u di n g i n patie nt o bser vati o n f or at least 4 8 h o urs 
f oll o wi n g t he i nitial P F-0 7 0 6 2 1 1 9 S C d ose a n d f or at least 8 h o urs f oll o wi n g t he sec o n d P F-
0 7 0 6 2 1 1 9 S C d ose i n t he c o h ort wit h o ut a pri mi n g d ose a n d at least 2 4 h o urs after t he first 
( pri mi n g) S C d ose a n d 2 4 h o urs after t he sec o n d (f ull) S C d ose i n t he c o h ort wit h a pri mi n g 
d ose, al o n g wit h safet y assess m e nts will occ ur t hr o u g h o ut t he st u d y. S u p p orti ve care 
meas ures as descri be d i n Secti o n 6. 6. 2 are a vaila ble t hat ma y be c o nsi dere d i n t he 
ma na ge me nt o f b ot h C R S a n d diarr hea ( Lee et al, 2 0 1 4; Lee et al, 2 0 1 9; Be ns o n et al, 
2 0 0 4). 2 4 ,2 5 ,7
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 7
At t his sta ge of de vel o p me nt, t he be nefit -ris k f or P F-0 7 0 6 2 1 1 9 is c o nsi dere d acce pta ble i n 
partici pa nts wi t h a d va nce d gastr oi ntesti nal a de n ocarci n o mas.
F or t his st u d y , t he st u d y i nter ve nti o n is P F-0 7 0 6 2 1 1 9. P F - 0 6 8 0 1 5 9 1 a n d be vaciz u ma b-Pfizer 
will be use d as c o m bi nati o n a ge nts wit h P F -0 7 0 6 2 1 1 9. M ore detaile d i nf or mati o n a b o ut t he 
k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y e x pecte d A Es of P F-0 7 0 6 2 1 1 9 a n d 
P F -0 6 8 0 1 5 9 1 ma y  be f o u n d i n t heir res pecti ve I Bs, w hic h are t heir S R S Ds f or t his st u d y. F or 
t he P E T i ma gi n g st u d y m ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d 
ris ks a n d reas o na bly e x pecte d A Es of t he P E T tracer bei n g use d ma y  be f o u n d i n t he 
I ma gi n A B I B w hic h is t he res pecti ve S R S D f or t his st u d y. Be vaciz u ma b -Pfizer is a p pr o ve d 
a n d will be c o m merciall y a vaila ble i n certai n re gi o ns a n d will be use d i n acc or da nce wit h its 
l ocal la bel. T he S R S D f or be vaciz u ma b-Pfizer is its C D S.
3. O B J E C TI V E S A N D E N D P O I N T S
D ose Esc al ati o n ( P art 1):
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y: 

T o assess safet y a n d t olera bilit y of i ncreasi n g d ose 
le vels of P F-0 7 0 6 2 1 1 9 wit h a n d wit h o ut pri mi n g d ose 
a d mi nistere d i n partici pa nts wit h a d va nce d 
gastr oi ntesti nal  t u m ors, i ncl u di n g c ol o n, gastric, a n d 
es o p ha geal a de n ocarci n o mas, f or w h o m n o sta n dar d 
t hera p y is a vaila ble i n or der t o esti mate t he Ma xi m u m 
T olerate d D ose ( M T D) a n d select t he Rec o m me n de d 
P hase 2 D ose ( R P 2 D) as a m o n ot hera p y i n Part 1 A 
a n d i n c o m bi nati o n t hera p y i n Part 1 B wit h select 
t u m or(s).

First c ycle D ose Li miti n g T o xicities ( D L Ts);

A d ve rse E ve nts as c haracterize d b y t y pe, fre q ue nc y, 
se verit y (as gra de d b y Nati o nal Ca ncer I nstit ute 
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts 
[N CI C T C A E ] versi o n 5) , ti mi n g, seri o us ness, a n d 
relati o ns hi p t o st u d y t hera p y;

La b orat or y a b n or malities as c har acterize d b y t y pe, 
fre q ue nc y, se verit y (as gra de d b y N CI C T C A E 
versi o n [ versi o n 5. 0]), a n d ti mi n g.
Sec o n d ar y: 
Sec o n d ar y: 

T o c haracterize t he si n gle a n d m ulti ple d ose P K of 
P F - 0 7 0 6 2 1 1 9;

T o e val uate t he i m m u n o ge nicit y of P F -0 7 0 6 2 1 1 9;

T o e val uate t he i m m u n o ge nicit y of P F- 0 6 8 0 1 5 9 1 a n d 
be vaciz u ma b -Pf izer gi ve n i n c o m bi nati o n wit h 
P F -0 7 0 6 2 1 1 9 ( Part 1 B);

T o e val uate i m m u ne cells i n arc hi val t u m or bi o psies 
a n d/ or pre a n d p ost treat me nt t u m or bi o psies (if 
a vaila ble);

T o e val uate preli mi nar y a nti- t u m or acti vit y.
P K para meters of P F - 0 7 0 6 2 1 1 9:

C y cle 1 a n d C ycle 4 P K para meters ma xi m u m 
c o nce ntrati o n ( C ma x), ti me t o ac hie ve Cma x ( Tma x ), 
area u n der t he c o nce ntrati o n vers us ti me c ur ve fr o m 
ti me zer o t o t he last q ua ntifia ble c o nce ntrati o n 
( A U Clast). If data per mits, ot her P K para meters will 
be deri ve d s uc h as a p pare nt cleara nce ( C L/ F), 
ter mi nal half-life (t1/ 2), a n d t he area u n der t he plas ma 
c o nce ntrati o n -ti me pr ofile fr o m ti me zer o 
e xtra p olate d t o i nfi nite ti me ( A U C i nf);

Pre d ose tr o u g h c o nce ntrati o ns after m ulti ple d oses of 
P F -0 7 0 6 2 1 1 9; 

I nci de nce a n d titers of A D A a n d NA b P F -0 7 0 6 2 1 1 9;

I nci de nce a n d titers of A D A a n d NA b a gai nst 
P F -0 6 8 0 1 5 9 1 a n d be vaciz u ma b -Pf izer gi ve n i n 
c o m bi nati o n wit h P F -0 7 0 6 2 1 1 9 ( Part 1 B); 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 8
O bjecti ves
E n d p oi nts

Assess me nt of le vels of i ntra- t u m or T cells (e g, C D 8 
I H C);

O bjecti ve res p o nse, as assesse d usi n g R E CI S T 
versi o n 1. 1.
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y:

T o e x pl ore preli mi nar y a nti- t u m or acti vit y b y sta n dar d 
a n d i m m u ne-relate d res p o nse criteria a n d ti me t o e ve nt 
e n d p oi nts;

T o e x pl ore t he relati o ns hi p bet wee n tar get e x pressi o n 
a n d bi o mar kers i n arc hi val t u m or bi o psies a n d/ or pre 
a n d p ost treat me nt t u m or bi o psies (if a vaila ble), w h ole 
bl o o d, a n d ser u m sa m ples i n or der t o el uci date 
mec ha nis m of acti o n a n d res p o nse t o t hera p y;

T o e x pl ore a d diti o nal bi o mar kers relate d t o cli nical 
res p o nse, i n or der t o el uci date t he mec ha nis m of 
acti o n of P F -0 7 0 6 2 1 1 9, pre dict res p o nse t o t hera p y, 
a n d t o u n dersta n d resista nce mec ha nis ms t hat ma y 
pre dict esca pe fr o m t hera p y;

T o e val uate T, B, a n d Nat ural Killer ( N K) s u bt y pes f or 
i m m u n o p he n ot y pi n g i n a d diti o n t o T cell pr oliferati o n, 
acti vati o n, a n d e x ha usti o n mar kers i n w h ole bl o o d; 

T o e x pl ore c yt o ki nes a n d c he m o ki nes as 
p har mac o d y na mic ( P D) mar kers i n pre a n d o n 
treat me nt ser u m sa m ples;

T o e x pl ore t he t u m or bi o mar ker carci n oe m br y o nic 
a nti ge n ( C E A) le vels;

T o e na ble e x pl orat or y researc h t hr o u g h c ollecti o n of 
ba n ke d bi os peci me ns, u nless pr o hi bite d b y l ocal 
re g ulati o ns or et hics c o m mittee decisi o n.

T o e val uate t he tr o u g h le vels of P F- 0 6 8 0 1 5 9 1 a n d 
be vaci z u ma b -Pf izer gi ve n i n c o m bi nati o n wit h 
P F -0 7 0 6 2 1 1 9 ( Part 1 B;

Pr o gressi o n free s ur vi val ( P F S) a n d d urati o n of 
res p o nse ( D O R) b y R E CI S T versi o n 1. 1;

O verall t u m or assess me nt b y t he I m m u ne Relate d 
Res p o nse Criteria i n S oli d T u m or (ir R E CI S T) 
(criteria a n d i m m un e -relate d pr o gressi o n free 
s ur vi val (ir P F S);

G U C Y 2c e x pressi o n le vels i n arc hi val a n d/ or pre a n d 
o n/ p ost treat me nt t u m or bi o psies;

I m m u n o p he n ot y pi n g of bl o o d I m m u ne cell s u bt y pes 
fre q ue nc y a n d acti vati o n;

I ntra-t u m or i m m u ne pat h wa y m o d ulati o n, ge ne 
e x pressi o n pr ofiles, D N A m utati o ns a n d i m m u ne cell 
bi o mar kers i n pre - a n d p ost - d ose t u m or bi o psies;

C y t o ki ne a n d c he m o ki ne P D mar kers i n pre a n d o n 
treat me nt ser u m sa m ples;

C E A le vels i n ser u m;

C ha n ges i n C D 8 P E T tracer u pta ke pre a n d p ost 
treat me nt f or p artici pa nts i n v ol ve d i n C D 8 P E T 
tracer s u bst u d y (Secti o n 1 0. 1 9. 3 )

P ote ntial res ults fr o m e x pl orat or y a nal ysis of ba n ke d 
bi os peci me ns (t hese res ults ma y or ma y n ot be 
ge nerate d i n t he c o nte xt of t he prese nt st u d y).

Tr o u g h le vels of P F - 0 6 8 0 1 5 9 1 a n d 
be vaciz u ma b -Pf izer
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 4 9
D ose E x p a nsi o n ( P art 2):
O bjecti ves
E n d p oi nts
Pri m ar y: 
Pri m ar y: 

T o c o nfir m safet y a n d t olera bilit y a n d e val uate 
preli mi nar y e vi de nce of a nti -t u m or acti vit y of 
P F - 0 7 0 6 2 1 1 9 at t he R P 2 D i n partici pa nts wit h 
a d va nce d c ol orectal a de n ocarci n o mas (as a 
m o n ot hera p y a n d i n c o m bi nati o n t hera p y).

A Es as c haracterize d b y t y pe, fre q ue nc y, se verit y (as 
gra de d b y Nati o nal Ca ncer I nstit ute C o m m o n 
Ter mi n ol o g y Criteria f or A d verse E ve nts ( N CI 
C T C A E versi o n [ versi o n 5. 0], ti mi n g, seri o us ness, a n d 
relati o ns hi p t o st u d y t hera p y;

La b orat or y a b n or malities as c haracterize d b y t y pe, 
fre q ue nc y, se verit y (as gra de d b y N CI C T C A E v 
5. 0]), a n d t i mi n g;

O R R as deter mi ne d b y t he R E CI S T versi o n 1. 1 
criteria.
Sec o n d ar y: 
Sec o n d ar y: 

T o e val uate t he P K of P F -0 7 0 6 2 1 1 9 at t he R P 2 D;

T o e val uate t he i m m u n o ge nicit y of P F -0 7 0 6 2 1 1 9;

T o e val uate t he i m m u n o ge nicit y of P F - 0 6 8 0 1 5 9 1 
a n d be vaciz u ma b -Pf izer gi ve n i n c o m bi nati o n wit h 
P F - 0 7 0 6 2 1 1 9;

T o e val uate i m m u ne P D effects of P F - 0 7 0 6 2 1 1 9 
bet wee n pre -treat me nt a n d p ost treat me nt t u m or 
bi o psies;

T o e val uate preli mi nar y a nti-t u m or acti vit y t hr o u g h 
ti me t o e ve nt e n d p oi nts.

P K c o nce ntrati o ns of P F -0 7 0 6 2 1 1 9; 

Pre d ose t r o u g h c o nce ntrati o ns after m ulti ple d oses of 
P F - 0 7 0 6 2 1 1 9;

I nci de nce a n d titers of A D A a n d NA b P F -0 7 0 6 2 1 1 9;

I nci de nce a n d titers of A D A a n d NA b a gai nst 
P F -0 6 8 0 1 5 9 1 a n d be vaciz u ma b -Pf izer gi ve n i n 
c o m bi nati o n wit h P F - 0 7 0 6 2 1 1 9;

Assess me nt of i ncrease d i ntra -tu m or T cells f oll o wi n g 
P F -0 7 0 6 2 1 1 9 treat me nt (e g, C D 8 I H C);

P F S a n d D O R b y R E CI S T versi o n 1. 1.
Terti ar y/ E x pl or at or y: 
Terti ar y/ E x pl or at or y:

T o d oc u me nt a n y a nti -t u m or acti vit y as assesse d b y 
i m m u ne relate d res p o nse criteria;

T o e x pl ore t he relati o ns hi p bet wee n tar get 
e x pressi o n a n d bi o mar kers i n arc hi val t u m or 
bi o psies a n d/ or pre - a n d p ost -treat me nt t u m or 
bi o psies, w h ole bl o o d, a n d ser u m sa m ples i n or der 
t o el uci date mec ha nis m of acti o n a n d res p o nse t o 
t hera p y;

T o e x pl ore a d di ti o nal bi o mar kers relate d t o cli nical 
res p o nse, i n or der t o el uci date t he mec ha nis m of 
acti o n of P F -0 7 0 6 2 1 1 9, pre dict res p o nse t o t hera p y, 
a n d t o u n dersta n d resista nce mec ha nis ms t hat ma y 
pre dict esca pe fr o m t hera p y;

T o e val uate T, B, a n d N K s u bt y pes f or 
im m u n o p he n ot y pi n g i n a d diti o n t o T cell 
pr oliferati o n, acti vati o n, a n d e x ha usti o n mar kers i n 
w h ole bl o o d; 

ir R E CI S T a n d ir P F S;

G U C Y 2c e x pressi o n le vels i n arc hi val a n d/ or pre - a n d 
o n/ p ost -treat me nt t u m or bi o psies;

I m m u n o p he n ot y pi n g of bl o o d I m m u ne cell s u bt y pes 
fre q ue nc y a n d acti vati o n;  

I ntra-t u m or i m m u ne pat h wa y m o d ulati o n, ge ne 
e x pressi o n pr ofiles, D N A m utati o ns a n d i m m u ne cell 
bi o mar kers i n pre - a n d p ost - d ose t u m or bi o psies;

C y t o ki ne a n d c he m o ki ne P D mar kers i n pre- a n d 
o n -treat me nt ser u m sa m ples;

C E A le vels i n ser u m;
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 0
O bjecti ves
E n d p oi nts

T o e x pl ore c yt o ki ne a n d c he m o ki ne P D mar kers i n 
pre a n d o n treat me nt ser u m sa m ples;

T o e x pl ore t he t u m or bi o mar ker C E A le vels;

T o e na ble e x pl orat or y r esearc h t hr o u g h c ollecti o n 
of ba n ke d bi os peci me ns, u nless pr o hi bite d b y l ocal 
re g ulati o ns or et hics c o m mittee decisi o n. 

T o e val uate t he tr o u g h le vels of P F -0 6 8 0 1 5 9 1 a n d 
be vaciz u ma b -Pf izer gi ve n i n c o m bi nati o n wit h 
P F -0 7 0 6 2 1 1 9;

C ha n ges i n C D 8 P E T tracer u pta ke pre a n d p ost 
treat me nt f or partici pa nts i n v ol ve d i n C D 8 P E T tracer 
s u bst u d y (Secti o n 1 0. 1 9. 3 )

P ote ntial res ults fr o m e x pl orat or y a nal ysis of ba n ke d 
bi os peci me ns (t hese res ults ma y or ma y n ot be 
ge nerate d i n t he c o nte xt of t he prese nt st u d y).

Tr o u g h le vels of P F -0 6 8 0 1 5 9 1 a n d be vaciz u ma b -
Pf izer
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a P hase 1, o pe n -la bel, m ulti-ce nter, m ulti ple-d ose, safet y, P K a n d P D st u d y  of 
P F -0 7 0 6 2 1 1 9 i n partici pa nts wit h selecte d a d va nce d or m etastatic gastr oi ntesti nal t u m ors. 
T his st u d y  c o ntai ns 2 parts: Part 1 d ose escalati o n of P F -0 7 0 6 2 1 1 9, wit h a n d wit h o ut a 
pri mi n g d ose, as a m o n ot hera p y ( Part 1 A) a n d i n c o m bi nati o n wit h a n a nti -P D - 1 or 
a nti-V E G F a ge nt ( Part 1 B) a n d Part 2 d ose e x pa nsi o n ( Fi g ure 3 ). T he P F-0 7 0 6 2 1 1 9 
a d mi nistrati o n re gi me n f or Parts 1 A, 1 B, a n d 2 ma y  be g ui de d b y S C d ose pri mi n g escalati o n 
c o h orts a n d all a vaila ble data will be use d t o ma ke a decisi o n o n f ut ure d ose re gi me ns.
Fi g ure 3.
C 3 8 6 1 0 0 1 St u d y Sc he m a
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 1
As t he R P 2 D/ M T D of P F - 0 7 0 6 2 1 1 9 is a p pr oac he d or has bee n deter mi ne d i n Parts 1 A a n d 
1 B, a n o pti o nal s u bset of partici pa nts ma y  be e nr olle d (a p pr o xi matel y 6 t o 1 2 partici pa nts) 
wit h t he re q uire me nt of pr o vi di n g ma n dat or y  paire d de n o v o pre-treat me nt a n d o n-treat me nt 
bi o ps y  sa m ples t o e na ble e val uati o n of tiss ue bi o mar ker P D acti vit y. T he o pti o n t o e nr oll t he 
s u bset of partici pa nts f or ma n dat or y paire d t u m or sa m ples will be base d o n e val uati o n of 
e mer gi n g cli nical data i ncl u di n g a vaila ble safet y/ t olera bilit y, P K, a n d P D fi n di n gs b y t he 
s p o ns or.
I n t he o verall FI P st u d y, a p pr o xi matel y 1 3 0 partici pa nts are e x pecte d t o be e nr olle d. Part 1 is 
esti mate d t o e nr oll a p pr o xi m atel y 7 0 partici pa nts ( 3 5 partici pa nts i n Part 1 A a n d 
3 5 partici pa nts i n Part 1 B). I n Part 2, a p pr o xi matel y 2 0 partici pa nts eac h will be e nr olle d i n 
t he m o n ot hera py a n d b ot h c o m bi nati o n c o h orts f or a t otal of a p pr o xi matel y 6 0 partici pa nts. If 
1 5 partici pa n ts ha ve bee n e nr olle d i n a c o h ort a n d < 5 paire d pre- a n d o n-treat me nt bi o psies 
ha ve bee n c ollecte d, c ollecti o ns ma y  be ma de ma n dat or y f or t he re mai ni n g partici pa nts 
a n d/ or t he c o h ort ma y be e x pa n de d b y u p t o 5 partici pa nts t o o btai n s ufficie nt n u m bers of 
p aire d pre- a n d o n -treat me nt bi o psies.
A s u bset of partici pa nts e nr olle d i n P art 1 a n d P art 2 will als o be eli gi ble f or e nr oll me nt i n 
t he P E T i ma gi n g s u bst u d y wit h t he C D 8 T-cell s pecific 8 9Zr -defer o xa mi ne ( Df )-I AB 2 2 M 2 C 
P E T tracer ( C D 8 P E T Tracer). T he C D 8 P E T tracer s u bst u d y is i ncl u de d t o facilitate
meas ure me nt of C D 8 T- cell distri b uti o n acr oss b ot h t u m or a n d n or mal tiss ues bef ore a n d 
after t hera p y wit h P F - 0 7 0 6 2 1 1 9. T he C D 8 P E T tracer s u bst u d y will be o pe ne d i nitiall y at a 
s u bset of U S sites t hat ha ve bee n q ualifie d f or use wit h 8 9Zr -Df -I AB 2 2 M 2 C .  A d diti o nal 
details are pr o vi de d i n Secti o n 1 0. 1 9 .
Partici pa nts i n c o h orts wit h o ut a pri mi n g d ose will be o bser ve d i n patie nt f or at least 4 8 h o urs 
after t he first S C d ose o n C 1 D 1 a n d f or at least 8 h o urs after t he sec o n d S C d ose o n C 1 D 1 5 
a n d f or at least 1 h o ur p ost d ose f or all s u bse q ue nt visits. Partici p a nts i n c o h orts wit h a 
pri mi n g d ose will be o bser ve d i n patie nt f or at least 2 4 h o urs after t he first ( pri mi n g) S C d ose 
o n C 1 D 1 a n d 2 4 h o urs after t he sec o n d (f ull) S C d ose o n C 1 D 1 5, a n d 1 h o ur p ost d ose f or all 
s u bse q ue nt visits. Partici pa nts s h o ul d be o bser ve d f or at least 1 h o ur p ost d ose f or all visits 
starti n g wit h C2 D 1 1 i n b ot h c o h orts , u ntil t he i n vesti gat or has c o nfir me d t he partici pa nt has 
n ot e x hi bite d si g ns of c y t o ki ne reacti o n. 
I n Part 2, all partici pa nts will be o bser ve d i n patie nt f or at least 2 4 h o urs after t he first S C 
d ose, a n d if a pri mi n g d ose a p pr oac h is use d, partici pa nts will be o bser ve d f or  u p t o 2 4 h o urs 
after t he sec o n d (f ull) S C d ose o n C 1 D 1 5. Partici pa nts ma y  o nly be release d after t he 
i n vesti gat or has c o nfir me d t he partici pa nt has not e x hi bite d si g ns of C R S.
T a ble 8 .  
Mi ni m u m I n p atie nt O bser v ati o n St a ys
P art
C o h ort
C 1 D 1
C 1 D 1 5
All Ot her Visits
1
Wit h o ut Pri mi n g
4 8 h o urs
8 h o urs
1 h o ur
Wit h Pri mi n g
2 4 h o urs
2 4 h o urs
1 h o ur
2
2 4 h o urs
2 4 h o urs if pri mi n g 
is use d
At i n vesti gat or’s 
discreti o n
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 2
All i n patie nt o bser vati o n sta y s ma y be e xte n de d at t he discreti o n of t he i n vesti gat or a n d/ or 
e v ol vi n g cli nical data. 
Treat me nt wit h st u d y i nter ve nti o n will c o nti n ue u ntil eit her disease pr o gressi o n, partici pa nt 
ref usal, or u nacce pta ble t o xicit y  occ urs, w hic he ver is earliest, u nless t he i n vesti gat or a n d 
me dical m o nit or a gree t o treat me nt be y o n d disease pr o gressi o n base d o n i n di vi d ual 
be nefit/ris k assess me nts.
T he bi o mar ker st u dies will be use d t o hel p u n dersta n d t he i n vi v o mec ha nis m of acti o n of t he 
a ge nt(s) u n der st u d y, as well as p ote ntial mec ha nis ms of resista nce. T he st u dies ma y hel p i n 
t he f ut ure de vel o p me nt of P F-0 7 0 6 2 1 1 9 as a si n gle a ge nt, or i n c o m bi nati o n wit h ot her 
c o m p o u n ds, a n d ma y pr o vi de i nf or mati o n o n t u m or s u b-t ypes t hat ma y  res p o n d t o t he st u d y 
i nter ve nti o n.
4. 1. 1. P art 1 A
Part 1 A will esti mate t he M T D a n d/ or R P 2 D of P F -0 7 0 6 2 1 1 9 as a m o n ot hera p y  wit h a n d 
wit h o ut a pri mi n g d ose. I n Part 1 A, se q ue ntial c o h orts of partici pa nts wit h a d va nce d 
gastr oi ntesti nal t u m ors, i ncl u di n g c ol orectal, gastric a n d es o p ha geal a de n ocarci n o mas, w h o 
are n ot ca n di dates f or re gi me ns k n o w n t o pr o vi de cli nical be nefit, will recei ve escalati n g 
d oses of P F - 07 0 6 2 1 1 9 a d mi nistere d as a n S C i njecti o n as g ui de d b y  t he Ba yesia n L o gistic 
Re gressi o n M o del ( B L R M). 
4. 1. 1. 1. P F -0 7 0 6 2 1 1 9 Tre at me nt Wit h o ut a Pri mi n g D ose
Wit h t he deter mi nati o n t hat a d ose le vel is safe f oll o wi n g a D L T o bser vati o n peri o d of 
2 8 da y s f or t he c o h ort wit h o ut a pri mi n g d ose a n d base d o n t he disc ussi o n b y  t he safety 
re vie w tea m, d ose escalati o n will pr ocee d t o t he ne xt d ose le vel. T he S C r o ute has t he 
p ote ntial t o re d uce t he C ma x w hic h is belie ve d t o be ass ociate d wit h C R S a n d i nfla m mat or y  
res p o nses, a co m m o n A E f or bis pecific a nti b o dies. T he starti n g S C d ose is 4 5 µ g Q 2 W. 
Ma xi m u m d ose i ncreases fr o m t he pre vi o us d ose le vels will be u p t o 2 0 0 %, w hic h is a 
c o nsiste nt a p pr oac h wit h bi ol o gic c o m p o u n ds i ncl u di n g a n a nti- C D 3 bis pecific ( Sa ber et al, 
2 0 1 7), 3 7 b ut will be a dj uste d t o n o m ore t ha n 1 0 0 % f oll o wi n g t he o bser vati o n of a D L T or if 
t here are t w o Gra de 2 or hi g her cli nically si g nifica nt treat me nt re late d A Es. C o h ort size will 
be a p pr o xi matel y  3 partici pa nts. T he first c o h ort of 4 5 µ g Q 2 W i n Part 1 A will ha ve at least 
1 D L T- e val ua ble partici pa nt. All ot her c o h orts i n Part 1 A will ha ve at least 2 D L T e val ua ble 
partici pa nts. Part 1 A is esti mate d t o e nr o ll a p pr o xi matel y 3 5 partici pa nts, b ut t he act ual 
n u m ber of partici pa nts e nr olle d will de pe n d o n t he t olera bilit y  of P F-0 7 0 6 2 1 1 9 a n d t he 
n u m ber of d ose le vels re q uire d t o i de ntif y  t he M T D, b ut will i ncl u de at least 6 partici pa nts 
treate d at t he rec o m me n de d R P 2 D/ M T D (see Secti o n 9. 4. 1 ).
4. 1. 1. 2. P F -0 7 0 6 2 1 1 9 Tre at me nt Wit h a Pri mi n g D ose
A n a d diti o nal d ose escalati o n c o h ort i n Part 1 A, w hic h i nc or p orates a l o wer pri mi n g d ose o n 
C 1 D 1 f oll o we d b y  a f ull d ose o n C 1 D 1 5 f or all d ose le vels, will be i nitiate d. A p pr o xi matel y 
2 0 partici pa nts will be e nr olle d i n t he Part 1 A c o h ort wit h a pri mi n g d o se, wit h 
a p pr o xi matel y 3 partici pa nts ( mi ni m u m of 2 D L T e val ua ble partici pa nts) per d ose le vel; 
a d diti o nal partici pa nts will be treate d at t he R P 2 D/ M T D f or a t otal of 6 t o 1 2 partici pa nts at 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 3
t hat d ose le vel. T he act ual n u m ber of partici pa nts e nr olle d will de pe n d o n t he t olera bilit y  of 
t he pri mi n g strate g y f or P F-0 7 0 6 2 1 1 9 a n d t he n u m ber of f ull d ose le vels re q uire d t o i de ntif y  
t he M T D (see Secti o n 9. 4. 1 ). 
T w o wee ks after t he pri mi n g d ose, partici pa nts will recei ve escalati n g f ull d oses of 
P F -0 7 0 6 2 1 1 9 a d mi nistere d Q 2 W as a n S C i njecti o n as g ui de d b y  t he B L R M. Wit h t he 
deter mi nati o n t hat a d ose le vel is safe f oll o wi n g a D L T o bser vati o n peri o d of 4 2 d a y s 
(i ncl u di n g b ot h pri mi n g a n d 2 f ull d oses) a n d base d o n t he disc ussi o n b y t he safety re vie w 
tea m, d ose escalati o n will pr ocee d t o t he ne xt d ose le vel. T he pri mi n g d ose will be 4 0 0 µ g. 
T he starti n g f ull d ose will be 8 0 0 µ g, w hi c h re prese nts t he M T D of t he Part 1 A c o h ort 
wit h o ut a pri mi n g d ose. T he i nitial P F - 0 7 0 6 2 1 1 9 re gi me n wit h a pri mi n g d ose satisfies 
E W O C criteria (see Secti o n 9. 4. 1 a n d A p pe n di x 1 0 , Secti o n 1 0. 1 0 ). T he ma xi m u m all o wa ble 
i ncrease i n t he f ull d ose, t o be gi ve n after t he pri mi n g d ose, will be 1 0 0 %. T he pri mi n g d ose 
ma y  be m o difie d base d o n e mer gi n g cli nical data t o a ma xi m u m of t he hi ghest d ose 
pre vi o usl y  deter mi ne d t o be safe. A n alter nate pri mi n g sc he d ule (e g, usi n g a ste p-u p d osi n g 
strate g y, wit h serially i ncreasi n g d oses t o reac h t he f ull d ose le vel), ma y be e x pl ore d if 
e v ol vi n g cli nical data s u p p ort t he nee d a n d t he D L T o bser vati o n peri o d will be a dj uste d 
acc or di n gl y (e g, t o i ncl u de t he a d mi nistrati o ns of 2 f ull d oses). If ste p-u p d osi n g is 
i n vesti gate d, partici pa nts will recei ve f ull d oses of P F - 0 7 0 6 2 1 1 9 2 wee ks after t he m ost 
rece nt pri mi n g d ose.
4. 1. 2. P art 1 B ( C o m bi n ati o n C o h orts)
U p o n deter mi ni n g t he si n gle -a ge nt P F -0 7 0 6 2 1 1 9 R P 2 D/ M T D, Part 1 B will be i nitiate d t o 
e x pl ore t he safet y, t olera bilit y , a n d preli mi nar y a nti-t u m or acti vit y of P F-0 7 0 6 2 1 1 9 i n 
c o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 (a nti -P D -1) a n d be vaciz u ma b -Pfizer (a nti -V E G F) i n 
partici p a nts wit h c ol orectal, gastric a n d es o p ha geal a de n ocarci n o mas. 
T he D L T peri o d will be 2 8 da y s. B L R M will be use d t o g ui de t he d ose 
escalati o n/ de -escalati o n pr ocess f or eac h c o m bi nati o n ( P F -0 7 0 6 2 1 1 9/ P F -0 6 8 0 1 5 9 1 a n d 
P F -0 7 0 6 2 1 1 9/ be vaciz u ma b -Pfizer) se paratel y. T he deter mi nati o n of safet y f or a gi ve n d ose 
le vel f or eac h c o m bi nati o n will be base d o n t he disc ussi o n b y t he safety re vie w tea m.
I n eac h c o m bi nati o n treat me nt, t here ma y be c o h orts wit h o ut a P F-0 7 0 6 2 1 1 9 pri mi n g d ose 
a n d  c o h orts wit h a P F -0 7 0 6 2 1 1 9 pri m i n g d ose; t he decisi o n t o use a pri mi n g d ose ( o n C 1 D 1 
f oll o we d by a f ull d ose o n C 1 D 1 5) will be ma de f oll o wi n g a re vie w of all a vaila ble cli nical 
data fr o m Part 1 A a n d i n c o ns ultati o n wit h t he St u d y C 3 8 6 1 0 0 1 Safet y Re vie w Tea m. I n t he 
e ve nt t hat t he P F- 0 7 06 2 1 1 9 d ose pri mi n g strate g y  is e m pl o ye d wit h eit her c o m bi nati o n 
t hera py, t he D L T peri o d will be i ncrease d t o 4 2 da y s t o e ns ure a f ull 2 8 da y c ycle f oll o wi n g 
t he i nitiati o n of t he f ull d ose. A d diti o nall y , a n alter nati ve P F- 0 7 0 6 2 1 1 9 d osi n g re gi me n (e g, 
Q 4 W) or a sta g gere d d osi n g a p pr oac h (e g, P F -0 7 0 6 2 1 1 9 t o be i nitiate d al o ne o n C 1 D 1 
f oll o we d by t he c o m bi nati o n t hera p y 1 or 2 wee ks later) ma y be i nitiate d as g ui de d b y t he 
cli nical data. T he starti n g d ose of ne w re gi me n will satisf y  E W O C criteria.
F or t he P F - 0 7 0 6 2 1 1 9/P F - 0 6 8 0 1 5 9 1 c o m bi nati o n, t he starti n g first d ose of P F-0 7 0 6 2 1 1 9 i n 
c o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 will be o ne d ose le vel l o wer t ha n t he P F -0 7 0 6 2 1 1 9 
m o n ot hera p y M T D t o acc o u nt f or a n y p ote ntial i ncrease i n C R S t hat mi g ht be ass ociate d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 4
wit h t he P F - 0 7 0 62 1 1 9/ P F -0 6 8 0 1 5 9 1 c o m bi nati o n. If t he P F -0 7 0 6 2 1 1 9 R P 2 D fr o m Part 1 A is 
l o wer t ha n t he M T D, t he R P 2 D will be use d i n c o m bi nati o n wit h P F-0 6 8 0 1 5 9 1. Ma xi m u m 
i ncreases of P F-0 7 0 6 2 1 1 9 fr o m t he pre vi o us le vel will be 1 0 0 %. H o we ver, P F -0 7 0 6 2 1 1 9 i n 
c o m bi nati o n will n ot be d ose -escalate d be yo n d t he c orres p o n di n g si n gle -a ge nt M T D/ R P 2 D 
as deter mi ne d wit h or wit h o ut pri mi n g f or P F -0 7 0 6 2 1 1 9 i n Part 1 A. T he d ose of 
P F -0 6 8 0 1 5 9 1 will be 3 0 0 m g Q 4 W S C ( Ta ble 1 0 ). St u d y partici pa nts will be e val uate d f or 
safety a n d t olera bilit y of t he c o m bi nati o n a n d t he P F -0 7 0 6 2 1 1 9 d ose use d i n t he ne xt c o h ort 
ma y  re mai n t he sa me, escalate d, or de-escalate d as g ui de d b y  e mer gi n g cli nical data a n d t he 
B L R M desi g n (see Secti o n 4. 3. 6 ). 
F or t he P F - 0 7 0 6 2 1 1 9/be vaciz u ma b - Pfizer c o m bi nati o n, t he starti n g d ose of P F- 0 7 0 6 2 1 1 9 
will be t he M T D or t he R P 2 D deter mi ne d i n Part 1 A wit h or wit h o ut pri mi n g. St u d y  
partici pa nts will be e val uate d f or safet y a n d t olera bilit y  of t he c o m bi nati o n a n d t he 
P F -0 7 0 6 2 1 1 9 d ose use d i n t he ne xt c o h ort ma y  re mai n t he sa me or de-escalate d as g ui de d b y 
e mer gi n g cli nical data a n d B L R M ( See Secti o n 4. 3. 6 ). H o we ver, P F-0 7 0 6 2 1 1 9 i n 
co m bi nati o n will n ot be d ose -escalate d be yo n d t he c orres p o n di n g si n gle -a ge nt M T D/ R P 2 D 
as deter mi ne d wit h or wit h o ut pri mi n g f or P F -0 7 0 6 2 1 1 9 i n Part 1 A. T he d ose of 
be vaciz u ma b -Pfizer will be 5 m g/ k g Q 2 W I V i nf usi o n ( Ta ble 1 0 ). 
T he c o h ort size at eac h d ose le vel of Part 1 B f or t he P F- 0 7 0 6 2 1 1 9/ P F -0 6 8 0 1 5 9 1 a n d 
P F -0 7 0 6 2 1 1 9/ be vaciz u ma b -Pfizer c o m bi nati o n will eac h be a p pr o xi matel y  3 partici pa nts; all 
c o h orts in Part 1 B will eac h ha ve at least 3 D L T e val ua ble partici pa nts. Part 1 B is esti mate d 
t o e nr oll a p pr o xi matel y 3 5 partici pa nts (a p pr o xi matel y 1 5 t o 2 0 partici pa nts f or eac h 
c o m bi nati o n), b ut t he act ual n u m ber of partici pa nts e nr olle d will de pe n d o n t he t oler a bilit y of 
P F -0 7 0 6 2 1 1 9 i n c o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 a n d wit h be vaciz u ma b -Pfizer a n d t he 
n u m ber of d ose le vels re q uire d t o i de ntif y  t he c orres p o n di n g P F-0 7 0 6 2 1 1 9 M T Ds i n t he 
c o m bi nati o n setti n g wit h or wit h o ut d ose pri mi n g, b ut will i ncl u de at least 6 pa rtici pa nts 
treate d at t he c orres p o n di n g rec o m me n de d R P 2 D/ M T Ds (see Secti o n 9. 4. 1 ). 
Alter nate pri mi n g strate gies (e. g. ste p u p pri mi n g strate g y  or pr o p hyl actic treat me nt) ma y be 
e x pl ore d if e v ol vi n g cli nical data s u p p orts t he nee d i n Part 1 B d ose pri mi n g. 
4. 1. 3. P art 2
I n Part 2, t he d ose e x pa nsi o n p hase will e val uate t he R P 2 D (as deter mi ne d eit her wit h or 
wit h o ut a pri mi n g d ose) of P F -0 7 0 6 2 1 1 9 as m o n ot hera p y  a n d wit h a c o m bi nati o n a ge nt (a nti-
P D -1 [ P F - 0 6 8 0 1 5 9 1] a n d a nti- V E G F [ be vaciz u ma b-Pfizer]) i n partici pa nts wit h c ol orect al 
a de n ocarci n o ma. A p pr o xi matel y  6 0 partici pa nts will be e nr olle d; 2 0 partici pa nts i n eac h 
m o n ot hera p y a n d c o m bi nati o n c o h orts. . Res p o nses i n t hese i nitial d ose e x pa nsi o n ar ms ma y  
lea d t o f urt her e val uati o n of P F-0 7 0 6 2 1 1 9 i n a d diti o nal t u m or i n dicati o ns a n d c o m bi nati o n 
t hera pies.
I n Part 2, de n o v o pre-treat me nt bi o psies will be re q uire d fr o m all partici pa nts, u nless n ot 
me dicall y  feasi ble, i n or der t o esta blis h relati o ns hi p bet wee n tar get e x pressi o n a n d efficac y 
o bser vati o ns. If a de n o v o pre- treat me nt bi ops y  is n ot me dicall y feasi ble, t he s p o ns or s h o ul d 
be c o ntacte d f or a p pr o val bef ore i nitiati n g scree ni n g acti vities. F or a s u bset of partici pa nts i n 
all c o h orts (a p pr o xi matel y 1 0 partici pa nts), ma n dat or y o n -treat me nt bi o psy sa m ples will als o 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 5
be c ollecte d i n or der t o c o nfir m t he mec ha nis m of acti o n a n d e val uate p ote ntial resista nce 
mec ha nis m d uri n g treat me nt. F or all ot her partici pa nts, o n-treat me nt bi o psies are o pti o nal b ut 
e nc o ura ge d.
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
I n t his cli nical st u dy, P F - 0 7 0 6 2 1 1 9 wit h a n d wit h o ut a pri mi n g d ose will be e val uate d f or t he 
treat me nt of a d ult partici pa nts wit h t u m or t ypes k n o w n t o e x press G U C Y 2c, s uc h as 
a d va nce d c ol orectal, gastric, a n d es o p ha geal a de n ocarci n o mas, f or w hic h n o sta n dar d t hera p y 
is a vaila ble ( Part 1). I n t he d ose e x pa nsi o n p hase ( Part 2), P F-0 7 0 6 2 1 1 9 wit h a n d wit h o ut a 
pri mi n g d ose will be e val uate d i n se parate d ose e x pa nsi o n ar ms as m o n ot hera p y  a n d i n 
c o m bi nati o n wit h a n ot her a ge nt (e g, i m m u ne c hec k p oi nt i n hi bit or, a nti -V E G F) i n a d va nce d 
C R C a n d t he n p ossi bl y  be e val uate d i n ot her gastr oi ntesti nal a de n ocarci n o mas, c ol orectal 
ca ncer s u bt y pes, or c o m bi nati o n o pti o ns, as i n dicate d. Ke y sta n dar d assess me nts i n t he st u d y 
will i ncl u de safet y/ t olera bilit y, P K, P D a n d preli mi nar y a nti-t u m or acti vity e n d p oi nts.
As part of t he P D e val uati o n, t he o bjecti ve of t he bi o mar ker assess me nts is t o pr o vi de i nsi g ht 
i nt o t he p har mac ol o gical effects of P F-0 7 0 6 2 1 1 9 al o ne a n d p ote ntiall y i n c o m bi nati o n wit h 
a nti-P D -1 ( P F -0 6 8 0 1 5 9 1) a n d i n c o m bi nati o n wit h a nti - V E G F ( be vaciz u ma b-Pfizer) b y 
c haracterizi n g t he cell ular a n d m olec ular pr ofile of t he partici pa nt pri or t o treat me nt, d uri n g 
treat me nt, a n d u p o n pr o gressi o n. T he bi o mar ker assess me nts, i ncl u di n g t he P E T i ma gi n g 
s u bst u d y, m a y  c o ntri b ute t o c o nfir mi n g tar get e n ga ge me nt, T cell acti vati o n, deter mi ni n g 
p har mac o d y n a mic effects of P F -0 7 0 6 2 1 1 9 al o ne a n d p ote ntiall y  i n c o m bi nati o n wit h ot her 
a ge nts, i de ntif yi n g t h ose partici pa nts w h o are m ost li kel y t o be nefit fr o m treat me nt, a n d 
i de ntif y p ote ntial resista nce mec ha nis ms t o P F- 0 7 0 6 2 11 9 al o ne a n d i n c o m bi nati o n wit h 
ot her a ge nts. T he c ollecti o n of arc hi val a n d/ or de n o v o pre- treat me nt a n d o n-treat me nt 
bi o psies will be use d t o e val uate t he ass ociati o n bet wee n tar get e x pressi o n a n d res p o nse 
para meters t o P F- 0 7 0 6 2 1 1 9 as descri be d i n t he Sc he d ule of Acti vities ) a n d t he 
St u d y / La b orat or y Ma n ual.
Ba n ke d bi os peci me ns will be c ollecte d f or e x pl orat or y / p har mac o ge n o mic/ ge n o mic/ 
bi o mar ker a nal ys es a n d retai ne d i n t he Bi os peci me n Ba n ki n g S ys te m ( B B S), w hic h ma kes it 
p ossi ble t o better u n dersta n d t he mec ha nis m of acti o n of t he st u d y  i nter ve nti o n t o see k 
e x pla nati o ns f or differe nces i n, f or e xa m ple, e x p os ure, t olera bilit y , safety, a n d/ or efficac y n ot 
a ntici pate d pri or t o t he be gi n ni n g of t he st u d y.
4. 3. J ustific ati o n f or D ose
4. 3. 1. St arti n g D ose f or M o n ot her a p y D ose Esc al ati o n Wit h o ut a Pri mi n g D ose 
( P art 1 A)
T he i nitial cli nical starti n g d ose f or P F -0 7 0 6 2 1 1 9 f or t his first-i n-partici pa nt ( FI P) st u d y is 
4 5 µ g a d mi nistere d as a S C i njecti o n o nce e ver y  2 wee ks ( Q 2 W). T he selecti o n of t he 
starti n g d ose f or t his st u d y was base d o n t he mi ni m u m a ntici pate d bi ol o gical effect le vel
( M A B E L) i n acc or da nce wit h t he Inter nati o nal C o nfere nce o n Har m o nizati o n (I C H) S 9 
G ui da nce, gi ve n t hat P F- 0 7 0 6 2 1 1 9 is a bis pecific T cell -e n ga gi ng a ge nt wit h i m m u ne 
a g o nistic pr o perties. T he 4 5 µ g Q 2 W S C starti n g d ose is pre dicte d t o res ult i n mi ni mal 
bi ol o gical effect c o nsi deri n g a) i n vitr o c y t o ki ne release a n d c yt ot o xicit y e x peri me nts, b) 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 6
rece pt or occ u pa nc y calc ulate d base d o n i n vitr o bi n di n g affi nities, a n d c) m o use P K/ P D 
st u dies.
T he i n vitr o bi ol o gical acti vities f or P F -0 7 0 6 2 1 1 9 were deter mi ne d via c y t o ki ne release a n d 
c yt ot o xicit y e x peri me nts a n d t he m ost se nsiti ve P F-0 7 0 6 2 1 1 9 c o nce ntrati o n t o ac hie ve 
5 0 % ma xi mal effect ( E C 5 0) acr oss all i n vitr o assa y s was esti mate d as 1 3. 6 n g/ m L. Wit h 
4 5 μ g Q 2 W as a starti n g d ose, t he pre dicte d P F- 0 7 0 6 2 1 1 9 C ma x at stea d y-state ass u mi n g 
5 0 % bi oa vaila bilit y  fr o m t he S C r o ute is 8. 9 n g/ m L, w hic h is ~ 3 4 % l o wer t ha n t he E C 5 0 of 
t he m ost se nsiti ve i n vitr o assa y.
T he rece pt or occ u pa nc y  ( R O) calc ulate d base d o n i n vitr o bi n di n g affi nities at a starti n g d ose 
of 4 5 μ g Q 2 W S C was ≤0. 3 % f or b ot h G U C Y 2c a n d C D 3.
T he pre dicte d tr o u g h c o nce ntrati o n ( C tr o u g h) after f o ur d oses ac hie ve d wit h 4 5 µ g Q 2 W 
starti n g d ose is 4. 5 n g/ m L w hic h is less t ha n t he pre dicte d cli nical efficaci o us c o nce ntrati o n 
( Ceff) esti mate d fr o m m o use P K/ P D st u dies.
Fi nall y , P F-0 7 0 6 2 1 1 9 e x p os ure at t he rec o m me n de d starti n g d ose is e x pecte d t o be l o wer 
(e g, 2 1-f ol d l o wer Cma x a n d 2 4-f ol d l o wer A U C1 6 8) c o m pare d t o t he H N S T D deter mi ne d i n 
t he G LP o ne -m o nt h t o xic ol o g y  st u d y ( 3 µ g/ k g S C).
T heref ore, as state d a b o ve, t he rec o m me n de d M A B E L starti n g d ose of 4 5 µ g Q 2 W via t he 
S C r o ute is e x pecte d t o res ult i n mi ni mal bi ol o gical effect a n d t o pr o vi de a n a de q uate safety 
mar gi n . If t he 4 5 µ g  Q 2 W d ose is  n ot t olerate d, t he n a l o wer d ose of 3 0 µ g  Q 2 W via S C 
r o ute will be e val uate d.
4. 3. 2. St arti n g D ose f or M o n ot her a p y D ose Esc al ati o n Wit h a Pri mi n g D ose ( P art 1 A)
A vaila ble data fr o m partici pa nts e nr olle d i n Part 1 A wit h o ut pri mi n g s h o ws t hat c y t o ki ne 
pr o d ucti o n a n d cli nical C R S occ ur pri maril y wit h t he i nitial d ose of P F -0 7 0 6 2 1 1 9,  
s u p p orti n g t he hy p ot hesis t hat i n d ucti o n of i m m u ne acti vati o n wit h a pri mi n g d ose atte n uates 
s u bse q ue nt occ urre nce of C R S. T he use of a pri mi ng a p pr oac h t o miti gate c yt o ki ne -me diate d 
A Es is als o s u p p orte d b y  data fr o m cli nical st u dies of t he bis pecific T-cell e n ga ger, 
bli nat u m o ma b, w hic h ha ve de m o nstrate d t hat use of a pri mi n g d ose (ie, usi n g a l o wer first 
d ose) ca n be effecti ve i n da m pe ni n g c y to ki ne release -me diate d A Es f oll o wi n g a d mi nistrati o n 
of s u bse q ue nt hi g her mai nte na nce d oses ( T o p p et al, 2 0 1 4a; T o p p et al, 2 0 1 4 b). 
T he first d ose le vel f or P F -0 7 0 6 2 1 1 9 i n t he Part 1 A c o h ort wit h a pri mi n g d ose will be a 
starti n g pri mi n g d ose of 4 0 0 μ g gi v e n as a S C i njecti o n o n C 1 D 1 f oll o we d b y  a f ull d ose of 
8 0 0 µ g, w hic h c orres p o n ds t o t he si n gle a ge nt M T D wit h o ut pri mi n g a d mi nistere d as a S C 
i njecti o n, o n C 1 D 1 5 a n d Q 2 W t hereafter.
T he starti n g pri mi n g d ose of 4 0 0 µ g P F- 0 7 0 6 2 1 1 9 was selecte d base d o n t he f oll o wi n g 
c o nsi derati o ns fr o m t he a vaila ble cli nical data fr o m t he c o h ort wit h o ut a pri mi n g d ose: 
( 1) P F -0 7 0 6 2 1 1 9 was o bser ve d t o be safe a n d t olera ble, wit h n o D L Ts after t he first or 
sec o n d d ose a n d n o C R S e ve nts Gra de ≥2 re p orte d; ( 2) it was t he l o west d ose t hat 
de m o nstrate d mea ni n gf ul i m m u ne acti vati o n t hat is necessar y  t o acc o m plis h a pri mi n g effect, 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 7
as e vi de nce d b y i ncrease d meas ura ble c yt o ki ne mar kers of T -cell acti vati o n a n d 
i nfla m mati o n; a n d ( 3) 4/ 6 partici pa nts at t his d ose le vel als o de m o nstrate d re d ucti o ns i n 
C E A, a t u m or mar ker. 
T he starti n g f ull d ose of P F -0 7 0 6 2 1 1 9 will be 8 0 0 µ g Q 2 W. T his d ose c orres p o n ds t o t he 
si n gle a ge nt M T D wit h o ut pri mi n g a n d t here is alrea dy a vaila ble cli nical data f or 
9 partici pa nts at t his d ose le vel. T his d ose w o ul d all o w f or o bjecti ve assess me nt of t he 
pri mi n g strate g y  base d o n c o m paris o n bet wee n t he pri mi n g a n d n o n-pri mi n g setti n gs at t he 
sa me f ull d ose ( 8 0 0 µ g) of P F-0 7 0 6 2 1 1 9, i n t he c o nte xt of  safet y  e ve nts a n d le vel of 
c yt o ki ne acti vati o n. A d diti o nall y, t he pri mi n g/f ull d ose of 4 0 0 µ g/ 8 0 0 µ g Q 2 W satisfies 
E W O C criteria (see Secti o n 9. 4. 1 a n d A p pe n di x 1 0 , Secti o n 1 0. 1 0 ).
4. 3. 3. S u bc ut a ne o us R o ute 
T he S C r o ute will be e m pl o y e d i n t his st u d y gi ve n t he p ote ntial t o re d uce t he Cma x, w hic h is 
belie ve d t o be ass ociate d wit h C R S a n d i nfla m mat or y res p o nses. De pe n di n g o n t he a vaila ble 
e mer gi n g cli nical data (i ncl u di n g safet y/ t olera bilit y, P K, P D) fr o m t he d ose escalati o n 
c o h orts wit h S C a d mi nistrati o n, I V a d mi nistrati o n, i ncl u di n g t he use of a n I V pri mi n g d ose 
ma y  be e val uate d a n d w o ul d be acc o m pa nie d wit h a pr ot oc ol a me n d me nt. 
I n case of c ha n ge of t he d osi n g re gi me n, D L T data acc u m ulate d d uri n g t he d ose escalati o n 
wit h t he pre vi o usl y  e x pl ore d re gi me n mi g ht be use d t o f or m a pri or ass u m pti o n f or f urt her 
B L R M a nal ys is. 
4. 3. 4. Fi xe d D osi n g A p pr o ac h 
A fi xe d -d ose a p pr oac h will be a p plie d f or t he FI P st u d y  of P F-0 7 0 6 2 1 1 9 gi ve n t hat fi xe d 
d osi n g a p pr oac h was s h o w n t o pr o vi de si milar P K varia bilit y  c o m pare d t o a b o d y-wei g ht 
a dj uste d d osi n g f or m o n ocl o nal a nti b o dies, t hera pe utic pe pti des, a n d pr otei ns ( Wa n g D et al; 
Z ha n g S et al). 4 9 ,5 1  I n a d diti o n, fi xe d d osi n g offers ease of pre parati o n a n d less c ha nce of 
d osi n g err ors. Alter nati vel y , base d o n e mer gi n g P K data, b o d y wei g ht, or b o d y s urface area 
base d d osi n g ma y  be c o nsi dere d.
4. 3. 5. D osi n g I nter v al ( Q 2 W)
T he Q 2 W d osi n g fre q ue nc y  of P F- 0 7 0 6 21 1 9 i n t his st u d y  was selecte d base d o n ( 1) t he 
pr ojecte d t1/ 2 of 2 1 da y s i n h u ma ns a n d ( 2) t he c o m bi nati o n a ge nts f or P F- 0 7 0 6 2 1 1 9 
( P F-0 6 8 0 1 5 9 1 a n d be vaciz u ma b -Pfizer) i n t his st u d y  will be a d mi nistere d Q 2 W or Q 4 W. A 
Q 2 W re gi me n was selecte d f or t his FI P s t u d y t o re d uce Cma x , w hic h is belie ve d t o be 
ass ociate d wit h C R S, c o m pare d t o Q 4 W a d mi nistrati o n (c o m pari n g d oses ac hie vi n g 
matc hi n g o verall e x p os ure bet wee n Q 2 W a n d Q 4 W re gi me ns). Base d o n e mer gi n g P K, P D, 
a n d safet y data, re gi me ns wit h alter nati ve d osi n g fre q ue ncies (e g, wee kly a d mi nistrati o n or 
Q 4 W) ma y  als o be c o nsi dere d.
4. 3. 6. St arti n g D ose f or C o m bi n ati o n D ose Fi n di n g ( P art 1 B)
T he d ose -fi n di n g e val uati o n of P F-0 7 0 6 2 1 1 9 i n c o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 or 
be vaciz u ma b -Pfizer will be i nitiate d after deter mi nat i o n of t he M T D a n d/ or R P 2 D f or 
P F -0 7 0 6 2 1 1 9 as m o n ot hera p y wit h or wit h o ut pri mi n g ( Part 1 A) a n d s u p p orte d b y  e mer gi n g 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 8
cli nical data i ncl u di n g a n y a vaila ble safet y/ t olera bilit y, P K, P D, or preli mi nar y e vi de nce of 
efficac y.
F or t he P F - 0 7 0 6 2 1 1 9/P F -0 6 8 0 1 5 9 1 c o m bi nati o n, t he starti n g d ose of P F-0 7 0 6 2 1 1 9 will be 
o ne d ose le vel l o wer t ha n t he P F -0 7 0 6 2 1 1 9 m o n ot hera p y M T D or t he R P 2 D  ( or t he hi g hest 
d ose le vel pre vi o usl y deter mi ne d t o be safe if t he M T D or R P 2 D has n ot yet bee n i de ntifie d) 
t o acc o u nt f or a ny p ote nt ial o verla p pi n g t o xicities t hat mi g ht be ass ociate d wit h t he 
P F -0 7 0 6 2 1 1 9/ P F -0 6 8 0 1 5 9 1 c o m bi nati o n.  T he starti n g d ose f or P F -0 7 0 6 2 1 1 9/ P F - 0 6 8 0 1 5 9 1 
c o m bi nati o n ( Part 1 B wit h o ut pri mi n g) will be 4 0 0 µ g. T he d ose of P F -0 6 8 0 1 5 9 1 will be 
3 0 0 m g Q 4 W S C.
F or t he P F -0 7 0 6 2 1 1 9 c o m bi nati o n wit h be vaciz u ma b -Pfizer, t he starti n g d ose of 
P F - 0 7 0 6 2 1 1 9 will be t he M T D or R P 2 D deter mi ne d wit h o ut pri mi n g i n Part 1 A, a n d t he d ose 
of be vaciz u ma b -Pfizer will be 5 m g/ k g Q 2 W I V i nf usi o n ( Ta ble 1 0 ).
T he starti n g d ose of a n y ne w re gi me n, i ncl u di n g c o m bi nati o n wit h pri mi n g will satisf y  
E W O C criteria (see Tec h nical S u p ple me nt t o A p pe n di x 1 0 ).
F or t he P F -0 7 0 6 2 1 1 9 c o m bi nati o ns wit h P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pfizer wit h pri mi n g, 
P F - 0 7 0 6 2 1 1 9 will be a d mi nistere d o n C 1 D 1 al o ne a n d will be a d mi nistere d o n C 1 D 1 5 i n 
c o m bi nati o n wit h eit her P F- 0 6 8 0 1 5 9 1 or be vaciz u ma b - Pfizer. F or a d diti o nal details, refer t o 
Secti o n 4. 1 .
4. 3. 7. Criteri a f or D ose Esc al ati o n
A B L R M, g ui de d b y t he E W O C pri nci ple, will be use d i n d ose escalati o n i n Part 1 A a n d 
d ose fi n di n g i n Part 1 B. See Secti o n 9. 4 a n d A p pe n di x 1 0 f or m ore details o n t he m o del. 
Usi n g D L T data at all teste d d ose le vels a n d pres pecifie d pri or distri b uti o n of m o del 
para meters, p osteri or pr o ba bilities of t he pr o ba bilit y  of ha vi n g a D L T falli n g i nt o 3 d osi n g 
i nter vals ( u n der d osi n g, tar get d osi n g, a n d o ver d osi n g) will be calc ulate d f or all d ose le vels. 
A d ose ma y  o nly be use d f or ne wl y e nr olle d partici pa nts if it satisfies E W O C pri nci ple 
(ie, t he ris k of o ver-d osi n g at t his d ose is pre dicte d t o be less t ha n 2 5 %). 
T y picall y , partici pa nts will be e nr olle d i n d ose le vel c o h orts of a p pr o xi matel y 3 partici pa nts 
wit h at least 1 D L T e val ua ble partici pa nt i n t he first d ose le vel i n Part 1 A wit h o ut a pri mi n g 
d ose a n d 2 D L T e val ua ble partici pa nts at all ot her d ose le vels i n Part 1 A wit h a n d wit h o ut a 
pri mi n g d ose. All d ose le vels i n Part 1 B wit h or wit h o ut a pri mi n g d ose will ha ve at least 
3 D L T e val ua ble partici pa nts.
T he ma xi m u m d ose i ncreases fr o m t he pre vi o us d ose le vels f or re gi me n will be u p t o 2 0 0 % 
f or c o h orts wit h o ut a pri mi n g d ose b ut will be a dj uste d t o n o m ore t ha n 1 0 0 % f oll o win g t he 
o bser vati o n of a D L T or if t here are t w o Gra de ≥2 cli nicall y  si g nifica nt treat me nt-relate d 
A Es. T he ma xi m u m all o wa ble d ose i ncre me nt f or d ose escalati o n will be 1 0 0 % f or c o h orts 
wit h a pri mi n g d ose.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 5 9
T a ble 9 . S C D ose Esc al ati o n Le vels f or A d mi nistr ati o n Wit h o ut Pri mi n g D ose
D ose Le vel *
D ose ( µ g)
D L 1 ( Starti n g D ose * *)
4 5
D L 2
1 3 5
D L 3 a n d hi g her
Escalati o n t o c o nti n ue t o M T D or desire d p har mac ol o gic acti vit y
* I nter me diate d oses ma y be e val uate d base d o n cli nical fi n di n gs; D L = D ose Le vel; M T D = Ma xi m u m 
T olerate d D ose; S C = S u bc uta ne o us.
* * If t he 4 5 μ g S C Q 2 W d ose is n ot t olerate d, t he n a l o wer d ose of 3 0 μ g Q 2 W via S C r o ute w ill be 
e val uate d.
D ose escalati o n will st o p w he n st o p pi n g criteria are met (see Secti o n 4. 3. 8 a n d 
A p pe n di x 1 0 ). Acc or di n g t o t he st o p pi n g criteria, at least 6 partici pa nts will be e val uate d at 
t he M T D.
I ntra partici pa nt d ose escalati o n t o t he ne xt d ose le vel ma y be c o nsi dere d i n c o ns ultati o n wit h 
t he s p o ns or f or partici pa nts(s) w h o ha ve c o m plete d t he D L T peri o d i n t he d ose escalati o n 
p hase if t he ne xt hi g her d ose le vel has bee n cleare d.
4. 3. 8. D ose Li miti n g T o xicit y Defi niti o n
A partici pa nt is classifie d as D L T e val ua ble if he/s he e x perie nces a D L T (irres pecti ve of 
w het her t he y  recei ve d all of t he pla n ne d d oses of eac h st u d y i nter ve nti o n a n d sc he d ule d 
safety assess me nts d uri n g t he D L T wi n d o w) or if he/s he ot h er wise i n t he a bse nce of a D L T 
recei ves all of t he pla n ne d d oses of eac h st u d y i nter ve nti o n a n d has recei ve d sc he d ule d safety 
assess me nts d uri n g t he D L T wi n d o w. If a partici pa nt fails t o meet t hese criteria, he/s he ma y 
be re place d. 
D L Ts will be assesse d t hr o u g h C ycl e 1 ( 2 8-d a y  c ycle wit h Da y 2 9 [e g, C 2 D 1]) f or c o h orts 
wit h o ut pri mi n g a n d will be assesse d t hr o u g h C 2 D 1 5 ( 4 2 -d a y c y cle wit h Da y 4 3 
[e g, C 2 D 1 5]) f or c o h orts wit h pri mi n g. 
F or t he p ur p ose of d ose escalati o n, t he D L T o bser vati o n peri o d f or Q 2 W S C re gi me n will be 
2 8 da y s f or c o h orts wit h o ut a pri mi n g d ose a n d 4 2 da ys  f or c o h orts wit h a pri mi n g d ose after 
t he start of st u d y treat me nt i n eac h partici pa nt.
Si g nifica nt A Es c o nsi dere d t o be relate d t o t he st u d y  i nter ve nti o n or treat me nt u n der 
i n vesti gati o n t hat occ ur after t he D L T o bser vati o n peri o d will be re vie we d i n c o nte xt of all 
safety data a vaila ble. T hat re vie w ma y res ult i n re -e val uati o n of t he d osi n g le vel or re gi me n.
Se verit y  of A Es will be gra de d acc or di n g t o C T C A E v 5. 0. 
F or t he p ur p ose of d ose escalati o n, a n y  of t he f oll o wi n g A Es wit h t he ass ociate d para meters 
t hat occ ur d uri n g t he D L T o bser vati o n peri o d t hat are attri b uta ble t o o ne, t he ot her, or b ot h 
a ge nts i n t he c o m bi nati o n will be classifie d as D L Ts:
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 0
He m at ol o gic al D L Ts:

Gra de 3 ne utr o pe nia lasti n g > 5 da y s is a D L T.

Fe brile ne utr o pe nia is a D L T defi ne d as a n a bs ol ute ne utr o p hil c o u nt ( A N C) 
< 1. 0 x 1 0 9/ L  wit h a si n gle te m perat ure of > 3 8. 3° C, or 1 0 1° F, or a s ustai ne d 
te m perat ure of 3 8 C , or 1 0 0.4 F , f or m ore t ha n o ne h o ur is a D L T.

Gra de 3 ne utr o pe nia wit h i nfecti o n is a D L T.

Gra de 3 t hr o m b oc y t o pe nia wit h Gra de 2 (cli nicall y  si g nifica nt) blee di n g is a D L T.

A n y  Gra de 4 t hr o m b oc yt o pe nia is a D L T.

A ne mia or t hr o m b oc y t o pe nia re q uiri n g tra nsf usi o n is a D L T.
N o n -He m at ol o gic al D L Ts:

Gra de ≥3 f ati g ue lasti n g ≥7 da y s is a D L T.

F or partici pa nts wit h li ver, b o ne, or l u n g metastasis, a n A S T or A L T i ncrease 
> 8 x U L N or al kali ne p h os p hatase > 1 0 x U L N is a D L T.

C o nfir me d dr u g i n d uce d li ver i nj ur y  ( DI LI) meeti n g H y’s la w criteria is a D LT.

Gra de 3 v o mit i n g or diarr hea lasti n g ≥3 d a y s des pite a de q uate treat me nt 
(e g, a ntie metic or a nti diarr heal me dicati o ns, res pecti vel y ) a n d ot her s u p p orti ve care is 
a D L T.

Gra de 4 v o miti n g or diarr hea is a D L T.

Gra de ≥3 C R S re gar dless of d urati o n is a D L T.

Gra de ≥3 Q Tc F pr ol o n gati o n irres pecti ve of d urati o n is a D L T.

A n y  deat h n ot clearly d ue t o t he u n derl yi n g disease or e xtra ne o us ca uses is a D L T.
Cli nicall y  i m p orta nt or persiste nt t o xicities (e g, t o xicities res p o nsi ble f or si g nifica nt d ose 
dela y ) t hat are n ot i ncl u de d i n t he a b o ve criteria ma y als o be c o nsi dere d a D LT f oll o wi n g 
re vie w by t he i n vesti gat ors a n d t he S p o ns or. All D L Ts nee d t o re prese nt a cli nicall y  
si g nifica nt s hift fr o m baseli ne.
Ot her wise, A Es of C T C A E Gra de greater t ha n or e q ual t o 3 will be c o nsi dere d t o b e D L Ts, 
wit h t he e xce pti o n of t he A Es liste d bel o w.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 1
T he f oll o wi n g A Es will n ot be a dj u dic ate d as D L Ts:

Is olate d Gra de 3 la b orat or y a b n or malities t hat are n ot ass ociate d wit h cli nical 
se q uelae a n d are c orrecte d wit h s u p ple me ntati o n/a p pr o priate ma na ge me nt wit hi n 
7 2 h o urs of t heir o nset.

Gra de 3 a m y lase or li pase ele vati o n n ot ass ociate d wit h cli nical s ym pt o ms or cli nical 
ma nifestati o ns of pa ncreatitis.
4. 3. 9. L ate O nset T o xicit y
Si g nifica nt A Es c o nsi dere d t o be relate d t o P F- 0 7 0 6 2 1 1 9 as m o n ot hera p y  or i n c o m bi nati o n
treat me nt u n der i n vesti gati o n t hat occ ur after t he D LT o bser vati o n peri o d will be re vie we d i n 
t he c o nte xt of all safety data a vaila ble. T his re vie w ma y res ult i n re -e val uati o n of t he d osi n g 
le vel or re gi me n.
Pfizer will sc he d ule a safet y  re vie w meeti n g wit h t he i n vesti gat ors t o re vie w t he details of t he 
p ote ntial late o nset t o xicit y  a n d deter mi ne if e nr oll me nt s h o ul d be hel d, c o nti n ue d or if d ose 
re d ucti o n s h o ul d be i m ple me nte d f or o n g oi n g partici pa nts. Late o nset t o xicities t hat meet t he 
defi niti o n of D L T will be c o nsi dere d i n t he e val uati o n of t he M T D.
4. 3. 1 0. M a xi m u m T oler ate d D ose Defi niti o n
M T D is defi ne d as a d ose wit h tr ue D L T rate fr o m t he tar get t o xicit y  i nter val. T he tar get 
i nter val f or t he D L T rate is defi ne d as ( 0. 1 6, 0. 3 3).
4. 3. 1 1. Rec o m me n de d P h ase 2 D ose Defi niti o n 
T he R P 2 D f or P F -0 7 0 6 2 1 1 9 will be retr os pecti vel y  deter mi ne d as a m o n ot hera p y wit h a n d 
wit h o ut pri mi n g, a n d i n c o m bi nati o n wit h P F - 0 6 8 0 1 5 9 1 or i n c o m bi nati o n wit h 
be vaciz u ma b -Pfizer f or f urt her st u d y  base d o n P hase 1 st u d y res ults. If t he M T D pro ves t o be 
cli nicall y feasi ble f or l o n g-ter m a d mi nistrati o n i n a reas o na ble n u m ber of partici pa nts, t he 
M T D wit h or wit h o ut a pri mi n g d ose c o ul d be selecte d as t he R P 2 D. F urt her e x perie nce wit h 
t he M T D ma y res ult i n a R P 2 D d ose l o wer t ha n t he M T D. Alter nati vel y, if data all o ws, t he 
R P 2 D c o ul d be selecte d as t he safe d ose t hat de m o nstrates t he desire d p har mac ol o gical 
acti vit y ( o pti mal bi ol o gical d ose). P K data as well p ote ntial e x p os ure-res p o nse relati o ns hi ps 
(safety a n d efficac y, as data per mits) will be c o nsi dere d i n i de ntif y i n g t he R P 2 D. D uri n g 
escalati o n a n d pri or t o a n M T D bei n g reac he d, t he s p o ns or ma y  c h o ose t o a d va nce a l o wer 
d ose i nt o e x pa nsi o n, partic ularl y  ( b ut n ot e xcl usi vel y) w he n c o nsi deri n g c o m bi nati o n 
c o h orts. T his decisi o n m ust be ma de base d o n safet y , P K, P D, a n d/ or efficac y data.
4. 3. 1 2. P art 2 Res pecti ve St arti n g D oses f or P F -0 7 0 6 2 1 1 9 as a Si n gle A ge nt a n d 
C o m bi n ati o n D ose E x p a nsi o n C o h orts
Part 2 d ose e x pa nsi o n is a n o pe n -la bel, m ulti-ce nter, n o n-ra n d o mize d st u d y t o assess t he 
preli mi nar y  a nti-t u mor acti vit y  al o n g wit h safet y/t olera bilit y, P K, a n d P D of P F- 0 7 0 6 2 1 1 9. 
P F - 0 7 0 6 2 1 1 9 will be e val uate d at t he R P 2 D i n 2 8-da y  c ycles i n d ose e x pa nsi o n ar ms as a 
si n gle a ge nt, i n c o m bi nati o n wit h P F-0 6 8 0 1 5 9 1, a n d i n c o m bi nati o n wit h 
be vaciz u ma b -Pfizer. F oll o wi n g a re vie w of all a vaila ble data i n Part 1 a n d i n c o ns ultati o n 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 2
wit h t he St u d y C 3 8 6 1 0 0 1 Safet y  Re vie w Tea m, a pri mi n g strate g y f or P F-0 7 0 6 2 1 1 9 ma y  be 
i nitiate d i n Part 2.
T he si n gle -a ge nt P F -0 7 0 6 2 1 1 9 R P 2 D fr o m Part 1 A will be use d t o i nitiate t he Part 2 
sin gle -a ge nt d ose -e x pa nsi o n ar m, w hic h ma y be de-escalate d base d o n e mer gi n g cli nical 
data. A d diti o nall y , t he P F-0 7 0 6 2 1 1 9 R P 2 D i n c o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 a n d 
P F -0 7 0 6 2 1 1 9 R P 2 D i n c o m bi nati o n wit h be vaciz u ma b - Pfizer fr o m Part 1 B will be use d t o 
i nitiate the Part 2 res pecti ve c o m bi nati o n d ose e x pa nsi o n ar m st u dies, w hic h ma y  be 
de-escalate d, if i n dicate d fr o m e mer gi n g cli nical data.
4. 3. 1 3. P art 2 P F - 0 7 0 6 2 1 1 9 as a Si n gle A ge nt i n A d v a nce d or Met ast atic C ol orect al 
A de n oc arci n o m a
P F -0 7 0 6 2 1 1 9 will be e val uate d as a si n gle a ge nt at t he R P 2 D i n a d va nce d or metastatic 
c ol orectal a de n ocarci n o ma t hat is resista nt t o sta n dar d t hera p y or f or w hic h n o sta n dar d 
t hera py is a vaila ble. T his e x pa nsi o n c o h ort will e nr oll a p pr o xi matel y 2 0 partici pa nts.
4. 3. 1 4. P art 2 P F -0 7 0 6 2 1 1 9 i n C o m bi n ati o n wit h P F -0 6 8 0 1 5 9 1 i n A d v a nce d or 
Met ast atic C ol orect al A de n oc arci n o m a
P F -0 7 0 6 2 1 1 9 will be e val uate d i n c o m bi nati o n wit h P F -0 6 8 0 1 5 9 1 at t he R P 2 D i n a d va nce d 
or metastatic c ol orectal a de n ocarci n o ma t hat is resista nt t o sta n dar d t hera p y or f or w hic h n o 
sta ndar d t hera p y is a vaila ble. T his e x pa nsi o n c o h ort will e nr oll a p pr o xi matel y 
2 0 partici pa nts.
4. 3. 1 5. P art 2 P F - 0 7 0 6 2 1 1 9 i n C o m bi n ati o n wit h Be v aciz u m a b- Pfizer i n A d v a nce d or 
Met ast atic C ol orect al A de n oc arci n o m a
P F - 0 7 0 6 2 1 1 9 will be e val uate d i n c o m bi nati o n wit h be vaciz u ma b -Pfizer at t he R P 2 D i n 
a d va nce d or metastatic c ol orectal a de n ocarci n o ma t hat is resista nt t o sta n dar d t hera p y  or f or 
w hic h n o sta n dar d t hera p y is a vaila ble. T his e x pa nsi o n c o h ort will e nr oll a p pr o xi matel y  
2 0 partici pa nts.
4. 4. E n d of St u d y Defi niti o n
A p artici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  if he/s he has c o m plete d all p hases of 
t he st u d y i ncl u di n g t he e n d of treat me nt visit.
T he e n d of t he st u d y is defi ne d as t he date of t he last visit of t he last partici pa nt i n t he st u d y.
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nts are e nr olle d. T he 
f oll o wi n g eli gi bilit y criteria are desi g ne d t o select partici pa nts f or w h o m partici pati o n i n t he 
st u d y is c o nsi dere d a p pr o priate. All rele va nt me dical a n d n o n me dical co n diti o ns s h o ul d be 
ta ke n i nt o c o nsi derati o n w he n deci di n g w het her a partic ular partici pa nt is s uita ble f or t his 
pr ot oc ol.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 3
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
5. 1. I ncl usi o n Criteri a
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:  
1.
Fe male a n d/ or male partici pa nts a ge ≥1 8 y ears a n d/ or ≥2 0 years i n Ja pa n.
Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d fe male 
(Secti o n 1 0. 4. 2 ) partici pa nts. 
2.
F or d ose escalati o n/fi n di n g c o h ort(s) ( Part 1 A a n d 1 B): Hist ol o gical or c y t ol o gical 
dia g n osis of a d va nce d/ metastatic c ol orectal, gastric, or es o p ha geal a de n ocarci n o ma 
t hat is resista nt t o sta n dar d t hera py or f or w hic h n o l ocal re g ulat or y a p pr o ve d 
sta n dar d t hera py is a vaila ble t hat w o ul d c o nfer si g nifica nt cli nical be nefit i n t he 
me di cal j u d ge me nt of t he i n vesti gat or.
3.
F or d ose escalati o n/fi n di n g c o h ort(s) ( Part 1 A a n d 1 B): M ust ha ve t u m or tiss ue 
a vaila ble f or s u b missi o n t o t he s p o ns or. Partici pa nts e nr olle d i n Part 1 s h o ul d ha ve 
access t o t heir arc hi val f or mali n-fi xe d paraffi n e m be d de d material c o ntai ni n g t u m or 
t hat is of dia g n ostic q ualit y a n d re prese ntati ve of t heir dia g n ose d mali g na nc y or 
c o nse nt t o u n der g o a bi o ps y  d uri n g scree ni n g.
4.
F or d ose e x pa nsi o n ( Part 2): Hist ol o gical or c y t ol o gical dia g n osis of pre vi o usl y 
treate d c ol orectal ade n ocarci n o ma t hat is resista nt t o sta n dar d t hera p y or f or w hic h n o 
l ocal re g ulat or y a p pr o ve d sta n dar d t hera p y is a vaila ble t hat w o ul d c o nfer cli nical 
be nefit i n t he me dical j u d ge me nt of t he i n vesti gat or.
5.
F or d ose e x pa nsi o n ( Part 2): M ust ha ve t u m or tiss ue a vaila ble f or s u b missi o n t o t he 
s p o ns or. Partici pa nts e nr olle d i n Part 2 s h o ul d eit her ha ve access t o t heir arc hi val 
F F P E material c o ntai ni n g t u m or t hat is of dia g n ostic q ualit y  a n d re prese ntati ve of 
t heir dia g n ose d mali g na nc y or c o nse nt t o u n der g o a bi o ps y d uri n g scree ni n g.
6.
Partici pa nts e nteri n g t he st u d y  i n t he e x pa nsi o n c o h ort(s) ( Part 2) ha ve at least 
1 meas ura ble lesi o n as defi ne d b y Res p o nse E val uati o n Criteria i n S oli d T u m ors 
( R E CIS T) versi o n 1. 1 t hat has n ot bee n pre vi o usl y  irra diate d.
7.
Partici pa nts e nteri n g t he st u d y i n t he s u b gr o u p(s) re q uiri n g ma n dat or y pre- a n d 
o n -treat me nt t u m or bi o psies i n t he d ose escalati o n/fi n di n g c o h ort(s) ( Part 1 A a n d 1 B) 
a n d d ose e x pa nsi o n i n Part 2 m ust ha ve a t u m or a me na ble t o bi o ps y  a n d c o nse nt t o 
t hese pla n ne d bi o psy pr oce d ures.
8.
B o d y wei g ht of > 7 0 k g f or D ose Le vel 1 o nl y.
9.
Easter n C o o perati ve O nc ol o g y  Gr o u p ( E C O G) Perf or ma nce Stat us ( P S) m ust be 
0 or 1.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 4
1 0. A de q uate b o ne marr o w f u ncti o n, i ncl u di n g:

A bs ol ute Ne utr o p hil C o u nt ( A N C) 1, 5 0 0/ m m 3 or 1. 5 x 1 0 9/ L;

Platelets 1 0 0, 0 0 0/ m m 3 or ≥1 0 0 x 1 0 9/ L;

He m o gl o bi n 9 g/ d L.
1 1. A de q uate re nal f u ncti o n, i ncl u di n g:

Esti mate d creati ni ne cleara nce 6 0 m L/ mi n f or Part 1 a n d 5 0 m L / mi n f or Part 2 
as calc ulate d usi n g t he met h o d sta n dar d f or t he i nstit uti o n. I n e q ui v ocal cases, a 
2 4 h o ur ur i ne c ollecti o n test ca n be use d t o esti mate t he creati ni ne cleara nce m ore 
acc uratel y.
1 2. A de q uate li ver f u ncti o n, i ncl u di n g:

T otal ser u m bilir u bi n 1. 5 x U L N u nless t he partici pa nt has d oc u me nte d Gil bert 
s yn dr o me;

As partate a n d ala ni ne tra nsa mi nase ( A S T a n d A L T) 2. 5 x U L N; 

Al kali ne p h os p hatase 2. 5 x U L N; ( 5 x U L N i n case of b o ne, li ver, or l u n g 
metastasis).
1 3. Res ol ve d ac ute effects of a n y  pri or t hera p y t o baseli ne se verity or C T C A E Gra de ≤1 
e xce pt f or a d verse e ve nts ( A Es) n ot c o nstit uti n g a safet y ris k b y i n vesti gat or 
j u d g me nt.
1 4. T h y r oi d sti m ulati n g h or m o ne ( T S H) wit hi n n or mal li mits ( W N L) f or i nstit uti o n; 
s u p ple me ntati o n is acce pta ble t o ac hie ve a T S H W N L; i n partici pa nts wit h a b n or mal 
T S H if Free T 4 a n d Free T h y r o xi ne are n or mal, a n d partici pa nt is cli nicall y 
e ut h yr oi d, partici pa nt is eli gi ble.
1 5. Partici pa nts w h o are willi n g a n d a ble t o c o m pl y wit h all sc he d ule d visits, treat me nt 
pla n, la b orat or y  tests, lifest yle c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
1 6. Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n A p pe n di x 1 , w hic h 
i ncl u des c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he i nf or me d 
c o nse nt d oc u me nt (I C D) a n d i n t his pr ot oc ol.
5. 2. E xcl usi o n Criteri a
Partici pa nts are e xcl u de d fr o m t he st u d y  if a n y of t he f oll o wi n g criteria a p pl y:
1.
Partici pa nts wit h k n o w n s y m pt o matic brai n metastases re q uiri n g c ortic oster oi ds. 
Partici pa nts wit h pre vi o usl y  dia g n ose d brai n metastases are eli gi ble if t he y ha ve 
c o m plete d t heir treat me nt a n d ha ve rec o vere d fr o m t he ac ute effects of ra diati o n 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 5
t hera py or s ur ger y pri or t o st u d y e ntr y, ha ve disc o nti n ue d c ortic oster oi d treat me nt f or 
t hese metastases f or at least 4 wee ks a n d are ne ur ol o gically sta ble f or 3 m o nt hs 
(re q uires ma g netic res o na nce i ma gi n g [ M RI] c o nfir mati o n). 
2.
Partici pa nts wit h a n y  ot her acti ve mali g na nc y wit hi n 3 ye ars pri or t o e nr oll me nt, 
e xce pt f or a de q uatel y treate d basal cell or s q ua m o us cell s ki n ca ncer, or carci n o ma i n 
sit u.
3.
Maj or s ur ger y  wit hi n 3 wee ks pri or t o st u d y  e ntr y (e xce pt i n partici pa nts recei vi n g 
be vaciz u ma b -Pfizer i n w hic h maj or s ur ger y  wit hi n 4 wee ks pri or t o st u d y e ntr y 
w o ul d be e xcl usi o nar y ).
4.
Ra diati o n t hera p y wit hi n 3 wee ks pri or t o st u d y e ntr y. Palliati ve ra di ot hera p y t o a 
li mite d fiel d ma y be all o wed after c o ns ultati o n wit h t he s p o ns or’s me dical m o nit or 
u nless it is clearl y  i n dicati ve of disease pr o gressi o n.
5.
S y ste mic a nti-ca ncer t hera p y wit hi n 4 wee ks pri or t o st u d y e ntr y ( 6 wee ks f or 
mit o m y ci n C or nitr os o ureas) or 5 half -li ves ( w hic he ver is s h orter) of t he a ge nt(s) 
pri or t o recei vi n g t he st u d y  i nter ve nti o n/st u d y treat me nt is re q uire d.
6.
Partici pa nts wit h acti ve, u nc o ntr olle d bacterial, f u n gal, or viral i nfecti o n, i ncl u di n g 
he patitis B vir us ( H B V), he patitis C vir us ( H C V), k n o w n h u ma n i m m u n o deficie nc y 
vir us ( HI V) or ac q uire d i m m u n o deficie nc y  s y n dr o me ( AI D S) relate d ill ness. I n 
e q ui v ocal cases, partici pa nts w h ose viral l oa d is ne gati ve, ma y  be eli gi ble. HI V 
ser o p ositi ve partici pa nts w h o are healt hy a n d l o w -ris k f or AI D S-relate d o utc o mes 
c o ul d be c o nsi der e d eli gi ble. Eli gi bilit y criteria f or HI V-p ositi ve partici pa nts s h o ul d 
be e val uate d a n d disc usse d wit h s p o ns or’s me dical m o nit or a n d will be base d o n 
c urre nt a n d past C D 4 a n d T- cell c o u nts, hist or y (if a n y) of AI D S-defi ni n g c o n diti o ns 
(e g, o p p ort u nistic i n fecti o ns), a n d stat us of HI V treat me nt. Als o, t he p ote ntial f or 
dr u g - dr u g i nteracti o ns will be ta ke n i nt o c o nsi derati o n.
7.
C O VI D -1 9/ S A R S - C o V 2: T his pr ot oc ol e xcl u des partici pa nts wit h acti ve i nfecti o ns, 
as n ote d a b o ve. W hile S A R S- C o V 2 testi n g is n ot ma n date d f or e ntr y  i nt o t his 
pr ot oc ol, testi n g s h o ul d f oll o w l ocal cli nical practice sta n dar ds. If a partici pa nt has a 
p ositi ve test res ult f or S A R S- C o V 2 i nfecti o n, is k n o w n t o ha ve as y m pt o matic 
i nfecti o n, or is s us pecte d of ha vi n g S A R S- C o V 2, he/s he will be e xcl ude d.
8.
Baseli ne 1 2 -lea d electr ocar di o gra m ( E C G) t hat de m o nstrates cli nicall y rele va nt 
a b n or malities t hat ma y affect partici pa nt safety or i nter pretati o n of st u d y res ults 
(e g, baseli ne c orrecte d Q T [ Q Tc F ] i nter val > 4 7 0 msec, c o m plete left b u n dle bra nc h 
bl oc k [ LB B B], si g ns of a n ac ute or i n deter mi nate a ge m y ocar dial i nfarcti o n, S T 
se g me nt or T wa ve i nter val c ha n ges s u g gesti ve of acti ve my ocar dial isc he mia, sec o n d 
or t hir d de gree atri o ve ntric ular [ A V] bl oc k, or seri o us bra d yarr h yt h mias or 
tac hyarr h yt h mias). If t he baseli ne u nc orrecte d Q T i nter val is > 4 7 0 msec, t his i nter val 
s h o ul d be rate c orrecte d usi n g t he Fri dericia met h o d a n d t he res ulti n g Q Tc F s h o ul d be 
use d f or decisi o n ma ki n g a n d re p orti n g. If Q Tc F e xcee ds 4 7 0 msec, or Q R S e xcee ds 
1 2 0 msec, t he E C G s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge of t he 3 Q Tc or 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 6
Q R S val ues s h o ul d be use d t o deter mi ne t he partici pa nts eli gi bilit y . C o m p uter 
i nter prete d E C Gs s h o ul d be o verrea d by a p h ys icia n e x perie nce d i n rea di n g E C Gs 
bef ore e xcl u di n g partici pa nts. Cases m ust be disc usse d i n detail wit h s p o ns or’s 
me dical m o nit or t o j u d ge eli gi bilit y .
9.
A n y  of t he f oll o wi n g i n t he pre vi o us 6 m o nt hs: m yocar dial i nfarcti o n, l o n g Q T 
s yn dr o me, T orsa de de P oi ntes, arr h y t h mias (i ncl u di n g s ustai ne d ve ntric ular 
tac hyarr h yt h mia a n d ve ntric ular fi brillati o n), seri o us c o n d ucti o n s y ste m a b n or malities 
(e g, left a nteri or he mi bl oc k, left b u n dle bra nc h bl oc k), u nsta ble a n gi na, 
c or o nar y/ peri p heral arter y b ypass graft, s y m pt o matic c o n gesti ve heart fail ure ( C H F, 
Ne w Y or k Heart Ass ociati o n class III o r I V), cere br o vasc ular acci de nt, tra nsie nt 
isc he mic attac k, sy m pt o matic p ul m o nar y  e m b olis m, a n d/ or ot her cli nical si g nifica nt 
e pis o de of t hr o m b o-e m b olic disease, o n g oi n g car diac d ysr h yt h mias of Nati o nal 
Ca ncer I nstit ute ( N CI) C T C A E > Gra de 2, atrial fi bril lati o n of a n y gra de ( > Gra de 2 
i n t he case of asy m pt o matic l o ne atrial fi brillati o n). If a partici pa nt has a car diac 
r h yt h m de vice/ pace ma ker place d a n d Q Tc F > 4 7 0 msec, t he partici pa nt ca n be 
c o nsi dere d eli gi ble. Partici pa nts wit h car diac r h yt h m de vice/ pace ma ker m ust be 
disc usse d i n detail wit h s p o ns or’s me dical m o nit or t o j u d ge eli gi bilit y .
1 0. A ntic oa g ulati o n wit h vita mi n K a nta g o nists or fact or Xa i n hi bit ors is n ot all o we d. 
A ntic oa g ulati o n wit h S C he pari n is all o we d.
1 1. H y perte nsi o n t hat ca n n ot be c o ntr olle d b y  me dicati o ns (e g, > 1 5 0/ 9 0 m m H g) des pite 
o pti mal me dical t hera p y.
1 2. Partici pati o n i n ot her st u dies i n v ol vi n g i n vesti gati o nal dr u g(s) wit hi n 2 wee ks of 
st u d y e ntr y e xce pt f or partici pati o n i n me dical i ma gi n g st u dies, w hic h is all o we d.
1 3. K n o w n or s us pecte d h y p ersensiti vit y  t o P F-0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1, or 
be vaciz u ma b - Pfizer, or e xci pie nts ass ociate d wit h t he prece di n g c o m p o u n ds f or t he 
res pecti ve pla n ne d i n vesti gati o nal st u dy treat me nts. Hist or y of Gra de 3 i m m u ne 
me d iate d or relate d A E (i ncl u di n g A S T/ A L T ele vati o ns t hat were c o nsi dere d dr u g 
relate d a n d c yt o ki ne release sy n dr o me) t hat was c o nsi dere d relate d t o pri or i m m u ne 
m o d ulat or y  t hera p y (e g, i m m u ne c hec k p oi nt i n hi bit ors, c o-sti m ulat or y a ge nts, etc) 
a n d re q uire d i m m u n os u p pressi ve t hera p y. A n e xce pti o n w o ul d be a partici pa nt wit h a 
hist or y  of vitili g o or t hyr oi d d y sf u ncti o n w h o has bee n off i m m u n os u p pressi ve 
t hera py f or at least 6 m o nt hs.
1 4. Acti ve or hist or y  of cli nicall y si g nifica nt a ut oi m m u ne disease t hat re q uire d s yste mic 
i m m u n os u p pressi ve t hera p y or a n ot her me dical c o n diti o n t hat re q uire d 
i m m u n os u p pressi o n wit hi n 2 years of treat me nt.
1 5. Re q uire me nt f or s ys te mic i m m u ne s u p pressi ve me dicati o n [e g, ≥1 0 m g  of pre d nis o ne 
or e q ui vale nt ( ≥1. 5 m g  of de xa met has o ne)]. I n hale d, i ntra nasal, i ntra oc ular, 
i ntraartic ular, a n d t o pical c ortic oster oi ds are all o we d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 7
1 6. Acti ve blee di n g dis or der, i ncl u di n g gastr oi ntesti nal blee di n g, as e vi de nce d b y  
he mate mesis, si g nifica nt he m o pt y sis or mele na i n t he past 6 m o nt hs.
1 7. Partici pa nts wit h t he prese nce of a n y o pe n, acti ve w o u n d.
1 8. Ser u m or uri ne pre g na nc y  test (f or fe males of c hil d beari n g p ote ntial) p ositi ve at 
scree ni n g or breast fee di n g fe male partici pa nts (i ncl u di n g partici pa nts w h o i nte n d t o 
i nterr u pt breastfee di n g).
1 9. Hist or y  of or acti ve cli nicall y si g nifica nt gastr oi ntesti nal disease (i ncl u di n g b ut n ot 
li mite d t o i nfla m mat or y gastr oi ntesti nal disease [e g, ulcerati ve c olitis, Cr o h n’s 
disease], pe ptic ulcer disease, gastr oes o p ha geal refl u x disease, gastr oi ntesti nal 
blee di n g, c hr o nic diarr hea) a n d ot her c o n diti o ns t hat are u nres ol ve d a n d/ or ma y  
i ncrease t he ris k ass ociate d wit h st u d y partici pati o n or st u d y i nter ve nti o n/st u d y 
treat me nt a d mi nistrati o n or ma y i nterfere wit h t he i nter pretati o n of st u d y res ults a n d, 
i n t he j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he partici pa nt i na p pr o priate f or 
e ntr y i nt o t his st u d y .
2 0. Ot her se vere ac ute or c hr o nic me dical or ps yc hi atric c o n diti o n, i ncl u di n g rece nt 
( wit hi n t he past year) or acti ve s uici dal i deati o n or be ha vi or, or la b orat or y  
a b n or malit y t hat ma y i ncrease t he ris k ass ociate d wit h st u d y partici pati o n or st u d y 
i nter ve nti o n/st u d y treat me nt a d mi nistrati o n or ma y i nterfere wit h t he i nter pretati o n of 
st u d y res ults a n d, i n t he j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he partici pa nt 
i na p pr o priate f or e ntr y i nt o t his st u d y.
2 1. I n vesti gat or site staff me m bers directl y i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir 
fa mil y me m bers, site staff me m bers ot her wise s u per vise d b y t he i n vesti gat or, or 
Pfizer e m pl o y ees, i ncl u di n g t heir fa mil y me m bers, directl y i n v ol ve d i n t he c o n d uct of 
t he st u d y.
Secti o n 1 0. 1 9. 4 lists a d diti o nal i ncl usi o n/e xcl usi o n criteria f or t he P E T tracer s u bst u d y.
5. 3. Lifest yle C o nsi der ati o ns
5. 3. 1. C o ntr ace pti o n
T he i n vesti gat or or his or her de si g nee, i n c o ns ultati o n wit h t he partici pa nt, will c o nfir m t hat 
t he partici pa nt has selecte d a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual 
partici pa nt [a n d his or her part ner(s)] fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see 
A p pe n di x 4 ) a n d will c o nfir m t hat t he partici pa nt has bee n i nstr ucte d i n its c o nsiste nt a n d 
c orrect use. At ti me p oi nts i n dicate d i n t he S o A , t he i n vesti gat or or desi g nee will i nf or m t he 
partici pa nt of t he nee d t o use hi g hl y effecti ve c o ntrace pti o n c o nsiste ntl y a n d c orrectl y a n d 
d oc u me nt t he c o n versati o n a n d t he partici pa nt’s affir mati o n i n t he partici pa nt’s c hart 
( partici pa nts nee d t o affir m t heir c o nsiste nt a n d c orrect use of at least 1 of t he se lecte d 
met h o ds of c o ntrace pti o n). I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he 
partici pa nt t o call i m me diatel y  if t he selecte d c o ntrace pti o n met h o d is disc o nti n ue d or if 
pre g na nc y  is k n o w n or s us pecte d i n t he partici pa nt or part ner.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 8
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y e ntere d i n t he st u d y. Scree n fail ure data are c ollecte d as s o urce a n d are 
re p orte d t o t he cli nical data base.
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his trial (scree n fail ure) beca use 
of a s pecific m o difia ble fact or (e g, la b a b n or malit y) ma y  be rescree ne d. Rescree ne d 
partici pa nts s h o ul d be assi g ne d t he sa me partici pa nt n u m ber as f or t he i nitial scree ni n g.
6. S T U D Y I N T E R V E N TI O N
St u d y  i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), 
place b o, or me dical de vice(s) i nte n de d t o be a d mi nistere d t o a st u d y  partici pa nt acc or di n g t o 
t he st u d y pr ot oc ol.
F or t he p ur p oses of t his pr ot oc ol, t h e ter m st u d y i nter ve nti o n ma y be use d s yn o n y m o usl y 
wit h st u d y  dr u g.
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
See Ta ble 1 0 f or st u d y i nter ve nti o ns a d mi nistere d.
T a ble 1 0 . A d mi nistere d St u d y I nter ve nti o ns
I nter ve nti o n N a me
P F -0 7 0 6 2 1 1 9
P F -0 6 8 0 1 5 9 1
Be vaciz u ma b -Pfizer
T y pe
Bi ol o gic
Bi ol o gic
Bi ol o gic
D ose F or m ul ati o n
L y o p hilize d p o w der f or 
s ol uti o n f or i njecti o n
a n d
dil ue nt s ol uti o n 
( histi di ne, s ucr ose, P S 8 0, 
E D T A) f or i njecti o n
S ol uti o n f or i njecti o n 
S ol uti o n f or i njecti o n
U nit D ose Stre n gt h(s)
1. 3 m L ( 5 m g/ m L) 
P F -0 7 0 6 2 1 1 9 s ol uti o n i n 
vial f oll o wi n g 
rec o nstit uti o n wit h water 
f or i njecti o n
a n d
dil ue nt wit h 9. 8 m L 
s ol uti o n i n 2 0 m L vial f or 
dil uti o n of rec o nstit ute d 
P F -0 7 0 6 2 1 1 9 
5 0 m g/ m L ( 2 m L vial)  
1 0 0 m g/ 4 m L 
( 2 5 m g / m L) or 
4 0 0 m g/ 1 6 m L 
( 2 5 m g / m L) i n a si n gle 
d ose vial
D os a ge Le vel(s)
D ose a m o u nt a n d 
fre q ue nc y – see t he st u d y 
sc he ma a n d 
acc o m pa n yi n g te xt i n 
Secti o n 4. 1
3 0 0 m g Q 4 W
5 m g/ k g Q 2 W 
R o ute of 
A d m i nistr ati o n
S C after rec o nstit uti o n 
wit h water f or i njecti o n
S C
I V
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 6 9
T a ble 1 0 . A d mi nistere d St u d y I nter ve nti o ns
I n vesti g ati o n al 
Me dici n al Pr o d uct 
(I M P) a n d N o n 
I n vesti g ati o n al 
Me dici n al Pr o d uct 
( NI M P)
I M P 
a n d
NI M P - dil ue nt
I M P
I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he 
s p o ns or
Pr o vi de d ce ntrall y b y t he 
s p o ns or
Pr o vi de d ce ntrall y b y t he 
s p o ns or
P ac k a gi n g a n d 
L a beli n g
St u d y i nter ve nti o n will be 
pr o vi de d i n o pe n la bel 
si n gle use vials 
Eac h vial a n d dil ue nt will 
be la bele d as re q uire d per 
c o u ntr y re q uire me nt
St u d y i nter ve nti o n will be 
pr o vi de d as 5 0 m g/ m L ( 2 
m L vial) i n vials
Eac h vial will be la bele d 
as re q uire d per c o u ntr y 
re q uire me nt
St u d y i nter ve nti o n will 
be pr o vi de d as si n gle use 
vial as 1 0 0 m g/ 4 m L 
( 2 5 m g / m L) or 
4 0 0 m g/ 1 6 m L 
( 2 5 m g / m L).
Eac h vial will be la bele d 
as re q uire d per c o u ntr y 
re q uire me nt
6. 1. 1. A d mi nistr ati o n
6. 1. 1. 1. P F -0 7 0 6 2 1 1 9 
P F -0 7 0 6 2 1 1 9 will be a d mi nistere d via S C i njecti o n wit h o ut a dj ust me nt f or b o d y  size at e ver y 
c ycle. 
Partici pa nts s h o ul d ha ve S C i njecti o ns i n t he a b d o me n. F or partici pa nts recei vi n g 2 or m ore 
S C i njecti o ns, st u d y dr u g s h o ul d be a d mi nistere d i n 2 or m ore differe nt q ua dra nts of t he 
a b d o me n ( wit h prefere nce gi ve n t o t he l o wer q ua dra nt w he n p ossi ble); 1 or 2 i njecti o ns per 
q ua dra nt. T he i njecti o n ca n be r otate d wit h eac h a d mi nistrati o n f or partici pa nt c o mf ort. 
A d diti o nal g ui da nce o n s u bc uta ne o us i njecti o n site l ocati o ns is pr o vi de d i n Secti o n 1 0. 2 0 . 
Details f or P F - 0 7 0 6 2 1 1 9 pre parati o n i nstr ucti o ns are pr o vi de d i n t he c urre nt P F - 0 7 0 6 2 1 1 9 I P 
Ma n ual. 
Pre me dicati o n wit h b ot h t he pri mi n g d ose(s) a n d i nitial f ull d ose of P F -0 7 0 6 2 1 1 9 f or all 
partici pa nts has bee n i m ple me nte d i nt o t his st u d y  t o f urt her i m pr o ve t olera bilit y a n d 
partici pa nt e x perie nce. 
T he f oll o wi n g pre me dicati o n s h o ul d be a d mi nistere d a p pr o xi matel y 1 h o ur pri or t o 
P F - 0 7 0 6 2 1 1 9:

Aceta mi n o p he n 6 5 0 m g ( or e q ui vale nt), oral

Di p he n h y dra mi ne 2 5 m g, oral or I V

De xa met has o ne 1 2 m g ( or e q ui vale nt), oral or I V
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 0
Pre me dicati o n s h o ul d be a d mi nistere d i n C y cle 1 o nl y o n C 1 D 1 i n c o h orts wit h o ut a pri mi n g 
d ose a n d s h o ul d be a d mi nistere d o n b ot h C 1 D 1 a n d C 1 D 1 5 i n c o h orts wit h a pri mi n g d ose. 
P re me dicati o n re gi me n b e y o n d t he first f ull d ose a n d m o dificati o ns t o t he pre me dicati o n 
re gi me n (e g, fre q ue nc y of pre me dicati o n, d oses of i n di vi d ual a ge nts, re m o val or a d diti o n of 
a ge nts) ma y be i m ple me nte d b y t he s p o ns or base d o n e mer gi n g data. A ny e xce pti o ns t o 
pre me dicati o n re q uire disc ussi o n a n d a gree me nt bet wee n t he s p o ns or a n d i n vesti gat or. 
Partici pa nts will be re q uire d t o re mai n i n t he cli nic t o o bser ve d f or s pecific peri o ds of ti me 
d uri n g t he first c y cle (see Secti o n 4. 1 f or details).
G ui da nce is pr o vi de d bel o w ( Secti o n 8 ) f or ma na ge me nt of treat me nt relate d a d verse e ve nts. 
G ui da nce f or e val uati o n of I njecti o n Site T olera bilit y  is pr o vi de d i n Secti o n Injecti o n Site 
T olera bilit y  Assess me nt ( S C O nl y) (Secti o n 8. 1. 7 ). Treat me nt-relate d A Es are all c o nsi dere d 
t o xicities e xce pt t h ose t hat are clearl y n ot relate d t o P F- 0 7 0 6 2 1 1 9 (e g, disease pr o gressi o n, 
e n vir o n me ntal, u nrelate d tra u ma, etc). Treat me nt relate d t o xicities i ncl u de a n y  e ve nt 
c o nsi dere d relate d, pr o ba bl y  relate d, or p ossi bly relate d t o P F - 0 7 0 6 2 1 1 9.
6. 1. 1. 2. P F -0 6 8 0 1 5 9 1
I n t he i n vesti gati o nal c o m bi nati o n t hera p y wit h P F-0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1 3 0 0 m g
( 5 0 m g/ m L ), will be a d mi nistere d S C Q 4 W t o t he a b d o me n. P F -0 6 8 0 1 5 9 1 s h o ul d be 
a d mi nistere d t o 2 or m ore differ e nt q ua dra nts of t he a b d o me n ( wit h prefere nce gi ve n t o t he 
l o wer q ua dra nts w he n p ossi ble); 1 or 2 i njecti o ns per q ua dra nt. 
I njecti o ns t o t he a b d o me n are preferre d. If S C i njecti o ns i n t he a b d o mi nal l ocati o n are n ot 
p ossi ble, S C i njecti o ns ca n be a d mi niste re d i n a distri b ute d ma n ner i n t he t hi g hs after 
disc ussi o n a n d a gree me nt bet wee n i n vesti gat or a n d t he S p o ns or. S C i njecti o ns i n t he u p per 
e xtre mities (e g, delt oi d, u p per a n d l o wer ar m) are n ot per mitte d.
P F -0 6 8 0 1 5 9 1 S C i njecti o n will be a d mi nistere d at lea st 3 0 mi n utes after a d mi nistrati o n of 
P F - 0 7 0 6 2 1 1 9. A d diti o nal g ui da nce o n s u bc uta ne o us i njecti o n site l ocati o ns is pr o vi de d i n
Secti o n 1 0. 2 0 . F or s pecific i nstr ucti o ns o n t he ha n dli n g a n d pre parati o n i nstr ucti o ns of st u d y  
dr u g, refer t o t he Pr o d uct S pecific I n vesti gati o nal Pr o d uct (I P) Ma n ual.
6. 1. 1. 3. Be v aciz u m a b -Pfizer
F or partici pa nts treate d wit h t he i n vesti gati o nal t hera p y  wit h P F-0 7 0 6 2 1 1 9,
be vaciz u ma b - Pfizer will be s u p plie d as 1 0 0 m g/ 4 m L  ( 2 5 m g / m L) or 4 0 0 m g/ 1 6 m L  
( 2 5 m g/ m L) i n a si n gle d ose vial. T he necessar y  a m o u nt of be vaciz u ma b- Pfizer s h o ul d be 
wit h dra w n, base d o n 5 m g / k g of b o dy wei g ht, a n d dil ute d i n a t otal v ol u me of 1 0 0 m L  of 
0. 9 % s o di u m c hl ori de s ol uti o n. T he first i nf usi o n of t he dil ute d s ol uti o n s h o ul d be 
a d mi nistere d wit h a n i nf usi o n p u m p o ver 9 0 mi n utes. T he sec o n d i nf usi o n s h o ul d be 
a d mi nistere d o ver 6 0 mi n utes if t he first i nf usi o n is well t olerate d. All s u bse q ue nt i nf usi o n s 
s h o ul d be a d mi nistere d o ver 3 0 mi n utes if t he sec o n d i nf usi o n a d mi nistere d o ver 6 0 mi n utes 
is well t olerate d. Be vaciz u ma b-Pfizer I V i nf usi o n will be a d mi nistere d at least 3 0 mi n utes 
after a d mi nistrati o n of P F - 0 7 0 6 2 1 1 9. F or s pecific i nstr ucti o ns o n t he ha n dli n g a n d 
pre parati o n i nstr ucti o ns of st u d y  dr u g, refer t o t he Pr o d uct S pecific I P Ma n ual. Partici pa nts 
pla n ne d t o recei ve P F -0 7 0 6 2 1 1 9 i n c o m bi nati o n wit h be vaciz u ma b -Pfizer s h o ul d be wei g he d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 1
wit hi n 7 2 h o urs pri or t o d osi n g f or e ver y  c ycle t o e ns ure t he y di d n ot e x perie nce eit her a 
wei g ht l oss or gai n > 1 0 % fr o m t he pri or wei g ht use d t o calc ulate t he a m o u nt of 
be vaciz u ma b - Pfizer re q uire d f or d ose pre parati o n. Decisi o n t o recalc ulate 
be vaciz u ma b -Pfizer d ose base d o n t he wei g ht o btai ne d at eac h c y cle ca n be i n acc or da nce 
wit h i nstit uti o nal practice, h o we ver if t he partici pa nt e x perie nce d eit her a wei g ht l oss or gai n 
> 1 0 % c o m pare d t o t he wei g ht use d t o calc ulate eit her t he i nitial or pre vi o us d ose, t he a m o u nt 
of be vaciz u ma b -Pfizer re q uire d f or pre parati o n a n d a d mi nistrati o n f or t he c urre nt c y cle m ust 
be recalc ulate d usi n g t his m ost rece nt wei g ht o btai ne d.
All partici pa nts recei vi n g be vaciz u ma b -Pfizer will re q uire a pr otei n uria assess me nt ( di pstic k 
is acce pta ble) pri or t o eac h d ose of be vaciz u ma b-Pfizer f or t he d urati o n of t he st u d y . If 
uri nal y sis de m o nstrates pr otei n greater t ha n or e q ual t o 2 +, t he n a 2 4-h o ur uri ne pr otei n 
c ollecti o n s h o ul d f oll o w. I n partici pa nts wit h pr otei n uria greater t ha n or e q ual t o 2 gra ms per 
2 4 h o urs, be vaciz u ma b -Pfizer s h o ul d be hel d u ntil rec o ver y  (less t ha n 2 gra ms per 2 4 h o urs). 
Disc o nti n ue be vaciz u ma b -Pfizer i n partici pa nts t hat de vel o p ne p hr otic s y n dr o me.
6. 2. Pre p ar ati o n/ H a n dli n g/ St or a ge/ Acc o u nt a bilit y
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve be e n 
mai ntai ne d d uri n g tra nsit f or all st u d y  i nter ve nti o ns recei ve d a n d a n y discre pa ncies are 
re p orte d a n d res ol ve d bef ore use of t he st u d y i nter ve nti o n, as a p plica ble f or 
te m perat ure-m o nit ore d s hi p me nts.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y a ut h orize d 
site staff ma y s u p pl y or a d mi nister st u d y i nter ve nti o n. All st u d y i nter ve nti o ns m ust be st ore d 
i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mate d rec or di n g) area 
i n acc or da nce wit h t he la bele d st ora ge c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d 
a ut h orize d site staff. At a mi ni m u m, dail y  mi ni m u m a n d ma xi m u m te m perat ures f or all site 
st ora ge l ocati o ns m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da ys 
m ust i n dicate t he mi ni m u m a n d ma xi m u m te m perat ure si nce pre vi o usly d oc u me nte d f or all 
site st ora ge l ocati o ns u p o n ret ur n t o b usi ness.
T he i n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or st u dy i nter ve nti o n acc o u nta b ilit y, rec o nciliati o n, a n d rec or d mai nte na nce 
(ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). All st u d y i nter ve nti o ns will be 
acc o u nte d f or usi n g a st u d y  i nter ve nti o n acc o u nta bilit y f or m/rec or d. 
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  i nter ve nti o ns are 
pr o vi de d i n t he I P ma n ual.
A n y  st ora ge c o n diti o ns state d i n t he S R S D will be s u perse de d b y t he st ora ge c o n diti o ns 
state d o n t he pr o d uct la bel.
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners a n d i n acc or da nce wit h t he 
la bels. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 2
See t he I P Ma n ual, or e q ui vale nt f or st ora ge c o n diti o ns of t he st u d y i nter ve nti o n o nce 
rec o nstit ute d a n d/ or dil ute d.
De viati o ns fr o m t he st ora ge re q uire me nts, i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d 
a n d re p orte d t o Pfizer u p o n disc o ver y. T he site s h o ul d acti vel y p urs ue o pti o ns f or ret ur ni n g 
t he st u d y i nter ve nti o n t o t he st ora ge c o n diti o ns descri be d o m t he la beli n g, as s o o n as 
p ossi ble. O nce a n e xc ursi o n is i de ntifie d, t he st u d y i nter ve nti o n m ust be q uara nti ne d a n d n ot 
use d u ntil Pfizer pr o vi des per missi o n t o use t he st u d y  i nter ve nti o n. It will n ot be c o nsi dere d a 
pr ot oc ol de viati o n if Pfizer a p pr o ves t he use of t he st u d y  i nter ve nti o n after t he te m perat ure 
e xc ursi o n. Use of t he st u d y i nter ve nti o n pri or t o Pfizer a p pr o val will be c o nsi dere d a pr ot oc ol 
de viati o n.
S pecific details re gar di n g t he defi niti o n of a n e xc ursi o n a n d i nf or mati o n t he site s h o ul d 
re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he IP ma n ual.
T he s p o ns or or desi g nee will pr o vi de g ui da nce o n t he destr ucti o n of u n use d st u d y  
i nter ve nti o n (e g, at t he site). If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti gat or site, 
t he i n vesti gat or m ust e ns ure t hat t he materials are destr o ye d i n c o m plia nce wit h a p plica ble 
e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti o ns pr o vi de d b y 
Pfizer, a n d all destr ucti o n m ust be a de q uatel y d oc u me nte d.
6. 3. Pre p ar ati o n a n d Dis pe nsi n g
Detaile d i nstr ucti o ns f or P F -0 7 0 6 2 1 1 9  o n h o w t o pre pare t he st u d y  i nter ve nti o n f or 
a d mi nistrati o n are pr o vide d i n t he c urre nt I P Ma n ual. I n vesti gati o nal pr o d uct s h o ul d be 
pre pare d a n d dis pe nse d b y  a n a p pr o priately q ualifie d a n d e x perie nce d me m ber of t he st u d y 
staff (e g, p hys icia n, n urse, p h ysicia n’s assista nt, n urse practiti o ner, p har mac y 
assista nt/tec h nicia n, or p har macist) as all o we d b y l ocal, state, a n d i nstit uti o nal g ui da nce.
See t he I P ma n ual f or i nstr ucti o ns o n h o w t o pre pare P F -0 6 8 0 1 5 9 1 a n d be vaciz u ma b -Pfizer 
f or a d mi nistrati o n. P F-0 6 8 0 1 5 9 1 a n d be vaciz u ma b -Pfizer s h o ul d be pre pare d a n d dis pe nse d 
b y  a n a p pr o priately q ualifie d a n d e x perie nce d me m ber of t he st u d y staff (e g, p h ys icia n, 
n urse, p h ys icia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or p har macist) 
as all o we d b y l ocal, state, a n d i nstit uti o nal g ui da nce.
All acti ve a n d dil ue nt vi als are f or si n gle use o nl y .
6. 4. Me as ures t o Mi ni mize Bi as: R a n d o miz ati o n a n d Bli n di n g
6. 4. 1. All oc ati o n t o I n vesti g ati o n al Pr o d uct/ St u d y I nter ve nti o n
D ose le vel all ocati o n will be perf or me d b y t he s p o ns or after partici pa nts ha ve gi ve n t heir 
writte n i nf or me d c o nse nt a n d ha ve c o m plete d t he necessar y  baseli ne assess me nts. T he site 
staff will fa x/e mail a c o m plete Re gistrati o n F or m t o t he desi g nate d s p o ns or st u d y tea m 
me m ber or desi g nee . T he s p o ns or will assi g n a partici pa nt i de ntificati o n n u m ber a n d s u p pl y 
t his n u m ber t o t he site. T he partici pa nt i de ntificati o n n u m ber will be use d o n all st u d y-relate d 
d oc u me ntati o n at t he site.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 3
N o partici pa nt s hall recei ve st u d y  i nter ve nti o n/st u d y treat me nt u ntil t he i n vesti gat or or 
desi g nee has recei ve d t he f oll o wi n g i nf or mati o n i n writi n g fr o m t he S p o ns or:

C o nfir mati o n of t he partici pa nt’s e nr oll me nt;

S pecificati o n of t he d ose le vel f or t hat pa rtici pa nt a n d; 

Per missi o n t o pr ocee d wit h d osi n g t he partici pa nt.
F or P art 2 of t he st u dy:
All ocati o n of partici pa nts t o treat me nt gr o u ps ma y pr ocee d t hr o u g h t he use of a n i nteracti ve 
res p o nse tec h n ol o g y (IR T) s y ste m (i nteracti ve We b-base d res p o nse [I W R]) . T he site 
pers o n nel (st u d y c o or di nat or or s pecifie d desi g nee) will be re q uire d t o ha ve a n acti ve or vali d 
acc o u nt a n d pass w or d wit h t he I R T s ys te m, e nter or select i nf or mati o n i ncl u di n g b ut n ot 
li mite d t o t he pr ot oc ol n u m ber, s pecific pr ot oc ol e ntra nce criteria i n dicate d i n t he s yste m a n d 
t he scree ni n g n u m ber. T he site pers o n nel will t he n be pr o vi de d wit h, at a mi ni m u m, a 
treat me nt assi g n me nt, ra n d o mizati o n n u m ber, a n d dis pe nsa ble u nit ( D U) or c o ntai ner n u m ber 
w he n st u d y  i nter ve nti o n/st u d y treat me nt is bein g s u p plie d via t he I R T s ys te m. T he IR T 
s yste m will pr o vi de a c o nfir mati o n re p ort c o ntai ni n g t he partici pa nt n u m ber, ra n d o mizati o n 
n u m ber, a n d D U or c o ntai ner n u m ber assi g ne d. T he c o nfir mati o n re p ort m ust be st ore d i n t he 
site’s files. I n vesti gati o nal pr o duct/st u d y  treat me nt will be dis pe nse d at t he st u d y visits as 
s u m marize d i n t he S o A . Ret ur ne d st u d y  i nter ve nti o n/st u d y treat me nt m ust n ot be re-
dis pe nse d t o t he partici pa nts.
T he st u d y  -s pecific I RT refere nce ma n ual will pr o vi de t he c o ntact i nf or mati o n a n d f urt her 
details o n t he use of t he I R T s yste m.
6. 5. St u d y I nter ve nti o n C o m pli a nce
All d oses of st u d y  i nter ve nti o n/st u d y treat me nt will be a d mi nistere d b y t he a p pr o priately 
desi g nate d st u d y  staff at t he i n vesti gat or site. 
T he site will c o m plete re q uire d d osa ge Pre parati o n Rec or d l ocate d i n t he I P ma n ual. T he use 
of t he Pre parati o n Rec or d is preferre d b ut it d oes n ot precl u de t he use of a n e xisti n g 
a p pr o priate cli nical site d oc u me ntati o n s y ste m. T he e xisti n g cli nical sites d oc u me ntati o n 
s yste m s h o ul d ca pt ure all perti ne nt/re q uire d i nf or mati o n o n t he pre parati o n a n d 
a d mi nistrati o n of t he d ose. T his ma y be use d i n place of t he Pre parati o n Rec or d after 
a p pr o val fr o m t he s p o ns or a n d/ or desi g nee.
6. 6. C o nc o mit a nt T her a p y
C o nc o mita nt treat me nt c o nsi dere d necessar y  f or t he partici pa nt’s well-bei n g ma y  be gi ve n at 
discreti o n of t he treati n g p h y sicia n. 
All c o nc o mita nt treat me nts, bl o o d pr o d ucts, as well as n o n dr u g i nter ve nti o ns 
(e g, parace ntesis) recei ve d b y partici pa nts fr o m scree ni n g u ntil t he e n d of st ud y  visit will be 
rec or de d o n t he C R F as o utli ne d i n t he data e ntr y g ui deli nes.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 4
All c o nc o mita nt treat me nts m ust be a p pr o ve d b y t he s p o ns or at st u d y e ntr y.
A ut h orize d or a p pr o ve d C O VI D -1 9 vacci nes are c o nsi dere d all o we d c o nc o mita nt 
me dicati o ns a n d sta n dar d A E c ollecti o n a n d re p orti n g pr ocesses s h o ul d be f oll o we d. T he 
ti mi n g of vacci ne d osi n g relati ve t o t he d osi n g of st u d y dr u g(s) is at t he discreti o n of t he 
i n vesti gat or, alt h o u g h it ma y best t o a v oi d t he 7 da ys pri or t o C 1 D 1 a n d t he D L T o bser vati o n 
peri o d, t o c o nsi der t he p ote ntial f or vacci ne -relate d a d verse e ve nts, a n d t o a d mi nister t he 
vacci ne d uri n g sc he d ule d d osi n g h oli da y s, if a p plica ble. Disc ussi o ns bet wee n t he i n vesti gat or 
a n d t he s p o ns or re gar di n g i n di vi d ual cases ma y  occ ur if f urt her clarificati o n is re q uire d.
P F -0 7 0 6 2 1 1 9 has bee n de m o nstrate d t o tra nsie ntl y  i ncrease c yt o ki ne le vels (e g, I L-6) i n vi v o 
i n m o n ke ys (als o de m o nstrate d via i n vitr o assa ys) w hic h is e x pecte d wit h C D 3-tar gete d 
bis pecifics. C y t o ki nes ha ve bee n s h o w n t o res ult i n m o dest i n hi biti o n of s o me 
c yt oc hr o me P 4 5 0 e nz y mes. T heref ore, treat me nt wit h P F- 0 7 0 6 2 1 1 9 has t he p ote ntial t o 
m o dest l y i ncrease t he e x p os ure of c o nc o mita nt me dicati o ns t hat are s u bstrates f or t hese 
e nz ymes. Ca uti o n s h o ul d be use d u p o n c o nc o mita nt use of se nsiti ve s u bstrates of c yt oc hr o me 
P 4 5 0 e nz ymes wit h narr o w t hera pe utic i n de x (e g, C Y P 3 A 4: alfe nta nil, c y cl os p ori ne, 
di h y dr oer g ota mi ne, er g ota mi ne, fe nta n yl , pi m ozi de, q ui ni di ne, sir oli m us a n d tacr oli m us; 
C Y P 2 C 9: p he n y t oi n, warfari n) es pecially d uri n g t he i nitial treat me nt c ycle.
6. 6. 1. Ot her A nti -t u m or/ A nti-c a ncer Tre at me nt 
N o a d diti o nal a nti -t u m or treat me nt will be per mitte d w hile partici pa nts are recei vi n g st u dy 
treat me nt. 
Palliati ve ra di ot hera p y o n st u d y  is per mitte d f or t he treat me nt of pai nf ul b o n y lesi o ns 
pr o vi de d t hat t he lesi o ns were k n o w n at t he ti me of st u d y  e ntr y a n d t he i n vesti gat or clearly 
i n dicates t hat t he nee d f or palliati ve ra di ot hera py i s n ot i n dicati ve of disease pr o gressi o n. I n 
vie w of t he c urre nt lac k of data a b o ut t he i nteracti o n of P F - 0 7 0 6 2 1 1 9 wit h ra di ot hera py, 
P F - 0 7 0 6 2 1 1 9 treat me nt s h o ul d be i nterr u pte d d uri n g palliati ve ra di ot hera p y, st o p pi n g 7 d a y s 
bef ore a n d res u mi n g treat me nt after rec o ver y  t o baseli ne.
6. 6. 2. S u p p orti ve C are
Palliati ve a n d s u p p orti ve care f or disease relate d s y m pt o ms ma y b e a d mi nistere d at t he 
i n vesti gat or’s discreti o n a n d acc or di n g t o t he s pecific s u p p orti ve care pr o d uct Prescri bi n g 
I nf or mati o n or t he c urre nt A merica n S ociety of Cli nical O nc ol o g y  ( A S C O) g ui deli nes.
6. 6. 2. 1. S u p p orti ve C are f or C yt o ki ne Rele ase S y n dr o me
S y m pt o ms ass ociate d wit h c y t o ki ne release sy n dr o me ( C R S) var y  greatl y a n d ma y be 
diffic ult t o disti n g uis h fr o m ot her c o n diti o ns. T he m ore c o m m o n s y m pt o ms i ncl u de fe ver, 
na usea, hea dac he, tac h yc ar dia, h y p ote nsi o n, ras h a n d s h ort ness of breat h. T he se verit y of 
s ym pt o ms ca n be mil d t o life t hreate ni n g a n d t h us t here s h o ul d be a hi g h s us pici o n f or C R S 
if t hese sy m pt o ms occ ur. T he gra di n g of C R S a n d cli nical ma na ge me nt c o nsi derati o ns are 
descri be d b y t he A S T C T c o nse ns us w or ki n g gr o u p a n d n ote d i n A p pe n di x 1 1 ( Lee et al 
2 0 1 9). 2 5  H o we ver, if l ocal sta n dar d of care f or C R S ma na ge me nt i n v ol ves a differe nt 
re gi me n t he n t hese g ui delines s h o ul d be c o nsi dere d a n d p ote ntiall y  utilize d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 5
T he decisi o n t o i nc or p orate a n d/ or c ha n ge t he pre me dicati o n strate g y  (see Secti o n 6. 1. 1 ) f or 
C R S pr o p h y la xis i n all partici pa nts will be ma de f oll o wi n g disc ussi o ns bet wee n t he s p o ns or 
a n d t he i n vesti gat ors. 
6. 6. 2. 2. S u p p orti ve C are f or I nf usi o n -Rel ate d Re acti o ns
A n I R R is c haracterize d b y  fe ver a n d c hills, a n d less c o m m o nl y h yp ote nsi o n, eit her 
e x perie nce d b y a partic ular part ici pa nt or if see n i n ot her partici pa nts, pretreat me nt 
me dicati o n s h o ul d be a d mi nistere d t o re d uce t he i nci de nce a n d se verit y . In t he e ve nt of 
i nf usi o n relate d reacti o ns, In vesti gat ors s h o ul d i nstit ute treat me nt meas ures acc or di n g t o best 
me dical a n d n ursi n g practice. A l ocal sta n dar d of care f or t he ma na ge me nt of I R R s h o ul d be 
utilize d.
6. 6. 2. 3. S u p p orti ve C are f or H y perse nsiti vit y Re acti o ns T y pes 1 a n d 3
T y pe 1 h y perse nsiti vit y  or aller gic (e g, s h ort ness of breat h, urticaria, a na p h yla xis, 
a n gi oe de ma) reacti o ns are t he oreticall y  p ossi ble i n res p o nse t o a n y i njecte d pr otei n. Im m u ne 
c o m ple x me diate d T ype 3 h y perse nsiti vit y  reacti o ns are si milar t o t he A Es of T yp e 1 
reacti o ns b ut are li kely t o be d ela ye d fr o m t he ti me of i nf usi o n a n d ma y  i ncl u de s ym pt o ms 
s uc h as ras h, urticaria, p ol yart hritis, m yal gia, p ol ys y n o vitis, fe ver, a n d, if se vere, 
gl o mer ul o ne p hritis.
All partici pa nts s h o ul d be cl osel y o bser ve d w hile recei vi n g st u d y i nter ve nti o n/st u d y  
treat me nt i nf usi o ns a n d m o nit ori n g f or cli nical si g ns of a s ys te mic reacti o n will c o nti n ue 
t hereafter f or cli nical si g ns of aller gic reacti o ns/ h yperse nsiti vit y .
I n t he case of a hy p erse nsiti vit y reacti o n, t he partici pa nt will be treate d sy m pt o maticall y  wit h 
s u p p orti ve care, f urt her m o nit ori n g, a n d treat me nt wit h a nti-hista mi nes a n d/ or 
c ortic oster oi ds. St u d y i nf usi o ns ma y be st o p pe d, a n d t he partici pa nt will be f oll o we d u ntil t he 
e n d of t he st u d y.
6. 6. 2. 4. S u p p orti ve C are f or I m m u ne -Rel ate d A d verse E ve nts
F or i m m u n ot hera pe utic a ge nts, treat me nt of i m m u ne- relate d a d verse e ve nts (ir A Es) is mai nl y 
de pe n de nt u p o n se verit y ( N CI C T C A E gra de v 5. 0). I n ge neral, Gra de 1 or 2 ir A Es are treate d 
s ym pt o maticall y a n d persiste nt Gra de 2, 3, or 4 ir A Es are treate d wit h m o derate t o hi g h
d oses of c ortic oster oi ds.
Treat me nt of ir A Es s h o ul d f oll o w g ui deli nes as s u m marize d i n A p pe n di x 1 3 .
6. 6. 3. He m at o p oietic Gr o wt h F act ors
Pri mar y  pr o p h ylactic use of gra n ul oc yte-c ol o n y sti m ulati n g fact ors is n ot per mitte d d uri n g 
t he first 2 8 d a y s of Cycle 1 f or c o h orts wit h o ut a pri mi n g d ose a n d t he first 4 2 da y s ( C 2 D 1 5) 
f or c o h orts wit h a pri mi n g d ose, b ut t he y ma y be use d t o treat treat me nt e mer ge nt 
ne utr o pe nia as i n dicate d b y  t he c urre nt A merica n S ociet y of Cli nical O nc ol o g y ( A S C O) 
g ui deli nes or l ocal re gi o nal g ui deli nes. D uri n g scree ni n g wi n d o w ( 2 8 da y s pri or t o Da y 1), 
G C S F is n ot per mitte d t o q ualif y a partici pa nt wit h l o w W B C c o u nts.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 6
Er y t hr o p oieti n ma y be use d at t he i n vesti gat or’s discreti o n f or t he s u p p orti ve treat me nt of 
a ne mia ( N ote: er yt hr o p oieti n is n ot a p pr o ve d f or a ne mia ca use d b y c he m ot hera p y i n all l ocal 
re gi o ns, n or is it c urre ntl y a p pr o ve d i n Ja pa n).
6. 6. 4. A nti -Di arr he al, A nti -E metic T her a p y 
Pri mar y  pr o p h yla xis be y o n d t he rec o m me n de d pre me dicati o n f or t he first c ycle (see 
Secti o n 6. 1. 1 ) is at t he i n vesti gat or’s discreti o n. T he c h oice of t he pr o p hyl actic dr u g as well 
as t he d urati o n of treat me nt is u p t o t he i n vesti gat or wit h s p o ns or a p pr o val ass u mi n g t here is 
n o k n o w n or e x pecte d dr u g- dr u g i nteracti o n a n d the dr u g is n ot pr o hi bite d i n t he 
C o nc o mita nt T hera p y secti o n.
Dia rr hea has bee n o bser ve d i n partici pa nts recei vi n g P F -0 7 0 6 2 1 1 9. (see Secti o n 2. 2. 8. 1 ). 
Earl y i de ntificati o n a n d i nter ve nti o n is critical f or t he o pti mal ma na ge me nt of diarr hea. A t 
t he first si g n of l o ose st o ols, partici pa nts s h o ul d be i nstr ucte d t o start a nti-diarr heal t hera p y
(e g, l o pera mi de 4 m g i nitial d ose f oll o we d b y  2 m g after e ver y s u bse q ue nt l o ose st o ol wit h 
n o m ore t ha n 1 6 m g dail y ), i ncrease oral fl ui ds, a n d n otif y t he pri nci pal i n vesti gat or f or 
f urt her i nstr ucti o ns a n d a p pr o priate f oll o w u p. Partici pa nts s h o ul d be e nc o ura ge d t o i ncrease 
oral fl ui ds. 
I n ge neral, ma na ge me nt of ca ncer treat me nt-i n d uce d diarr hea has bee n descri be d ( Be ns o n et 
al, 2 0 0 4). 7 I nitial ma na ge me nt f or mil d t o m o derate diarr hea ma y i ncl u de dietar y 
m o dificati o ns (eli mi nati n g lact ose a n d ot her hi g h -os m olar dietar y  s u p ple me nts), l o pera mi de 
or di p he n o x yl ate/atr o pi ne, al o n g wit h oral a nti bi otics if persiste nt wit h c o ncer n f or i nfecti o n. 
Ma na ge me nt of hi g her se verit y  or m ore c o m plicate d diarr hea ma y als o i ncl u de c o nsi derati o n 
of i ntra ve n o us fl ui ds f or h y drati o n, electr ol yt e re place me nt, octre oti de, st o ol w or k u p al o n g 
wit h h os pitalizati o n f or o bser vati o n a n d treat me nt if i n dicate d i n t he i n vesti gat or’s me dical 
j u d ge me nt. 
I n a d diti o n, ma na ge me nt of diarr hea as descri be d i n s u p p orti ve care f or i m m u ne-relate d 
a d verse e ve nts f or diarr hea ( A p pe n di x 1 3 ) ma y als o be c o nsi dere d if t he cli nical i m pressi o n 
of t he eti ol o g y  of diarr hea is ass ociate d wit h i m m u ne d ysf u ncti o n.
6. 6. 5. A nti -I nfl a m m at or y T her a p y
A nti- i nfla m mat or y or narc otic a nal gesic ma y be offere d as nee de d ass u mi n g t here is n o 
k n o w n or e x pecte d dr u g- dr u g i nteracti o n a n d ass u mi n g t he dr u g is n ot i ncl u de d i n 
Secti o n 6. 6 .
6. 6. 6. C ortic oster oi ds 
C hr o nic s y ste mic c ortic oster oi d use (pre d nis o ne > 1 0 m g/ da y  or e q ui vale nts) f or palliati ve or 
s u p p orti ve p ur p oses is n ot per mitte d. H o we ver, s yste mic c ortic oster oi d use at a lo w d ose f or 
a s h ort d urati o n (e g, 5 m g  Q D of pre d nis o ne, f or 2 wee ks) as s y m pt o matic treat me nt o n 
i n di vi d ual basis a n d u p o n disc ussi o n wit h t he s p o ns or. Ac ute e mer ge nc y  a d mi nistrati o n, 
t o pical a p plicati o ns, i n hale d s pra ys, e ye dr o ps, or l ocal i njecti o ns of c ortic oster oi ds are 
all o we d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 7
6. 6. 7. S ur ger y 
Ca uti o n is a d vise d o n t he oretical gr o u n ds f or a n y s ur gical pr oce d ures d uri n g t he st u d y. T he 
a p pr o priate i nter val of ti me bet wee n s ur ger y  a n d P F-0 7 0 6 2 1 1 9 re q uire d t o mi ni mize t he ris k 
of i m paire d w o u n d heali n g a n d blee di n g has n ot bee n deter mi ne d. St o p pi n g P F - 0 7 0 6 2 1 1 9 
a n d/ or P F-0 6 8 0 1 5 9 1 is rec o m me n de d at least 7 da y s pri or t o s ur ger y. P ost o perati vely, t he 
decisi o n t o rei nitiate P F- 0 7 0 6 2 1 1 9 treat me nt s h o ul d be base d o n a cli nical assess me nt of 
satisfact or y w o u n d heali n g a n d rec o ver y fr o m s ur ger y.
I n t he setti n g of be vaciz u ma b-Pfizer use as part of i n vesti gati o nal c o m bi nati o n t hera p y , 
be vaciz u ma b -Pfizer s h o ul d be disc o nti n ue d f or at least 2 8 da y s pri or t o electi ve s ur ger y. 
Als o, d o n ot a d mi nister be vaciz u ma b -Pfizer f or at least 2 8 da ys f oll o wi n g s ur ger y a n d u ntil 
t he w o u n d is f ull y heale d.
6. 6. 8. Resc ue Me dici ne
T here is n o resc ue t hera p y t o re verse t he A Es o bser ve d wit h P F- 0 7 0 6 2 1 1 9 ; sta n dar d me dical 
s u p p orti ve care m ust be pr o vi de d t o ma na ge t he A Es.
6. 7. D ose M o dific ati o n 
E ver y  eff ort s h o ul d be ma de t o a d mi nister st u d y i nter ve nti o n/st u d y treat me nt o n t he pla n ne d 
d ose a n d sc he d ule. I n t he e ve nt of si g nifica nt t o xicit y, w hic h ma y i ncl u de a D L T, d osi n g ma y 
be dela y e d, re d uce d a n d/ or disc o nti n ue d as descri be d bel o w a n d i n Secti o ns 6. 7. 1 , 6. 7. 2 a n d 
6. 7. 3 . Partici pa nts e x perie nci n g a D L T ma y  res u me d osi n g at t he ne xt l o wer d ose level (if 
a p plica ble) o nce a de q uate rec o ver y  is ac hie ve d, a n d i n t he o pi ni o n of t he i n vesti gat or a n d 
s p o ns or, t he partici pa nt is be nefiti n g fr o m t hera p y. In t he e ve nt of m ulti ple t o xicities, d ose 
m o dificati o n s h o ul d be base d o n t he w orst t o xicit y  o bser ve d (an d attri b uti o n f or t he 
c o m bi nati o n treat me nt i n Part 1 B a n d Part 2). Partici pa nts are t o be i nstr ucte d t o n otif y  
i n vesti gat ors at t he first occ urre nce of a ny a d verse s ym pt o m.
D ose m o dificati o ns ma y  occ ur i n o ne of t hree wa ys:

Wit hi n a c y cle: d osi n g i nterr upti o n u ntil a de q uate rec o ver y  a n d d ose re d ucti o n, if 
re q uire d, d uri n g a gi ve n treat me nt c ycle; 

Bet wee n c y cles: ne xt c ycle a d mi nistrati o n ma y be dela ye d d ue t o persisti n g t o xicit y 
w he n a ne w c y cle is d ue t o start;

I n t he ne xt c ycle: d ose re d ucti o n ma y be re q uire d i n a s u bse q ue nt c ycle base d o n 
t o xicit y e x perie nce d i n t he pre vi o us c ycle.
6. 7. 1. D osi n g I nterr u pti o ns
Wit h res pect t o st u d y  i nter ve nti o n or i n vesti gati o nal c o m bi nati o n t hera p y, partici pa nts 
e x perie nci n g Gra de 3 or 4 p ote ntiall y  treat me nt relate d t o xicity or i nt olera ble Gra de 2 
t o xicit y des pite s u p p orti ve care s h o ul d ha ve t heir treat me nt i nterr u pte d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 8
C o m bi nati o n t hera p y  wit h i m m u ne o nc ol o g y c o m p o u n ds ma y a u g me nt ir A Es, p ne u m o nitis, 
c olitis, creati ni ne, a n d li ver f u ncti o n test ( L F T) ele vati o n s h o ul d be m o n it ore d caref ully wit h 
t his class of a ge nts. T o facilitate t he early rec o g niti o n a n d pr o m pt i nter ve nti o n of cli nicall y 
rele va nt A Es relate d t o st u d y treat me nt, ma na ge me nt al g orit h ms ha ve bee n de vel o pe d f or 
s us pecte d p ul m o nar y, gastr oi ntesti nal, li ver, e n d ocri ne, s ki n, car diac, re nal, or ot her 
i m m u ne-relate d t o xicities (see A p pe n di x 1 3 ).
All partici pa nts recei vi n g be vaciz u ma b -Pfizer will re q uire a pr otei n uria assess me nt ( di pstic k 
is acce pta ble) pri or t o eac h d ose of be vaciz u ma b -Pfizer f or t he d urati o n of t he st u d y . If 
uri nal y sis de m o nstrates pr otei n greater t ha n or e q ual t o 2 +, t he n a 2 4-h o ur uri ne pr otei n 
c ollecti o n s h o ul d f oll o w. I n partici pa nts wit h pr otei n uria greater t ha n or e q ual t o 2 gra ms per 
2 4 h o urs, be vaci z u ma b-Pfizer s h o ul d be hel d u ntil rec o ver y  (less t ha n 2 gra ms per 2 4 h o urs). 
Disc o nti n ue be vaciz u ma b -Pfizer i n partici pa nts t hat de vel o p ne p hr otic s y n dr o me.
A p pr o priate f oll o w- u p assess me nts s h o ul d be d o ne u ntil a de q uate rec o ver y occ urs as 
assesse d b y t he i n vesti gat or. Criteria re q uire d bef ore treat me nt ca n res u me are descri be d i n 
t he D ose Dela y s secti o n.
D oses ma y  be hel d u p t o 4 wee ks u ntil t o xicit y  res ol uti o n. De pe n di n g o n w he n t he a d verse 
e ve nt res ol ve d, a treat me nt i nterr u pti o n ma y  lea d t o t he partici pa nt missi n g all s u bse q ue nt 
pla n ne d d oses wit hi n t hat sa me c y cle or e ve n t o dela y t he i nitiati o n of t he s u bse q ue nt c ycle.
If t he a d verse e ve nt t hat le d t o t he treat me nt i nterr u pti o n rec o vers wit hi n t he sa me c ycle, t he n 
re-d osi n g i n t hat c y cle is all o we d. D oses o mitte d f or t o xicit y are n ot re place d wit hi n t he sa me 
c ycle. T he nee d f or a d ose re d ucti o n at t he ti me of treat me nt res u m pti o n s h o ul d be base d o n 
t he criteria defi ne d i n t he D os e Re d ucti o ns secti o n, u nless e x pressl y a gree d ot her wise 
f oll o wi n g disc ussi o n bet wee n t he i n vesti gat or a n d t he s p o ns or. 
I n t he e ve nt of a treat me nt i nterr u pti o n f or reas o ns ot her t ha n treat me nt -relate d t o xicit y 
(e g, electi ve s ur ger y) lasti n g > 4 wee ks, treat me nt res u m pti o n will be deci de d i n c o ns ultati o n 
wit h t he s p o ns or.
6. 7. 1. 1. D ose I nterr u pti o n of P artici p a nts wit h Pres u me d or Acti v e 
C O VI D -1 9/ S A R S -C o V 2 I nfecti o n
O n g oi n g partici pa nts w h o ha ve acti ve (c o nfir me d p ositi ve [ b y  re g ulat or y a ut h orit y-a p pr o ve d 
test] or pres u me d test [ pe n di n g/cli nical s us pici o n]) S A R S-C o V 2 i nfecti o n, s h o ul d f oll o w t he 
treat me nt g ui deli nes bel o w:

F or s y m pt o mati c partici pa nts wit h acti ve S A R S- C o V 2 i nfecti o n, i n vesti gati o nal 
treat me nt s h o ul d be dela ye d f or at least 1 4 da ys fr o m start of s ym pt o ms. T his dela y  is 
i nte n de d t o all o w res ol uti o n of s ym pt o ms of S A R S -C o V 2 i nfecti o n.

Pri or t o restarti n g treat me nt, t he parti ci pa nt s h o ul d be afe brile f or 7 2 h o urs a n d 
S A R S -C o V 2 -relate d sy m pt o ms s h o ul d ha ve rec o vere d t o Gra de ≤1 f or a mi ni m u m of 
7 2 h o urs. T he s p o ns or s h o ul d be i nf or me d w he n restarti n g treat me nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 7 9

C o nti n ue t o c o nsi der p ote ntial dr u g -dr u g i nteracti o ns f or a n y  c o nco mita nt me dicati o n 
a d mi nistere d f or treat me nt of S A R S -C o V 2 i nfecti o n.
M ore i nf or mati o n o n C O VI D- 1 9 is pr o vi de d i n A p pe n di x 1 8 .
6. 7. 2. D ose Del a ys
Re -treat me nt f oll o wi n g treat me nt i nterr u pti o n f or treat me nt-relate d t o xicit y or at t he start of 
a n y ne w c ycle ma y n ot occ ur u ntil all of t he f oll o wi n g para meters ha ve bee n met:

A N C 1, 0 0 0/ m m 3.

Platelets c o u nt 5 0, 0 0 0/ m m 3.

N o n he mat ol o gic t o xicities ha ve ret ur ne d t o baseli ne or Gra de 1 se verit y  ( or, at t he 
i n vesti gat or’s discreti o n, Gra de 2 if n ot c o nsi dere d a safet y ris k f or t he partici pa nt).
If a treat me nt dela y  res ults fr o m w orse ni n g of he mat ol o gic or bi oc he mical para meters, t he 
fre q ue nc y of rele va nt bl o o d tests s h o ul d be i ncrease d as cli nically i n dicate d.
If t hese c o n diti o ns are met wit hi n 4 wee ks of treat me nt i nterr u pti o n, P F -0 7 0 6 2 1 1 9 ma y  be 
res u me d. Refer t o t he D os e Re d ucti o ns secti o n f or a d verse e ve nts re q uiri n g d ose re d ucti o n at 
t he ti me of treat me nt res u m pti o n.
If partici pa nts re q uire disc o nti n uati o n of P F -0 7 0 6 2 1 1 9 f or m ore t ha n 4 wee ks at a n y ti me 
d uri n g t he st u d y, t he n st u d y treat me nt s h o ul d be per ma ne ntl y disc o nti n ue d, u nless t he 
i n vesti gat or’s be nefit/ris k assess me nt s u g gests ot her wise after disc ussi o n wit h t he S p o ns or’s 
me dical m o nit or. 
If a treat me nt i nterr u pti o n c o nti n ues be yo n d Da y  2 8 of t he c urre nt c y cle, t he n t he da y w he n 
treat me nt is restarte d will be c o u nte d as Da y 1 of t he ne xt c ycle.
6. 7. 3. D os e Re d ucti o ns
F oll o wi n g d osi n g i nterr u pti o n or c y cle dela y d ue t o t o xicit y, t he P F-0 7 0 6 2 1 1 9 d ose ma y  nee d 
t o be re d uce d w he n treat me nt is res u me d.
N o s pecific d ose a dj ust me nts are rec o m me n de d f or Gra de 1/ 2 treat me nt -relate d t o xicit y. 
H o we ver, i n vesti gat ors s h o ul d al wa ys ma na ge t heir partici pa nts acc or di n g t o t heir me dical 
j u d g me nt base d o n t he partic ular cli nical circ u msta nces.
F or n o n -i m m u ne-relate d t o xicities, t o xicities n ot ot her wise s pecifie d i n Ta ble 1 1 , a n d 
i m m u ne-relate d t o xicities, d ose re d ucti o n of P F -0 7 0 6 2 1 1 9 b y  1 a n d, if nee de d, 2 d ose le vels 
will be all o we d de pe n di n g o n t he t y pe a n d se verit y of t o xicit y e nc o u ntere d a n d base d o n t he 
dis creti o n of t he i n vesti gat or a n d i n c o m m u nicati o n wit h t he s p o ns or. Partici pa nts re q uiri n g 
m ore t ha n 2 d ose re d ucti o ns will be disc o nti n ue d fr o m t he treat me nt a n d e ntere d i nt o t he 
f oll o w-u p p hase, u nless ot her wise a gree d bet wee n t he i n vesti gat or a n d t he s p o ns or . 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 0
F or i n vesti gati o nal c o m bi nati o n t hera p y, d ose m o dificati o ns, dela y s or i nterr u pti o ns s h o ul d 
be assi g ne d t o eac h pr o d uct base d o n attri b uti o n t o eac h c o m p o ne nt (ie, w he n c o m p o u n d 
A a n d B are c o m bi ne d, a n d t o xicit y occ urs a n d is attri b ute d t o c o m p o u n d A, a d ose l o weri n g, 
dela y , or i nterr u pti o n of c o m p o u n d A ma y be a p plica ble b ut n ot necessaril y t o c o m p o u n d B). 
If i n t he i n vesti gat or’s me dical j u d ge me nt, a t o xicit y lea di n g t o d ose i nterr u pti o n or dela y is 
attri b ute d t o t he c o m bi nati o n a ge nt ( eit her P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pfizer), a n d 
treat me nt wit h P F- 0 7 0 6 2 1 1 9 al o ne is e x pecte d t o deri ve cli nical be nefit, t he n t he treat me nt 
wit h P F -0 7 0 6 2 1 1 9 ma y  be res u me d at t he sa me or re d uce d d ose le vel (acc or di n g t he ta bles 
bel o w) wit h disc o nti n uati o n of t he c o m b i nati o n a ge nt f oll o wi n g disc ussi o n a n d a gree me nt 
wit h t he S p o ns or.
F or n o n -i m m u ne-relate d t o xicities s pecifie d i n Ta ble 1 1 : In t he setti n g of i n vesti gati o nal 
c o m bi nati o n t hera p y wit h P F -0 7 0 6 2 1 1 9 a n d c o m bi nati o n a ge nt (eit her P F -0 6 8 0 1 5 9 1 or 
be vaciz u ma b -Pfizer), disc o nti n uati o n, b ut n o d ose re d ucti o n f or t he c o m bi na ti o n a ge nt 
(eit her P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pfizer), is all o we d. All d ose 
disc o nti n uati o ns/ m o dificati o ns/a dj ust me nts m ust be clearl y  d oc u me nte d i n t he partici pa nt’s 
s o urce n otes a n d C R F.
F or i m m u ne -relate d t o xicities s pecifie d i n Ta ble 1 2 : In t he setti n g of i n vesti gati o nal 
c o m bi nati o n t hera p y wit h P F -0 7 0 6 2 1 1 9 a n d c o m bi nati o n a ge nt (eit her P F -0 6 8 0 1 5 9 1 or 
be vaciz u ma b -Pfizer), disc o nti n uati o n, b ut n o d ose r e d ucti o n f or t he c o m bi nati o n a ge nt 
(eit her P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pfizer), is all o we d de pe n di n g o n t he t o xicit y  a n d 
se verity. All d ose disc o nti n uati o ns/ m o dificati o ns/a dj ust me nts m ust be clearl y d oc u me nte d i n 
t he partici pa nt’s s o urce n otes a n d C R F.
O nce a d ose has bee n re d uce d f or a gi ve n partici pa nt, all s u bse q ue nt c y cles s h o ul d be 
a d mi nistere d at t hat d ose le vel, u nless f urt her d ose re d ucti o n is re q uire d. I ntra partici pa nt d ose 
re-escalati o n is n ot all o we d.
Partici pa nts e x perie nci n g a D L T ma y  res u me d osi n g at t he ne xt l o wer d ose le vel (if 
a p plica ble) o nce a de q uate rec o ver y  is ac hie ve d, a n d i n t he o pi ni o n of t he i n vesti gat or a n d 
s p o ns or, t he partici pa nt is be nefiti n g fr o m t hera py. 
I n s o me cases, partici pa nts e x perie nci n g rec urre nt a n d i nt olera ble Gra de 2 t o xicit y ma y 
res u me d osi n g at t he ne xt l o wer d ose le vel o nce rec o ver y t o Gra de ≤1 or baseli ne is 
ac hie ve d. 
St u d y  treat me nt f or partici pa nts s h o ul d i ncl u de P F -0 7 0 6 2 1 1 9 a n d n ot be li mite d t o a 
c o m bi nati o n a ge nt ( P F-0 6 8 0 1 5 9 1 or be vaciz u ma b -Pfizer) o nl y .
Rec o m me n de d d ose re d ucti o ns f or n o n-i m m u ne relate d t o xicities a n d t o xicities n ot ot her wise 
s pecifie d i n Ta ble 1 2 t hat are attri b ute d t o st u d y i nter ve nti o n or i n vesti gati o nal c o m bi nati o n 
t hera py are descri be d i n Ta ble 1 1 . D ose M o dificati o ns f or A d verse Reacti o ns relate d t o 
Be vaciz u ma b -Pfizer ca n be f o u n d bel o w i n Ta ble 1 4 .
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 1
T a ble 1 1 .
D ose M o dific ati o ns f or T o xicit y Attri b ute d t o I n vesti g ati o n al Pr o d uct or 
I n vesti g ati o n al C o m bi n ati o n T her a p y f or N o n-I m m u ne-Rel ate d A Es c
T o xicit y
Gr a de 1  
Gr a de 2
Gr a de 3
Gr a de 4
N o n he mat ol o gic 
C o nti n ue at 
t he sa me d ose 
le vel
C o nti n ue at t he 
sa me d ose le vel 

Wit h h ol d d ose u ntil 
t o xicit y is Gra de 1, 
or has ret ur ne d t o 
baseli ne, t he n res u me 
treat me nt at t he sa me 
d ose le vel or re d uce 
t he P F-0 7 0 6 2 1 1 9 
d ose b y 1 le vel a n d 
s u bse q ue ntl y a n 
a d diti o nal 1 le vel at 
t he discreti o n of t he 
in vesti gat or. a,b d

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h P F-0 6 8 0 1 5 9 1), 
P F -0 6 8 0 1 5 9 1 ma y 
res u me treat me nt at 
t he sa me d ose le vel 
or disc o nti n ue at t he 
discreti o n of t he 
in vesti gat or. a, b

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h 
be vaciz u ma b -Pfizer), 
be vaciz u ma b -Pfizer 
ma y res u me 
treat me nt at t he sa me 
d ose le vel or 
disc o nti n ue at t he 
discreti o n of t he 
i n vesti gat or.a, b

Wit h h ol d d ose u ntil 
t o xicit y is Gra de 1, 
or has ret ur ne d t o 
baseli ne, t he n re d uce 
t he P F-0 7 0 6 2 1 1 9 d ose 
b y 1 le vel a n d 
s u bse q ue ntl y a n 
a d diti o nal 1 le vel or 
disc o nti n ue at t he 
discreti o n of t he 
i n vesti gat or.a, b d

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h P F-0 6 8 0 1 5 9 1), 
disc o nti n ue 
P F -0 6 8 0 1 5 9 1. a, b

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h be vaciz u ma b-
Pfizer), disc o nti n ue 
t he be vaciz u ma b-
Pfizer d ose. a, b
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 2
T a ble 1 1 .
D ose M o dific ati o ns f or T o xicit y Attri b ute d t o I n vesti g ati o n al Pr o d uct or 
I n vesti g ati o n al C o m bi n ati o n T her a p y f or N o n-I m m u ne-Rel ate d A Es c
T o xicit y
Gr a de 1  
Gr a de 2
Gr a de 3
Gr a de 4
H e m at ol o gic
C o nti n ue at 
t he sa me d ose 
le vel
C o nti n ue at t he 
sa me d ose le vel

Wit h h ol d d ose u ntil 
t o xicit y is Gra de ≤2, 
or has ret ur ne d t o 
baseli ne, t he n res u me 
treat me nt at t he sa me 
d ose le vel at t he 
discreti o n of t he 
i n vesti gat or.a, b, d

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h P F-0 6 8 0 1 5 9 1), 
P F -0 6 8 0 1 5 9 1 ma y 
res u me treat me nt at 
the sa me d ose le vel 
or disc o nti n ue at t he 
discreti o n of t he 
i n vesti gat or.a, b

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h be vaciz u ma b-
Pfizer), be vaciz u ma b -
Pfizer ma y res u me 
treat me nt at t he sa me 
d ose le vel or 
disc o nti n ue at t he 
discreti o n of t he 
i n vesti gat or.a, b

Wit h h ol d d ose u ntil 
t o xicit y is Gra de ≤2, 
or has ret ur ne d t o 
baseli ne, t he n re d uce 
t he P F-0 7 0 6 2 1 1 9 d ose 
b y 1 le vel a n d 
s u bse q ue ntl y a n 
a d diti o nal 1 le vel at 
a n d res u me treat me nt 
at t he discreti o n of t he 
i n vesti gat or.a, b, d

A d diti o nall y, i n 
c o m bi natio n t hera p y 
( wit h P F-0 6 8 0 1 5 9 1), 
disc o nti n ue t he 
P F -0 6 8 0 1 5 9 1 d ose. a, b

A d diti o nall y, i n 
c o m bi nati o n t hera p y 
( wit h be vaciz u ma b-
Pfizer), disc o nti n ue 
t he be vaciz u ma b-
Pfizer d ose .a, b
a Na usea, v o miti n g, or diarr hea m ust persist at Gra de 3 or 4 des pite ma xi mal me dical t hera p y t o re q uire d ose 
m o dificati o n.
b C y cle will n ot be e xte n de d t o c o ver f or t he missi n g d oses.
c If t o xicit y is c o nsi dere d i m m u ne relate d t he n s h o ul d f oll o w T a ble 1 2 – D ose M o dificati o ns f or S pecific 
I m m u ne Relate d T o xicit y Attri b ute d t o I n vesti gati o nal Pr o d uct or C o m bi nati o n I n vesti gati o nal T hera p y 
(T a ble 1 2 ).
d D ose re d ucti o n of P F -0 7 0 6 2 1 1 9 ma y be re d uce d t o t he ne xt l o w er d ose le vel(s) t hat was pre vi o usl y 
deter mi ne d t o be safe/t olera ble d uri n g t he d ose escalati o n p h ase of t he st u d y.
Rec o m me n de d d ose re d ucti o ns f or i m m u ne relate d t o xicities t hat are attri b ute d t o st u d y  
i nter ve nti o n or i n vesti gati o nal c o m bi nati o n t hera p y are descri be d i n Ta ble 1 2 .
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 3
T a ble 1 2 .
D ose M o dific ati o ns f or S pecific I m m u ne Rel ate d T o xicit y Attri b ute d t o 
I n vesti g ati o n al Pr o d uct or C o m bi n ati o n I n vesti g ati o n al T her a p y
Or g a n S yste m
Gr a de 1  
Gr a de 2
Gr a de 3
Gr a de 4
GI 
( diarr hea)
C o nti n ue 
i n vesti gati o nal 
treat me nt.
Wit h h ol d 
i n vesti gati o nal 
treat me nt.
If d iarr hea 
i mpr o ves t o 
Gra de ≤1, 
res u me 
treat me nt at t he 
sa me d ose le vel.
Wit h h ol d i n vesti gati o nal 
treat me nt.
If diarr hea i mpr o ves t o 
Gra de ≤1, res u me treat me nt at 
t he sa me d ose le vel or re d uce 
P F -0 7 0 6 2 1 1 9 d ose b y 1 le vel
at t he discreti o n of t he 
i n vesti gat or.
A d diti o nall y, i n c o m bi nati o n 
t hera p y ( wit h P F-0 6 8 0 1 5 9 1), 
P F -0 6 8 0 1 5 9 1 ma y res u me 
treat me nt at t he sa me d ose 
le vel or disc o nti n ue at t he 
discreti o n of t he 
i n vesti gat or.*
A d diti o nall y, i n c o m bi nati o n 
t hera p y ( wit h be vaciz u ma b-
Pfizer), be vaciz u ma b -Pfizer 
ma y res u me treat me nt at t he 
sa me d ose le vel or 
disc o nti n ue at t he discreti o n 
of t he i n vesti gat or.*
Disc o nti n ue 
i n vesti gati o nal 
treat me nt.
S ki n
( Der matitis)
C o nti n ue 
i n vesti gati o nal 
treat me nt.
If persists > 1-2 
wee ks, wit h h ol d. 
If i m pr o ves after 
treat me nt wit h 
c ortic oster oi ds, 
t he n res u me 
i n vesti gati o nal 
treat me nt.
C o nti n ue 
i n vesti gati o nal 
treat me nt.
If persists > 1-2 
wee ks, 
wit h h ol d. If 
i mpr o ves after 
treat me nt wit h 
c ortic oster oi ds, 
t he n res u me 
i n vesti gati o nal 
treat me nt.
Wit h h ol d or disc o nti n ue 
i n vesti gati o nal treat me nt.
If i m pr o ves t o Gra de ≤1 , 
res u me i n vesti gati o nal 
t hera p y at t he discreti o n of 
t he i n vesti gat or.
Wit h h ol d or 
disc o nti n ue 
i n vesti gati o nal 
treat me nt.
If i m pr o ves t o 
Gra de 1 after 
treat me nt, 
res u me 
i n vesti gati o nal 
t hera p y at t he 
discreti o n of 
t he 
i n vesti gat or.
L u n g
( p ne u m o nitis)
C o nsi der dela y of 
i n vesti gati o nal 
treat me nt
M o nit or
Wit h h ol d 
i n vesti gati o nal 
treat me nt; re-
i ma ge.
If s y m pt o ms 
ret ur n t o 
baseli ne t he n 
res u me 
Disc o nti n ue
Disc o nti n ue
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 4
T a ble 1 2 .
D ose M o dific ati o ns f or S pecific I m m u ne Rel ate d T o xicit y Attri b ute d t o 
I n vesti g ati o n al Pr o d uct or C o m bi n ati o n I n vesti g ati o n al T her a p y
Or g a n S yste m
Gr a de 1  
Gr a de 2
Gr a de 3
Gr a de 4
i n vesti gati o nal 
treat me nt.
Li ver
( he patitis)
C o nti n ue 
i n vesti gati o nal 
treat me nt
Wit h h ol d 
i n vesti gati o nal 
treat me nt a n d 
i ncrease 
m o nit ori n g of 
tra nsa mi nases.
If tra nsa mi nases 
i mpr o ve wit h i n 
≤7 da ys t o 
Gra de ≤1 , 
res u me 
treat me nt at 
sa me d ose le vel.
If tra nsa mi nases 
d o n ot i m pr o ve 
wit hi n ≤7 da ys 
t o Gra de ≤1 , 
treat wit h 
c ortic oster oi ds
a n d re d uce d ose 
of P F -0 7 0 6 2 1 1 9
b y 1 le vel w he n 
tra nsa mi nases 
i mpr o ve t o 
Gra de ≤1.
Disc o nti n ue
Disc o nti n ue
C yt o ki ne 
Release 
S y n dr o me
H ol d 
i n vesti gati o nal 
treat me nt; after 
res ol uti o n, 
c o nti n ue 
i n vesti gati o nal 
treat me nt,
after res ol ves, 
c o nti n ue 
i n vesti gati o nal 
treat me nt
H ol d
i n vesti gati o nal 
treat me nt; after 
res ol uti o n, 
c o nti n ue 
i n vesti gati o nal 
treat me nt,
after res ol ves, 
c o nti n ue 
i n vesti gati o nal 
treat me nt
H ol d i n vesti gati o nal 
treat me nt; after res ol uti o n, 
c o nti n ue i n vesti gati o nal 
treat me nt, after res ol ves, 
re d uce d ose of P F -0 7 0 6 2 1 1 9
b y 1 le vel
Disc o nti n ue
E n d ocri ne:
T S H 
a b n or malit y
C o nti n ue i n vesti gati o nal treat me nt
S y m pt o matic 
e n d ocri n o pat h y
If s y m pt o matic, a b n or mal la bs, a b n or mal pit uitar y sca n- wit h h ol d i n vesti gati o nal 
treat me nt. After treat me nt, a n d wit h n or mal la bs a n d M RI, res u me i n vesti gati o nal 
treat me nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 5
T a ble 1 2 .
D ose M o dific ati o ns f or S pecific I m m u ne Rel ate d T o xicit y Attri b ute d t o 
I n vesti g ati o n al Pr o d uct or C o m bi n ati o n I n vesti g ati o n al T her a p y
Or g a n S yste m
Gr a de 1  
Gr a de 2
Gr a de 3
Gr a de 4
S us pici o n of 
a dre nal crisis
Wit h h ol d or disc o nti n ue i n vesti gati o nal treat me nt. If a dre nal crisis r ule d o ut, treat as f or 
s y m pt o matic e n d ocri n o pat h y.
* D ose re d ucti o n of P F -0 7 0 6 2 1 1 9 ma y be re d uce d t o t he ne xt l o w er d ose le vel(s) t hat was pre vi o usl y 
deter mi ne d t o be safe/t olera ble d uri n g t he d ose escalati o n p hase of t he st u d y.
T a ble 1 3 . D os a ge M o dific ati o ns f or A d verse Re acti o ns 
Se verit y 
D os a ge M o dific ati o n 
Gastr oi ntesti nal Perf orati o ns 
a n d Fist ulae

Gastr oi ntesti nal perf orati o n, a n y gra de 

Trac he oes o p ha geal fist ula, a n y gra de 

Fist ula, Gra de 4 

Fist ula f or mati o n i n v ol vi n g a n y 
i nter nal or ga n 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  
W o u n d Heali n g 
C o m plicati o ns 

W o u n d heali n g c o mplicati o ns 
re q uiri n g me dical i nter ve nti o n

Necr otizi n g fasciitis 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  
H e m orr ha ge 

Gra de 3 or 4 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  

Rece nt hist or y of he m o pt ysis of ½ 
teas p o o n ( 2. 5 m L) or m ore 
Wit h h ol d B E V A CI Z U M A B -
P FI Z E R  
T hr o m b oe m b olic E ve nts 

Arterial t hr o m b oe m b olis m, se vere 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  

Ve n o us t hr o m b oe m b olis m, Gra de 4 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  
H y perte nsi o n 

H y perte nsi ve crisis H y perte nsi ve 
e nce p hal o pat h y 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  

H y perte nsi o n, se vere 
Wit h h ol d B E V A CI Z U M A B -
P FI Z E R  if n ot c o ntr olle d wit h 
me dical ma na ge me nt; res u me 
o nce c o ntr olle d 
P osteri or Re versi ble 
E nce p hal o pat h y S y n dr o me 
( P R E S) 

A n y 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 6
T a ble 1 3 . D os a ge M o dific ati o ns f or A d verse Re acti o ns 
Se verit y 
D os a ge M o dific ati o n 
Re nal I nj ur y a n d Pr otei n uria 

Ne p hr otic s y n dr o me 
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R  

Pr otei n uria greater t ha n or e q ual t o 2 
gra ms per 2 4 h o urs i n a bse nce of 
ne p hr otic s y n dr o me
Wit h h ol d B E V A CI Z U M A B -
P FI Z E R  u ntil pr otei n uria less 
t ha n 2 gra ms per 2 4 h o urs
I nf usi o n-Relate d Reacti o ns 

Se vere
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R 

Cli nicall y si g nifica nt
I nterr u pt i nf usi o n; res u me at a 
decrease d rate of i nf usi o n 
after s y m pt o ms res ol ve

Mil d, cli nicall y i nsi g nifica nt 
Decrease i nf usi o n rate
C o n gesti ve Heart Fail ure 

A n y
Disc o nti n ue 
B E V A CI Z U M A B -P FI Z E R 
6. 8. I nter ve nti o n After t he E n d of t he St u d y
N o i nter ve nti o n will be pr o vi de d t o st u d y partici pa nts at t he e n d of t he st u d y .
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1. Disc o nti n u ati o n of St u d y I nter ve nti o n
See t he S o A f or data t o be c ollecte d at t he ti me of i nter ve nti o n disc o nti n uati o n a n d f oll o w- u p 
a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.
7. 1. 1. Re q uest t o C o nti n ue Tre at me nt
If t he i n vesti gat or feels t he partici pa nt is still deri vi n g be nefit fr o m treat me nt, f oll o wi n g 
disc ussi o n wit h t he s p o ns or t he partici pa nt ma y ha ve a n o pti o n t o c o nti n ue d osi n g at t he 
sa me d ose or o ne d ose l o wer, as l o n g as t he criteria bel o w are met, u ntil s uc h be nefit n o 
l o n ger e xists.
Criteria t hat m ust be met t o e ns ure t hat partici pa nts are n ot e x p ose d t o u nreas o na ble ris ks b y 
c o nti n ue d use of t he i n vesti gati o nal a ge nt i n s pite of pr o gressi o n of disease. S uc h criteria 
ma y  i ncl u de t he f oll o wi n g:

A bse nce of s y m pt o ms a n d si g ns i n dicati n g cli nicall y  si g nifica nt pr o gressi o n of 
disease.

N o decli ne i n E C O G perf or ma nce stat us.

A bse nce of s y m pt o matic ra pi d disease pr o gressi o n re q uiri n g ur ge nt me dical 
i nter ve nti o n (e g, sy m pt o matic ple ural eff usi o n, s pi nal c or d c o m pressi o n).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 7
At t he ti me of ra di o gra p hic pr o gressi o n of disease, o btai n t he re -c o nse nt of partici pa nts usi n g 
a writte n i nf or me d c o nse nt d oc u me nt t hat details all F D A -a p pr o ve d t hera p y, a n d p ote ntial 
cli nical be nefit, t hat t he partici pa nt ma y  be f ore g oi n g i n or der t o c o nti n ue recei vi n g t he st u d y 
i nter ve nti o n.
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al Fr o m t he St u d y 
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at his/ her o w n re q uest or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or f or safet y, be ha vi oral, c o m plia nce , 
or a d mi nistrati ve reas o ns.
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi ble, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d. See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d. 
T he earl y disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are ra n d o mize d a n d t he n are 
pre mat urel y wit h dra w n fr o m t he st u d y. Partici pa nts s h o ul d be q uesti o ne d re gar di n g t heir 
reas o n f or wit h dra wal. T he partici pa nt will be per ma ne ntl y  disc o nti n ue d b ot h fr o m t he st u d y 
i nter ve nti o n a n d fr o m t he st u d y at t hat ti me.
If a partici pa nt wit h dra ws fr o m t he st u d y, he/s he ma y re q uest destr ucti o n of a n y re mai ni n g 
sa m ples, b ut data alrea dy ge nerate d fr o m t he sa m ples will c o nti n ue t o be a vaila ble a n d ma y  
be use d t o pr otect t he i nte grit y  of e xisti n g a nalys es. T he i n vesti gat or m ust d oc u me nt a n y  
s uc h re q uests i n t he site st u d y rec or ds.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt (see bel o w) f or 
discl os ure of f ut ure i nf or mati o n, n o f urt her e val uati o ns s h o ul d be perf or me d, a n d n o 
a d diti o nal data s h o ul d be c ollecte d. T he s p o ns or ma y  retai n a n d c o nti n ue t o use a n y data 
c ollecte d bef ore s uc h wit h dra wal of c o nse nt.
W he n a partici pa nt wit h dra ws fr o m t he st u d y beca use of a n S A E, t he S A E m ust be rec or de d 
o n t he C R F a n d re p orte d o n t he Cli nical Trial S A E Re p ort.
Lac k of c o m pleti o n of all or a n y of t he wit h dra wal/earl y ter mi nati o n pr oce d ures will n ot be 
vie we d as pr ot oc ol de viati o ns s o l o n g as t he partici pa nt’s safety was preser ve d.
Reas o ns f or wit h dra wal of st u d y  treat me nt ma y i ncl u de:

O bjecti ve disease pr o gressi o n; 

Gl o bal deteri orati o n of healt h stat us re q uiri n g disc o nti n uati o n;

U nacce pta ble t o xicit y ;

Pre g na nc y ;

Si g nifica nt pr ot oc ol vi olati o n;
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 8

L ost t o f oll o w - u p;

Partici pa nt ref use d f urt her treat me nt;

St u d y  ter mi nate d b y s p o ns or;

Deat h.
Wit h dr a w al of C o nse nt: 
Partici pa nts w h o re q uest t o disc o nti n ue recei pt of st u d y  treat me nt will re mai n i n t he st u d y 
a n d m ust c o nti n ue t o be f oll o we d f or pr ot oc ol- s pecifie d f oll o w- u p pr oce d ures. T he o nly 
e xce pti o n t o t his is w he n a partici pa nt s pecificall y wit h dra ws c o nse nt f or a n y f urt her c o ntact 
wit h hi m or her or pers o ns pre vi o usl y  a ut h orize d b y t he partici pa nt t o pr o vi de t his 
i nf or mati o n. Partici pa nts s h o ul d n otif y  t he i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w 
c o nse nt fr o m f ut ure f oll o w - u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be 
e x plai ne d i n detail i n t he me dical rec or ds b y t he i n vesti gat or, as t o w het her t he wit h dra wal is 
o nl y  fr o m furt her recei pt of st u d y  i nter ve nti o n or als o fr o m st u d y pr oce d ures a n d/ or 
p osttreat me nt st u d y  f oll o w-u p a n d e ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt t hat 
vital stat us ( w het her t he partici pa nt is ali ve or dea d) is bei n g meas ure d, p u blicl y  a vaila ble
i nf or mati o n s h o ul d be use d t o deter mi ne vital stat us o nl y as a p pr o priately directe d i n 
acc or da nce wit h l ocal la w.
7. 3. L ost t o F oll o w -u p 
A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if he or s he re peate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u nable t o be c o ntacte d b y t he st u d y  site.
Reas o ns f or wit h dra wal fr o m st u d y  f oll o w-u p ma y i ncl u de:

C o m plete d st u d y  f oll o w- u p;

St u d y  ter mi nate d b y s p o ns or;

L ost t o f oll o w - u p;

Ref use d f urt her f oll o w -u p;

Deat h.
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa n t fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble a n d c o u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d as certai n w het her or n ot t he partici pa nt wis hes t o a n d/ or 
s h o ul d c o nti n ue i n t he st u d y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 8 9

Bef ore a partici pa nt is dee me d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y  eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d.

S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y.
Disc o nti n uati o n of s pecific sites or of t he st u d y  as a w h ole is ha n dle d as part of A p pe n di x 1 .
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) m ust o btai n a si g ne d a n d 
date d I C D bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures. 
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe m pti o ns are n ot a ll o we d.
I m me diate safet y c o ncer ns s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n 
occ urre nce or a ware ness t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y  
i nter ve nti o n.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all e li gi bilit y criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here ma y  be 
circ u msta nces o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma y  ma ke it u nfeasi ble t o perf or m 
t he test. In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y t o e ns ure t he safety a n d 
well - bei n g of t he partici pa nt. W he n a pr ot oc ol-re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t he misse d test a n d a ny c orrecti ve a n d pre ve nti ve 
acti o ns t hat he or s he has t a ke n t o e ns ure t hat re q uire d pr ocesses are a d here d t o as s o o n as 
p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns an d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 0
8. 1. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y  assess me nts are pr o vi de d i n t he S o A . U nsc he d ule d cli nical 
la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u dy t o assess a n y 
percei ve d safet y  c o ncer ns.
Safet y  assess me nts will i ncl u de c ollecti o n of A Es, seri o us a d verse e ve nts ( S A Es), vital si g ns 
a n d p h ysical e xa mi nati o n, electr ocar di o gra m ( E C G [ 1 2-lea d]), la b orat or y assess me nts, 
i ncl u di n g pre g na nc y tests a n d verificati o n of c o nc o mita nt treat me nts. 
8. 1. 1. P h ysic al E x a mi n ati o ns
Partici pa nts will ha ve a p h y sical e xa mi nati o n t o i ncl u de wei g ht, vital si g ns, assess me nt of 
E C O G perf or ma nce stat us a n d hei g ht; hei g ht will be meas ure d at baseli ne o nl y.
A c o m plete p h ys ical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of t he 
car di o vasc ular, res pirat or y, gastr oi ntesti nal, a n d ne ur ol o gical s ys te ms.
A brief p h ys ical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of t he s ki n, l u n gs, 
car di o vasc ular s ys te m, a n d a b d o me n (li ver a n d s plee n).
I n vesti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us 
ill nesses.
8. 1. 2. C O VI D ‑ 1 9: Use of Alter n ati ve Met h o ds f or I n-Pers o n Visits
I n li g ht of t he C O VI D- 1 9 pa n de mic, alternati ve met h o ds f or c o n d ucti n g safet y  assess me nts 
m ust be c o nsi dere d, w he n feasi ble a n d w he n safet y  ca n be ass ure d. T hese ma y i ncl u de:

C o n d ucti n g tele healt h visits (e g, p h o ne/ vi de o [ usi n g HI P A A ‑c o m plia nt vi de o‑c o nfere nce 
t o ols or as per mitte d b y l ocal re g ulati o ns]) 

M o vi n g partici pa nts t o less cr o w de d fa mil y  healt h ce nters a n d l ocal la b orat ories f or bl o o d 
dra ws, a n d i ma gi n g/ra di o gra p hs.

Refer t o A p pe n di x 1 8 f or a m ore c o m pre he nsi ve list of acce pta ble alter nati ve meas ures 
d uri n g t he C O VI D -1 9 p u blic e mer ge nc y .
8. 1. 3. Vit al Si g ns
Vital si g ns will be meas ure d wit h t he partici pa nt i n a se mi -s u pi ne p ositi o n or seate d p ositi o n 
after 5 mi n utes of rest a n d will i ncl u de te m perat ure, s y st olic a n d diast olic bl o o d press ure, 
p ulse rate , p ulse o xi metr y a n d wei g ht. 
8. 1. 4. Electr oc ar di o gr a ms
Sta n dar d 1 2 - Lea d E C Gs utilizi n g li m b lea ds ( wit h a 1 0-sec o n d r h yt h m stri p) s h o ul d be 
c ollecte d i n tri plicate at ti mes s pecifie d i n t he S o A secti o n of t his pr ot oc ol usi n g a n E C G 
mac hi ne t hat a ut o maticall y  calc ulates t he heart rate a n d meas ures P R, Q T, a n d Q Tc i nter vals 
a n d Q R S c o m ple x. Alter nati ve lea d place me nt met h o d ol o g y  usi n g t ors o lea ds 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 1
(e g, Mas o n - Li kar) is n ot rec o m me n de d gi ve n t he p ote ntial ris k of discre pa ncies wit h E C Gs 
ac q uire d usi n g sta n dar d li m b lea d place me nt. All sc he d ule d E C Gs s h o ul d be perf or me d after 
t he partici pa nt has reste d q uietl y f or at least 1 0 mi n utes i n a s u pi ne p ositi o n.
At eac h ti me p oi nt (S o A ), 3 c o nsec uti ve E C Gs will be perf or me d at a p pr o xi matel y  ( 1 t o 4) 
mi n utes a part t o deter mi ne t he mea n Q Tc F i nter val. T o e ns ure safet y of t he partici pa nts, a 
q ualifie d i n di vi d ual at t he i n vesti gat or site will ma ke c o m paris o ns t o baseli ne meas ure me nts. 
A d diti o nal E C G m o nit ori n g will o cc ur if a) t he mea n val ue fr o m t he tri plicate meas ure me nts 
f or a ny p ost d ose Q Tc F i nter val is i ncrease d b y 6 0 msec fr o m t he baseli ne a n d is 
> 4 5 0 msec; or b) a n a bs ol ute Q Tc F val ue is 5 0 0 msec f or a n y s c he d ule d E C G. If eit her of 
t hese c o n diti o ns occ urs, t he n a si n gle E C G meas ure me nt m ust be re peate d at least h o url y 
u ntil Q Tc F val ues fr o m 2 s uccessi ve E C Gs fall bel o w t he t hres h ol d val ue t hat tri g gere d t he 
re peat meas ure me nt. I n a d diti o n, if verifie d Q Tc F val ues c o nti n ue t o e xcee d t he criteria 
a b o ve, i m me diate c orrecti o n f or re versi ble ca uses i ncl u di n g electr ol yt e a b n or malities, 
h y p o xia, a n d c o nc o mita nt me dicati o ns f or dr u gs wit h t he p ote ntial t o pr ol o n g t he Q Tc F 
i nter val s h o ul d be perf or me d.
I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y. It is i m p orta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs. If a mac hi ne-rea d 
Q Tc F val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y  n ot be necessar y if a 
q ualifie d me dical pr o vi der’s i nter pretati o n deter mi nes t hat t he Q Tc F val ues are i n t he 
acce pta ble ra n ge.
If a partici pa nt e x perie nces a car diac or ne ur ol o gic A E (s pecifically s y nc o pe, dizzi ness, 
seiz ures, or str o ke), a n E C G (tri plicate) s h o ul d be o btai ne d at t he ti me of t he e ve nt.
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 7 .
8. 1. 5. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y  tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F. 
Cli nicall y  si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hic h are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y  t he i nvesti gat or t o be m ore se vere t ha n e x pecte d f or 
t he partici pa nt’s c o n diti o n.
All la b orat or y  tests wit h val ues c o nsi dere d cli nicall y si g nifica ntly a b n or mal d uri n g 
partici pati o n i n t he st u d y  or wit hi n 8 4 da y s after t he last d ose of st u d y i nter ve nti o n s h o ul d be 
re peate d u ntil t he val ues ret ur n t o n or mal or baseli ne or are n o l o n ger c o nsi dere d cli nicall y 
si g nifica nt by t he i n vesti gat or or me dical m o nit or.
If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d ge d reas o na ble b y 
t he i n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d, a n d t he s p o ns or n otifie d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 2
All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n A p pe n di x 2 , m ust be c o n d ucte d 
i n acc or da nce wit h t he L a b orat or y M a n ual a n d t he S o A .
If la b orat or y val ues fr o m n o n-pr ot oc ol -s pecifie d la b orat or y assess me nts perf or me d at t he 
i nstit uti o n’s l ocal la b orat or y re q uire a c ha n ge i n partici pa nt ma na ge me nt or are c o nsi dere d 
cli nicall y si g nifica nt by t he i n vesti gat or (e g, S A E or A E or d ose m o dificati o n), t he n t he 
res ults m ust be rec or de d i n t he C R F.
8. 1. 6. Pre g n a nc y Testi n g 
Pre g na nc y  tests ma y be uri ne or ser u m tests b ut m ust ha ve a se nsiti vit y of at least 
2 5 mI U/ m L. Pre g na nc y  tests will be perf or me d i n w o me n of c hil d beari n g p ote ntial 
( W O C B P) at t he ti mes liste d i n t he S o A . F oll o wi n g a ne gati ve pre g na nc y test res ult at 
scree ni n g, a p pr o priate c o ntrace pti o n m ust be c o m me nce d, a n d a sec o n d ne gati ve pre g na nc y 
test res ult will be re q uire d at t he baseli ne visit prior t o t he partici pa nt’s recei vi n g t he 
P F -0 7 0 6 2 1 1 9. Pre g na nc y tests will als o be d o ne w he ne ver 1 me nstr ual c y cle is misse d d uri n g 
t he acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y is ot her wise s us pecte d) a n d at t he 
e n d of t he st u d y. Pre g na nc y tests m a y als o be re peate d if re q ueste d b y IR Bs/ E Cs or if 
re q uire d by l ocal re g ulati o ns. If a uri ne test ca n n ot be c o nfir me d as ne gati ve (e g, a n 
a m bi g u o us res ult), a ser u m pre g na nc y  test is re q uire d. I n s uc h cases, t he partici pa nt m ust be 
e xcl u de d if t he ser u m pre g na nc y res ult is p ositi ve.
8. 1. 7. I njecti o n Site T oler a bilit y Assess me nt 
Assess me nts of t he i njecti o n sites i n t he a b d o mi nal fat f ol d t o m o nit or l ocal t olera bilit y  t o 
P F - 0 7 0 6 2 1 1 9 a n d P F-0 6 8 0 1 5 9 1 S C i njecti o ns will be perf or me d f or at least 1 h o ur f oll o wi n g 
st u dy dr u g a d mi nistrati o n i n C y cle 1, as per t he S o A . A n assess me nt s h o ul d als o be 
perf or me d 2 4 h o urs ( ± 1 h o ur) after t he C 1 D 1 d ose. I njecti o n site t olera bilit y  assess me nts f or 
at least 1 h o ur p ost t he P F-0 7 0 6 2 1 1 9 i nje cti o n s h o ul d c o nti n ue after eac h d osi n g da y visit i n 
C y cle 2 a n d be y o n d, o nl y  if i njecti o n site pai n or I S R c haracteristics c o nti n ue t o persist. T he 
assess me nts s h o ul d c o nti n ue at re g ularl y sc he d ule d visits u ntil t he s ym pt o ms res ol ve. T he 
i njecti o n sites will be assesse d f or er yt he ma, i n d urati o n, ecc hy m osis, i njecti o n site pai n, 
i njecti o n site pr urit us, or ot her o bser ve d c haracteristics after P F-0 7 0 6 2 1 1 9 a n d P F - 0 6 8 0 1 5 9 1 
a d mi nistrati o n. T he dia meter of t he affecte d area will be meas ure d, a n d t he c o n diti o n of t he 
i njecti o n site will be rec or de d o n t he i njecti o n site reacti o n C R F. A ny o bser ve d a b n or malit y 
at t he i njecti o n site will be j u d ge d b y t he i n vesti gat or t o deter mi ne if t he e ve nt s h o ul d als o be 
re p orte d as a n A E. I SRs s h o ul d be i m me diatel y  p h ot o gra p he d in c ol or, wit h scale d r uler 
place d b y t he reacti o n, a n d t hese p h ot o gra p hs s h o ul d be i ncl u de d i n t he partici pa nt’s s o urce 
d oc u me ntati o n. W he n a p pr o priate, at t he discreti o n of t he i n vesti gat or, a partici pa nt wit h a n 
I S R ma y be referre d f or a der mat ol o gical co ns ultati o n a n d s ki n bi o ps y  ma y be o btai ne d f or 
f ut ure e xa mi nati o n of t he IS R. 
8. 2. A d verse E ve nts a n d Seri o us A d verse E ve nts
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
A Es will be re p orte d b y t he partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or 
t he partici pa nt’s le gall y a ut h orize d re prese ntati ve).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 3
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o 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 or t hat ca use d t he partici pa nt t o disc o nti n ue t he 
st u d y (Secti o n 7. 1 ).
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.
8. 2. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g A Es a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d c o nse nt, 
w hic h is o btai ne d bef ore t he partici pa nt’s partici pati o n i n t he st u d y  (ie, bef ore u n der g oi n g 
a n y st u d y-relate d pr oce d ure a n d/ or recei vi n g st u d y i nter ve nti o n), t hr o u g h a n d i ncl u di n g a 
mi n i m u m of 2 8 cale n dar da ys, e xce pt as i n dicate d bel o w, after t he last a d mi nistrati o n of t he 
st u d y i nter ve nti o n.
F or partici pa nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n.
Me dical occ urre nces t hat be gi n bef ore t he start of st u d y  i nter ve nti o n b ut after o btai ni n g 
i nf or me d c o nse nt will be rec or de d o n t he Me dical Hist or y/ C urre nt Me dical C o n diti o ns 
secti o n of t he case re p ort f or m ( C R F), n ot t he A E secti o n.
F oll o w -u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut a n d after t he acti ve c ollecti o n peri o d a n d 
u ntil t he A E or S A E or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he 
i n vesti gat or, a n d Pfizer c o nc urs wit h t hat assess me nt.
I n vesti gat ors are n ot o bli gate d t o acti vely see k A Es or S A Es after t he partici pa nt has 
c o ncl u de d st u d y partici pati o n . H o we ver, if t he i n vesti gat or lear ns of a n y  S A E, i ncl u di n g a 
deat h, at a n y ti me after a partici pa nt has c o m plete d t he st u d y, a n d he/s he c o nsi ders t he e ve nt 
t o be reas o na bl y relate d t o t he st u d y i nter ve nti o n or st u d y partici pati o n, t he i n vesti gat or m ust 
pr o m ptl y  re p ort t he S A E t o Pfizer usi n g t he C T S A E Re p ort F or m. 
8. 2. 1. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d are re p orte d t o Pfizer 
Safet y  o n t he C T S A E Re p ort F or m im me diatel y a n d u n der n o circ u msta nce s h o ul d t his 
e xcee d 2 4 h o urs, as i n dicate d i n A p pe n di x 3 . T he i n vesti gat or will s u b mit a n y u p date d S A E 
data t o t he s p o ns or wit hi n 2 4 h o urs of it bei n g a vaila ble.
If a partici pa nt be gi ns a ne w a ntica ncer t hera py, S A Es occ urri n g d uri n g t he a b o ve- i n dicate d 
acti ve c ollecti o n peri o d m ust still be re p orte d t o Pfizer Safet y  irres pecti ve of a n y i nter ve ni n g 
treat me nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 4
S A Es occ urri n g i n a partici pa nt after t he acti ve c ollecti o n peri o d has e n de d are re p orte d t o 
Pfizer Safet y  if t he i n vesti gat or bec o mes a ware of t he m; at a mi ni m u m, all S A Es t hat t he 
i n vesti gat or belie ves ha ve at least a reas o na ble p ossi bilit y of bei n g relate d t o st u d y 
i nter ve nti o n m ust be re p orte d t o Pfizer Safety.
8. 2. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
D uri n g t he acti ve c ollecti o n per i o d, b ot h n o nseri o us A Es a n d S A Es are rec or de d o n t he C R F.
If a partici pa nt be gi ns a ne w a ntica ncer t hera py, t he rec or di n g peri o d f or n o nseri o us A Es 
e n ds at t he ti me t he ne w treat me nt is starte d; h o we ver, S A Es m ust c o nti n ue t o be rec or de d o n 
t he C R F d uri n g t he a b o ve-i n dicate d acti ve c ollecti o n peri o d.
8. 2. 2. Met h o d of Detecti n g A Es a n d S A Es
T he met h o d of rec or di n g, e val uati n g, a n d assessi n g ca usalit y  of A Es a n d S A Es a n d t he 
pr oce d ures f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A Es a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 2. 3. F oll o w - u p of A Es a n d S A Es
Af ter t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vely f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. F or eac h e ve nt, 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 u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot h er wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti 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 case a n d i n de pe n de nt deter mi nati o n of 
p oss i ble ca usalit y. A ny i nf or mati o n rele va nt t o t he e ve nt, s uc h as c o nc o mita nt me dicati o ns 
a n d ill nesses, m ust be pr o vi de d. I n t he case of a partici pa nt 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 s u b mitte d as s o o n as p ossi ble t o Pfizer Safet y.
F urt her i nf or mati o n o n f oll o w -u p pr oce d ures is gi ve n i n A p pe n di x 3 .
8. 2. 4. Re g ul at or y Re p orti n g Re q uire me nts f or S A Es
Pr o m pt n otificati o n b y  t he i n vesti gat or t o t he s p o ns or of a n S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b out t he safet y of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut h ority, I RBs/ E Cs , a n d i n vesti gat ors.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 5
I n vesti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d seri o us a d verse 
reacti o ns ( S U S A Rs) acc or di n g t o l ocal re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d 
f or war de d t o i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a n S A E or ot her 
s pecific safety i nf or mati o n (e g, s u m mar y or listi n g of S A Es) fr o m t he s p o ns or will re vie w 
a n d t he n file it al o n g wit h t he i n vesti gat or’s br oc h ure a n d will n otif y  t he I R B/ E C, if 
a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 2. 5. E x p os ure D uri n g Pre g n a n c y or Bre astfee di n g, a n d Occ u p ati o n al E x p os ure
E x p os ure t o t he st u d y  i nter ve nti o n u n der st u d y d uri n g pre g na nc y or breastfee di n g a n d 
occ u pati o nal e x p os ure are re p orta ble t o Pfizer Safet y  wit hi n 2 4 h o urs of i n vesti gat or 
a ware ness.
8. 2. 5. 1. E x p os ure D uri n g Pre g n a nc y
D etails of all pre g na ncies i n fe male partici pa nts a n d, if i n dicate d, fe male part ners of male 
partici pa nts will be c ollecte d after t he start of st u d y i nter ve nti o n a n d u ntil 1 0 5 da y s after t he 
last d ose.
If a pre g na nc y is re p orte d, t he i n vesti gat or s h o ul d i nfor m t he s p o ns or wit hi n 2 4 h o urs of 
lear ni n g of t he pre g na nc y a n d s h o ul d f oll o w t he pr oce d ures o utli ne d i n A p pe n di x 4 .
A b n or mal pre g na nc y  o utc o mes (e g, s p o nta ne o us a b orti o n, fetal deat h, still birt h, c o n ge nital
a n o malies, ect o pic pre g na nc y ) are c o nsi dere d S A Es.
8. 2. 5. 2. E x p os ure D uri n g Bre astfee 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 S A E, t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s a ware ne ss, usi n g t he 
C T S A E Re p ort F or m. A n e x p os ure d uri n g breastfee di 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 nce s a n S A E ass ociate d wit h s uc h 
a dr u g’s a d mi nistrati o n, t he S A E is re p orte d t o get her wit h t he e x p os ure d uri n g breastfee di n g.
8. 2. 5. 3. Occ u p ati o n al E x p os ure
A n occ u pati o nal e x p os ure occ urs w he n, d uri n g t he perf or ma nce of j o b d uties, a pers o n 
( w het her a healt hcare pr ofessi o nal or ot her wise) gets i n u n pla n ne d direct c o ntact wit h t he 
pr o d uct, w hic h ma y  or ma y n ot lea d t o t he occ urre nce of a n A E.
A n occ u pati o nal e x p os ure is re p orte d t o Pfizer Safet y  wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, usi n g t he C T S A E Re p ort F or m, re gar dless of w het her t here is a n ass ociate d 
S A E. Si nce t he i nf or mati o n d oes n ot pertai n t o a partici pa nt e nr olle d i n t he st u d y , t he 
i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y of t he c o m plete d C T S A E Re p ort 
F or m is mai ntai ne d i n t he i n vesti gat or site file.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 6
8. 2. 6. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he st u d y 
i nter ve nti o n/st u d y treat me nt b y t he wr o n g partici pa nt, or at t he wr o n g ti me, or at t he wr o n g 
d osa ge stre n gt h. 
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E Re p ort 
F or m t o Pfizer S afet y Wit hi n 
2 4 H o urs of A w are ness
Me dicati o n err ors 
All (re gar dless of w het her 
ass ociate d wit h a n A E)
O nl y  if ass ociate d wit h a n S A E
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y  i nter ve nti o n;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y  partici pa nt.
S uc h me dicati o n err ors occ urri n g t o a st u d y partici pa nt are t o be ca pt ure d o n t he me dicati o n
err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge.
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d i m me diatel y ( wit hi n 
2 4 h o urs).
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, as deter mi ne d b y t he 
i n vesti gat or, t he me dicati o n err or is rec or de d o n t he me dicati o n err or pa ge of t he C R F a n d, if 
a p plica ble, a n y ass ociate d A E(s), seri o us a n d n o nseri o us, are rec or de d o n a n A E pa ge of t he 
C R F. 
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4
h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E.
8. 3. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of P F-0 7 0 6 2 1 1 9 as a m o n ot hera p y or wit h a c o m bi nati o n a ge nt 
gr eater t ha n t he i nte n de d d ose wit hi n a 2 4- h o ur ti me peri o d will be c o nsi dere d a n o ver d ose, 
u nless t his d ose le vel has bee n declare d as safe i n t he d ose escalati o n p hase. A d diti o nall y  a ny 
d ose of P F -0 6 8 0 1 5 9 1 or be vaciz u ma b - Pfizer greater t ha n t he i nte n de d d ose wit hi n a 2 4-h o ur 
ti me peri o d will be c o nsi dere d a n o ver d ose. 
S p o ns or d oes n ot rec o m me n d s pecific treat me nt f or a n o ver d ose.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or/treati n g p hys icia n s h o ul d:
1.
C o ntact t he me dical m o nit or wit hi n 2 4 h o urs.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 7
2.
Cl osel y m o nit or t he partici pa nt f or a n y A Es/ S A Es a n d la b orat or y  a b n or malities f or at 
least 5 half-li ves or 2 8 cale n dar da ys after t he o ver d ose of st u d y i nter ve nti o n 
( w hic he ver is l o n ger).
3.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n t w o wee ks fr o m t he date of t he last 
d ose of t he st u d y i nter ve nti o n if re q ueste d b y t he me dical m o nit or ( deter mi ne d o n a 
case-b y -case basis).
4.
D oc u me nt t he q ua ntit y of t he e xcess d ose as well as t he d urati o n of t he o ver d ose i n 
t he C R F.
5.
O ver d ose is re p orta ble t o Safet y  o nl y w he n ass oci ate d w it h a n S A E.
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y  t he i n vesti gat or i n 
c o ns ultati o n wit h t he me dical m o nit or base d o n t he cli nical e val uati o n of t he partici pa nt.
8. 4. P h ar m ac o ki netics a n d I m m u n o ge nicit y 
8. 4. 1. P h ar m ac o ki netic Assess me nts
Bl o o d sa m ples of a p pr o xi matel y  4 m L , t o pr o vi de a mi ni m u m of 2 m L ser u m, will be 
c ollecte d f or meas ure me nt of ser u m c o nce ntrati o ns of P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1 or 
be vaciz u ma b - Pfizer as s pecifie d i n t he S o A . I nstr ucti o ns f or t he c ollecti o n a n d ha n dli n g of 
bi ol o gical sa m ples will be pr o vi de d i n t he L a b orat or y M a n ual or b y t he s p o ns or. T he act ual 
date a n d ti me ( 2 4 -h o ur cl oc k ti me) of eac h sa m ple will be rec or de d.
T he act ual c ollecti o n ti mes ma y c ha n ge, b ut t he n u m ber of pla n ne d sa m ples will re mai n t he 
sa me. All eff orts will be ma de t o o btai n t he sa m ples at t he e xact n o mi nal ti me relati ve t o 
d osi n g. C ollecti o n of sa m ples t hat are o btai ne d wit hi n t he s pecifie d ti me wi n d o w will n ot be 
ca pt ure d as a pr ot oc ol de viati o n, as l o n g as t he e xact ti me of t he c ollecti o n is n ote d o n t he 
s o urce d oc u me nt a n d data c ollecti o n t o ol (e g, C R F).
Sa m ples will be use d t o e val uate t he P K of P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1 or 
be vaciz u ma b - Pfizer. Sa m ples c ollecte d f or a nalyses of ser u m dr u g c o nce ntrati o ns ma y als o 
be use d t o e val uate safet y or efficac y  as pects relate d t o c o ncer ns arisi n g d uri n g or after t he 
st u d y a n d/ or e val uati o n of t he bi oa nalyt ical met h o d, or f or ot her i nter nal e x pl orat or y 
p ur p oses.
Ge netic a nal ys es will n ot be perf or me d o n t hese ser u m sa m p les u nless c o nse nt f or t his was 
i ncl u de d i n t he i nf or me d c o nse nt. Partici pa nt c o nfi de ntialit y will be mai ntai ne d.
Sa m ples c ollecte d f or meas ure me nt of ser u m c o nce ntrati o ns of P F- 0 7 0 6 2 1 1 9, P F - 0 6 8 0 1 5 9 1 
or be vaciz u ma b -Pfizer as i n dicate d will be a nal yz e d usi n g a vali date d a nal yt ical met h o d i n 
c o m plia nce wit h a p plica ble sta n dar d o perati n g pr oce d ures ( S O Ps).
T he P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns pr o vi de d t o 
t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y de viati o ns fr o m t he P K sa m ple 
ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, i nteri m st ora ge or s hi p pi n g 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 8
c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o t he s p o ns or. 
O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as t o w het her sa m ple 
i nte grity has bee n c o m pr o mise d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he 
s p o ns or a n d site st u d y files b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 4. 2. A n al ysis of A nti - Dr u g A nti b o dies a n d Ne utr alizi n g A nti-A nti b o dies 
( PF- 0 7 0 6 2 1 1 9, P F - 0 6 8 0 1 5 9 1, or be v aciz u m a b-Pfizer)
Bl o o d sa m ples of a p pr o xi matel y  4 m L , t o pr o vi de a mi ni m u m of ser u m 2 m L, will be 
c ollecte d f or deter mi nati o n of A D A a n d N A b a gai nst P F -0 7 0 6 2 1 1 9, P F -0 6 8 0 1 5 9 1 or 
be vaciz u ma b -Pfizer, as i n dicate d as s pecifie d i n t he S o A . I nstr ucti o ns f or t he c ollecti o n a n d 
ha n dli n g of bi ol o gical sa m ples will be pr o vi de d i n t he L a b orat or y M a n ual or b y t he s p o ns or. 
T he act ual date a n d ti me ( 2 4- h o ur cl oc k ti me) of eac h sa m ple will be rec or de d.
Sa m ples c ollecte d f or deter mi nati o n of A D A a n d N A b ma y  als o be use d f or a d diti o nal 
c haracterizati o n of t he i m m u ne res p o nse a n d/ or e val uati o n of t he bi oa nal ytical met h o d, or f or 
ot her i nter nal e x pl orat or y p ur p oses. T hese data will be use d f or i nter nal e x pl orat or y  
p ur p oses.
Ge netic a nal ys es will n ot be perf or me d o n t hese ser u m sa m ples u nless c o nse nt f or t his was 
i ncl u de d i n t he i nf or me d c o nse nt. Partici pa nt c o nfi de ntialit y will be mai ntai ne d.
Sa m ples will be a nal y ze d usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h a p plica ble 
S O Ps. Sa m ples deter mi ne d t o be p ositi ve f or A D A ma y  be f urt her c haracterize d f or N A b.
T he i m m u n o ge nicit y sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns 
pr o vi de d t o t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y . A ny de viati o ns fr o m t he 
i m m u n o ge nicity sa m ple ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, 
i nteri m st ora ge, or s hi p pi n g c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d 
a n d re p orte d t o t he s p o ns or. O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n 
as t o w het her sa m ple i nte grit y has bee n c o m pr o mise d.
A n y  c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u dy assess me nts m ust 
be d oc u me nte d a n d a p pr o ve d b y  t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d in t he 
s p o ns or a n d site st u d y files b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he IR B/ E C will 
be i nf or me d of a n y safet y iss ues t hat re q uire alterati o n of t he safet y m o nit ori n g sc he me or 
a me n d me nt of t he I C D.
8. 5. P h ar m ac o d y n a mics
P har mac o d y na mic ( P D) para met ers will be e val uate d i n t his st u d y. See Secti o n 8. 8
Bi o mar kers.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 9 9
8. 6. Bi o m ar ker a n d P h ar m ac o d y n a mic Assess me nts
A ke y  ele ment of t his st u d y  is t he e val uati o n of p ote ntial cell ular a n d m olec ular si g nat ures 
t hat e xist bef ore treat me nt a n d c o ul d be m o difie d i n vi v o b y P F-0 7 0 6 2 1 1 9 use d i n t his st u d y  
t o tar get G U C Y 2 C a n d acti vate T cells. T he bi o mar ker st u dies will be use d t o hel p 
u n dersta n d t he i n vi v o mec ha nis m of acti o n of P F -0 7 0 6 2 1 1 9, t o e val uate t he m o n ot hera p y 
P F -0 7 0 6 2 1 1 9, a n d p ote ntial c o m bi nat orial effects of P F - 0 7 0 6 2 1 1 9 wit h ot her a ge nts, as well 
as e val uate p ote ntial mec ha nis ms of resista nce. Bi o mar ker st u dies ma y  hel p i n t he f ut ure 
de vel o p me nt of t his dr u g as a si n gle a ge nt, or i n c o m bi nati o n wit h ot her c o m p o u n ds.
Ta ble 1 4 bel o w s u m marizes t he bi o mar ker assa y s t hat i ncl u de, b ut are n ot li mite d t o, t h ose 
w hic h will be use d a n d t he s o urce of t he sa m ples. A d diti o nal bi os peci me ns c ollecte d o ver t he 
c o urse of partici pa nt disease ma na ge me nt ma y  be s u b mitte d f or bi o mar ker a nalys es. Refer t o 
t he S o A f or details pertai ni n g t o s pecific da ys of sa m ple c ollecti o n a n d t o t he st u d y ma n ual 
f or details of sa m ple pre parati o n.
T a ble 1 4 . Bi o m ar ker C ollecti o ns a n d A n al yses
Ass a y
S a m ple T y pe
Meas ure me nt of G U C Y 2 C E x pressi o n Le vels
Arc hi val a n d de n o v o pre -treat me nt t u m or bi o psies
I m m u n o p he n ot y pi n g of bl o o d i m m u ne cell s u bt y pes 
fre q ue nc y a n d acti vati o n m o d ulati o n
W h ole bl o o d
Meas ure me nt
of peri p heral c yt o ki nes a n d ot her 
circ ulati n g mar kers
W h ole bl o o d
M o d ulati o n of i ntra -t u m oral tar get pat h wa y m o d ulati o n 
(ie, ge ne e x pressi o n si g nat ure, cell ular a n d pr otei n 
c ha n ges)
De n o v o pre -, o n-, p ost-treat me nt t u m or bi o psies
P har mac o d y na mic para meters will be e val uate d i n t his st u d y . See Secti o n 8. 8 Bi o mar kers.
8. 7. Ge netics
8. 7. 1. S pecifie d Ge netics
Ge netics (s pecifie d a nal yses) are n ot e val uate d i n t his st u d y .
8. 7. 2. B a n ke d Bi os peci me ns f or Ge netics
A 4 m L  w h ole bl o o d sa m ple o pti mize d f or D N A is olati o n ( Pre p D 1/ Pre p D 1. 5) will be 
c ollecte d as l ocal re g ulati o ns a n d IR Bs/ E Cs all o w (refer t o t he S o A f or c ollecti o n 
ti me p oi nts). 
Ba n ke d bi os peci me ns ma y be use d f or researc h relate d t o dr u g res p o nse a n d disease u n der 
st u d y. Ge nes a n d ot her a nal ytes (e g, pr otei ns, R N A, n o n dr u g meta b olites) ma y  be st u die d 
usi n g t he ba n ke d sa m ples. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 0
U nless pr o hi bite d b y  l ocal re g ulati o ns or I R B/ E C decisi o n, partici pa nts will be as ke d t o 
i n dicate o n t he c o nse nt d oc u me nt w het her t he y will all o w t heir ba n ke d bi os peci me ns t o als o 
be use d t o desi g n a n d c o n d uct researc h i n or der t o gai n a f urt her u n dersta n di n g of ot her 
diseases a n d t o a d va nce scie nce, i ncl u di n g de vel o p me nt of ot her me dici nes f or partici pa nts. 
T his c o m p o ne nt of t he sa m pli n g ba n ki n g is o pti o nal f or partici pa nts; t he y  ma y still 
partici pate i n t he st u d y e ve n if t he y d o n ot a gree t o t he a d diti o nal researc h o n t heir ba n ke d 
bi os peci me ns. T he o pti o nal a d diti o nal researc h d oes n ot re q uire t he c ollecti o n of a n y  f urt her 
sa m ples.
See A p pe n di x 5 f or i nf or mati o n re gar di n g ge netic researc h. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n b e f o u n d i n t he st u d y ma n ual.
Details o n pr ocesses f or c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n L a b orat or y 
Ma n ual.
8. 8. Bi o m ar kers
Bi os peci me ns c ollecte d f or p har mac o d y na mic a n d ot her bi o mar ker assess me nts ma y i ncl u de, 
b ut are n ot li mite d t o peri p heral bl o o d, t u m or tiss ues a n d ma y  be use d t o a nal yze D N A, 
R N A, pr otei ns, or meta b olic bi o mar kers, f or ac hie vi n g pla n ne d bi o mar ker o bjecti ves. Refer 
t o t he S o A f or sa m ple c ollecti o n ti me p oi nts a n d St u d y/ La b orat or y Ma n ual f or sa m ple
pr ocessi n g a n d s hi p pi n g. T he f oll o wi n g bi os peci me n t y pes are pla n ne d t o be c ollecte d i n 
s u p p ort of st u d y o bjecti ves. A d diti o nal bi os peci me ns c ollecte d o ver t he c o urse of partici pa nt 
disease ma na ge me nt ma y be s u b mitte d f or bi o mar ker a nal ys es.
T u m or bi os pec i me ns fr o m arc hi val a n d/ de n o v o bi o psies will be use d t o a nal yze ca n di date 
n ucleic aci d a n d pr otei n a n d cell ular bi o mar kers f or t heir a bilit y  t o i nf or m t h ose partici pa nts 
w h o are m ost li kel y t o be nefit fr o m treat me nt wit h t he st u d y dr u gs. Bi o mar kers ma y i n cl u de, 
b ut are n ot li mite d t o tar get e x pressi o n, n ucleic aci d a nal ys es, as well as cell t ypes a n d 
c o nstit ue nts of t he t u m or micr oe n vir o n me nt ( T M E). O pti o nal, a n d/ or de n o v o t u m or bi o psies 
o btai ne d d uri n g t hera p y a n d u p o n disease pr o gressi o n ma y  be use d t o hel p c o nfir m 
p har mac o d y n a mic effects of treat me nt a n d i n vesti gate p ote ntial ac q uire d mec ha nis ms of 
resista nce (ie, prese nce of b ut n ot li mite d t o re g ulat or y T-cells or m yel oi d -deri ve d s u p press or 
cells a n d ot her i m m u ne s u p pressi ve cells or pr otei ns). 
8. 8. 1. Arc hi v al Pre -tre at me nt a n d O pti o n al De N o v o Pre- a n d O n -Tre at me nt T u m or 
Bi o psies f or P art 1 A a n d P art 1 B
All partici pa nts i n Part 1 A a n d Part 1 B m ust pr o vi de a n arc hi ve d F F P E t u m or tiss ue sa m ple 
( bl oc k preferre d). Sa m ples pr o vi de d s h o ul d be ta ke n fr o m t he m ost rece ntl y c o n d ucte d 
a vaila ble bi o ps y, prefera bl y  wit hi n 6 m o nt hs of start of st u d y  treat me nt. Tiss ue bl oc ks are 
prefera ble, b ut fres hl y c ut paraffi n secti o ns are acce pta ble. Sites s h o ul d c o ntact s p o ns or f or 
a p pr o val t o s u b mit sli des a n d refer t o La b orat or y /St u d y  ma n ual f or i nstr ucti o ns o n s u b mitti n g 
sli des. C yt ol o gical or fi ne- nee dle as pirati o n sa m ples are n ot acce pta ble. 
If t he arc hi ve d sa m ple is ol der t ha n 6 m o nt hs, t he i n vesti gat or m ust c o ntact t he s p o ns or’s 
Me dical M o nit or t o disc uss eli gi bilit y  pri or to e nr oll me nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 1
If a n a p pr o priate arc hi val F F P E t u m or sa m ple is n ot a vaila ble, a de n o v o fres h F F P E t u m or 
sa m ple s h o ul d be c ollecte d. Eac h de n o v o c ollecti o ns ( pre-treat me nt a n d o n-treat me nt) 
s h o ul d atte m pt t o o btai n 6 c ore bi o psies, wit h a mi ni m u m of prefera bl y 3 c ores. Sa m ples 
s h o ul d be o btai ne d i n acc or da nce wit h l ocal i nstit uti o nal practice f or t u m or bi o psies.
I n Part 1 A a n d Part 1 B, o pti o nal de n o v o pre - a n d o n-treat me nt t u m or bi o psies are 
e nc o ura ge d f or all partici pa nts o n t he trial w he n partici pa nts ha ve accessi ble lesi o ns. 
O pti o nal o n -treat me nt t u m or bi o psies are prefere ntiall y c ollecte d after t he t hir d d ose, wit hi n 
7 da y s of C 3 D 1 ( C 3 D 1 ± 7 da y s). If o n treat me nt t u m or c ollecti o n ta kes places greater t ha n 
± 3 da y s fr o m C 3 D 1, a d diti o nal u nsc he d ule d bl o od sa m ple f or c y t o ki ne a n d circ ulati n g 
mar kers a n d a n u nsc he d ule d bl o o d sa m ple f or T- cell i m m u n o p he n ot ypi n g sa m ple s h o ul d be 
c ollecte d t o matc h t he da y of bi o ps y c ollecti o n.
A d diti o nal i nf or mati o n o n tiss ue c ollecti o n pr oce d ures ca n be f o u n d i n t he La b orat o r y/ St u d y 
Ma n ual.
8. 8. 2. M a n d at or y De N o v o
Pre - a n d O n -Tre at me nt T u m or Bi o psies at R P 2 D i n P art 1 A, 
P art 1 B, a n d P art 2
As t he R P 2 D/ M T D is a p pr oac he d or t he R P 2 D/ M T D of P F- 0 7 0 6 2 1 1 9 has bee n deter mi ne d, 
a n o pti o nal s u bset of partici pa nts ma y  be e nr olle d (a p pr o xi matel y 6 t o 1 2 partici pa nts) base d 
o n e mer gi n g cli nical data wit h t he re q uire me nt of pr o vi di n g ma n dat or y  paire d de n o v o 
pretreat me nt a n d o n -treat me nt bi o ps y sa m ples i n Parts 1 A a n d P art 1 B wit hi n 7 da y s of 
C 3 D 1 ( ± 7 d a y s) t o e na ble e val uati o n of tiss ue bi o mar ker P D acti vit y. T he o pti o n t o e nr oll t he 
s u bset of partici pa nts f or ma n dat or y paire d t u m or sa m ples will be base d o n e val uati o n of 
e mer gi n g cli nical data i ncl u di n g a vaila ble safet y/ t olera bilit y, P K, a n d P D fi n di n gs b y t he 
s p o ns or.
I n Part 2, de n o v o pre-treat me nt bi o psies will be re q uire d fr o m all partici pa nts, u nless n ot 
me dicall y  feasi ble, i n or der t o esta blis h relati o ns hi p bet wee n tar get e x pressi o n a n d efficac y 
o bser vati o ns. If a de n o v o pre- treat me nt bi o ps y is n ot me dicall y feasi ble, t he s p o ns or s h o ul d 
b e c o ntacte d f or a p pr o val bef ore i nitiati n g scree ni n g acti vities. F or a s u bset of partici pa nts i n 
all c o h orts (a p pr o xi matel y 1 0 partici pa nts), ma n dat or y o n -treat me nt bi o psy sa m ples will als o 
be c ollecte d i n or der t o c o nfir m t he mec ha nis m of acti o n a n d e val u ate p ote ntial resista nce 
mec ha nis m d uri n g treat me nt. F or all ot her partici pa nts, o n-treat me nt bi o psies are o pti o nal b ut 
e nc o ura ge d. I n Part 2, a p pr o xi matel y 2 0 partici pa nts eac h will be e nr olle d i n t he 
m o n ot hera p y a n d b ot h c o m bi nati o n c o h orts. If 1 5 partic i pa nts ha ve bee n e nr olle d i n a c o h ort 
a n d < 5 paire d pre - a n d o n-treat me nt bi o psies ha ve bee n c ollecte d, c ollecti o ns ma y be ma de 
ma n dat or y  f or t he re mai ni n g partici pa nts a n d t he c o h ort ma y be e x pa n de d b y u p t o 
5 partici pa nts t o o btai n s ufficie nt n u m bers of paire d pre - a n d o n-treat me nt bi o psies.
Fr o m t hese partici pa nts wit h paire d pre - a n d o n-treat me nt bi o psies, a n o pti o nal sec o n d o n 
treat me nt- bi o ps y is als o e nc o ura ge d after C 4 D 1 5 or at disease pr o gressi o n t o e val uate 
p ote ntial res p o nses t o treat me nt or s us p ecte d ac q uire d resista nce t o t hera p y.
Ma n dat or y  de n o v o t u m or c ollecti o ns ( pre-treat me nt a n d o n-treat me nt) s h o ul d atte m pt t o 
o btai n 6 c ore bi o psies, wit h a mi ni m u m of prefera bl y 3 c ores. Sa m ples s h o ul d be o btai ne d i n 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 2
acc or da nce wit h l ocal i nstit uti o nal pra ctice f or t u m or bi o psies. A d diti o nal i nf or mati o n o n 
tiss ue c ollecti o n pr oce d ures ca n be f o u n d i n t he La b orat or y/ St u d y Ma n ual.
Ma n dat or y  pre-treat me nt de n o v o t u m or bi o psies are t o be c ollecte d wit hi n 2 8 da ys of first 
st u d y treat me nt d ose. O n-treat me nt t u m or bi o psies are prefera bly c ollecte d after t he t hir d 
d ose, wit hi n 7 da y s of C 2 D 1 5 ( C 2 D 1 5 ± 7 d a y s). 
If o n-treat me nt t u m or c ollecti o n ta kes place greater t ha n ± 3 d a y s fr o m C 2 D 1 5, u nsc he d ule d 
bl o o d sa m ples f or c y t o ki ne a n d circ ulati n g mar kers a n d T-cell i m m u n o p he n ot y pi n g sa m ple 
s h o ul d be c ollecte d t o matc h t he da y of bi o psy c ollecti o n.
O pti o nal bi o psies are e nc o ura ge d at disease pr o gressi o n a n d/ or e n d of treat me nt (ass u mi n g 
a vaila ble t u m or t o bi o ps y) a n d as cli nicall y i n dicate d t hr o u g h o ut treat me nt f or all 
par tici pa nts. If bi o psy is t o be c o m plete d t he sa me da y as C T sca n, it m ust be c o m plete d after 
t he C T sca n.
8. 8. 3. Peri p her al Bl o o d S a m ple Assess me nts
Peri p heral bl o o d a n d deri vati ves ma y  be use d t o c haracterize cell p he n oty p es, meas ure 
s ol u ble pr otei ns a n d a nal yze n ucleic aci ds t o s u p p ort st u d y  o bjecti ves. E xa m ples ma y i ncl u de 
b ut are n ot li mite d t o t u m or e x os o mes, cell free D N A, circ ulati n g t u m or cells ( C T C), 
c yt o ki nes. A d diti o nal a nal yses ma y be warra nte d base d o n e mer gi n g data. I nstr ucti o ns f or 
sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt will be pr o vi de d i n t he La b orat or y/ St u d y
ma n ual.
8. 8. 4. C yt o ki ne Assess me nts
Sa m ples will be c ollecte d f or ce ntral e val uati o n of c y t o ki nes at t he ti me p oi nts s pecifie d i n t he 
S o A . T he c yt o ki nes t o be meas ure d ma y i ncl u de, b ut n ot li mite d t o I F N-, T N F-, I L- 1, 
I L-2, I L -4, I L -5, I L -6, I L -8, I L -1 0, I L 1 2 -p 7 0 a n d s ol u ble I L -2 R (s C D 2 5). A d diti o nal 
e x pl orat or y circ ulati n g meas ures will als o be e val uate d t o meas ure c ha n ges i n i m m u ne 
acti vati o n after t hera p y. I nstr ucti o ns f or sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt 
will be pr o vi de d i n t he La b orat or y / St u d y ma n ual.
8. 8. 5. T Cell I m m u n o p he n ot y pi n g 
W h ole bl o o d sa m ples f or e val uati o n of T -cell, B -cell, a n d N K i m m u n o p he n ot ypi n g as well 
as c har acterizati o n of T cells f or mar kers s uc h as b ut n ot li mite d t o KI 6 7, P D -1, H L A -D R 
a n d ot her pr oliferati o n, acti vati o n, a n d e x ha usti o n mar kers t o meas ure c ha n ges i n i m m u ne 
acti vati o n after t hera p y. Sa m ples will be c ollecte d at t he ti mes s pecifie d i n t he S o A . 
I nstr ucti o ns f or sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt will be pr o vi de d i n t he 
La b orat or y / St u d y ma n ual.
Sa m ples ma y  be use d f or fl o w c yt o metr y assa y de vel o p me nt. Sa m ples use d f or t his p ur p ose 
will be retai ne d i n acc or da nce wit h l ocal re g ulati o ns a n d if n ot use d wit hi n t his ti mefra me, 
will be destr o y e d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 3
8. 9. T u m or Res p o nse Assess me nts 
T u m or assess me nts will i ncl u de all k n o w n or s us pecte d disease sites. I ma gi n g will i ncl u de 
c o ntrast e n ha nce d c hest, a b d o me n a n d pel vis C T or M RI  sca ns; brai n C T or M RI sca n f or 
partici pa nts wit h k n o w n or s us pecte d brai n metastases; b o ne sca n a n d/ or b o ne x -ra ys f or 
partici pa nts wit h k n o w n or s us pecte d b o ne metastases. F or partici pa nts wit h k n o w n C T 
c o ntrast aller g y, a n o n-c o ntrast C T of t he c hest wit h c o ntrast e n ha nce d a b d o mi nal a n d pel vic 
M RI  ca n be use d. T he sa me i ma gi n g tec h ni q ue use d t o c haracterize eac h i de ntifie d a n d 
re p orte d lesi o n at baseli ne will be e m pl o ye d i n t he f oll o wi n g t u m or assess me nts.
A nti- t u m or acti vit y will be assesse d t hr o u g h ra di ol o gical t u m or assess me nts c o n d ucte d at 
baseli ne, d uri n g treat me nt as s pecifie d i n t he S o A , w he ne ver disease pr o gressi o n is s us pecte d 
(e g, sy m pt o matic deteri orati o n), a n d at t he ti me of wit h dra wal fr o m treat me nt (if n ot d o ne i n 
t he pre vi o us 4 wee ks). Assess me nt of res p o nse will be ma de usi n g R E CI S T versi o n 1. 1 
(A p pe n di x 1 4 ).
All partici pa nts’ files a n d ra di ol o gic i ma ges a n d pat h ol o g y  m ust be a vaila ble f or s o urce 
verificati o n a n d f or p ote ntial peer re vie w. 
Disease res p o nse assess me nts will be base d u p o n disease- s pecific res p o nse criteria 
(A p pe n di x 1 4 ).
8. 1 0. He alt h Ec o n o mics
Healt h ec o n o mics/ me dical res o urce utilizati o n a n d healt h ec o n o mics para meters are n ot 
e val uate d i n t his st u d y.
9. S T A TI S TI C A L C O N SI D E R A TI O N S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y  
is o utli ne d here a n d f urt her detaile d i n a statistical a nalys is pla n ( S A P), w hic h will be 
mai ntai ne d b y t he s p o ns or. 
T he data will be s u m marize d wit h res pect t o de m o gra p hic a n d baseli ne c haracteristics, 
efficac y o bser vati o ns a n d meas ure me nts, safety o bser vati o ns a n d meas ure me nts, 
p har mac o ki netic a n d bi o mar ker meas ure me nts.
9. 1. St atistic al H y p ot heses
T here will be n o f or mal h y p ot hesis testi n g i n t his st u d y .
9. 2. S a m ple Size Deter mi n ati o n
T otal n u m ber of partici pa nts is esti mate d t o be a p pr o xi matel y 1 3 0 partici pa nts.
9. 2. 1. P art 1 D ose Esc al ati o n
A p pr o xi matel y  3 5 partici pa nts eac h will be e nr olle d i n t he Part 1 A ( m o n ot hera p y) a n d 
Part 1 B (c o m bi nati o n) d ose escalati o n p orti o ns of t he st u d y . H o we ver, t he t otal n u m ber of 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 4
partici pa nts will de pe n d o n t he n u m ber of d ose le vels nee de d t o deter mi ne t he M T D a n d 
n u m ber of partici pa nts e val ua ble f or D L T at eac h d ose le vel.
9. 2. 2. P art 2 D ose E x p a nsi o n
Eac h of e x pa nsi o n c o h orts will e nr oll a p pr o xi matel y  2 0 t o 3 0 partici pa nts. Partici pa nts fr o m 
Part 1 A a n d Part 1 B w h o were treate d at t he d ose le vel selecte d f or Part 2 a n d f ulfilli n g 
Part 2 i ncl usi o n/e xcl usi o n cri teria ma y be c o u nte d t o war ds t he sa m ple size of Part 2 at t he 
c orres p o n di n g re gi me n ( m o n ot hera p y a n d c o m bi nati o ns).
Ass u mi n g a n o n -i nf or mati ve pri or (ie, Jeffre y’s pri or) if 6 o ut of 2 0 partici pa nts ha ve t u m or 
res p o nse, t his w o ul d pre dict a p osteri or pr o ba bilit y ( Beta Bi n o mial) e q ual t o 0. 7 1 t hat t he 
tr ue res p o nse is n ot i nferi or t o tar get res p o nse rate of 2 5 % a n d a p osteri or pr o ba bilit y cl ose t o 
0 (e q ual t o 4e -0 7) t hat t he tr ue res p o nse is i nferi or t o be nc h mar k rate of 2 %.
9. 3. P o p ul ati o ns f or A n al ysis

F ull a na l ysis set.

T he f ull a nal ys is set i ncl u des all e nr olle d partici pa nts.

Safet y  a nalys is set.

T he safet y a nal ys is set i ncl u des all e nr olle d partici pa nts w h o recei ve at least o ne d ose 
of st u d y  treat me nt. U nless ot her wise s pecifie d t he safety a nal ysis set will be t he defa ult 
a nal ys is set use d f or all a nal yses.

Per pr ot oc ol a nal ys is set (e val ua ble f or M T D).

T he per pr ot oc ol a nal ys is set i ncl u des all e nr olle d partici pa nts w h o ha d at least o ne 
d ose of st u d y  treat me nt a n d eit her e x perie nce d D L T or d o n ot ha ve maj or treat me nt 
de viati o ns d uri n g t he D L T o bser vati o n peri o d.

M o difie d I nte nt t o Treat ( mI T T) P o p ulati o n.

T he mI T T is t he a nal ys is p o p ulati o n t hat will f oll o w t he I T T pri nci ple a n d i ncl u de 
partici pa nts recei vi n g at least 1 d ose of st u d y me dicati o n wit h baseli ne assess me nt a n d at 
least 1 p ost baseli ne assess me nt, disease pr o gressi o n, or deat h bef ore t he first t u m or 
assess me nt. T he mI T T p o p ulati o n ma y  be use d f or i nteri m a nalys is a n d c o nfere nce 
prese ntati o ns w he n t he st u d y is still o n g oi n g.

P K a nal y sis sets.

T he P K para meter a nal ys is p o p ulati o n is defi ne d as all e nr olle d partici pa nts treate d 
w h o d o n ot ha ve pr ot oc ol de viati o ns i nfl ue nci n g P K assess me nt a n d ha ve s ufficie nt 
i nf or mati o n t o esti mate at least 1 of t he P K para meters of i nterest.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 5

T he P K c o nce ntrati o n p o p ul ati o n is defi ne d as all e nr olle d partici pa nts w h o are 
treate d a n d ha ve at least 1 a nalyt e c o nce ntrati o n.

Res p o nse E val ua ble Set.

T he res p o nse e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o recei ve d at least 
o ne d ose of st u d y treat me nt a n d ha d basel i ne disease a n d at least o ne p ost baseli ne 
disease assess me nt.

P D/ Bi o mar ker a nal ys is set(s).

T he P D/ Bi o mar ker a nal ysis p o p ulati o n is defi ne d as all e nr olle d partici pa nts wit h at 
least 1 of t he P D/ Bi o mar kers e val uate d at pre a n d/ or p ost d ose.

I m m u n o ge nicity a nal ys is set.

T he i m m u n o ge nicit y a nal y sis set i ncl u des all e nr olle d partici pa nts w h o recei ve at 
least o ne d ose of st u dy treat me nt a n d ha ve at least o ne sa m ple teste d f or A D A.
9. 4. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore data base l oc k a n d will descri be t he 
partici pa nt p o p ulati o ns t o be i ncl u de d i n t he a nal y ses, a n d pr oce d ures f or acc o u nti n g f or 
missi n g, u n use d, a n d s p uri o us data. T his secti o n is a s u m mar y  of t he pla n ne d statistical 
a nal ys es of t he pri mar y a n d sec o n dar y e n d p oi nts.
9. 4. 1. M a xi m u m T oler ate d D ose Deter mi n ati o n
Deter mi nati o n of M T D will be perf or me d usi n g Per- pr ot oc ol a nal y sis set (e val ua ble f or 
M T D).
B ayesi a n a d a ptive a p pr o ac h:
T he d ose escalati o n i n t he Part 1 A a n d Part 1 B ( wit h a n d wit h o ut pri mi n g se paratel y ) of t he 
st u d y will be g ui de d b y a Ba yesia n a nal ys is of D L T data f or P F-0 7 0 6 2 1 1 9. T o xicit y  is 
m o delle d usi n g t w o - para meter l o gistic re gressi o n f or t he pr o ba bility of a partici pa nt 
e x perie nci n g a D L T at t he gi ve n d ose f or t he m o n ot hera p y a n d usi n g B L R M m o del 
s pecifically de vel o pe d f or c o m bi nati o ns se paratel y  f or re gi me ns wit h a n d wit h o ut pri mi n g. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 6
Assess me nt of p artici p a nt risk (t he t hree d osi n g i nterv als b o u n d aries c a n be m o difie d): 
After eac h c o h ort of partici pa nts, t he p osteri or distri b uti o n f or t he ris k of D L T f or ne w 
part ici pa nts at differe nt d oses of i nterest f or P F-0 7 0 6 2 1 1 9 will be e val uate d se paratel y  f or 
c o h orts wit h a n d wit h o ut pri mi n g, ta ki n g i nt o acc o u nt t he differe nt D L T o bser vati o n peri o ds 
( 2 8 da ys f or t he re gi me n wit h o ut pri mi n g a n d 4 2 da ys f or t he re gi me n wit h pri mi n g). T he 
p osteri or distri b uti o ns will be s u m marize d t o pr o vi de t he p osteri or pr o ba bilit y  t hat t he ris k of 
D L T lies wit hi n t he f oll o wi n g i nter vals: 
U n der -d osi n g:
[ 0, 0. 1 6]
Tar gete d d osi n g:
[ 0. 1 6, 0. 3 3]
O ver d osi n g:
[ 0. 3 3, 1]
T he E W O C pri nci ple: 
D osi n g decisi o ns are g ui de d b y  t he escalati o n wit h o ver d ose c o ntr ol pri nci pal. 3 1  A d ose ma y  
o nl y  be use d f or ne wly e nr olle d partici pa nts if t he ris k of e xcessi ve t o xicit y  at t hat d ose is 
less t ha n 2 5 %.
Pri or distri b uti o ns:
Wea kl y  i nf or mati ve pri or distri b uti o ns base d o n pre-cli nical/e x pert o pi ni o n i nf or mati o n will 
be c h ose n f or t he l o gistic para meters f or pri or distri b uti o n i n Part 1 A, see A p pe n di x 1 0 .
A meta -a nal ytic-pre dicti ve ( M A P) a p pr oac h will be use d t o deri ve t he pri or distri b uti o n f or 
m o del para meters use d i n Part 1 B base d o n t he data c ollecte d i n Part 1 A. T he M A P pri or f or 
t he l o gistic m o del para meters f or t his st u dy is t he c o n diti o nal distri b uti o n of t he para meters 
gi ve n t he hist orical data. 4 0 ,2 7 ,3 1  M A P pri ors are deri ve d fr o m
hierarc hical m o dels, w hic h 
ta ke i nt o acc o u nt p ossi ble differe nces bet wee n t he st u dies. A f ull descri pti o n of t he 
a p plicati o n of t he M A P a p pr oac h t o deri ve t he pri or distri b uti o ns of t he m o del para meters is 
pr o vi de d i n A p p e n di x 1 0 .
St arti n g d ose: 
T he starti n g d ose of Part 1 A wit h o ut pri mi n g is 4 5 µ g. F or t his d ose t he pri or ris k of 
o ver d osi n g is 9. 7 %, w hic h satisfies t he E W O C criteri o n. A f ull assess me nt of t he pri or ris k t o 
partici pa nts is gi ve n i n A p pe n di x 1 0 .
T he starti n g d ose of Part 1 A wit h pri mi n g is 4 0 0 µ g f or t he pri mi n g d ose a n d 8 0 0 µ g f or t he 
f ull d ose. F or t his d ose t he pri or ris k of o ver d osi n g is 1 2. 8 %, w hic h satisfies t he E W O C 
criteri o n. A f ull assess me nt of t he pri or ris k t o partici pa nts is gi ve n i n A p pe n di x 1 0 .
T he ma xi m u m n u m ber of partici pa nts i n d ose escalati o n part of t he st u d y  was set t o 5 0. T he 
trial will be st o p pe d w he n t he f oll o wi n g criteria are met:

At least 6 partici pa nts ha ve bee n treate d at t he rec o m me n de d M T D/ R P 2 D.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 7

T he d ose  satisfies o ne of t he f oll o wi n g c o n diti o ns:
T he pr o ba bilit y  of tar get t o xicit y at d ose  e xcee ds 5 0 %, ie, Pr( 0. 1 6 ≤  < 0. 3 3) ≥5 0 %.

A mi ni m u m of 1 5 partici pa nts ha ve bee n treate d i n t he trial.
9. 4. 2. Effic ac y A n al yses
Res p o nse E val ua ble Set will be use d f or all res p o nse relate d a nal ys es i ncl u di n g O R R, D O R, 
a n d P F S.
T u m or res p o nse will be prese nte d i n t he f or m of partici pa nt data listi n gs t hat i ncl u de, b ut are 
n ot li mite d t o t u m or t y pe, d ose o n Da y  1, t u m or res p o nse at eac h visit, a n d best o verall 
res p o nse.
Part 1 A a n d Part 1 B: pr o gressi o n date, deat h date, date of first res p o nse a n d last t u m or 
assess me nt date a n d date of last c o ntact will be liste d.
Part 2: T he Ka pla n -Meier met h o ds will be use d t o a nal yz e all ti me t o e ve nt e n d p oi n ts. 
Me dia n P F S (if reac he d). Details of t hese e n d p oi nt a nal ys es met h o ds will be i ncl u de d i n t he 
S A P.
P F S is defi ne d t he ti me fr o m start date t o date of first d oc u me ntati o n of pr o gressi o n, or deat h 
d ue t o a n y ca use. Pr o gressi o n is defi ne d as t he a p peara nce of l ocal, re gi o nal or dista nt 
disease of t he sa me t y pe after c o m plete res p o nse or pr o gressi o n of pre -e xisti n g lesi o ns. It 
d oes n ot i ncl u de sec o n d pri mar y  mali g na ncies of u nrelate d ty pes.
T he defi niti o n of eac h res p o nse cate g or y  is pr o vi de d i n A p pe n di x 1 4 ( R E CI S T v 1. 1) a n d 
A p pe n di x 1 5 (ir R E CIS T).
9. 4. 3. S afet y A n al yses
All safet y a nal ys es will be perf or me d o n t he safet y p o p ulati o n.
S u m maries a n d a nal ys es of safet y para meters wil l i ncl u de all partici pa nts i n t he safety 
a nal ys is set.
A Es, E C Gs, B P, P R, c o nti n u o us car diac m o nit ori n g, a n d safet y la b orat or y  data will be 
re vie we d a n d s u m marize d o n a n o n g oi n g basis d uri n g t he st u dy t o e val uate t he safet y of 
partici pa nts. A n y cli nical la b orat or y , E C G, B P, a n d p ulse rate a b n or malities of p ote ntial 
cli nical c o ncer n will be descri be d. Safet y data will be prese nte d i n ta b ular a n d/ or gra p hical 
f or mat a n d s u m marize d descri pti vely, w here a p pr o priate.
Me dical hist or y  a n d p h ysical e xa mi nati o n a n d ne ur ol o gical e xa mi nati o n i nf or mati o n, as 
a p plica ble, c ollecte d d uri n g t he c o urse of t he st u d y will be c o nsi dere d s o urce data a n d will 
n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. H o we ver, a n y u nt o war d fi n di n gs 
i de ntifie d o n p h ysical a n d/ or ne ur ol o gical e xa mi nati o ns c o n d ucte d d uri n g t he acti ve 
c ollecti o n peri o d will be ca pt ure d as A Es, if t h ose fi n di n gs meet t he defi niti o n of a n A E. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 8
Data c ollecte d at scree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n criteria, s uc h as la b orat or y  
data, E C Gs, a n d vital si g ns, will be c o nsi dere d s o urce data, a n d will n ot be re q uire d t o be 
re p orte d, u nless ot her wise n ote d. De m o gra p hic data c ollecte d at scree ni n g will be re p orte d.
9. 4. 3. 1. Electr oc ar di o gr a m A n al yses
C ha n ges fr o m baseli ne f or t he E C G para meters Q T i nter val, heart ra te, Q Tc i nter val, P R 
i nter val, a n d Q R S c o m ple x will be s u m marize d b y treat me nt a n d ti me.
T he n u m ber ( %) of partici pa nts wit h ma xi m u m p ost d ose Q Tc val ues a n d ma xi m u m i ncreases 
fr o m baseli ne i n t he f oll o wi n g cate g ories will be ta b ulate d by treat me nt: 
S afet y Q Tc Assess me nt
De gree of Pr ol o n g ati o n
Mil d ( msec)
M o der ate ( msec)
Se vere ( m sec)
A bs ol ute val ue
> 4 5 0 -4 8 0
> 4 8 0 -5 0 0
> 5 0 0
I ncrease fr o m baseli ne
3 0 -6 0
> 6 0
I n a d diti o n, t he n u m ber of partici pa nts wit h u nc orrecte d Q T val ues > 5 0 0 msec will be 
s u m marize d.
If m ore t ha n 1 E C G is c ollecte d at a n o mi nal ti me after d ose a d mi nistrati o n (f or e xa m ple, 
tri plicate E C Gs), t he mea n of t he re plicate meas ure me nts will be use d t o re prese nt a si n gle 
o bser vati o n at t hat ti me p oi nt. I f a n y of t he 3 i n di vi d ual E C G traci n gs has a Q Tc val ue 
> 5 0 0 msec, b ut t he mea n of t he tri plicates is n ot > 5 0 0 msec, t he data fr o m t he partici pa nt’s 
i n di vi d ual traci n g will be descri be d i n a safety secti o n of t he cli nical st u d y  re p ort ( C S R) i n 
or der t o place t he > 5 0 0 - msec val ue i n a p pr o priate cli nical c o nte xt. H o we ver, val ues fr o m 
i n di vi d ual traci n gs wit hi n tri plicate meas ure me nts t hat are > 5 0 0 msec will n ot be i ncl u de d i n 
t he cate g orical a nal ysis u nless t he a vera ge fr o m t he tri plicate meas ure me nts is als o 
> 5 0 0 msec. C ha n ges fr o m baseli ne will be d efi ne d as t he c ha n ge bet wee n t he p ost d ose Q Tc 
val ue a n d t he a vera ge of t he ti me- matc he d baseli ne tri plicate val ues o n Da y -1, or t he 
a vera ge of t he pre d ose tri plicate val ues o n Da y 1. 
I n a d diti o n, a n atte m pt will be ma de t o e x pl ore a n d c haracterize t he relati o ns hi p bet wee n 
plas ma c o nce ntrati o n a n d Q T i nter val le n gt h usi n g a P K/ P D m o deli n g a p pr oac h. If a P K/ P D 
relati o ns hi p is f o u n d, t he i m pact of partici pa nt fact ors (c o variates) o n t he relati o ns hi p will be 
e xa mi ne d.
T he a nal ys is of E C G res ults will be base d o n partici pa nts i n t he safet y a nal ysis set wit h 
baseli ne a n d o n -treat me nt E C G data. Baseli ne is defi ne d as a C 1 D 1 pre d ose.
E C G meas ure me nts (a n a vera ge of t he tri plicate meas ure me nts) will be use d f or t he 
statistical a nal ysis a n d all data prese ntati o ns. An y  data o btai ne d fr o m E C Gs re peate d f or 
safety reas o ns after t he n o mi nal ti me -p oi nts will n ot be a vera ge d al o n g wit h t he prece di n g 
tri plicates. I nter val meas ure me nts fr o m re peate d E C Gs will be i ncl u de d i n t he o utlier 
a nal ys is (cate g orical a nal ysis) as i n divi d ual val ues o btai ne d at u nsc he d ule d ti me p oi nts.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 9
Q T i nter vals will be c orrecte d f or heart rate ( H R) ( Q Tc) usi n g sta n dar d c orrecti o n fact ors 
(ie, Fri dericia’s ( Q Tc F; defa ult c orrecti o n), Bazett’s ( Q Tc B), a n d p ossi bl y a st u d y-s pecific 
fact or, as a p pr o priate). Data will be s u m marize d a n d liste d f or Q T, H R, res p o nse rate ( R R), 
partial res p o nse ( P R), Q R S, Q Tc F (a n d ot her c orrecti o n fact ors, e g, Q Tc B as a p pr o priate) b y  
st u d y ar m a n d prese nte d b y  ti me a n d d ose. I n di vi d ual Q T (all e val uate d c orrecti o ns) i nter vals 
will be liste d b y  st u d y, ti me a n d d ose. T he m ost a p pr o priate c orrecti o n fact or will be selecte d 
a n d use d f or t he f oll o wi n g a nal ys es of ce ntral te n de nc y a n d o utliers a n d use d f or t he st u d y 
c o ncl usi o ns. Descri pti ve statistics ( n, mea n, me dia n, sta n dar d de viati o n, mi ni m u m, a n d 
ma xi m u m) will be use d t o s u m marize t he a bs ol ute c orrecte d Q T i nter val a n d c ha n ges fr o m 
baseli ne i n c orrecte d Q T after treat me nt b y d ose a n d ti me p oi nt. Details of a d diti o nal a nal ys is 
(if a ny) will be s pecif ie d i n S A P. 
9. 4. 3. 2. A d verse E ve nts
A Es will gra de d b y t he i n vesti gat or acc or di n g t o t he C T C A E versi o n 5. 0 a n d c o de d usi n g t he 
Me dical Dicti o nar y  f or Re g ulat or y Acti vities ( Me d D R A). A d verse e ve nt data will be 
re p orte d i n ta bles a n d listi n gs. S u m maries of a d verse eve nt b y ma p pe d ter ms, a p pr o priate 
t hesa ur us le vel, t o xicit y gra de, a n d seri o us ness a n d relati o ns hi p t o st u d y treat me nt will be 
prese nte d, as well as s u m maries of a d verse e ve nts lea di n g t o deat h a n d pre mat ure wit h dra wal 
fr o m st u d y treat me nt. T he n u m ber a n d perce nta ge of partici pa nts w h o e x perie nce d a n y  A E, 
S A E, treat me nt relate d A E, a n d treat me nt relate d S A E will be s u m marize d acc or di n g t o 
w orst t o xicit y  gra des. T he s u m maries will prese nt A Es b ot h o n t he e ntire st u d y peri o d a n d b y 
c ycle ( C ycl e 1 a n d C ycles b e yo n d 1). Listi n gs of D L Ts a n d deat hs will be pr o vi de d.
9. 4. 3. 3. L a b or at or y Test A b n or m alities
T he n u m ber a n d perce nta ge of partici pa nts w h o e x perie nce d la b orat or y  test a b n or malities 
will be s u m marize d acc or di n g t o w orst t o xicit y  gra de o bser ve d f or eac h la b orat or y assa y. 
T he a nal ys es will s u m marize la b orat or y tests b ot h o n t he e ntire st u d y peri o d a n d b y c ycle 
( C ycle 1 a n d C ycles b e y o n d 1). F or la b orat or y  tests wit h o ut C T C A E gra de defi niti o ns, 
res ults will be cate g orize d as n or mal, a b n or mal, or n ot d o ne.
9. 4. 4. Ot her A n al ys es 
9. 4. 4. 1. P h ar m ac o ki netic A n al yses
Si n gle - D ose a n d M ulti ple-D ose P F -0 7 0 6 2 1 1 9 P K A n al ysis
T he c o nce ntrati o ns of P F -0 7 0 6 2 1 1 9 will be s u m marize d b y  descri pti ve statistics ( n, mea n, 
sta n dar d de viati o n, c oefficie nt of variati o n, me dia n, mi ni m u m ma xi m u m, a n d ge o metric
mea n) b y d osi n g c o h ort, c ycle, a n d n o mi nal ti me. Me dia n pr ofiles of t he c o nce ntrati o n -ti me 
pr ofiles after t he C 1 D 1 d ose, C 1 D 1 5 d ose ( pri mi n g a p pr oac h), a n d d ose will be pl otte d 
se paratel y b y d osi n g c o h ort a n d c ycle usi n g n o mi nal ti mes. Me dia n pr ofiles wil l be prese nte d 
o n b ot h li near -li near a n d l o g-li near scales.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 0
T he i n di vi d ual c o nce ntrati o n -ti me data of P F-0 7 0 6 2 1 1 9 f oll o wi n g t he C 1 D 1 d ose, C 1 D 1 5 
d ose ( pri mi n g a p pr oac h), a n d C 4 D 1 d ose will be a nal y ze d se paratel y usi n g 
n o n -c o m part me ntal a nal ysis t o esti mate t he P K para meters. T he P K para meters esti mate d 
will i ncl u de C ma x , ti me t o ma xi m u m c o nce ntrati o n ( Tma x ), a n d c o nce ntrati o n vers us ti me 
c ur ve ( A U Clast). If data per mit or if c o nsi dere d a p pr o priate, ot her P K para meters i ncl u di n g 
ter mi nal eli mi nati o n half-life (t1/ 2), cleara nce ( C L/ F), A U Ci nf, a n d vol u me of distri b uti o n at 
stea d y state (V ss/ F) ma y be deter mi ne d. N o n-c o m part me ntal P K para meters will be 
s u m marize d descri pti vel y by d ose a n d c ycle. Act ual sa m ple c ollecti o n ti mes will be use d f or 
t he para meter calc ulati o ns.
T he c o nce ntrati o ns of P F -0 6 8 0 1 5 9 1 or be vaciz u ma b -Pfizer fr o m Part 1 B a n d Part 2 will be 
s u m marize d b y descri pti ve statistics ( n, mea n, sta n dar d de viati o n, c oefficie nt of variati o n, 
me dia n, mi ni m u m ma xi m u m, a n d ge o metric mea n) b y d osi n g c o h ort, c ycle, a n d n o mi nal 
ti me. 
P o p ul ati o n P h ar m ac o ki netic A n al ysis or P h ar m ac o ki netic/ P h ar m ac o d y n a mic ( P K/ P D) 
M o deli n g 
P F -0 7 0 6 2 1 1 9 P K a n d P D data fr o m t his st u d y  ma y be a nalyz e d usi n g p o p ulati o n m o deli n g 
a p pr oac hes a n d ma y als o be p o ole d wit h data fr o m ot her f ut ure st u dies t o i n vesti gate a n y 
ass ociati o n bet wee n P F- 0 7 0 6 2 1 1 9 e x p os ure a n d bi o mar kers or selecte d safet y  a n d/ or efficac y 
e n d p oi nts. T he res ults of t hese a nal ys es, if perf or me d, ma y be re p orte d se parately fr o m t he 
cli nical st u d y re p ort.
9. 4. 4. 2. P h ar m ac o d y n a mic A n al yses 
A n al ysis of Bi o m ar ker E n d p oi nts
F or bi o ps y sa m ples, s u m mar y statistics (e g, t he mea n a n d sta n dar d de viati o n, me dia n, a n d 
mi ni m u m/ ma xi m u m le vels of c o nti n u o us, a n d fre q ue ncies a n d perce nta ges of cate g orical 
bi o mar ker meas ures) will be deter mi ne d a t baseli ne a n d p ost-treat me nt. F urt her a nalys is will 
be s pecifie d i n S A P.
Cli nicall y  rele va nt a n d i nter preta ble bi o mar ker assess me nts ge nerate d f or Pri mar y a n d 
Sec o n dar y  o bjecti ves will be s u m marize d i n t he C S R. Ot her bi o mar ker data mi g ht be 
s u m marize d i n a se parate tec h nical d oc u me nt.
I m m u n o ge nicit y A n al ysis  
F or t he i m m u n o ge nicit y data, t he perce nta ge of partici pa nts wit h p ositi ve A D A will be 
s u m marize d. Listi n gs a n d s u m mar y ta b ulati o ns of t he A D A data at baseli ne a n d 
p ost -ra n d o mizati o n will be ge nerate d. Sa m ples ma y als o be a nal yze d f or t he prese nce of 
N A b, a n d a n y data will be si milarl y s u m marize d. F or partici pa nts wit h p ositi ve A D A or 
N A b, t he ma g nit u de (titer), ti me of o nset, a n d d urati o n of A D A or N A b res p o nse will als o be 
descri be d, if data per mit. T he p ote ntial i m pact of i m m u n o ge nicit y o n P K a n d cli nical 
res p o nse i ncl u di n g p har mac o dy na mic mar kers, safet y/ t olera bilit y a n d efficac y will be 
e x pl ore d, if warra nte d b y t he data.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 1
9. 5. I nteri m A n al yses 
N o f or mal i nteri m a nal ys is will be c o n d ucte d f or t his st u d y. As t his is a n o pe n-la bel st u dy, 
t he s p o ns or ma y c o n d uct u n bli n de d re vie ws of t he data d uri n g t he c o urse of t he st u d y f or t he 
p ur p ose of safet y assess me nt, facilitati n g d ose -escalati o n decisi o ns, facilitati n g P K/ P D 
m o deli n g, a n d/ or s u p p orti n g cli nical de vel o p me nt.
9. 5. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will n ot use a data m o nit ori n g c o m mittee ( D M C). F or t he p ur p ose of t his pr ot oc ol, 
Pfizer pr oce d ures f or peri o dic safet y re vie w b y a safet y re vie w tea m, c o m prise d of t he 
i n vesti gat ors a n d t he s p o ns or, will be a p plie d i n or der t o re vie w i n di vi d ual a n d s u m mar y data 
c ollecte d i n t he safet y a n d cli nical data bases. T hese i n di vi d ual a n d s u m mar y data w o ul d als o 
i ncl u de partici pa nts w h o are deter mi ne d t o be n ot e val ua ble f or D L T assess me nt.
Disc ussi o ns bet wee n t he i n v esti gat ors a n d t he s p o ns or re gar di n g safet y will occ ur i n a n 
o n -g oi n g ma n ner at re g ular telec o nfere nces a n d/ or meeti n gs t o deter mi ne t he safet y pr ofile 
a n d ris k/ be nefit rati o a n d deter mi ne if f urt her partici pa nt e nr oll me nt is a p pr o priate.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 2
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S
1 0. 1. A p pe n di x 1: Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns
1 0. 1. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declarati o n of Helsi n ki a n d C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces ( CI O M S) I nter nati o nal Et hical G ui deli nes;

A p plica ble I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or 
P har mace uticals f or H u ma n Use (IC H) G o o d Cli nical Practice ( G C P) g ui deli nes;

A p plica ble la ws a n d re g ulati o ns, i ncl u di n g a p plica ble pri vac y  la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, i n vesti gat or’s br oc h ure (I B), a n d ot her rele va nt 
d oc u me nts (e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y  t he s p o ns or a n d 
s u b mitte d t o a n IR B/ E C b y  t he i n vesti gat or a n d re vie we d a n d a p pr o ve d by t he I R B/ E C 
bef ore t he st u d y  is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate 
hazar d t o st u d y  partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I RB/ E C a n n uall y  or 
m ore fre q ue ntl y  i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/ E C.

N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safety fi n di n gs as re q uire d b y 
I RB/ E C pr oce d ures.

Pr o vi di n g o versi g ht of t he c o n d u ct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C o de of Fe deral Re g ulati o ns ( C F R), I C H g ui deli nes, t he I R B/ E C, 
E ur o pea n re g ulati o n 5 3 6/ 2 0 1 4 f or cli nical st u dies (if a p plica ble), a n d all ot her 
a p plica ble l ocal re g ulati o ns.
1 0. 1. 1. 1. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority 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 t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n/st u d y treat me nt, Pfizer s h o ul d be i nf or me d i m me diatel y. 
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nts a gai nst a n y i m me diate hazar d, a n d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 3
of a n y seri o us breac hes of t his pr ot oc ol or of I C H G C P t hat t he i n vesti gat or bec o mes a ware 
of.
1 0. 1. 2. Fi n a nci al Discl os ure
I n vesti gat ors a n d s u b-i n vesti gat ors will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate 
fi na ncial i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate 
fi na ncial certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y a ut h orities. 
I n vesti gat ors are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he 
c o urse of t he st u d y a n d f or 1 ye ar after c o m pleti o n of t he st u d y.
1 0. 1. 3. I nf or me d C o nse nt Pr ocess
T he i n vesti gat or or his/ her re prese ntati ve will e x plai n t he nat ure of t he st u d y t o t he 
partici pa nt or his/ her le gall y  acce pta ble re prese ntati ve a n d a ns wer all q uesti o ns re gar di n g t he 
st u d y.
Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y . Partici pa nts or t heir 
le gall y acce pta ble re prese ntati ve will be re q uire d t o si g n a state me nt of i nf or me d c o nse nt t hat 
meets t he re q u ire me nts of 2 1 C F R 5 0, l ocal re g ulati o ns, IC H g ui deli nes, Healt h I ns ura nce 
P orta bilit y  a n d Acc o u nta bilit y Act ( HI P A A) re q uire me nts, w here a p plica ble, a n d t he I R B/ E C 
or st u d y  ce nter.
T he i n vesti gat or m ust e ns ure t hat eac h st u d y  is f ull y i nf or me d a b o ut t he nat ure a n d o bjecti ves 
of t he st u d y , t he s hari n g of data relate d t o t he st u d y, a n d p ossi ble ris ks ass ociate d wit h 
partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt’s pers o nal 
data.
T he partici pa nt m ust be i nf or me d t hat his/ her pers o nal st u d y -relate d data will be use d b y t he 
s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici pa nt.
T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y  be e xa mi ne d b y Cli nical 
Q ualit y  Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y 
a p pr o priate I RB/ E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt is f ull y i nf or me d a b o ut his or 
her ri g ht t o access a n d c orrect his or her pers o nal data a n d t o wit h dra w c o nse nt f or t he 
pr ocessi n g of his or her pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr ol le d i n t he st u d y a n d t he date t he writte n c o nse nt was o btai ne d. 
T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C D.
Partici pa nts m ust be rec o nse nte d t o t he m ost c urre nt versi o n of t he I C D(s) d uri n g t heir 
partici pati o n i n t he st u d y .
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 4
A c o p y of t he I C Ds m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt’s le gall y acce pta ble 
re prese ntati ve.
1 0. 1. 4. D at a Pr otecti 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 gar 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 partici pa nt data.
Partici pa nts’ pers o nal data will be st ore d at t he st u d y  site i n e ncr ypte 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 ke 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 have access. T he st u d y site 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 
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 has 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, partici pa nts will be assi g ne d a si n gle, partici pa nt -s pecific n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt-s pecific c o de. T he st u d y site will 
mai ntai n a c o nfi de ntial list of partici pa nts w h o partici pate d i n t he st u d y , li n ki n g eac h 
partici pa nt’s n u merical c o de t o his or her act ual i de ntit y. I n case of data tra nsfer, t he s p o ns or 
will pr otect t he c o nfi de ntialit y  of partici pa nts’ pers o nal data c o nsiste nt wit h t he cli nical st u d y 
a gree me nt a n d a p plica ble pri vac y  la ws.
1 0. 1. 5. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials. g o v ( Cli nical Trials. g o v), t he E ur o pea n Cli nical Trials 
Data base ( E u dra C T), a n d/ or w w w. pfizer.c o m, a n d ot her p u blic re gistries i n acc or da nce wit h 
a p plica ble l ocal la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y  res ults o utsi de of t he 
re q uire me nts of l ocal la ws/re g ulati o ns p urs ua nt t o its sta n dar d o perati n g pr oce d ures ( S O Ps).
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u dy or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
w w w.cli nicaltrials. g o v
Pfizer p osts cli nical trial U S Basic Res ults o n w w w.cli nicaltrials. g o v f or Pfizer -s p o ns ore d 
i nter ve nti o nal st u dies (c o n d ucte d i n partici pa nts) t hat e val uate t he safety a n d/ or efficac y of a 
pr o d uct, re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. U S Basic 
Res ults are ge nerall y s u b mitte d f or p osti n g wit hi n 1 ye ar of t he pri mar y c o m pleti o n date 
( P C D) f or st u dies i n ad ult p o p ulati o ns or wit hi n 6 m o nt hs of t he P C D f or st u dies i n pe diatric 
p o p ulati o ns.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 5
P C D is defi ne d as t he date t hat t he fi nal partici pa nt was e xa mi ne d or recei ve d a n i nter ve nti o n 
f or t he p ur p oses of fi nal c ollecti o n of data f or t he pri mar y o utc o me, w het her t he cli nical 
st u d y c o ncl u de d acc or di n g t o t he pres pecifie d pr ot oc ol or was ter mi nate d.
E u dra C T
Pfizer p osts E ur o pea n U ni o n ( E U) Basic Res ults o n E u dra C T f or all Pfizer -s p o ns ore d 
i nter ve nti o nal st u dies t hat are i n sc o pe of E U re q uire me nts. E U Basic Res ults are s u b mitte d 
f or p osti n g wit hi n 1 year of t he P C D f or st u dies i n a d ult p o p ulati o ns or wit hi n 6 m o nt hs of 
t he P C D f or st u dies i n pe diatric p o p ulati o ns.
w w w. pfizer.c o m
Pfizer p osts p u blic discl os ure s y n o pses ( C S R s y n o pses i n w hic h a n y data t hat c o ul d be use d 
t o i de ntif y i n di vi d ual partici pa nts ha ve bee n re m o ve d) o n w w w. pfizer.c o m f or 
Pfizer -s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he U S Basic Res ults d oc u me nt is 
p oste d t o w w w.cli nicaltrials. g o v.
D oc u me nts wit hi n mar keti n g a ut h orizati o n pac k a ges/s u b missi o ns
Pfizer c o m plies wit h t he E ur o pea n U ni o n P olic y  0 0 7 0, t he pr oacti ve p u blicati o n of cli nical 
data t o t he E ur o pea n Me dici nes A ge nc y ( E M A) we bsite. Cli nical data, u n der P hase 1 of t his 
p olic y , i ncl u des cli nical o ver vie ws, cli nical s u m maries, CS Rs, a n d a p pe n dices c o ntai ni n g t he 
pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d statistical met h o ds. Cli nical data, 
u n der P hase 2 of t his p olic y , i ncl u des t he p u blis hi n g of i n di vi d ual partici pa nt data. 
P olic y 0 0 7 0 a p plies t o ne w mar keti n g a ut h orizati o n a p plicati o ns s u b mitte d via t he 
ce ntralize d pr oce d ure si nce 0 1 Ja n uar y 2 0 1 5 a n d a p plicati o ns f or li ne e xte nsi o ns a n d f or ne w 
i n dicati o ns s u b mitte d via t he ce ntralize d pr oce d ure si nce 0 1 J ul y 2 0 1 5.
Data S hari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na -fi de scie ntific researc h” t hat c o ntri b ute t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke a vaila ble data fr o m t hese trials 
2 4 m o nt hs after st u d y  c o m pleti o n. Patie nt-le vel data will be a n o ny m ize d i n acc or da nce wit h 
a p plica ble pri vac y la ws a n d re g ulati o ns. C S Rs will ha ve pers o nall y i de ntifia ble i nf or mati o n 
re dacte d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal yses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 0. 1. 6. D at a Q u a lit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he s p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he i n vesti gat or is 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 6
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he C R F.
T he i n vesti gat or m ust e ns ure t hat t he C R Fs are sec urel y st ore d at t h e st u d y site i n e ncr ypte d 
electr o nic a n d/ or pa per f or m a n d are pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o 
pre ve nt access b y u na ut h orize d t hir d parties.
T he i n vesti gat or m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts. T his 
verificati o n ma y  als o occ ur after st u d y c o m pleti o n. It is i m p orta nt t hat t he i n vesti gat or(s) a n d 
t heir rele va nt pers o n nel are a vaila ble d uri n g t he m o nit ori n g visits a n d p ossi ble a udits or 
i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he pr ocess.
M o nit ori n g details descri bi n g strate g y  (e g, ris k-base d i nitiati ves i n o perati o ns a n d q ualit y  
s uc h as ris k ma na ge me nt a n d miti gati o n strate gies a n d a nalyt ical ris k-base d m o nit ori n g), 
me t h o ds, res p o nsi bilities, a n d re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d 
m o nit ori n g tec h ni q ues (ce ntral, re m ote, or o n -site m o nit ori n g), are pr o vi de d i n t he 
m o nit ori n g pla n.
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y, i ncl u di n g 
q ualit y  c hec ki n g of t he data.
St u d y  m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d 
i nt o t he C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce 
d oc u me nts; t hat t he safet y a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y  a p pr o ve d pr ot oc ol a n d a n y ot her st u d y 
a gree me nts, IC H G C P, a n d all a p plica ble re g ulat or y  re q uire me nts.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C Ds, pertai ni n g t o t he c o n d uct of t his st u d y  m ust 
be retai ne d b y t he i n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be destr o ye d d uri n g 
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y be 
tra nsferre d t o a n ot her l ocati o n or party wit h o ut writte n n otificati o n t o t he s p o ns or. T he 
i n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms.
T he i n vesti gat or(s) will n otif y t he s p o ns or or its a ge nts i m me diatel y  of a n y re g ulat or y 
i ns pecti o n n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he i n vesti gat or will c o o perate 
wit h t he s p o ns or or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w 
t he s p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n. T he 
i n vesti gat or site a n d i n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 7
bet wee n t he st u d y data a n d t he partici pa nt’s me dical rec or ds. T he i n vesti gat or will pr o m ptl y  
pr o vi de c o pies of t he i ns pecti o n fi n di n gs t o t he s p o ns or or its a ge nt. Bef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orities, t he i n vesti gat or will pr o vi de t he s p o ns or or its 
a ge nts wit h a n o p p ort u nit y t o re vie w a n d c o m me nt o n res p o nses t o a n y s uc h fi n di n gs.
1 0. 1. 7. S o urce D oc u me nts
S o urce d oc u m e nts pr o vi de e vi de nce f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate t he 
i nte grity of t he data c ollecte d. S o urce d oc u me nts are file d at t he i n vesti gat or site.
Data re p orte d o n t he C R F or e ntere d i n t he electr o nic C R F (e C R F) t hat are tra nscri be d fr o m
s o urce d oc u me nts m ust be c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be 
e x plai ne d. T he i n vesti gat or ma y nee d t o re q uest pre vi o us me dical rec or ds or tra nsfer rec or ds, 
de pe n di n g o n t he st u d y . Als o, c urre nt me dical rec or ds m ust be a vaila ble.
Defi niti o n of w hat c o nstit utes s o urce data ca n be f o u n d i n t he st u d y  ma n ual.
1 0. 1. 8. St u d y a n d Site Cl os ure
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or. St u d y  sites will be cl ose d u p o n st u d y 
c o m pleti o n. A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y 
s u p plies ha ve bee n c ollecte d a n d a st u dy- site cl os ure visit has bee n perf or me d.
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a ny ti me u p o n n otificati o n t o t he c o ntract 
researc h or ga nizati o n ( C R O) if re q ueste d t o d o s o b y t he res p o nsi ble I R B/ E C or if s uc h 
ter mi nati o n is re q uire d t o pr otect t he healt h of st u d y partici pa nts.
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns o r ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti gat or t o c o m pl y  wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or's pr oce d ures, or G C P g ui deli nes;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gator;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
1 0. 1. 9. P u bl ic ati o n P olic y
T he res ults of t his st u d y  ma y be p u blis he d or prese nte d at scie ntific meeti n gs by t he 
i n vesti gat or after p u blicati o n of t he o verall st u d y res ults or 1 ye ar after e n d of t he st u d y ( or 
st u d y ter mi nati o n), w hic he ver c o mes first. 
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns 
s uc h as sec o n dar y ma n uscri pts a n d s u b mits all ma n uscri pts or a bstracts t o t he s p o ns or 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 8
3 0 da y s bef ore s u b missi o n. T his all o ws t he s p o ns or t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m me nts a n d t he i n vesti gat or will, o n re q uest, re m o ve a n y pre vi o usl y  u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y- or Pfizer 
i nter ve nti o n-relate d i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or 
u n dersta n di n g of t he st u d y  res ults.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or will c o m pl y wit h rec o g nize d et hical 
sta n dar ds c o ncer ni n g p u blicati o ns a n d a ut h ors hi p, i ncl u di n g t h ose esta blis he d b y t he 
I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors.
T he s p o ns or will c o m pl y  wit h t he re q uire me nts f or p u blicati o n of t he o verall st u d y res ults 
c o veri n g all i n vesti gat or sites. I n acc or da nce wit h sta n dar d e dit orial a n d et hical practice, t he 
s p o ns or will s u p p ort p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as 
i n di vi d ual site data. In t his case, a c o or di nati n g i n vesti gat or will be desi g nate d b y  m ut ual 
a gree me nt.
A ut h ors hi p of p u blicati o ns f or t he o verall st u d y  res ults will be deter mi ne d b y m ut ual 
a gree me nt a n d i n li ne wi t h Inter nati o nal C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p 
re q uire me nts. 
If p u blicati o n is a d dresse d i n t he cli nical st u d y a gree me nt, t he p u blicati o n p olic y set o ut i n 
t his secti o n will n ot a p pl y.
1 0. 1. 1 0. S p o ns or’s Q u alifie d Me dic al Pers o n nel
T he c o ntact i n f or mati o n f or t he s p o ns or’s a p pr o priatel y q ualifie d me dical pers o n nel f or t he 
st u d y is d oc u me nte d i n t he st u d y c o ntact list l ocate d i n t he tea m S hare P oi nt site. 
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel o n st u d y- relate d me dical 
q uesti o ns or pr o ble ms, partici pa nts are pr o vi de d wit h a c o ntact car d. T he c o ntact car d 
c o ntai ns, at a mi ni m u m, pr ot oc ol a n d st u d y  i nter ve nti o n i de ntifiers, partici pa nt n u m bers, 
c o ntact i nf or mati o n f or t he i n vesti gat or site, a n d c o ntact details f or a c o ntact ce nter i n t he 
e ve nt t hat t he i n vesti gat or site staff ca n n ot be reac he d t o pr o vi de a d vice o n a me dical 
q uesti o n or pr o ble m ori gi nati n g fr o m a n ot her healt hcare pr ofessi o nal n ot i n v ol ve d i n t he 
partici pa nt’s partici pati o n i n t he st u d y . T he co ntact n u m ber ca n als o be use d b y  i n vesti gat or 
staff if t he y are see ki n g a d vice o n me dical q uesti o ns or pr o ble ms; h o we ver, it s h o ul d be use d 
o nl y  i n t he e ve nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he i n vesti gat or site 
a n d t he st u d y tea m are n ot a vaila ble. It is t heref ore i nte n de d t o a u g me nt, b ut n ot re place, t he 
esta blis he d c o m m u nicati o n pat h wa y s bet wee n t he i n vesti gat or site a n d t he st u d y tea m f or 
a d vice o n me dical q uesti o ns or pr o ble ms t hat ma y arise d uri n g t he st u d y. T he c o ntact n u m ber 
is n ot i nte n de d f or use b y t he partici pa nt directl y, a n d if a partici pa nt calls t hat n u m ber, he or 
s he will be directe d bac k t o t he i n vesti gat or site.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 9
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol. A d diti o nal la b orat or y res ults ma y be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nalys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y; or as deri ve d 
fr o m calc ulate d values. T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d. U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he 
st u d y t o assess a ny percei ve d safet y c o ncer ns.
T a ble 1 5 . S afet y L a b or at or y Tests
He m at ol o g y
C he mi str y
Ser ol o g y
C o a g ul ati o n
Uri n al ysis
Pre g n a nc y Test
A d h oc L oc al 
L a b C yt o ki ne 
A n al ysis †
He m o gl o bi n
A L T
H B V 
P T
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
Ur o bili n o ge n
Uri ne bilir u bi n
Micr osc o p y
a
2 4 h o ur uri ne 
( pr otei n 
c ollecti o n) b
F or fe male 
partici pa nts of 
c hil d beari n g 
p ote ntial, ser u m.
I L-6, I L - 1, 
I L-1 0, I F N , 
T N F -, ot her 
c yt o ki nes
Platelets
A S T
H C V
P T T or A P T T
W B C
Bicar b o nate
A bs ol ute 
Ne utr o p hils
C R P
A bs ol ute 
L y m p h oc ytes
Al k P h os
A bs ol ute 
M o n oc ytes
S o di u m
A bs ol ute 
E osi n o p hils
P otassi u m
A bs ol ute 
Bas o p hils
Ma g nesi u m
Retic ul oc ytes
C hl ori de
T otal calci u m
T otal 
bilir u bi n * * *
T otal Pr otei n
B U N or Urea
Creati ni ne
Uric Aci d
Gl uc ose 
( n o nfaste d)
L D H
Al b u mi n
P h os p h or us or 
P h os p hate
A m ylase
Li pase
T h yr oi d Pa nel §
A b bre viati o ns: Al k P h os = a l kali ne p h os p hatase; A L T = ala ni ne a mi n otra nsferase; A S T = as partate a mi n otra nsferase; 
B U N = bl o o d urea nitr o ge n; C R P = C -reacti ve pr otei n; H B V = he patitis B; H C V = he patitis C; I F N = 
i nterfer o n-ga m ma; I L = i nterle u ki n; I N R = I nter nati o nal N or malize d; L D H = lactate de h y dr o ge nase; P T T = partial 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 0
T a ble 1 5 . S afet y L a b or at or y Tests
He m at ol o g y
C he mi str y
Ser ol o g y
C o a g ul ati o n
Uri n al ysis
Pre g n a nc y Test
A d h oc L oc al 
L a b C yt o ki ne 
A n al ysis †
t hr o m b o plasti n ti me; T N F= T u m or necr osis fact or - al p ha; T S H = T h yr oi d -sti m ulati n g h or m o ne; W B C = w hite bl o o d 
cells.
* * * F or p ote ntial H y’s La w cases, i n a d diti o n t o re peati n g A S T a n d A L T, la b orat or y tests s h o ul d i ncl u de 
al b u mi n, creati ne ki nase, t otal bilir u bi n, direct a n d i n direct bilir u bi n, ga m ma -gl uta m yl tra nsferase, 
pr ot hr o m bi n ti me ( P T)/I N R, al kali ne p h os p hatase, t otal bile aci ds a n d aceta mi n o p he n dr u g a n d/ or pr otei n 
a d d uct le vels.
§ T h yr oi d pa nel s h o ul d be o btai ne d at scree ni n g o nl y ( T S H, free t h yr o xi ne [ T 4], free trii o d ot h yr o ni ne [t otal 
or free T 3]). 
† C yt o ki nes f or l ocal la b e val uati o n will be c ollecte d if C R S is s us pecte d. L ocal la b e val uati o n of c yt o ki ne is 
o nl y re q uire d if t he site re q uire t his i nf or mati o n f or partici pa nt ma na ge me nt.
a. O nl y if uri ne di pstic k is p ositi ve f or bl o o d, pr otei n, nitrites, or le u k oc yte esterase.
b. If uri nal ysis ( di pstic k acce pta ble) de m o nstrates pr otei n greater t ha n or e q ual t o 2 +, t he n a 2 4- h o ur ur i ne pr otei n 
c ollecti o n s h o ul d f oll o w. I n partici pa nts wit h pr otei n uria greater t ha n or e q ual t o 2 gra ms per 2 4 h o urs, be vaciz u ma b -
Pf izer s h o ul d be hel d u ntil rec o ver y (less t ha n 2 gra ms per 2 4 h o urs). Disc o nti n ue be vaciz u ma b- Pf izer i n partici pa nts 
t hat de vel o p ne p hr otic s y n dr o me.
I n vesti gat ors m ust d oc u me nt t heir re vie w of eac h la b orat or y safety re p ort, i ncl u di n g 
deter mi nati o n of cli nical si g nifica nce.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 1
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi ni ti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, F oll o w -u p, a n d Re p orti n g
1 0. 3. 1. Defi niti o n of A E
A E Defi niti o n

A n A E is a n y u nt o war d me dical occ urre nce i n a partici pa nt or cli nical st u d y 
partici pa nt, te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or 
n ot c o nsi dere d relate d t o t he st u d y  i nter ve nti o n.

N O T E: A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g 
a n a b n or mal la b orat or y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) 
te m p orall y ass ociate d wit h t he use of st u d y inter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or 
uri nal y sis) or ot her safet y assess me nts (e g, E C G, ra di ol o gical sca ns, vital si g n 
meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nicall y  
si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or (ie, n ot 
relate d t o pr o gressi o n of u n derl yi n g disease).

E xacer bati o n of a c hr o nic or i nter mitte nt pree xisti n g c o n diti o n i ncl u di n g eit her 
a n i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o ns detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n 
e ve n t h o u g h it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y  
i nter ve nti o n or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as 
a n A E/ S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble 
s uici dal/selfhar mi n g i nte nt. S uc h o ver d oses s h o ul d be re p orte d re gar dless of 
se q uelae.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 2
E ve nts N O T Meeti n g t he A E Defi niti o n

A n y  cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safety 
assess me nts w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y  
t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms 
of t he disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he 
partici pa nt’s c o n diti o n.

Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is t he A E.

Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pita l).

A ntici pate d da y  t o da y fl uct uati o ns of pree xisti n g disease(s) or c o n diti o n(s) 
prese nt or detecte d at t he start of t he st u d y  t hat d o n ot w orse n.

W orse ni n g of si g ns a n d s y m pt o ms of t he mali g na nc y  u n der st u d y s h o ul d be 
rec or de d as A Es i n t he a p pr o priate secti o n of t he C R F. Disease pr o gressi o n 
assesse d b y meas ure me nt of mali g na nt lesi o ns o n ra di o gra p hs or ot her met h o ds 
s h o ul d n ot be re p orte d as A Es.
1 0. 3. 2. Defi niti o n of S A E
If a n e ve nt is n ot a n A E per defi niti o n a b o ve, t he n it ca n n ot be a n S A E e ve n if seri o us 
c on diti o ns are met (e g, h os pitalizati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y , deat h 
d ue t o pr o gressi o n of disease).
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:
a.
Res ults i n deat h
b.
Is life t hreate ni n g
T he ter m “life t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h t he 
partici pa nt was at ris k of deat h at t he ti me of t he e ve nt. I t d oes n ot refer t o a n e ve nt t hat 
h y p ot heticall y  mi g ht ha ve ca use d deat h if it were m ore se vere.
c.
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
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n detai ne d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or o bser vati o n 
a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h ys icia n’s office or 
o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es. If a 
c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he e ve nt is 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 3
seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or was necessar y, t he 
A E s h o ul d be c o nsi dere d seri o us.
H os pitalizati o n f or electi ve treat me nt of a pree xisti n g c o n diti o n t hat di d n ot w orse n fr o m 
baseli ne is n ot c o nsi dere d a n A E.
d.
Res ults i n persiste nt disa bilit y /i nca pacity

T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e g, s prai ne d a n kle) w hic h ma y i nterfere wit h or 
pre ve nt e ver y d a y  life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
e.
Is a c o n ge nital a n o maly/ birt h defect
f.
Ot her sit uati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w het her S A E 
re p orti n g is a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical e ve nts t hat 
ma y  n ot be i m me diately l ifet hreate ni n g or res ult i n deat h or h os pitalizati o n b ut 
ma y  je o par dize t he partici pa nt or ma y re q uire me dical or s ur gical i nter ve nti o n t o 
pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve defi niti o n. T hese e ve nts 
s h o ul d us uall y be c o nsi dere d seri o us.

E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, 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 y scrasias or c o n v ulsi o ns 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.

Pr o gressi o n of t he mali g na nc y  u n der st u dy (i ncl u di n g si g ns a n d sy m pt o ms of 
p r o gressi o n) s h o ul d n ot be re p orte d as a n S A E u nless t he o utc o me is fatal wit hi n 
t he acti ve c ollecti o n peri o d. H os pitalizati o n d ue t o si g ns a n d sy m pt o ms of 
disease pr o gressi o n s h o ul d n ot be re p orte d as a n S A E. If t he mali g na nc y  has a 
fatal o utc o me d uri n g t he st u d y or wit hi n t he acti ve c ollecti o n peri o d, t he n 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 o n t he C R F, a n d as a n S A E 
wit h C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts ( C T C A E) Gra de 5 (see 
t he A ssess me nt of I nte nsit y secti o n).

S us pecte d tra ns missi o n via a Pfizer pr o d uct of a n i nfecti o us a ge nt, pat h o ge nic or 
n o n -pat h o ge nic, is c o nsi dere d seri o us. T he e ve nt ma y  be s us pecte d fr o m cli nical 
s ym pt o ms or la b orat or y  fi n di n gs i n dicati n g a n i nfecti o n i n a partici pa nt e x p ose d 
t o a Pfizer pr o d uct. T he ter ms “s us pecte d tra ns missi o n” a n d “tra ns missi o n” are 
c o nsi dere d s y n o n y m o us. T hese cases are c o nsi dere d u ne x pecte d a n d ha n dle d as 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 4
seri o us e x pe dite d cases b y p har mac o vi gila nce pers o n nel. S uc h cases are als o 
c o nsidere d f or re p orti n g as pr o d uct defects, if a p pr o priate.
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w -u p of A Es a n d/ or S A Es
A E a n d S A E Rec or di n g/ 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 a d verse e ve nts o n t he C R F 
a n d f or re p orti n g seri o us a d verse e ve nts o n t he Cli nical Trial ( C T) Seri o us A d verse 
E ve nt ( S A E) 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 ypes 
of e ve nts: ( 1) S A Es; ( 2) n o nseri o us a d verse e ve nts ( A Es); a n d ( 3) e x p os ure t o t he st u d y  
i nter ve nti o n u n der st u dy d uri n g pre g na nc y  or breastfee di n g, a n d occ u pati o nal e x p os ure. 
It s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf or mati o n is n ot 
t he sa me as t he A E pa ge of t he C R F. W he n t he sa me data are c ollecte d, t he f or ms m ust 
be c o m plete d i n a c o nsiste nt ma n ner. A Es s h o ul d be rec or de d usi n g c o ncise me dical 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E 
Re p ort F or m f or re p orti n g of S A E i nf or mati o n.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs 
of A w are ness
S A E
All
All
N o nseri o us A E
All
N o ne
E x p os ure t o t he st u d y  
i nter ve nti o n u n der st u dy 
d uri n g pre g na nc y  or 
breastfee di n g, a n d 
occ u pati o nal e x p os ure
All A Es/ S A Es ass oci ate d 
wit h e x p os ure d uri n g 
pre g na nc y ( E D P) or 
bre astfee di n g
Occ u pati o nal e x p os ure is 
n ot rec or de d.
All i nsta nces of E D P a n d 
e x p os ure d uri n g 
breastfee di n g ( w het her or 
n ot t here is a n ass ociate d 
S A E ).
All S A Es ass ociate d wit h 
occ u pati o nal e x p os ure. 
N ote: I ncl u de all S A Es 
ass ociate d wit h e x p os ure 
d uri n g pre g na nc y  or 
breastfee di n g. I ncl u de all 
A Es/ S A Es ass ociate d wit h 
occ u pati o nal e x p os ure.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 5

W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he i n vesti gat or t o re vie w all 
d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y  re p orts, a n d dia g n ostic 
re p orts) relate d t o t he e ve nt.

T he i n vesti gat or will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t he C R F.

It is n ot acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s 
me dical rec or ds t o Pfizer Safet y  i n lie u of c o m pleti o n of t he C T S A E Re p ort 
F or m/ A E/ S A E C R F pa ge.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q uested b y  Pfizer Safet y. In t his case, all partici pa nt i de ntifiers, wit h t he 
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y.

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis 
( n ot t he i n di vi d ual si g ns/s ym pt o ms) will be d oc u me nte d as t he A E/ S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y  for eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 
G R A D E
Cli nical Descri pti o n of Se verit y
1
MI L D a d verse e ve nt
2
M O D E R A T E a d verse e ve nt
3
S E V E R E a d verse e ve nt
4
LI F E -T H R E A T E NI N G c o nse q ue nces; ur ge nt i nter ve nti o n i n dicate d
5
D E A T H R E L A T E D T O a d verse e ve nt
Assess me nt of C a us alit y

T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y 
i nter ve nti o n a n d eac h occ urre nce of eac h A E/ S A E.

A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, 
e vi de nce, a n d/ or ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a 
relati o ns hi p ca n n ot be r ule d o ut.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 6

T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p.

Alter nati ve ca uses, s uc h as u n derl yi n g dis ease(s), c o nc o mita nt t hera p y, a n d ot her 
ris k fact ors, as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y i nter ve nti o n 
a d mi nistrati o n will be c o nsi dere d a n d i n vesti gate d.

T he i n vesti gat or will als o c o ns ult t he i n vesti gat or’s br oc h ure (I B) a n d/ or pr o d uct 
i nf or mati o n, f or mar kete d pr o d ucts, i n his/ her assess me nt.

F or eac h A E/ S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat 
he/s he has re vie we d t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has 
mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o t he s p o ns or. H o we ver, it is 
ver y i m p ort a nt t h at t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E dat a t o t he 
s p o ns or.

T he i n vesti gat or ma y  c ha n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w- u p 
i nf or mati o n a n d se n d a n S A E f oll o w-u p re p ort wit h t he u p date d ca usalit y  
assess me nt.

T he ca usalit y  assess me nt is o ne of t he criteria use d w he n deter mi ni n g re gulat or y  
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n ca use d 
t he e ve nt, t he n t he e ve nt will be ha n dle d as “relate d t o st u d y i nter ve nti o n” f or 
re p orti n g p ur p oses, as defi ne d b y t he s p o ns or. I n a d diti o n, if the i n vesti gat or 
deter mi nes t hat a n S A E is ass ociate d wit h st u d y  pr oce d ures, t he i n vesti gat or 
m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d re p ort 
s uc h a n assess me nt i n t he de dicate d secti o n of t he C T S A E Re p ort F or m a n d i n 
acc orda nce wit h t he S A E re p orti n g re q uire me nts.
F oll o w - u p of A Es a n d S A Es

T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of 
s u p ple me ntal meas ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d or as 
re q ueste d by t he s p o ns or t o el uci date t he nat ure a n d/ or ca usality of t he A E or 
S A E as f ull y  as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests or 
i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her 
healt hcare pr ofessi o nals.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 7

If a partici pa nt dies d uri n g partici patio n i n t he st u d y  or d uri n g a rec o g nize d 
f oll o w- u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safety wit h a c o p y of a n y 
p ost m orte m fi n di n gs i ncl u di n g hist o pat h ol o g y, w he n a vaila ble.

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  c o m plete d C RF.

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A Es
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D at a C ollecti o n T o ol

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y  will be t he 
electr o nic data c ollecti o n t o ol.

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E data 
c ollecti o n t o ol (see ne xt secti o n) i n or der t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T he site will e nter t he S A E data i nt o t he electr o nic s yste m as s o o n as t he data 
bec o me a vaila ble.

After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic data c ollecti o n t o ol 
will be ta ke n offli ne t o pre ve nt t he e ntr y  of ne w data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves 
u p date d data o n a pre vi o usl y  re p orte d S A E after t he electr o nic data c ollecti o n 
t o ol has bee n ta ke n offli ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per 
S A E f or m (see ne xt secti o n) or t o Pfizer S afet y b y tele p h o ne.
S A E Re p orti n g t o Pfizer S afet y vi a C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is t he preferre d met h o d t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y.

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, n otificati o n b y tele p h o ne is 
acce pta ble wit h a c o p y of t he C T S A E Re p ort F or m se nt b y  o ver ni g ht mail or 
c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d 
re p orti n g ti me fra mes.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 8
1 0. 4. A p pe n di x 4: C o ntr ace pti ve G ui d a nce a n d C ollecti o n of Pre g n a nc y I nf or m ati o n
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 1 0 5 d a y s after t he last d ose of st u d y i nter ve nti o n of 
P F -0 7 0 6 2 1 1 9 a n d f or at least 6 m o nt hs after t he last d ose of P F -0 6 8 0 1 5 9 1 (sasa nli ma b) a n d 
be vaciz u ma b -Pfizer, w hic h c orres p o n ds t o t he ti me nee de d t o eli mi nate st u d y  i nter ve nti o n(s):

Refrai n fr o m d o nati n g s per m.
P L U S eit her :

Be a bsti ne nt fr o m heter ose x ual i nterc o urse wit h a fe male of c hil d beari n g p ote ntial as 
t heir preferre d a n d us ual lifest yle (a bsti ne nt o n a l o n gter m a n d persiste nt basis) a n d 
a gree t o re mai n a bsti ne nt.
O R

M ust a gree t o use a male c o n d o m w he n e n ga gi n g i n a n y  acti vit y t hat all o ws f or 
passa ge of ejac ulate t o a n ot her pers o n.

I n a d diti o n t o male c o n d o m use, a hi g hly effecti ve met h o d of c o ntrace pti o n ma y be 
c o nsi dere d i n W O C B P part ners of male partici pa nts (refer t o t he list of hi g hl y  
effecti ve met h o ds bel o w i n Secti o n 1 0. 4. 4 ).
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
A fe male partici pa nt is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g, a n d at 
least 1 of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o ns bel o w i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d usi n g a c o ntrace pti ve met h o d t hat is hi g hl y effecti ve ( wit h a fail ure 
rate of < 1 % per year), as descri be d bel o w, d uri n g t he i nter ve nti o n peri o d a n d f or at 
least 1 0 5 d a y s after t he last d ose of P F -0 7 0 6 2 1 1 9 i nter ve nti o n a n d at least 6 m o nt hs 
after t he last d ose of P F - 0 6 8 0 1 5 9 1 (sasa nli ma b) a n d be vaciz u ma b-Pfizer, w hic h 
c orres p o n ds t o t he ti me nee de d t o eli mi nate a n y st u d y  i nter ve nti o n(s). T he 
i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he c o ntrace pti ve met h o d i n 
relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n earl y u n detecte d 
pre g na nc y . 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 9
1 0. 4. 3. W o m a n of C hil d be ari n g P ote nti al ( W O C B P)
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me n orr hea i n a d olesce nts or at hletes) a n d a me nstr ual c ycle ca n n ot 
be c o nfir me d bef ore t he first d ose of st u d y  i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:
1.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y ;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a n alter nate me dical ca use ot her 
t ha n t he a b o ve, (e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or 
di screti o n s h o ul d be a p plie d t o deter mi ni n g st u dy e ntr y.
N ote: D oc u me ntati o n f or a n y  of t he a b o ve cate g ories ca n c o me fr o m t he site 
pers o n nel’s re vie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or 
me dical hist or y  i nter vie w. T he met h o d of d oc ume ntati o n s h o ul d be rec or de d i n 
t he partici pa nt’s me dical rec or d f or t he st u dy.
2.
P ost me n o pa usal fe male.

A p ost me n o pa usal state is defi ne d as a ge 6 0 ye ars or ol der or n o me nses f or 
1 2 m o nt hs wit h o ut a n alter nati ve me dical ca use.

A hi g h f ollicle -sti m ulati n g h or m o ne ( F S H) le vel i n t he p ost me n o pa usal ra n ge 
ma y  be use d t o c o nfir m a p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal 
c o ntrace pti o n or h or m o ne re place me nt t hera p y ( H R T). W he n t here is a hi g h F S H 
le vel, it s h o ul d be c o nfir me d t hat t here is n o ot her me dical ca use.

Fe males o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o use 
o ne of t he n o nestr o ge n h or m o nal hi g hl y effecti ve c o ntrace pti o n met h o ds if t he y 
wis h t o c o nti n ue t heir H R T d uri n g t he st u d y. Ot her wise, t he y m ust disc o nti n ue 
H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y e nr oll me nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 0
1 0. 4. 4. C o ntr ace pti o n Met h o ds
1.
I m pla nta ble pr o gest o ge n-o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n.
2.
I ntra uteri ne de vice (I U D).
3.
I ntra uteri ne h or m o ne-releasi n g sys te m (I U S).
4.
Bilateral t u bal occl usi o n.
5.
Vasect o mize d part ner.

Vasect o mize d part ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat t he 
part ner is t he s ole se x ual part ner of t he w o ma n of c hil d beari n g p ote ntial a n d t he 
a bse nce of s per m has bee n c o nfir me d. If n ot , a n a d diti o nal hi g hl y effecti ve 
met h o d of c o ntrace pti o n s h o ul d be use d. T he s per mat o ge nesis c y cle is 
a p pr o xi matel y 9 0 d a y s.
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n.

Oral;

I ntra va gi nal ( n ot a p pr o ve d i n Ja pa n);

Tra ns der mal ( n ot a p pr o ve d i n Ja pa n);

I njecta ble ( n ot a p pr o ve d i n Ja pa n).
7.
Pr o gest o ge n - o nly h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n.

Oral ( n ot a p pr o ve d i n Ja pa n);

I njecta ble ( n ot a p pr o ve d i n Ja pa n).
8.
Se x ual a bsti ne nce.

Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d 
wit h t he st u d y  i nter ve nti o n. T he relia bilit y of se x ual a bsti ne nce nee ds t o be 
e val uate d i n relati o n t o t he d urati o n of t he st u d y a n d t he preferre d a n d us ual 
lifest yle of t he partici pa nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 1
C ollecti o n of Pre g n a nc y I nf or m ati o n
F or b ot h u na p pr o ve d/ u nlice nse d pr o d ucts a n d f or mar kete d pr o d ucts, a n e x p os ure d uri n g 
pre g na nc y  ( E D P) occ urs if:

A fe mal e 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 
e x p ose d (e g, beca use of treat me nt or e n vir o n me ntal e x p os ure) t o t he st u d y  
i nter ve nti o n; or t he 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 
a n d/ or bei n g e x p ose d t o t he st u d y  i nter ve nti o n;

A n e xa m ple of e n vir o n me ntal e x p os ure w o ul d be a case i n v ol vi n g direct c o ntact 
wit h a Pfizer pr o d uct i n a pre g na nt w o ma n (e g, a n urse re p orts t hat s he is pre g na nt 
a n d has bee n e x p ose d t o c he m ot hera pe utic pr o d ucts).

A male has bee n e x p ose d (e g, beca use of treat me nt or e n vir o n me ntal e x p os ure) t o t he 
st u d y i nter ve nti o n pri or t o or ar o u n d t he ti me of c o nce pti o n a n d/ or is e x p ose d d uri n g 
his part ner’s pre g na nc y .
If a partici pa nt or partici pa nt’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 
partici pa nt’s treat me nt wit h t he st u d y i nter ve nti o n, t he i n vesti gat or m ust re p ort t his 
i nf or mati o n t o Pfizer Safet y  o n t he C T S A E Re p ort F or m a n d a n E D P s u p ple me ntal f or m, 
re gar dless of w het her a n S A E has occ urre d. I n a d diti o n, t he i n vesti gat or m ust s u b mit 
i nf or mati o n re gar di n g e n vir o n me ntal e x p os ure t o a Pfizer pr o d uct i n a pre g na nt w o ma n (e g, a 
partici pa nt re p orts t hat s he is pre g na nt a n d has bee n e x p ose d t o a c yt ot o xi c pr o d uct b y 
i n halati o n or s pilla ge) t o Pfizer Safet y usi n g t he E D P s u p ple me ntal f or m. T his m ust be d o ne 
irres pecti ve of w het her a n A E has occ urre d a n d wit hi n 2 4 h o urs of a ware ness of t he 
e x p os ure. T he i nf or mati o n s u b mitte d s h o ul d i ncl u de t he a ntici pate d d ate of deli ver y (see 
bel o w f or i nf or mati o n relate d t o ter mi nati o n of pre g na nc y ).
F oll o w -u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me. T he i n vesti gat or will f oll o w t he pre g na nc y  until 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w- u p t o t he i nitial E D P s u p ple me ntal f or m. I n t he case of a li ve birt h, t he str uct ural 
i nte grity of t he ne o nate ca n be assesse d at t he ti me of 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 he str uct ural 
i nte grity 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 
pre -pr oce d ure test fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o mal y a n d t he fi n di n gs are 
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 (ie, 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 de mise, ne o natal deat h, or c o n ge nital a n o mal y [i n a 
li ve-b or n ba b y, 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 
i n vesti gat or s h o ul d f oll o w t he pr oce d ures f or re p orti n g S A Es.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 2
A d diti o nal i nf or mati o n a b o ut pre g na nc y  o utc o mes t hat are re p orte d t o Pfizer Safety as S A Es 
f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d es 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, wit h o ut re gar d 
t o ca usalit y, as S A Es. I n a d diti o n, i nfa nt deat hs after 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 d eat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n.
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or. 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 n ts t o i de ntif y de vel o p me ntal dela ys). In t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he partici pa nt 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. T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u me nts t h at 
t he partici pa nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his 
part ner.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 3
1 0. 5. A p pe n di x 5: Ge netics
Use/ A n al ysis of D N A

Ge netic variati o n ma y  i m pact a partici pa nt’s res p o nse t o st u d y i nter ve nti o n, 
s usce pti bilit y t o, a n d se verit y a n d pr o gressi o n of disease. T heref ore, w here l ocal 
re g ulati o ns a n d I R Bs/ E Cs all o w, a bl o o d sa m ple will be c ollecte d f or D N A a nalys is.

Ge netic researc h ma y  c o nsist of t he a nal ysis of 1 or m ore ca n di date ge nes or t he 
a nal ys is of ge netic mar kers t hr o u g h o ut the ge n o me or a nal ys is of t he e ntire ge n o me 
(as a p pr o priate).

T he sa m ples ma y  be a nal yze d as part of a m ulti-st u d y assess me nt of ge netic fact ors 
i n v ol ve d i n t he res p o nse t o st u d y i nter ve nti o n or st u d y treat me nts of t his class t o 
u n dersta n d treat me nts f or t h e disease(s) u n der st u d y or t he disease(s) t he msel ves.

T he res ults of ge netic a nal y ses ma y be re p orte d i n t he cli nical st u d y re p ort ( C S R) or 
i n a se parate st u d y s u m mar y or ma y be use d f or i nter nal decisi o n ma ki n g wit h o ut 
bei n g i ncl u de d i n a st u d y re p ort.

T he s p o ns or will st ore t he D N A sa m ples i n a sec ure st ora ge s pace wit h a de q uate 
meas ures t o pr otect c o nfi de ntialit y .

T he sa m ples will be retai ne d as i n dicate d:
Sa m ples f or ba n ki n g (see Secti o n 8. 7. 2 ) will be st ore d i n defi nitely or ot her peri o d as per 
l ocal re q uire me nts.

Partici pa nts ma y  wit h dra w t heir c o nse nt f or t he st ora ge a n d/ or use of t heir ba n ke d 
bi os peci me ns at a n y ti me b y  ma ki n g a re q uest t o t he i n vesti gat or; i n t his case, a n y 
re mai ni n g material will be destr oye d. Data alrea d y ge nerate d fr o m t he sa m ples will 
be retai ne d t o pr otect t he i nte grit y of e xisti n g a nal yses.

Ba n ke d bi os peci me ns will be la bele d wit h a c o de. T he k e y  bet wee n t he c o de a n d t he 
partici pa nt’s pers o nall y  i de ntif yi n g i nf or mati o n (e g, na me, a d dress) will be hel d at t he 
st u d y site a n d will n ot be pr o vi de d t o t he sa m ple ba n k. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 4
1 0. 6. A p pe n di x 6: Li ver S afet y: S u g geste d Acti o ns a n d F oll o w - u p Assess me nts 
P ote nti al C ases of Dr u g -I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y, b ut a da pt 
are ter me d “a da pt ors.”  I n s o me partici pa nts, tra nsa mi nase ele vati o ns are a har bi n ger of a 
m ore seri o us p ote ntial o utc o me. T hese partici pa nts fail t o a da pt a n d t heref ore are 
“s usce pti ble” t o pr o gressi ve a n d seri o us li ver i nj ur y , c o m m o nly referre d t o as dr u g -i n d uce d 
li ver i nj ur y ( DI LI). Partici pa nts w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 ti mes t he 
u p per li mit of n or mal ( × U L N) s h o ul d be m o nit ore d m ore fre q ue ntl y t o deter mi ne if t he y  are 
a n “a da pt or” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n as partate a mi n otra nsferase ( A S T) a n d/ or ala ni ne 
a mi n otra nsferase ( A L T) prece de t otal bilir u bi n ( T bili) ele vati o ns ( > 2 × U L N) b y  se veral da ys 
or wee ks. T he i ncrease i n T bili t y picall y  occ urs w hile A S T/ A LT is/are still ele vate d a b o ve 3 
× U L N (ie, A S T/ A L T a n d T bili val ues will be ele vate d wit hi n t he sa me la b orat or y  sa m ple). 
I n rare i nsta nces, by t he ti me T bili ele vati o ns are detecte d, A S T/ A L T val ues mi g ht ha ve 
decrease d. T his occ urre nce is still re gar de d as a p ote ntial DI LI. T heref ore, a b n or mal 
ele vati o ns i n eit her A S T O R A L T i n a d diti o n t o T bili t hat meet t he criteria o utli ne d bel o w 
are c o nsi dere d p ote ntial DI LI (assesse d per H y ’s la w criteria) cases a n d s h o ul d al wa ys be 
c o nsi dere d i m p orta nt me dical e ve nts, e ve n bef ore all ot her p ossi ble ca uses of li ver i nj ur y 
ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he 
partici pa nt’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa nts w h o prese nt 
wit h t he f oll o wi n g la b orat or y  a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI 
( Hy’s la w) cases t o defi niti vel y  deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

Partici pa nts wit h A S T/ A L T a n d T bili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h A S T O R A LT val ues > 3 × U L N A N D a T bili val ue 
> 2 × U L N wit h n o e vi de nce of he m ol ys is a n d a n al kali ne p h os p hatase val ue 
< 2 × U L N or n ot a vaila ble.

F or partici pa nts wit h baseli ne A S T O R A L T O R T bili val ues a b o ve t he U L N, t he 
f oll o wi n g t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, 
de pe n di n g o n w hic h val ues are a b o ve t he U L N at baseli ne:
Pree xisti n g A S T or A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T or A L T val ues 
> 2 ti mes t he baseli ne val ues A N D > 3 × U L N; or > 8 × U L N ( w hic he ver is s maller).
Pree xisti n g val ues of T bili a b o ve t he n or mal ra n ge: T bili le vel i ncrease d fr o m baseli ne val ue 
b y  a n a m o u nt of at least 1 × U L N or if t he val ue reac hes > 3 × U L N ( w hic he ver is s maller).
Rises i n A S T/ A L T a n d T bili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 5
T he partici pa nt s h o ul d ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wi t hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal res ults. T his e val uati o n s h o ul d 
i ncl u de la b orat or y tests, detaile d hist or y, a n d p h ysical assess me nt. 
I n a d diti o n t o re peati n g meas ure me nts of A S T a n d A LT a n d T bili f or s us pecte d cases of 
H y ’s la w, a d diti o nal lab orat or y  tests s h o ul d i ncl u de al b u mi n, creati ne ki nase ( C K), direct a n d 
i n direct bilir u bi n, ga m ma-gl uta m yl  tra nsferase ( G G T), pr ot hr o m bi n ti me ( P T)/i nter nati o nal 
n or malize d rati o (I N R), t otal bile aci ds, a n d al kali ne p h os p hatase. C o nsi derati o n s h o ul d als o 
be gi ve n t o dra wi n g a se parate t u be of cl otte d bl o o d a n d a n a ntic oa g ulate d t u be of bl o o d f or 
f urt her testi n g, as nee de d, f or f urt her c o nte m p ora ne o us a nalys es at t he ti me of t he rec o g nize d 
i nitial a b n or malities t o deter mi ne eti ol o g y. A detaile d hist or y, i ncl u di n g rele va nt i nf or mati o n, 
s uc h as re vie w of et ha n ol, aceta mi n o p he n (eit her b y itself or as a c o -f or m ulate d pr o d uct i n 
prescri pti o n or o ver -t he- c o u nter me dicati o ns), recreati o nal dr u g, s u p ple me nt ( her bal) use a n d 
c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, tra vel hist or y, hist or y of c o ntact wit h a 
ja u n dice d pers o n, s ur ger y, bl o o d tra nsf usi o n, hist or y of li ver or aller gic disease, a n d p ote ntial 
occ u pati o nal e x p os ure t o c he micals, s h o ul d be c ollecte d. F urt her testi n g f or ac ute he patitis A, 
B, C, D, a n d E i nfecti o n a n d li ver i ma gi n g (e g, biliar y  tract) a n d c ollecti o n of ser u m sa m ple 
f or aceta mi n o p he n dr u g a n d/ or pr otei n a d d uct le vels ma y be warra nte d.
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
T bili ele vati o n d efi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y ’s la w) cases if n o 
ot her reas o n f or t he li ver f u ncti o n test ( L F T) a b n or malities has y et bee n f o u n d. S uc h 
p ote nti al DI LI ( H y’s l a w) c ases are t o be re p orte d as S A Es, irres pecti ve of a v ail a bilit y 
of all t h e res ults of t he i n vesti g ati o ns perf or me d t o deter mi ne eti ol o g y of t he L F T 
a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all res ults of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 6
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote nti al Cli nic al C o ncer n 
E C G Fi n di n gs T h at M a y
Q u alif y as A d verse E ve nts ( A Es)

Mar ke d si n us bra d y car dia (rate < 4 0 b p m) lasti n g mi n utes.

Ne w P R i nter val pr ol o n gati o n > 2 8 0 msec.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 msec (a bs ol ute) or b y ≥6 0 msec fr o m 
baseli ne.

Ne w o nset - atrial fl utter or fi brillati o n, wit h c o ntr olle d ve ntric ular res p o nse rate:
ie, rate < 1 2 0 b p m.

Ne w -o nset t y pe I sec o n d de gree- ( We nc ke bac h) A V bl oc k of > 3 0 sec o n ds’ 
d urati o n.

Fre q ue nt pre mat ure ve ntric ular c o m ple xes ( P V Cs), tri plets, or s h ort i nter vals 
( < 3 0 sec o n ds) of c o nsec uti ve ve ntric ular c o m ple xes.
E C G Fi n di n gs T h at M a y
Q u alif y as Seri o us A d verse E ve nts ( S A Es)

Q Tc F pr ol o n gati o n > 5 0 0 msec.

Ne w S T -T c ha n ges s u g gesti ve of m y o car dial isc he mia.

Ne w o nset left b u n dle bra nc h bl oc k ( Q R S > 1 2 0 msec).

Ne w o nset ri g ht b u n dle bra nc h bl oc k ( Q R S > 1 2 0 msec).

S y m pt o matic bra d y car dia.

As y st ole:
I n a wa ke, sy m pt o m free partici pa nts i n si n us r h y t h m, wit h d oc u me nte d peri o ds of 
as yst ole ≥3. 0 sec o n ds or a n y esca pe rate < 4 0 b p m, or wit h a n esca pe r h yt h m t hat is bel o w 
t he A V n o de.
I n a wa ke, sy m pt o m free partici pa nts wit h atrial fi brillati o n a n d bra d y car dia wit h 1 or 
m ore pa uses of at least 5 sec o n ds or l o n ger.
Atrial fl utter or fi brillati o n, wit h ra pi d ve ntric ular res p o nse rate: ra pi d = rate > 1 2 0 b p m.

S ustai ne d s u pra ve ntric ular tac h yc ar dia (rate > 1 2 0 b p m) (“s ustai ne d” = s h ort 
d urati o n wit h rele va nt s y m pt o ms or lasti n g > 1 mi n ute).

Ve ntric ular r h yt h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r hyt h m (rate 
< 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( 4 0 < x < 1 0 0), a n d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 7
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h y car dia > 1 0 0 b p m (s uc h as t orsa des de 
p oi ntes).

T y pe II sec o n d- de gree ( M o bitz II) A V bl oc k.

C o m plete (t hir d- de gree) heart bl oc k.
E C G Fi n di n gs T h at Q u alif y as Seri o us A d verse E ve nts

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n.

S ustai ne d ve ntric ular tac h y arr h yt h mias ( > 3 0 sec o n ds’ d urati o n).

Sec o n d - or t hir d -de gree A V bl oc k re q uiri n g pace ma ker place me nt.

As y st olic pa uses re q uiri n g pace ma ker place me nt.

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g 
car di o versi o n.

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he e n u merate d list of maj or e ve nts of p ote ntial cli nical c o ncer n are rec o m me n de d as “alerts” or 
n otificati o ns fr o m t he c ore E C G la b orat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be 
c o nsi dere d as all -i ncl usi ve of w hat t o be re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 8
1 0. 8. A p pe n di x 8: C o u ntr y -S pecific Re q uire me nts
T he i n vesti gat or a grees t o a bi de b y t he et hical pri nci ples set f ort h i n t he W orl d Healt h 
Or ga nizati o n’s G ui di n g Pri nci ples f or H u m a n Cell, Tiss ue a n d Or g a n Tr a ns pl a nt ati o n 
( W H A 6 3. 2 2) ( htt p:// w w w. w h o.i nt/tra ns pla ntati o n/e n/) wit h re gar d t o t he st u d y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 9
1 0. 9. A p pe n di x 9: Preli mi n ar y Cli nic al S u m m ar y f or St u d y B 8 0 1 1 0 0 1 P h ase 1 FI H 
( P F-0 6 8 0 1 5 9 1) 
Data C ut off Date: 2 9 A u g ust 2 0 1 9
St u d y Desi g n: 
B 8 0 1 1 0 0 1 is a n o n g oi n g P hase 1, o pe n- la bel, d ose escalati o n a n d e x pa nsi o n st u d y of 
P F -0 6 8 0 1 5 9 1 i n partici pa nts wit h l ocall y  a d va nce d or metastatic mela n o ma, S C C H N, 
o varia n ca ncer, sarc o ma, N S C L C, ur ot helial carci n o ma or ot her s oli d t u m ors. T he pri mar y  
p ur p ose of t his st u d y  is t o e val uate safety a n d earl y si g ns of efficac y of P F-0 6 8 0 1 5 9 1. T his 
cli nical st u d y was di vi de d i nt o a d ose escalati o n ( Part 1) p hase, a n d a d ose e x pa nsi o n ( Part 2) 
p hase.
P art 1 D ose Esc al ati o n
Part 1 d ose escalati o n e val uate d 4 pre -s pecifie d I V d ose le vels ( 0. 5, 1, 3, a n d 1 0 m g/ k g 
a dmi nistere d e ver y  3 wee ks [ Q 3 W]), a n d 1 s u bc uta ne o us ( S C) d ose le vel ( 3 0 0 m g 
a d mi nistere d e ver y 4 wee ks [ Q 4 W]) i n a d ult partici pa nts wit h l ocall y a d va nce d or metastatic 
mela n o ma, s q ua m o us cell ca ncer of hea d a n d nec k ( S C C H N), o varia n ca ncer, sarc o ma, s mall 
cell l u n g ca ncer ( S C LC), a de n ocarci n o ma of sali var y  gla n d, e n d o metrial a de n ocarci n o ma, 
mali g na nt perit o neal ne o plas m, es o p ha geal a de n ocarci n o ma or re nal cell carci n o ma. Pat ie nts 
ha d pr o gressi ve disease o n ≥1 pri or li ne of t hera p y f or l ocall y a d va nce d or me tastatic disease 
or ref use d sta n dar d of care t hera p y;  were n ot pre vi o usl y treate d wit h a n a nti -P D -1/ P D -L 1  
a ge nt; a n d ha d a de q uate re nal, b o ne marr o w, li ver, a n d car diac f u ncti o n, wit h Easter n 
C o o perati ve O nc ol o g y  Gr o u p ( E C O G)  perf or ma nce stat us 0 or 1. F o rty partici pa nts were 
e nr olle d i nt o Part 1 wit h 2 5 partici pa nts t otal e nr olle d i nt o t he I V d ose c o h orts a n d 1 5 
partici pa nts e nr olle d i nt o t he S C d ose c o h ort. 
P art 2 D ose Ex p a nsi o n
T he 3 0 0 m g S C d ose was e val uate d i n a n e x pa n de d p o p ulati o n of 1 0 6 partici pa nts. T his 
i ncl u de d 6 8 partici pa nts wit h l ocall y  a d va nce d or metastatic n o n-s mall cell l u n g ca ncer 
( N S C LC) a n d 3 8 partici pa nts wit h l ocall y  a d va nce d or metastatic ur ot helial carci n o ma ( U C) 
w h o were a nti -P D -1 or a nti -P D -L 1  treat me nt-naï ve a n d w h o ha d pr o gres si ve disease o n or 
were i nt olera nt t o s y ste mic t hera p y or f or w h o m sta n dar d of care sys te mic t hera p y was 
ref use d or u na vaila ble. Patie nts wit h N S C LC c o ul d ha ve recei ve d u p t o o ne li ne of pri or 
s yste mic t hera p y f or l ocall y a d va nce d or metastatic disease a n d if t he y ha d k n o w n e pi der mal 
gr o wt h fact or rece pt or ( E G F R) acti vati n g m utati o n or a n a na plastic l y m p h o ma ki nase ( A L K) 
rearra n ge me nt were re q uire d t o ha ve, i n a d diti o n, at least o ne tar gete d t hera p y f or t heir 
disease. Patie nts wit h U C c o ul d ha ve recei ve d u p t o 2 li nes of pri or sys te mic t hera pies f or 
l ocall y a d va nce d or metastatic disease. T he selecte d partici pa nts ha d a de q uate re nal, b o ne 
marr o w, li ver, a n d car diac f u ncti o n, wit h E C O G perf or ma nce stat us 0 or 1. All partici pa nts 
recei ve d 3 0 0 m g of P F -0 6 8 0 1 5 9 1 S C e ver y  4 wee ks. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 0
Cli nic al O ver vie w
St u d y  B 8 0 1 1 0 0 1 is a n o n g oi n g P hase 1, o pe n-la bel, d ose escalati o n a n d e x pa nsi o n st u d y of 
sasa nli ma b i n partici pa nts wit h l ocall y a d va nce d or metastatic mela n o ma, s q ua m o us cell 
carci n o ma of t he hea d a n d nec k, o varia n c a ncer, sarc o ma, N S C L C, U C, or ot her s oli d 
t u m ors.  T he pri mar y p ur p ose of t he st u d y was t o e val uate safety a n d earl y si g ns of efficac y 
of sasa nli ma b.  T he cli nical st u d y  was di vi de d i nt o a d ose escalati o n ( Part 1) p hase, a n d a 
d ose e x pa nsi o n ( Part 2) p hase .  O ne h u n dre d f ort y-si x ( 1 4 6) partici pa nts ha ve bee n d ose d o n 
t he st u d y.  F orty ( 4 0) partici pa nts were e nr olle d i nt o Part 1 a n d 1 0 6 partici pa nts ( 6 8 wit h 
N S C L C a n d 3 8 wit h U C) were e nr olle d i nt o Part 2.  I n Part 1, 4 pre -s pecifie d I V d ose le vels 
( 0. 5, 1, 3, a n d 1 0 m g / k g a d mi nistere d Q 3 W), a n d 1 S C d ose le vel ( 3 0 0 m g a d mi nistere d 
Q 4 W) were e val uate d f or safet y.  N o D L Ts were o bser ve d a n d t h us, t here was n o ma xi m u m 
t olerate d d ose i de ntifie d.  T he 3 0 0 m g S C d ose was selecte d base d o n be nefit/ris k 
assess me nt.
As of t he data c ut off of 2 8 A u g ust 2 0 1 9, 1 3 of 1 5 partici pa nts treate d wit h sasa nli ma b 
3 0 0 m g S C d ose ( Part 1) e x perie nce d at least 1 treat me nt-relate d A E.  T he m ost c o m m o n 
treat me nt-relate d A Es re p orte d were diarr hea, fati g ue a n d decrease a p petite 
( n = 4 partici pa nts eac h, 2 6. 7 %), a n d na usea, c o u g h, a n d d ys p nea ( n = 3 partici pa nts eac h, 
2 0. 0 %).  O ne partici pa nt e x perie nce d a Gra de 3 treat me nt -relate d A E (a ne mia).  T here were 
n o Gra de 4 or Gra de 5 treat me nt -relate d A Es.
A t otal of 6 0 of 1 0 6 partici pa nts e x p erie nce d at least 1 treat me nt-relate d A E i n Part-2.  M ost 
c o m m o nl y re p orte d treat me nt-relate d A Es e x perie nce d by > 5 % of partici pa nts were 
h y pert h y r oi dis m ( n = 1 1; 1 0. 4 %), li pase i ncrease d a n d pr urit us ( n = 7; 6. 6 %) eac h a n d 
a m ylase i ncrease d, h yp ot h y r oi dism, a n d a ne mia ( n = 6; 5. 7 %) eac h.  Gra de 3 treat me nt -
relate d A Es i ncl u de d li pase i ncrease, a myl ase i ncrease d (eac h n = 2, 1. 9 %), bl o o d al kali ne 
p h os p hatase i ncrease d, decrease d a p petite, h y per ma g nese mia, p ne u m o nitis, a ge usia, 
a n os mia, a n d ja u n dice (eac h n = 1, 0. 9 %).  Gra de 4 treat me nt -relate d A Es i ncl u de d li pase 
i ncrease d, ne utr o p hil c o u nt decrease d, w hite bl o o d cell c o u nt decrease d (eac h n = 1, 0. 9 %). 
Gra de 5 treat me nt -relate d A E i ncl u de d arr hyt h mia ( n = 1, 0. 9 %).  F or treat me nt -relate d S A Es 
re p orte d, refer t o t he sasa nli ma b ( P F- 0 6 8 0 1 5 9 1) I B.
N o si g nifica nt i njecti o n site reacti o ns were re p orte d, e xce pt f or 1 case of Gra de 1 i njecti o n 
site pai n.  Safety data i ncl u di n g p ossi ble ir A E are m ostl y  c o nsiste nt wit h t he k n o w n safet y 
pr ofile of a nti -P D -1 treat me nt .
Detaile d safet y i nf or mati o n fr o m cli nical st u dies, as well as n o ncli nical i nf or mati o n, ca n be 
f o u n d i n t he sasa nli ma b ( P F-0 6 8 0 1 5 9 1) I B .
C o ncl usi o ns:
Base d o n t he a vaila ble safet y  a n d efficac y data f or P F-0 6 8 0 1 5 9 1, t he be nefit ris k pr ofile of 
P F - 0 6 8 0 1 5 9 1 is e x pecte d t o be fa v ora ble.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 1
1 0. 1 0. A p pe n di x 1 0: Det aile d D ose Esc al ati o n/ Fi n di n g Sc he me f or B L R M 
T his a p pe n di x pr o vi des t he details of t he statistical m o del, t he descri pti o n of pri or 
distri b uti o n. T he res ults of t he Ba y esia n a nal ys es a n d res pecti ve d osi n g dec isi o ns f or s o me 
h y p ot hetical data sce nari os, a n d a si m ulati o n st u d y  of t he o perati n g c haracteristics of t he 
m o del c o ul d be f o u n d i n t he se parate Tec h nical s u p ple me nt t o t his a p pe n di x. 
1 0. 1 0. 1. St atistic al M o del
Let π ( d) be t he ris k of D L T f or P F - 0 7 0 6 2 1 1 9 gi ve n as a si n gle a ge nt at d ose d. T he 
d ose -D L T m o del is l o gistic:
l o git ( π ( d)) =l o g () +l o g( d ⁄ d *)
d * = 1 8 0 0 µ g a n d use d t o scale t he d oses of P F- 0 7 0 6 2 1 1 9. He nce, ( > 0) are t he 
P F -0 7 0 6 2 1 1 9 o d ds of a D L T at d * µ g; a n d ( > 0) is t he i ncrease i n t he l o g-o d ds o f a D L T by 
a u nit i ncrease i n l o g- d ose.
1 0. 1 0. 2. Pri or S pecific ati o ns f or M o n ot her a p y Wit h o ut Pri mi n g
T he Ba y esia n a p pr oac h re q uires t he s pecificati o n of pri or distri b uti o ns f or all m o del 
para meters, w hic h i ncl u de t he para meters a n d . A wea kly i nf or mati ve pri or was use d as 
t here were n o rele va nt h u ma n hist orical D L T data a vaila ble. It was ass u me d t hat m o del 
para meters will f oll o w a bi variate n or mal ( B V N) distri b uti o n
(l o g(),l o g( )) ~ N2 ( m, S)
wit h pri or mea ns m = ( m 1, m2), a n d pri or c o varia nce matri x S c o m p osed of sta n dar d 
de viati o ns s 1, s2 a n d c orrelati o n ρ. It was ass u me d t hat
( m1, m2, s1, s2, ρ) = (l o git( p *), 0, 2, 1, 0)
Here, p * is t he a ntici pate d D L T rate at t he scali n g d ose d *. I t was ass u me d base d o n 
pre -cli nical data t hat D L T rate at 1 8 0 0 µ g  was 0. 3 3.
T his pri or is c o nsi dere d t o be wea kl y i nf or mati ve ( Ne ue nsc h wa n der et al. 2 0 1 4). 3 1
T he pri or distri b uti o ns of t he m o del para meters are pr o vi de d i n Ta ble 1 6 . Ta ble 1 7 ill ustrates 
t he res ulti n g pri or distri b uti o n of D L T rate deri ve d fr o m t he pri or gi ve n i n Ta ble 1 6 a n d 
r o u n de d t o 3 deci mal p oi nts. Base d o n t he a vaila ble i nf or mati o n t he starti n g d ose of 
P F - 0 7 0 6 2 1 1 9 of 4 5 µ g satisfies t he E W O C cri teria.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 2
T a ble 1 6 .
Pri or Distri b uti o n f or t he M o del P ar a meters
P F -0 7 0 6 2 1 1 9 si n gle a ge nt p ar a m eters: B V N we a kl y i nf or m ati ve pri or
Para meters
Mea ns
Sta n dar d de viati o ns
C orrelati o n
(l o g (α ),l o g (β  ))
-0. 7 0 8, 0
2, 1
0
T a ble 1 7 .
S u m m ar y of Pri or Distri b uti o n of D ose Li miti n g T o xicit y R ates f or 
P F -0 7 0 6 2 1 1 9
              ( ∗=      μ   )
P F -0 7 0 6 2 1 1 9 
D ose ( µ g)
Pri or Pr o b a bilities t h at D L T R ate is i n 
t he I nter v al
Me a n
S D
Q u a ntiles
[ 0, 0. 1 6)
[ 0. 1 6, 0. 3 3)
[ 0. 3 3, 1]
2. 5 %
5 0 %
9 7. 5 %
4 5
0. 8 2 9 
0. 0 7 4 
0. 0 9 7 
0. 0 9 3 
0. 1 8 6 
0. 0 0 0 
0. 0 0 8 
0. 7 2 7
9 0
0. 7 8 8 
0. 0 9 1 
0. 1 2 1 
0. 1 1 3 
0. 2 0 3 
0. 0 0 0 
0. 0 1 6 
0. 7 8 0
1 8 0
0. 7 3 6 
0. 1 0 7 
0. 1 5 7 
0. 1 4 1 
0. 2 2 3 
0. 0 0 0 
0. 0 3 0 
0. 8 2 8
3 6 0
0. 6 6 4 
0. 1 2 7 
0. 2 0 9 
0. 1 8 1 
0. 2 4 7 
0. 0 0 0 
0. 0 6 0 
0. 8 7 4
7 2 0
0. 5 5 3 
0. 1 5 8 
0. 2 8 8 
0. 2 4 2 
0. 2 7 3 
0. 0 0 0 
0. 1 2 2 
0. 9 1 4
1 4 4 0
0. 3 8 2 
0. 1 8 6 
0. 4 3 1 
0. 3 4 6 
0. 2 9 7 
0. 0 1 0 
0. 2 5 8 
0. 9 5 0
2 8 8 0
0. 2 1 4 
0. 1 5 3 
0. 6 3 3 
0. 5 0 4 
0. 3 2 4 
0. 0 1 6 
0. 5 0 0 
0. 9 8 9
Fi g ure 4.
S u m m ar y of D L T R ates f or P F -0 7 0 6 2 1 1 9
1 0. 1 0. 3. Pri or S pecific ati o ns f or M o n ot her a p y wit h Pri mi n g
A wea kl y i nf or mati ve pri or si milar t o o ne descri be d i n pre vi o us secti o n was use d. T he 
scali n g d ose f or t he re gi me n wit h pri mi n g is 8 0 0 µ g
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 3
As pre vi o usl y , it was ass u me d t hat ( m 1, m 2, s 1, s 2, ρ) = (l o git( p *), 0, 2, 1, 0)
Here, p * is t he a ntici pate d D LT rate at t he scali n g d ose d *. I t was ass u me d base d o n a nalys is 
of m o n ot hera p y d ose escalati o n wit h o ut pri mi n g t hat D L T rate at f ull d ose 8 0 0 µ g after 
pri mi n g wit h 4 0 0 µ g  was 0. 0 4 8 via matc hi n g D L T rates at 4 0 0 µ g  m o n ot hera p y wit h o ut 
pr i mi n g wit h pri mi n g/f ull d ose of 4 0 0 µ g/ 8 0 0 µ g.
T he pri or distri b uti o ns of t he m o del para meters are pr o vi de d i n Ta ble 1 8. Ta ble 1 9 ill ustrates 
t he res ulti n g pri or distri b uti o n of D LT rate deri ve d fr o m t he pri or gi ve n i n Ta ble 1 8 a n d 
r o u n de d t o 3 deci mal p oi nts. Base d o n t he a vaila ble i nf or mati o n t he starti n g d ose of 
P F - 0 7 0 6 2 1 1 9 of 4 0 0 µ g/ 8 0 0 µ g satisfies t he E W O C criteria.
T a ble 1 8 .
Pri or Distri b uti o n f or t he M o del P ar a meters ( Wit h Pri mi n g)
P F -0 7 0 6 2 1 1 9 si n gle a ge nt p ar a m eters: B V N we a kl y i nf or m ati ve pri or
Para meters
Mea ns
Sta n dar d de viati o ns
C orrelati o n
(l o g(α ),l o g(β ))
-2. 9 8 7 , 0
2, 1
0
T a ble 1 9 .
S u m m ar y of Pri or Distri b uti o n of D ose Li miti n g T o xicit y R ates f or 
P F -0 7 0 6 2 1 1 9 ( Wit h Pri mi n g D ose of 4 0 0 µ g)
( ∗=    μ  )
P F -0 7 0 6 2 1 1 9 
D ose ( µ g)
Pri or Pr o ba bilities t hat D L T Rate is i n t he 
I nter val
Mea n
S D
Q ua ntiles
[ 0, 0. 1 6)
[ 0. 1 6, 0. 3 3)
[ 0. 3 3, 1]
2. 5 %
5 0 %
9 7. 5 %
8 0 0
0. 7 4 7 
0. 1 2 5 
0. 1 2 8 
0. 1 3 1 
0. 1 8 8 
0. 0 0 1 
0. 0 4 7 
0. 7 1 6
1 0 0 0
0. 6 8 4 
0. 1 4 0 
0. 1 7 6 
0. 1 6 5 
0. 2 1 8 
0. 0 0 1 
0. 0 6 7 
0. 8 0 6
1 2 0 0
0. 6 3 1 
0. 1 4 9 
0. 2 2 0 
0. 1 9 8 
0. 2 4 6 
0. 0 0 2 
0. 0 8 5 
0. 8 9 0
1 4 0 0
0. 5 9 0 
0. 1 5 1 
0. 2 5 9 
0. 2 2 7 
0. 2 6 9 
0. 0 0 2 
0. 1 0 4 
0. 9 3 7
1 6 0 0
0. 5 5 8 
0. 1 5 2 
0. 2 9 0 
0. 2 5 2 
0. 2 8 7 
0. 0 0 2 
0. 1 2 0 
0. 9 6 4
1 8 0 0
0. 5 3 2 
0. 1 5 2 
0. 3 1 7 
0. 2 7 3 
0. 3 0 1 
0. 0 0 2 
0. 1 3 7 
0. 9 8 1
2 0 0 0
0. 5 0 9 
0. 1 5 0 
0. 3 4 1 
0. 2 9 2 
0. 3 1 2 
0. 0 0 2 
0. 1 5 3 
0. 9 8 9
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 4
1 0. 1 1. A p pe n di x 1 1: S u g geste d C yt o ki ne Rele ase S y n dr o me M a n a ge me nt Al g orit h m 
a n d Re vise d C R S Gr a di n g S yste m
A d a pte d fr o m Lee D W, et al: A S T C T C o nse ns us Gr a di n g f or Cyt oki ne Rele ase Sy n dr o me a n d 
Ne ur ol o gic T oxicity Ass oci ate d wit h I m m u ne Effect or Cells 2 0 1 9. 2 5: 6 2 5 -6 3 8.
* N ote – H y p o xia re q uiri n g l o w -fl o w si m ple face mas k defi ne d as o x y ge n deli vere d at ≤6 L/ mi n ute is Gra de 2 
C R S, w hereas h y p o xia re q uiri n g hi g h -fl o w sim ple face mas k defi ne d as o x y ge n deli vere d at > 6 L/ mi n ute is 
Gra de 3 C R S.
C R S m a n a ge me nt g ui deli nes
A S T C T Gr a de 1 C R S:

M o nit or vital si g ns f or w orse ni n g of c o n diti o n.
Fe ver

Aceta mi n o p he n/ paraceta m ol a n d h y p ot her mia bla n ket f or t he treat me nt of fe ver.

N o n- ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds) s uc h as i b u pr ofe n ca n be use d as 
sec o n d treat me nt o pti o n f or fe ver if n ot c o ntrai n dicate d.

Assess f or i nfecti o n usi n g bl o o d a n d uri ne c ult ures, a n d c hest ra di o gra p h y.

E m piric br oa d -s pectr u m a nti bi otics a n d fil grasti m if ne utr o pe nic.

Mai nte na nce I V fl ui ds f or h y drati o n.

S y m pt o matic ma na ge me nt of c o nstit uti o nal s y m pt o ms or or ga n t o xicit y .

C o nsi der t ociliz u ma b 8 m g/ k g * I V or silt u xi ma b 1 1 m g/ k g I V f or persiste nt (lasti n g 
> 3 da y s) a n d refract or y fe ver.
A S T C T Gr a de 2 C R S:

M o nit or vital si g ns e ver y 4 h o urs f or w orse ni n g of c o n diti o n.
Fe ver

Ma na ge as i n Gra de 1 C R S.
H y p ote nsi o n

I V fl ui d b ol us of 5 0 0-1 0 0 0 m L of n or mal sali ne. Ca n gi ve sec o n d I V fl ui d b ol us if
s yst olic bl o o d press ure re mai ns < 9 0 m m H g.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 5

C o nsi der t ociliz u ma b 8 m g/ k g ( ma xi m u m d ose 8 0 0 m g) I V or silt u xi ma b 1 1 m g/ k g 
I V f or treat me nt of hy p ote nsi o n refract or y t o fl ui d b ol uses; t ociliz u ma b ca n be 
re peate d after 6 h if nee de d.

If hy p ote nsi o n persists after 2 fl ui d b ol uses a n d a nti -I L-6 t hera p y, start vas o press ors, 
c o nsi der tra nsfer t o i nte nsi ve care u nit (I C U), o btai n ec h ocar di o gra m ( E C H O), a n d 
i nitiate ot her met h o ds of he m o d y na mic m o nit ori n g.

I n patie nts at hi g h-ris k ( b ul k y disease, ol der a ge or c o m or bi dities) or if h y p ote nsi o n 
persists after 1 -2 d oses of a nti -I L-6 t hera p y , de xa met has o ne ca n be use d at 1 0 m g I V 
e ver y 6 hrs.
H y p o xi a

S u p ple me ntal o x y ge n.

T ociliz u ma b or silt u xi ma b ±
c ortic oster oi ds a n d s u p p orti ve care, as i n dicate d f or
h y p ote nsi o n.
A S T C T Gr a de 3 C R S:

M o nit or patie nt (i ncl u di n g c o nti n u o us E C G m o nit ori n g) i n a n I C U a n d o btai n E C H O
if n ot d o ne alrea dy.
Fe ver

Ma na ge as i n Gra de 1 C R S.
H y p ote nsi o n

I V b ol uses, as nee de d, as rec o m me n de d f or Gra de 2 C R S.

T ociliz u ma b a n d silt u xi ma b as rec o m me n de d f or Gra de 2 C R S if n ot a d mi nistere d 
pre vi o usl y .

Vas o press ors as nee de d.

De xa met has o ne 1 0 m g I V e ver y 6 hrs; if refract or y, i ncrease t o 2 0 m g I V e ver y 6 hrs.
H y p o xi a

S u p ple me ntal o x y ge n i ncl u di n g hi g h -fl o w o xy ge n deli ver y.

T ociliz u ma b or silt u xi ma b pl us c ortic oster oi ds a n d s u p p orti ve care, as desc ri be d
a b o ve.
A S T C T Gr a de 4 C R S:

M o nit or patie nt (i ncl u di n g c o nti n u o us E C G m o nit ori n g) i n a n I C U a n d o btai n E C H O
if n ot d o ne alrea dy.
Fe ver

Ma na ge as i n Gra de 1 C R S.
H y p ote nsi o n

I V b ol uses, a nti-I L-6 t hera p y , vas o press ors, a n d he m o d yna mic m o nit ori n g as
rec o m me n de d f or gra de 3 C R S.

Met h y l pre d nis ol o ne 1 g/ da y IV.
H y p o xi a

S u p ple me ntal o x y ge n via p ositi ve press ure/ mec ha nical ve ntilati o n.

T ociliz u ma b or silt u xi ma b pl us c ortic oster oi ds a n d s u p p orti ve care, as descri be d
a b o ve.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 6
1 0. 1 2. A p pe n di x 1 2: E C O G Perf or m a nce St at us
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)
C O P Y RI G H T E D M A T E RI A L

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 7
1 0. 1 3. A p pe n di x 1 3: S u p p orti ve C are f or I m m u ne - Rel ate d A d verse E ve nts (ir A Es)
T a ble 2 0 .
M a n a ge me nt of I m m u ne Rel ate d A d verse E ve nts (ir A Es)
Gr a de
M a n a ge m e nt
F oll o w u p
Gastr oi ntesti nal 
ir A Es
Gr a de 1
Diarr hea: 
< 4 st o ols/ da y o ver 
baseli ne;
C olitis: 
as y m pt o matic
A nti -diarr heal me dicati o n 
(e g, l o pera mi de 4 m g i nitial 
d ose f oll o w e d b y 2 m g after 
e ver y s u bse q ue nt l o ose st o ol 
wit h n o m ore t ha n 1 6 m g 
dail y)
C o nti n ue st u d y i nter ve nti o n 
t hera p y.
If persists >4 8 h o urs, a d d sec o n d 
a nti -diarr heal me dicati o n (e g, 
L o m o til 2 ta blets 4 ti mes dail y).
Gr a de 2
Diarr hea: 4 t o 6 
st o ols per da y o ver 
baseli ne; I V fl ui ds 
i n dicate d < 2 4 
h o urs; n ot 
i nterferi n g wit h 
A D L
C olitis: a b d o mi nal 
pai n; bl o o d i n st o ol
Wit h h ol d st u d y i nter ve nti o n 
t hera p y.
A nti -diarr heal me dicati o n 
(e g, l o pera mi de 4 m g i nitial 
d ose f oll o w e d b y 2 m g after 
e ver y s u bse q ue nt l o ose st o ol 
wit h n o m ore t ha n 1 6 m g 
dail y) .
If i m pr o ves t o Gra de 1: 
Res u me st u d y  i nter ve nti o n 
t hera p y.
If persists >4 8 h o urs, a d d sec o n d 
a nti -diarr heal me dicati o n (e g, 
L o m o til 2 ta blets 4 ti mes dail y).
If persists >9 6 h o urs or rec ur s:
Met h yl pre d nis ol o ne 0. 5 t o 
1. 0 m g/ k g/ da y or e q ui vale nt. 
W he n s y m pt o ms i m pr o ve t o 
Gra de 1, ta per ster oi ds o ver at 
least 1 m o nt h, c o nsi der 
pr o p h ylactic a nti bi otics f or 
o p p ort u nistic i nfecti o ns, a n d 
res u me st u d y i nter ve nti o n 
t hera p y per pr ot oc ol.
If worse ns or persists > 3 da ys 
wit h ster oi ds:
Treat as Gra de 3 t o 4.
Gr a de 3 t o 4
Diarr hea ( Gra de 3): 
≥7 st o ols per da y 
o ver baseli ne; 
i nc o nti ne nce; I V 
fl ui ds ≥2 4 hrs.; 
i nterferi n g wit h 
A D L
C olitis ( Gra de 3): 
se vere a b d o mi nal 
pai n, me dical 
i nter ve nti o n 
i n dicate d, perit o neal 
si g ns
Wit h h ol d st u d y i nter ve nti o n 
t hera p y.
A nti -diarr heal me dicati o n 
(e g, l o pera mi de 4 m g i nitial 
d ose f oll o w e d b y 2 m g after 
e ver y s u bse q ue nt l o ose st o ol 
wit h n o m ore t ha n 1 6 m g 
dail y) .
Met h yl pre d nis ol o ne
1. 0 t o 
2. 0 m g/ k g/ da y I V or 
e q ui vale nt.
C o nsi der a d d iti o n of
pr o p h ylactic a nti bi otics f or 
o p p ort u nistic i nfecti o ns .
C o nsi der e n d osc o p y.
I n vesti gati o nal pr o d uct t hera p y –
See Ta ble 1 2 – D ose 
M o dificati o ns f or S pecific 
I m m u ne Relate d T o xicit y.
C o nti n ue ster oi ds u ntil Gra de 1, 
t he n ta per o ver at least 1 m o nt h.
If persists > 4 8 h o urs, a d d sec o n d 
a nti -diarr heal me dicati o n (e g, 
L o m o til 2 ta blets 4 ti mes dail y).
If persists > 9 6 h o urs or rec urs:
C o nsi der a d diti o n of i nfli xi ma b 
5 m g/ k g (if n o c o ntrai n dicati o n). 
N ote: I nfli xi ma b s h o ul d n ot be 
use d i n cases of perf orati o n or 
se psis.
Der m atitis ir A E
Gr a de 1 t o 2 
C o veri n g 3 0 % 
b o d y s urface area
S y m pt o matic t hera p y 
(e g, a nti hista mi nes, t o pical 
ster oi ds) C o nti n ue st u d y
i nter ve nti o n t hera p y
If persists > 1 t o 2 wee ks or 
rec urs: C o nsi der s ki n bi o ps y 
Wit h h ol d st u d y i nter ve nti o n 
t hera p y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 8
T a ble 2 0 .
M a n a ge me nt of I m m u ne Rel ate d A d verse E ve nts (ir A Es)
Gr a de
M a n a ge m e nt
F oll o w u p
C o nsi der 0. 5 t o 1. 0 m g/ k g/ da y 
met h yl pre d nis ol o ne I V or oral 
e q ui vale nt. O nce i m pr o vi n g, 
ta per ster oi ds o ver at least 
1 m o nt h, c o nsi der pr o p h ylactic 
a nti bi otics f or o p p ort u nistic 
i nfecti o ns, a n d res u me st u d y 
i nter ve nti o n t hera p y
If worse ns: 
Treat as Gra de 3 t o 4.
Gr a de 3 t o 4
C o veri n g > 3 0 % 
b o d y s urface area; 
life t hreate ni n g 
c o nse q ue nces
Wit h h ol d or disc o nti n ue 
st u d y i nter ve nti o n t hera p y 
C o nsi der s ki n bi o ps y 
Der m at ol o g y c o ns ult 
1. 0 t o 2. 0 m g/ k g/ da y 
met h yl pre d nis ol o ne I V or 
I V e q ui vale nt
If i m pr o ves t o Gra de 1: 
Ta per ster oi ds o ver at least 
1 m o nt h a n d a d d pr o p h ylactic 
a nti bi otics f or o p p o rt u nistic 
i nfecti o ns.
Res u me st u d y i nter ve nti o n 
t hera p y.
P ne u m o nitis 
ir A Es
Gr a de 1
Ra di o gra p hic 
c ha n ges o nl y
C o nsi der dela y of st u d y 
i nter ve nti o n t hera p y 
M o nit or f or s y m pt o ms e ver y 
2 t o 3 da ys 
C o nsi der P ul m o nar y a n d 
I nfecti o us Disease c o ns ults
Re -i ma ge at least e ver y 3 wee ks 
If worse ns, treat as Gra de 2 or 
Gra de 3 t o 4
Gr a de 2
Mil d t o m o derate 
ne w s y m pt o ms
Wit h h ol d st u d y i nter ve nti o n 
t hera p y
P ul m o nar y a n d I nfecti o us 
Disease c o ns ults
M o nit or s y m pt o ms dail y, 
c o nsi der h os pitalizati o n 
1. 0 m g/ k g/ da y 
met h yl -pre d nis ol o ne I V or 
oral e q ui vale nt 
C o nsi der br o nc h osc o p y, 
l u n g bi o ps y
Re -i ma ge e ver y 1 t o 3 da ys 
If i m pr o ves: 
W he n s y m pt o ms ret ur n t o near 
baseli ne, ta per ster oi ds o ver at 
least 1 m o nt h a n d t he n res u me 
st u d y i nter ve nti o n t hera p y a n d 
c o nsi der pr o p h ylacti c a nti bi otics 
If n ot i m pr o vi n g after 2 wee ks or 
w orse ni n g: 
Treat as Gra de 3 t o 4
Gr a de 3 t o 4
Se vere ne w 
s y m pt o ms; 
Ne w/ w orse ni n g 
h y p o xia; 
life-t hreate ni n g
Disc o nti n ue st u d y 
i nter ve nti o n t hera p y
H os pitalize 
P ul m o nar y a n d I nfecti o us 
Disease c o ns ults
2 t o 4 m g/ k g/ da y 
met h yl pre d nis ol o ne I V or 
I V e q ui vale nt 
A d d pr o p h ylactic a nti bi otics 
f or o p p ort u nistic i nfecti o ns 
C o nsi der br o nc h osc o p y, 
l u n g bi o ps y
If i m pr o ves t o baseli ne: 
Ta per ster oi ds o ver at least 
6 we e ks. If n ot i m pr o vi n g after 
4 8 h o urs or w orse ni n g: 
A d d a d diti o nal 
i m m u n os u p pressi o n 
(e g, i nfli xi ma b, 
c ycl o p h os p ha mi de, i ntra ve n o us 
i m m u n o gl o b uli n, or 
m yc o p he n olate m ofetil).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 9
T a ble 2 0 .
M a n a ge me nt of I m m u ne Rel ate d A d verse E ve nts (ir A Es)
Gr a de
M a n a ge m e nt
F oll o w u p
He patitis ir A Es
Gr a de 1
Gra de 1 A S T or 
A L T > U L N t o 
3. 0 x U L N a n d/ or 
T otal bilir u bi n 
> U L N t o 1. 5 x 
U L N
C o nti n ue st u d y i nter ve nti o n 
t hera p y
C o nti n ue li ver f u ncti o n 
m o nit ori n g . If worse ns, treat as 
Gra de 2 or 3 t o 4.
Gr a de 2
A S T or A L T > 3. 0 
t o ≤5 x U L N a n d/ or 
t otal bilir u bi n 
> 1. 5 t o ≤3 x U L N
Wit h h ol d st u d y i nter ve nti o n 
t hera p y
I ncrease fre q ue nc y of 
m o nit ori n g t o e ver y 3 da ys
If ele vati o ns ret ur n w it hi n ≤7 
da ys t o G ra de ≤1:
Res u me r o uti ne m o nit ori n g a n d
treat me nt at sa me d ose le vel.
If ele vati o ns d o n ot i m pr o ve 
wit hi n ≤7 da ys t o Gra de ≤1 :
M et h yl pre d nis ol o ne 0. 5 t o 1 
m g/ k g/ da y ( or oral /I V
e q ui vale nt ) a n d , w he n ele vati o ns
i mpr o ve t o Gra de ≤1 , ta per 
ster oi ds o ver at least 1 m o nt h, 
c o nsi der pr o p h ylactic a nti bi otics 
f or o p p ort u nistic i nfecti o ns, a n d 
re d uce d ose of P F -0 7 0 6 2 1 1 9 b y 
1 le vel.
Gr a de 3 t o 4
A S T or A L T > 5 x 
U L N a n d/ or t otal 
bilir u bi n > 3 x U L N
Disc o nti n ue st u d y 
i nter ve nti o n t hera p y.
I ncrease fre q ue nc y of 
m o nit ori n g t o e ver y 1 t o 2 
da ys.
1. 0 t o 2. 0 m g/ k g/ da y 
met h yl pre d nis ol o ne I V or 
I V e q ui vale nt.
A d d pr o p h ylactic a nti bi otics 
f or o p p ort u nistic i nfecti o ns. 
C o ns ult gastr oe nter ol o gist.
C o nsi der o btai ni n g M RI/ C T 
sca n of li ver a n d li ver 
bi o ps y if cli nicall y 
warra nte d.
If ret ur ns t o Gra de 2: 
Ta per ster oi ds o ver at least 
1 m o nt h. If d oes n ot i m pr o ve i n 
> 3 t o 5 da ys, w orse ns or 
re b o u n ds: 
A d d m yc o p he n olate m ofetil 
1 gra m ( g) t wice dail y.
If n o res p o nse wit hi n a n 
a d diti o nal 3 t o 5 da ys, c o nsi der 
ot her i m m u n os u p pressa nts per 
l ocal g ui deli nes.
E n d ocri ne ir A Es
As y m pt o matic 
t h yr oi d-sti m ulati n g 
h or m o ne ( T S H) 
a b n or malit y
C o nti n ue st u d y i nter ve nti o n 
t hera p y
If T S H < 0. 5 x l o wer li mit of 
n or m al ( L L N), or T S H 
> 2 x U L N, or c o nsiste ntl y o ut of 
ra n ge i n 2 s u bse q ue nt 
meas ure me nts: i ncl u de free 
t h yr o xi ne ( T 4) at s u bse q ue nt 
c ycles as cli nicall y i n dicate d; 
c o nsi der e n d ocri n ol o g y c o ns ult.
S y m pt o matic 
e n d ocri n o pat h y
E val uate e n d ocri ne f u ncti o n 
C o nsi der pit uitar y M RI 
sca n.
If i m pr o ves ( wit h or wit h o ut 
h or m o ne re place me nt): 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 0
T a ble 2 0 .
M a n a ge me nt of I m m u ne Rel ate d A d verse E ve nts (ir A Es)
Gr a de
M a n a ge m e nt
F oll o w u p
If s y m pt o matic wit h 
a b n or mal la b/ pit uitar y sca n: 
Wit h h ol d st u d y i nter ve nti o n 
t hera p y:
1 t o 2 m g/ k g/ da y 
met h yl pre d nis ol o ne I V or 
oral e q ui vale nt.
I nitiate a p pr o priate h or m o ne 
re place me nt t herap y .
If n or mal la b/ pit uitar y M RI 
sca n b ut s y m pt o ms persist: 
Re peat la bs i n 1 t o 3 
wee ks/ M RI i n 1 m o nt h.
Ta per ster oi ds o ver at least 
1 m o nt h a n d c o nsi der 
pr o p h ylactic a nti bi otics f or 
o p p ort u nistic i nfecti o ns.
Res u me st u d y i nter ve nti o n 
t hera p y.
Partici pa nts wit h a dre nal 
i ns ufficie nc y ma y nee d t o 
c o nti n ue ster oi ds wit h 
mi neral oc ortic oi d c o m p o ne nt.
S us pici o n of 
a dre nal crisis (e g, 
se vere de h y drati o n, 
h y p ote nsi o n, s h oc k 
o ut of pr o p orti o n t o 
c urre nt ill ness)
Wit h h ol d or disc o nti n ue 
st u d y i nter ve nti o n t hera p y.
R ule o ut se psis 
Stress d ose of I V ster oi ds 
wit h mi neral oc ortic oi d 
acti vit y I V fl ui ds.
C o ns ult e n d ocri n ol o gist 
If a dre nal crisis r ule d o ut, 
t he n treat as a b o ve f or 
s y m pt o matic 
e n d ocri n o pat h y.
A D L =acti vities of dail y li vi n g, A L T =ala ni ne a mi n otra nsferase, A S T =as partate a mi n otra nsferase, 
C T =c o m p ute d t o m o gra p h y, ir A E =i m m u ne -relate d a d verse e ve nt, I V =i ntra ve n o us, L F T =li ver f u ncti o n test, 
L L N =l o wer li mit of n or mal, M RI = ma g netic res o na nce i ma gi n g, N CI -C T C A E = Nati o nal Ca ncer 
I nstit ute-C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts, N S AI Ds = n o nster oi dal a nti -i nfla m mat or y 
dr u gs, T 4 =t h yr o xi ne, T S H =t h yr oi d -sti m ulati n g h or m o ne, U L N = u p per li mit of n or mal.
* N ote – See Ta ble 1 2 – D ose M o dificati o ns f or S pecific I m m u ne Relate d T o xicit y Attri b ute d t o 
I n vesti gati o nal Pr o d uct or C o m bi nati o n I n vesti gati o nal T hera p y f or a d diti o nal details o n d ose 
c o nsi derati o ns wit h st u d y i nter ve nti o n t hera p y.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 1
1 0. 1 4. A p pe n di x 1 4: R E CI S T ( Res p o nse E v al u ati o n Criteri a i n S oli d T u m ors) 
Versi o n 1. 1 G ui deli nes
A d a pte d fr o m E. A. Eise n h a uer, et al: Ne w res p o nse ev al u ati o n criteri a i n s oli d t u m ors: 
Revise d R E CI S T g ui deli ne (versi o n 1. 1). E ur o pe a n J o ur n al of C a ncer 4 5 ( 2 0 0 9) 2 2 8– 2 4 7.
C ate g orizi n g Lesi o ns at B aseli ne
Me as ur a ble Lesi o ns
Lesi o ns t hat ca n be acc uratel y  meas ure d i n at least o ne di me nsi o n.

Lesi o ns wit h l o n gest dia meter t wice t he slice t hic k ness a n d at least 1 0 m m or greater 
w he n assesse d b y  C T or M RI (slice t hic k ness 5-8 m m).

Lesi o ns wit h l o n gest dia meter at least 2 0 m m w he n assesse d b y  C hest X-ra y.

S u perficial lesi o ns wit h l o n gest dia meter 1 0 m m or greater w he n assesse d b y  cali per.

Mali g na nt l y m p h n o des wit h t he s h ort a xis 1 5 m m or great er w he n assesse d b y C T.
N O T E: T he s h ortest axis is use d as t he di a meter f or m ali g n a nt ly m p h n o des, l o n gest axis f or 
all ot her me as ur a ble lesi o ns.
N o n - me as ur a ble Dise ase 

N o n -meas ura ble disease i ncl u des lesi o ns t o o s mall t o be c o nsi dere d meas ura ble
(i ncl u din g n o des wit h s h ort a xis bet wee n 1 0 a n d 1 4. 9 m m) a n d tr ul y  n o n-meas ura ble 
disease s uc h as ple ural or pericar dial eff usi o ns, ascites, i nfla m mat or y  breast disease, 
le pt o me ni n geal disease, l y m p ha n gitic i n v ol ve me nt of s ki n or l u n g, cli nical lesi o ns 
t hat ca n n ot be acc uratel y meas ure d wit h cali pers, a b d o mi nal masses i de ntifie d b y 
p h y sical e xa m t hat are n ot meas ura ble b y re pr o d uci ble i ma gi n g tec h ni q ues.

B o ne disease: B o ne disease is n o n- meas ura ble wit h t he e xce pti o n of s oft tiss ue 
c o m p o ne nts t hat ca n be e val uate d b y  C T or M RI a n d meet t he defi niti o n of 
meas ura bilit y  at baseli ne.

Pre vi o us l ocal treat me nt: A pre vi o usl y irra diate d lesi o n ( or lesi o n patie nti ve t o ot her 
l ocal treat me nt) is n o n-meas ura ble u nless it has pr o gresse d si nce c o m pleti o n of 
treat me nt.
N or m al Sites

C y stic lesi o ns: Si m ple c ysts s h o ul d n ot be c o nsi dere d as mali g na nt lesi o ns a n d s h o ul d 
n ot be rec or de d eit her as tar get or n o n -tar get disease. C ystic lesi o ns t h o u g ht t o 
re prese nt c ystic metastases ca n be meas ura ble lesi o ns, if t he y meet t he s pecific 
d efi niti o n a b o ve. If n o nc ystic lesi o ns are als o prese nt, t hese are preferre d as tar get 
lesi o ns.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 2

N or mal n o des: N o des wit h s h ort a xis < 1 0 m m are c o nsi dere d n or mal a n d s h o ul d n ot 
be rec or de d or f oll o we d eit her as meas ura ble or n o n -meas ura ble disease.
Rec or di n g T u m or Assess me nts 
All sites of disease m ust be assesse d at baseli ne. Baseli ne assess me nts s h o ul d be d o ne as 
cl ose as p ossi ble pri or t o st u d y  start. F or a n a de q uate baseli ne assess me nt, all re q uire d sca ns 
m ust be d o ne wit hi n 2 8 da y s pri or t o treat me nt a n d all disease m ust be d oc u me nte d 
a p pr o priatel y. If baseli ne assess me nt is i na de q uate, s u bse q ue nt stat uses ge nerall y s h o ul d be 
i n deter mi nate.
N ote: F or t he p artici p a nt p o p ul ati o n bei n g ev al u ate d i n t his pr ot oc ol, t he b aseli ne 
assess me nt m ay be c o m plete d wit h i n 6 weeks pri or t o r a n d o miz ati o n.
T ar get Lesi o ns
All meas ura ble lesi o ns u p t o a ma xi m u m of 2 lesi o ns per or ga n, 5 lesi o ns i n t otal, 
re prese ntati ve of all i n v ol ve d or ga ns, s h o ul d be i de ntifie d as tar get lesi o ns at baseli ne. Tar get 
lesi o ns s h o ul d be selecte d o n t he basis of size (l o n gest lesi o ns) a n d s uitabilit y  f or acc urate 
re peate d meas ure me nts. Rec or d t he l o n gest dia meter f or eac h lesi o n, e xce pt i n t he case of 
pat h ol o gical l y m p h n o des f or w hic h t he s h ort a xis s h o ul d be rec or de d. T he s u m of t he 
dia meters (l o n gest f or n o n -n o dal lesi o ns, s h ort a xis f or n o da l lesi o ns) f or all tar get lesi o ns at 
baseli ne will be t he basis f or c o m paris o n t o assess me nts perf or me d o n st u d y.

If t w o tar get lesi o ns c oalesce t he meas ure me nt of t he c oalesce d mass is use d. If a 
lar ge tar get lesi o n s plits, t he s u m of t he parts is use d.

Meas ure me nts f or tar get lesi o ns t hat bec o me s mall s h o ul d c o nti n ue t o be rec or de d. If 
a tar get lesi o n bec o mes t o o s mall t o meas ure, 0 m m s h o ul d be rec or de d if t he lesi o n is 
c o nsi dere d t o ha ve disa p peare d; ot her wise a defa ult val ue of 5 m m s h o ul d be 
rec or de d.
N O T E: W he n n o d al lesi o ns decre ase t o < 1 0 m m ( n or m al), t he act u al me as ure me nt s h o ul d 
still be rec or de d.
N o n -t ar get Dise ase 
All n o n - meas ura ble disease is n o n-tar get. All meas ura ble lesi o ns n ot i de ntifie d as tar get 
lesi o ns are als o i ncl u de d as n o n-tar get disease. Meas ure me nts are n ot re q uire d b ut rat her 
assess me nts will be e x presse d as A B S E N T, I N D E T E R MI N A T E, P R E S E N T/ N O T 
I N C R E A S E D, I N C R E A S E D. M ulti ple n o n-tar get lesi o ns i n o ne or ga n ma y be rec or de d as a 
si n gle ite m o n t he case re p ort f or m (e g, ‘ m ulti ple e nlarge d pel vic l y m p h n o des’ or ‘ m ulti ple 
li ver metastases’).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 3
O bjecti ve Res p o nse St at us at E ac h E v al u ati o n
Disease sites m ust be assesse d usi n g t he sa me tec h ni q ue as baseli ne, i ncl u di n g c o nsiste nt 
a d mi nistrati o n of c o ntrast a n d ti mi n g of sca n ni n g. If a c ha n ge nee ds t o be ma de t he case m ust 
be disc usse d wit h t he ra di ol o gist t o deter mi ne if s u bstit uti o n is p ossi ble. I f n ot, s u bse q ue nt 
o bjecti ve stat uses are i n deter mi nate.
T ar get Dise ase

C o m plete Res p o nse ( C R): C o m plete disa p peara nce of all tar get lesi o ns wit h t he 
e xce pti o n of n o dal disease. All tar get n o des m ust decrease t o n or mal size (s h ort a xis 
< 1 0 m m). All tar get lesi o ns m ust be assesse d.

Partial Res p o nse ( P R): Greater t ha n or e q ual t o 3 0 % decrease u n der baseli ne of t he 
s u m of dia meters of all tar get meas ura ble lesi o ns. T he s h ort dia meter is use d i n t he 
s u m f or tar get n o des, w hile t he l o n gest dia meter is use d i n t he s u m f or all ot her tar get 
lesi o ns. All tar get lesi o ns m ust be assesse d.

Sta ble: D oes n ot q ualif y f or C R, P R or Pr o gressi o n. All tar get lesi o ns m ust b e 
assesse d. Sta ble ca n f oll o w P R o nl y i n t he rare case t hat t he s u m i ncreases b y less 
t ha n 2 0 % fr o m t he na dir, b ut e n o u g h t hat a pre vi o usl y d oc u me nte d 3 0 % decrease n o 
l o n ger h ol ds.

O bjecti ve Pr o gressi o n ( P D): 2 0 % i ncrease i n t he s u m of dia meters of tar get 
meas ura ble lesi o ns a b o ve t he s mallest s u m o bser ve d ( o ver baseli ne if n o decrease i n 
t he s u m is o bser ve d d uri n g t hera py), wit h a mi ni m u m a bs ol ute i ncrease of 5 m m.

I n deter mi nate. Pr o gressi o n has n ot bee n d oc u me nte d, a n d 
o ne or m ore tar get meas ura ble lesi o n s ha ve n ot bee n assesse d; 
or assess me nt met h o ds use d were i nc o nsiste nt wit h t h ose use d at baseli ne;
or o ne or m ore tar get lesi o ns ca n n ot be meas ure d acc uratel y (e g, p o orl y visi ble u nless d ue t o 
bei n g t o o s mall t o meas ure);
or o ne or m ore tar get lesi o ns were e xcise d or irra diate d a n d ha ve n ot rea p peare d or i ncrease d.
N o n -t ar get Dise ase

C R: Disa p peara nce of all n o n- tar get lesi o ns a n d n or malizati o n of t u m or mar ker 
le vels. All l ym p h n o des m ust be ‘ n or mal’ i n size ( < 1 0 m m s h ort a xis).

N o n -C R/ N o n - P D: Persiste nce of a n y  n o n-tar get lesi o ns a n d/ or t u m or mar ker le vel 
a b o ve t he n or mal li mits.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 4

P D: U ne q ui v ocal pr o gressi o n of pre- e xisti n g lesi o ns. Ge nerall y, t he o verall t u m or 
b ur de n m ust i ncrease s ufficie ntl y  t o merit disc o nti n uati o n of t hera p y. I n t he prese nce 
of S D or P R i n tar get disease, pr o gressi o n d ue t o u ne q ui v ocal i ncrease i n n o n -tar get 
disease s h o ul d be rare.

I n deter mi nate: Pr o gressi o n has n ot bee n deter mi ne d a n d o ne or m ore n o n-tar get sites 
were n ot assesse d or assess me nt met h o ds were i nc o nsiste nt wit h t h ose use d at 
baseli ne.
Ne w Lesi o ns 
T he a p peara nce of a n y ne w u ne q ui v ocal mali g na nt lesi o n i n dicates P D. If a ne w lesi o n is 
e q ui v ocal, f or e xa m ple d ue t o its s mall size, c o nti n ue d assess me nt will clarif y  t he eti ol o g y. If 
re peat assess me nts c o nfir m t he lesi o n, t he n pr o gressi o n s h o ul d be rec orde d o n t he date of t he 
i nitial assess me nt. A lesi o n i de ntifie d i n a n area n ot pre vi o usl y  sca n ne d will be c o nsi dere d a 
ne w lesi o n.
S u p ple me nt al I n vesti g ati o ns

If C R deter mi nati o n de pe n ds o n a resi d ual lesi o n t hat decrease d i n size b ut di d n ot 
disa p pear c o m p letely, it is rec o m me n de d t he resi d ual lesi o n be i n vesti gate d wit h 
bi o ps y  or fi ne nee dle as pirate. If n o disease is i de ntifie d, o bjecti ve stat us is C R.

If pr o gressi o n deter mi nati o n de pe n ds o n a lesi o n wit h a n i ncrease p ossi bl y d ue t o 
necr osis, t he lesi o n m a y be i n vesti gate d wit h bi o ps y or fi ne nee dle as pirate t o clarif y 
stat us.
S u bjecti ve Pr o gressi o n
Patie nts re q uiri n g disc o nti n uati o n of treat me nt wit h o ut o bjecti ve e vi de nce of disease 
pr o gressi o n s h o ul d n ot be re p orte d as P D o n t u m or assess me nt C R Fs. T his s h o ul d be 
i n dicate d o n t he e n d of treat me nt C R F as off treat me nt d ue t o Gl o bal Deteri orati o n of Healt h 
Stat us. E ver y  eff ort s h o ul d be ma de t o d oc u me nt o bjecti ve pr o gressi o n e ve n after 
disc o nti n uati o n of treat me nt.
T a ble 2 1 . O bjecti ve Res p o nse St at us at E ac h E v al u ati o n
T ar get Lesi o ns
N o n -t ar get Dise ase
Ne w 
Lesi o ns
O bjecti ve St at us
C R
C R
N o
C R
C R
N o n -C R/ N o n -P D
N o
P R
C R
I n deter mi nate or Missi n g
N o
P R
P R
N o n -C R/ N o n -P D, I n deter mi nate, or Missi n g
N o
P R
S D
N o n -C R/ N o n -P D, I n deter mi nate, or Missi n g
N o
Sta ble
I n deter mi nate or Missi n g
N o n -P D
N o
I n deter mi nate
P D
A n y
Yes or N o
P D
A n y
P D
Yes or N o
P D
A n y
A n y
Yes
P D
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 5
T a ble 2 2 . O bjecti ve Res p o nse St at us at E ac h E v al u ati o n f or P atie nts wit h N o n 
T ar get Dise ase O nl y
N o n -t ar get Dise ase
Ne w Lesi o ns
O bjecti ve St at us
C R
N o
C R
N o n -C R/ N o n -P D
N o
N o n -C R/ N o n -P D
I n deter mi nate
N o
I n deter mi nate
U ne q ui v ocal pr o gressi o n
Yes or N o
P D
A n y
Yes
P D
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 6
1 0. 1 5. A p pe n di x 1 5: I m m u ne- Rel ate d Res p o nse Criteri a Deri ve d fr o m R E CI S T 1. 1 
(ir R E CI S T)
I ncreasi n g cli nical e x perie nce i n dicates t hat tra diti o nal res p o nse criteria ma y n ot be s ufficie nt 
t o f ull y c haracterize acti vit y i n t his ne w era of tar gete d t hera pies a n d/ or bi ol o gics.
T his is partic ularl y  tr ue f or i m m u n ot hera pe utic a ge nts s uc h as a nti- CT L A 4 a n d 
a nti-P D -1/a nti -P D -L 1 a nti b o dies w hic h e xert t he a ntit u m or acti vit y  b y a u g me nti n g acti vati o n 
a n d pr oliferati o n of T cells, t h us lea di n g t o t u m or i nfiltrati o n b y  T cells a n d t u m or re gressi o n 
rat her t ha n direct c yt ot o xic effects.1 8 ,1 9  Cli nical o bser vati o ns of partici pa nts wit h a d va nce d 
mela n o ma treate d wit h i pili m u ma b, f or e xa m ple, s u g geste d t hat c o n ve nti o nal res p o nse 
assess me nt criteria s uc h as Res p o nse E val uati o n Criteria i n S oli d T u m ors ( R E CI S T) a n d 
W H O criteria are n ot s ufficie nt t o f ull y  c haracterize patter ns of t u m or res p o nse t o 
i m m u n ot hera p y beca use t u m ors treate d wit h i m m u n ot hera pe utic a ge nts ma y s h o w a d diti o nal 
res p o nse patter ns t hat are n ot descri be d i n t hese c o n ve nti o nal criteria.4 6 ,2 9
F urt her m ore, t he c o n ve nti o nal t u m or assess me nt criteria ( R E CI S T a n d W H O criteria) ha ve 
bee n re p orte d as n ot ca pt uri n g t he e xiste nce of a s u bset of partici pa nts w h o ha ve a n O S 
si milar t o t h ose w h o ha ve e x perie nce d C R or P R b ut were fla g ge d as P D b y W H O 
criteria. 4 9 ,2 9
O n t hese gr o u n ds, a t u m or assess me nt s ys te m has bee n de vel o pe d t hat i nc or p orates t hese 
dela y e d or flare -t ype res p o nses i nt o t he R E CI S T v 1. 1 (ir R E CI S T). 3 0
F or ir R E CI S T, o nl y  tar get a n d meas ura ble lesi o ns are ta ke n i nt o acc o u nt. I n c o ntrast t o 
R E CI S T v 1. 1, ir R E CI S T: 

Re q uires c o nfir mati o n of b ot h pr o gressi o n a n d res p o nse b y i ma gi n g at least 4 wee ks 
fr o m t he date first d oc u me nte d, a n d 

D oes n ot necessaril y sc ore t he a p peara nce of ne w lesi o ns as pr o gressi ve disease if t he 
s u m of lesi o n dia meters of tar get lesi o ns ( mi ni m u m of 1 0 m m l o n gest dia meter per 
n o n -n o dal lesi o n a n d 1 5 m m s h ortest dia mete r per n o dal lesi o n, ma xi m u m of 5 tar get 
lesi o ns, ma xi m u m of 2 per or ga n) a n d meas ura ble ne w lesi o ns d oes n ot i ncrease b y 
≥2 0 %.
T he sa me met h o d of assess me nt a n d t he sa me tec h ni q ue s h o ul d be use d t o c haracterize eac h 
i de ntifie d a n d re p orte d tar get lesi o n(s) at baseli ne a n d t hr o u g h o ut t he trial.
ir R E CIS T is defi ne d as f oll o ws: 
1.
O verall i m m u ne -relate d c o m plete res p o nse (ir C R): C o m plete disa p peara nce of all 
lesi o ns ( w het her meas ura ble or n ot) a n d n o ne w lesi o ns. All meas ura ble ly m p h n o des 
als o m ust ha ve a re d ucti o n i n s h ort a xis t o < 1 0 m m.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 7
2.
O verall i m m u ne -relate d partial res p o nse (ir P R): S u m of t he dia meters (l o n gest f or 
n o n -n o dal lesi o ns, s h ortest f or n o dal lesi o ns) of tar get a n d ne w meas ura ble lesi o ns 
decreases ≥3 0 %.
3.
O verall i m m u ne -relate d sta ble disease (ir S D): S u m of t he dia meters (l o n gest f or 
n o n -n o dal lesi o ns, s h ortest f or n o dal lesi o ns) of tar get a n d ne w meas ura ble lesi o ns is 
neit her ir C R, ir P R, (c o m pare d t o baseli ne) or i m m u ne -relate d pr o gressi ve disease 
(ir P D, c o m pare d t o na dir).
4.
O verall i m m u ne -relate d pr o gressi ve disease (ir P D): S u m of t he dia meters (l o n gest f or 
n o n -n o dal lesi o ns, s h ortest f or n o dal lesi o ns) of tar get a n d ne w meas ura ble lesi o ns 
i ncreases ≥2 0 % (c o m pare d t o na dir), c o nfir me d b y  a re peat, c o nsec uti ve o bser vati o n 
at least 4 wee ks fr o m t he d ate first d oc u me nte d.
Ne w meas ura ble lesi o ns: I nc or p orate d i nt o t u m or b ur de n (ie, a d de d t o t he tar get lesi o n 
meas ure me nts). A l y m p h n o de has t o be ≥1 5 m m i n s h ort a xis t o be a meas ura ble ne w lesi o n 
a n d its s h ort a xis meas ure me nt is i ncl u de d i n t he s u m. U p t o 2 ne w lesi o ns per or ga n a n d u p 
t o 5 ne w lesi o ns i n t otal ca n be a d de d t o t he meas ure me nts.
Ne w n o n - meas ura ble lesi o ns: D o n ot defi ne pr o gressi o n b ut precl u de ir C R.
O verall res p o nses deri ve d fr o m c ha n ges i n i n de x, n o n- i n de x, a n d ne w lesi o ns are o utli nes i n 
Ta ble 2 3 .
T a ble 2 3 . O ver all Res p o nse Deri ve d fr o m C h a n ges i n I n de x, N o n i n de x a n d Ne w 
Lesi o ns
M e as ur a ble Res p o nse
N o n -me as ur a ble Res p o nse
O ver all Res p o nse 
Usi n g ir R E CI S T b
I n de x a n d Ne w 
M e as ur a ble Lesi o ns 
( T u m or B ur de n)a
N o n -I n de x Lesi o ns
Ne w N o n -M e as ur a ble 
Lesi o ns
Decrease 1 0 0 %
A bse nt
A bse nt
ir C R
Decrease 1 0 0 %
Sta ble
A n y
ir P R
Decrease 1 0 0 %
U ne q ui v ocal pr o gressi o n
A n y
ir P R
Decrease ≥3 0 %
A bse nt/sta ble
A n y
ir P R
Decrease ≥3 0 %
U ne q ui v ocal pr o gressi o n
A n y
ir P R
Decrease < 3 0 % a n d 
i ncrease < 2 0 %
A bse nt/sta ble
A n y
ir S D
Decrease < 3 0 % a n d 
i ncrease < 2 0 %
U ne q ui v ocal pr o gressi o n
A n y
ir S D
I ncrease ≥2 0 %
A n y
A n y
ir P D
a.
Decrease assesse d relati ve t o baseli ne.
b.
Res p o nse (ir C R a n d ir P R) a n d pr o gressi o n (ir P D) m ust be c o nfir me d b y a sec o n d, c o nsec uti ve 
assess me nt at least 4 wee ks a part.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 8
1 0. 1 6. A p pe n di x 1 6: A b bre vi ati o ns
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y  be use d i n t he pr ot oc ol. 
A b bre vi ati o n
Ter m
A b
a nti b o d y
A C RI N
A merica n C olle ge of Ra di ol o g y  Ima gi n g Net w or k
A D A
a nti dr u g a nti b o dies
A E
a d verse e ve nt(s)
AI D S
ac q uire d i m m u n o deficie nc y  sy n dr o me
A L L
Ac ute L y m p h oc y tic Le u ke mia
A L T
ala ni ne a mi n otra nsferase
A M L
Ac ute M yel oi d Le u ke mia
A N C
a bs ol ute ne utr o p hil c o u nt
a nti-P D -1
a nti-pr o gra m me d cell deat h pr otei n -1
a nti-E G F R
A nti -e pi der mal gr o wt h fact or rece pt or pat h wa y
a nti-V E G F
A nti – vasc ular e n d ot helial gr o wt h fact or t hera p y
A PI
acti ve p har mace utical i n gre die nt
A S C O
A merica n S ociet y of Cli nical O nc ol o g y
A S T
as partate a mi n otra nsferase
A S T C T
A merica n S ociet y f or Tra ns pla ntati o n a n d Cell ular T hera py
A U C
area u n der t he c ur ve
A U C i nf
A U C fr o m ti me zer o e xtra p olate d t o i nfi nite ti me
A U C last
A U C fr o m ti me zer o t o t he last q ua ntifia ble c o nce ntrati o n
A U C ta u
A U C wit hi n t he first d osi n g i nter val
A V
atri o ve ntric ular
B A
bi oa vaila bilit y
B B S
Bi os peci me n Ba n ki n g S yste m
BI D
t wice daily
B L R M
Ba yesia n l o gistic re gressi o n m o del
B P
bl o o d press ure
B R A F
seri ne/t hre o ni ne-pr otei n ki nase B -Raf.
B S A
b o d y  s urface area
B U N
bl o o d urea nitr o ge n
C A R
c hi meric a nti ge n rece pt or
C E A
carci n oe m br yo nic a nti ge n
Ceff
cli nical efficaci o us c o nce ntrati o n 
C D S
c ore data s heet 
C F R
C o de of Fe deral Re g ulati o ns
c G M P
c yclic g ua n osi ne m o n o p h o s p hate
CI
c o nfi de nce i nter val
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C L
Cleara nce
C L / F
a p pare nt cleara nce
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 9
A b bre vi ati o n
Ter m
Cl x
Cell li ne xe n o graft 
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C M C
C he mistr y , Ma n ufact uri n g, a n d C o ntr ols
C N S
ce ntral ner v o us s ys te m
C O N S O R T
C o ns oli date d Sta n dar ds of Re p orti n g Trials
C R
c o m plete res p o nse
C R A
cli nical researc h ass ociate
C R C
c ol orectal ca ncer
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C R P
c- reacti ve pr otei n 
C R S
c yt o ki ne release sy n dr o me
C R U
cli nical researc h u nit
C S F
cere br os pi nal fl ui d
C S R
cli nical st u d y re p ort
C T
c o m p ute d t o m o gra p h y
C T C
circ ulati n g t u m or cells
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C T L s
C y t ot o xic T l ym p h oc y tes 
C T M S
cli nical trial ma na ge me nt s yste m
C tr o u g h
pre dicte d tr o u g h c o nce ntrati o n 
C V
Car di o vasc ular
C # D #
c ycle #, Da y#
D C R
disease c o ntr ol rate
D C T
data c ollecti o n t o ol
Df
defer o xa mi ne
DI LI
dr u g -i n d uce d li ver i nj ur y
D LI
D o n or L y m p h oc y te I nf usi o n
D L T
d ose -li miti n g t o xicit y
D M C
data m o nit ori n g c o m mittee
D N A
de o x yri b o n ucleic aci d
D O R
d urati o n of res p o nse
D R E
disease -relate d e ve nt
D U
dis pe nsa ble u nit
E C
et hics c o m mittee
E C 5 0
c o nce ntrati o n c orres p o n di n g t o 5 0 % of t he ma xi m u m effect
E C G
electr ocar di o gra m
E C H O
ec h ocar di o gra m
E C O G
Easter n C o o perati ve O nc ol o g y  Gr o u p
e C R F
electr o nic case re p ort f or m
E -D M C
e xter nal data m o nit ori n g c o m mittee 
E D P
e x p os ure d uri n g pre g na nc y
E F S
E ve nt -Free S ur vi val
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 0
A b bre vi ati o n
Ter m
E G F R
e pi der mal gr o wt h fact or rece pt or
E M A
E ur o pea n Me dici nes A ge nc y
E O T
E n d of Trial 
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n Cli nical Trials Data base
E W O C
escalati o n wit h o ver d ose c o ntr ol
F D A
F o o d a n d Dr u g A d mi nistrati o n ( U nite d States)
F F P E
f or mali n-fi xe d paraffi n-e m be d de d
FI H
first-i n-h u ma n
FI P
first-i n-patie nt
FI S H
Fl u oresce nt i n sit u h y bri dizati o n
F S H
f ollicle-sti m ulati n g h or m o ne
G C P
G o o d Cli nical Practice
G C S F
gra n ul oc y te c ol o ny -sti m ulati n g fact or
G G T
ga m ma -gl uta m y l tra nsferase
G L P
G o o d La b orat or y  Practice
G U C Y 2c
a nti-G ua n yl yl  Cycl ase 2 C ( G U C Y 2c)/a nti -C D 3 bis pecific Fc 
dia b o d y
G V H D
graft vers us h ost disease
H b A 1c
he m o gl o bi n A 1c
H bc A b
he patitis B c ore a nti b o d y
H bs A g 
he patitis B s urface a nti ge n
H B V
he patitis B vir us
H C V
he patitis C vir us
H C V A b
he patitis C a nti b o d y
H E R
h u ma n e pi der mal gr o wt h fact or rece pt or
H E R 2
h u ma n e pi der mal gr o wt h fact or rece pt or 2
HI P A A
Healt h I ns ura nce P orta bilit y  a n d Acc o u nta bilit y Act
HI V
h u ma n i m m u n o deficie nc y vir us
H N S T D
hi g hest n o n -se verel y t o xic d ose
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
In vesti gat or’s B r oc h ure
I C D
i nf or me d c o nse nt d oc u me nt
I C U
I nte nsi ve care u nit
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use
I F N
i nterfer o n-ga m ma
I g G
i m m u n o gl o b uli n G
I g G 1
i m m u n o gl o b uli n 1
I g G 4
i m m u n o gl o b uli n 4
I H C
i m m u n o hist oc he mistr y
I L
i nterle u ki n
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 1
A b bre vi ati o n
Ter m
I M P
I n vesti gati o nal Me dici nal Pr o d uct
I ND
i n vesti gati o nal ne w dr u g a p plicati o n
I N R
i nter nati o nal n or malize d rati o
I P 
i n vesti gati o nal pr o d uct 
ir A E
i m m u ne-relate d a d verse e ve nts
I RB
Instit uti o nal R e vie w B oar d
I R C
i nter nal re vie w c o m mittee
ir P F S
i m m u ne-relate d P F S
I R R
i nf usi o n relate d reacti o n
ir R E CIS T
I m m u ne Relate d Res p o nse Criteria i n S oli d T u m or
I R T
i nteracti ve res p o nse tec h n ol o g y
I S R
injecti o n site reacti o n 
I UD
i ntra uteri ne de vice
I U S
i ntra uteri ne h or m o ne-releasi n g sys te m
I V
intra ve n o us
I W R
i nteracti ve We b-base d res p o nse
K R A S
Kirste n Rat Sarc o ma viral o nc o ge ne
L B B B
left b u n dle bra nc h bl oc k
L D H
lactate de hy d r o ge nase
L F T
li ver f u ncti o n test
L V E F
left ve ntric ular ejecti o n fracti o n
m A b
m o n ocl o nal a nti b o d y
M A B E L
mi ni m u m a ntici pate d bi ol o gical effect le vel
M A C
maj or hist oc o m pati bilit y  c o m ple x
M A D
ma xi m u m a d mi nistere d d ose
M A P
meta -a nal yt ic-pre dicti ve
M b
m i ni b o d y
M H C
maj or hist oc o m pati bilit y  c o m ple x
M D
m ulti ple d ose
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
M F D
ma xi m u m feasi ble d ose
mI T T
m o difie d i nte nt t o treat
M RI
ma g netic res o na nce i ma gi n g
M SI -H
micr osatellite i nsta ble – hi g h
M S S
micr osatellite sta ble
M T D
ma xi m u m t olerate d d ose
m T PI
m o difie d t o xicit y  pr o ba bilit y i nter val
M U G A
m ulti gate d ac q uisiti o n sca n
N/ A
n ot a p plica ble
N A b
ne utralizi n g a nti b o dies
N CI
Nati o nal Ca ncer I nstit ute
NI M P
n o n -i n vesti gati o nal me dici nal pr o d uct
N K
nat ural killer
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 2
A b bre vi ati o n
Ter m
N M C T G
N uclear Me dici ne Cli nical Trial Gr o u p, L L C
N O A E L
n o -o bser ve d -a d verse-effect le vel
N S AI D
n o n ster oi dal a nti-i nfla m mat or y dr u g
N S C L C
n o n -s mall cell l u n g ca ncer
N S G
Fe male N O D -sci d I L-2 R n ull
O R
o bjecti ve res p o nse
O R R
o verall res p o nse rate
O S
o verall s ur vi val
P A C L
Pr ot oc ol A d mi nistrati ve C ha n ge Letter
P B M C
peri p heral bl o o d m o n o n uclear cell
P C D
pri mar y  c o m pleti o n date
P D
p har mac o d y n a mics(s)
P D L -1
pr o gra m me d cell deat h pr otei n -1
P D L -2
pr o gra m me d cell deat h pr otei n -2
P D X
partici pa nt deri ve d xe n o graft 
P E T
p ositr o n e missi o n t o m o gra p h y
P F S
Pr o gressi o n -Free S ur vi val
P G x 
p har mac o ge n o mic(s)
PI
pri nci pal i n vesti gat or
PI B
p o w der i n b ottle
P K
p har mac o ki netic(s)
P R
partial res p o nse
P R E S
P osteri or Re versi ble E nce p hal o pat h y S y n dr o me
P S
perf or ma nce stat us
P T
pr ot hr o m bi n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q 2 W
e ver y 2 wee ks
Q 4 W
e ver y 4 wee ks
Q D
e ver y da y
Q Tc
c orrecte d Q T
Q Tc B
c orrecte d Q T ( Bazett met h o d)
Q Tc F
c orrecte d Q T ( Fri dericia met h o d)
R ac
acc u m ulati o n rati o
R E CI S T
Res p o nse E val uati o n Criteria i n S oli d T u m ors
R F S
Rela pse -Free S ur vi val
R N A
ri b o n ucleic aci d
R O
rece pt or occ u pa nc y
R P 2 D
rec o m me n de d P hase 2 d ose
R R
res p o nse rate
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal y sis Pla n
S C
S u bc uta ne o us(l y)
S D
si n gle d ose
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 3
A b bre vi ati o n
Ter m
S o A
sc he d ule of acti vities
S O P
sta n dar d o perati n g pr oce d ure(s)
S R S D
si n gle refere nce safety d oc u me nt
S U S A R
S us pecte d U ne x pecte d S eri o us A d verse R eacti o n
S U V
sta n dar d u pta ke v al ues
t1/ 2
ter mi nal half-life
T bili
t otal bilir u bi n
T B R
t u m or bac k gr o u n d rati o
T C Rs
t-cell rece pt ors 
TI L
T u m or i nfiltrati n g l y m p h oc y tes 
T M E
t u m or micr oe n vir o n me nt
T N F
t u m or necr osis fact or
T ma x
ti me t o ma xi m u m c o nce ntrati o n
T M D D
Tar get me dicati o n dr u g dis p ositi o n 
T M E
t u m or micr oe n vir o n me nt
T S H
t h yr oi d sti m ulati n g h or m o ne
T T P
ti me t o pr o gressi o n
U C
ur ot helial carci n o ma
U L N
u p per li mit of n or mal
U S
U nite d States
U S PI
U nite d States Pac ka ge I nsert 
U V B
ultra vi olet B
V E G F -A
vasc ular e n d ot helial gr o wt h fact or
Vss
stea d y state v ol u me distri b uti o n 
W B C
w hite bl o o d cell
W B S
w h ole b o d y  sca n
W N L
wit hi n n or mal li mits
W O C B P
w o ma n / w o me n of c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 4
1 0. 1 7. A p pe n di x 1 7: J a p a n S pecific M atters
J a p a n p artici p ati o n
a)
S u g geste d C yt o ki ne Rele ase S y n dr o me M a n a ge me nt
T ociliz u ma b is n ot a p pr o ve d i n Ja pa n f or t he treat me nt of C R S ot her t ha n t he e ve nts 
ass ociate d wit h c hi meric a nti ge n rece pt or ( C A R) T cell t hera p y.
b)
C o n diti o n t o be disc h ar ge d:
W he n a partic i pa nt is disc har ge d fr o m t he h os pital d uri n g t he D L T e val uati o n peri o d, t he 
f oll o wi n g c o n diti o ns (tests, me dical e xa mi nati o ns, etc.) s h o ul d be perf or me d o n t he da y of 
t he sc he d ule d disc har ge b y t he i n vesti gat ors, a n d t he pr o priety of disc har ge s h o ul d be 
de ter mi ne d. T he tests/ me dical e xa mi nati o ns w hic h are nee de d t o c o nfir m t he partici pa nt’s 
stat us will be c o n d ucte d per cli nical practice i n t he st u d y site as a p pr o priate.

T here are n o c urre nt cli nicall y  si g nifica nt a d verse or si de effects, i ncl u di n g C R S, or 
me dical reas o ns t hat re q uire m o nit ori n g i n a h os pital setti n g.

If a cli nicall y si g nifica nt a d verse or si de effect has occ urre d or c o nti n ues t o be 
prese nt, t he i n vesti gat or will deter mi ne t hat t he e ve nt is ma na gea ble b y a p pr o priate 
treat me nt or pr o p hyl a xis i n a n o ut of t he h os pital setti n g.

O verall p h ys ical c o n diti o n is sta ble a n d acce pta ble.

I n case of e mer ge nc y, t he partici pa nt ma y ret ur n t o t he cli nical st u d y site or ot her 
me dical i nstit uti o n. If partici pa nts g o t o a me dical i nstit uti o n ot her t ha n t he cli nical 
st u d y site, t he cli nical st u d y site as ks t hat t he partici pa nts c o ntact t he st u d y site, st u d y 
i n vesti gat or a n d t he d oct or at t he me dical i nstit uti o n w h o will c o m m u nicate t o disc uss 
a p pr o priate treat me nts. A st u d y  site kee ps fra me w or k t o rea d y f or e merge nc y  
sit uati o ns t hat is a vaila ble e ve n d uri n g ni g hts a n d h oli da ys, a n d t he s p o ns or will 
e ns ure t hat t he selecte d st u d y  site will t h or o u g hl y f oll o w all partici pa nts acc or di n g t o 
st u d y pr oce d ures.
c)
Secti o n 8. 7 - Ge netics a n d Secti o n 8. 8 – Bi o m ar kers:
Gi ve n t he ge netic testi n g is f or e x pl orat or y  p ur p oses o nl y a n d f oll o wi n g Pfizer pr ocess, t here 
is n o e x pectati o n t o discl ose t hese ge netic testi n g res ults t o t he st u d y partici pa nts, at a n y 
ti me.
A st u d y  partici pa nt’s partici pati o n i n a cli nical st u d y s hall n ot be c o n diti o ne d o n his or her 
i nf or me d c o nse nt f or t he use of bi os peci me ns that is n ot relate d t o a cli nical e n d p oi nt, t he 
dr u g bei n g i n vesti gate d i n t he trial, or t he i ncl usi o n/e xcl usi o n criteria f or t he st u d y .
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 5
1 0. 1 8. A p pe n di x 1 8: Alter n ati ve Me as ures D uri n g P u blic E mer ge ncies
T he alter nati ve st u d y meas ures descri be d i n t his secti o n are t o be f oll o we d d uri n g p u blic 
e mer ge ncies, i ncl u di n g t he C O VI D -1 9 pa n de mic. T his a p pe n di x a p plies f or t he d urati o n of 
t he C O VI D-1 9 pa n de mic gl o ball y a n d will bec o me effecti ve f or ot her p u blic e mer ge ncies 
o nl y  u p o n writte n n otificati o n fr o m Pfizer.
T hese pla n ne d c ha n ges are bei n g i m ple me nte d i m me diatel y  i n res p o nse t o t he C O VI D- 1 9 
pa n de mic a n d are pla n ne d f or t he d urati o n of t he C O VI D- 1 9 pa n de mic. T his a p plies t o 
partici pa nts w h o are q uara nti ne d or wis h t o n ot atte n d sc he d ule d visits or perf or m st u d y  
pr oce d ures or tests o n site d ue t o safet y  c o ncer ns a n d/ or l ocal g o ver n me nt healt h or healt h 
i nstit ute s u g gesti o ns a n d/ or g ui deli nes iss ue d i n a n eff ort t o li mit e x p os ure of v ul nera ble 
p o p ulati o ns t o t he vir us.
Use of t hese alter nati ve st u d y  meas ures are e x pected t o cease u p o n t he ret ur n of b usi ness as 
us ual circ u msta nces (i ncl u di n g t he lifti n g of a n y q uara nti nes a n d tra vel ba ns/a d vis ories).
Eli gi bilit y
W hile S A R S -C o V 2 testi n g is n ot ma n date d f or t his st u d y , l ocal cli nical practice sta n dar ds f or 
testi n g s h o ul d be f oll o we d. A partici pa nt s h o ul d be e xcl u de d if he/s he has a p ositi ve test 
res ult f or S A R S-C o V 2 i nfecti o n, is k n o w n t o ha ve as y m pt o matic i nfecti o n, or is s us pecte d of 
ha vi n g S A R S -C o V 2. Patie nts wit h acti ve i nfecti o ns are e xcl u de d fr o m st u d y  partici pati o n as
per e xcl usi o n criteri o n # 6: “ Acti ve a n d cli nicall y  si g nifica nt bacterial, f u n gal, or viral 
i nfecti o n, i ncl u di n g H B V, H C V, k n o w n HI V or AI D S relate d ill ness. I n e q ui v ocal cases, 
wit h p ositi ve ser ol o g y , t h ose partici pa nts wit h a ne gati ve viral l oa d are p otentiall y  eli gi ble 
pr o vi de d t he ot her e ntr y  criteria are met.
Tele he alt h Visits
St u d y  partici pa nts w h o ca n atte n d sc he d ule d st u d y visits o n site a n d c o m plete all st u d y 
pr oce d ures as descri be d i n t he pr ot oc ol per t he Sc he d ule of t he Acti vities s h o ul d d o s o; all 
ot her partici pa nts s h o ul d ma ke e ver y  eff ort t o partici pate i n st u d y visits b y tele p h o ne via a 
tele healt h visit. Vi de o c o ntact ca n be use d if a vaila ble a n d per mitte d b y l ocal re g ulati o ns.
I n t he e ve nt t hat i n- cli nic st u d y visits ca n n ot be c o n d ucte d, e ver y  eff ort s h o ul d be ma de t o 
f oll o w u p o n t he safet y of st u d y partici pa nts at sc he d ule d visits per t he Sc he d ule of t he 
Acti vities or u nsc he d ule d visits. Tele healt h visits ma y  be use d t o c o nti n ue t o assess 
partici pa nt safet y  a n d c ollect data p oi nts. Tele healt h i ncl u des t he e xc ha n ge of healt hcare 
i nf or mati o n a n d ser vices via telec o m m u nicati o n tec h n ol o gies (e g, a u di o, vi de o, 
vi de o -c o nfere nci n g s oft ware) re m otel y, all o wi n g t he partici pa nt a n d t he i n vesti gat or t o 
c o m m u nicate o n as pects of cli nical care, i ncl u di n g me dical a d vice, re mi n ders, e d ucati o n, a n d 
safety m o nit ori n g. T he f oll o wi n g assess me nts m ust be perf or me d d uri n g a tele healt h visit:

Re vie w a n d rec or d a n y A Es a n d S A Es since t he last c o ntact. Refer t o Secti o n 8. 1 .

Re vie w a n d rec or d a n y ne w c o nc o mita nt me dicati o ns or c ha n ges i n c o nc o mita nt 
me dicati o ns si nce t he last c o ntact.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 6

Re vie w a n d rec or d c o ntrace pti ve met h o d a n d res ults of pre g na nc y testi n g. C o nfir m 
t hat t he partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he 
pr ot oc ol. Refer t o A p pe n di x 4 of t h is a p pe n di x re gar di n g pre g na nc y tests.

Re vie w of p h ys ical sy m pt o ms i n place of ma n date d p h y sical e xa ms
St u d y  partici pa nts m ust be re mi n de d t o pr o m ptl y n otif y site staff a b o ut a ny c ha n ge i n t heir 
healt h stat us.
Alter n ati ve F acilities f or S afet y Assess me nts
If t he st u dy partici pa nt is u na ble t o visit t he st u d y  site, pr ot oc ol s pecifie d safet y la b orat or y 
tests a n d/ or t u m or assess me nts ma y alter nati vely be perf or me d at a n alter nati ve l ocal 
la b orat or y or facility, w here all o wa ble b y la w or l ocal g ui da nce. I n t hese cases: 

L ocal la b orat or y  refere nce ra n ges nee d t o be d oc u me nte d a n d s u b mitte d t o st u d y 
tea m. 

Rec or ds of l ocal la b orat or y  tests, la b accre ditati o n, a n d re p orts of t u m or assessme nts 
s h o ul d be retrie ve d a n d d oc u me nte d i n site me dical rec or ds.

Rele va nt data fr o m l ocal la b orat ories a n d testi n g facilities are t o be e ntere d i n t he 
C R F.

Visits m ust be c o n d ucte d b y  staff w h o are a p pr o priatel y q ualifie d a n d trai ne d o n t he 
st u d y pr ot oc ol

A n y  res ults t hat are c o nsi dere d cli nicall y si g nifica nt m ust be re p orte d i n a ti mel y 
ma n ner a n d as directe d i n t he pr ot oc ol.
L a b or at or y Testi n g
If a st u dy partici pa nt is u na ble t o visit t he site f or pr ot oc ol -s pecifie d safet y la b orat or y 
e val uati o ns, testi n g m a y  be c o n d ucte d at a l ocal la b orat or y  if per mitte d b y l ocal re g ulati o ns. 
T he l ocal la b orat or y  ma y be a sta n dal o ne i nstit uti o n or wit hi n a h os pital. At t he discreti o n of 
t he treati n g p hys icia n h o me bl o o d dra ws ma y be per mitte d. All safety la b orat or y  tests
o utli ne d i n t his pr ot oc ol ca n be d o ne at a l ocal la b orat or y .
If a l ocal la b orat or y is use d, q ualifie d st u d y site pers o n nel m ust or der, recei ve, a n d re vie w 
res ults. Site staff m ust c ollect t he l ocal la b orat or y refere nce ra n ges a n d 
certificati o ns/accre ditati o ns f or fili n g at t he site. La b orat or y  test res ults are t o be pr o vi de d t o 
t he site staff as s o o n as p ossi ble.  T he l ocal la b orat or y  re p orts s h o ul d be file d i n t he 
partici pa nt’s s o urce d oc u me nts/ me dical rec or ds. Rele va nt data fr o m t he l ocal la b orat or y 
re p ort s h o ul d be rec or de d o n t he C R F. 
If a partici pa nt re q uiri n g pre g na nc y testi n g ca n n ot visit a l ocal la b orat or y f or pre g na nc y 
testi n g, a h o me uri ne pre g na nc y testi n g kit wit h a se nsiti vit y of at least 2 5 I U/ m L ma y be 
use d b y  t he p artici pa nt t o perf or m t he test at h o me, if c o m plia nt wit h l ocal re g ulat or y 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 7
re q uire me nts. T he pre g na nc y test o utc o me s h o ul d be d oc u me nte d i n t he partici pa nt ’s s o urce 
d oc u me nts/ me dical rec or ds a n d rele va nt data rec or de d o n t he C R F. C o nfir m t hat t he 
partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he pr ot oc ol.
A n y  res ults t hat are c o nsi dere d cli nicall y si g nifica nt m ust be re p orte d i n a ti mel y ma n ner a n d 
as directe d i n t he pr ot oc ol.
I m a gi n g a n d Effic ac y Assess me nts
If t he partici pa nt is u na ble t o visit t he st u d y site f or pla n ne d or u n pla n ne d i ma gi n g 
assess me nts t he partici pa nt ma y  visit a n alter nati ve facility t o ha ve t hese assess me nts 
perf or me d. Q ualifie d st u d y  site pers o n nel m ust or der, recei ve, a n d re vie w res ults a n d a n y 
a b n or malities, i nclu di n g pr o gressi o n of disease m ust be re p orte d t o t he Pfizer cli nical ti me i n 
a ti mel y ma n ner a n d as directe d i n t he pr ot oc ol.
Electr oc ar di o gr a ms
If t he partici pa nt is u na ble t o visit t he st u d y site f or E C Gs, t he partici pa nt ma y  visit a n 
alter nati ve facilit y t o ha ve t he E C Gs perf or me d. Q ualifie d st u d y site pers o n nel m ust or der, 
recei ve, a n d re vie w res ults.
St u d y I nter ve nti o n
If t he safety of a trial partici pa nt is at ris k beca use t he y ca n n ot c o m plete re q uire d e val uati o ns 
or a d here t o critical miti gati o n ste ps, t he n disc o nti n ui n g t hat partici pa nt fr o m st u d y 
i nter ve nti o n m ust be c o nsi dere d.
T he f oll o wi n g is rec o m me n de d f or t he a d mi nistrati o n of P F - 0 7 0 6 2 1 1 9, P F-0 6 8 0 1 5 9 1, a n d 
Be vaciz u ma b -Pfizer, partici pa nts w h o ha ve acti ve [c o nfir me d ( p ositi ve b y  re g ulat or y 
a uth orit y - a p pr o ve d test) or pres u me d (test pe n di n g/cli nical s us pici o n)] S A R S-C o V 2 
i nfecti o n:
F or s y m pt o matic partici pa nts wit h acti ve S A R S- C o V 2 i nfecti o n, st u d y  i nter ve nti o n s h o ul d 
be dela y e d f or at least 1 4 da ys fr o m t he start of sy m pt o ms. T his dela y  is i nten de d t o all o w t he 
res ol uti o n of s ym pt o ms of S A R S -C o V 2 i nfecti o n.
Pri or t o restarti n g treat me nt, t he partici pa nt s h o ul d be afe brile f or 7 2 h o urs, a n d S A R S -
C o V 2 -relate d sy m pt o ms s h o ul d ha ve rec o vere d t o ≤ Gra de 1 f or a mi ni m u m of 7 2 h o urs. 
N otif y  t he st u d y tea m w he n treat me nt is restarte d.
C o nti n ue t o c o nsi der p ote ntial dr u g -dr u g i nteracti o ns as descri be d i n t his pr ot oc ol f or a n y  
c o nc o mita nt me dicati o n a d mi nistere d f or treat me nt of S A R S -C o V 2 i nfecti o n.
H o me He alt h Visits
A h o me healt h care ser vice ma y be utilize d t o facilitate sc he d ule d visits per t he Sc he d ule of 
Acti vities at t he discreti o n of t he treati n g p h ys icia n a n d i n c o ns ultati o n wit h t he S P O N S O R. 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 8
H o me healt h visits i ncl u de a healt hcare pr o vi der c o n d ucti n g a n i n -pers o n st u d y  visit at t he 
partici pa nt ’s l ocati o n, rat her t ha n a n i n-pers o n st u d y  visit at t he site. T he f oll o wi n g ma y be 
perf or me d d uri n g a h o me healt h visit:

Re vie w a n d rec or d st u d y i nter ve nti o n(s), i ncl u di n g c o m plia nce a n d misse d d oses.

Re vie w a n d rec or d a n y A Es a n d S A Es si nce t he last c o ntact. Refer t o Secti o n 8. 2 . 

Re vie w a n d rec or d a n y ne w c o nc o mita nt me dicati o ns or c ha n ges i n c o nc o mita nt 
me dicati o ns si nce t he last c o ntact.

Re vie w a n d rec or d c o ntrace pti ve met h o d a n d res ults of pre g na nc y testi n g. C o nfir m 
t hat t he partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he 
pr ot oc ol. Refer t o A p pe n di x 4 .
A d verse E ve nts a n d Seri o us A d verse E ve nts
St u d y  treat me nt s h o ul d c o nti n ue u nless t he i n vesti gat or/treati n g p h ysicia n is c o ncer ne d a b o ut 
t he safety of t he partici pa nt , i n w hic h case te m p orar y or per ma ne nt disc o nti n uati o n ma y be 
re q uire d.
It is rec o m me n de d that t he i n vesti gat or disc uss te m p orar y  or per ma ne nt disc o nti n uati o n of 
st u d y i nter ve nti o n wit h t he st u d y me dical m o nit or.
1 0. 1 0. 8 P atie nt D at a M o nit ori n g a n d Pr ot oc ol De vi ati o ns 
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat re q uire d pr ot oc ol tests a n d pr oce dures are 
c o m plete d as descri be d wit h t he pr ot oc ol. H o we ver, t he circ u msta nces ar o u n d t he o n g oi n g 
C O VI D -1 9 pa n de mic ma y  ma ke it u nfeasi ble t o perf or m s o me of t he tests a n d pr oce d ures. I n 
t hese cases, t he i n vesti gat or m ust ta ke all of t he necessar y ste ps t o e ns ure t he safet y a n d 
well bei n g of t he st u d y partici pa nt. W he n a re q uire d pr ot oc ol test or pr oce d ure ca n n ot be 
perf or me d, t he i n vesti gat or will pr o m ptl y  d oc u me nt t he reas o n f or t he misse d test or 
pr oce d ure a n d a n y c orrecti ve a n d pre ve nti ve acti o ns t he y ha v e ta ke n t o e ns ure t hat re q uire d 
pr ocesses will be a d here d t o as s o o n as p ossi ble. T he st u d y  tea m m ust be i nf or me d of t hese 
i nci de nts i n a ti mel y ma n ner.
If t he st u dy partici pa nt is u na ble t o visit t he st u d y site, re q uire d pr ot oc ol pr oce d ures t hat ca n 
be pe rf or me d t o t he best of st u d y site’s a bilit y via tele p h o ne c o ntact or vi de o ( w here all o we d) 
s h o ul d be c o nsi dere d, if i n t he o pi ni o n of t he i n vesti gat or it is t he safest a p pr oac h, e g, 
e val uati o n of p h ys ical sy m pt o ms i n place of pr ot oc ol ma n date d p h ys ical e xami nati o ns, 
re vie w of a d verse e ve nts or seri o us a d verse e ve nts, d osi n g c o m plia nce, c o ntrace pti o n c hec k, 
a n d c o nc o mita nt me dicati o n c hec ks, etc. St u d y partici pa nts s h o ul d ma ke e ver y  atte m pt t o 
c o nti n ue t o mai ntai n a d osi n g diar y ( w here a p pr o priate) a n d ma y se n d t his t o t he site 
electr o nicall y or via mail.
Patie nt data m o nit ori n g will c o nti n ue wit h o ut i nterr u pti o n. Re m ote data m o nit ori n g will be 
per mitte d, w here ver p ossi ble. T he C R A will c o nti n ue m o nit ori n g data i n a n o n g oi n g ma n ner 
via re m ote access f oll o wi n g all i nstit uti o nal pr ocesses, if a p plica ble.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 9
A n y  ot her de viati o ns t o t he pr ot oc ol, e xce pt f or t hese a p pr o ve d m o dificati o ns, m ust be 
d oc u me nte d as pr ot oc ol de viati o ns, a n d if relate d t o t he pa n de mic, t he reas o n s h o ul d clearl y 
state “ C O VI D-1 9”. T hese are n ot i m me diately re q uire d t o be re p orte d t o healt h a ut h orities or 
I RB/ E Cs u nless re q ueste d l ocall y .
T he i m pact of C O VI D -1 9 o n pr ot oc ol visits a n d st u d y  tests or pr oce d ures a n d ass ociate d 
ti mefra mes s h o ul d be re p orte d, prefera bl y, o n a case re p ort f or m ( C R F) if at all p ossi ble. F or 
partici pa nt disc o nti n uati o n re p orti n g i n t he C R F: Please select t he m ost a p pr o priate stat us f or 
disc o nti n uati o n. I f t he disc o nti n uati o n is ass ociate d wit h t he c urre nt C O VI D-1 9 pa n de mic, 
e nter “ C O VI D -1 9” i n t he “ S pecif y  Stat us” fiel d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 0
1 0. 1 9. P E T I ma gi n g S u b st u d y wit h 8 9Zr -Df -I A B 2 2 M 2 C
1 0. 1 9. 1. O ver all desi g n a n d Scie ntific R ati o n al f or S u bs t u d y 
T his s u bst u d y  will e val uate C D 8 P E T tracer u pta ke, at b aseli ne a n d o n- treat me nt, i n t u m or 
lesi o ns a n d refere nce tiss ues (i ncl u di n g T-cell ric h tiss ues a n d t h ose e x pecte d t o e x press 
G U C Y 2c) wit h t he ai m t o meas ure p ote ntial c ha n ge i n C D 8 P E T tracer u pta ke i n t u m or 
lesi o ns bet wee n b aseli ne a n d o n -treat me nt a n d i n refere nce tiss ues.
T he P E T i ma gi n g s u bst u d y will be o pe ne d i nitiall y at a s ubset of U S sites partici pati n g i n 
St u d y C 3 8 6 1 0 0 1 , w hic h ha ve bee n q ualifie d f or use wit h 8 9Zr -Df -I AB 2 2 M 2 C.  
Site s q ualifie d f or use m ust ha ve lice nses w hic h i ncl u de ha n dli n g of Zirc o ni u m - 8 9 a n d 
a p pr o priate pr oce d ures i n place f or ha n dli n g of sa m ples t hat are c o nsi dere d ra di oacti ve . T his 
i nclu des pr ocessi n g a n d a nal ys is of bl o o d sa m ples t hat are c ollecte d wit hi n 3 0 da y s of C D 8 
P E T tracer i nf usi o n.
St u d y  p o p ulati o n: A p pr o xi matel y  1 0 t o 1 5 partici pa nts e nr olle d acr oss t he st u d y ( prefera bly 
t h ose e nr olle d i n t he ma n dat or y  bi o psy c o h orts i n P art 1 a n d P art 2) will als o be eli gi ble f or 
e nr oll me nt i n t he P E T i ma gi n g s u bst u dy wit h t he C D 8 T cell s pecific 8 9Zr -Df -I AB 2 2 M 2 C 
P E T tracer ( C D 8 P E T tracer).
As part of its mec ha nis m of acti o n, P F - 0 7 0 6 2 1 1 9 is e x pecte d t o i ncrease T-cell i nfiltrati o n 
selecti vely i nt o t u m ors e x pressi n g G U C Y 2c.  C D 8 P E T tracer st u dies are i nte n de d t o e na ble 
meas ure me nt of C D 8 + T cells t hr o u g h o ut t he b o d y, per mitti n g t he c o m paris o n of C D 8 + T -
cell le vels i n t u m ors (bef ore a n d after a d mi nistrati o n of P F - 0 7 0 6 2 1 1 9) wit h C D 8 T cell 
distri b uti o n i n refere nce tiss ues.  A d diti o nall y , C D 8 P E T tracer met h o d ol o g y  i ma ges m ulti ple 
t u m or lesi o ns si m ulta ne o usl y i n c o m paris o n t o paire d bi o ps y pr oced ures w hic h are us uall y  
li mite d t o a si n gle accessi ble lesi o n.   C D 8 P E T tracer st u dies ma y t heref ore c o ntri b ute 
t o war d a br oa der u n dersta n di n g of t he P D effects of P F -0 7 0 6 2 1 1 9 al o ne a n d p ote ntiall y  i n 
c o m bi nati o n wit h ot her a ge nts.  T his i nf or mati o n is i nte n de d t o c haracterize t he mec ha nis m 
of acti o n P F - 0 7 0 6 2 1 1 9, i de ntif y partici pa nts w h o are m ost li kel y t o be nefit fr o m treat me nt, 
a n d i de ntif y p ote ntial resista nce mec ha nis ms t o P F -0 7 0 6 2 1 1 9 al o ne a n d i n c o m bi nati o n wit h 
ot her a ge nts.
T he C D 8 P E T tracer is a ~ 8 0 k Da mi ni b o d y  ( M b) wit h hi g h affi nit y ( bi n di n g E C5 0 = 0. 4 n M) 
f or t he C D 8 glyc o pr otei n t hat is c o nj u gate d wit h Df a n d ra di ola bele d wit h 8 9Zr f or i ma gi n g 
C D 8 + T cells i n h u ma ns. It bi n ds t o b ot h C D 8 α α a n d C D 8 α β a n d will t heref ore bi n d t o 
mat ure T cells, de vel o pi n g t h y m o c y tes, T C R α β -e x pressi n g g ut i ntrae pit helial T cells, s o me 
γ δ T cells a n d s o me N K a n d de n dritic cells. T he M b desi g n of t he C D 8 P E T tracer is 
i nte n de d t o a d dress t he li mitati o ns of m olec ular i ma gi n g usi n g i ntact m o n ocl o nal a nti b o dies
( pr ol o n ge d bl o o d circ ulati o n, si g nifica nt bac k gr o u n d si g nal) a n d t o pre ve nt acti vati o n of 
i m m u ne cell Fc effect or f u ncti o ns. T he s maller size a n d i na bilit y  of t he M b t o i nteract wit h 
t he Fc R a n d t he ne o natal Fc rec ycli n g rece pt or res ults i n a relati vel y  i nert i ma gi n g a ge nt 
wit h ra pi d cleara nce. I A B 2 2 M 2 C was e n gi neere d fr o m t he h u ma nize d hea v y  a n d li g ht c hai n 
se q ue nces of t he m uri ne O K T 8 a nti b o d y  t hat tar gets h u man C D 8.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 1
T he C D 8 P E T tracer has c o m plete d a P hase 1 st u d y ( N C T 0 3 1 0 7 6 6 3) a n d is c urre ntly bei n g 
e val uate d i n a P hase 2 , o pe n -la bel st u d y (N C T 0 3 8 0 2 1 2 3 ) i n partici pa nts wit h select a d va nce d 
or metastatic s oli d t u m ors selecte d t o recei ve sta n dar d of care i m m u n ot hera p y o nly. T his 
st u d y is e val uat i n g t he safet y of re peat d oses of t he C D 8 P E T tracer a n d ai mi n g t o assess a n d 
q ua ntif y  a n y detecta ble c ha n ges i n u pta ke bet wee n b aseli ne a n d o n -treat me nt.  Interi m res ults 
fr o m t his st u d y ha ve esta blis he d t he a bility of t he C D 8 P E T tracer t o detect C D 8 + T cells i n 
t u m ors a n d c o nfir me d t he safet y pr ofile of t he C D 8 P E T tracer after re peat d oses. A d diti o nal 
i nf or mati o n relate d t o safet y a n d i ma gi n g res ults is prese nte d i n t he 8 9Zr -Df -I AB 2 2 M 2 C 
i n vesti gat or br oc h ure.  T h ese data ha ve esta blis he d t he p ote ntial utilit y  of usi n g t he C D 8 P E T 
tracer f or partici pa nts i n St u d y C 3 8 6 1 0 0 1 .
1 0. 1 9. 2. Be nefit /Ris k Asse ssme nt
P E T Sc a ns wit h 8 9 Zr -Df -I A B 2 2 M 2 C
Base d o n t he a vaila ble data, t he pri nci pal ris k is e x p os ure t o i o nizi n g ra diati o n release d b y 
8 9Zr . Ad diti o nall y , t here is l o w li keli h o o d t hat t he C D 8 P E T tracer m a y be ass ociate d wit h a n 
a d verse reacti o n or i m m u n o ge nic res p o nse. T he n o ncli nical data ha ve de m o nstrate d t hat 
I AB 2 2 M 2 C a n d Df- I AB 2 2 M 2 C ha d n o meas ura ble effects o n T cell pr oliferati o n/ acti vati o n 
or c y t o ki ne release. As of 0 4 A u g u st 2 0 2 1 , 8 8 patie nts ha ve recei ve d t he C D 8 P E T t racer. 
M o nit ori n g of partici pa nts is rec o m me n de d. T he p ote ntial ris ks after i nf usi o n wit h t he C D 8 
P E T tracer i ncl u de i nf usi o n site reacti o ns of re d ness, itc hi n g a n d pai n, aller gic reacti o n 
(i ncl u di n g a na p hyl a xis), ki d ne y /li ver/res pirat or y fail ure, t hr o m b oc yt o pe nia, art hritis, a n d/ or 
h y p ote nsi o n. I nserti o n of I V cat heters f or i nf usi o n s a n d bl o o d dra ws m a y  ca use mi n or pai n, 
br uisi n g, a n d/ or i nfecti o n at t he i nf usi o n site.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 2
1 0. 1 9. 3. P E T I ma gi n g S u b st u d y O bjecti ves
I n a d diti o n t o t he c ore st u d y o bjecti ves (Secti o n 3 ), t he P E T i ma gi n g su b st u d y
(Secti o n 1 0. 1 9 ) will i ncl u de t he f oll o wi n g e x pl orat or y o bjecti ves:
O bjecti ves:
Terti ar y/ E x pl or at or y
E n d p oi nts:
Terti ar y/ E x pl or at or y
• Meas ure p ote ntial c ha n ge i n C D 8 P E T tracer u pta ke 
a n d bi o distri b uti o n i n t u m or lesi o ns a n d refere nce 
tiss ues, i ncl u di n g C D 8 + T cell ric h refere nce tiss ues 
bet w ee n baseli ne a n d o n- treat me nt wit h 
P F -0 7 0 6 2 1 1 9 .
• Meas ure p ote ntial c ha n ges i n C D 8 P E T tracer 
u pta ke o n baseli ne a n d o n -treat me nt P E T sca ns 
c o m pare d t o c ha n ge i n C D 8 + T cells i n t u m or 
lesi o ns b y I H C if t he sa me lesi o n was bi o psie d at 
b aseli ne a n d o n-t reat me nt visits.
• Ex pl ore t he q ualitati ve a n d q ua ntitati ve C D 8 P E T 
tracer meas ure me nts wit h cli nical o utc o mes of 
P F -0 7 0 6 2 1 1 9 treat me nt.
• Eval uate t he ass ociati o n of  C D 8 P E T tracer u pta ke 
wit h i m m u ne i nfiltrates a n d ot her m olec ular 
bi o mar kers (s uc h as C D 4, C D 8, P D -1 a n d P D -L 1) .
Bi o ps y lesi o n :  S U V meas ure me nt at baseli ne vs 
S U V meas ure me nt f oll o wi n g treat me nt .
Tar get lesi o n :  S U V meas ure me nt at baseli ne vs 
S U V meas ure me nt
f oll o wi n g treat me nt.
N o ntar get lesi o ns (if a p plica ble) :  S U V meas ure me nt
at baseli ne vs S U V meas ure me nt f oll o wi n g 
treat me nt.
Refere nce tiss ues (i ncl u di n g b ut n ot li mite d t o 
n or m al c ol o n a n d ot her G U C Y 2c e x pressi n g tiss ues 
w here a p plica ble) :  S U V meas ure me nt at baseli ne vs 
S U V meas ure me nt f oll o wi n g treat me nt
C ha n ge i n S U V meas ure me nt at baseli ne vs cli nical 
bi o mar ker or ra di o gra p hic res p o nses
S U V = sta n dar d u pta ke val ues 
1 0. 1 9. 4. P E T I ma gi n g S u b st u d y Desi g n 
Partici pa nts i n t his s u bst u d y will ha ve 2 pla n ne d i ma gi n g sessi o ns:
1.
T he f irst i ma gi n g sessi o n will ta ke place pri or t o t hera py ( P E T Baseli ne ).  C D 8 P E T 
tracer will be a d mi nistere d wit h w h ole b o d y  P E T/ C T i ma gi n g ac q uire d 2 4 hr ( ± 3 hr) 
later a n d 7 t o 9 da y s pri or t o t he i nitiati o n of treat me nt wit h P F - 0 7 0 6 2 1 1 9.
2.
T he s ec o n d i ma gi n g sessi o n will ta ke place after recei vi n g t he first 3 d oses of 
P F - 0 7 0 6 2 1 1 9, o n C 2 D 8 , w hic h will be a p pr o xi matel y 5 t o 6 wee ks after i nitiati o n of 
treat me nt. C D 8 P E T tracer i ma gi n g a ge nt will be a d mi nistere d o n C 2 D 8 a n d w h ole 
b o d y P E T/ C T i ma gi n g ac q uire d 2 4 hr ( ± 3 hr) later.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 3
3.
A n a d diti o nal t hir d o pti o nal i ma gi n g sessi o n is i ncl u de d i n C y cle 3 or later. T he 
o pti o nal t hir d i ma gi n g sessi o n ma y  o nly be perf or me d after disc ussi o n a n d a gree me nt 
bet wee n t he i n vesti gat or a n d s p o ns or .
Partici pa nts i n t he P E T i ma gi n g s u bst u d y s h o ul d be e nr olle d , if p ossi ble, i n c o h orts re q uiri n g 
ma n dat or y  pretreat me nt a n d on -treat me nt bi o psies a n d will ha ve 2 pla n ne d bi o ps y  
pr oce d ures t o c oi nci de wit h P E T i ma gi n g sessi o ns.
1.
Baseli ne d e n o v o bi o ps y c ollecti o ns will occ ur after t he first i nf usi o n of t he C D 8 P E T 
tracer a n d its ass ociate d P E T sca n.
2.
O n treat me nt bi o ps y c ollecti o n will o cc ur wit hi n 1 wee k after t he sec o n d i nf usi o n of 
t he C D 8 P E T tracer a n d its ass ociate d P E T sca n.
I ncl usi o n Criteri a 
1.
Part ici pa nts m ust meet all eli gi bilit y criteria f or e nr oll me nt i n St u d y C 3 8 6 1 0 0 1 pri or 
t o bei n g e nr olle d i n t he P E T i ma gi n g s u bst u dy a n d i nitiati o n of pr oce d ures.
2.
Partici pa nts s h o ul d ha ve a t u m or a me na ble t o bi o ps y  a n d c o nse nt t o t hese pla n ne d 
bi o ps y  pr oce d ures. Partici pa nts wit h o ut a t u m or a me na ble t o bi o ps y  m ust be 
a p pr o ve d b y t he s p o ns or.
E xcl usi o n Criteri a
1.
Partici pa nts are e xcl u de d fr o m t he P E T i ma gi n g s u bst u d y  if a ny of t he e xcl usi o n 
criteria are met f or St u d y C 3 8 6 1 0 0 1.
2.
Partici pa nts f or w h o m t he o nl y  t u m or a me na ble t o bi o ps y is als o a tar get lesi o n.
3.
Partici pa nts w h o ha ve pre vi o usl y  recei ve d C D 8 P E T tracers or ot her 8 9Zr la bele d P E T 
tracers i n t he pri or 4 5 da y s.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 4
1 0. 1 9. 5. C D 8 P E T Tr acer I m a gi n g Pr oce d ures :
T a ble 2 4 . O ver vie w of P E T I m a gi n g S u bst u d y Visits
P E T I m a gi n g 
Pr oce d ures
B aseli ne Sc a n / Bi o ps y
St u d y 
St art
O n -Tre at m e nt Sc a ns / Bi o ps y
Visit 1 
Visit 2
Visit 3
C 1 D 1
Visit 4
Visit 5
Visit 6
D a y -7 t o -
9
fr o m 
C 1 D 1
2 4 hr 
( ± 3 hr) 
p ost 
i nf usi o n
P ost C D 8 
Tracer 
C T/ P E T 
sca n pri or 
t o C 1 D 1 
C 2 D 8
( ± 2 
da ys)
2 4 hr
( ± 3 hr) 
p ost 
i nf usi o n
C 2 D 1 5
( ±7 da ys ) 
p ost C D 8 
Tracer 
C T/ P E T Sca n
Vit al Si g ns 1
( bef ore a n d after 
i nf usi o n)
X
X
C D 8 P E T Tr acer 
inf usi o n
X
X
C D 8 P E T Tr acer
P E T/ C T sc a n 2
X
X
T u m or Bi o ps y 3
X
X
1 . Vital si g ns assesse d 1 5 ( ± 5) mi n utes pri or t o i nf usi o n a n d wit hi n 6 0 mi n utes after i nf usi o n of t he C D 8 P E T 
tracer.
2 . T u m or assess me nt sca ns sc he d ule d per pr ot oc ol f or e val uati o n of res p o nse per R E CI S T criteria are t o be 
c ollecte d se paratel y fr o m C D 8 P E T tracer s u bst u d y sca ns .
3 . T u m or bi o psies ca n be c ollecte d o n t he sa me da y as i ma gi n g as l o n g as t he y occ ur after t he P E T/ C T sca n
C D 8 P E T tr acer i nf usi o n:
D osi n g i nf or mati o n:
T he C D 8 P E T tracer is a n ~ 8 0 k Da M b wit h hi g h affi nit y  t o C D 8 glyc o pr otei n ( bi n di n g 
E C 5 0 = 0. 4 n M) t hat is c o nj u gate d wit h D f a n d ra di ola bele d wit h 8 9Zr f or i ma gi n g C D 8 + 
T- cells i n h u ma ns. 
A d ose of 1. 0 ( ± 2 0 %) m Ci of C D 8 P E T tracer as 1. 5 m g of A PI will be a d mi nistere d I V o ver 
5 t o 1 0 mi n utes, wit hi n 1 w ee k pri or t o t he i nitiati o n of t hera py wit h P F -0 7 0 6 2 1 1 9 , a n d 
a p pr o xi matel y 5 wee ks after start of treat me nt wit h P F- 0 7 0 6 2 1 1 9.
Dis pe nsati o n of C D 8 P E T tracer
T he C D 8 P E T tracer will be deli ve re d fr o m a ce ntral ma n ufact uri n g facilit y t o t he 
i n vesti gati o nal site’s ra di o p har mac y or N uclear Me dici ne De part me nt. U p o n recei pt, 
q ualifie d pers o n nel will e ns ure t hat t he st u d y  dr u g has bee n deli vere d i n g o o d c o n diti o n, 
i n ve nt orie d, st ore d pr o perl y, la bele d a n d dis pe nse d i n c o m plia nce wit h t he p har mac y ma n ual, 
all re g ulat or y a ge ncies a n d per t he i n vesti gat or’s prescri pti o n or der.
T he 8 9Zr d ose will be meas ure d b y t he q ualifie d pers o n nel i n a d ose cali brat or pri or t o 
dis pe nsi n g. T he n t he s yri n ge will be pl ace d i n a s hiel de d carrier al o n g wit h a desi g nate d I V 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 5
i nf usi o n p u m p f or ra di oacti ve i nf usi o n a n d a d mi nistrati o n. After d ose a d mi nistrati o n, t he 
q ualifie d pers o n nel will ret ur n t he s yri n ge f or resi d ual meas ure me nt b y t he q ualifie d 
pers o n nel (s uc h as t he n uc lear me dici ne tec h n ol o gist) at t he site. Meas ure d ra di oacti vit y 
val ues a n d ti mes of meas ure me nt will be d oc u me nte d, as well as t he t otal i njecte d v ol u me.
Re g ulat or y  a ge ncies re q uire acc o u nti n g f or t he dis p ositi o n of all i n vesti gati o nal dr u gs 
recei ve d by ea c h cli nical site. Inf or mati o n o n dr u g dis p ositi o n re q uire d b y  la w c o nsists of t he 
date recei ve d, date dis pe nse d, q ua ntit y  dis pe nse d, a n d t he partici pa nt i de ntificati o n n u m ber t o 
w h o m t he dr u g was dis pe nse d. T he I n vesti gat or is res p o nsi ble f or acc o u nti n g f o r all u n use d 
st u d y dr u g a n d destr oyi n g all use d st u d y  dr u g c o ntai ners i n c o m plia nce wit h t he 
Ra di o p har mac y  M a n ual.
I nf usi o n of C D 8 P E T tracer
T he dis pe nse d d ose will be i nf use d u n der t he s u per visi o n of a q ualifie d n uclear me dici ne 
pers o n nel as a n I V i nf usi o n wit h a n i nf usi o n p u m p o ver n o less t ha n 5 mi n utes f oll o we d b y a 
sali ne fl us h. T he t otal i nf usi o n ti me s h o ul d be bet wee n 5 a n d 1 0 mi n utes. V ital si g ns will be 
assesse d 1 5 ( ± 5) mi n utes pri or t o i nf usi o n a n d wit hi n 6 0 mi n utes after i nf usi o n of t he C D 8 
P E T tracer.
Pre me dicati o n (f or e xa m ple, wit h aceta mi n o p he n a n d di p he n h y dra mi ne) is n ot re q uire d b ut 
ma y  be a d mi nistere d at t he discreti o n of t he i n vesti gat or a p pr o xi matel y 1 h o ur pri or t o 
i nf usi o n of t he C D 8 P E T tracer.
8 9Zr -Df -I A B 2 2 M 2 C P E T/ C T sc a n:
P E T/ C T sca n ner vali dati o n:
I n a n eff ort t o ge nerate t he m ost acc urate a n d c o nsiste nt i ma gi n g data acr oss all partici pati n g 
i n vesti gati ve sites, t o s u p p ort t he data c ollecti o n a n d a nalys is f or t his cli nical st u d y, t he 
S p o ns or is c o ntracti n g wit h t he N uclear Me dicine Cli nical Trial Gr o u p, L L C ( N M C T G) t o 
c o n d uct t he vali dati o n of P E T/ C T sca n ners at eac h partici pati n g site t hat will be use d i n t his 
st u d y.
T he N M C T G will pr o vi de a p ha nt o m al o n g wit h detaile d i nstr ucti o ns of t he P E T/ C T 
vali dati o n pr oce d ures o n h o w t o fi ll a n d sca n t he p ha nt o m a n d c o or di nate deli ver y of a d ose 
of 8 9Zr t o t he site. Eac h P E T/ C T sca n ner i nte n de d f or use i n t his cli nical st u d y will be 
vali date d b y t he N M C T G. O nce t he vali dati o n is c o m plete d, t he site will s u b mit t he data t o 
t he N M C T G f or a nalys is. T he site will st ore t he p ha nt o m i n a sec ure, dr y area f or 3 3 d a y s 
( u ntil t he ra di oacti vit y has deca y e d t o a n u n detecta ble le vel) bef ore tra ns p orti n g bac k t o t he 
N M C T G.
U p o n c o m pleti o n of t he P E T/ C T sca n ner vali dati o n, t he N M C T G will pr o vi de a vali dat i o n 
certificate a n d t he setti n g para meters s pecific t o t he vali date d sca n ner t hat s h o ul d be sa ve d 
i nt o t he site’s sca n ner pr ot oc ol f or t his cli nical trial bef ore  i ma gi n g t he first e nr olle d 
partici pa nt . It is re q uire d t hat sites o nl y use N M C T G-vali date d P E T/ C T sca n ner(s) , wit h t he 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 6
setti n g para meters ge nerate d fr o m t he p ha nt o m-vali dati o n pr oce d ure , t o i ma ge partici pa nts 
e nr olle d i n t his trial as per pr ot oc ol.
Pri or P E T/ C T sca n ner vali dati o n b y  N M C T G f or use wit h t he C D 8 P E T tracer is acce pta ble 
f or use of a P E T/ C T sca n ner i n t his trial as l o n g as P E T/ C T sca ns ta ke place pri or t o 
e x pirati o n of sca n ner certificati o n.
P E T/ C T Sca ns:
8 9Zr -Df -I AB 2 2 M 2 C ( C D 8 P E T Tracer) P E T / C T sca n i ma ges m ust o nl y  be ac q uire d o n 
P E T/ C T sca n ners t hat ha ve bee n a p pr o ve d b y t he s p o ns or. T he S p o ns or m ust be c o ntacte d 
f or per missi o n t o use alter nate sca n ners i n case of e q ui p me nt fail ure a n d/ or maj or e q ui p me nt 
u p gra des or re place me nt. Ac q uisiti o n a n d rec o nstr ucti o n para meters s h o ul d be o btai ne d 
acc or di n g t o t he rec o m me n dati o n pr o vi de d t o eac h site base d u p o n p ha nt o m vali dati o n of t he 
sca n ner a n d s h o ul d be o btai ne d i n List M o de, w he ne ver p ossi ble, t o all o w f or virt ual 
ra di oacti ve d ose rec o nstr ucti o n at a later date.
Sca ns are prefera b l y w h ole b o d y sca ns fr o m t he base of t he s k ull t hr o u g h u p per-t hi g hs 
(e nc o m passi n g t he pel vis). A d diti o nal areas of k n o w n or s us pecte d disease s h o ul d be 
o btai ne d (if t he y  are o utsi de of t his area) at e ver y sca n visit usi n g ac q uisiti o n setti n gs 
o pti mize d f or 8 9Zr i ma gi n g. Please refer t o t he i ma gi n g ma n ual re gar di n g partici pa nt
pre parati o n, sca n ni n g ti mes per be d p ositi o n, 8 9Zr -o pti mizati o n, ac q uisiti o n a n d 
rec o nstr ucti o n para meters, slice t hic k ness, a n d ot her para meters as well as t he i nstr ucti o ns f or 
h o w t o s u b mit i ma ges f or ce ntral re vie w.
P E T/ C T sca ns as part of t he C D 8 P E T tracer st u d y ma y  be c ollecte d f or ce ntral re vie w. 
A d diti o nall y , baseli ne a n d t u m or assess me nt sca ns sc he d ule d per pr ot oc ol f or e val uati o n per 
R E CI S T criteria s h o ul d be c ollecte d se parat el y fr o m C D 8 P E T tracer s u bst u d y sca ns a n d 
s h o ul d be perf or me d i n acc or da nce wit h i nstit uti o nal practices.
T u m or Bi o ps ies:
Pretreat me nt a n d o n -treat me nt de n o v o t u m or bi o psies s h o ul d be c ollecte d as descri be d i n 
Bi o mar ker Secti o n 8. 8. 2 a n d t he La b orat or y Ma n ual wit h t he f oll o wi n g a d diti o nal 
re q uire me nts:

Pretreat me nt de n o v o t u m or bi o psies m ust be c ollecte d at least 2 4 hr after C D 8 P E T 
tracer i nf usi o n a n d after t he ass ociate d baseli ne P E T/ C T sca n. Bi o psies s h o ul d n ot be 
c ollecte d bef ore C D 8 P E T tracer i nf usi o n. Pretreat me nt t u m or bi o psies m ust als o be 
c ollecte d pri or t o treat me nt wit h P F - 0 7 0 6 2 1 1 9.

O n -treat me nt bi o psies are sc he d ule d f or c ollecti o n o n C 2 D 1 5 ( ± 7 d a y s).  O ntreat me nt 
bi o psies m ust be c ollecte d after C 2 D 8 a n d at least after 2 4 hr p ost i nf usi o n, a n d 
wit hi n 2 wee ks after i nf usi o n of C D 8 P E T tracer f or t he o n- treat me nt P E T/ C T sca n.  
All eff ort s h o ul d be ma de t o c ollect o n -treat ment bi o psies fr o m t he sa me lesi o n t hat 
was bi o psie d bef ore t hera p y . If bi o psy of t he sa me lesi o n is n ot p ossi ble, t he bi o ps y 
s h o ul d be prefera bly c ollecte d fr o m a lesi o n at t he sa me metastatic or ga n.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 7

After bi o ps y  tiss ues (fr o m b ot h pretreat me nt a n d o n-treatme nt sa m ples) ha ve bee n 
c ollecte d a n d u n der g o ne pr ocessi n g pr oce d ures as o utli ne d i n t he La b orat or y Ma n ual, t he 
bi o ps y  m ust be st ore d o n site at r o o m te m perat ure f or 3 0 da y s ( p ost i nf usi o n of C D 8 P E T 
tracer) bef ore bei n g s hi p pe d (t o all o w f or deca y of ra dioacti vit y).
A d diti o nal details ca n be f o u n d bel o w i n Ta ble 2 5 , a n d i n t he La b orat or y Ma n ual.  
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 8
T a ble 2 5 .
Sc he d ule of Assess me nts f or 8 9Zr -Df -I A B 2 2 M 2 C I m m u n o-P E T C D 8 Mi ni -b o d y I m a gi n g S u bst u d y
Visit I de ntifier
Scree ni n g
Pre -Tre at me n t P E T S u b St u d y 
Assess me nts
C ycle 1
C ycle 2
C ycle ≥3
Tr acer 
I nf usi o n
P E T 
I ma gi n g
Pre -tre atme nt 
Bi o ps y
Tr acer 
I nf usi o n
P E T 
I ma gi n g
O n Tre at me nt 
Bi o ps y
Tr acer 
I nf usi o n
P E T 
I ma gi n g
E O T/
Wit h dr a w al
P ost 
tre atme nt 
f oll o w u p
St u d y D a y
-2 8 t o - 9
d a ys
- 7- 9
- 6
-6 t o - 1
1
1 5
1
8
9
1 5
8
9
H o urs Pre -/P ost -D ose 1
0
0
0
0
Visit wi n d o w 2
Tracer i nf usi o n starti n g - 9 t o -7 
da ys pre treat me nt
± 2 4 hrs
± 7 d a ys
E nr oll me nt eli gi bilit y 
c o nfir mati o n pri or t o e nteri n g 
P E T S u b -St u d y
X
P K a n d P D  sa m ples
P atie nts s h o ul d f oll o w all sc he d ule d assess me nt, i ncl u di n g s afety l a bs, b ase d o n t he tri al c o h ort 
t h at t hey are p artici p ati n g i n
Ma n dat or y Pre -treat me nt  a n d 
o n treat me nt T u m or Bi o ps y 3,
X
X
( ± 7 da ys)
O pti o nal Sec o n d 
O n -Treat me nt T u m or 
Bi o ps y 3 , 4,
X
Vital Si g ns bef ore a n d after 
i nf usi o n
X
X
X
8 9Zr -Df -I AB 2 2 M 2 C i nf usi o n5
X
X
8 9Zr -Df -I AB 2 2 M 2 C 6      
P E T/ C T sca n
X
X
O pti o nal Re peat P E T I ma gi n g 
Assess me nts 7
X  
X
1 Sa m pli n g ti mes i n dicate d are relate d t o t he e n d of t he S C i njecti o n. All eff orts s h o ul d be ma de t o o btai n sc he d ule d P E T assess me nts i ncl u di n g bi o psies pri or t o treat me nt if 
c ollecti o n occ urs o n a da y of a sc he d ule d d ose of P F- 0 7 0 6 2 1 1 9.
2 Visit wi n d o w is base d o n t he i nitiati o n of P E T tracer i nf usi o n.
3 Bi o psies ca n be c ollecte d o n t he sa me da y as P E T i ma gi n g b ut m ust be c ollecte d after P E T i ma gi n g has occ urre d.
4 O pti o nal sec o n d o n treat me nt bi o ps y ma y be c ollecte d eit her after o pti o nal re peat P E T i ma gi n g or at E O T.
5 Pretreat me nt i nf usi o n m ust occ ur wit hi n 7- 9 da ys bef ore treat me nt ( C 1 D 1), a n d wit hi n 2 4 hrs of C 2 D 8.
6 P E T sca n m ust ta ke place 2 4 h o urs ± 3 hrs after i nf usi o n of 8 9Zr -Df -I AB 2 2 M 2 C, t u m or assess me nt sca ns sc he d ule d per pr ot oc ol f or e val uati o n of R E CI S T criteria s h o ul d b e 
c ollecte d se paratel y fr o m C D 8 P E T tracer s u bst u d y.
7 O pti o nal re peat P E T i ma gi n g ma y o nl y be perf or me d after disc ussi o n a n d a gree me nt bet wee n t he i n vesti gat or a n d s p o ns or.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 9
1 0. 2 0. S u bc ut a ne o us I njecti o n Site L oc ati o ns
I njecti o n site l ocati o ns i ncl u de a ma xi m u m of 8 u ni q ue a d mi nistrati o n sites distri b ute d acr oss 
4 a b d o mi nal q ua dra nts wit h a p ossi bilit y  of u p t o 2 i njecti o n l ocati o ns per q ua dra nt. F or a 
gi ve n q ua dra nt, L o cati o n 1 is pr o xi mal t o t he u m bilic us a n d L ocati o n 2 is distal t o t he 
u m bilic us. 
I njecti o ns t o t he a b d o me n are preferre d. If S C i njecti o ns i n t he a b d o mi nal l ocati o n are n ot 
p ossi ble, S C i njecti o ns ca n be a d mi nistere d i n a distri b ute d ma n ner i n t he t hi g hs after 
disc ussi o n a n d a gree me nt bet wee n i n vesti gat or a n d t he S p o n s or. S C i njecti o ns i n t he u p per 
e xtre mities (e g, delt oi d, u p per a n d l o wer ar m) are n ot per mitte d.
T he f oll o wi n g pri nci ples  s h o ul d g ui de selecti o n of sites f or S C i njecti o n:
Pri nci ple [ 1]:  F or partici pa nts recei vi n g c o m bi nati o n t hera p y i n v o l vi n g > 1 dr u g a d mi nistere d 
s u bc uta ne o usly (f or e xa m ple, b ot h P F - 0 7 0 6 2 1 1 9 a n d P F-0 6 8 0 1 5 9 1), eac h dr u g s h o ul d be 
a d mi nistere d i n se parate a b d o mi nal q ua dra nt(s).
Pri nci ple [ 2]:  I f t he t otal n u m ber of S C i njecti o ns per mits, t he n i njecti o n sites (e ve n f or t he 
sa me dr u g) s h o ul d be distri b ute d a m o n g q ua dra nts t o t he e xte nt p ossi ble bef ore utilizi n g 2 
sites wit hi n t he sa me q ua dra nt, s u bject t o c o nstrai nt of pri nci ple [ 1].
Pri nci ple [ 3]:  I n t he e ve nt of s pecial circ u msta nces (f or e xa m ple, a n i ns ufficie nt n u m ber of
s uita ble i njecti o n sites o n t he a b d o me n), t he n t he i n vesti gat or s h o ul d c o ns ult wit h t he 
S p o ns or f or f urt her g ui da nce.
Trac k t he partici pa nt’s i njecti o n sites (s) se q ue ntiall y  o n t his dia gra m wit h a re d pe n a n d 
mar k t he i njecti o n sites o n t he partici pa nt’s a b d o me n acc or di n g t o yo ur cli nic’s sta n dar d 
practice.
Rec or d t he l ocati o n a n d ti me of eac h i njecti o n a n d a n y  IS R i n t he partici pa nt’s s o urce rec or ds 
a n d st u d y C R F. See e C R F g ui deli nes f or m ore i nf or mati o n.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 0
1 0. 2 1. Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble T h r o u g h A me n d me nt 6
D oc u me nt Hist or y:
Pr ot oc ol A me n d me nt 6 ( 0 8 -Oct -2 0 2 1)
R ati o n ale f or Pr ot oc ol A me n d me nt 6 : T his a me n d me nt descri be d a ne w C D 8 P E T tracer 
s u bst u d y i nte n de d t o pr o vi de e x pl orat or y data t o e na ble n o ni n vasi ve vis ualizati o n of t he 
rele va nt C D 8 + T-cell p o p ulati o n of t he i m m u ne s yste m. I n a d diti o n, t his a me n d me nt 
pr o vi des m o difie d g ui da nce o n ( 1) i njecti o n site l ocati o ns a n d m o nit ori n g f or I S Rs; a n d ( 2) 
m a na ge me nt of diarr hea.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
Sc he d ule of 
Acti vities 
Ta ble 2 i n 
Secti o n 1
C ha n ge d uri nal ys is c ollecti o n 
da y  fr o m C 1 D 1 9 t o C 1 D 1 5
C ha n ge descri be d i n 0 6 A pril 2 0 2 1 
P A C L
Sc he d ule of 
Acti vities 
Ta ble 2 i n 
Secti o n 1
Re m o ve d te xt fr o m f o ot n ote 
n u m ber 2 pertai ni n g t o 
a d diti o nal si g ni n g of c o nse nt 
d oc u me nt i n Ja pa n after at 
least C ycle 1 of Part 1 A bef ore 
c o nti n ui n g wit h C ycle 2.
C ha n ge descri be d i n 0 6 A pril 2 0 2 1 
P A C L
Sc he d ule of 
Acti vities 
Ta ble 4 i n 
Secti o n 1
Bl o o d sa m ples f or 
P K/ A D A/ N A b f or 
P F - 0 6 8 0 1 5 9 1 a n d 
be vaciz u ma b -Pfizer will n ot be 
re q uire d o n C 1 D 1.
O n C 2 D 1 (a n d all s u bse q ue nt 
c ycles wit h sc he d ule d 
c ollecti o ns) “ Bl o o d sa m ples 
f or P K/ A D A/ NA b a gai nst 
P F - 0 6 8 0 1 5 9 1” will n ot be 
re q uire d. I nstea d, “ Bl o o d 
sa m ples f or P K/ A D A/ NA b 
a gai nst P F-0 6 8 0 1 5 9 1” will be 
c ollecte d o n Da y 1 5 of all 
c ycles
C ha n ge descri be d i n 0 6 A pril 2 0 2 1 
P A C L
Sc he d ule of 
Acti vities 
Ta ble 4 i n 
Secti o n 1
F o ot n ote # 3 is clarifie d as 
f oll o ws: All pre-d ose bl o o d 
sa m ples f or P F-0 6 8 0 1 5 9 1 will 
b e c ollecte d o n Da y 1 5 visit of 
C ha n ge descri be d i n 0 6 A pril 2 0 2 1 
P A C L
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 1
D oc u me nt Hist or y:
Pr ot oc ol A me n d me nt 6 ( 0 8 -Oct -2 0 2 1)
R ati o n ale f or Pr ot oc ol A me n d me nt 6 : T his a me n d me nt descri be d a ne w C D 8 P E T tracer 
s u bst u d y i nte n de d t o pr o vi de e x pl orat or y data t o e na ble n o ni n vasi ve vis ualizati o n of t he 
rele va nt C D 8 + T-cell p o p ulati o n of t he i m m u ne s yste m. I n a d diti o n, t his a me n d me nt 
pr o vi des m o difie d g ui da nce o n ( 1) i njecti o n site l ocati o ns a n d m o nit ori n g f or I S Rs; a n d ( 2) 
m a na ge me nt of diarr hea.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
eac h sc he d ule d c ollecti o n 
C y cle. Pre-d ose bl o o d sa m ples 
f or be vaciz u ma b-Pfizer will be 
c ollecte d o n Da y 1 5 visit i n 
C y cle 1 a n d s u bse q ue ntl y o n 
D a y  1 visit of eac h sc he d ule d 
c ollecti o n C ycle. T he c ha n ges 
t o Ta ble 4 were ma de t o better 
ali g n wit h t he d ose pri mi n g 
strate g y, w here P F-0 6 8 0 1 5 9 1 
or be vaciz u ma b -Pfizer will be 
a d mi nistere d f or t he first ti me 
o n C 1 D 1 5, t heref ore 
c ollecti o ns fr o m C 1 D 1 were 
re m o ve d a n d/ or m o ve d t o 
acc o m m o date t hese c ha n ges
Sc he d ule of 
Acti vities 
Ta ble 4 i n 
Secti o n 1
F o ot n ote # 3 was re vise d t o 
clarif y t he c ollecti o n sc he d ules 
f or P K/ A D A/ N A b f or 
P F -0 7 0 6 2 1 1 9/ be vaciz u ma b -
Pfizer a n d P F -0 6 8 0 1 5 9 1 i n 
C y cles 5 a n d be yo n d.
Clarifie d bl o o d c ollecti o n sc he d ule f or 
P K/ A D A/ N A b f o r 
P F -0 7 0 6 2 1 1 9/ be vaciz u ma b -Pfizer a n d 
P F -0 6 8 0 1 5 9 1 i n C y cles 5 a n d be yo n d.
Sc he d ule of 
Acti vities 
Ta ble 6 i n 
Secti o n 1
Bl o o d sa m ples f or 
P K/ A D A/ N A b f or 
P F - 0 6 8 0 1 5 9 1 a n d 
be vaciz u ma b -Pfizer will n ot be 
re q uire d o n C 1 D 1.
O n C 2 D 1 (a n d all s u bse q ue nt 
c ycles wit h sc he d ule d 
c ollecti o ns) “ Bl o o d sa m ples 
f or P K/ A D A/ NA b a gai nst 
P F -0 6 8 0 1 5 9 1” will n ot be 
C ha n ge descri be d i n 0 6 A pril 2 0 2 1 
P A C L
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 2
D oc u me nt Hist or y:
Pr ot oc ol A me n d me nt 6 ( 0 8 -Oct -2 0 2 1)
R ati o n ale f or Pr ot oc ol A me n d me nt 6 : T his a me n d me nt descri be d a ne w C D 8 P E T tracer 
s u bst u d y i nte n de d t o pr o vi de e x pl orat or y data t o e na ble n o ni n vasi ve vis ualizati o n of t he 
rele va nt C D 8 + T-cell p o p ulati o n of t he i m m u ne s yste m. I n a d diti o n, t his a me n d me nt 
pr o vi des m o difie d g ui da nce o n ( 1) i njecti o n site l ocati o ns a n d m o nit ori n g f or I S Rs; a n d ( 2) 
m a na ge me nt of diarr hea.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
re q uire d. I nstea d, “ Bl o o d 
sa m ples f or P K/ A D A/ NA b 
a gai nst P F-0 6 8 0 1 5 9 1” will be 
c ollecte d o n Da y 1 5 of all 
c ycles
Sc he d ule of 
Acti vities 
Ta ble 6 i n 
Secti o n 1
F o ot n ote # 3 is clarifie d as 
f oll o ws: All pre-d ose bl o o d 
sa m ples f or P F-0 6 8 0 1 5 9 1 will 
be c ollecte d o n Da y  1 5 visit of 
eac h sc he d ule d c ollecti o n 
C y cle. Pre-d ose bl o o d sa m ples 
f or be vaciz u ma b-Pfizer will be 
c ollecte d o n Da y 1 5 visit i n 
C y cle 1 a n d s u bse q ue ntl y o n 
D a y  1 visit of eac h sc he d ule d 
c ollecti o n C ycle. T he c ha n ges 
t o Ta ble 6 were ma de t o better 
ali g n wit h t he d ose pri mi n g 
strate g y, w here P F-0 6 8 0 1 5 9 1 
or be vaciz u ma b -Pfizer will be 
a d mi nistere d f or t he first ti me 
o n C 1 D 1 5, t heref ore 
c ollecti o ns fr o m C 1 D 1 were 
re m o ve d a n d/ or m o ve d t o 
acc o m m o date t hese c ha n ges
C ha n ge descri be d i n 0 6 A pril 2 0 2 1 
P A C L
Sc he d ule of 
Acti vities 
Ta ble 6 i n 
Secti o n 1
F o ot n ote # 3 was re vise d t o 
clarif y t he c ollecti o n sc he d ules 
f or P K/ A D A/ N A b f or 
P F - 0 7 06 2 1 1 9/ be vaciz u ma b -
Pfizer a n d P F -0 6 8 0 1 5 9 1 i n 
C y cles 5 a n d be yo n d.
Clarifie d bl o o d c ollecti o n sc he d ule f or 
P K/ A D A/ N A b f or 
P F -0 7 0 6 2 1 1 9/ be vaciz u ma b -Pfizer a n d 
P F -0 6 8 0 1 5 9 1 i n C y cles 5 a n d be yo n d.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 3
D oc u me nt Hist or y:
Pr ot oc ol A me n d me nt 6 ( 0 8 -Oct -2 0 2 1)
R ati o n ale f or Pr ot oc ol A me n d me nt 6 : T his a me n d me nt descri be d a ne w C D 8 P E T tracer 
s u bst u d y i nte n de d t o pr o vi de e x pl orat or y data t o e na ble n o ni n vasi ve vis ualizati o n of t he 
rele va nt C D 8 + T-cell p o p ulati o n of t he i m m u ne s yste m. I n a d diti o n, t his a me n d me nt 
pr o vi des m o difie d g ui da nce o n ( 1) i njecti o n site l ocati o ns a n d m o nit ori n g f or I S Rs; a n d ( 2) 
m a na ge me nt of diarr hea.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 2. 5 
Be nefit/ Ris k 
Assess me nt
Para gra p h 2 was re vise d t o 
clarif y t hat C R S a n d diarr hea 
has alrea d y bee n o bser ve d i n 
t he st u d y. F urt her m ore, t he 
q ualif y i n g te xt, “ p ote ntiall y at 
hi g her d oses” has bee n 
re m o ve d.
T o u p date t he pr ot oc ol t hat C R S a n d 
diarr hea are n o l o n ger e x pecte d A Es 
of P F -0 7 0 6 2 1 1 9.  Rat her t he y  ha ve
bee n o bser ve d i n t he st u d y. 
F urt her m ore, t hat as of t he date of t his 
pr ot oc ol a me n d me nt, t here is n o clear 
d ose -A E relati o ns hi p.
Secti o n 2. 5 
Be nefit/ Ris k 
Assess me nt
I n para gra p h 4, ne w te xt was 
i nc or p orate d t hat refers t he 
rea der t o t he I ma gi n A B I B f or 
d etaile d i nf or mati o n o n t he 
e x pecte d be nefits a n d ris ks a n d 
e x pecte d A Es of t he P E T 
tracer.
T o direct rea der t o c o m plete 
i nf or mati o n o n t he be nefits, ris ks a n d 
e x pecte d A Es of t he P E T tracer f or 
t he ne wly i nc or p orate d s u bst u d y.
Secti o n 3, 
O bjecti ves a n d 
E n d p oi nts
A d de d ne w tertiar y  / 
e x pl orat or y e n d p oi nt of 
meas uri n g c ha n ges i n C D 8 
P E T tracer u pta ke f or b ot h 
Part 1 ( d ose escalati o n) a n d 
Part 2 ( d ose e x pa nsi o n)
D oc u me nts t he a d diti o n of ne w 
e n d p oi nts pertai ni n g t o C D 8 P E T 
tracer s u bst u d y.
Secti o n 4. 1, 
O verall Desi g n
A d de d para gra p h s u m marizi n g 
t he C D 8 P E T tracer s u bst u d y, 
al o n g wit h a n i ntra-d oc li n k t o 
t he c o m plete descri pti o n of t he 
s u bst u d y i n Secti o n 1 0. 1 9
Ca pt ures t he ne w C D 8 P E T tracer 
s u bst u d y i n t he hi g h-le vel st u d y 
descri pti o n.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 4
D oc u me nt Hist or y:
Pr ot oc ol A me n d me nt 6 ( 0 8 -Oct -2 0 2 1)
R ati o n ale f or Pr ot oc ol A me n d me nt 6 : T his a me n d me nt descri be d a ne w C D 8 P E T tracer 
s u bst u d y i nte n de d t o pr o vi de e x pl orat or y data t o e na ble n o ni n vasi ve vis ualizati o n of t he 
rele va nt C D 8 + T-cell p o p ulati o n of t he i m m u ne s yste m. I n a d diti o n, t his a me n d me nt 
pr o vi des m o difie d g ui da nce o n ( 1) i njecti o n site l ocati o ns a n d m o nit ori n g f or I S Rs; a n d ( 2) 
m a na ge me nt of diarr hea.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 4. 2 
Sci e ntific 
Rati o nale f or 
St u d y  Desi g n
A d de d italicize d te xt t o sec o n d 
para gra p h.  “ T he bi o mar ker 
assess me nts, i ncl u di n g t he P E T 
i m a gi n g s u bst u dy, ma y  
c o ntri b ute t o c o nfir mi n g tar get 
e n ga ge me nt….”
T o pr o vi de a f ull descri pti o n of t he 
bi o mar ker g oals i n t he o ve r vie w 
secti o n.
Secti o n 6. 1. 1. 2 
P F - 0 6 8 0 1 5 9 1
Te xt was re vise d pertai ni n g t o 
sit uati o ns w here a b d o mi nal 
i njecti o n site l ocati o ns are n ot 
p ossi ble.
Te xt was re vise d t o ali g n wit h t he ne w 
Secti o n 1 0. 2 0 A p pe n di x 2 0 
S u bc uta ne o us I njecti o n Site 
L ocati o ns. T his a n d t he a d de d 
A p pe n di x 2 0, facilitate l ocati o n of 
i njecti o n sites l ocati o ns w he n 
i n vesti gati o nal c o m bi nati o n t hera pies 
are a d mi nistere d. T his will facilitate 
m o nit ori n g f or I S Rs t o eit her 
i n vesti gati o nal t hera py.
Secti o n 6. 6. 4, 
A nti Diarr heal, 
A nti E metic 
T hera p y a n d
Secti o n 6. 7. 3 
D ose 
Re d ucti o ns –
Ta ble 1 2
A d de d te xt wit h a d diti o nal 
g ui da nce f or ma na gi n g 
diarr hea A Es ( Secti o n 6. 6. 4), 
re vise d Ta ble 1 2 ( Secti o n 
6. 7. 3)
E m p hasizes i m p orta nce of m o nit ori n g 
f or diarr hea a n d prescri bi n g 
i m me diate i nter ve nti o n t o war ds earl y 
res ol uti o n.
Secti o n 1 0. 1 3 
A p pe n di x 1 3
S u p p orti ve Care 
f or I m m u ne-
Relate d 
A d verse E ve nts 
(ir A Es)
T o Ta ble 2 0, a d de d te xt wit h 
a d diti o nal g ui da nce f or 
ma na gi n g diarr hea A Es
Pr o vi des detaile d i nstr ucti o ns f or 
treat me nt of diarr hea i ncl u di n g d osi n g
a dj ust me nts, a n d use of a nti- diarr heal 
me dicati o ns (l o pera mi de, L o m otil, 
a n d met h yl pre d nis ol o ne).
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 5
D oc u me nt Hist or y:
Pr ot oc ol A me n d me nt 6 ( 0 8 -Oct -2 0 2 1)
R ati o n ale f or Pr ot oc ol A me n d me nt 6 : T his a me n d me nt descri be d a ne w C D 8 P E T tracer 
s u bst u d y i nte n de d t o pr o vi de e x pl orat or y data t o e na ble n o ni n vasi ve vis ualizati o n of t he 
rele va nt C D 8 + T-cell p o p ulati o n of t he i m m u ne s yste m. I n a d diti o n, t his a me n d me nt 
pr o vi des m o difie d g ui da nce o n ( 1) i njecti o n site l ocati o ns a n d m o nit ori n g f or I S Rs; a n d ( 2) 
m a na ge me nt of diarr hea.
Secti o n # a n d 
N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n 1 0. 1 9 
P E T I ma gi n g 
S u bst u d y  wit h 
8 9Zr -Df -
I AB 2 2 M 2 C
A d de d c o m plete descri pti o n of 
t he ne w C D 8 P E T tracer 
s u bst u d y i ncl u di n g an S o A
de dicate d t o t he s u b st u d y 
pr oce d ures
Pr o vi de c o m pre he nsi ve i nf or mati o n t o 
t he sites f or c o n d ucti n g t he C D 8 P E T 
tracer s u bst u d y
Secti o n 1 0. 2 0 
S u bc uta ne o us 
I njecti o n Site 
L ocati o ns
A d de d clarif y i n g i nstr ucti o ns 
o n a b d o mi nal s u bc uta ne o us 
i njecti o ns i n t he c o m bi nati o n 
st u dies ( Parts 1 B a n d 2)
T he m ore detaile d i nstr ucti o ns will 
facilitate m o nit ori n g f or a n d 
d oc u me nti n g I S Rs f oll o wi n g 
c o m bi nati o n re gi me ns wit h 
P F -0 7 0 7 6 2 1 1 9 t hat are i njecte d 
S u bc uta n e o us
M ulti ple 
Secti o ns
Mi n or e dit orial c ha n ges a n d 
c orrecti o ns
Mi n or re visi o ns a n d
c orrecti o ns f or 
i m pr o vi n g u n dersta n di n g
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
A me n d me nt 5
1 6 Marc h 2 0 2 1
T he pri mar y  p ur p ose of t he a me n d me nt is 
t o re vise t he st u d y desi g n t o i nc or p orate 
c o h orts t hat recei ve a pri mi n g d ose 2 
wee ks bef ore recei vi n g a f ull d ose of P F-
0 7 0 6 2 1 1 9. T he pri mi n g d ose is a d de d t o 
miti gate t he occ urre nce of c y t o ki ne-
me diate d A Es f oll o wi n g s u bse q ue nt 
a d mi nistrati o ns of hi g her d oses.
S O A f or P art 1 A, 1 B, a n d P art 2 
Wit h o ut a Pri mi n g D ose ( T a ble 1)
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 6
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
A r o w f or pre me dicati o n was a d de d wit h 
a c orres p o n di n g f o ot n ote (als o a d de d t o 
Secti o n 6. 1. 1. 1). Pre me dicati o n has bee n 
i m ple me nte d i nt o t his st u d y t o f urt her 
i m pr o ve t olera bilit y a n d partici pa nt 
e x perie nce.
F or partici pa nts recei vi n g P F - 0 6 8 0 1 5 9 1, a
pre g na nc y  test is re q uire d 3 0 da ys after 
E O T a n d t he f oll o w -u p visit will occ ur 
3 0, 9 0, a n d 1 8 0 da y s after E O T.
P K, P D, a n d I m m u n o ge nicit y 
Assess me nts f or P art 2 Wit h o ut a 
Pri mi n g D ose ( T a ble 5)
T he 4 -h o ur ti me p oi nt o n Da y  1 was 
re m o ve d.
S O As f or P art 1 A, P art 1 B, a n d P art 2 
Wit h a Pri mi n g D ose ( T a ble 2);
P K, P D, a n d I m m u n o ge nicit y 
Assess me nts f or P art 1 a n d P art 1 B 
Wit h a Pri mi n g D ose S O A ( T a ble 4); 
a n d P K, P D, a n d I m m u n o ge nicit y 
Assess me nts f or P art 2 Wit h a Pri mi n g 
D ose ( T a ble 6)
T hese ta bles were a d de d f or t he c o h ort 
wit h a pri mi n g d ose; sc he d ules are si milar 
t o Ta ble 1 e xce pt m o difie d t o 
acc o m m o date t he pri mi n g d ose. 
Secti o n 2. 2. 8 S u m m ar y of C urre nt 
Cli nic al D at a fr o m St u d y 3 8 6 1 0 0 1
S u m mar y  of data as of 2 8 Dece m ber 2 0 2 0 
was a d de d.
Secti o n 2. 3. 1 P F -0 6 8 0 1 5 9 1, a n A nti -P D -
1 A nti b o d y: Cli nic al E x perie nce i n 
St u d y B 8 0 1 1 0 0 1 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 7
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
( N C T 0 2 5 7 3 2 5 9)/ A p pe n di x 9
Preli mi n ar y Cli nic al S u m m ar y f or 
St u d y B 8 0 1 1 0 0 1 P h ase 1 FI H ( P F 
0 6 8 0 1 5 9 1)
Data as of 1 0 Fe br uar y  2 0 2 1 was 
i ncl u de d.
Secti o n 2. 5 Be nefit/ Ris k Assess me nt
E x pa n de d t o i ncl u de t he be nefit/ris k 
assess me nt f or c o h orts wit h a pri mi n g 
d ose.
Secti o n 3 O bjecti ves a n d E n d p oi nts
Pri mar y  o bjecti ve was m o difie d t o 
i ncl u de t he c o h ort wit h a pri mi n g d ose.
Secti o n 4 St u d y Desi g n
U p date d a n d re or ga nize d t o i ncl u de 
details of t he c o h orts wit h t he pri mi n g 
d ose, i ncl u di n g D L T o bser vati o n peri o d 
f or Part 1 c o h orts wit h a pri mi n g d ose ( 4 2 
da y s), j ustificati o n f or t he starti n g d ose 
( m o n ot hera py, c o m bi nati o n d ose -fi n di n g, 
a n d d ose e x pa nsi o n [ Part 2]), criteria f or 
d ose escalati o n, a n d t he t otal n u m ber of 
st u d y partici pa nts.
Fi g ure 3 C 3 8 6 1 0 0 1 St u d y Sc he m a
U p date d t o i ncl u de t he c o h orts wit h a 
pri mi n g d ose.
Secti o n 5 St u d y P o p ul ati o n
I ncl usi o n criteri o n 5: t u m or tiss u e is n o w 
re q uire d f or Part 2 d ose e x pa nsi o n.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 8
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
E xcl usi o n criteri o n 1 2: partici pati o n i n 
me dical i ma gi n g st u dies wit hi n 2 wee ks 
of st u d y  e ntr y is all o we d.
Secti o n 6. 1. 1. 1 P F -0 7 0 6 2 1 1 9
Pre me dicati o n t o i m pr o ve partici pa nt 
t olera bilit y has bee n a d de d. 
Secti o n 6. 6 C o nc o mit a nt T her a p y
G ui deli nes ar o u n d C O VI D -1 9 vacci nes 
ha ve bee n a d de d.
Secti o n 6. 6. 4 A nti -Di arr he al, A nti -
E metic T her a p y
A d diti o nal details were pr o vi de d 
re gar di n g ma na ge me nt of diarr hea.
Secti o n 7. 1. 1 E C G C h a n ges
T his secti o n was re m o ve d si nce it was
u n necessar y . Rele va nt E C G re q uire me nts 
are i n t he I/ E criteria a n d D LT 
defi niti o ns.
Secti o n 8. 1. 4 E C G
Te xt clarifie d t o i n dicate t hat Q Tc F will 
be t he c orrecti o n fact or f or deter mi ni n g 
Q Tc.
Secti o n 8. 1. 7 I njecti o n Site T oler a bilit y 
Assess me nt
T o be perf or me d after P F- 0 6 8 0 1 5 9 1 
i njecti o ns as well.
Secti o n 8. 3 Tre at me nt of O ver d ose
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 9
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
U p date d t o i ncl u de defi niti o n of o ver d ose 
f or P F-0 6 8 0 1 5 9 1 a n d 
be vaciz u ma b -Pfizer.
Secti o n 9 St atistic al 
C o nsi der ati o ns/ A p pe n di x 1 0
U p date d t o i ncl u de statistical 
c o nsi derati o ns f or t he c o h orts wit h a 
pri mi n g d ose.
A p pe n di x 4: C o ntr ace pti ve G ui d a nce 
a n d C ollecti o n of Pre g n a nc y 
I nf or m ati o n
I ncrease d le n gt h of ti me t hat a hi g hl y 
effecti ve c o ntrace pti ve met h o d m ust be 
use d after t he last d ose of P F - 0 6 8 0 1 5 9 1 
a n d be vaciz u ma b- Pfizer.
A p pe n di x 9  Preli mi n ar y Cli nic al 
S u m m ar y f or St u d y B 8 0 1 1 0 0 1 P h ase 1 
FI H ( P F - 0 6 8 0 1 5 9 1)
A p pe n di x 9 has bee n u p date d t o i ncl u de 
m ore rece nt safet y i nf or mati o n a n d t o 
ali g n wit h all ot her P F-0 6 8 7 0 1 5 9 1 
pr ot oc ols refers directl y  t o t he m ost 
rece nt P F- 0 6 8 0 1 5 9 1 I B f or ot her 
i m p orta nt i nf or mati o n. 
Ot her mi n or clarificati o ns, a d mi nistrati ve, 
a n d t yp o gra p hical c ha n ges were ma de. 
T he ter m ‘ patie nt’ was re place d wit h 
‘ partici pa nt t hr o u g h o ut t he pr ot oc ol.
A me n d me nt 4
0 5 Oct o ber 2 0 2 0 
T he pri mar y  p ur p ose of t he a me n d me nt is 
t o i nc or p orate fee d bac k recei ve d fr o m t he 
U nite d States ( U S) F o o d a n d Dr u g 
A d mi nistrati o n ( F D A).
S O A f or P art 1 A, 1 B, a n d P art 2
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 0
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
T he f oll o wi n g re visi o ns were m a de :
Ma n dat or y  pr otei n uria assess me nt 
( di pstic k is acce pta ble) assess me nt is 
re q uire d pri or t o e ver y be vaciz u ma b-
Pfizer d ose t hr o u g h o ut t he c o urse of t he 
st u d y. If uri nalys is de m o nstrates pr otei n >
2 +, t he n a 2 4 -h o ur uri ne pr otei n 
c ollecti o n s h o ul d f oll o w. I n p atie nts wit h 
pr otei n uria greater t ha n or e q ual t o 2 
gra ms per 2 4 h o urs, be vaciz u ma b- Pfizer 
s h o ul d be hel d u ntil rec o ver y (less t ha n 2 
gra ms per 2 4 h o urs). Patie nts w h o 
de vel o p ne p hr otic s y n dr o me s h o ul d 
disc o nti n ue be vaciz u ma b -Pfizer.
I n a d diti o n, t his i nf or mati o n was als o 
a d de d t o: 

Secti o n 6. 1. 1. 3 Be vaciz u ma b-
Pfizer.

Secti o n 6. 7. 1 D osi n g I nterr u pti o ns

A p pe n di x 2: Cli nical L a b orat or y 
Tests
Secti o n 6. 7. 3 D ose Re d ucti o ns:
Ta ble 5 D ose M o dificati o ns f or A d verse 
Reacti o ns relate d t o Be vaciz u ma b -Pfizer 
was a d de d t o t he pr ot oc ol f or a d diti o nal 
g ui da nce. 
Ot her, mi n or clarificati o ns, a d mi nistrati ve 
a n d t yp o gra p hical c ha n ges were ma de. 
A me n d me nt 3
1 7 A u g ust 2 0 2 0
T he pri mar y  p ur p ose of t he a me n d me nt is 
t o u p date t he pr ot oc ol t o i ncl u de 
o perati o nal details nee de d f or t he 
pre pla n ne d e x pa nsi o n of t he st u d y  
( Part 2).
S O A f or P art 1 A, 1 B, a n d P art 2
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 1
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
F or p artici p a nts i n P art 2 t he f oll o wi n g 
re visi o ns were m a de : 

A ± 1 da y  wi n d o w was a d de d t o t he 
Da y  5 visit (f o ot n ote 2 3).

S u bjects i n Part 2 will n ot re q uire a 
Da y  3 visit, s o f or clarity, t he f o ot n ote 
f or t he E C G assess me nt was m o difie d 
(f o ot n ote 6).

T he la n g ua ge detaili n g t he fre q ue nc y  
of C T/ M RI  sca ns was clarifie d i n t he 
ta ble r o w.

T he la n g ua ge i n f o ot n ote 1 4 was 
clarifie d.

T he C E A assess me nts were m o ve d 
fr o m t he P K Assess me nts ta ble t o t he 
sta n dar d assess me nts ta ble.
S O A f or P K, P D, a n d I m m u n o ge nicit y 
f or P art 1 A a n d P art 1 B

C ha n ge d wi n d o w of Da y 5 ( 9 6 h o ur) 
P K c ollecti o n t o ± 2 4 h o urs.

T he o pti o nal or ma n dat or y 
o ntreat me nt bi o ps y  sa m ple c ollecti o n 
sc he d ule f or wit hi n 2 8 da ys pri or t o 
re gistrati o n was re m o ve d.

A Da y  1 5, 8 h o ur sa m ple c ollecti o n 
f or P F-0 7 0 6 2 1 9 9 c o nce ntrati o n 
c yt o ki nes a n d circ ulati n g mar kers was 
a d de d f or partici pa nts i n Part 1 B.

A d de d c ollecti o n of P K sa m ple s t o 
t he alrea dy s c he d ule d A D A/ N A b 
c ollecti o ns f or Part 1 B.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 2
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
o
F o ot n ote 3 u p date d t o reflect 
t he a b o ve c ha n ge t o P K 
sa m pli n g f or Part 1 B

F o ot n otes 5 a n d 6 u p date d t o clarif y  
t u m or sa m ple c ollecti o n re q uire me nts.

S O A a n d f o ot n otes f or P K, P D, a n d 
I m m u n o ge nicity Assess me nts f or 
P art 2 a d de d.
Secti o n 3 O bjecti ves a n d E n d p oi nts

Tertiar y / E x pl orat or y O bjecti ve a d de d 
f or Part 1 B a n d Part 2. T he tertiar y 
e n d p oi nt f or Part 1 B a n d Part 2 ha ve 
bee n u p date d t o reflect t he o ut p ut f or 
t hese pres pecifie d c ollecti o ns.
Secti o n 4. 1 O ver all Desi g n

T u m or tiss ue sa m ple la n g ua ge 
m o difie d t o i nc or p orate Part 2 
re q uire me nts.

La n g ua ge was a d de d t o clarif y  
i n patie nt o bser vati o n peri o d f or 
Part 2.
Secti o n 4. 3. 3 Fi xe d D osi n g A p pr o ac h

La n g ua ge was a d de d t o all o w f or  
b o d y  wei g ht or B S A base d d osi n g.
Secti o n 5. 1 I ncl usi o n Criteri a

I C # 5 was re vise d t o i nc or p orate 
t u m or tiss ue sa m ple re q uire me nts.
Secti o n 5. 2 – E xcl usi o n Criteri a
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 3
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
Clarificati o n was a d de d t o E C # 6 t o 
i nc or p orate C O VI D-1 9 testi n g 
re q uire me nts.
Secti o n 6. 1. 1. 1 – P F -0 7 0 6 2 1 1 9

La n g u a ge was a d de d t o clarif y 
i n patie nt o bser vati o n peri o d f or 
Part 2.
Secti o n 6. 1. 1. 3 – Be v aciz u m a b -Pfizer

A d mi nistrati o n i nstr ucti o ns were 
u p date d.
Secti o n 6. 6. 3 He m at o p oietic Gr o wt h 
F act ors

Clarifie d t hat er y t hr o p oieti n is n ot 
a p pr o ve d i n Ja pa n.
A d de d Secti o n 6. 7. 1. 1 – D ose 
I nterr u pti o n of P artici p a nts wit h 
Pres u me d or Acti ve C O VI D -1 9/ S A R S 
C o V 2 I nfecti o n
A d de d Secti o n 8. 1. 2 C O VI D -1 9: Use of 
Alter n ati ve Met h o ds f or I n- Pers o n 
Visits
Secti o n 8. 2. 1.- Ti me Peri o d a n d 
Fre q ue nc y f or C ollecti n g A E a n d S A E
I nf or m ati o n

U p date d t he te xt i n dicati n g h o w t he 
i n vesti gat or s h o ul d n otif y Pfizer of a n 
S A E, ie, usi n g t he C T S A E Re p ort 
F or m.
Secti o n 8. 2. 6 Me dic ati o n Err ors
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 4
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

Clarifie d t hat me dicati o n d osi n g 
err ors s h o ul d be re p orte d t o t he 
s p o ns or wit hi n 2 4 h o urs.
Secti o n 8. 3 Tre at me nt of O ver d ose

Cl arifie d t h at m o nit ori n g of a n y 
p artici p a nt s h o ul d c o nti n ue f or 5 
h alf -li ves or 2 8 c ale n d ar d a ys after 
t he o ver d ose.
Secti o n 8. 8, 8. 8. 1, 8. 8 2 - T u m or tiss ue 
sa m ple la n g ua ge re vise d t o i nc or p orate 
Part 2 re q uire me nts.
Secti o n 1 0. 3. 2 Defi niti o n of S A E

Te xt a d de d t o i ncl u de t he e ve nt of 
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.
Secti o n 1 0. 3. 3. – Rec or di n g/ Re p orti n g 
a n d F oll o w -u p of A Es a n d/ or S A Es 

U p date d E x p os ure d uri n g 
pre g na nc y/ breastfee di n g A E/ S A E 
rep orti n g pr oce d ures.
Secti o n 9. 5. 1 D at a M o nit ori n g 
C o m mittee:

La n g ua ge a d de d t o clarif y  c ollecte d 
data w hic h will be re vie we d d uri n g 
t he peri o dic safety re vie w tea m.
Secti o n 1 0. 4. 3 W o m a n of C hil d be ari n g 
P ote nti al

La n g ua ge was a d de d t o clarif y  t he 
pr oce d ure f or partici pa nts wit h a hi g h 
F S H.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 5
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
Secti o n 1 0. 4. 4 C o ntr ace pti o n Met h o d

Clarifie d  c o ntrace pti o n met h o ds n ot 
a p pr o ve d i n Ja pa n.
Secti o n 1 0. 1 0. 2 Pri or S pecific ati o ns

T he D L T rate was c orrecte d.
A d de d Secti o n 1 0. 1 7 J a p a n S pecific 
M atters
A d de d Secti o n 1 0. 1 8: Alter n ati ve 
Me as ures D uri n g P u blic E mer ge ncies
Ot her, mi n or clarificati o ns, a d mi nistrati ve 
a n d t yp o gra p hical c ha n ges were ma de.
A me n d me nt 0 2
1 0 Oct o ber 2 0 1 9 
T he pri mar y  p ur p ose of t he a me n d me nt is 
t o i nc or p orate fee d bac k recei ve d fr o m t he 
U nite d States ( U S) F o o d a n d Dr u g 
A d mi nistrati o n ( F D A).
I n a d diti o n, clarificati o ns, a d mi nistrati ve 
a n d t yp o gra p hical m o dificati o ns were 
ma de.
4. 3. 7 Criteria f or D ose Escalati o n 

Clarificati o n, i ncl u di n g 
t yp o gra p hical m o dificati o ns 
ar o u n d i ntra -partici pa nt d ose 
escalati o n c o nsi derati o ns were 
ma de.
Secti o n 4. 3. 8 D ose L i miti n g T o xicit y 
Defi niti o n

Clarificati o n ma de t hat all C R S 
e ve nts Gra de 3 or hi g her, 
re gar dless of d urati o n will be 
c o nsi dere d a D L T.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 6
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

Gra de 3 i nf usi o n relate d reacti o ns 
(II R), aller gic reacti o ns or 
a na p h yl a xis will n o w be 
c o nsi dere d D L Ts.
Secti o n 5. 1 I ncl usi o n Criteria

T y p o gra p hical err or was c orrecte d 
s plitti n g i ncl usi o n criteria # 3 a n d 
# 4 i nt o t w o se parate criteri o n.
Secti o n 6. 7. 3 D ose Re d ucti o ns
T y p o gra p hical err or was c orrecte d 
pr o perl y li n k Ta bl e 3 i n t he te xt f or t he 
n o n -i m m u ne-relate d t o xicities.
A me n d me nt 0 1
0 8 Oct o ber 2 0 1 9 
T he pri mar y  p ur p ose of t he a me n d me nt is 
t o i nc or p orate fee d bac k recei ve d fr o m t he 
U nite d States ( U S) F o o d a n d Dr u g 
A d mi nistrati o n ( F D A).
I n a d diti o n, clarificati o ns, a d ministrati ve 
a n d t yp o gra p hical m o dificati o ns were 
ma de.
S C H E D U L E O F A C TI VI TI E S ( S O A)

I n patie nt m o nit ori n g f or C ycle 1 
Da y  1 5 ( C 1 D 1 5) has bee n 
e xte n de d t o 8 h o urs p ost d ose. 
Patie nts ma y  be release d o nl y 
after t he i n vesti gat or has 
c o nfir me d t he partici pa nt has n ot 
e x hi bite d si g ns a n d s ym pt o ms of a 
c yt o ki ne reacti o n.

C 1 D 1 2 -h o ur ti me p oi nt has bee n 
re m o ve d, w hic h was rele va nt t o 
I n vtra ve n o us (I V) d osi n g o nl y, 
w hic h has bee n re m o ve d fr o m t he 
pr ot oc ol.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 7
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

I n- h o use m o nit ori n g re q uire me nts  
a n d I V i nf usi o n i nstr ucti o ns f or I V 
d osi n g ha ve bee n re m o ve d fr o m 
t he S O A, wit h re m o val of I V 
d osi n g fr o m t he pr ot oc ol.

Sc he d ule of P har mac o ki netic, 
P har mac o d y na mic, a n d 
I m m u n o ge nicit y Assess me nts f or 
Parts 1 A a n d 1 B -f o ot n ote 7 
“ Bl o o d Sa m ple f or C yt o ki nes & 
Circ ulati n g Mar kers (c e ntral la b) 
a n d Bl o o d sa m ple f or T cell 
I m m u n o p he n oty pi n g” clarifies 
t hat: t w o ( 5 m L) bl o o d sa m ples 
will be c ollecte d t o is olate ser u m 
f or ce ntral la b orat or y tests f or 
safety c ollecte d pre -d ose o n 
C 1 D 1.
Secti o n 2. 5 Be nefit/ Ris k Assess me nt

I n patie nt o bser vati o n of I V d osi n g 
was re m o ve d fr o m t he pr ot oc ol.
Secti o n 4. 1 O verall Desi g n

Clarificati o n was a d de d ar o u n d 
t he Ba ye sia n l o gistic re gressi o n 
m o del ( B L R M) a n d ma xi m u m 
d ose i ncreases i n Part 1 A a n d 1 B.

Clarificati o n was a d de d ar o u n d 
c o h ort size f or d ose le vel of Part 
1 B a n d Part 2.

Clarificati o n t hat Part 1 B will 
ha ve at least 3 D ose Li miti n g 
T o xicit y  ( D L T) e val ua ble 
partici pa nts, w hic h was c ha n ge d 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 8
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
fr o m pre vi o us at least 2 D LT 
e val ua ble partici pa nt.

Fi g ure 3: C 3 8 6 1 0 0 1 St u d y 
Sc he ma was u p date d t o refl ect 
n u m ber of partici pa nts i n Part 1 B.

I n patie nt m o nit ori n g f or C 1 D 1 5 
has bee n e xte n de d t o 8 h o urs p ost 
d ose. Patie nts ma y  be release d 
o nl y  after t he i n vesti gat or has 
c o nfir me d t he partici pa nt has n ot 
e x hi bite d si g ns a n d s ym pt o ms of a 
c yt o ki ne reacti o n.
Secti o n 4. 3. 2 S u bc uta ne o us R o ute

T he pr ot oc ol has bee n u p date d t o 
clarif y t he use of s u bc uta ne o us 
d osi n g o nl y at t his ti me. If 
i ntra ve n o us d ose a d mi nistrati o n, 
i ncl u di n g i ntra ve n o us d ose 
pri mi n g is g oi n g t o be e x pl ore d i n 
t his st u d y, a f ut ure pr ot oc ol 
a men d me nt w o ul d occ ur pri or t o 
pr ocee di n g.
Secti o n 4. 3. 5 Starti n g D ose f or 
C o m bi nati o n D ose Fi n di n g ( Part 1 B)

Clarificati o n a d de d ar o u n d d ose 
a dj ust me nts usi n g B L R M wit h 
res pect t o P F- 0 7 0 6 2 1 1 9.
Secti o n 4. 3. 7 Criteria f or D ose Escalati o n

Clarificati o n t hat Part 1 B will 
ha ve at least 3 D L T e val ua ble 
partici pa nts, w hic h was c ha n ge d 
fr o m pre vi o us at least 2 D LT 
e val ua ble partici pa nt.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 9
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

F o ot n ote was a d de d t o Ta ble 1 f or 
clarificati o n, if t he 4 5 μ g 
s u bc uta ne o us ( S C) Q 2 W d ose is 
n ot t olerate d, t he n a l o wer d ose of 
3 0 μ g Q 2 W via S C r o ute will be 
e val uate d.

I ntra-partici pa nt d ose escalati o n 
g ui deli nes ha ve bee n re vise d s o 
t hat at least 2 c ycles be y o n d t he 
D L T peri o d f or t he ne xt 
i m me diate hi g her d ose le vel ha ve 
passe d pri or t o pr ocee di n g t o a 
hi g her d ose.
Secti o n 4. 3. 8 D ose L i miti n g T o xicit y 
Defi niti o n

T he defi niti o n of D L T e val ua ble 
partici pa nts ha ve bee n re vise d t o 
i ncl u de a ny partici pa nt t hat has a 
D L T irres pecti ve of w het her t he y  
recei ve d all pla n ne d d oses a n d 
recei ve d t he sc he d ule d safet y 
assess me nts.

D L T criteria ha ve bee n clarifie d 
f or c o nsiste nc y.

Gra de 4 v o miti n g or Gra de 4 
diarr hea has bee n a d de d as a D L T.

Gra de 3 C yt o ki ne Release 
S y n dr o me ( C R S) e ve nt criteria 
ha ve bee n clarifie d.
Secti o n 5. 1 I ncl usi o n Criteria 

I ncl usi o n criteria # 2 a n d # 3 ha ve 
bee n u p date d t o i ncl u de t hat f or 
Parts 1 A a n d 1 B partici pa nts m ust 
ha ve e x ha uste d all F D A or l ocal 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 0
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
re g ulat or y a p pr o ve d treat me nts 
t hat w o ul d c o nfer si g nifica nt 
cli nicall y be nefit f or t heir disease.
Secti o n 5. 2 E xcl usi o n Criteria
E xcl usi o n criteri o n # 1 3 has bee n 
a d de d t o i ncl u de t he e xcl usi o n of 
partici pa nts wit h acti ve or hist or y  
of cli nicall y  si g nifica nt 
a ut oi m m u ne disease t hat re q uire d 
s yste mic i m m u n os u p pressi ve 
t hera py or a n ot her me dical 
c o n diti o n t hat re q uire d 
i m m u n os u p pressi o n wit hi n 2 
ye ars of treat me nt.
Secti o n 6. 1 St u d y  Inter ve nti o ns 
A d mi nistere d

Secti o n has bee n u p date d t o 
re m o ve i ntra ve n o us d ose 
a d mi nistrati o n a n d  i ntra ve n o us 
d ose pri mi n g.
Secti o n 6. 1. 1 A d mi nistrati o n 

Secti o n has bee n u p date d t o 
re m o ve i ntra ve n o us i nf usi o n 
a d mi nistrati o n a n d i ntra ve n o us 
d ose pri mi n g.

G ui da nce o n w here S C i njecti o ns 
s h o ul d be a d mi nistere d was a d de d 
f or clarificati o n.

I n patie nt m o nit ori n g f or C 1 D 1 5 
has bee n e xte n de d t o 8 h o urs p ost 
d ose.
Secti o n 6. 7 D ose M o dificati o n 
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 1
D oc u me nt Hist or y
Pr ot oc ol A me n d me nt s -0 1 t hr o u g h - 0 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale

Clarificati o n of d ose 
m o dificati o ns a n d d osi n g o pti o ns 
as a res ult of D L T ha ve bee n 
i ncl u de d.
Secti o n 8. 1. 6 I njecti o n Site T olera bilit y  
Assess me nt

Clarificati o n ma de f or S C d osi n g 
o nl y .
Secti o n 9. 2. 1 Part 1 D ose Escalati o n

Clarificati o n ar o u n d t otal n u m ber 
of partici pa nts i n t he c o m bi nati o n 
ar ms of Part 1 B.
Secti o n 9. 4. 1 Ma xi m u m T olerate d D ose 
Deter mi nati o n

Clarificati o n of t he starti n g d ose 
i n Part 1 A ( 4 5 µ g).
Secti o n 9. 4. 4. 1 P har mac o ki netic A nal ys es 

P har mac o ki netic ( P K) para meters 
i n v ol vi n g I V d osi n g (e g, C L a n d 
Vss) ha ve bee n re m o ve d.
Ori gi nal Pr ot oc ol
2 0 A u g ust 2 0 1 9
n/a
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 2
1 1. R E F E R E N C E S
1.  
A h me di n, J., et al., Ca ncer Statistics. C A A Ca ncer J o ur nal f or Cli nicia ns.
2 0 0 9 ;5 9( 4): 2 2 5 - 4 9.
2.
Alle gra CJ, Jess u p J M, S o merfiel d M R, et al. A merica n S ociet y of Cli nical O nc ol o g y 
pr o visi o nal cli nical o pi ni o n: testi n g f or K R A S ge ne m utati o ns i n partici pa nts wit h 
metastatic c ol orectal carci n o ma t o pre dict res p o nse t o a nti- e pi der mal gr o wt h fact or 
rece pt or m o n ocl o nal a nti b o d y t hera p y. J Cli n O nc ol. 2 0 0 9;2 7( 1 2): 2 0 9 1 - 6.
3.
Alle n E, Ja b o uill e A, Ri vera L B et al. C o m bi ne d a ntia n gi o ge nic a n d a nti – P D -L 1 
t hera py sti m ulates t u m or i m m u nit y  t hr o u g h H E V f or mati o n. Sci Tra nsl Me d .
2 0 1 7 ;9( 3 8 5) :eaa k 9 6 7 9.
4. 
Ba n h olzer M L, Wa n del C, Barr o w P, et al. Cli nical trial c o nsi derati o ns o n male 
c o ntrace pti o n a n d c ollecti o n of pre g na nc y i nf or mati o n fr o m fe male part ner: u p date. 
Cli n Tra nsl Me d/ 2 0 1 6; 5( 1) : 2 3- 3 7.
5.
Bas hir et al. Sile nci n g t he G U C A 2 A -G U C Y 2 C t u m or s u p press or a xis i n CI N, serrate d, 
a n d M SI c ol orectal ne o plasia. H u ma n Pat h ol o g y. 2 0 1 9;8 7: 1 0 3 - 1 4.
6.
E M D Ser o n o, I nc ( 2 0 1 9). Hi g hli g hts of prescri bi n g i nf or mati o n. Ba ve nci o ® (a vel u ma b) 
i njecti o n. Retrie ve d fr o m htt ps:// w w w.e m dser o n o.c o m/c o nte nt/ da m/ we b/c or p orate/ n o n -
i ma ges/c o u ntr y-s pecifics/ us/ pi/ ba ve nci o-pi. p df.
7.
Be ns o n A B 3 r d, Aja ni J A, Catala n o R B et al. Rec o m me n de d g ui deli nes f or t he treat me nt 
of ca ncer treat me nt -i n d uce d diarr hea. J Cli n O nc ol. 2 0 0 4;2 2( 1 4): 2 9 1 8 - 2 6.
8.
A m ge n, I nc ( 2 0 1 9). Bli nc yt o ™ ( bli nat u m o ma b). Hi g hli g hts of prescri bi n g i nf or mati o n.
Retrie ve d fr o m htt ps:// w w w. pi.a m ge n.c o m/ ~/ me dia/a m ge n/re p osit or y sites/ pi-a m ge n-
c o m/ bli nc yt o/ bli nc yt o _ pi _ hc p _e n glis h. p df.
9. 
Bir be R, Palazz o J P, Walters R et al. H u m Pat h. 2 0 0 5; 3 6( 2): 1 7 0 - 9.
1 0.
Bra y F, Ferla y  J, S oerj o matara m I, et al. Gl o bal Ca ncer Statistics 2 0 1 8: G L O B O C A N 
esti mates of i nci de nce a n d m ortalit y  w orl d wi de f or 3 6 ca ncers i n 1 8 5 c o u ntries. Ca 
Ca ncer J Cli n. 2 0 1 8 ;6 8: 3 9 4 - 2 4.
1 1.
Brist ol M y ers S q ui b b ( 2 0 1 9). Hi g hli g hts of prescri bi n g i nf or mati o n. O p di v o ® i njecti o n. 
Retrie ve d fr o m htt ps:// pac ka gei nserts. b ms.c o m/ pi/ pi _ o p di v o. p df.
1 2.
C ha u, I . a n d C u n ni n g ha m D , Treat me nt i n a d va nce d c ol orectal ca ncer: w hat, w he n a n d 
h o w [ q uest]. Br J Ca ncer . 2 0 0 9;1 0 0( 1 1): 1 7 0 4 - 1 9.
1 3.
Da naee H, Kale bic T, W ya nt T et al. C o nsiste nt e x pressi o n of g ua n yl yl  c yclase-C i n 
pri mar y  a n d metastatic gastr oi ntesti nal ca ncers. Pl os O ne . 2 0 1 7;1 2( 1 2):e 0 1 8 9 9 5 3.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 3
1 4.
Di Nic ola nt o ni o F, Marti ni M,
M oli nari F,
Sart ore -Bia nc hi A et al. Wil d -t ype B R A F is 
re q uire d f or res p o nse t o pa nit u m u ma b or cet u xi ma b i n metastatic c ol orectal ca ncer. 
J Cli n O nc ol . 2 0 0 8;2 6( 3 5): 5 7 0 5 - 1 2.
1 5.
E dler, L utz a n d B ur k h ol der, Iris. O ver vie w of P hase I Trials. I n: Ha n d b o o k of Statistics 
i n Cli nical O nc ol o g y, 2 n d E diti o n. E dite d b y J o h n Cr o wle y a n d D o n na Pa uler A n kerst.
B oca Rat o n, F L, C ha p ma n a n d Hall, 2 0 0 6: 3 - 3 0.
1 6.
Ge ne ntec h, I nc ( 2 0 1 9). Hi g hli g hts of prescri bi n g i nf or mati o n. Tece ntri q ® 
(atez oliz u ma b) i njecti o n. Retrie ve d fr o m 
htt ps:// w w w.tece ntri q.c o m/? _ ga = 2. 2 2 2 8 9 2 1 2 3. 1 9 5 3 5 4 7 4 6 5. 1 5 6 3 4 0 9 7 1 8 -
3 7 5 9 3 9 4 0 0. 1 5 6 3 4 0 9 7 1 8 & _ gac = 1. 2 2 1 8 2 8 3 3 0. 1 5 6 3 4 0 9 7 1 8. Cj 0 K C Qj wjr v p B R C 0 A RI s A
Fr F u V _ U K K 7 L- U 7 w Sl 4 S A p M V 6 -
3c T G H 0 k S M 5 U Oc H v 8 n S b X N Nl 7 F N _ _t 0 V F 8a Ar d S E A L w _ wc B.
1 7.
Gr ot he y  A, et al., Re g orafe ni b m on ot hera p y f or pre vi o usl y treate d metastatic c ol orectal 
ca ncer ( C O R R E C T): a n i nter nati o nal, m ultice ntre, ra n d o mise d, place b o -c o ntr olle d, 
p hase 3 trial. T he La ncet . 2 0 1 3; 3 8 1( 9 8 6 3):3 0 3 - 1 2.
1 8.
H o di F S, B utler M, O ble D A, Sei de n M V, Hal us ka F G et.al: I m m u n ol o gic a n d cli nical 
effects of a nti b o d y bl oc ka de of c yt ot o xic T l y m p h oc yte -ass ociate d a nti ge n 4 i n 
pre vi o usl y  vacci nate d ca ncer partici pa nts. Pr oc Natl Aca d Sci U S A.
2 0 0 8; 1 0 5( 8): 3 0 0 5 - 1 0.
1 9.
H o os A, E g ger m o nt A M, Ja netz ki S, H o di F S, I bra hi m R, et.al: I m pr o ve d e n d p oi nts f or 
ca ncer i m m u n ot hera p y trials. J Natl Ca ncer I nst. 2 0 1 0; 1 0 2( 1 8): 1 3 8 8 - 9 7.
2 0.
H ur witz, H.I ., et al., T he Cli nical Be nefit of Be vaciz u ma b i n Metastatic C ol orectal 
Ca ncer Is I n de pe n de nt of K-ras M utati o n Stat us: A nal ysis of a P hase III St u d y of 
Be vaciz u ma b wit h C he m ot hera p y i n Pre vi o usl y U ntreate d Metastatic C ol orectal 
Ca ncer. O nc ol o gist . 2 0 0 9;1 4( 1): 2 2 - 8.
2 1.
Ge ne ntec h, I nc ( 2 0 1 9). Hi g hli g hts of prescri bi n g i nf or mati o n. Ke y tr u da®
( pe m br oliz u ma b) i njecti o n. Retrie ve d fr o m 
htt p:// w w w. merc k. c o m/ pr o d uct/ usa/ pi _circ ulars/ k/ ke y tr u da/ ke ytr u da _ pi. p df.
2 2.
Astra Ze neca ( 2 0 1 8). Hi g hli g hts of prescri bi n g i nf or mati o n. I mfi nzi ® ( d ur val u ma b) 
i njecti o n. Retrie ve d fr o m htt ps:// w w w.i mfi nzi hc p.c o m/ n o n-s mall-cell-l u n g-
ca ncer/sta ge -3/ d ur val u ma b -nsclc -cli nical-
trials. ht ml?s o urce =i mz _ n _ h _ 9 & u me di u m =c pc & ua d p u b = g o o gle & uca m pai g n = 2 0 1 9i mfi
nzi hc p nsclc bra n de d _ ge neral _ hc p & ucreati ve = bra n de d _al o ne _ p h & u place =i mfi nzi & o utc
o me = hc p &c m pi d = 1.
2 3.
Ki y oz u mi Y, I wats u ki M, Ya mas hita K, et al. U p date o n tar gete d t hera p y a n d i m m u ne 
t hera py f or gastric ca ncer, 2 0 1 8. J Ca ncer Metastasis Treat. 2 0 1 8;4: 3 1.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 4
2 4.
Lee D W, Gar d ner R, P orter D L, et al. C urre nt c o nce pts i n t he dia g n osis a n d 
ma na ge me nt of c y t o ki ne release s yn dr o me. Bl o o d . 2 0 1 4; 1 2 4: 1 8 8 - 1 9 5.
2 5.
Lee D W, Sa nt o mass o B D, L oc ke F L, et al: A S T C T C o nse ns us Gra di n g f or C y t o ki ne 
Release S y n dr o me a n d Ne ur ol o gic T o xicit y  Ass ociate d wit h Im m u ne Effect or Cells 
2 0 1 9 ;2 5: 6 2 5 - 3 8.
2 6.
“ Meta b olis m a n d Tra ns p ort, Dr u g I nteracti o n Data base”, De part me nt of P har mace utics, 
U ni versit y  of Was hi n gt o n. w w w. dr u gi nteracti o ni nf o. or g. A ccesse d Ma y 2 0 0 9.
2 7.
M o ore P A, S ha h K, Ya n g Y, Al ders o n R et al.
De vel o p me nt of M G D 0 0 7, a g p A 3 3 x 
C D 3 - Bis pecific D A R T Pr otei n f or T-Cell I m m u n ot hera p y  of Metastatic C ol orectal 
Ca ncer. M ol Ca ncer T her. 2 0 1 8 ;1 7( 8): 1 7 6 1 - 7 2.
2 8.
M ulli n J M, La u g hli n K V, Gi na n ni N, et al. I ncrease d ti g ht j u ncti o n per mea bilit y ca n 
res ult fr o m pr otei n ki nase C acti vati o n/tra nsl ocati o n a n d act as a t u m or pr o m oti o nal 
e ve nt i n e pit helial ca ncers. A n n N Y Aca d Sci . 2 0 0 0; 9 1 5: 2 3 1 - 6.
2 9.
Nis hi n o, Miz u ki M. D., A nita Gi o b bie - H ur der, M. S., Maria Gar ga n o et.al: De vel o pi n g a 
C o m m o n La n g ua ge f or T u m or Res p o nse t o I m m u n ot hera p y : I m m u ne-relate d Res p o nse 
Criteria usi n g U ni di me ns i o nal meas ure me nts. Cli n Ca ncer Res. 2 0 1 3; 1 9( 1 4): 3 9 3 6 – 4 3.
3 0.
Nis hi n o M, Gar ga n o M, S u da M, et al. O pti mizi n g i m m u ne- relate d t u m or res p o nse 
assess me nt: D oes re d uci n g t he n u m ber of lesi o ns i m pact res p o nse assess me nt i n 
mela n o ma partici pa nts treate d wit h i pili m u ma b? J I m m u n ot her Ca ncer . 2 0 1 4; 2: 1 7.
3 1.
Ne ue nsc h wa n der B, Ca p k u n -Ni g gli G, Bra ns o n M, S pie gel halter DJ, S u m marizi n g 
hist orical i nf or mati o n o n c o ntr ols i n cli nical trials. Cli n Trials. 2 0 1 0; 7( 1): 5 - 1 8.
3 2.
Ne ue nsc h wa n der B, Mata n o A, Ta n g Z, R o yc h o u d h ur y S, Wa n del S a n d Baile y S. A 
Ba yesia n I n d ustr y A p pr oac h t o P hase I C o m bi nati o n Trials i n O nc ol o g y . I n St atistic al 
Met h o ds i n Dr u g C o m bi n ati o n St u dies . Z ha o W a n d Ya n g H (e ds), C ha p ma n & 
Hall/ C R C, 2 0 1 4.
3 3.
Na gaic h N a n d S har ma R. Gastric ca ncer – a n u p date. J of T u m or Me d Pre v . 2 0 1 8. 2( 5).
3 4.
Pfizer, I nc.( 2 0 1 9). Hi g hli g hts of prescri bi n g i nf or mati o n. Zira be v ™ ( be vaciz u ma b) 
i njecti o n. Retrie ve d fr o m: htt p://la beli n g. pfizer.c o m/ S h o w L a beli n g.as p x?i d = 1 1 8 6 0.
3 5.
Pratilas C A, Ha nra ha n AJ, Halil o vic E, et al. Ge netic pre dict ors of M E K de pe n de nce i n 
n o n -s mall cell l u n g ca ncer. Ca ncer Res 2 0 0 8; 6 8( 2 2): 9 3 7 5- 8 3.
3 6.
R o gat k o A 1, Sc h oe nec k D, J o nas W, Ti g hi o uart M, K h uri F R, P orter A. Tra nslati o n of 
i n n o vati ve desi g ns i nt o p hase I trials. J Cli n O nc ol. 2 0 0 7; 2 5( 3 1): 4 9 8 2 - 6.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 5
3 7.
Sa ber H, Del Valle P, Ric ks T K, Lei g ht o n J K. A n F D A o nc ol o g y  a nalys is of C D 3 
bis pecific c o nstr ucts a n d first- i n-h u ma n d ose selecti o n. Re g ul T o xic ol P har ma c ol.
2 0 1 7 ;9 0: 1 4 4 - 5 2.
3 8.
Saltz, L . B., et al., Be vaciz u ma b i n C o m bi nati o n Wit h O xali plati n-Base d C he m ot hera p y 
As First -Li ne T hera p y i n Metastatic C ol orectal Ca ncer: A Ra n d o mize d P hase III St u d y.
J Cli n O nc ol. 2 0 0 8;2 6( 1 2): 2 0 1 3 - 9.
3 9.
Sal ma ni neja d A, Valil o u S F, S ha b ga h A G, et al. P D -1/ P D -L 1 pat h wa y : Basic bi ol o g y 
a n d r ole i n ca ncer i m m u n ot hera p y. J Cell P h y si ol. 2 0 1 9: 1- 1 4.
4 0.
Sc h mi dli, H., Gstei ger, S., R o y c h o u d h ur y, S., O' Ha ga n, A., S pie gel halter, D., & 
Ne ue nsc h wa n der, B. R o b ust meta -a nal yt ic-pre dicti ve pri ors i n cli nical trials wit h 
hist orical c o ntr ol i nf or mati o n. Bi o metrics . 2 0 1 4;7 0( 4 ):1 0 2 3 - 3 2.
4 1.
S oler A P, Miller R D, L a u g hli n K V, et al. I ncrease d ti g ht j u ncti o nal per mea bilit y  is 
ass ociate d wit h t he de vel o p me nt of c ol o n ca ncer. Carci n o ge nesis . 1 9 9 9; 2 0( 8): 1 4 2 5 - 3 1.
4 2.
S olit D B, Garra wa y  LA, Pratilas C A et al. B R A F m utati o n pre dicts se nsiti vit y  t o M E K 
i n hi biti o n. Nat ure. 2 0 0 6; 4 3 9( 7 0 7 4): 3 5 8 - 6 2.
4 3.
S mit h -Gar vi n J E 1, K oretz k y  G A, J or da n M S: T cell acti vati o n. A n n u Re v I m m u n ol. 
2 0 0 9; 2 7: 5 9 1 -6 1 9. d oi: 1 0. 1 1 4 6/a n n u re v. i m m u n ol. 0 2 1 9 0 8. 1 3 2 7 0 6.
4 4.
S pie gel halter, D.J. I nc or p orati n g Ba y esia n I deas i nt o Healt h-Care E val uati o n: Statist.
Sci. 2 0 1 4; 1 9( 1): 1 5 6 - 1 7 4.
4 5.
Ta ber ner o J, I g naci o M, Wille ke R, et al. P hase 1a a n d 1 b st u dies of t he n o vel 
carci n oe m br yo nic a nti ge n ( C E A) T- cell bis pecific ( C E A C D 3 T C B) a nti b o d y  as a 
si n gle a ge nt a n d i n c o m bi nati o n wit h atez oliz u ma b: Preli mi nar y efficac y a n d safety i n 
partici pa nts wit h metastatic c ol orectal ca ncer ( m C R C). J C O. 2 0 1 7; 3 5 ( n o. 1 5 
s u p pl):3 0 0 2.
4 6.
Tai h o O nc ol o g y .( 2 0 1 9). Hi g hli g hts of prescri bi n g i nf or mati o n. L o ns urf ®
(trif uri di ne/ti piracil). Retrie ve d fr o m: htt ps:// w w w.tai h o o nc ol o g y.c o m/ us/ prescri bi n g-
i nf or mati o n. p df.
4 7.
T o p p M S, G ö k b u get N, Z u g maier G, et al: P hase II trial of t he a nti -C D 1 9 bis pecific T 
cell-e n ga ger bli nat u m o ma b s h o ws he mat ol o gic a n d m olec ular re missi o ns i n patie nts 
wit h rela pse d or refract or y B -prec urs or ac ute l y m p h o blastic le u ke mia. J Cli n O nc ol. 
2 0 1 4; 3 2( 3 6): 4 1 3 4 - 4 0.
4 8.
T o p p M S, G ö k b u get N, Stei n A S, et al: Safet y  a n d acti vit y of bli nat u m o ma b f or a d ult 
patie nts wit h rela pse d or refract or y  B-prec urs or ac ute l y m p h o blastic le u ke mia: a 
m ultice nter, si n gle -ar m, p hase 2 st u d y. La ncet O nc ol. 2 0 1 5 ; 1 6: 5 7- 6 6.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)

P F -0 7 0 6 2 1 1 9
C 3 8 6 1 0 0 1
Fi nal Pr ot oc ol A me n d me nt 7, 1 9 N o ve m ber 2 0 2 1
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 6
4 9.
Wa n g D.et al: Fi xe d D osi n g Vers us B o d y Size – Base d D osi n g of M o n ocl o nal 
A nti b o dies i n A d ult Cli nical Trials.
5 0.
W olc h o k J D, H o os A, O' Da y  S, We ber J S, Ha mi d O, et.al: G ui deli nes f or t he e val uati o n 
of i m m u ne t hera p y acti vit y  i n s oli d t u m ors: i m m u ne-relate d res p o nse criteria. Cli n 
Ca ncer Res. 2 0 0 9; 1 5( 2 3): 7 4 1 2 - 2 0.
5 1.
Z ha n g S , S hi R, Li  C., et al: Fi xe d D osi n g Vers us B o d y Size – Base d D osi n g of 
T hera pe utic Pe pti des a n d Pr otei ns i n A d ults. J Cli n P har mac ol. 2 0 1 2; 5 2( 1): 1 8- 2 8.
5 2.
Zi m mer ma n, Ma niar T, Na g orse n D:  U nleas hi n g t he cli nical p o wer of T cells: 
C D 1 9/ C D 3 bi -s pecific T cell e n ga ger ( Bi T E® ) a nti b o d y c o nstr uct bli nat u m o ma b as a 
p ote ntial t hera p y. I nt I m m u n ol. 2 0 1 5 ;2 7( 1 ): 3 1- 7. d oi: 1 0. 1 0 9 3/i nti m m/ d x u 0 8 9. E p u b.
5 3.
2 0 0 6 U p date of Rec o m me n dati o ns f or t he Use of W hite Bl o o d Cell Gr o wt h Fact ors: A n 
E vi de nce - Base d Cli nical Practice G ui deli ne. J C O. 2 0 0 6: 3 1 8 7 - 2 0 5.
5 4.
Neela p u S S. Ma na gi n g t he t o xicities of C A R T -cell t hera p y. He mat ol O nc ol. 2 0 1 9; 3 7 
S u p pl 1: 4 8 - 5 2.
5 5.
Neela p u S S, T u m mala S, Ke briaei P, et al. C hi meric a nti ge n rece pt or T -cell t hera p y -
assess me nt a n d ma na ge me nt of t o xicities. Nat Re v Cli n O nc ol. 2 0 1 8; 1 5( 1): 4 7 - 6 2.
0 9 0 1 7 7 e 1 9 8 a 5 b 3 4 8\ A p pr o v e d\ A p pr o v e d O n: 1 9- N o v- 2 0 2 1 1 8: 4 9 ( G M T)