A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMIC, AND ANTITUMOR ACTIVITY OF PF-07260437 IN ADVANCED OR METASTATIC SOLID TUMORS
Phase: PHASE1
Conditions: Ovarian Neoplasms, Endometrial Neoplasms, Breast Neoplasms
Sponsor: Pfizer

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
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 T O E V A L U A T E 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, P H A R M A C O D Y N A MI C, A N D A N TI -
T U M O R A C TI VI T Y O F P F -0 7 2 6 0 4 3 7 I N A D V A N C E D O R M E T A S T A TI C S O LI D T U M O R S
St u d y I nter ve nti o n N u m ber:
P F -0 7 2 6 0 4 3 7
St u d y I nter ve nti o n N a me:
N/ A
U S I N D N u m ber:
1 5 6 5 5 3
E u dr a C T N u m ber:
N/ A 
Cli nic al Tri als. g o v I D:
N/ A
Pr ot oc ol N u m ber:
C 4 4 3 1 0 0 1
P h ase:
1
Brief Title: A P hase 1 D ose Escalati o n a n d E x pa nsi o n St u d y of P F -0 7 2 6 0 4 3 7 i n A d va nce d or 
Metastatic S oli d 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
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 1
0 9 A u g ust 2 0 2 1
Ori gi nal pr ot oc ol
2 2 J u ne 2 0 2 1
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.
A me n d me nt 1 ( 0 9- A u g -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 his 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 F D A.  I n a d diti o n, clarificati o n, 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 ale
Secti o n 1. 1. S y n o psis; 
Secti o n 1. 2. Sc he ma; 
Secti o n 2. 3. Be nefit/ Ris k 
Assess me nt; Secti o n 4. 1. 1. 
D ose Escalati o n ( Part 1)
I n Part 1, t he first c o h ort of 
patie nts at d ose le vel 1 will be 
sta g gere d b y 4 8 ho u rs
bet wee n eac h patie nt .
T o miti gate o verall ris k t o patie nts
e nr olle d i n Part 1 .
Secti o n 1. 3. 1. Part 1 –
Sc he d ule of Assess me nt -
Wit h o ut Pri mi n g; Secti o n 
1. 3. 2. Part 1 – Sc he d ule of 
Assess me nts – Wit h 
Pri mi n g; Secti o n 1. 3. 3. 
Part 2 - Sc he d ule of 
Assess me nts – Wit h or 
Wit h o ut Pri mi n g; Secti o n 
2. 3. 1. Ris k Assess me nt; 
Secti o n 4. 1. O verall 
Desi g n; Secti o n 6. 1. St u d y 
I nter ve nti o n(s) 
A d mi nistere d; 
Partici pa nts e x perie nci n g ≥ 
Gra de 3 i nf usi o n-relate d A Es 
(I V a d mi nistrati o n) or 
cli nicall y si g nifica nt C R S 
m ust be h os pitalize d f or at 
least 2 4 h o urs f or at least 4 
s u bse q ue nt d oses (t w o c ycles) .
T o f urt her e ns ure patie nt safet y a n d 
t o re d uce a n y p ote ntial ris k fr o m
C R S.
Secti o n 1. 1. S y n o psis; 
Secti o n 5. 1 I ncl usi o n 
Criteria
Eli gi bilit y f or E R/ P R a n d 
H E R 2 stat us were u p date d.
T o clarif y acc or di n g t o res pecti ve 
A S C O/ C A P g ui deli nes.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
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 ale
Secti o n 1. 3. 1. St u d y 
Sc he d ule of Assess me nts –
Part 1 Wit h o ut Pri mi n g; 
Secti o n 1. 3. 2. St u d y 
Sc he d ule of Assess me nts –
Part 1 Wit h Pri mi n g; 
Secti o n 2. 3. 2. Ris k 
Assess me nt; Secti o n 4. 1. 
O verall Desi g n Secti o n 
6. 1. 1. 1. Pre me dicati o n; 
Secti o n 6. 8. 4. 
A nti diarr h eal, A ntie metic 
T hera p y; 
Ma n dat or y p r o p h ylactic 
pre me dicati o n d uri n g t he first 
c ycle of treat me nt was 
re m o ve d.
T o a v oi d o bsc uri n g t he 
i de ntificati o n of st u d y- dr u g relate d 
t o xicit y d uri n g t he first c ycle.
Secti o n 1. 3. 1. St u d y 
Sc he d ule of Assess me nts –
Part 1 Wit h o ut Pri mi n g; 
Secti o n 1. 3. 2. St u d y 
Sc he d ule of Assess me nts –
Part 1 Wit h Pri mi n g
Secti o n 4. 1. O verall 
Desi g n
A d diti o nal m o nit ori n g of all 
partici pa nts f or a p pr o xi matel y 
9 0 da ys after treat me nt 
disc o nti n uati o n was i ncl u de d.
T o m o nit or p ossi ble lat e i m m u ne -
relate d t o xicities.
Secti o n 4. 3. 6. 2. N o n -
He mat ol o gic D L Ts
A d diti o nal i m m u ne -me diate d 
D L Ts were i ncl u de d.
T o miti gate safet y ris ks t o patie nts.
Secti o n 4. 4 E n d of St u d y 
Defi niti o n
St o p pi n g r ules were 
i nc or p orate d i nt o t he pr ot oc ol.
T o miti gate safet y ris k t o a d diti o nal 
patie nts.
Secti o n 1. 3. 1. Part 1 –
Sc he d ule of Assess me nt –
Wit h o ut Pri mi n g; Secti o n 
1. 3. 2. Part 1 – Sc he d ule of 
As sess me nt – Wit h 
Pri mi n g
A d diti o nal E C G ti me p oi nts 
a d de d.
T o c orrelate wit h P K ti me p oi nts.
Secti o n 6. 8. C o nc o mita nt
T hera p y ; A p pe n di x 1 5. 
Ca uti o nar y Use of 
C o nc o mita nt Me dicati o ns 
wit h Narr o w T hera pe utic 
I n de x D ue t o Dr u g-Dr u g 
I nteracti o n ( D DI) 
P ote ntial.
A d de d refere nce t o A p pe n di x 
1 5 – a c o nc o mita nt me dicati o n 
list t hat has p ote ntial D DIs 
a n d s h o ul d be use d wit h 
ca uti o n f or c o nc o mita nt 
treat me nt wit h P F-0 7 2 6 0 4 3 7.
T o miti gate ris k a gai nst p ote ntial 
dr u g - dr u g i nteracti o ns.
Secti o n 4. 1. O verall 
Desi g n; Ta ble 7. I n patie nt 
O bser vati o n Sta ys f or S C 
A d mi nistrati o n
O ut patie nt was a d de d t o t he 1 
h o ur o bser vati o n peri o d.
T o clarif y visit as a n o ut patie nt
visit .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
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 2
LI S T O F FI G U R E S .................................................................................................................1 2
1. P R O T O C O L  S U M M A R Y...................................................................................................1 3
1. 1. S y n o psis ..................................................................................................................1 3
1. 2. Sc he ma ....................................................................................................................2 3
1. 3. Sc he d ule of Acti vities .............................................................................................2 4
1. 3. 1. Part 1 – Sc he d ule of Assess me nt - Wit h o ut Pri mi n g ..................................2 4
1. 3. 1. 1. Part 1 - P K, I m m u n o ge nicit y , P D, Bi o mar ker, a n d 
Bi os peci me n – Wit h o ut
Pri mi n g .......................................................3 4
1. 3. 2. Part 1 – Sc he d ule of Assess me nts - Wit h Pri mi n g
.....................................3 8
1. 3. 2. 1. Part 1 - P K, I m m u n o ge nicit y , P D, Bi o mar ker, a n d 
Bi os peci me n – Wit h Pri mi n g
............................................................4 9
1. 3. 3. Part 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
..................5 3
1. 3. 3. 1. Part 2- P K, I m m u n o ge nicit y , P D, Bi o mar ker, a n d 
Bi os peci me n – Wit h or Wit h o ut Pri mi n g ..........................................6 3
2. I N T R O D U C TI O N................................ ...............................................................................6 8
2. 1. St u d y  Rati o nale.......................................................................................................6 8
2. 2. Bac k gr o u n d .............................................................................................................6 9
2. 2. 1. N o ncli nical P har mac ol o g y ..........................................................................6 9
2. 2. 1. 1. I n Vitr o P har mac o d y na mics ......................................................6 9
2. 2. 1. 2. I n Vi v o P har mac o d y na mics ......................................................7 0
2. 2. 2. N o ncli nical P har mac o ki netics a n d Meta b olis m ......................................... 7 0
2. 2. 3. N o ncli nical Safet y ...................................................................................... 7 1
2. 2. 4. Cli nical O ver vie w .......................................................................................7 1
2. 2. 5. Bis pecific Re directe d T -cell E n ga gi n g T hera pies...................................... 7 1
2. 3. Be nefit/ Ris k Assess me nt................................ .........................................................7 2
2. 3. 1. Ris k Assess me nt......................................................................................... 7 4
2. 3. 2. Be nefit Assess me nt .....................................................................................7 6
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................7 6
3. O BJ E C TI V E S, E N D P O I N T S, A N D E S TI M A N D S ...........................................................7 6
4. S T U D Y D E SI G N .................................................................................................................7 9
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5
4. 1. O verall Desi g n................................ .........................................................................7 9
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n.....................................................................8 3
4. 2. 1. H or m o ne Rece pt or ( E R a n d/ or P R) P ositi ve Br Ca..................................... 8 4
4. 2. 2. Tri ple Ne gati ve Br Ca.................................................................................. 8 5
4. 2. 3. Di versit y  of St u d y P o p ulati o n ....................................................................8 5
4. 2. 4. D ose Le vel Re vie w .....................................................................................8 6
4. 2. 5. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts .........................................8 6
4. 2. 6. C ollecti o n of Retai ne d Researc h Sa m ples ..................................................8 6
4. 3. J ustificati o n f or D ose ..............................................................................................8 6
4. 3. 1. Starti n g D ose ..............................................................................................8 6
4. 3. 1. 1. S u bc uta ne o us A d mi nistrati o n ...................................................8 6
4. 3. 1. 2. Alter nati ve I ntra ve n o us A d mi nistrati o n ....................................8 7
4. 3. 2. J ustificati o n f or Pri mi n g D ose Re gi me n .....................................................8 7
4. 3. 3. Fi xe d D osi n g A p pr oac h ..............................................................................8 7
4. 3. 4. D osi n g I nter val ( Q 2 W) ...............................................................................8 8
4. 3. 5. Criteria f or D ose Escalati o n........................................................................ 8 8
4. 3. 6. D ose L i miti n g T o xicit y  ( D L T) Defi niti o n..................................................8 9
4. 3. 6. 1. He mat ol o gical D L Ts .................................................................9 0
4. 3. 6. 2. N o n - He mat ol o gic D L Ts............................................................ 9 0
4. 3. 6. 3. Ot her D L Ts ...............................................................................9 1
4. 3. 7. L ate T o xicit y Defi niti o n a n d Ma na ge me nt.................................................9 1
4. 3. 8. Ma xi m u m T olerate d D ose ( M T D) Defi niti o n............................................ 9 2
4. 3. 9. Rec o m me n de d P hase 2 D ose ( R P 2 D) Defi niti o n....................................... 9 2
4. 4. E n d of St u d y  Defi niti o n ..........................................................................................9 2
5. S T U D Y P O P U L A T I ON................................ ......................................................................9 3
5. 1. I ncl usi o n Criteria .....................................................................................................9 3
5. 2. E xcl u si o n Criteria....................................................................................................9 6
5. 3. L ifest yle C o nsi derati o ns........................................................................................1 0 0
5. 3. 1. C o ntrace pti o n ............................................................................................1 0 0
5. 4. Scree n Fail ures ......................................................................................................1 0 0
6. S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y ...............................1 0 0
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ......................................................................1 0 1
6. 1. 1. A d mi nistrati o n ..........................................................................................1 0 2
6. 1. 1. 1. Pre me dicati o n ..........................................................................1 0 2
6. 1. 1. 2. S C A d mi nistrati o n................................ ...................................1 0 2
6. 1. 1. 3. I V A d mi nistrati o n ................................ ...................................1 0 3
6. 2. Pre parati o n, Ha n dli n g, St ora ge a n d Acc o u nta bilit y ..............................................1 0 3
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ......................................................................1 0 4
6. 3. Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g ...................................1 0 4
6. 3. 1. All ocati o n t o St u d y I nter ve nti o n ..............................................................1 0 4
6. 4. St u d y  Inter ve nti o n C o m plia nce .............................................................................1 0 5
6. 5. D ose M o dificati o n .................................................................................................1 0 6
6. 5. 1. D osi n g I nterr u pti o ns .................................................................................1 0 6
6. 5. 2. D ose Dela y s.............................................................................................. 1 0 7
6. 5. 3. D ose Re d ucti o ns .......................................................................................1 0 8
6. 6. C o nti n ue d Access t o St u d y  Inter ve nti o n After t he E n d of t he S t u d y....................1 1 0
6. 7. Treat me nt of O ver d ose................................ ..........................................................1 1 0
6. 8. C o nc o mita nt T hera p y ............................................................................................1 1 1
6. 8. 1. P r o hi bite d a n d/ or Li mite d use of A nti-t u m or/ A nti-Ca ncer or 
E x peri me ntal Dr u gs, or Pr oce d ures ...............................................................1 1 2
6. 8. 2. S u p p orti ve Care ........................................................................................1 1 2
6. 8. 2. 1. S u p p orti ve Care f or C y t o ki ne Release Sy n dr o me ...................1 1 2
6. 8. 2. 2. S u p p orti ve Care f or I m m u ne Effect or Cell- Ass ociate d 
Ne ur ot o xicit y  Sy n dr o me (I C A N S) ..................................................1 1 2
6. 8. 2. 3. S u p p orti ve Care f or I nf usi o n Relate d Reacti o ns (I V 
i nf usi o n o nl y)...................................................................................1 1 3
6. 8. 2. 4. S u p p orti ve Care f or I njecti o n Site Reacti o ns (I S R) ................1 1 3
6. 8. 2. 5. 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 ................................................................................................1 1 3
6. 8. 2. 6. S u p p orti ve Care f or I m m u ne- Relate d A d verse E ve nts........... 1 1 3
6. 8. 3. He mat o p oietic Gr o wt h Fact ors .................................................................1 1 4
6. 8. 4. A nti diarr heal, A ntie metic T hera p y........................................................... 1 1 4
6. 8. 5. C ortic oster oi ds.......................................................................................... 1 1 4
6. 8. 6. A nti- I nfla m mat or y T hera py ......................................................................1 1 5
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7
6. 8. 7. S ur ger y ......................................................................................................1 1 5
6. 8. 8. Resc ue Me dici ne .......................................................................................1 1 5
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 .........................................................................1 1 5
7. 1. Dis c o nti n uati o n of St u d y Inter ve nti o n ..................................................................1 1 5
7. 1. 1. E C G C ha n ges ............................................................................................1 1 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 .....................................1 1 6
7. 2. 1. Wit h dra wal of C o nse nt .............................................................................1 1 7
7. 3. L ost t o F oll o w -U p .................................................................................................1 1 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 .............................................................1 1 8
8. 1. Efficac y  Assess me nts............................................................................................1 1 8
8. 1. 1. T u m or Res p o nse Assess me nts ..................................................................1 1 8
8. 2. Safet y Assess me nts ...............................................................................................1 1 9
8. 2. 1. P h y sical E xa mi nati o ns ..............................................................................1 1 9
8. 2. 2. Vital Si g ns ................................................................................................1 2 0
8. 2. 3. Electr o car di o gra ms ...................................................................................1 2 0
8. 2. 4. Cli nical Safet y  La b orat or y Assess me nts..................................................1 2 2
8. 2. 5. Pre g na nc y  Testi n g ....................................................................................1 2 2
8. 2. 6. I njecti o n Site T olera bilit y  Assess me nts....................................................1 2 3
8. 3. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g ...............1 2 3
8. 3. 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.....1 2 4
8. 3. 1. 1. Re p orti n g S A Es t o Pfizer Safet y .............................................1 2 4
8. 3. 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................. 1 2 5
8. 3. 2. Met h o d of Detecti n g A Es a n d S A Es ........................................................1 2 5
8. 3. 3. F oll o w -U p of A Es a n d S A Es ....................................................................1 2 5
8. 3. 4. Re g ulat or y Re p orti n g Re q uire me nts f or S A Es .........................................1 2 6
8. 3. 5. E n vir o n me ntal E x p os ure, 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 ...................................................1 2 6
8. 3. 5. 1. E x p os ure D uri n g Pre g na nc y ....................................................1 2 6
8. 3. 5. 2. E x p os ure D uri n g Breastfee di n g ..............................................1 2 8
8. 3. 5. 3. Occ u pati o nal E x p os ure ...........................................................1 2 8
8. 3. 6. Car di o vasc ular a n d Deat h E ve nts .............................................................1 2 8
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8
8. 3. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es ............................................................................1 2 9
8. 3. 8. A d verse E ve nts of S pecial I nterest........................................................... 1 2 9
8. 3. 8. 1. Lac k of Efficac y ......................................................................1 2 9
8. 3. 9. Me dical De vice Deficie ncies ....................................................................1 2 9
8. 3. 1 0. Me dicati o n Err ors ...................................................................................1 2 9
8. 4. P har mac o ki netics ..................................................................................................1 3 0
8. 5. Ge netics .................................................................................................................1 3 1
8. 5. 1. S pecifie d Ge netics ....................................................................................1 3 1
8. 5. 2. Retai ne d Researc h Sa m ples f or Ge netics................................................. 1 3 1
8. 6. Bi o mar kers ............................................................................................................1 3 2
8. 6. 1. T u m or Sa m ple C ollecti o n f or Part 1 .........................................................1 3 3
8. 6. 2. T u m or Sa m ple C ollecti o n f or Part 2......................................................... 1 3 3
8. 6. 2. 1. B 7 -H 4 e x pressi o n f or Part 2 eli gi bilit y ...................................1 3 4
8. 6. 3. Peri p heral Bl o o d Sa m ple C ollecti o n a n d Assess me nts............................ 1 3 4
8. 6. 4. T Cell I m m u n o p he n ot y pi n g ......................................................................1 3 5
8. 6. 5. Retai ne d Researc h Sa m ples f or Bi o mar kers .............................................1 3 5
8. 6. 6. S ol u ble B 7 -H 4 Assess me nt ......................................................................1 3 5
8. 7. I m m u n o ge nicit y Assess me nts ...............................................................................1 3 6
8. 8. Healt h Ec o n o mics .................................................................................................1 3 6
9. S T A TI S TI C A L C O N SI D E R A TI O N S .............................................................................. 1 3 6
9. 1. Statistical H y p ot heses ...........................................................................................1 3 7
9. 1. 1. Esti ma n ds ..................................................................................................1 3 7
9. 1. 1. 1. Pri mar y  Esti ma n d/ C o-Pri mar y  Esti ma n ds..............................1 3 7
9. 2. A nal y sis Sets .........................................................................................................1 3 8
9. 3. Statistical A nal y ses ...............................................................................................1 3 8
9. 3. 1. Ge neral C o nsi derati o ns .............................................................................1 3 9
9. 3. 2. Pri mar y  E n d p oi nts/ Esti ma n ds/ A nal ysis ...................................................1 3 9
9. 3. 3. Sec o n dar y  E n d p oi nt A nal ysis ...................................................................1 4 1
9. 3. 4. Tertiar y / E x pl orat or y E n d p oi nt(s) .............................................................1 4 2
9. 3. 5. Ot her Safet y A nal yses ..............................................................................1 4 2
9. 3. 5. 1. Electr ocar di o gra m A nal y ses....................................................1 4 2
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9
9. 3. 5. 2. A Es ..........................................................................................1 4 4
9. 3. 5. 3. La b orat or y  Test A b n or malities ...............................................1 4 4
9. 3. 6. Ot her A nal ys is(es) ....................................................................................1 4 4
9. 3. 6. 1. A nal y sis of Bi o mar ker E n d p oi nts ...........................................1 4 4
9. 3. 6. 2. P o p ulati o n P har mac o ki netic A nal ys is or P K/ P D M o deli n g ...1 4 4
9. 4. I nteri m A nal ys es ...................................................................................................1 4 4
9. 5. Sa m ple Size Deter mi nati o n ...................................................................................1 4 5
9. 5. 1. Part 1 D ose Escalati o n ..............................................................................1 4 5
9. 5. 2. Part 2 D o se E x pa nsi o n ..............................................................................1 4 5
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 4 6
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 4 6
1 0. 1. 1. Re g ulat or y  a n d Et hical C o nsi derati o ns ..................................................1 4 6
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 4 6
1 0. 1. 2. Fi na ncial Discl os ure ...............................................................................1 4 7
1 0. 1. 3. I nf or me d C o nse nt Pr ocess ......................................................................1 4 7
1 0. 1. 4. Data Pr otecti o n .......................................................................................1 4 8
1 0. 1. 5. C o m mittees Str uct ure .............................................................................1 4 8
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee .................................................1 4 8
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ....................................................1 4 8
1 0. 1. 7. Data Q ualit y Ass ura nce ..........................................................................1 5 0
1 0. 1. 8. S o urce D oc u me nts ..................................................................................1 5 1
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ............................................................1 5 1
1 0. 1. 1 0. P u blicati o n P olic y .................................................................................1 5 2
1 0. 1. 1 1. S p o ns or’s Q ualifie d Me dical Pers o n nel ...............................................1 5 3
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Assess me nts...................................................1 5 4
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 5 5
1 0. 3. 1. Defi niti o n of A E .....................................................................................1 5 5
1 0. 3. 2. Defi niti o n of a n S A E ..............................................................................1 5 6
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 D uri n g 
t he Acti ve C ollecti o n Peri o d..........................................................................1 5 8
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0
1 0. 3. 4. Re p orti n g of S A Es.................................................................................. 1 6 1
1 0. 3. 5. G ui da nce f or I m m u ne -Relate d A d verse E ve nts .....................................1 6 2
1 0. 4. A p pe n di x 4: C o ntrace pti ve a n d Barrier G ui da nce ..............................................1 7 1
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria.................................. 1 7 1
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria ...............................1 7 1
1 0. 4. 3. W o ma n of C hil d beari n g a n d N o n -C hil d bea ri n g P ote ntial .....................1 7 2
1 0. 4. 4. C o ntrace pti o n Met h o ds ...........................................................................1 7 3
1 0. 5. A p pe n di x 5: Ge netics................................ ..........................................................1 7 5
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 7 6
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 7 8
1 0. 8. A p pe n di x 8: Alter n ati ve Meas ures D uri n g P u blic E mer ge ncies ........................1 8 0
1 0. 8. 1. Eli gi bilit y ................................................................................................1 8 0
1 0. 8. 2. Tele healt h Visits .....................................................................................1 8 0
1 0. 8. 3 . Alter nati ve Facilities f or Safety Assess me nts ........................................1 8 1
1 0. 8. 3. 1. La b orat or y  Testi n g................................................................1 8 1
1 0. 8. 3. 2. I ma gi n g ..................................................................................1 8 1
1 0. 8. 3. 3. Electr ocar di o gra ms................................ ................................1 8 1
1 0. 8. 4. St u d y  Inter ve nti o n ..................................................................................1 8 2
1 0. 8. 5. H o me Healt h Visits .................................................................................1 8 2
1 0. 8. 6. A d verse E ve nts a n d Seri o us A d verse E ve nts .........................................1 8 2
1 0. 8. 7. Efficac y  Assess me nts .............................................................................1 8 3
1 0. 9. A p pe n di x 9: Detaile d D ose Escalati o n/ De- Escalati o n Sc he me f or B L R M 
Desi g n ......................................................................................................................1 8 4
1 0. 9. 1. Statistical M o del .....................................................................................1 8 4
1 0. 9. 2. Pri or S pecificati o ns f or M o n ot hera p y Wit h o ut P ri mi n g ........................1 8 4
1 0. 1 0. A p pe n di x 1 0. B o ne Marr o w Reser ve i n A d ults ................................................1 8 5
1 0. 1 1. A p pe n di x 1 1: C R S a n d IC A N S Gra di n g , Miti gati o n, a n d Ma na ge me nt..........1 8 7
1 0. 1 1. 1. C y t o ki ne Release S yn dr o me .................................................................1 8 7
1 0. 1 1. 2. I m m u ne effect or cell -ass ociate d ne ur ot o xicit y sy n dr o me (I C A N S) ....1 9 0
1 0. 1 2. A p pe n di x 1 2: R E CI S T ( Res p o nse E val uati o n Criter ia i n S oli d T u m ors) 
Versi o n 1. 1 G ui deli nes ............................................................................................1 9 5
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1
1 0. 1 3. A p pe n di x 1 3: 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 CIS T) ........................................................................................................2 0 0
1 0. 1 4. A p pe n di x 1 4: S u bc uta ne o us I njecti o n Site L ocati o ns................................ .......2 0 2
1 0. 1 5. A p pe n di x 1 5. Ca uti o nar y  Use of C o nc o mita nt Me dicati o ns wit h Narr o w 
T hera pe utic I n de x D ue t o Dr u g -Dr u g I nteracti o n ( D DI) P ote ntial. ........................2 0 3
1 0. 1 6. A p pe n di x 1 6: E C O G Perf or ma nce Stat us .........................................................2 0 5
1 0. 1 7. A p pe n di x 1 7: A b bre viati o ns .............................................................................2 0 6
1 1. R E F E R E N C E S ................................................................................................................2 1 3
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2
LI S T O F T A B L E S
Ta ble 1.
St u d y  Sc he d ule of Assess me nts – Part 1 Wit h o ut Pri mi n g ......................2 4
Ta ble 2.
P K, I m m u n o ge nicit y, P D, Bi o mar ker, a n d Bi os peci me n Sc he d ule 
of Assess me nts – Part 1 – Wit h o ut Pri mi n g .............................................3 4
Ta ble 3.
St u d y  Sc he d ule of Assess me nts – Part 1 Wit h Pri mi n g ...........................3 8
Ta ble 4.
P K, I m m u n o ge nicit y, P D, Bi o mar ker, a n d Bi os peci me n Sc he d ule 
of Assess me nts – Part 1 - Wit h Pri mi n g ....................................................4 9
Ta ble 5.
Part 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
................5 3
Ta ble 6.
P K, I m m u n o ge nicit y, P D, Bi o mar ker, a n d Bi os peci me n Sc he d ule 
of Assess me nts – Wit h or Wit h o ut Pri mi n g
.............................................6 3
Ta ble 7.
I n patie nt O bser vati o n Sta ys f or S C A d mi nistrati o n .................................8 2
Ta ble 8.
Pr o visi o nal D ose Le vels i n D ose -Escalati o n ( S C A d mi nistrati o n) ..........8 8
Ta ble 9.
A vaila ble D ose Re d ucti o n L e vels Fr o m Starti n g D ose ..........................1 0 8
Ta ble 1 0.
D ose M o dificati o ns f or St u d y  f or N o n-I m m u ne-Relate d T o xicit y ........1 0 8
Ta ble 1 1.
D ose M o dificati o ns f or I m m u ne-Relate d T o xicit y .................................1 0 9
Ta ble 1 2.
Bi o mar ker C ollecti o ns a n d A nal y ses......................................................1 3 2
Ta ble 1 3. 
C ore La b Tests ........................................................................................1 5 4
Ta ble 1 4.
A S T C T C R S Gra di n g S yste m................................................................ 1 8 7
Ta ble 1 5.
Defi niti o n of Hi g h D ose Vas o press or .....................................................1 8 8
Ta ble 1 6.
I m m u ne Effect or Cell-Ass ociate d E nce p hal o pat h y  (IC E) Sc ore ...........1 9 1
Ta ble 1 7.
A S T C T I C A N S Gra di n g ......................................................................... 1 9 1
Ta ble 1 8.
O bjecti ve Res p o nse Stat us at Eac h E val uati o n ......................................1 9 8
Ta ble 1 9.
O bjecti ve Res p o nse Stat us at Eac h E val uati o n f or Partici pa nts wit h 
N o n -Tar get Disease O nl y .......................................................................1 9 9
Ta ble 2 0.
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 ...........................................................................................2 0 1
LI S T O F FI G U R E S
Fi g ure 1 St u d y Sc he ma ............................................................................................................2 3
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
A P hase 1, d ose escalati o n a n d e x pa nsi o n st u d y  t o e val uate t he safety, t olera bilit y , P K, P D , 
a n d a ntit u m or acti vit y of P F-0 7 2 6 0 4 3 7 , a B 7-H 4 x C D 3 bis pec ific mA b, i n partici pa nts a ge d 
≥1 8 ye ars of a ge wit h a d va nce d or metastatic Br Ca, O v Ca or e n d o metrial ca ncer. A d ult 
partici pa nts wit h ot her a d va nce d or metastatic hi g h B 7 -H 4 e x pressi n g t u m ors ma y  be 
c o nsi dere d after disc ussi o n wit h a n d a p pr o val fr o m sp o ns or .
Brief Title
A P hase 1 D ose Escalati o n a n d E x pa nsi o n St u d y  of P F- 0 7 2 6 0 4 3 7 i n A d va nce d or Metastatic 
S oli d T u m ors.
R ati o n ale
P F -0 7 2 6 0 4 3 7 is a T cell re directi n g B 7 -H 4 x C D 3 bis pecific m A b wit h 2 bi n di n g d o mai ns: a 
d o mai n t hat rec o g nizes t u m or a nti ge n B 7 -H 4 wit h hi g h affi nit y  a n d a d o mai n t hat rec o g nizes 
, e x presse d o n T cells, wit h m o derate affi nit y. C o-e n ga ge me nt of B 7- H 4 o n t u m or cells 
a n d
o n T cells lea ds t o a t u m or -l ocalize d T-cell c yt ot o xic res p o nse a n d re d uces 
s yste mic 
 tar geti n g a n d t o xicit y. T his mec ha nis m circ u m ve nts t he nee d f or T cells t o 
rec o g nize s pecific a nti ge nic pe pti des i n t he c o nte xt of 
 o n mali g na nt cells. 
C y t ot o xicit y is me diate d b y release a n d tra nsfer of 
 fr o m t he T cell t o t he B 7-H 4 
e x pressi n g tar get cell. P F- 0 7 2 6 0 4 3 7 a d dresses a si g nifica nt u n met me dical nee d f or Br Ca, as 
its tar get is e x presse d i n t he maj orit y of Br Cas acr oss all m olec ular s u bt ypes.
I n Part 1 of t his cli nical st u d y, P F- 0 7 2 6 0 4 3 7 will be e val uate d f or t he treat me nt of a d ult 
pa rtici pa nts wit h a d va nce d or metastatic Br Ca, O v Ca or e n d o metrial ca ncer f or w h o m n o 
sta n dar d t hera py is a vaila ble wit h n o bi o mar ker selecti o n . T he maj or o bjecti ves are t o 
e val uate safet y, t olera bilit y , P K a n d P D a n d t o i de ntif y  R D E . 
I n Part 2 d ose e x pa nsi o n p hase of t he st u d y, P F- 0 7 2 6 0 4 3 7 will be f urt her e val uate d i n 
partici pa nts wit h a d va nce d or metastatic H R + H E R 2- Br Ca ( Part 2 A) a n d T N B C ( Part 2 C) 
wit h hi g h B 7 - H 4 e x pressi o n t o assess early si g ns of cli nical efficac y . I n a d diti o n, a c o h ort of 
2 0 partici pa nts wit h a d va nce d or metastatic H R + H E R 2 - Br Ca a n d T N B C n ot pre selecte d f or 
B 7 -H 4 e x pressi o n will be i ncl u de d i n Part 2 B t o f urt her e x pl ore bi o mar ker c ha n ges i n t u m or 
micr oe n vir o n me nt a n d vali date t he M o A . 
De n o v o paire d pre - a n d o n-treat me nt bi o psies are ma n dat or y f or 5 partici pa nts i n Part 2 A 
a n d Part 2 C eac h, a n d f or 5 H R + H E R 2 - Br Ca a n d 5 T N B C partici pa nts eac h i n Part 2 B. If 
si g nifica nt TI L i nfiltrates are o bser ve d d uri n g P F -0 7 2 6 0 4 3 7 treat me nt c o nsiste nt wit h t he 
precli nical M o A , t his c o ul d j ustif y f urt her cli nical de vel o p me nt i n c o m bi nati o n wit h 
e n d ocri ne t hera p y a n d/ or C D K 4/ 6 i n hi bit ors i n a d va nce d or metastatic H R + H E R 2- Br Ca as 
well as i n c o m bi nati o n wit h i m m u ne c hec k p oi nt i n hi bit ors i n T N B C .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4
O bjecti ves, E n d p oi nts, a n d Esti m a n ds
D ose Esc al ati o n ( P art 1):
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y

T o assess safet y a n d t olera bilit y 
at i ncreasi n g d ose le vels of 
P F -0 7 2 6 0 4 3 7 i n s uccessi ve 
c o h orts of partici pa nts wit h 
l ocall y a d va nce d or metastatic 
Br Ca, O v Ca or e n d o metrial 
ca ncer.

T o esti mate t he M T D a n d t o 
select R D E .

Occ urre nce of D L Ts .

A E s 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 or C R S 
gra di n g s yste m) 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 ( gra de d b y 
N CI C T C A E v 5), a n d ti mi n g.

D L T rate esti mate d 
base d o n data fr o m 
D L T -e val ua ble 
partici pa nts d uri n g t he 
D L T e val uati o n peri o d.

I nci de nce of A Es 
esti mate d i n t he safet y 
a nal ysis p o p ulati o n 
d uri n g t he A E
e val uati o n per i o d.
Sec o n d ar y 

T o assess i m m u ne relate d safet y 
a n d t olera bilit y at i ncreasi n g 
d ose le vels of P F -0 7 2 6 0 4 3 7 i n 
s uccessi ve c o h orts of 
partici pa nts wit h l ocall y 
a d va nce d or metastatic Br Ca, 
O v Ca or e n d o metrial ca ncer.

ir 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 N CI C T C A E v 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. 

N/ A

T o e val uate t he si n gle a n d 
m ulti ple d ose P K of 
P F -0 7 2 6 0 4 3 7 as m o n ot hera p y. 

P har m ac o ki netic para meters of 
P F -0 7 2 6 0 4 3 7 as m o n ot hera p y: 
S D C ma x , T ma x , A U C last, a n d as 
data per mit, t ½, A U C i nf, C L/ F , 
a n d V z/ F. 
M D (ass u mi n g stea d y state is 
ac hie ve d) C ma x,ss, T ma x ,ss, Cmi n ,ss, 
A U C ss,τ, a n d as data per mit, 
C L ss/ F, V z/ F, a n d R ac
( A U Css,τ/ A U Cs d,τ ).

N/ A

T o e val uate i m m u n o ge nicit y of 
P F -0 7 2 6 0 4 3 7.

I nci de nce a n d titers of A D A a n d 
N A b a gai nst P F -0 7 2 6 0 4 3 7.

N/ A

Tertiar y/ E x pl orat or y

T o e val uate preli mi nar y 
a ntit u m or acti vit y of P F-
0 7 2 6 0 4 3 7 i n partici pa nts wit h 
l ocall y a d va nce d or metastatic 
Br Ca , O v Ca or e n d o metrial 
ca ncer .

O R R, as assesse d b y 
i n vesti gat or base d o n 
R E CI S T v 1. 1 a n d ir R E CI S T.

D O R as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

N/ A 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5
O bjecti ves
E n d p oi nts
Esti m a n ds

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 .

C ha n ges i n pre - a n d 
o n -treat me nt c yt o ki ne a n d 
c he m o ki ne mar kers i n ser u m 
sa m ples.

N/ A

T o e val uate T, B, a n d 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 a n d 
acti vati o n mar kers i n w h ole 
bl o o d .

C ha n ges i n s u bt y pes of i m m u ne 
cell, acti vati o n, a n d pr oliferati o n 
mar kers o n T cells. 

N/ A

T o e x pl ore a d diti o nal 
bi o mar kers i n t u m or bi o psies, 
w h ole bl o o d, a n d ser u m sa m ples 
t o 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.

Bi o mar kers fr o m ge n o mic, 
tra nscri pt o mic, a n d/ or pr otei n 
pr ofili n g fr o m t u m or, bl o o d, 
ser u m or plas ma a n d t heir 
relati o ns hi p t o cli nical o utc o me.

N/ A

T o e val uate t he effect of 
P F -0 7 2 6 0 4 3 7 o n s ol u ble B 7 -H 4.

Pre - a n d p ost-d ose le vels of 
s ol u ble B 7-H 4 i n ser u m.

N/ A
D ose E x p a nsi o n ( P art 2):
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y

T o assess safet y a n d t olera bilit y of 
P F -0 7 2 6 0 4 3 7 at t he R D E i n 
partici pa nts wit h a d va nce d or 
metastatic H R + H E R 2 - Br Ca a n d 
T N B C w it h hi g h B 7-H 4 e x pressi o n 
or wit h o ut bi o mar ker selecti o n. 

A E s 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 or C R S gra di n g 
s yste m) 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 ( gra de d b y N CI C T C A E 
v 5), a n d ti mi n g.

I nci de nce of A Es 
esti mate d i n t he 
safet y a nal ysis 
p o p ulati o n d uri n g 
t he A E-e val uati o n 
peri o d.
Sec o n d ar y 

T o assess ir A Es of P F -0 7 2 6 0 4 3 7 at 
t he R D E i n partici pa nts wit h 
a d va nce d or metastatic H R + 
H E R 2- Br Ca a n d T N B C w it h hi g h 
B 7 -H 4 e x pressi o n or wit h o ut 
bi o mar ker selecti o n.

ir 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 
N CI C T C A E v 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. 

N/ A

T o e val uate preli mi nar y a ntit u m or
acti vit y of P F -0 7 2 6 0 4 3 7 at t he 
R D E i n partici pa nts wit h a d va nce d 
or metastatic H R + H E R 2 - Br Ca 
a n d T N B C wit h hi g h B 7 -H 4 
e x pressi o n or n o bi o mar ker 
selecti o n.

O R R, as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

D O R as assesse d b y i n vesti gat o r 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

N/ A
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6
O bjecti ves
E n d p oi nts
Esti m a n ds

P F S as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

T T P as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

O S.

T o f urt her e val uate t he ser u m P K 
of P F -0 7 2 6 0 4 3 7 at R D E .

P K c o nce ntrati o n of P F -0 7 2 6 0 4 3 7 
at selecte d ti me p oi nts . 

N/ A

T o f urt her e val uate 
i m m u n o ge nicit y of P F-0 7 2 6 0 4 3 7.

I nci de nce a n d titers of A D A a n d 
N A b a gai nst P F -0 7 2 6 0 4 3 7.

N/ A

T o e val uate i m m u ne cells i n pre 
a n d/ or p ost treat me nt t u m or 
bi o psies.

P he n ot y pes, a n d q ua ntit y of TI L
bef ore a n d after P F -0 7 2 6 0 4 3 7 
treat me nt (e g, C D 3, C D 8, 
Gra nz y me B, Ki 6 7 I H C) .

N/ A
Terti ar y/ E x pl or at or y

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.

C ha n ges i n pre - a n d o n -treat me nt 
c yt o ki ne a n d c he m o ki ne mar kers i n 
ser u m sa m ple.

N/ A

T o e val uate T, B, a n d 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 a n d 
acti vati o n mar kers i n w h ole bl o o d .

C ha n ges i n s u bt y pes of i m m u ne 
cell, acti vati o n, a n d pr oliferati o n 
mar kers o n T cells. 

N/ A

T o e x pl ore a d diti o nal bi o mar kers i n 
t u m or bi o psies, w h ole bl o o d, a n d 
ser u m sa m ples t o 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 .

Bi o mar kers fr o m ge n o mic, 
tra nscri pt o mic, a n d/ or pr otei n 
pr ofili n g fr o m t u m or, bl o o d, ser u m 
or plas ma a n d t heir relati o ns hi p t o 
cli nical o utc o me. 

N/ A

T o e val uate t he effect of 
P F -0 7 2 6 0 4 3 7 o n s ol u ble B 7 -H 4.

Pre - a n d p ost-d ose le vels of s ol u ble 
B 7 -H 4 i n ser u m.

N/ A
O ver all Desi g n
T his is a n o pe n la bel, m ulti- ce nter, first-i n-h u ma n P hase 1 d ose escalati o n a n d d ose 
e x pa nsi o n st u d y t o e val uate t he safety, t olera bilit y, P K, P D , a n d preli mi nar y  a ntit u m or 
acti vit y of P F - 0 7 2 6 0 4 3 7, a B 7- H 4 x C D 3 bis pecific m A b i n a d va nce d or metastatic selecte d 
s oli d t u m ors ( Br Ca, O v Ca a n d e n d o metrial ca ncer). T his st u d y  c o ntai ns 2 parts, d ose 
escalati o n ( Part 1) a n d d ose e x pa nsi o n ( Part 2). 
Part 1 c o ntai ns d ose escalati o n i n partici pa nts wit h l ocall y  a d va nce d or metastatic Br Ca, 
O v Ca or e n d o metrial ca ncer t hat is resista nt or i nt olera nt t o sta n dar d t hera p y  or f or w h o m n o 
sta n dar d t hera py is a vaila ble, t o deter mi ne t he M T D
a n d select t he R D E . Partici pa nts wit h 
ot her a d va nce d or metastatic hi g h B 7 -H 4 e x pressi n g t u m ors ma y  be c o nsi dere d after 
disc ussi o n wit h a n d a p pr o val fr o m s p o ns or.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7
O nce t he P F -0 7 2 6 0 4 3 7 m o n ot hera p y  R D E is selecte d, eit her wit h or wit h o ut pri mi n g, Part 2 
d ose e x pa nsi o n c o h orts ma y  be i nitiate d t o f urt her e val uate t he safet y  a n d preli mi nar y 
a ntit u m or acti vit y of P F - 07 2 6 0 4 3 7 m o n ot hera p y i n a d va nce d or metastatic 2 L + H R + H E R 2 -
Br Ca wit h hi g h B 7 -H 4 e x pressi o n ( Part 2 A) a n d 2 L + T N B C wit h hi g h B 7 - H 4 e x pressi o n 
( Part 2 C) as well as u nselecte d H R + H E R 2 - Br Ca or T N B C ( Part 2 B) .
N u m ber of P artici p a nts
T otal n u m ber of partici pa nts f or Part 1 a n d Part 2 c o m bi ne d, is esti mate d t o be a p pr o xi matel y  
1 0 0.
A p pr o xi matel y  3 5 partici pa nts are e x pecte d t o be e nr olle d i nt o 1 of 5 - 7 se q ue ntial d ose le vels 
i n Part 1 i ncl u di n g at least 6 partici pa nts treate d at t he M T D . T he act ual n u mber 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 2 6 0 4 3 7 a n d t he n u m ber of d ose 
le vels t hat are re q uire d t o deter mi ne M T D/R D E . 
A p pr o xi matel y  6 0 partici pa nts are e x pecte d t o be e nr olle d i nt o 3 c o h orts i n Part 2: Part 2 A, 
Part 2 B a n d Part 2 C, wit h a p pr o xi matel y  n = 2 0 partici pa nts i n eac h c o h ort. T we nt y 
partici pa nts f or eac h c o h ort is cli nicall y  s ufficie nt t o eva l uate safety si g nals .
St u d y P o p ul ati o n a n d S pecific I ncl usi o n/ E xcl usi o n Criteri a
K e y  i ncl usi o n a n d e xcl usi o n criteria are liste d bel o w:
I ncl usi o n Criteri a 
Partici pa nts m ust meet t he f oll o wi n g ke y  i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o 
t he st u d y:
1.
Partici pa nts ≥1 8 ye ars of a ge.
2.
Pri mar y  disease:

P art 1: Hist ol o gical or c y t ol o gical dia g n osis of l ocall y a d va nce d or metastatic Br Ca, 
e n d o metrial ca ncer a n d O v Ca t hat is resista nt t o sta n dar d t hera py or f or w hic h n o 
sta n dar d t hera py is a vaila ble. Partici pa nts wit h ot her a d va nce d or metastatic s oli d 
t u m ors wit h hi g h B 7 -H 4 e x pressi o n ma y  be c o nsi dere d after disc ussi o n wit h a n d 
a p pr o val b y sp o ns or. Si milarl y , t h ose partici pa nts wit h ot her a d va nce d or metastatic 
s oli d t u m ors s h o ul d be resista nt t o sta n dar d t hera p y or ha ve n o a vaila ble sta n dar d 
t hera py.

P art 2 A: 2 L + partici pa nts wit h hist ol o gical or c y t ol o gical dia g n osis of l ocall y 
a d va nce d or metastatic H R + H E R 2 - Br Ca s h o wi n g hi g h B 7 -H 4 e x pressi o n w h o ha ve 
pr o gresse d after at least 1 li ne of S O C C D K 4/ 6 i n hi bit or a n d 1 li ne of S O C e n d ocri ne 
treat me nt. De n o v o paire d pre - a n d o n -treat me nt bi o psies are ma n dat or y f or 5 
partici pa nts .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8

P art 2 B: 2 L + partici pa nts wit h hist ol o gical or c y t ol o gical dia g n osis of l ocall y 
a d va nce d or metastatic H R + H E R 2 - Br Ca w h o ha ve pr o gresse d after at least 1 li ne of 
S O C C D K 4/ 6 i n hi bit or a n d 1 l i ne of S O C e n d ocri ne treat me nt, or 2 L + T N B C w h o 
ha ve pr o gresse d after at least 1 li ne of S O C s yste mic t hera p y (e g, c he m ot hera py i n 
c o m bi nati o n wit h a c hec k p oi nt i n hi bit or if P D-L 1  p ositi ve or c he m ot hera p y al o ne if 
P D -L 1  ne gati ve/l o w). De n o v o paire d pre- a n d o n-treat me nt bi o psies are ma n dat or y 
f or 5 H R + H E R 2- Br Ca partici pa nts a n d 5 T N B C partici pa nts. N o bi o mar ker 
selecti o n base d o n B 7- H 4 e x pressi o n is nee de d f or Part 2 B.

P art 2 C: 2 L + partici pa nts wit h hist ol o gical or c y t ol o gical dia g n osis of l ocall y 
a d va nc e d or metastatic T N B C s h o wi n g hi g h B 7 - H 4 e x pressi o n w h o ha ve pr o gresse d 
after at least 1 li ne of S O C c he m ot hera p y a n d 1 li ne of S O C s yste mic t hera p y (e g, 
c he m ot hera p y i n c o m bi nati o n wit h a c hec k p oi nt i n hi bit or if P D-L 1  p ositi ve or 
c he m ot hera p y al o ne if P D-L 1 ne gati ve/l o w) . De n o v o paire d pre- a n d o n -treat me nt 
bi o psies are ma n dat or y  f or 5 partici pa nts . 
3.
Partici pa nts m ust be a ble t o pr o vi de 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 fres h bi o ps y d uri n g scree ni n g. Te n ( 1 0 ) partici pa nts e nr olli n g i n Part 2 B, a n d 
5 partici pa nts e nr olli n g i n eac h of Parts 2 A a n d 2 C m ust a gree t o paire d pre- a n d o n-
treat me nt bi o psies. A bilit y of a partici pa nt t o u n der g o bi o psy safel y s h o ul d be deter mi ne d 
d uri n g scree ni n g. E xce pti o ns t hat bi o psies ca n n ot be o btai ne d d ue t o safet y r is k s h o ul d be 
disc usse d a n d a p pr o ve d b y  t he sp o ns or .
4.
Partici pa nts wit h H R + H E R 2 - a d va nce d or metastatic Br Ca m ust ha ve: 
a.
D oc u me ntati o n of E R or P R -p ositi ve t u m or (≥1 % p ositi ve stai ne d cells) base d o n 
m ost rece nt t u m or tiss ue utilizi n g a n assa y c o nsiste nt wit h l ocal sta n dar ds a n d 
A S C O/ C A P g ui deli nes (Allis o n et al, 2 0 2 0 ).
b.
D oc u me ntati o n t hat t u m or is H E R 2- ne gati ve as deter mi ne d wit h I H C of sc ore 0/ 1 + 
or ne gati ve b y i n sit u h y bri dizati o n ( FI S H/ CI S H/ SI S H/ DI S H) defi ne d as a 
H E R 2/ C E P 1 7 rati o < 2 or f or si n gle pr o be assess me nt a H E R 2 c o py n u m ber < 4 , 
c o nsiste nt wit h A S C O/ C A P g ui deli ne s (W olff et al, 2 0 1 8 ).
5.
Partici pa nts wit h T N B C m ust ha ve d oc u me ntati o n t hat t u m or tiss ue is ne gati ve ( < 1 % 
cells wit h n uclear p ositi vit y ) f or E R a n d P R as well as ne gati ve f or H E R 2 as deter mi ne d 
b y I H C sc ore 0/ 1 + or ne gati ve b y  I SH ( FIS H/ CI S H/ SI S H/ DI S H) defi ne d as a 
H E R 2/ C E P 1 7 rati o < 2 or f or si n gle pr o be assess me nt a H E R 2 c o p y n u m ber < 4 , 
c o nsiste nt wit h A S C O/ C A P g ui deli nes (W olff et al, 2 0 1 8 ; Allis o n et al, 2 0 2 0 ).
6.
T S H 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 
patie nts wit h a b n or mal T S H if Free T 4 i s 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9
E xcl usi o n Criteri a 
Partici pa nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will be e xcl u de d:
1.
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. 
Partici pa nts wit h sec o n dar y  mali g na nc y t hat has bee n a de q uately treate d, or i n d ole nt 
t u m ors t hat w o ul d n ot i nterfere wit h safety a n d efficac y assess me nts mi g ht be all o we d 
after disc ussi o n wit h a n d a p pr o val fr o m t he s p o ns or.
2.
Partici pa nts wit h a d va nce d/ metastatic, s y m pt o matic, visceral s prea d, t hat are at ris k of 
life-t hreate ni n g c o m plicati o ns i n t he s h ort ter m (i ncl u di n g partici pa nts wit h massi ve 
u nc o ntr olle d eff usi o ns [ ple ural, pericar dial, perit o neal], p ul m o nar y l y m p ha n gitis, a n d 
o ver 5 0 % li ver i n v ol ve me nt). N ote: Partici pa nts wit h i n d welli n g cat heter f or drai na ge, or 
re q uire me nt f or drai na ge n o m ore fre q ue ntl y t ha n m o nt hl y will be all o we d. 
3.
Hist or y  of Gra de ≥3 i m m u ne me diate d A E (i ncl u di n g A S T/ A L T ele vati o ns t hat w here 
c o nsi dere d dr u g relate d a n d c y t 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 wit hi n 1 y ear of treat me nt . 
Partici pa nts wit h Gra de 2 h y p ot h yr oi dis m or h y p o pit uitaris m res ulti n g fr o m 
i m m u n ot hera p y o n sta ble h or m o ne re place me nt t hera p y a n d partici pa nts wit h c hr o nic 
a dre nal i ns ufficie nc y recei vi n g d oses < 1 0 m g/ da y of pre d nis o ne e q ui vale nts are eli gi ble.
I nter ve nti o n Gr o u ps a n d D ur ati o n
P art 1
Pa rtici pa nts will recei ve escalati n g d oses of P F-0 7 2 6 0 4 3 7 a d mi nistere d as S C i njecti o n wit h 
a starti n g d ose le vel of 1 0 0 µ g Q 2 W as m o n ot hera p y . A d diti o nal d osi n g fre q ue nc y s uc h as 
Q 1 W or Q 3 W ma y  be c o nsi dere d if s u p p orte d b y e mer gi n g cli nical P K, P D, a n d safet y data. 
B L R M g ui de d b y  E W O C pri nci ple will be use d t o g ui de t he d ose escalati o n pr ocess a n d 
deter mi ne t he M T D/ R D E. T he ma xi m u m all o wa ble P F- 0 7 2 6 0 4 3 7 d ose i ncre me nt is 2 0 0 % 
( d ose tri pli n g fr o m t he pre vi o us d ose le vel) f or c o h orts b ut will be a dj uste d t o no m ore t ha n 
1 0 0 % ( d ose d o u bli n g fr o m t he pre vi o us d ose le vel) 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 cli nicall y  si g nifica nt treat me nt-relate d A Es. F or m o n ot hera py wit h o ut 
pri mi n g strate g y , D L T will be assesse d d uri n g t he first 2 8 d a ys. F or m o n ot hera p y wit h 
pri mi n g, t he D L T assess me nt peri o d will e xte n d t o i ncl u de pri mi n g d oses pl us 2 f ull d oses 
(e g, first 4 2 da ys). Eac h d ose le vel gr o u p will i ncl u de 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 per c o h ort in t he first 2 c o h orts a n d at least 2 D L T 
e val ua ble partici pa nts per d ose le vel gr o u p i n t he re mai ni n g c o h orts f or Part 1. A sta g gere d 
e nr oll me nt strate g y will be a p plie d f or partici pa nts e nteri n g Part 1 at d ose le vel 1. Eac h 
partici pa nt d ose d will be o bser ve d f or 4 8 h o urs. If n o safety c o ncer ns arise d uri n g t his 
4 8 h o u r peri o d, t he n a n a d diti o nal partici pa nt ma y be e nr olle d at d ose le vel 1.  Per B L R M 
desi g n, e x pa n di n g a d diti o nal partici pa nts at l o wer d ose le vels are all o we d t o assess safet y. 
D ose escalati o n c o h orts ma y  be s witc he d fr o m S C a d mi nistrati o n t o I V a d mi nistrati o n if S C 
a d mi nistrati o n is n ot c o nsi dere d as t he preferre d r o ute d ue t o se vere s ki n t o xicities, l o w P K 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0
e x p os ure or ot her reas o ns. I V a d mi nistrati o n c o h orts ma y  i nitiate at a dose le vel t hat is n o 
greater t ha n 2 0 % of t he hi g hest S C d ose le vel t hat is dee me d t olera ble (e g, starti n g at 6 0 µ g 
I V Q 2 W if 3 0 0 µ g S C Q 2 W is dee me d t olera ble) de pe n di n g o n e mer gi n g P K a n d safety data .
A pri mi n g d ose a p pr oac h i n t he ne xt d ose le vel ma y  be i nitiate d if a d ose le vel i n d uces ≥
Gra de 2 C R S (lasti n g f or > 2 4 h o urs) occ urs i n > 1 partici pa nt des pite treat me nt wit h 
t ociliz u ma b a n d/ or vas o press ors. If t he d ose escalati o n has reac he d t he M T D a n d a pri mi n g 
d ose has n ot bee n pre vi o usl y  i nc or p orate d t o the d ose re gi me n, a p ri mi n g d ose escalati o n 
c o h ort t o mi ni mize C ma x ma y  be i nitiate d base d o n cli nical safety, P K/ P D, a n d cli nical 
efficac y. 
T he D L T peri o d f or S C or I V d osi n g wit h o ut pri mi n g will be 2 8 da y s. T he D LT peri o d wit h 
pri mi n g will e xte n d t o i ncl u de t he d urati o n of t he pri mi n g d oses a n d 2 f ull d oses after 
pri mi n g (e g, if a pri mi n g d ose is gi ve n o n Da y  1 a n d t he first f ull d ose o n Da y 1 5, t he t otal 
D L T o bser vati o n peri o d will be 4 2 da y s). A tra diti o nal 2- para meter B L R M will be use d t o 
m o del t he D L T relati o ns hi p t o t he dr u g a n d i nf or m d ose escalati o n wit h or wit h o ut pri mi n g. 
T he ma xi m u m d ose le vel i ncrease will be 2 0 0 % ( d ose tri pli n g fr o m t he pre vi o us d ose le vel).
P art 2
T he Part 2 d ose e x pa nsi o n p hase will e nr oll partici pa nts i nt o 3 c o h orts detaile d as f oll o ws: 

P art 2 A ( N = 2 0): P F -0 7 2 6 0 4 3 7 as m o n ot hera p y  i n partici pa nts wit h H R + H E R 2-
Br Ca s h o wi n g hi g h B 7 -H 4 e x pressi o n, 2 L + w h o ha ve pr o gresse d after at least 1 li ne 
of sta n dar d of care C D K 4/ 6 i n hi bit or a n d 1 li ne of sta n dar d of care e n d ocri ne 
treat me nt. De n o v o paire d pre - a n d o n -treat me nt bi o psies are ma n dat or y f or 5 
partici pa nts .

P art 2 B ( N = 2 0): P F -0 7 2 6 0 4 3 7 as m o n ot hera p y  i n partici pa nts wit h H R + H E R 2-
Br Ca, 2 L + w h o ha ve pr o gresse d after at least 1 li ne of sta n dar d of care C D K 4/ 6 
i n hi bit or a n d 1 li ne of sta n dar d of care e n d ocri ne treat me nt, or 2 L + T N B C w h o ha ve 
pr o gresse d after at least 1 li ne of S O C s y ste mic t hera p y (e g 1 L c he m ot hera p y i n 
c o m bi nati o n wit h a n i m m u ne c hec k p oi nt i n hi bit or if P D -L 1 + or c he m ot hera p y al o ne 
if P D-L 1  ne gati ve/l o w). A p pr o xi matel y 1 0 H R + H E R 2- Br Ca a n d a p pr o xi matel y  1 0 
T N B C partici pa nts s h o ul d be e nr olle d. De n o v o paire d pre- a n d o n -treat me nt bi o psies 
are ma n dat or y f or a p pr o xi matel y 5 H R + H E R 2- Br Ca partici pa nts a n d 5 T N B C 
partici pa nts. N o bi o mar ker selecti o n base d o n B 7 - H 4 e x pressi o n. 

P art 2 C ( N = 2 0): P F -0 7 2 6 0 4 3 7 as m o n ot hera p y  i n partici pa nts wit h T N B C s h o wi n g 
hi g h B 7 -H 4 e x pressi o n, 2 L + w h o ha ve pr o gresse d after at least 1 li ne of S O C 
s yste mic t hera p y (e g, 1 L  c he m ot hera py i n c o m bi nati o n wit h a n i m m u ne c hec k p oi nt 
i n hi bit or if P D-L 1  p ositi ve or c he m ot hera py al o ne if P D-L 1 ne gati ve/l o w). De n o v o 
paire d pre - a n d o n -treat me nt bi o psies will be ma n dat or y f or 5 partici pa nts. 
De pe n di n g o n t he res ults of precli nical c o m bi nati o n i n vi v o efficac y  data, e mer gi n g cli nical 
m o n ot hera p y safet y a n d efficac y, P F -0 7 2 6 0 4 3 7 c o m bi nati o n c o h orts ma y  be a d de d, 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1
i ncl u di n g c o m bi nati o n wit h C D K 4/ 6 i n hi bit or a n d/ or e n d ocri ne t hera pies i n H R + H E R 2-
Br Ca a n d c o m bi nati o n wit h chec k p oi nt i n hi bit ors i n T N B C .
All partici pa nts will u n der g o u p t o 2 8 da ys of scree ni n g pri or t o first d ose. Eli gi ble 
partici pa nts will t he n recei ve st u d y  i nter ve nti o n f or u p t o 2 years, or u ntil disease pr o gressi o n 
defi ne d b y ir R E CI S T, u nacce pta ble t o xicit ies, a decisi o n b y t he partici pa nt ( wit h dra wal of 
c o nse nt or n o l o n ger willi n g t o partici pate) or i n vesti gat or t o disc o nti n ue treat me nt, or st u d y  
ter mi nati o n. N ote: If a partici pa nt is classifie d as ha vi n g P D d uri n g a n o n-treat me nt t u m or 
assess me nt, t he n co nfir mati o n of P D b y  a sec o n d sca n i n t he a bse nce of ra pi d cli nical 
deteri orati o n is re q uire d per ir R E CI S T.
D at a M o nit ori n g C o m mittee or Ot her I n de pe n de nt O versi g ht C o m mittee: N o
T his st u d y  will n ot use a D M C or i n de pe n de nt o versi g ht c o m mittees i n t his st ud y .
St atistic al Met h o ds
T here is n o f or mal h y p ot hesis testi n g i n t his st u d y. 
U nless ot her wise s pecifie d, s u m maries will be prese nte d b y  d ose gr o u p a n d o verall. 
Descri pti ve statistics, s uc h as t he 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, a n d ma xi m u m val ues, will be pr o vi de d f or c o nti n u o us e n d p oi nts. T he rates of 
bi nar y  e n d p oi nts will be pr o vi de d al o n g wit h t he c orres p o n di n g 2-si de d 9 5 % CIs usi n g a n 
e xact met h o d. Ti me -t o-e ve nt e n d p oi nts will be s u m marize d usi n g t he Ka pla n-Meier me t h o d 
a n d dis pla ye d gra p hicall y w he n a p pr o priate. Me dia n e ve nt ti mes a n d 2-si de d 9 5 % CIs f or 
eac h ti me-t o- e ve nt e n d p oi nt will be pr o vi de d.
T he d ose escalati o n i n Part 1 of t he st u d y  will be g ui de d b y a Ba yesia n a nal ysis of D L T data 
f or P F- 0 7 2 6 0 4 3 7. D ose t o xicit y is m o delle d usi n g 2 - para meter l o gistic re gressi o n f or t he 
pr o ba bilit y  of a partici pa nt e x perie nci n g a D L T at t he gi ve n d ose.
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 
partici pa nts at differe nt d oses of i nterest f or P F-0 7 2 6 0 4 3 7 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 d a y s f or t he re gi me n wit h o ut pri mi n g; pri mi n g d oses pl us 2 f ull d oses 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]
D osi n g decisi o ns are g ui de d b y  t he E W O C pri nci pal (R o gat k o et al, 2 0 0 7 ). A d ose ma y o nl y 
be use d f or ne wl y e nr olle d partici pa nts if t he ris k of o ver d osi n g at t hat d ose is less t ha n 2 5 %.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 2
Rec o m me n dati o n fr o m t he B L R M, al o n g wit h safet y  ( A Es, S A Es), la b orat or y, P K, 
bi o mar ker, a n d ot her rele va nt data, will be use d at t he ti me of eac h d ose es calati o n a n d f or 
M T D/ R D E deter mi nati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 3
1. 2. Sc he m a
Fi g ure 1 St u d y Sc he m a
P art 1 - D ose Esc al ati o n
Ba yesia n desi g n B 7 -H 4 x C D 3 m o n ot hera p y d ose escalati o n ( 5 -7 d ose le vels) 
i n partici pa nts wit h l ocall y a d va nce d or metastatic Br Ca ,  O v Ca or e n d o metrial 
ca ncer t o assess safet y a n d P K/P D . 
Part 2 – D ose E x pa nsi o n
B 7 -H 4 x C D 3 m o n ot hera p y i n H R + H E R 2 - Br Ca an d 
T N B C t o e val uate O R R a n d D o R a n d assess earl y si g n of 
cli nical efficac y
* A pri mi n g d ose escalati o n ma y be i nitiate d if criteria is met .
D ose Le vel 1, S C, Q 2 W, Br Ca , O v Ca 
or e n d o metrial ca ncer , n o bi o mar ker 
selecti o n
D ose Le vel 2, S C
D ose Le ve l 3+
Part 2 B – N o t selecte d f or B 7-H 4 e x pressi o n, H R + 
H E R 2 - Br Ca a n d T N B C, 2 L +
M o n ot hera p y, N = 2 0, a p pr o xi matel y 5 ma n dat or y 
paire d bi o ps ies f or eac h, H R + H E R 2 - Br Ca a n d 
T N B C
Part 2 A – Bi o mar ker selecti o n, hi g h B 7 -H 4, H R + 
H E R 2 - Br Ca, 2 L + 
M o n ot hera p y, N = 2 0, a p pr o xi matel y 5 ma n dat or y 
paire d bi o ps ies
M T D/ R D E
M T D/ R D E wit h 
pri mi n g *
Part 2 C – Bi o mar ker selecti o n, hi g h B 7 -H 4, 
T N B C, 2 L +
M o n ot hera p y , N = 2 0, a p pr o xi matel y 5 ma n dat or y 
paire d bi o ps ies
Base d o n e mer gi n g data, c o nsi der 
c o m bi nati o n ar m wit h e n d ocri ne t hera p y  
a n d/ or C D K i n hi bit or i n 2 L+ H R + H E R 2 -
Br Ca or a c hec k p oi nt i n hi bit or i n T N B C.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 4
1. 3. Sc he d ule of Acti vities
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 well-bei n g of t he partici pa nt. 
1. 3. 1. P art 1 – Sc he d ule of Assess me nt - Wit h o ut Pri mi n g
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Inf or me d c o nse nt a n d 
re gistrati o n
X
I nf or me d c o nse nt s h o ul d be 
o btai ne d pri or t o a n y st u d y -s pecific 
pr oce d ures.
At re gistrati o n, e nr ol lme nt 
(ra n d o mizati o n) n u m ber a n d d ose 
le vel will be assi g ne d b y Pfizer.
Scree n f or 
i ncl usi o n/e xcl usi o n 
criteria
X
See Secti o n 5. 1 a n d 5. 2
D e m o gra p hics
X
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 5
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Me dic al hist or y a n d P h ysic al E x a mi n ati o n
See Secti o n 8. 2 f or a d diti o nal 
i nf or mati o n.
Pri mar y ca ncer 
dia g n osis a n d pri or 
treat me nt hist or y
X
I ncl u de date of i nitial dia g n osis a n d 
metastatic disease, pri or s yste mic 
treat me nts, s ur geries, ra di ot hera p y,
a n d rec urre nce hist or y. 
Ge n o mic testi n g if a vaila ble. 
Ge neral me dical 
hist or y
X
I ncl u de a n y c o nc urre nt or res ol ve d 
ill ness ot her t ha n t he ca ncer u n der 
st u d y.
Baseli ne si g ns a n d 
s y m pt o ms
X  
X
Si g ns a n d s y m pt o ms e x perie nce d 
wit hi n t he 2 8 da ys pri or t o first 
d ose .
C o m plete p h ysical 
e xa mi nati o n
X
X
I ncl u de hei g ht at scree ni n g. 
See Secti o n 8. 2. 1 f or a d diti o nal 
i nf or mati o n.
Brief p h ysical 
e xa mi nati o n
X  
X  
X  
X  
X  
X  
X
X
P E a n d vital si g ns s h o ul d be 
c o m plete d pri or t o d osi n g.

See Secti o n 8. 2. 1 f or a d diti o nal 
i nf or mati o n.
Wei g ht
X  
X
X
X
T o be meas ure d pri or t o d osi n g.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 6
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Vital s i g ns ( B P/ p ulse 
rate/R R /t e mperat ure)
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
B P a n d p ulse rate s h o ul d be 
rec or de d i n t he sitti n g p ositi o n or 
se mi-rec u mbe nt p ositi o n prece de d 
b y at least 5 mi n utes of rest.
See Secti o n 8. 2. 2 f or a d diti o nal 
i nf or mati o n.
E C O G pe rf or ma nce 
stat us
X  
X
X  
X  
X  
X  
X  
X
See Secti o n 8. 2. 1 .
C o ntrac e pti o n c hec k
X  
X
X
X  
X
C o nfir m a p pr o priate selecti o n 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). 
See Secti o n 5. 3. 1 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 7
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
E C G (sta n dar d 
1 2 -lea d)
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
At scree ni n g: si n gle 1 2 -lea d E C G. 
C y cles 1 t o 3: tri plicate 1 2 -lea d 
E C Gs t o deter mi ne mea n Q Tc F 
i nter val. F or t he da ys of d ose 
a d mi nistrati o n, perf or m E C G u p t o 
6 0 mi n utes pri or t o d osi n g ( S C or 
I V), a n d at t he e n d of i nf usi o n (I V 
o nl y). 
Fr o m  C ycle 4 o n war ds: Tri plicate 
1 2 -lea d E C G u p t o 6 0 mi n utes pri or 
t o d osi n g o n D a y 1 of e ver y 3 c ycles 
( C 4 D 1, C 7 D 1, etc.).
Refer t o Secti o n 8. 2. 3 f or a d diti o nal 
i nf or mati o n.
St u d y I nter ve nti o n
P F -0 7 2 6 0 4 3 7 
a d mi nistrati o n
X
X  
X  
X
F ull d ose at e ver y d osi n g ti me p oi nt.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 8
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Pre m e dicati o n
( X)
( X) 
( X) 
( X)
Pr o p h ylactic p r e me dicati o n is n ot 
all o wed d uri n g t he D L T e val uati o n 
peri o d d uri n g i nitial d ose escalati o n.   
H o w e ver , if t he partici pa nt 
e x perie nces a n i nf usi o n relate d 
reacti o n (I V), aller gic reacti o n, 
si g nifica nt i njecti o n site reacti o n, 
C R S, fe ver/c hills, aller gic reacti o n, 
na usea/ v o miti n g, h y p ote nsi o n, or 
pai n, a p pr o priate treat me nt s h o ul d 
i nitiate a n d pre me dicati o n as 
pr o p h yla xis ma y be c o nsi dere d f or 
s u bse q ue nt i njecti o ns as we ll as f or 
ne w partici pa nts . See Secti o n 
6. 1. 1. 1 f or a d diti o nal i nf or mati o n.
C o nc o mita nt t hera p y
◄--------------------------------------------------------------------------------------------- ►
I ncl u de me dicati o ns gi ve n t o treat 
A E s, c hr onic c o n diti o ns, a n d 
s u p p orti ve me dicati o ns (e xce pt 
pre me dicati o n).
See Secti o n 6. 8 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 9
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
I n patie nt o bser vati o n
X  
X  
X  
X
( X) 
( X)
Partici pa nts 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 ( or t he first I V 
d ose a d mi nistrati o n, as a p plica ble)
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 ( or t he 
sec o n d I V d ose a d mi nistrati o n, as 
a p plica ble) o n C 1 D 1 5.   See
Secti o n 4. 1 .
Partici pa nts w h o e x perie nce ≥ 
Gra de 3 i nf usi o n-relate d a d verse 
e ve nts (I V a d mi nistrati o n) or 
cli nicall y si g nifica nt C R S m ust be 
h os pitalize d f or at least 2 4 h o urs f or 
at least 4 d oses s u bse q ue ntl y (t w o 
c ycles).  See Secti o n 4. 1 .
See Secti o n 6. 1 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 0
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
I njecti o n site 
t olera bilit y 
assess me nt
X  
X
X
As cli nicall y 
i n dicate d
C 1 D 1: at least 1 h o ur a n d 2 4 h o urs 
( ± 1 hr) after S C i njecti o n. 
C 1 D 1 5: at least 1 h o ur after S C 
i njecti o n. 
See Secti o n 8. 2. 6 f or a d diti o nal 
i nf or mati o n.
Effic ac y Assess me nt
T u m or res p o nse 
assess me nt
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 T/ M RI sca ns of hea d, c hest, 
a b d o me n, pel vis, a n y cli nicall y 
i n dicate d sites of disease (see
Secti o n 8. 1. 1 ).
B o ne sca n or P E T
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
F or b o ne metastasis (see
Secti o n 8. 1. 1 ).
S afet y Assess me nt
Seri o us a n d 
n o nseri o us A E 
m o nit ori n g
◄-------------------------------------------------------------------------------------------------►
See Secti o ns 8. 2 a n d Secti o n 8. 3 .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 1
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Cli nic al S afet y L a b or at or y Assess me nts
See Secti o n 8. 2. 4 .
See A p pe n di x 2 f or a list of Cli nical 
La b orat or y tests t o be d o ne.
H e m at ol o g y
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
N o nee d t o re peat o n C 1 D 1 if 
scree ni n g wa s perf or me d wit hi n 
7 pri or da ys. All sa m ples will be 
c ollecte d pri or t o d osi n g. 
Bl o o d c he mistr y
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C oa g ul ati o n
X
E ver y 8 wee ks fr o m C 1 D 1
X
N o nee d t o re peat o n C 1 D 1 if 
scree ni n g wa s perf or me d wit hi n 
7 pri or da ys.
Li pase a n d a m ylase
X
X
X
T S H a n d free T 4
X
T S H W N L f or i nstit uti o n; i n 
partici pa nts wit h a b n or mal T S H, if 
free T 4 is W N L a n d partici pa nt is 
cli nicall y e ut h yr oi d, partici pa nt is 
eli gi ble. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 2
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Viral disease scree n
X
I ncl u de H Bs A g, H Bc A b, a n d H C V 
a nti b o d y. I n t he case of a p pare nt 
o n g oi n g H B V or H C V i nfecti o n, 
refle x ser u m D N A or R N A viral 
l oa d testi n g, res pecti vel y, will be 
perf or me d.

See A p pe n di x 2 f or a d diti o nal 
i nf or mati o n.
Uri nal ysis
X  
X
X  
X
Micr osc o pic a nal yses if di pstic k is 
cli nicall y a b n or mall y i n dicate d. N o 
nee d t o re peat o n C 1 D 1 if scree ni n g
wa s perf or me d wit hi n 7 pri or da ys. 
F oll o w i n g C 1 D 1, o nl y o btai n as 
cli nicall y i n dicate d u ntil f oll o w-u p .
C y t o ki ne (l ocal la b)
C y t o ki nes s h o ul d be assesse d wit h l ocal la b orat or y 
st u dies i n t he e ve nt of s us pecte d C R S.
T o be c ollecte d if C R S is s us pecte d 
a n d e val uati o n of c yt o ki ne is 
re q uire d f or partici pa nt 
ma na g e me nt.
See A p pe n di x 2 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 3
T a ble 1 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y
F oll o w - u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 
d a ys)
St u d y D a y
-2 8 t o - 1
1
2
3 a
8
1 5 a
2 2
1
C 3 D 8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a.
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns ).
b.
P K / P D a n d E C G o nl y .
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Pre g na nc y test
X  
X
X
X  
X
Ser u m or uri ne pre g na nc y test f or 
W O C B P .
See Secti o n 8. 2. 5 f or a d diti o nal 
i nf or mati o n.
P ost Tre at m e nt
Late ir A E f oll o w- u p 
X
Partici pa nts will u n der g o tele p h o ne 
f oll o w-u ps at 9 0 da ys ( ± 7 da ys) 
after t he last d ose of P F -0 7 2 6 0 4 3 7 
t o assess p ote ntial late ir A Es.  If a n y 
c o ncer n arises, t he partici pa nt 
s h o ul d be c o ntacte d f or a n i n-pers o n 
f oll o w-u p visit.   
P h ar m ac o ki netic Assess me nts
See Ta ble 2
I m m u n o ge nicit y Assess me nts
P h ar m ac o d y n a mic, Bi o m ar ker a n d Bi os peci me ns Assess me nts
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 4
1. 3. 1. 1. P art 1 - P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n – Wit h o ut Pri mi n g
T a ble 2 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 – Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
D a y 1
D a y 
2
D a y 
3
D a y 
8
D a y 1 5
D a y 
2 2
H o urs
Bef ore/ After D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
4 8 hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose 
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 
hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 4 hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 2 4 
hr
P K Assess me nts
P K bl o o d sa m pli n g
A, 
B, 
C, D
A, C 
(I V 
o nl y)
A, C  
A, C  
A  
A
A, C
A, 
C
A  
A  
A  
X
If C R S is s us pecte d, 
a d diti o nal P K sa m ple 
s h o ul d be c ollecte d at 
ti me of A E occ urre nce if 
n ot alrea d y sc he d ule d.
I V o nl y: if act ual d urati o n 
of i nf usi o n differs fr o m 1 
h o ur, 1 -h o ur p oi nt s h o ul d 
be a dj uste d f or t he 
sa m ple t o be c ollecte d at 
t he e n d of i nf usi o n.
See Secti o n 8. 4 f or 
a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 5
T a ble 2 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 – Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
D a y 1
D a y 
2
D a y 
3
D a y 
8
D a y 1 5
D a y 
2 2
H o urs
Bef ore/ After D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
4 8 hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose 
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 
hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 4 hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 2 4 
hr
I m m u n o ge nicit y Assess me nts
Bl o o d sa m ples f or 
A D A a n d N A b
A, 
B, 
C, D
X
Fr o m  C ycle 4 o n war ds: 
collecti o n o n Da y 1 of 
e ver y 3 c ycle s. ( C 4 D 1, 
C 7 D 1, etc.)
See Secti o n 8. 7 f or 
a d diti o nal i nf or mati o n.
P h ar m ac o d y n a mic a n d Bi o m ar ker Assess me nts
S ol u ble B 7 -H 4
bl o o d sa m pli n g
A, 
B, 
C, D
A, C
A, C  
A  
A
A, C
A, 
C
A  
X
Fr o m  C ycle 4 o n war ds: 
collecti o n o n Da y 1 of 
e ver y 3 c ycle s. ( C 4 D 1, 
C 7 D 1, etc.)
See Secti o n 8. 6. 6 f or 
a d diti o nal i nf or mati o n.
Ser u m f or c yt o ki ne 
a n d circ ulati n g 
mar kers (ce ntral la b)
A , B
A  
A  
A  
A  
A  
A  
A  
A  
A  
A
See Secti o n 8. 6. 3 .
Bl o o d f or 
I m m u n o p he n ot y pi n g
A, B
A  
A  
A  
A
A
Refer t o Secti o n 8. 6. 4 .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 6
T a ble 2 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 – Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
D a y 1
D a y 
2
D a y 
3
D a y 
8
D a y 1 5
D a y 
2 2
H o urs
Bef ore/ After D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
4 8 hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose 
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 
hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 4 hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 2 4 
hr
Ma n dat or y a rc hi val 
t u m or tiss ue
X
All partici pa nts m ust 
pr o vi de arc hi val tiss ue.
M ust refer t o 
Secti o n 8. 6. 1 f or s pecific 
i nstr ucti o n/acce pta ble 
tiss ue sa m ples.
O pti o nal de n o v o 
pre -d ose a n d paire d 
o n -treat me nt bi o ps y
( X)
( B)
( X)
( B) (X ) = O pti o nal.
M ust refer t o 
Secti o n 8. 6. 1 f or s pecific 
i nstr ucti o n/acce pta ble 
tiss ue sa m ples.
Plas ma f or cell free
D N A a nal ysis
A
X
Refer t o Secti o n 8. 6. 3 .
A: 1 0 m L -bl o o d 
s peci me ns o pti mize d f or 
plas ma pre parati o n will 
be c ollecte d. 
Bl o o d f or ger mli ne 
s u btracti o n
A
2 m L w h ole bl o o d will be 
c ollecte d a n d se q ue nce d 
al o n g wit h t u m or sa m ples 
e na bli n g s u btracti o n of 
ger mli ne variati o ns fr o m 
s o matic m utati o ns.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 7
T a ble 2 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 – Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d 
i n t his t a ble m a y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
D a y 1
D a y 
2
D a y 
3
D a y 
8
D a y 1 5
D a y 
2 2
H o urs
Bef ore/ After D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
4 8 hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose 
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 
hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 4 hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 2 4 
hr
Retai ne d Researc h 
Sa m ple f or Ge netics
[ Pre p D 1]
A
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 
will be c ollecte d. See 
L a b orat or y M a n ual -
Retai ne d Researc h 
Sa m ple c ollecti o n.
Pre p D 1 Retai ne d 
Researc h Sa m ples f or 
Ge netics: 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. 
See Secti o n 8. 5. 2 f or 
a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 8
1. 3. 2. P art 1 – Sc he d ule of Assess me nts - Wit h Pri mi n g
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
I nf or me d c o nse nt a n d 
re gistrati o n
X
I nf or me d c o nse nt s h o ul d be o btai ne d 
pri or t o a n y st u d y -s pecific pr oce d ures.
At re gistrati o n, e nr oll me nt 
(ra n d o mizati o n) n u m ber a n d d ose le vel 
will be assi g ne d b y s p o ns or.
Scree n f or 
i ncl usi o n/e xcl usi o n 
criteria
X
See Secti o n 5. 1 a n d 5. 2 .
D e m o gra p hics
X
Me dic al hist or y a n d P h ysic al E x a mi n ati o n
See Secti o n 8. 2 f or a d diti o nal 
i nfor m ati o n
Pri mar y ca ncer 
dia g n osis a n d pri or 
treat me nt hist or y
X
I ncl u de date of i nitial dia g n osis a n d 
metastatic disease, pri or s yste mic 
treat me nts, s ur geries, ra di ot hera p y, 
a n d rec urre nce hist or y. 
Ge n o mic testi n g if a vaila ble. 
Ge neral me dical hist or y
X
I ncl u de a n y c o nc urre nt or res ol ve d 
ill ness ot her t ha n t he ca ncer u n der 
st u d y.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 3 9
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Baseli ne si g ns a n d 
s y m pt o ms
X
X
Si g ns a n d s y m pt o ms e x perie nce d 
wit hi n t he 2 8 da ys pri or t o first d ose.
C o m plete p h ysical 
e xa mi nati o n 
X
X
I ncl u de hei g ht at scree ni n g.
See Secti o n 8. 2. 1 f or a d diti o nal 
i nf or mati o n.
Brief p h ysical 
e xa mi nati o n 
X
X
X
X
X
X
( C 2 
o nl y)
X
X
P E a n d vital si g ns s h o ul d be c o m plete d 
pri or t o d osi n g.
See Secti o n 8. 2. 1 f or a d diti o nal 
i nf or mati o n.
Wei g ht
X
X
X
X
T o be meas ure d pri or t o d osi n g.
Vital si g ns ( B P/ p ulse 
rate/ R R/te m perat ure)
X
X
X
X
X
X
X
X
X
( C 2 
o nl y)
X
X
X
B P a n d p ulse rate s h o ul d be rec or de d
i n t he sitti n g or se mi-rec u m be nt 
p ositi o n prece de d b y at least 5 mi n utes 
of rest.
See Secti o n 8. 2. 2 f or a d diti o nal 
i nf or mati o n.
E C O G perf or ma nce 
stat us
X
X
X
X
X
X
( C 2 
o nl y)
X
X
X
See Secti o n 8. 2. 1 .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 0
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
C o ntrace pti o n c hec k
X
X
X
X
X
C o nfir m a p pr o priate selecti o n 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). 
See Secti o n 5. 3. 1 f or a d diti o nal 
i nf or mati o n.
E C G (sta n dar d 1 2 -lea d)
X
X
X
X
X
X
X
X
X
( C 2 & 
C 3 o nl y)
X
X
X
At scree ni n g: si n gle 1 2-lea d E C G. 
C y cles 1 t o 3: tri plicate 1 2 -lea d E C Gs 
t o deter mi ne mea n Q Tc F i nter val. F or 
t he da ys of d ose a d mi nistrati o n, 
perf or m E C G u p t o 6 0 mi n utes pri or t o 
d osi n g ( S C or I V), a n d at t he e n d of 
i nf usi o n (I V o nl y). 
Fr o m  C ycle 4 o n war ds: Tri plicate 
1 2 -lea d E C G u p t o 6 0 mi n utes pri or t o 
d osi n g o n Da y 1 of e ver y 3 c ycles 
( C 4 D 1, C 7 D 1, etc.).
Refer t o Secti o n 8. 2. 3 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 1
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
St u d y I nter ve nti o n
P F -0 7 2 6 0 4 3 7
X 
( pri mi n g 
d ose)
( Xc)
X
X
X
C 1 D 1 is pri mi n g d ose a n d C 1 D 1 5 is 
f ull/ mai nte na nce d ose. 
c: A 2 -ste p pri mi n g ma y be c o nsi dere d 
o n C 1 D 1 a n d C 1 D 8.
See Secti o n 4. 1 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 2
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Pre m e dicati o n
( X)
( Xd) ( X)
( X)
( X)
Pr o p h ylactic pre me dicati o n is n ot 
all o we d d uri n g t he D L T e val uati o n 
peri o d d uri n g i nitial d ose escalati o n.   
H o w e ver , if t he partici pa nt 
e x perie nces a n i nf usi o n relate d 
reacti o n (I V), aller gic reacti o n, 
si g nifica nt i njecti o n site reacti o n, C R S, 
fe ver/c hills, aller gic reacti o n, 
na usea/ v o miti n g, h y p ote nsi o n, or pai n, 
a p pr o priate treat me nt s h o ul d i nitiate 
a n d pre me dicati o n as pr o p h yla xis ma y 
be c o nsi dere d f or s u bse q ue nt 
i njecti o ns as well as f or new 
partici pa nts. See Secti o n 6. 1. 1. 1 f or 
a d diti o nal i nf or mati o n.
d: O nl y a p plica ble t o 2 -ste p pri mi n g
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 3
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
C o nc o mita nt t hera p y
◄--------------------------------------------------------------------------------------►
I ncl u de me dicati o ns gi ve n t o treat 
A E s, c hr o nic c o n diti o ns, a n d 
s u p p orti ve me dicati o ns (e xce pt 
pre me dicati o n).
See Secti o n 6. 8 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 4
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
I n patie nt o bser vati o n
X
X e
X
X e
( X)
( X)
e: 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 pri mi n g S C d ose ( or t he first I V 
pri mi n g d ose a d mi nistrati o n, as 
a p plica ble) 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 ( or t he 
sec o n d (f ull) I V d ose a d mi nistrati o n, 
as a p plica ble) o n C 1 D 1 5. Ma y n ot 
re q uire o ver ni g ht sta y.
Partici pa nts w h o e x perie nce ≥ Gra de 3 
i nf usi o n-relate d a d verse e ve nts (I V 
a d mi nistrati o n) or cli nicall y si g nifica nt 
C R S m ust be h os pitalize d f or at least 
2 4 h o urs f or at least 4 d oses 
s u bse q ue ntl y (t w o c ycles).  See
Secti o n 4. 1 .
See Secti o n 6. 1 f or a d diti o nal 
i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 5
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
I njecti o n site 
t olera bilit y assess me nt
X
X
X
As cli nicall y i n dicate d
C 1 D 1: at least 1 h o ur a n d 2 4 h o urs 
( ± 1 hr) after i njecti o n. 
C 1 D 1 5: at least 1 h o ur after i njecti o n.
See Secti o n 8. 2. 6 f or a d diti o nal 
i nf or mati o n
Effic ac y Assess me nt
T u m or res p o nse 
assess me nt
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 we e 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 T/ M RI sca ns of hea d, c hest, 
a b d o me n, pel vis, a n y cli nicall y 
i n dicate d sites of disease (see 
Secti o n 8. 1. 1 ).
B o ne Sca n or P E T 
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 we e 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
F or b o ne metastasis (see 
Secti o n 8. 1. 1 ).
S afet y Assess me nt
Seri o us a n d n o nseri o us 
A E m o nit ori n g
◄--------------------------------------------------------------------------------------►
See Secti o ns 8. 2 a n d Secti o n 8. 3 .
Cli nic al S afet y L a b or at or y Assess me nts
See Secti o n 8. 2. 4
See A p pe n di x 2 f or a list of Cli nical 
La b orat or y tests t o be d o ne.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 6
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
H e m at ol o g y
X  
X
X  
X  
X  
X  
X
( C 2 
o nl y)
X  
X  
X
N o nee d t o re peat o n C 1 D 1 if 
scree ni n g was perf or me d wit hi n 
7 pri or da ys. All sa m ples will be 
c ollecte d pri or t o d osi n g.
Bl o o d C he mistr y
X  
X
X  
X  
X  
X  
X
( C 2 
o nl y)
X  
X
C oa g ulati o n
X
E ver y 8 wee ks fr o m C 1 D 1
X
N o nee d t o re peat o n C 1 D 1 if 
scree ni n g was perf or me d wit hi n 
7 pri or da ys.
Li pase a n d a m ylase
X
X
X
T S H a n d free T 4
X
T S H W N L f or i nstit uti o n; i n 
partici pa nts wit h a b n or mal T S H, if 
free T 4 is W N L a n d partici pa nt is 
cli nicall y e ut h yr oi d, partici pa nt is 
eli gi ble.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 7
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Viral disease scree n
X
I ncl u de H Bs A g, H Bc A b, a n d H C V 
a nti b o d y. I n t he case of a p pare nt 
o n g oi n g H B V or H C V i nfecti o n, refle x 
ser u m D N A or R N A viral l oa d testi n g, 
res pecti vel y, will be perf or me d.
See A p pe n di x 2 f or a d diti o nal 
i nf or mati o n.
Uri nal ysis
X  
X
X  
X
Micr osc o pic a nal yses if di pstic k is 
cli nicall y a b n or mall y i n dicate d. N o 
nee d t o re peat o n C 1 D 1 if s cree ni n g 
wa s perf or me d wit hi n 7 pri or da ys. 
F oll o w i n g C 1 D 1, o nl y o btai n as 
cli nicall y i n dicate d u ntil f oll o w -u p.
C y t o ki ne (l ocal la b)
C y t o ki nes s h o ul d be assesse d wit h l ocal la b orat or y st u dies 
i n t he e ve nt of s us pecte d C R S.
T o be c ollecte d if C R S is s us pecte d 
a n d e val uati o n of c yt o ki ne is re q uire d 
f or partici pa nt ma na ge me nt.
See A p pe n di x 2 f or a d diti o nal 
i nf or mati o n
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 8
T a ble 3 .
St u d y Sc he d ule of Assess me nts – P a rt 1 Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns use d i n 
t his t a ble ma y be 
f o u n d i n A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w -
u p
9 0 -d a y  
F oll o w -
u p f or 
ir A Es
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2 ( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5
1 6 a
2 2
1
8 b
1 5
A d diti o nal visit wi n d o w  m a y b e 
all o we d after disc ussi o n a n d 
a gree me nt bet wee n i n vesti gat or a n d 
s p o ns or.
a:
E n d of i n patie nt o bser vati o n ( P K, 
E C G, vital si g ns). 
b: T his D 8 visit is o nl y a p plica ble f or 
C y cles 2 a n d 3, w hereas, C 3 D 8 is 
a p plica ble f or P K/ P D a n d E C G o nl y.
Visit Wi n d o w ( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
Pre g na nc y test 
X  
X
X
X  
X
Ser u m or uri ne pre g na nc y test f or 
W O C B P.
See Secti o n 8. 2. 5 f or a d diti o nal 
i nf or mati o n.
P ost Treat me nt
Late ir A E f oll o w u p
X
Partici pa nts will u n der g o tele p h o ne 
f oll o w-u ps at 9 0 da ys ( ± 7 da ys) after 
t he last d ose of P F-0 7 2 6 0 4 3 7 t o assess 
p ote ntial late ir A Es.  If a n y c o ncer n 
arises, t he partici pa nt s h o ul d be 
c o ntacte d f or a n i n -pers o n f oll o w  u p 
visit.   
P h ar m ac o ki netic Assess me nts
See Ta ble 4
I m m u n o ge nicit y Assess me nts
P h ar m ac o d y n a mic, Bi o m ar ker a n d Bi os peci me ns Assess me nts
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 4 9
1. 3. 2. 1. P art 1 - P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n – Wit h Pri mi n g
T a ble 4 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 - Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his 
t a ble ma y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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 
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
1 hr
4 
hr
8 
hr
2 4 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 1 0 
mi n
± 
3 0 
mi
n
± 1 
hr
± 3 
hr
± 2 4 
hr
P K Assess me nts
P K bl o o d 
sa m pli n g
A, B, 
C, D
A, C 
(I V 
o nl y)
A, 
C
A,
C
A
A, 
C
A, 
C
A
(I V 
o nl y)
A  
A  
A  
A  
X
If C R S is s us pecte d, 
a d diti o nal P K sa m ple 
s h o ul d be c ollecte d at 
ti me of A E occ urre nce if 
n ot alrea d y sc he d ule d
I V o nl y: if act ual d urati o n 
of i nf usi o n differs fr o m 1 
h o ur, 1 -h o ur p oi nt s h o ul d 
be a dj uste d f or t he sa m ple 
t o be c ollecte d at t he e n d 
of i nf usi o n.
See Secti o n 8. 4 f or 
a d diti o nal i nf or mati o n.
I m m u n o ge nicit y Assess me nts
Bl o o d sa m ples 
f or A D A a n d 
N A b
A, B, 
C, D
X
Fr o m  C ycle 4 o n war ds: 
collecti o n o n Da y 1 of 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 0
T a ble 4 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 - Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his 
t a ble ma y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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 
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
1 hr
4 
hr
8 
hr
2 4 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 1 0 
mi n
± 
3 0 
mi
n
± 1 
hr
± 3 
hr
± 2 4 
hr
e ver y 3 c ycle s. ( C 4 D 1, 
C 7 D 1 etc.)
See Secti o n 8. 7 f or 
a d diti o nal i nf or mati o n.
P h ar m ac o d y n a mic a n d Bi o m ar ker S a m ples
S ol u ble B 7 -H 4 
bl o o d sa m ple
A, B, 
C, D
A , 
C
A , C
A  
A , C
A , C
A  
A  
A  
A  
X
Fr o m  C ycle 4 o n war ds: 
collecti o n o n Da y 1 of 
e ver y 3 c ycle s ( C 4 D 1, 
C 7 D 1, etc.)
See Secti o n 8. 6. 6 f or 
a d diti o nal i nf or mati o n.
Ser u m f or 
c yt o ki ne a n d 
circ ulati n g 
mar kers (ce ntral 
la b)
A , B
A  
A  
A  
A  
A  
A  
A  
A  
A  
A  
A
Refer t o Secti o n 8. 6 . 3.
Bl o o d sa m ple 
f or 
i m m u n o p he n ot y
pi n g
A, B
A  
A  
A
A  
A
Refer Secti o n 8. 6. 4 . 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 1
T a ble 4 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 - Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his 
t a ble ma y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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 
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
1 hr
4 
hr
8 
hr
2 4 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 1 0 
mi n
± 
3 0 
mi
n
± 1 
hr
± 3 
hr
± 2 4 
hr
Ma n dat or y 
arc hi val t u m or 
tiss ue
X
All partici pa nts m ust 
pr o vi de arc hi val tiss ue.
M ust refer t o 
Secti o n 8. 6. 1 f or s pecific 
i nstr ucti o n/acce pta ble 
tiss ues sa m ples.
O pti o nal de 
n o v o pre -d ose 
a n d paire d o n-
treat me nt 
bi o ps y
( X)
( B)
( X)
( B) a n d (X ) = O pti o nal.
M ust refer t o
Secti o n 8. 6. 1 f or s pecific 
i nstr ucti o n/acce pta ble 
tiss ues sa m ples.
Plas ma sa m ple 
f or cell free
D N A a nal ysis
A
X
Refer t o Secti o n 8. 6. 3 .
A: 1 0 m L -bl o o d 
s peci me ns o pti mize d f or 
plas ma pre parati o n will 
be c ollecte d. 
Bl o o d f or 
ger mli ne 
s u btracti o n
A
2 m L w h ole bl o o d sa m ple 
will be c ollecte d a n d 
se q ue nce d al o n g wit h 
t u m or sa m ples e na bli n g 
s u btracti o n of ger mli ne 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 2
T a ble 4 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – P art 1 - Wit h Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his 
t a ble ma y be 
f o u n d i n
A p pe n di x 1 6
Scree ni n
g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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 
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
1 hr
4 
hr
8 
hr
2 4 
hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate 
d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 1 0 
mi n
± 
3 0 
mi
n
± 1 
hr
± 3 
hr
± 2 4 
hr
variati o ns fr o m s o matic 
m utati o ns.
Retai ne d 
Researc h 
Sa m ple f or 
Ge netics
[ Pre p D 1]
A
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 
will be c ollecte d . See 
L a b orat or y M a n ual -
Retai ne d Researc h 
Sa m ple c ollecti o n.
Pre p D 1 Retai ne d 
Researc h Sa m ples f or 
Ge netics: 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. 
See Secti o n 8. 5. 2 f or 
a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 3
1. 3. 3. P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
I nf or me d c o nse nt
X
I nf or me d c o nse nt s h o ul d be 
o btai ne d pri or t o a n y 
st u d y-s pecific pr oce d ures.
E nr ol me nt (ra n d o mizati o n) 
n u m ber  ma y be assi g ne d b y 
I R T.
Scree n f or 
i ncl usi o n/e xcl usi o n 
criteria
X
See Secti o n 5. 1 a n d 5. 2 .
D e m o gra p hics
X
Me dic al hist or y a n d P h ysic al E x a mi n ati o n
See Secti o n 8. 2 f or a d diti o nal 
i nf or mati o n.
Pri mar y ca ncer 
dia g n osis a n d pri or 
treat me nt hist or y
X
I ncl u de date of i nitial 
dia g n osis a n d metastatic 
disease, pri or s yste mic 
treat me nts, s ur geries, 
ra di ot hera p y, a n d rec urre nce 
hist or y. 
Ge n o mic testi n g if a vaila ble. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 4
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
Ge neral Me dical 
hist or y
X
I ncl u de a n y c o nc urre nt or 
res ol ve d ill ness ot her t ha n 
t he ca ncer u n der st u d y.
Baseli ne si g ns a n d 
s y m pt o ms
X  
X
Si g ns a n d s y m pt o ms 
e x perie nce d wit hi n t he 
2 8 da ys pri or t o first d ose.
C o m plete p h ysical 
e xa mi nati o n
X
X
I ncl u de hei g ht at scree ni n g. 
Secti o n 8. 2. 1 f or a d diti o nal 
i nf or mati o n.
Brief p h ysical 
e xa mi nati o n
X  
X  
X  
X  
X  
X
X
P E a n d vital si g ns s h o ul d be 
c o m plete d pri or t o d osi n g .
See Secti o n 8. 2. 1 f or 
a d diti o nal i nf or mati o n.
Wei g ht
X  
X
X
X
T o be meas ure d pri or t o 
d osi n g.
Vital si g ns 
( B P/res pirat or y 
rate/p ulse 
rate/te m perat ure)
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
B P a n d p ulse rate s h o ul d be 
rec or de d i n t he sitti n g or 
se mi-rec u mbe nt p ositi o n 
prece de d b y at least 
5 mi n utes of rest.
See Secti o n 8. 2. 2 f or 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 5
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
a d diti o nal i nf or mati o n.
E C O G perf or ma nce 
stat us
X  
X  
X  
X  
X  
X  
X  
X
See Secti o n 8. 2. 1 .
C o ntrace pti o n 
C hec k
X  
X
X
X  
X
C o nfir m a p pr o priate 
selecti o n 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). 
See Secti o n 5. 3. 1 f or 
a d diti o nal i nf or mati o n.
E C G (sta n dar d 
1 2 -lea d)
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
At scree ni n g: si n gle 1 2 -lea d 
E C G. 
C y cles 1 t o 3: tri plicate 
1 2 -lea d E C Gs t o deter mi ne 
mea n Q Tc F i nter val. F or t he 
da ys of d ose a d mi nistrati o n, 
perf or m E C G u p t o 6 0 
mi n utes pri or t o d osi n g ( S C 
or I V), a n d at t he e n d of 
i nf usi o n (I V o nl y). 
Fr o m  C ycle 4 o n war ds: 
Tri plicate 1 2 -lea d E C G u p t o 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 6
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
6 0 mi n utes pri or t o d osi n g o n
D a y 1 of e ver y 3 c ycles 
( C 4 D 1, C 7 D 1, etc.).
Refer t o Secti o n 8. 2. 3 f or 
a d diti o nal i nf or mati o n.
St u d y I nter ve nti o n
P F -0 7 2 6 0 4 3 7
X  
X
X  
X
Wit h o ut pri mi n g: F ull d ose 
at e ver y d osi n g ti me p oi nt.
Wit h pri mi n g: Pri mi n g d ose 
o n C 1 D 1; f ull d ose o n 
C 1 D 1 5 a n d be y o n d.
See Secti o n 4. 1 f or a d diti o nal 
i nf or mati o n.
Pre m e dicati o n
( X) 
( X)
( X) 
( X)
Pre m e dicati o n is o pti o nal 
( X). 
B ase d o n a re vie w of all 
acc u m ulate d safet y data (e g, 
> 5 0 % of partici pa nts 
e x perie nce d si g nifica nt 
aller gic reacti o n or C R S 
relate d s y m pt o ms a n d si g ns), 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 7
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
pr o p h ylactic pre me dicati o n 
ma y be c o nsi dere d d uri n g t he 
D L T o bser vati o n peri o d f or 
ne w partici pa nts after 
a gree me nt bet wee n 
i n vesti gat ors a n d t he s p o ns or 
t o deter mi ne t he M T D/ R D E 
wit h pr o p h yla xis.  
See Secti o n 6. 1. 1. 1 f or 
a d diti o nal i nf or mati o n.
C o nc o mita nt 
t hera p y
◄--------------------------------------------------------------------------------------►
I ncl u de me dicati o ns gi ve n t o 
treat A Es, c hr o nic 
c o n diti o ns, a n d s u p p orti ve 
me dicati o ns (e xce pt 
pre me dicati o n).
See Secti o n 6. 8 f or a d diti o nal 
i nf or mati o n.
I n patie nt 
o bser vati o n
X  
X  
X  
X
( X) 
( X)
Wit h o ut pri mi n g d ose : 
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 d ose o n C 1 D 1 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 8
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
a n d f or at least 8 h o urs after 
t he sec o n d d ose o n C 1 D 1 5.
Wit h pri mi n g d ose:
P artici pa nts will be o bser ve d 
i n patie nt f or at least 2 4 h o urs 
after t he pri mi n g 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) d ose o n C 1 D 1 5.
Partici pa nts w h o e x perie nce 
≥ Gra de 3 i nf usi o n -relate d 
a d verse e ve nts (I V 
a d mi nistrati o n) or cli nicall y 
si g nifica nt C R S m ust be 
h os pitalize d f or at least 2 4 
h o urs f or at least 4 d oses 
s u bse q ue ntl y (t w o c ycles).  
See Secti o n 4. 1 .
See Secti o n 6. 1 f or 
a d diti o nal i nf or mati o n.
I njecti o n site 
t olera bilit y 
assess me nt
X  
X  
X
As cli nicall y 
i n dicate d
C 1 D 1: 1 h o ur a n d 2 4 h o urs 
( ± 1 hr) after S C i njecti o n. 
C 1 D 1 5: 1 h o ur after S C 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 5 9
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
i njecti o n.
See Secti o n 8. 2. 6 f or 
a d diti o nal i nf or mati o n.
Effic ac y Assess me nts
T u m or res p o nse 
assess me nt
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 we e ks ( ± 7 d a y s) 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 T/ M RI sca ns of h ea d, 
chest, ab d o m e n, p el vis, a n y 
cli nicall y i n dicate d sites of 
disease (see Secti o n 8. 1. 1 ).
B o ne sca n or P E T
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 we e ks ( ± 7 d a y s) 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
F or b o ne metastasis (se e 
Secti o n 8. 1. 1 ).
S afet y Assess me nts
Seri o us a n d 
n o nseri o us A E 
m o nit ori n g
◄--------------------------------------------------------------------------------------------------------►
See Secti o ns 8. 2 a n d 
Secti o n 8. 3 .
Cli nic al S afet y L a b or at or y Assess me nts
See Secti o n 8. 2. 4
See A p pe n di x 2 f or a list of 
Cli nical La b orat or y tests t o 
be d o ne.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 0
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
H e m at ol o g y
X
X
X
X
X
X
X
X
X
X
N o nee d t o re peat o n C 1 D 1 if 
scree ni n g wa s perf or me d 
wit hi n 7 pri or da ys. All 
sa m ples will be c ollecte d 
pri or t o d osi n g. 
Bl o o d C he mistr y
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C oa g ulati o n
X
E ver y 8 wee ks fr o m C 1 D 1
X
N o nee d t o re peat o n C 1 D 1 if 
scree ni n g wa s perf or me d 
wit hi n 7 pri or da ys.
Li pase a n d a m ylase
X
X
X
T S H a n d free T 4
X
T S H W N L f or i nstit uti o n; i n 
partici pa nts wit h a b n or mal 
T S H, if free T 4 is W N L a n d 
partici pa nt is cli nicall y 
e ut h yr oi d, partici pa nt is 
eli gi ble.
B 7 -H 4 e x pressi o n 
( bi o ps y)
X
C LI A -vali date d B 7 -H 4 I H C 
La b orat or y De vel o pe d Test 
o n arc hi val t u m or bi o psies
Viral disease scree n
X
I ncl u de H Bs A g, H Bc A b, a n d 
H C V a nti b o d y. I n t he case of 
a p pare nt o n g oi n g H B V or 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 1
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
H C V i nfecti o n, refle x ser u m 
D N A or R N A viral l oa d 
testi n g, res pecti vel y, will be 
perf or me d .
See A p pe n di x 2 f or 
a d diti o nal i nf or mati o n.
Uri nal ysis
X  
X
X  
X
Di pstic k is acce pta ble. 
Micr osc o pic a nal yses 
cli nicall y i n dicate d. N o nee d 
t o re peat o n C 1 D 1 if 
scree ni n g wa s perf or me d 
wit hi n 7 pri or da ys. 
F oll o w i n g C 1 D 1, o nl y o btai n 
as cli nicall y i n dicate d u ntil 
f oll o w-u p.
C y t o ki ne (l ocal la b)
C y t o ki nes s h o ul d be assesse d wit h l ocal 
la b orat or y st u dies i n t he e ve nt of s us pecte d C R S.
T o be c ollecte d if C R S is 
s us pecte d a n d e val uati o n of 
c yt o ki ne is re q uire d f or 
partici pa nt ma na ge me nt.
See A p pe n di x 2 f or 
a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 2
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
Pre g na nc y test
X  
X
X
X  
X
Ser u m or uri ne pre g na nc y 
test f or W O C B P.
See Secti o n 8. 2. 5 f or 
a d diti o nal i nf or mati o n.
P h ar m ac o ki netic Assess me nts
See Ta ble 6 .
I m m u n o ge nicit y Assess me nts
P h ar m ac o d y n a mic, Bi o m ar ker a n d Bi os peci me ns Assess me nts
P ost -Tre at m e nt
Late ir A E f oll o w -u p
X
Partici pa nts will u n der g o 
tele p h o ne f oll o w-u ps at 
9 0 da ys ( ± 7 da ys) after t he 
last d ose of P F-0 7 2 6 0 4 3 7 t o 
assess p ote ntial late ir A Es.  
If a n y c o ncer n arises, t he 
partici pa nt s h o ul d be 
c o ntacte d f or a n i n-pers o n 
f oll o w-u p visit.    
S ur vi val f oll o w -u p
X
S ur vi val stat us will be 
c ollecte d b y tele p h o ne e ver y 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 3
T a ble 5 .
P art 2 – Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 7
Scree ni n g
Tre at m e nt Peri o d
E O T
4- wee k 
F oll o w - u p
9 0 -d a y 
F oll o w -u p f or 
ir A Es
S ur vi v al 
F oll o w - u p
N otes
C ycle 1 = 2 8 d a ys
C ycle ≥2
( 2 8 d a ys)
St u d y D a y
-2 8 t o - 1
1
2 a
8
1 5 a
1 6 a
2 2
1
1 5
A d diti o nal visit wi n d o w  m a y 
be all o w e d after disc ussi o n 
a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.
a: E n d of i n patie nt o bser vati o n 
( P K, E C G, vital si g ns). Da y 2 
f or all partici pa nts; Da y 1 6 f or 
pri mi n g d ose sc he d ule o nl y.
Visit Wi n d o w 
( d a ys)
± 2
± 2
± 2
± 2
± 2
± 2
± 7
± 7
± 1 4
3 m o nt hs u ntil deat h, or u p t o 
2 4 m o nt hs after first d ose of 
t he last partici pa nt.
1. 3. 3. 1. P art 2 - P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n – Wit h or Wit h o ut Pri mi n g
T a ble 6 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 6
Scree ni n g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 
hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
2 4 hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 3 hr
± 2 4 
hr
P K Assess me nts
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 4
T a ble 6 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 6
Scree ni n g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 
hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
2 4 hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 3 hr
± 2 4 
hr
P K bl o o d 
sa m pli n g
A, B, 
C, D
A, C 
(I V 
o nl y)
A, C
A,
C
A  
A
A, 
C
A  
A  
A
( Pri mi n g 
o nl y)
A  
X
If C R S is s us pecte d, 
a d diti o nal P K sa m ple 
s h o ul d be c ollecte d at ti me 
of A E occ urre nce if n ot 
alrea d y sc he d ule d
I V o nl y: if act ual d urati o n 
of i nf usi o n differs fr o m 1 
h o ur, 1 -h o ur p oi nt s h o ul d 
be a dj uste d f or t he sa m ple 
t o be c ollecte d at t he e n d 
of i nf usi o n.
See Secti o n 8. 4 f or 
ad diti o nal i nf or mati o n .
I m m u n o ge nicit y Assess me nts
Bl o o d sa m ples f or 
A D A a n d N A b
A, B, 
C, D
X
Fr o m  C ycle 4 o n war ds: 
c ollecti o n o n Da y 1 of 
e ver y 3 c ycles. ( C 4 D 1, 
C 7 D 1, etc.)
See Secti o n 8. 7 f or 
a d diti o nal i nf or mati o n.
P h ar m ac o d y n a mic a n d Bi o m ar ker S a m ples
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 5
T a ble 6 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 6
Scree ni n g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 
hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
2 4 hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 3 hr
± 2 4 
hr
S ol u ble B 7 -H 4 
bl o o d sa m ple
A, B, 
C, D
A  
A
X
Fr o m  C ycle 4 o n war ds: 
c ollecti o n o n Da y 1 of 
e ver y 3 c ycles. ( C 4 D 1, 
C 7 D 1, etc.)
See Secti o n 8. 6. 6 f or 
a d diti o nal i nf or mati o n.
Ser u m f or 
c yt o ki ne a n d 
circ ulati n g 
mar kers (ce ntral 
la b)
A, B
A  
A  
A  
A  
A  
A  
A  
A
A 
( Pri mi n g 
o nl y)
A
Refer t o Secti o n 8. 6. 3 .
Bl o o d sa m ple f or 
i m m u n o p he n ot y pi
n g
A, B
A  
A  
A
A 
( Pri mi n g 
o nl y)
A
Refer t o Secti o n 8. 6. 4 .
O pt i o nal or 
ma n dat or y
arc hi val tiss ue
X
O pti o nal if de n o v o tiss ue 
sa m ple is pr o vi de d.
M a n dat or y if a de n o v o 
tiss ue sa m ple is n ot 
pr o vi de d .
Refer t o Secti o n 8. 6. 2 f or 
details.
Ma n dat or y or 
o pti o nal de n o v o 
X
B
( X)
( x) = O pti o nal
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 6
T a ble 6 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 6
Scree ni n g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 
hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
2 4 hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 3 hr
± 2 4 
hr
pre -d ose a n d 
paire d o n -
treat me nt bi o ps y
Ma n dat or y f or 5 
partici pa nts i n Part 2 A a n d 
Part 2 C eac h, a n d f or 5 
H R + H E R 2 - Br Ca a n d 5 
T N B C partici pa nts i n Part 
2 B. 
O pti o nal f or t he rest of t he 
partici pa nts. 
E O T sa m ple is o pti o nal 
f or all partici pa nts
See Secti o n 8. 6. 2 .
Plas ma sa m ple f or 
cell free D N A 
a nal ysis
A
X
Refer t o Secti o n 8. 6. 3 .
A 1 0 m L -bl o o d s peci me n 
o pti mize d f or plas ma 
pre parati o n will be 
c ollecte d. 
Bl o o d f or 
ger mli ne 
s u btracti o n
A
2 m L w h ole bl o o d sa m ple 
will be c ollecte d a n d 
se q ue nce d al o n g wit h 
t u m or sa m ples e na bli n g 
s u btracti o n of ger mli ne 
variati o ns fr o m s o matic 
m utati o ns.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 7
T a ble 6 .
P K, I m m u n o ge nicit y, P D, Bi o m ar ker, a n d Bi os peci me n Sc he d ule of Assess me nts – Wit h or Wit h o ut Pri mi n g
Visit I de ntifier
A b bre vi ati o ns 
use d i n t his t a ble 
m a y be f o u n d i n 
A p pe n di x 1 6
Scree ni n g
C Y C L E 1 - A
C Y C L E 2 - B
C Y C L E 3 - C
C Y C L E ≥4 - D
E O T
N otes
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
2 2
H o urs
Bef ore/ After 
D ose
Pre 
( 0)
1 hr
4 hr
8 
hr
2 4 
hr
1 6 8 
hr
Pre 
( 0)
4 hr
8 
hr
2 4 hr
1 6 8 
hr
Pr e -d ose sa m ples: h o urs 
bef ore t he i m me diate d ose
P ost -d ose sa m ples: h o urs 
after t he m ost rece nt 
sc he d ule d d ose
Visit Wi n d o w
-6 hr
+ 1 0 
mi n
± 3 0 
mi n
± 1 
hr
± 3 
hr
± 2 4 
hr
-6 
hr
± 3 0 
mi n
± 1 
hr
± 3 hr
± 2 4 
hr
Retai ne d Researc h 
Sa m ple f or 
Ge netics [ Pre p 
D 1]
A
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 
will be c ollecte d. See 
L a b orat or y M a n ual -
Retai ne d Researc h Sa m ple 
c ollecti o n.
Pre p D 1 Retai ne d 
Researc h Sa m ples f or 
Ge netics: 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. 
See Secti o n 8. 5. 2 f or 
a d diti o nal i nf or mati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 8
2. I N T R O D U C TI O N
T his is a P hase 1, d ose escalati o n a n d e x pa nsi o n st u d y  t o e val uate t he safety, t olera bilit y , P K, 
P D , a n d a ntit u m or acti vit y of P F-0 7 2 6 0 4 3 7 , a B 7-H 4 x C D 3 bi -s pecific m A b, i n partici pa nts 
a ge d ≥1 8 y ears of a ge wit h a d va nce d or metastatic Br Ca , O v Ca or e n d o metrial ca ncer. A d ult 
partici pa nts wit h ot her a d va nce d or metastatic hi g h B 7 -H 4 e x pressi n g t u m ors ma y  be 
c o nsi dere d after disc ussi o n wit h a n d a p pr o val fr o m s p o ns or.
B 7 - H 4, a me m ber of t he B 7 fa mil y of pr otei ns e nc o de d b y ge ne 
, has bee n s h o w n t o 
ha ve wi de e x pressi o n i n Br Ca al o n g wit h ot her g y nec ol o gic mali g na ncies ( o varia n, 
e n d o metrial). I n a d diti o n, its li mite d e x pressi o n i n n or mal tiss ues ma kes B 7 -H 4 a n a p peali n g 
t u m or-ass ociate d a nti ge n f or tar geti n g Br Ca s wit h C D 3 bis pecific m olec ules. P F-0 7 2 6 0 4 3 7 is 
a first i n class bis pecific m A b wit h 2 bi n di n g d o mai ns: a d o mai n t hat rec o g nizes t u m or 
a nti ge n B 7-H 4 wit h hi g h affi nit y , a n o vel tar get i n breast, O v Ca a n d uteri ne ca ncer, a n d a 
d o mai n t hat rec o g nizes  
, e x presse d o n T-cells, wit h m o derate affi nit y . Bis pecific 
a nti b o dies are a ble t o si m ulta ne o usl y  bi n d t o C D 3 a n d t he t u m or a nti ge n, t here b y i nitiati n g a 
M H C -i n de pe n de nt c yt ot o xic res p o nse t o war ds t he b o u n d t u m or cell. B y directly tar geti n g 
c yt ot o xic T-cells t o t u m ors, bis pecific a nti b o dies offer a n o vel i m m u n ot hera pe utic a p pr oac h 
f or ca ncer a n d is c urre ntl y bei n g i n vesti gate d i n partici pa nts wit h a d va nce d or metastatic 
Br Ca, O v Ca a n d e n d o metrial ca ncer.
2. 1. St u d y R ati o n ale 
P F -0 7 2 6 0 4 3 7 is a T cell re directi n g B 7 -H 4 x C D 3 bis pecific m A b wit h 2 bi n di n g d o mai ns: a 
d o mai n t hat rec o g nizes t u m or a nti ge n B 7 -H 4 wit h hi g h affi nit y  a n d a d o mai n t hat rec o g nizes 
, e x presse d o n T cells, wit h m o derate affi nit y. C o-e n ga ge me nt of B 7- H 4 o n t u m or cells 
a n d 
o n T cells lea ds t o a t u m or -l ocalize d T-cell c yt ot o xic res p o nse a n d re d uces 
s yste mic 
tar geti n g a n d t o xicit y. T his mec ha nis m circ u m ve nts t he nee d f or T cells t o 
rec o g nize 
ific a nti ge nic pe pti des i n t he c o nte xt of 
 o n mali g na nt cells. 
C y tot o xicit y  is me diate d b y release a n d tra nsfer of 
 fr o m t he T cell t o t he B 7-H 4 
e x pressi n g tar get cell. P F - 0 7 2 6 0 4 3 7 a d dresses a si g nifica nt u n met me dical nee d f or Br Ca, as 
its tar get is e x presse d i n t he maj orit y of Br Ca s acr oss all m olec ular s u bt ypes.
Precli nicall y P F -0 7 2 6 0 4 3 7 de m o nstrate d B 7 -H 4 e x pressi o n -de pe n de nt a ntit u m or acti vit y 
a gai nst a pa nel of cell li ne xe n o graft a n d patie nt deri ve d xe n o graft breast t u m ors gr o w n i n 
i m m u ne-c o m pr o mise d mice t hat were i m pla nte d wit h h u ma n T cells.
T he p ur p os e of t his FI H st u d y is t o e val uate t he safety, t olera bilit y , P K, P D , a n d p ote ntial 
cli nical acti vit y of escalati n g d oses of P F-0 7 2 6 0 4 3 7 i n a d va nce d or metastatic s oli d t u m ors 
i ncl u di n g B r Ca, O v Ca a n d e n d o metrial ca ncer.
I n Part 1 of t his cli nical st u d y, P F-0 7 2 6 0 4 3 7 will be e val uate d f or t he treat me nt of a d ult 
partici pa nts wit h a d va nce d or metastatic Br Ca, O v Ca or e n d o metrial ca ncer f or w h o m n o 
sta n dar d t hera py is a vaila ble wit h n o bi o mar ker selecti o n. A d ult partici pa nts wit h ot her 
a d va nce d or metastatic hi gh B 7 -H 4 e x pressi n g t u m ors ma y  be c o nsi dere d after disc ussi o n 
wit h a n d a p pr o val fr o m t he sp o ns or.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI
C CI
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 6 9
T he maj or o bjecti ves are t o e val u ate safety, t olera bilit y  P K a n d P D a n d t o i de ntif y R D E , see 
Secti o n 4. 3. 9 . 
I n Part 2 d ose e x pa nsi o n p hase of t he st u dy, P F - 0 7 2 6 0 4 3 7 will be f urt her e val uate d i n 
partici pa nts wit h a d va nce d or metastatic H R + H E R 2- Br Ca ( Part 2 A) a n d T N B C ( P art 2 C) 
wit h hi g h B 7 - H 4 e x pressi o n t o assess early si g ns of cli nical efficac y . I n a d diti o n, a c o h ort of 
2 0 partici pa nts wit h a d va nce d or metastatic H R + H E R 2- Br Ca a n d T N B C n ot pre selecte d f or 
B 7 -H 4 e x pressi o n will be i ncl u de d i n Part 2 B t o f urt her e x pl ore bi o mar ker c ha n ges i n t u m or 
micr oe n vir o n me nt a n d vali date t he M o A . 
De n o v o paire d pre - a n d o n-treat me nt bi o psies are ma n dat or y f or 5 partici pa nts i n Part 2 A 
a n d Part 2 C eac h, a n d f or 5 H R + H E R 2 - Br Ca a n d 5 T N B C partici pa nts eac h i n Part 2 B. If 
si g nifica nt TI L i nfiltrates are o bser ve d d uri n g P F -0 7 2 6 0 4 3 7 treat me nt c o nsiste nt wit h t he 
precli nical M o A, t his c o ul d j ustif y  f urt her cli nical de vel o p me nt i n c o m bi nati o n wit h 
e n d ocri ne t hera p y a n d/ or C D K 4/ 6 i n hi bit ors i n a d va nce d or metastatic H R + H E R 2- Br Ca as 
well a s i n c o m bi nati o n wit h i m m u ne c hec k p oi nt i n hi bit ors i n T N B C .
2. 2. B ac k gr o u n d 
B 7 -H 4 is a n o vel m olec ular tar get t hat o vere x presse d i n breast, o varia n, e n d o metrial a n d a 
si g nifica nt perce nta ge of ot her s oli d t u m ors. Des pite t he a d va nce me nt of c he m ot hera p y, 
h or m o nal t hera pies, tar gete d t hera pies a n d i m m u n ot hera pies, metastatic s oli d t u m ors ha ve 
hi g h u n met me dical nee d. Effecti ve t hera p ies are nee de d t o i m pr o ve patie nt o utc o mes. 
P F - 0 7 2 6 0 4 3 7 is a first i n class C D 3 bis pecific m A b tar geti n g B 7- H 4. Precli nical researc h has 
de m o nstrate d p ote nt m o n ot hera p y a ntit u m or acti vi ties i n m ulti ple i n vi v o a ni mal m o dels a n d 
g o o d t hera pe utic i n de x, w hic h j ustifies f urt her cli nical de vel o p me nt.
2. 2. 1. N o ncli nic al P h ar m ac ol o g y
P F -0 7 2 6 0 4 3 7 is a 
 m olec ule c o m prise d of 2 rec o m bi na nt h u ma nize d I g G 
c hai ns, o ne a gai nst B 7-H 4 a n d t he ot her a gai nst C D 3  
 ( B 7- H 4 x C D 3 bis pecific), wit h 
. P F‑ 0 7 2 6 0 4 3 7 de m o nstrate d bi n di n g t o a pa nel of 
t u m or cell li nes t hat e x press B 7-H 4 pr otei n a n d h u ma n T l y m p h oc y tes t hat e x press C D 3. T he 
bis pecific m olec ule e x hi bite d c o nce ntrati o n -de pe n de nt bi n di n g acr oss a pa nel of ca ncer cell 
li nes wit h var yi n g le vels of e n d o ge n o us B 7-H 4 e x pressi o n, as well as c o nce ntrati o n -
de pe n de nt bi n di n g o n a pa nel of h u ma n d o n or T cells. I n t he prese nce of T cells, 
P F ‑ 0 7 2 6 0 4 3 7 elicite d C T L res p o nses a gai nst a pa nel of ca ncer cell li nes e x pressi n g B 7-H 4. 
I n t he a bse nce of T cells P F‑ 0 7 2 6 0 4 3 7 di d n ot affect t u m or cell gr o wt h. I n vi v o, 
P F ‑ 0 7 2 6 0 4 3 7 de m o nstrate d B 7- H 4 e x pressi o n‑ de pe n de nt a ntit u m or acti vit y a gai nst a pa nel 
of cell li ne xe n o graft a n d patie nt deri ve d xe n o graft breast t u m ors gr o w n i n 
i m m u ne‑c o m pr o mised mice t hat were i m pla nte d wit h h u ma n T cells. T u m or gr o wt h 
i n hi biti o n f oll o wi n g P F‑ 0 7 2 6 0 4 3 7 treat me nt was d ose de pe n de nt.
2. 2. 1. 1. I n Vitr o P h ar m ac o d y n a mics
P F -0 7 2 6 0 4 3 7 was s h o w n t o bi n d t o a pa nel of cell li nes e x pressi n g B 7 - H 4
 
 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 0
 
 
 
 
 
 
T he B 7 -H 4 bi n di n g s pecificit y  of P F- 0 7 2 6 0 4 3 7 tra nslate d t o T cell-de pe n de nt i n vitr o 
c yt ot o xic acti vit y. C T L acti vit y was o bser ve d 
 i n cell li nes 
e x pressi n g B 7 -H 4. T he p ote nc y  of P F-0 7 2 6 0 4 3 7 directl y  c orrelate d wit h t he le vel of B 7-H 4 
e x pressi o n o n eac h cell li ne. N o C T L acti vit y  was o bser ve d i n a B 7-H 4 ne gati ve cell li ne. 
A d diti o nall y , C T L acti vit y i n all B 7 - H 4 p ositi ve cell li nes was ass ociate d wit h a c o nc o mita nt 
i ncrease i n c yt o ki nes release d i n s u per nata nts.
P F -0 7 2 6 0 4 3 7 was f urt her c haracterize d i n a cell pr oliferati o n assa y  i n t he a bse nce of T cells 
a n d s h o w n n ot t o affect cell gr o wt h i n Br Ca cell li nes of H R + H E R 2-, H E R 2 +, a n d T N B C 
m olec ular s u bt y pes.
2. 2. 1. 2. I n Vi v o P h ar m ac o d y n a mics
P F -0 7 2 6 0 4 3 7 de m o nstrate d B 7 - H 4 e x pressi o n- de pe n de nt a ntit u m or efficac y 
 
 
 P F-0 7 2 6 0 4 3 7 s h o we d efficac y  i n m o dels of H R + H E R 2-, H E R 2 +, a n d 
T N B C m olec ular s u bt y pes. Efficac y  o bser ve d wit h P F-0 7 2 6 0 4 3 7 was d ose de pe n de nt. 
P F ‑ 0 7 2 6 0 4 3 7 treat me nt s h o we d a ntit u m or efficac y i n m o dels
 
 
T he efficac y  o bser ve d wit h P F- 0 7 2 6 0 4 3 7 was t he res ult of t he i n d ucti o n of acc u m ulati o n a n d 
acti vati o n of T cells i n B 7 -H 4 e x pressi n g t u m ors. P F -0 7 2 6 0 4 3 7 b o u n d B 7 -H 4 o n t u m or cells 
a n d C D 3 o n T cells, i n d uce d f or mati o n of i m m u ne s y na pse s, a n d res ulte d i n T cell acti vati o n. 
 
 
 T cell acti vati o n, pr oliferati o n, a n d 
recr uit me nt res ulte d i n T- cell acc u m ulati o n i n t he t u m or. Acc u m ulate d T cells , a m o n g ot her 
p ote ntial mec ha nis ms, pr o d uce f u ncti o nal c y t ot o xic m olec ule gra nz yme B t o kill t u m or cells.
2. 2. 2. N o ncli nic al P h ar m ac o ki netics a n d Met a b olis m
After si n gle I V a d mi nistrati o n of P F- 0 7 2 6 0 4 3 7, li near P K was o bser ve d wit h C L  of 
a p pr o xi matel y 0. 3 m L/ h/ k g a n d l o w Vss of 4 7. 9 – 8 6. 2 m L / k g. F oll o wi n g a si n gle S C d ose, 
t he bi oa vaila bilit y was a p pr o xi matel y 7 6 %.
I n t he G LP t o xicit y st u d y, mea n s yste mic e x p os ure i ncrease d wit h i ncreasi n g d ose f oll o wi n g 
S C a d mi nistrati o n. Base d o n mea n A U C 1 6 8 val ues, mi ni m u m acc u m ulati o n ( < 2 x) occ urre d 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 1
bet wee n Da y s 1 a n d 2 2.  N o c o nsiste nt se x-relate d differe nces i n sys te mic e x p os ure were 
o bs er ve d. T he o verall i nci de nce of A D A i n d ucti o n t o P F -0 7 2 6 0 4 3 7 was a p pr o xi matel y  8 9 % 
acr oss all d ose gr o u ps.
I n h u ma n, t he P K of P F-0 7 2 6 0 4 3 7 is pr ojecte d t o be li near wit h C L a n d V ss val ues of 
0. 2 m L / h/ k g a n d 8 4 m L/ k g, res pecti vely.  T he ter mi nal t ½ is pr ojecte d t o be 1 5 da ys. S C 
bi oa vaila bilit y  of P F-0 7 2 6 0 4 3 7 i n h u ma ns is e x pecte d t o be si milar t o t hat i n m o n ke y s, 
w hic h is a p pr o xi matel y 7 0 %. T he pr ojecte d cli nical d ose of P F -0 7 2 6 0 4 3 7 t hat is e x pecte d t o 
ac hie ve t he mi ni mal C eff is 2 0 0 µ g S C ( Q 2 W).
2. 2. 3. N o ncli nic al S afet y
P F -0 7 2 6 0 4 3 7 was c haracterize d i n t o xicit y  st u dies u p t o 1 m o nt h i n d urati o n i n c y n o m ol g us 
m o n ke y s (ie, t he o nly p har mac ol o gicall y rele va nt s pecies). T he hi g hest d oses teste d i n t he 
1 -m o nt h st u d y  ( 0. 3 m g / k g/ wee k S C a n d 0. 1 m g/ k g/ wee k I V) are t he H N S T Ds a n d N O A E Ls. 
A m ore c o nser vati ve M A B E L a p pr oac h was use d i nstea d of t he 1/ 6 H N S T D calc ulati o n t o 
select t he cli nical starti n g d ose. F or m ore i nf or mati o n a b o ut t he cli nical starti n g d ose, see 
Secti o n 4. 3. 1 .
Ba se d o n t he n o ncli nical t o xicit y st u dies, t he or ga ns of p ote ntial cli nical i m p orta nce are t he 
i m m u ne s yste m a n d pa ncreas. T he ke y fi n di n gs were i m m u ne-me diate d effects fr o m t he 
pri mar y  p har mac ol o g y of P F-0 7 2 6 0 4 3 7 (ie, c y t o ki ne i n d ucti o n a n d T cell acti vati o n). 
C R S -li ke cli nical o bser vati o ns i ncl u de d e mesis, h y p oacti vit y, a n d re d uce d a p petite. Mil d t o 
m o derate i ncreases of circ ulati n g c y t o ki nes were m ostl y o bser ve d after t he first d ose, 
t ypicall y pea ke d b y 7 h o urs, a n d ret ur ne d t o baseli ne val ues wit hi n 4 8 h o urs. I m m u ne -relate d 
t o xicities (e g, m o n o n uclear cell i nfiltrati o n, vac u olati o n, a n d de ge nerati o n) i n tiss ues wit h 
B 7 -H 4 e x pressi o n were t y picall y  mi ni mal t o mil d i n se verit y a n d f ully or partiall y res ol ve d 
after a rec o ver y peri o d. T here were n o fi n di n gs i n t he pa ncreas; h o we ver, e x pressi o n of 
B 7 -H 4 i n h u ma n pa ncreas ma y  res ult i n i nfla m mati o n n ot o bser ve d i n c yn o m ol g us m o n ke y s 
d ue t o lac k of e x pressi o n of B 7 -H 4 i n t he latter. Gi ve n t his, t he pa ncreas has bee n i ncl u de d as 
a p ote ntial tar get or ga n.
O verall, t he n o ncli nical t o xicit y  of P F-0 7 2 6 0 4 3 7 ca use d p har mac ol o g y -base d, 
e x p os ure -res p o nsi ve fi n di n gs e x pecte d t o be re versi ble a n d cli nicall y m o nit ora ble.
M ore details of t he n o ncli nical safet y pr o gra m are pr o vi de d i n t he I B.
2. 2. 4. Cli nic al O ver vie w 
T his is a first i n h u ma n st u d y  a n d n o cli nical data are a vaila ble.
2. 2. 5. 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 S F D A’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 y m p h o blastic le u ke mia (S olit et al, 2 0 0 6 ). 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 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. 
C T L s c o n ve nti o nall y rec o g nize cell pr otei n a nti ge ns prese nte d i n c o m ple x wit h M H C Class I 
m olec ules o n t he cell s urface via t heir T C Rs . 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. C y t ot o xicit y is me diate d b y release a n d tra nsfer of 
 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 2 6 0 4 3 7 
re directs T cells t o tar get B 7-H 4 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 B 7-H 4 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 og nize t u m ors a n d act as effect or cells.
2. 3. Be nefit/ Ris k Assess me nt
F or t his st u d y , t he i n vesti gati o nal pr o d uct is P F-0 7 2 6 0 4 3 7. 
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 Br Ca or ot her s oli d t u m ors . C urre ntl y  a vaila ble t hera pies ha ve 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 . N o h u ma n st u dies ha ve 
bee n c o n d ucte d t o date e val uati n g P F- 0 7 2 6 0 4 3 7. I n precli nical p har mac ol o g y  st u dies wit h 
P F -0 7 2 6 0 4 3 7, B 7 -H 4 e x pressi o n- de pe n de nt a ntit u m or efficac y was ob ser ve d 
 
 P F-0 7 2 6 0 4 3 7 s h o we d efficac y  i n 
m o dels of H R + H E R 2 -, H E R 2 +, a n d T N B C m olec ular s u bty pes.
T he safet y of P F -0 7 2 6 0 4 3 7 has bee n c haracterize d i n t o xicit y st u dies u p t o 1 m o nt h i n 
d urati o n i n c y n o m ol g us m o n ke y s (ie, t he o nly p har mac ol o gicall y rele va nt s pecies). 
T he hi g hest d oses teste d i n t he 1 -m o nt h st u d y  ( 0. 3 m g/ k g/ wee k S C a n d 0. 1 m g/ k g/ wee k I V) 
are t he H N S T Ds a n d N O A E Ls. A m ore c o nser vati ve M AB E L a p pr oac h was use d i nstea d of 
t he 1/ 6 H N S T D calc ulati o n t o select t he cli nical starti n g d ose.
It is a ntici pate d t hat C R S a n d ir A Es ma y occ ur i n t he cli nical st u d y p ote ntiall y at hi g her 
d oses. Cl ose me dical m o nit ori n g, i ncl u di n g a sta g gere d e nr oll me nt st rate g y will be a p plie d 
f or partici pa nts e nteri n g Part 1 at d ose le vel 1.  Eac h partici pa nt d ose d will be o bser ve d
i n patie nt f or at least 4 8 h o urs 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 2 6 0 4 3 7 S C 
d ose will be re q uire d, al o n g wit h safet y assess me nts t hr o u g h o ut t he st u d y. If n o safet y 
c o ncer ns arise d uri n g t his 4 8 -h o ur peri o d, t he n a n a d diti o nal partici pa nt ma y  be e nr olle d at 
d ose le vel 1.  S u p p orti ve care meas ures as descri be d i n Secti o n 6. 8. 2 are a vaila ble t hat ma y 
be c o nsi dere d i n t he ma na ge me nt of C R S a n d ir A Es (Be ns o n et al, 2 0 0 4 ; Lee et al, 2 0 1 4 ; Lee 
et al, 2 0 1 9).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 3
At t his sta ge of de vel o p me nt, t he a ntici pate d be nefit -ris k f or P F- 0 7 2 6 0 4 3 7 is c o nsi dere d 
acce pta ble i n patie nts wit h a d va nce d or metastatic Br Ca or ot her s oli d t u m ors w h o d o n ot 
ha ve access t o c urati ve treat me nt o pti o ns. 
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 2 6 0 4 3 7 ma y  be f o u n d i n t he I B, w hic h is t he S R S D f or t his st u d y.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 4
2. 3. 1. Ris k Assess me nt
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale
f or Ris k
Miti g ati o n Str ate g y
St u d y I nter ve nti o n(s) P F - 0 7 2 6 0 4 3 7
C R S ( o n -tar get off-t u mor 
effect)
T he p ote ntial ris ks are base d o n 
pre -cli nical t o xic ol o g y data f or 
P F - 0 7 2 6 0 4 3 7
A sta g gere d e nr oll me nt strate g y will be a p plie d f or partici pa nts e nteri n g 
Part 1 at d ose le vel 1.
All Part 1 partici pa nts, re gar dless of d ose le vel, will be h os pitalize d f or at 
least 2 4-4 8 h o urs o n C 1 D 1 a n d 8 -2 4 h o urs o n C 1 D 1 5 t o cl osel y m o nit or
a n d ma na ge ac ute t o xicities. See S O A a n d Secti o n 4. 1 .
Partici pa nts w h o e x perie nce Gra de ≥3 i nf usi o n -relate d A E (I V 
a d mi nistrati o n) or cli nicall y si g nifica nt C R S m ust be h os pitalize d f or at 
least 2 4 h o urs f or at least 4 s u bse q ue nt d oses  (t w o c ycles).  See S O A a n d 
Secti o n 4. 1 .
A pri mi n g d ose a p pr oac h i n t he ne xt d ose le vel ma y be i nitiate d if a d ose 
le vel i n d uces ≥Gra de 2 C R S (lasti n g f or > 2 4 h o urs) occ urs i n 
> 1 partici pa nt des pite S O C. See S O A a n d Secti o n 4. 1 .
M A B E L starti n g d ose wit h str o n g c o nfi de nce i n hi g h e x pressi o n i n 
t u m ors vs n or mal tiss ues.
Fre q ue nt safet y la b tests, cl osel y m o nit or f or A Es a n d ma na ge A Es per 
pr ot oc ol/cli nical g ui da nce.
Pre me dicati o n will be c o nsi dere d base d o n safet y pr ofile.
B 7 -H 4 e x pressi o n i n n or mal 
h u ma n tiss ues (ie, ki d ne y)
B 7 -H 4 e x pressi o n i n n or mal 
h u ma n tiss ues 
Fre q ue nt cli nical la b orat or y assess me nts i ncl u di n g he mat ol o g y (c o m plete 
bl o o d c o u nts a n d differe ntials), c oa g ulati o n, a n d cli nical c he mistr y. See 
S O A .
A Es will be m o nit ore d o n a n o n g oi n g basis.
P F -0 7 2 6 0 4 3 7 d oses ma y be i nterr u pte d o r re d uce d base d o n t o xicities 
o bser ve d.
Effecti ve c o ntrace pti o n met h o ds will be use d i n all partici pa nts 
Pa ncreatitis ( base d o n B 7 -H 4 
e x pressi n g i n h u ma n Pa ncreas, 
li ke ot her B 7-H 4 p ositi ve
healt h tiss ues/ or ga ns)
R o uti ne a m ylase a n d li pase m o nit ori n g. S u p p orti n g i ma gi n g (a b d o mi nal 
ultras o u n d, C T/ M RI) will be c o n d ucte d t o c o nfir m t he dia g n osis of ac ute 
pa ncreatitis. D ose m o dificati o ns a n d disc o nti n uati o n criteria are 
i nc or p orate d i n t he pr ot oc ol.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 5
P ote nti al Ris k of Cli nic al 
Si g nific a nce
S u m m ar y of D at a/ R ati o n ale
f or Ris k
Miti g ati o n Str ate g y
I m m u ne-relate d t o xicit y
Caref ul m o nit ori n g of p ote ntial i m m u ne relate d t o xicit y. G ui deli nes o n 
t he ma na ge me nt of ir A Es are pr o vi de d i n A p pe n di x 3 , Secti o n 1 0. 3. 5 .
Pre m e dicati o n will be c o nsi dere d base d o n safet y pr ofile. 
St u d y Pr oce d ures
De n o v o (fres h) t u m or bi o ps y
Blee di n g, s welli n g, scarri n g, 
s ore ness, or br uisi n g, ner ve 
da ma ge, infecti o n of w o u n d, 
c o nta mi nati o n of ca ncer cells t o 
u naffecte d tiss ue.
L ocal a nest hetic will be a d mi nistere d.
Sterile tec h ni q ues will be use d.
Pr oce d ures will be perf or me d b y q ualifie d me dical practiti o ners.
Partici pa nts s h o ul d n ot be s u bjecte d t o a si g nifica nt ris k pr oce d ure t o 
o btai n t he bi o psies (ie, t he a bs ol ute ris k of m ortalit y or maj or m or b i dit y 
i n t he partici pa nt’s cli nical setti n g a n d at t he i nstit uti o n c o m pleti n g t he 
pr oce d ure s h o ul d be < 2 %).
S C I S R.
I S Rs will be m o nit ore d at eac h i njecti o n.
C T or M RI pr oce d ures f or 
t u m or assess me nts
I ncrease d ra diati o n e x p os ure 
( C T sca ns) 
C o ntrast a ge nt aller g y
W orse ni n g of ki d ne y f u ncti o n. 
( C T sca ns)  
Partici pa nts i n t his st u d y will 
ha ve m ore fre q ue nt (e ver y 8 
wee ks) C T/ M RI sca ns t ha n per 
S O C (e ver y 1 2 wee ks) f or t he 
first 6 m o nt hs of t he st u d y f or a 
t otal of 1 a d diti o nal sca n 
assess me nt . 
O nl y e x perie nce d pr ofessi o nals will c o n d uct t he C T or M RI pr oce d ures . 
T he partici pa nt will be as ke d a b o ut aller gies t o t he c o ntrast d ye . 
Me dical hist or y will be re vie we d f or ki d ne y disease, a n d i nf or mati o n will 
be pr o vi de d t o mi ni mize de h y drati o n . 
C O VI D - 1 9 
P artici pa nts ma y ha ve 
i ncrease d ris k of S A R S-C o V - 2 
i nfecti o n b y u n der g oi n g a st u d y 
pr oce d ure at a st u d y facilit y
I ncl usi o n of C O VI D-1 9 s pecific preca uti o ns ( See A p pe n di x 8 ).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 6
2. 3. 2. Be nefit Assess me nt
T his is a FI H st u d y t o e val uate P F - 0 7 2 6 0 4 3 7. T he st u d y  i nter ve nti o n s h o ul d be use d wit h 
a p pr o priate ca uti o n t y pical f or a n i n vesti gati o nal dr u g . Partici pa nt be nefits i ncl u de 
c o ntri b uti n g t o t he pr ocess of de vel o pi n g ne w t hera pies i n o nc ol o g y  areas of u n met nee d, 
recei vi n g st u d y i nter ve nti o n t hat ma y ha ve cli nical utilit y, a n d recei vi n g me dical e val uati o ns 
a n d assess me nts ass ociate d wit h t he st u d y  pr oce d ures.
2. 3. 3. O ver all Be nefit/ Ris k C o ncl usi o n
Precli nicall y , P F-0 7 2 6 0 4 3 7 has de m o nstrate d B 7 - H 4 e x pressi o n- de pe n de nt a ntit u m or
efficac y 
. 
P F -0 7 2 6 0 4 3 7 s h o we d efficac y  i n m o dels of H R + H E R 2-, H E R 2 +, a n d T N B C m olec ular 
s u bt ypes. Efficac y  o bser ve d wit h P F-0 7 2 6 0 4 3 7 was d ose de pe n de nt. T he efficac y  o bser ve d 
wit h P F -0 7 2 6 0 4 3 7 was t he res ult of t he i n d ucti o n of acc u m ulati o n a n d acti vati o n of T cells i n 
B 7 -H 4 e x pressi n g t u m ors. P F -0 7 2 6 0 4 3 7 has dis pla y e d a t olera ble safet y pr ofile a n d 
pr o misi n g t hera pe utic i n de x.
Ta ki n g i nt o acc o u nt t he meas ures ta ke n t o mi ni mize ris k t o st u d y partici pa nts, t he p ote ntial 
ris ks i de ntifie d i n ass ociati o n wit h P F- 0 7 2 6 0 4 3 7 are j ustifie d b y t he a ntici pate d be nefits t hat 
ma y  be aff or de d t o partici pa nts wit h a d va nce d or metastatic B 7-H 4 e x pressi n g s oli d t u m ors 
i ncl u di n g H R + H E R 2- Br Ca, H R + H E R 2 + Br Ca, T N B C, O v Ca , a n d e n d o metrial ca ncer.
3. O B J E C TI V E S, E N D P OI N T S, A N D E S TI M A N D S
D ose Esc al ati o n ( P art 1):
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y

T o assess safet y a n d t olera bilit y 
at i ncreasi n g d ose le vels of 
P F -0 7 2 6 0 4 3 7 i n s uccessi ve 
c o h orts of partici pa nts wit h 
l ocall y a d va nce d or metastatic 
Br Ca, O v Ca or e n d o metrial 
ca ncer.

T o esti mate t he M T D  a n d t o 
select R D E .

Occ urre nce of D L Ts
(Secti o n 4. 3. 6 ).

A E s 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 or C R S 
gra di n g s yste m) 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 maliti es as 
c haracterize d b y t y pe, 
fre q ue nc y, se verit y ( gra de d b y 
N CI C T C A E v 5), a n d ti mi n g.

D L T rate esti mate d 
base d o n data fr o m 
D L T -e val ua ble 
partici pa nts d uri n g t he 
D L T e val uati o n peri o d.

I nci de nce of A Es 
esti mate d i n t he safet y 
a nal ysis p o p ulati o n 
d uri n g t h e A E 
e val uati o n peri o d.
Sec o n d ar y 

T o assess i m m u ne relate d safet y 
a n d t olera bilit y at i ncreasi n g 
d ose le vels of P F -0 7 2 6 0 4 3 7  i n 
s uccessi ve c o h orts of 
partici pa nts wit h l ocall y 

ir 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 N CI C T C A E v 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. 

N/ A
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 7
O bjecti ves
E n d p oi nts
Esti m a n ds
a d va nce d or metastatic  Br Ca, 
O v Ca or e n d o metrial ca ncer.

T o e val uate t he si n gle a n d 
m ulti ple d ose P K of 
P F -0 7 2 6 0 4 3 7 as m o n ot hera p y. 

P har m ac o ki netic para meters of 
P F -0 7 2 6 0 4 3 7 as m o n ot hera p y: 
S D C ma x , Tma x , A U Clast, a n d as 
data per mit, t ½, A U C i nf, C L/ F, 
a n d V z/ F. 
M D (ass u mi n g stea d y state is 
ac hie ve d) C ma x,ss, Tma x,ss , Cmi n,ss , 
A U C ss,τ, a n d as data per mit, 
C L ss/ F, Vz/ F, a n d Rac
( A U Css,τ/ A U Cs d,τ ).

N/ A

T o e val uate i m m u n o ge nicit y of 
P F -0 7 2 6 0 4 3 7.

I nci de nce a n d titers of A D A a n d 
N A b a gai nst P F -0 7 2 6 0 4 3 7.

N/ A

Tertiar y/ E x pl orat or y

T o e val uate preli mi nar y 
a ntit u m or acti vit y of P F-
0 7 2 6 0 4 3 7 i n partici pa nts wit h 
l ocall y a d va nce d or metastatic 
Br Ca,  O v Ca or e n d o metrial 
ca ncer

O R R, as assesse d b y 
i n vesti gat or base d o n 
R E CI S T v 1. 1 a n d ir R E CI S T.

D O R as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

N/ A 

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.

C ha n ges i n pre - a n d o n -
treat me nt c yt o ki ne a n d 
c he m o ki ne mar kers i n ser u m 
sa m ples.

N/ A

T o e val uate T, B, a n d 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 a n d 
acti vati o n mar kers i n w h ole 
bl o o d .

C ha n ges i n s u bt y pes of i m m u ne 
cell, acti vati o n, a n d pr oliferati o n 
mar kers o n T cells.

N/ A

T o e x pl ore a d diti o nal 
bi o mar kers i n t u m or bi o psies, 
w h ole bl o o d, a n d ser u m sa m ples 
t o 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.

Bi o mar kers fr o m ge n o mic, 
tra nscri pt o mic, a n d/ or pr otei n 
pr ofili n g fr o m t u m or, bl o o d, 
ser u m or plas ma a n d t heir 
relati o ns hi p t o cli nical o utc o me.

N/ A

T o e val uate t he effect of 
P F -0 7 2 6 0 4 3 7 o n s ol u ble B 7 -H 4.

Pre - a n d p ost-d ose le vels of 
s ol u ble B 7-H 4 i n ser u m.

N/ A
D ose E x p a nsi o n ( P art 2)
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y

T o assess safet y a n d t olera bilit y of 
P F -0 7 2 6 0 4 3 7 at t he R D E i n 

A E s as c haracterize d b y t y pe, 
fre q ue nc y, se verit y (as gra de d b y 

I nci de nce of A Es 
esti mate d i n t he 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 8
O bjecti ves
E n d p oi nts
Esti m a n ds
partici pa nts wit h a d va nce d or 
metastatic H R + H E R 2 - Br Ca a n d 
T N B C w it h hi g h B 7-H 4 e x pressi o n 
or wit h o ut bi o mar ker selecti o n. 
N CI C T C A E v 5 or C R S gra di n g 
s yste m) 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 ( gra de d b y N CI C T C A E 
v 5), a n d ti mi n g.
safet y a nal ysis 
p o p ulati o n d uri n g 
t he A E-e val uati o n 
peri o d.
Sec o n d ar y 

T o assess ir A Es of P F -0 7 2 6 0 4 3 7 at 
t he R D E i n partici pa nts wit h 
a d va nce d or metastatic H R + 
H E R 2- Br Ca a n d T N B C w it h hi g h 
B 7 -H 4 e x pressi o n or wit h o ut 
bi o mar ker selecti o n.

ir 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 
N CI C T C A E v 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. 

N/ A

T o e val uate preli mi nar y a ntit u m or
acti vit y of P F -0 7 2 6 0 4 3 7 at t he 
R D E i n partici pa nts wit h a d va nce d 
or metastatic H R + H E R 2 - Br Ca 
a n d T N B C wit h hi g h B 7 -H 4 
e x pressi o n or n o bi o mar ker 
selecti o n.

O R R, as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

D O R as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

P F S as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

T T P as assesse d b y i n vesti gat or 
base d o n R E CI S T v 1. 1 a n d 
ir R E CI S T.

O S.

N/ A

T o f urt her e val uate t he ser u m P K 
of P F -0 7 2 6 0 4 3 7 at R D E .

P K c o nce ntrati o n of P F -0 7 2 6 0 4 3 7 
at selecte d ti me p oi nts. 

N/ A

T o f urt her e val uate 
i m m u n o ge nicit y of P F-0 7 2 6 0 4 3 7.

I nci de nce a n d titers of A D A a n d 
N A b a gai nst P F -0 7 2 6 0 4 3 7.

N/ A

T o e val uate i m m u ne cells i n pre 
a n d/ or p ost treat me nt t u m or 
bi o psies.

P he n ot y pes, a n d q ua ntit y of TI L
bef ore a n d after P F -0 7 2 6 0 4 3 7 
treat me nt (e g, C D 3, C D 8, 
Gra nz y me B, Ki 6 7 I H C) .

N/ A
Terti ar y/ E x pl or at or y

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.

C ha n ges i n pre - a n d o n -treat me nt 
c yt o ki ne a n d c he m o ki ne mar kers i n 
ser u m sa m ple.

N/ A

T o e val uate T, B, a n d 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 a n d 
acti vati o n mar kers i n w h ole bl o o d .

C ha n ges i n s u bt y pes of i m m u ne 
cell, acti vati o n, a n d pr oliferati o n 
mar kers o n T cells. 

N/ A

T o e x pl ore a d diti o nal bi o mar kers i n 
t u m or bi o psies, w h ole bl o o d, a n d 
ser u m sa m ples t o 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 .

Bi o mar kers fr o m ge n o mic, 
tra nscri pt o mic, a n d/ or pr otei n 
pr ofili n g fr o m t u m or, bl o o d, ser u m 
or plas ma a n d t heir relati o ns hi p t o 
cli nical o utc o me.

N/ A

T o e val uate t he effect of 
P F -0 7 2 6 0 4 3 7 o n s ol u ble B 7 -H 4.

Pre - a n d p ost-d ose le vels of s ol u ble 
B 7 -H 4 i n ser u m.

N/ A
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 7 9
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a n o pe n la bel, m ulti- ce nter, first-i n-h u ma n P hase 1 d ose escalati o n a n d d ose 
e x pa nsi o n st u d y t o e val uate t he safety, t olera bilit y, P K, P D , a n d preli mi nar y  a ntit u m or 
acti vit y of P F - 0 7 2 6 0 4 3 7, a B 7- H 4 x C D 3 bis pecific m A b, i n a d va nce d or metastatic selecte d 
s oli d t u m ors (Br Ca, O v Ca , a n d e n d o metrial ca ncer). T his st u d y  c o ntai ns 2 parts, d ose 
escalati o n ( Part 1) a n d d ose e x pa nsi o n ( Part 2). T he o verall st u d y  desi g n is de picte d i n t he 
Sc he ma . 
Part 1 c o ntai ns d ose escalati o n i n partici pa nts wit h l ocall y  a d va nce d or metastatic Br Ca,
O v Ca or e n d o metrial ca ncer t hat is resista nt or i nt olera nt t o sta n dar d t hera p y  or f or w h o m n o 
sta n dar d t hera py is a vaila ble, t o deter mi ne t he M T D
a n d select t he R D E . Partici pa nts wit h 
ot her a d va nce d or metastatic hi g h B 7 -H 4 e x pressi n g t u m ors ma y  be c o nsi dere d after 
disc ussi o n wit h a n d a p pr o val fr o m s p o ns or. 
Partici pa nts will recei ve escalati n g d oses of P F- 0 7 2 6 0 4 3 7 a d mi nistere d as S C i njecti o n wit h 
a starti n g d ose le vel of 1 0 0 µ g Q 2 W as m o n ot hera p y . Ad diti o nal d osi n g fre q ue nc y  s uc h as 
Q 1 W or Q 3 W ma y  be c o nsi dere d if s u p p orte d b y e mer gi n g cli nical P K, P D, a n d safet y data. 
B L R M g ui de d b y  E W O C pri nci ple will be use d t o g ui de t he d ose escalati o n pr ocess a n d 
deter mi ne t he M T D/ R D E . T he m a xi m u m all o wa ble P F- 0 7 2 6 0 4 3 7 d ose i ncre me nt is 2 0 0 %
( d ose tri pli n g fr o m t he pre vi o us d ose le vel) f or c o h orts b ut will be a dj uste d t o n o m ore t ha n 
1 0 0 % ( d ose d o u bli n g fr o m t he pre vi o us d ose le vel) 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 cli nicall y  si g nifica nt treat me nt-relate d A Es. F or m o n ot hera p y wit h o ut 
pri mi n g strate g y , D L T will be assesse d d uri n g t he first 2 8 d a y s. F or m o n ot hera p y wit h 
pri mi n g, t he D L T assess me nt peri o d will e xte n d t o i ncl u de pri mi n g d oses pl us 2 f ull d oses 
(e g, first 4 2 da ys). Eac h d ose le vel gr o u p will i ncl u de 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 per c o h ort i n t he first 2 c o h orts a n d at least 2 D L T 
e val ua ble partici pa nts per d ose le vel gr o u p i n t he re mai ni n g c o h orts f or Part 1. Per B L R M 
desi g n, e x p a n di n g a d diti o nal partici pa nts at l o wer d ose le vels are all o we d t o assess safet y. 
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 c o m m o n A E f or bis pecific a nti b o dies. De pe n di n g o n 
e mer gi n g P K a n d safet y data, I V a d mi nistrati o n ma y  be i n vesti gate d d uri n g d ose escalati o n
after t he disc ussi o n bet wee n i n vesti gat ors a n d s p o ns or a n d a p pr o val fr o m sp o ns or.
Base d o n t he M o A
a n d precli nical t o xic ol o g y st u dies, P F- 0 7 2 6 0 4 3 7 has t he p ote ntial t o ca use 
C R S a n d ir A Es . T he f oll o wi n g meas ures will be ta ke n i n or der t o mi ni mize t he ris k i n st u d y 
partici pa nts:

A sta g gere d e nr oll me nt strate g y  will be a p plie d f or partici pa nts e nteri n g Part 1 c o h ort 
1. Eac h partici pa nt d ose d will be o bser ve d f or at least 4 8 h o urs t o e ns ure n o ac ute 
safety c o ncer ns bef ore d osi n g t he ne xt partici pa nt i n c o h ort 1.

Pr o p h y lactic pre me dicati o n is n ot all o we d d uri n g t he D L T e val uati o n peri o d d uri n g 
i nitial d ose escalati o n.   H o we ver, if t he partici pa nt e x perie nces a n i n f usi o n relate d
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 0
reacti o n (IV) , aller gic reacti o n, si g nifica nt i njecti o n site reacti o n, C R S, fe ver/c hills, 
aller gic reacti o n, na usea/ v o miti n g, h y p ote nsi o n, or pai n, a p pr o priate treat me nt s h o ul d 
i nitiate a n d pre me dicati o n as pr o p h yl a xis ma y  be c o nsi dere d f or s u bse q ue nt i njecti o ns 
as well as f or ne w partici pa nts. (See Secti o n 6. 1. 1. 1 ).  

D ose escalati o n c o h orts ma y  be s witc he d fr o m S C a d mi nistrati o n t o IV 
a d mi nistrati o n if S C a d mi nistrati o n is n ot c o nsi dere d as t he preferre d r o ut e d ue t o 
se vere s ki n t o xicities, l o w P K e x p os ure or ot her reas o ns. I V a d mi nistrati o n c o h orts
ma y  i nitiate at a d ose le vel t hat is n o greater t ha n 2 0 % of t he hi g hest S C d ose le vel 
t hat is dee me d t olera ble (e g, starti n g at 6 0 µ g I V Q 2 W if 3 0 0 µ g S C Q 2 W is dee me d 
t olera ble) de pe n di n g o n e mer gi n g P K a n d safet y data.

Pri mi n g D ose: A pri mi n g d ose a p pr oac h i n t he ne xt d ose le vel ma y  be i nitiate d if a 
d ose le vel i n d uces ≥Gra de 2 C R S (lasti n g f or > 2 4 h o urs) occ urs i n > 1 partici pa nt
des pite treat me nt wit h t ociliz u ma b a n d/ or vas o press ors. I nitiall y, a si n gle pri mi n g 
d ose ma y  be a d mi nistere d o n C 1 D 1 at 1 d ose le vel bel o w t he d ose le vel i n w hic h t he
rec urre nt ≥Gra de 2 C R S e ve nt was o bser ve d. T he first f ull d ose will be a d mi nistere d 
o n C 1 D 1 5 wit h a starti n g f ull d ose t hat is n ot hi g her t ha n t he f ull d ose at w hic h t he
rec urre nt > Gra de 2 C R S e ve nt occ urre d. De pe n di n g o n t he o bser ve d safet y a n d 
t olera bilit y pr ofile, d ose escalati o n of t he f ull d ose ma y pr ocee d wit h f ull d ose 
i ncrease d by a ma xi m u m of 2 0 0 %. If ≥Gra de 2 C R S is o bser ve d after t he 
a d mi nistrati o n of f ull d oses, a 2 ( or m ore) ste p-u p pri mi n g d ose a p pr oac h ma y  als o be 
i m ple me nte d (f or e xa m ple, 2 pri mi n g d oses a d mi nistere d o n C 1 D 1 a n d C 1 D 8, 
res pecti vely) ; t he i nitial  pri mi n g d ose will be at a d ose le vel w here pre dicte d 
pr o ba bilit y  of ≥Gra de 2 C R S is < 2 0 %. I n a d diti o n, d ose fi n di n g wit h o ut pri mi n g ma y 
still c o nti n ue i n parallel if M T D wit h o ut pri mi n g has not bee n reac he d a n d R D E
wit h o ut pri mi n g has n ot bee n deter mi ne d. Fi nall y,  a d diti o nal pri mi n g d ose strate gies 
(e g, a d diti o nal d oses, differe nt d osi n g le vels a n d i nter vals) ma y be i n vesti gate d base d 
o n e mer gi n g data. 
All Part 1 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 ( or t he first I V d ose, as a p plica ble) 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 ( or t he sec o n d I V d ose, as 
a p plica ble) o n C 1 D 1 5. Partici pa 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 S C pri mi n g d ose (or t he first I V pri mi n g 
d ose a d mi nistrati o n, as a p plica ble) o n C 1 D 1 a n d 2 4 h o urs after t he sec o n d (f ull) d ose 
o n C 1 D 1 5 (Ta ble 7 ). M o dificati o n of i n patie nt o bser vati o n peri o d mi g ht be all o we d 
base d o n e mer gi n g safet y data a n d will re q uire disc ussi o n a n d a gree me nt bet wee n 
i n vesti gat or a n d s p o ns or.

Partici pa nts w h o e x per ie nce Gra de ≥3 i nf usi o n -relate d a d verse e ve nts (I V 
a d mi nistrati o n) or cli nicall y  si g nifica nt c yt o ki ne release sy n dr o me m ust be 
h os pitalize d f or at least 2 4 h o urs f or at least 4 d oses s u bse q ue ntl y (t w o c ycles). If 
s u bse q ue nt d oses are t olerate d wit h o ut rec urre nce of Gra de ≥3 i nf usi o n -relate d 
a d verse e ve nts or cli nicall y si g nifica nt c yt o ki ne release sy n dr o me, o ut patie nt P F -
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 1
0 7 2 6 0 4 3 7 a d mi nistrati o n d uri n g cli nical visits ma y be res u me d after a gree me nt 
bet wee n i n vesti gat or a n d s p o ns or.

Partici pa nts sh o ul d be o bs er ve d f or at least 1 h o ur p ost d ose f or all o ut patie nt visits 
starti n g wit h C 2 D 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 R S (Ta ble 7 ).

Partici pa nts will u n der g o a tele p h o ne f oll o w-u p at 9 0 da y s (± 7 d a y s) after t he last 
d ose of P F -0 7 2 6 0 4 3 7 t o assess p ote ntial late ir A Es.  If a n y  c o ncer n arises, t he 
partici pa nt s h o ul d be c o ntacte d f or a n i n-pers o n f oll o w -u p visit.
D ose escalati o n will c o nti n ue u ntil M T D
has bee n reac he d (if a n M T D is i de ntifie d) a n d t he 
R D E has bee n deter mi ne d. At t hat ti me, if t he d ose escalati o n has reac he d t he M T D a n d a 
pri mi n g d ose has n ot bee n pre vi o usl y  i nc orp orate d t o t he d ose re gi me n, a p ri mi n g d ose 
escalati o n c o h ort t o mi ni mize C ma x ma y  be i nitiate d base d o n cli nical safety, P K/ P D , a n d 
cli nical efficac y. T he sa me a p pr oac h t o pri mi n g as descri be d a b o ve will be utilize d . Pri mi n g 
d ose escalati o n c o h orts will c o nti n ue u ntil M T D
wit h pri mi n g has bee n reac h e d (if a n M T D 
is i de ntifie d) a n d t he R D E wit h pri mi n g has bee n deter mi ne d. De pe n di n g o n e mer gi n g safet y  
data, a 2 ( or m ore) ste p-u p pri mi n g d ose a p pr oac h ma y  als o be i m ple me nte d as descri be d 
a b o ve.
T he D L T peri o d f or S C or I V d osi n g wit h o ut pri mi n g will be 2 8 da y s. T he D LT peri o d wit h 
pri mi n g will e xte n d t o i ncl u de t he d urati o n of t he pri mi n g d oses a n d 2 f ull d oses after 
pri mi n g . (e g, if a pri mi n g d ose is gi ve n o n Da y 1 a n d t he first f ull d ose o n Da y 1 5, t he t otal 
D L T o bser vati o n peri o d will be 4 2 da y s). A tra diti o nal 2- para meter B L R M will be use d t o 
m o del t he D L T relati o ns hi p t o t he dr u g a n d i nf or m d ose escalati o n wit h or wit h o ut pri m i n g. 
T he ma xi m u m d ose le vel i ncrease will be 2 0 0 % ( d ose tri pli n g fr o m t he pre vi o us d ose le vel).
A p pr o xi matel y  3 5 partici pa nts are e x pecte d t o be e nr olle d i nt o 1 of 5 - 7 se q ue ntial d ose le vels 
i n Part 1 i ncl u di n g at least 6 partici pa nts treate d at t he M T D. 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 2 6 0 4 3 7 a n d t he n u m ber of d ose 
le vels t hat are re q uire d t o deter mi ne M T D/R D E . 
O nce t he P F -0 7 2 6 0 4 3 7 m o n ot hera p y  R D E is selecte d, eit her wit h or wit h o ut pri mi n g, Part 2 
d ose e x pa nsi o n c o h orts ma y  be i nitiate d t o f urt her e val uate t he safet y  a n d preli mi nar y 
a ntit u m or acti vit y of P F -0 7 2 6 0 4 3 7 m o n ot hera p y i n a d va nce d or metastatic 2 L + H R + H E R 2-
Br Ca wit h hi g h B 7 -H 4 e x pressi o n ( Part 2 A) a n d 2 L + T N B C wit h hi g h B 7 - H 4 e x pressi o n 
( Part 2 C) as well as u nselecte d H R + H E R 2 - Br Ca or T N B C ( Part 2 B) . 
A p pr o xi matel y  6 0 partici pa nts are e x pecte d t o be e nr olle d i nt o Part 2. 
T he Part 2 d ose e x pa nsi o n p hase will e nr oll partici pa nts i nt o 3 c o h orts detaile d as f oll o ws: 

P art 2 A ( N = 2 0): P F -0 7 2 6 0 4 3 7 as m o n ot hera p y i n partici pa nts wit h H R + H E R 2 -
Br Ca s h o wi n g hi g h B 7 -H 4 e x pressi o n, 2 L + w h o ha ve pr o gresse d after at least 1 li ne 
of sta n dar d of care C D K 4/ 6 i n hi bit or a n d 1 li ne of sta n dar d of care e n d ocri ne 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 2
treat me nt. De n o v o paire d pre - a n d o n -treat me nt bi o psies are ma n dat or y f or 5 
partici pa nts .

P art 2 B ( N = 2 0): P F -0 7 2 6 0 4 3 7 as m o n ot hera p y  i n partici pa nts wit h H R + H E R 2-
Br Ca, 2 L + w h o ha ve pr o gresse d after at least 1 li ne of sta n dar d of care C D K 4/ 6 
i n hi bit or a n d 1 L of sta n dar d of care e n d ocri ne treat me nt, or 2 L + T N B C w h o ha ve 
pr o gresse d after at least 1 li ne of S O C s yste mic t hera p y (e g 1 L  c he m ot hera p y i n 
c o m bi nati o n wit h a n i m m u ne c hec k p oi nt i n hi bit or if P D-L 1 + or c he m ot hera p y  al o ne 
if P D-L 1  ne gati ve/l o w). A p pr o xi matel y  1 0 H R + H E R 2- Br Ca a n d a p pr o xi matel y  1 0 
T N B C partici pa nts s h o ul d be e nr olle d. De n o v o paire d pre - a n d o n -treat me nt bi o psies
are ma n dat or y f or a p pr o xi matel y 5 H R + H E R 2- Br Ca a n d 5 T N B C partici pa nts. N o 
bi o mar ker selecti o n base d o n B 7 -H 4 e x pressi o n. 

P art 2 C ( N = 2 0): P F -0 7 2 6 0 4 3 7 as m o n ot hera p y  i n partici pa nts wit h T N B C s h o wi n g 
hi g h B 7 -H 4 e x pressi o n, 2 L + w h o ha ve pr o gresse d after at least 1 li ne of S O C 
s yste mic t hera p y (e g 1 L c he m ot hera py i n c o m bi nati o n wit h an i m m u ne c hec k p oi nt 
i n hi bit or if P D-L 1  p ositi ve or c he m ot hera p y al o ne if P D-L 1 ne gati ve/l o w ). De n o v o 
paire d pre - a n d o n -treat me nt bi o psies will be ma n dat or y f or 5 partici pa nts . 
De pe n di n g o n t he res ults of precli nical c o m bi nati o n i n vi v o efficac y , e mer gi n g cli nical 
m o n ot hera p y safet y a n d efficac y data , P F-0 7 2 6 0 4 3 7 c o m bi nati o n c o h orts ma y be a d de d, 
i ncl u di n g c o m bi nati o n wit h C D K 4/ 6 i n hi bit or a n d/ or e n d ocri ne t hera pies i n H R + HE R 2 -
Br Ca a n d c o m bi nati o n wit h i m m u ne c hec k p oi nt i n hi bit ors i n T N B C.
Partici pa nts i n Part 2 will recei ve P F- 0 7 2 6 0 4 3 7 at t he R D E ( wit h or wit h o ut pri mi n g, base d 
o n res ults fr o m Part 1) . De pe n di n g o n t he e val uati o n of safety a n d P K data of t he pri mi n g 
d ose c o h orts, Part 2 partici pa nts ma y  be s witc he d t o a pri mi n g d ose sc he d ule deter mi ne d 
fr o m Part 1 d ose escalati o n wit h pri mi n g. All Part 2 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 o n C 1 D 1, 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 first f ull d ose o n C 1 D 1 5
( o bser vati o n after a d diti o nal pri mi n g d oses if gi ve n will be base d o n e mer gi n g data). 
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 n ot 
e x hi bite d si g ns of C R S (Ta ble 7 ). 
T a ble 7 .
I n p atie nt O bser v ati o n St a ys f or S C A d mi nistr ati o n
P art
Sc he d ule
C 1 D 1
C 1 D 1 5
All ot her o ut p atie nt 
visits
1
Wit h o ut Pri mi n g
U p t o 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
Wit h or Wit h o ut 
Pri mi n g
2 4 h o urs
2 4 h o urs if pri mi n g is use d; 
8 h o urs wit h o ut pri mi n g
At i n vesti gat or’s 
discreti o n
* T he le n gt h a n d n u m ber of i n patie nt o bser vati o n sta ys ma y be m o difie d base d o n e mer gi n g data b ut i n a n y case, 
partici pa nts ma y o nl y be release d after c o nfir mati o n of t he a bse nce of cli nicall y si g nifica nt C R S .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 3
If t he 2 ( or m ore) ste p- u p pri mi n g d oses a p pr oac h is i m ple me nte d, t he o bser vati o n peri o d 
after t he sec o n d pri mi n g S C d ose o n C 1 D 8 will be deter mi ne d base d o n e mer gi n g safet y data 
a n d cli nical i n vesti gat or’s assess me nt.
Please refer t o Secti o n 6. 1 f or ge neral rec o m me n dati o n o n i n patie nt o bser vati o n sta ys f or S C 
a n d I V a d mi nistrati o n as a p plica ble. 
M o dificati o n of i n patie nt o bser vati o n peri o d mi g ht be all o we d base d o n e mer gi n g safet y data 
a n d will re q uire disc ussi o n a n d a gree me nt bet wee n i n vesti gat or a n d s p o ns or.
All partici pa nts will be re q uire d t o pr o vi de 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 
fres h bi o psy d uri n g scree ni n g 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. 
F or 5 partici pa nts i n eac h of Part 2 A a n d 2 C a n d f or 5 H R + H E R 2 - Br Ca partici pa nts a n d 
5 T N B C partici pa nts i n Part 2 B, paire d pre- a n d o n-treat me nt bi o psy sa m ples will be 
ma n dat or y . T hese bi o psies will be t o c o nfir m t he M o A, u n dersta n d t u m or-base d
p har mac o d y n a mics a n d e val uate p ote ntial resista nce mec ha nis m d uri n g treat me nt. 
All partici pa nts will u n der g o u p t o 2 8 da y s of scree ni n g pri or t o first d ose. Eli gi ble 
partici pa nts will t he n recei ve st u d y  i nter ve nti o n f or u p t o 2 years, or u ntil disease pr o gressi o n 
defi ne d b y ir R E CI S T, u nacce pta ble t o xicities, a decisi o n b y  t he partici pa nt ( wit h dra wal of 
c o nse nt or n o l o n ger willi n g t o partici pate) or i n vesti gat or t o disc o nti n ue treat me nt, or st u d y 
ter mi nati o n. N ote: If a partici pa nt is classifie d as ha vi n g P D d uri n g a n o n-treat me nt t u m or 
assess me nt, t he n c o nfir mati o n of P D b y  a sec o n d sca n i n t he a bse nce of ra pi d cli nical 
deteri orati o n is re q uire d per ir R E CI S T (A p pe n di x 1 3 ).
A n y  a d diti o nal treat me nt be yo n d 2 y ears s hall be disc usse d a n d a p pr o ve d b y t he s p o ns or. 
After E O T , all partici pa nts will c o m plete a 2 8-da y p ost -treat me nt f oll o w-u p visit f or A Es . 
All partici pa nts will be c o ntacte d b y  tele p h o ne a p pr o xi matel y 9 0 d a y s p ost treat me nt t o 
assess late ir A Es. Partici pa nts i n Part 2 d ose e x pa nsi o n c o h orts will be c o ntacte d b y 
tele p h o ne a p pr o xi matel y e ver y 3 m o nt hs f or s ur vi val data c ollecti o n u ntil e n d of trial ( 2 years 
fr o m last partici pa nt first d ose), u nless ot her wise n otifie d b y t he s p o ns or. 
A partici 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 last sc he d ule d pr oce d ure s h o w n i n t he S O A i ncl u di n g O S, if
a p plica ble. O S f oll o w-u p s h o ul d n ot c o nti n ue after e n d of t he st u d y  (Secti o n 4. 4 ).
D uri n g treat me nt wit h st u d y  i nter ve nti o n, all c ycles will be 2 8 d a y s i n le n gt h. 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 on 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 xicities, d osi n g ma y  be i nterr u pte d, m o difie d, or disc o nti n ue d as 
descri be d i n Secti o n 6. 5 a n d 7. 1 .
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
P F - 0 7 2 6 0 4 3 7 will be e val uate d f or t he treat me nt of Br Ca (a n d ot her mali g na ncies, i ncl u di n g 
uteri ne a n d O v Ca s). P F‑ 0 7 2 6 0 4 3 7 a d dresses a si g nifica nt u n met me dical nee d f or Br Ca , as 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 4
its tar get B 7-H 4 is e x presse d i n t he ma j orit y of Br Ca s acr oss all m olec ular s u bt ypes (Le o n g 
et al, 2 0 1 5). B 7-H 4, a me m ber of t he B 7 fa mil y of pr otei ns e nc o de d b y ge ne  
, has 
bee n s h o w n t o ha ve wi de e x pressi o n i n Br Ca al o n g wit h ot her g ynec ol o gic mali g na ncies. I n 
a d diti o n, its li mite d e x pressi o n i n n or mal tiss ues ma kes B 7 - H 4 a n a p peali n g t u m or-
ass ociate d a nti ge n f or tar geti n g Br Ca s wit h C D 3 bis pecific m olec ules.
P F ‑ 0 7 2 6 0 4 3 7 de m o nstrate d bi n di n g t o a pa nel of t u m or cell li nes t hat e x press B 7-H 4 pr otei n 
a n d h u ma n T l y m p h oc y tes t hat e x press C D 3. T he bis pecific m olec ule e x hi bite d 
c o nce ntrati o n-de pe n de nt bi n di n g acr oss a pa nel of ca ncer cell li nes wit h var y i n g le vels of 
e n d o ge n o us B 7 -H 4 e x pressi o n, as well as c o nce ntrati o n -de pe n de nt bi n di n g o n a pa nel of 
h u ma n d o n or T cells. I n t he prese nce of T cells, P F ‑ 0 7 2 6 0 4 3 7 elicite d C T L res p o nses a gai nst 
a pa nel of ca ncer cell li nes e x pressi n g B 7 -H 4. I n t he a bse nce of T cells , P F ‑ 0 7 2 6 0 4 3 7 di d n ot 
affect t u m or cell gr o wt h. I n vi v o, P F ‑ 0 7 2 6 0 4 3 7 de m o nstrate d B 7-H 4 e x pressi o n ‑ de pe n de nt 
a ntit u m or acti vit y a gai nst a pa nel of cell li ne xe n o graft a n d patie nt deri ve d xe n o graft breast 
t u m ors gr o w n i n i m m u ne‑c o m pr o mise d mice t hat were i m pla nte d wit h h u ma n T cells. T u m or 
gr o wt h i n hi biti o n f oll o wi n g P F‑ 0 7 2 6 0 4 3 7 treat me nt was d ose de pe n de nt.
T he o bjecti ve of t he bi o mar ker assess me nts i n t his st u d y 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 2 6 0 4 3 7 o n t he t u m or a n d i m m u ne s y ste m. T he assess me nts 
will c o ntri b ute t o c o nfir mi n g tar get e n ga ge me nt a n d meas uri n g T -cell acti vati o n. E val uati o n 
of tar get e x pressi o n a n d m o d ulati o n of i m m u ne si g nat ures ass ociate d wit h t he mec ha nis m of 
P F - 0 7 2 6 0 4 3 7 will re q uire t he c ollecti o n of rece nt 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 t o esta blis h t he ass ociati o n bet wee n B 7- H 4 e x pressi o n, bi o mar kers, 
a n d res p o nse para meters t o P F -0 7 2 6 0 4 3 7 as descri be d i n t he S O A a n d t he La b orat or y 
Ma n ual. Bi o mar ker assess me nts are i nte n de d t o el uci date p ote ntial resista nce mec ha nis ms t o 
P F -0 7 2 6 0 4 3 7 a n d 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
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 B B S, w hic h ma kes it p ossi ble t o better u n dersta n d t he 
i n vi v o M o A a n d p ote ntial mec ha nis ms of resista nce of t he i n vesti gati o nal pr o d uct a n d 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, safet y, 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. T hese 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 2 6 0 4 3 7 as a si n gle a ge nt a n d ma y  pr o vi de i nf or mati o n o n t u m or 
s u bt ypes t hat ma y  res p o n d t o t he st u d y i nter ve nti o n.
T he P K a nal ys es w o ul d ser ve t o c haracterize t he P K of P F -0 7 2 6 0 4 3 7 i n h u ma n a n d its 
relati o ns hi p wit h vari o us fact ors (e g, b o d y  wei g ht). F urt her i de ntificati o n of t he P K-P D a n d 
e x p os ure -res p o nse relati o ns hi p f or efficac y, safet y, a n d t he rele va nt bi o mar kers w o ul d g ui de 
t he d ose selecti o n i n s u bse q ue nt trials.
4. 2. 1. H or m o ne Rece pt or ( E R a n d/ or P R) P ositi ve Br C a
Br Ca is t he m ost c o m m o n n o nc uta ne o us ca ncer i n w o me n wit h o ver 2 7 5, 0 0 0 ne w cases 
e x pecte d t o be dia g n ose d i n t he U S i n 2 0 2 0 . A p pr o xi matel y  7 0 %-8 0 % of ne w Br Ca s e x press 
t he estr o ge n a n d/ or pr o gester o ne rece pt or. Patie nts wit h a d va nce d or metastatic H R-p ositi ve 
t u m ors be nefit fr o m h or m o nal t hera p y a n d C D K 4/ 6 i n hi bit ors. I n a d diti o n, rece ntl y Al pelisi b 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 5
was a p pr o ve d b y F D A i n treati n g a d va nce d or metastatic H R + H E R 2 -, PI K 3 C A-m uta nt 
Br Ca after a n e n d ocri ne - base d re gi me n. H o we ver, m ost patie nts de vel o p resista nce t o t hese 
t hera pies, a n d all are ass ociate d wit h si g nifica nt t o xicities. T heref ore, t here re mai ns a n ur ge nt 
nee d t o i de ntif y  ne w treat me nts.
4. 2. 2. Tri ple Ne g ati ve Br C a
T N B C acc o u nts f or 1 5 % of Br Ca s a n d is ass ociate d wit h p o or l o n g-ter m o utc o mes. 
C o m pare d wit h ot her Br Ca s u bt y pes, T N B C affects yo u n ger w o me n, is m ore fre q ue nt i n 
blac k a n d His pa nic w o me n a n d s h o ws hi g her pre vale nce of ger mli ne Br Ca m utati o n. T N B C 
is us uall y hi g h gra de, s h o ws s h orter ti me t o rela pse a n d hi g her ris k f or visceral metastases
(S har ma, 2 0 1 6 ).
T he lac k of E R, P R a n d H E R 2 e x pressi o n precl u des t he use of tar gete d t hera pies i n T N B C 
(C osta et al, 2 0 1 9 ). S yste mic t hera p y re gi me ns f or a d va nce d or metastatic T N B C i ncl u de 
ta xa nes as si n gle a ge nts or i n c o m bi nati o n wit h a nt hrac ycli nes, plati n u m, or ge mcita bi ne. A 
p o ole d a nal ys is of P hase 3 trials i n t he first -li ne setti n g s h o we d O R R of 2 3 %, me dia n P F S of
5. 4 m o nt hs a n d me dia n O S of 1 7. 5 m o nt hs. Rece ntl y , F D A has gra nte d accelerate d a p pr o val 
t o c o m bi ne c hec k p oi nt i n hi bit ors ( Pe m br oliz u ma b a n d Atez oliz u ma b) wit h c he m ot hera py as 
first-li ne t hera py i n P D -L 1 p ositi ve a d va nce d or metastatic T N B C. M ost rece ntl y , F D A has 
gra nte d re g ular a p pr o val t o sacit uz u ma b g o viteca n f or patie nts wit h u nresecta ble l ocall y 
a d va nce d or metastatic T N B C w h o ha ve recei ve d 2 or m ore pri or s ys te mic t hera pies, at least 
o ne of t he m f or metastatic disease. I n a d diti o n, talaz o pari b a n d o la pari b ha ve bee n a p pr o ve d 
b y  F D A i n treati n g ger mli ne Br Ca m uta nt H E R 2- ne gati ve a d va nce d or metastatic Br Ca.
H o we ver, n o ne of t hese t hera pies is c urati ve, a n d all are ass ociate d wit h si g nifica nt t o xicities. 
T heref ore, ne w t hera pies f or m T N B C are ur ge ntl y  nee de d. 
Precli nicall y , P F-0 7 2 6 0 4 3 7 has de m o nstrate d B 7 - H 4 e x pressi o n- de pe n de nt a ntit u m or
acti vit y a gai nst H R + H E R 2-, H E R 2 +, a n d T N B C m olec ular s u bty pe cell li ne xe n o graft a n d 
patie nt -deri ve d xe n o graft breast t u m ors gr o w n i n i m m u ne -c o m pr o mise d mice t hat wer e 
i m pla nte d wit h h u ma n T cells. P F-0 7 2 6 0 4 3 7 treat me nt di d n ot s h o w a ntit u m or efficac y  i n a 
m o del t hat d oes n ot e x press B 7 -H 4.
T hese data pr o vi de rati o nale f or e x pl ori n g p ote ntial use of P F- 0 7 2 6 0 4 3 7 i n H R + H E R 2 -
Br Ca a n d T N B C.
4. 2. 3. Di versit y of St u d y P o p ul ati o n
Part 1 of t he st u d y will e nr oll a d ult partici pa nts wit h l ocall y  a d va nce d or metastatic s oli d 
t u m ors i ncl u di n g Br Ca, O v Ca a n d e n d o metrial ca ncer. A d ult partici pa nts wit h ot her B 7 -H 4 
e x pressi n g t u m ors ma y be i ncl u de d after disc ussi o n wit h a n d a p pr o val fr o m sp o ns or . Part 2 
will e nr oll partici pa nts wit h H R + H E R 2- Br Ca a n d T N B C wit h hi g h B 7 -H 4 e x pressi o n a n d a 
c o h ort of 2 0 partici pa nts wit h H R + H E R 2 - Br Ca or T N B C n ot selecte d f or B 7-H 4 
e x pressi o n . 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 6
4. 2. 4. D ose Le vel Re vie w
T he deter mi nati o n of safet y  f or eac h d ose le vel wit h or wit h o ut pri mi n g will be base d o n t he 
disc ussi o n b y  t he 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 sp o ns or. I n 
a d diti o n, Pfizer will c o n d uct u n bli n de d data re vie ws 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 n t, facilitati n g P K/ P D m o deli n g or s u p p orti n g cli nical 
de vel o p me nt.
4. 2. 5. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
St u dies t o e val uate t he de vel o p me nt t o xicit y  of P F-0 7 2 6 0 4 3 7 ha ve n ot bee n c o n d ucte d . 
T heref ore, t he use of a hi g hl y effecti ve met h o d of c o ntrace pti o n is re q uire d (see A p pe n di x 4 ).
4. 2. 6. C ollecti o n of Ret ai ne d Rese arc h S a m ples
Retai ne d Researc h Sa m ples will be c ollecte d a n d st ore d f or f urt her a nal ys es w hic h ma y, f or 
e xa m ple, pr o vi de greater u n dersta n di n g of t he st u d y  i nter ve nti o n.
4. 3. J ustific ati o n f or D ose
D oses prese nte d are pr ojecte d base d o n n o ncli nical data a n d ma y be m o difie d base d o n e mer gi n g 
safet y, t olera bilit y, a n d P K data.
4. 3. 1. St arti n g D ose
4. 3. 1. 1. S u bc ut a ne o us A d mi nistr ati o n
T he starti n g d ose will be 1 0 0 µ g S C Q 2 W i n 2 8 -da y c ycles. 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 M A B E L i n acc or da nce wit h t he I C H S 9 G ui da nce, gi ve n t hat 
P F -0 7 2 6 0 4 3 7 is a bis pecific T cell -e n ga gi n g a ge nt wit h i m m u ne a g o nistic pr o perties. T he 
1 0 0 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 
i n vitr o c yt o ki ne release a n d c yt ot o xicit y e x peri me nts.
T he i n vitr o bi ol o gical acti vities f or P F -0 7 2 6 0 4 3 7 were deter mi ne d via c y t ot o xicit y a n d 
c yt o ki ne release assa ys. T he E C 5 0 val ue fr o m t he m ost se nsiti v e i n vitr o assa y was 0. 0 6 2 n M. 
Wit h a starti n g d ose of 1 0 0 μ g Q 2 W, t he pre dicte d P F- 0 7 2 6 0 4 3 7 C ma x after si n gle d ose, 
ass u mi n g 7 0 % bi oa vaila bilit y fr o m t he S C r o ute, is 9. 2 n g/ m L ( 0. 0 6 3 n M), w hic h is si milar 
t o t he E C 5 0 ( 0. 0 6 2 n M) of t he m ost se nsiti ve i n vitr o assa y. Si nce C ma x 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 , t he bl u nte d Cma x offere d b y  S C r o ute is 
e x pecte d t o i ncrease t he patie nt t olera bilit y.
I n a d diti o n, t he pr o p ose d M A B E L starti n g d ose is l o wer c o m pare d t o t he 1/ 6 of H N S T D 
( 1 1 0 0 μ g ass u mi n g 7 0 k g b o d y  wei g ht) deter mi ne d i n t he G LP 1 -m o nt h t o xic ol o g y  st u d y 
( 0. 3 m g/ k g/ wee k S C) i n c y n o m ol g us m o n ke y s.
I n s u m mar y, t he pr o p ose d M A B E L starti n g d ose of 1 0 0 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 eff ect a n d t o pr o vi de a n a de q uate safet y  mar gi n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 7
4. 3. 1. 2. Alter n ati ve I ntr a ve n o us A d mi nistr ati o n
If P K a n d safety data s u g gest t hat S C r o ute is n ot a via ble a p pr oac h (e g, ver y l o w S C 
bi oa vaila bilit y  or i nt olera ble I SR) , I V a d mi nistrati o n ma y als o be e val uate d i n s u bseq ue nt 
d ose c o h orts. T o pr o vi de s ufficie nt safet y  mar gi n, the I V starti n g d ose will be 2 0 % of t he 
hi g hest safe/t olera ble S C d ose wit h ass u m pti o n of 2. 5 L  of plas ma v ol u me f or 
I V a d mi nistrati o n . F or e xa m ple, if t he 3 0 0 µ g S C d ose le vel is dee me d t olera ble, the I V 
starti n g d ose will be 6 0 µ g. N ota bl y, i n t he a bse nce of a ny cli nical safet y data fr o m S C 
d osi n g, t he M A B E L a p pr oac h w o ul d yi el d a n I V starti n g d ose of 2 3 μ g as t he pre dicte d C ma x
is si milar t o t he E C 5 0 val ue fr o m t he m ost se nsiti ve i n vitr o assa y ( 0. 0 6 2 n M). W hile it is n ot 
feasi ble t o a d mi nister t his IV d ose of 2 3 µ g base d o n t he c urre nt f or m ulati o n ( wit h a l o west 
feasi ble I V d ose of 4 5 µ g), t he I V r o ute will n ot be p ote ntiall y i m ple me nte d u ntil a S C d ose 
le vel of ≥3 0 0 μ g . T heref ore, t he l o west p ossi ble I V d ose is 6 0 μ g, w hic h is e x pecte d t o 
pr o vi de si milar e x p os ure c o vera ge wit h 3 0 0 μ g at S C d ose le vel 2 (see Ta ble 8 ).
I n a d diti o n, the H N S T D was 0. 1 m g/ k g/ wee k fr o m t he I V ar m of t he G L P 1 -m o nt h t o xicit y  
st u d y i n c yn o m ol g us m o n ke y s. T his yi el de d a n I V starti n g d ose of 3 7 6 µ g ( 1/ 6 H N S T D 
ass u mi n g 7 0 k g b o d y  wei g ht i n h u ma ns), w hic h is hi g her t ha n o ur pr o visi o nal I V starti n g 
d ose of 6 0 μ g .
If I V r o ute is e val uate d, i n patie nt m o nit ori n g i n a h os pital f or at least 4 8 h o urs after t he first 
d ose i n C y cle 1 i n d ose escalati o n will be i m ple me nte d as descri be d i n Secti o n 6. 1 . 
A d diti o nal i n patie nt o bser vati o n f or s u bse q ue nt c ycles be y o n d C ycle 1 ma y be c o nsi dere d 
base d o n t he i n vesti gat or’s discreti o n a n d s h o ul d be disc usse d wit h t he sp o ns or.
4. 3. 2. J ustific ati o n f or P ri mi n g D ose Re gi me n
Pri mi n g d ose a p pr oac hes are c o m m o nl y a p plie d f or T- cell e n ga ger bis pecific m o dalities t o 
i nitiall y se nsitize t he i m m u ne s yste m at l o wer d oses t o re d uce rate a n d gra de of C R S (C osta 
et al, 2 0 1 9; Garfall, 2 0 2 0 ; Ma d d uri et al, 2 0 2 0 ; B LI N C Y T O ( bli nat u m o ma b), 2 0 2 1 ). A 
pri mi n g d ose a p pr oac h ma y  be i nitiate d if a d ose le vel i n d uces ≥Gra de 2 C R S (lasti n g f or 
> 2 4 h o urs) occ urs i n > 1 partici pa nt des pite treat me nt wit h t ociliz u ma b a n d/ or vas o press ors. 
I nitially, a si n gle pri mi n g d ose will be a d mi nistere d o n C 1 D 1 at 1 d ose le vel bel o w t he d ose 
le vel w here by t he ≥Gra de 2 C R S e ve nt was o bser ve d. T he first f ull d ose will be 
a d mi nistere d o n C 1 D 1 5 wit h a starti n g f ull d ose t hat is 1 0 0 % hi g her t ha n t he pri mi n g d ose. 
De pe n di n g o n t he o bser ve d safet y a n d t olera bilit y pr ofile, d ose escalati o n o n t he f ull d ose 
ma y  still pr ocee d wit h u p t o 3 -f ol d i ncre me nt fr o m c urre nt f ull d ose le vel . If ≥Gra de 2 C R S 
is o bser ve d after t he a d mi nistrati o n of f ull d oses, a 2 ste p-u p pri mi n g d oses a p pr oac h ma y  
als o be i m ple me nte d wit h t he 2 pri mi n g d oses a d mi nistere d o n C 1 D 1 a n d C 1 D 8, 
res pecti vely;  b ot h pri mi n g d oses will be at d ose le vels w here pre dicte d pr o ba bilit y of ≥
Gra de 2 C R S is < 2 0 %.
4. 3. 3. 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 H st u d y of P F-0 7 2 6 0 4 3 7 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 et al, 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 8
2 0 0 9 ; Z ha n g et al, 2 0 1 2 ; He n dri k x et al, 2 0 1 7 ). 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.
4. 3. 4. 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 2 6 0 4 3 7 i n t his st u d y  was selecte d base d o n t he 
pr ojecte d t½ of 1 5 da y s i n h u ma ns. Base d o n e mer gi n g P K, P D, a n d safety data, re gi me ns 
wit h alter nati ve d osi n g fre q ue ncies (e g, wee kl y a d mi nistrati o n, or Q 4 W) ma y als o be 
c o nsi dere d.
4. 3. 5. Criteri a f or D os e Esc al ati o n
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. See Ta ble 8 a n d 
A p pe n di x 9 f or m ore details o n t he m o del. Usi n g D LT 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 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, 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 t he 
ris k of e xcessi ve t o xicit y, ie, t o xicit y hi g her t ha n 0. 3 3 at t hat d ose is less t ha n 2 5 %.
T y picall y , partici pa nts will be e nr olle d i n 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 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 wit h or wit h o ut a pri mi n g d ose. 
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 % 
( d ose tri pli n g fr o m t he pre vi o us d ose le vel) b ut will be a dj uste d t o n o m ore t ha n 1 0 0 % ( d ose 
d o u bli n g fr o m t he pre vi o us d ose le vel) 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 cli nica ll y si g nifica nt treat me nt-relate d A Es.
T he pr o visi o nal d ose le vels t o be e val uate d are liste d i n Ta ble 8. 
T a ble 8.
Pr o visi o n al D ose Le vels i n D ose -Esc al ati o n ( S C A d mi nistr ati o n)
D ose Le vel a
D ose ( µ g)
-1 (if a p plica ble)
6 0
1 b
1 0 0
2
3 0 0
3 
9 0 0
≥ 4
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
a.
I nter me diate d oses ma y be e val uate d base d o n cli nical fi n di n gs. M a xi m u m 3- f ol d i ncre me nt (d ose tri pli n g ) at eac h 
d ose le vel.
b.
If t he 1 0 0 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 6 0 μ g Q 2 W via S C r o ute will 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 A p pe n di x 9 ). 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. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 8 9
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) e nr olle d i n t he first d ose le vel wit h t he f oll o wi n g 
c o n diti o ns: 1) ha ve cleare d t he D L T peri o d i n t he d ose escalati o n p hase, 2) t he ne xt 
i m me diate hi g her d ose le vel is safe i n all partici pa nts wit h n o D LTs, a n d 3) a peri o d of a 
mi ni m u m of 2 c y cles after t he D L T o bser vati o n peri o d wit h t he ne xt i m me diate hi g her d ose 
le vel has c o nfir me d t here are n o cli nicall y si g nifica nt t o xicities.
St o p pi n g criteri a:
T he s p o ns or esti mates t hat t he ma xi m u m n u m ber of partici pa nts i n t he Part 1 d ose escalati o n 
p orti o n of t h e trial is 4 0 partici pa nts. H o we ver, t he act ual n u m ber ma y  be m ore or less base d 
o n o bser ve d P K a n d safet y . T he d ose escalati o n will st o p 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 or R D E .

T he d ose d f or P F -0 7 2 6 0 4 3 7 satisfies 1 of t he f oll o wi n g c o n diti o ns f or t he m o n o -
escalati o n part:
o
T he pr o ba bilit y  of tar get t o xicit y at d ose d e xcee ds 5 0 %, ie, Pr ( 0. 1 6 
≤п d < 0. 3 3) ≥5 0 %, or
o
A mi ni m u m of 1 5 partici pa nts ha ve bee n treate d i n Part 1.
4. 3. 6. D ose Li miti n g T o xicit y ( D L T) Defi niti o n
A partici pa nt is classifie d as D L T e val ua ble if t he y eit her 1) recei ve all t he pla n ne d d oses of 
t he st u d y i nter ve nti o n a n d ha ve recei ve d all sc he d ule d safety assess me nts d uri n g t he D L T 
o bser vati o n peri o d or 2) ha ve e x perie nce d a D L T. If a partici pa nt fails t o meet t hese criteria, 
t he y ma y be re place d. T he s ole e xce pti o n t o criteri o n 1) is if t he partici pa nt has misse d a 
mi n orit y  of safety assess me nts d ue t o e mer ge nc y sit uati o ns (e g, site accessi bilit y  iss ues, 
i na bilit y t o g o t o a n e xter nal la b, etc). In s uc h cases, t he D ose Le vel Re vie w C o m mittee ma y  
j u d ge t he partici pa nt e val ua ble, de pe n di n g o n t he a b u n da nce of t he a vaila ble data.
D L T o bser vati o n peri o d: 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 
S C or I V d o si n g wit h o ut pri mi n g will be 2 8 da ys i ncl u di n g la b orat or y res ults o btai ne d o n t he 
m or ni n g of D a y  2 9 i n eac h partici pa nt. T he D L T peri o d f or d osi n g wit h pri mi n g will e xte n d 
t o i ncl u de t he d urati o n of pri mi n g d oses a n d 2 f ull d oses (e g, if a si n gle pri mi n g d ose is 
a d mi nistere d 2 wee ks pri or t o t he first f ull d ose, t he D L T e val uati o n peri o d will be 4 2 da y s 
(1 4 da y s pl us 2 8 da ys) i ncl u di n g la b orat or y res ults o btai ne d o n t he m or ni n g of Da y  4 3 
( C 2 D 1 5).
A n y  of t he f oll o wi n g treat me nt-relate d A Es occ urri n g d uri n g t he D L T o bser vati o n peri o d 
t hat i n t he o pi ni o n of t he i n vesti gat or ca n n ot be reas o na bl y attri b ute d t o t he partici pa nt’s 
u n derl y i n g disease, c o nc o mita nt me dicati o ns or pree xisti n g c o n diti o ns are c o nsi dere d D L Ts. 
Se verit y  of A Es will be gra de d acc or di n g t o C T C A E versi o n 5. 0, wit h t he e xce pti o n of C R S, 
w hic h will be gra de d acc or di n g t o t he A S T C T C R S C o nse ns us Gra di n g f or C R S 
(A p pe n di x 1 1 ). F or t h ose e ve nts i n v ol vi n g a w orse ni n g of a baseli ne a b n or malit y, a D L T
m ust re prese nt a cli nicall y si g nifica nt (i n t he o pi ni o n of t he I n vesti gat or after disc ussi o n wit h 
t he s p o ns or) s hift fr o m baseli ne.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 0
4. 3. 6. 1. He m at ol o gic al D L Ts

Gra de 4 ne utr o pe nia

Fe brile ne utr o pe nia, defi ne d as A N C < 1. 0 x 1 0 9/ L [ < 1 0 0 0/ m m3] wit h a si n gle 
te m perat ure of > 3 8. 3° C [ 1 0 1° F], or a s ustai ne d te m perat ure of 3 8° C [ 1 0 0. 4° F] f or 
m ore t ha n 1 h o ur.

Gra de ≥3 ne utr o pe nia lasti n g 7 d a y s;

Gra de 3 ne utr o pe nia wit h i nfecti o n; 

Gra de 4 t hr o m b oc y t o pe nia

Gra de 3 t hr o m b oc y t o pe nia wit h blee di n g or re q uiri n g platelet tra nsf usi o n

Gra de 4 a ne mia

Gra de 3 a ne mia re q uiri n g bl o o d tra nsf usi o n.
4. 3. 6. 2. N o n -He m at ol o gic D L Ts
A n y  treat me nt-relate d Gra de ≥3 n o n- he mat ol o gic t o xicit y  (see bel o w f or s pecificati o ns 
a p pl yi n g t o s pecial circ u msta nces):

He patic t o xicit y :

Cli nical e ve nts c o nsiste nt wi t h H y’s La w, ie,

≥3- f ol d ele vati o ns a b o ve t he U L N of A L T or A S T A N D;

2 x U L N ele vati o n of ser u m t otal bilir u bi n wit h o ut alter nati ve e x pla nati o n 
(e g, c h olestasis or Gil bert’s s yn dr o me) A N D;

A bse nce of i nitial fi n di n gs of c h olestasis (e g, ele vate d ser u m A L P) A N D;

A bse nce of ot her reas o n(s) t o e x plai n t he c o m bi nati o n of i ncrease d A T a n d 
T Bili , s uc h as viral he patitis A, B, or C; pree xisti n g or ac ute li ver disease; or 
a n ot her dr u g ca pa ble of ca usi n g t he o bser ve d i nj ur y.

F or partici pa nts wit h Gra de 2 he patic tra nsa mi nase or al kali ne p h os p hatase le vels 
at baseli ne as a res ult of li ver metastasis or b o ne metastasis, a he patic 
tra nsa mi nase or al kali ne p h os p hatase le vel > 1 0 ti mes t he U L N. 

Gra de ≥3 fati g ue lasti n g ≥5 da y s.

Gra de ≥3 na usea/ v o miti n g or diarr hea lasti n g ≥3 da y s des pite a de q uate a ntie metic 
a n d ot her s u p p orti ve care. 

Gra de ≥3 C R S of a n y  d urati o n.

Gra de ≥3 Q Tc F pr ol o n gati o n ( Re peat testi n g, re -e val uate b y a q ualifie d pers o n, a n d 
c orrect re versi ble ca uses (s uc h as electr ol yt e a b n or malities or h yp o xia). If, after 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 1
c orrecti o n of a n y re versi ble ca uses, t he Gra de 3 Q Tc F pr ol o n gati o n persists, t he n t he 
e ve nt s h o ul d be c o nsi dere d a D L T).

A treat me nt -relate d A E i n d uci n g a dela y b y > 2 wee ks i n recei vi n g t he ne xt sc he d ule d 
c ycle. 

Gra de ≥3 a na p h y la xis.

A n y  Gra de 5 A E ( deat h) n ot clearly d ue t o eit her t he u n derl yi n g disease or ot her 
eti ol o gies.
I n a d diti o n, ir A Es t hat meet t he f oll o wi n g criteria will be c o nsi dere d as D L Ts:

A n y  Gra de 4 ir A E re gar dless of d urati o n, a n y ≥ Gra de 4 c olitis re gar dless of d urati o n; 

A n y  Gra de 3 or Gra de 4 n o n-i nfecti o us p ne u m o nitis re gar dless of d urati o n; 

A n y  Gra de 3 ir A E, e xcl u di n g c olitis a n d p ne u m o nitis, t hat d oes n ot start d o w n gra di n g 
t o ≤ Gra de 2 wit hi n 3 da ys after o nset of t he e ve nt des pite ma xi mal s u p p orti ve care 
i ncl u di n g sys te mic c ortic oster oi ds or d ose n ot d o w n gra de t o ≤ Gra de 1 or baseli ne 
wit hi n 1 4 da y s; 

A n y  Gra de 2 p ne u m o nitis t hat d oes n ot res ol ve t o ≤ Gra de 1 wit hi n 3 da y s of t he 
i nitiati o n of ma xi mal s u p p orti ve care.
4. 3. 6. 3. Ot her D L Ts
Cli nicall y  i m p orta nt, persiste nt (e g, res p o nsi ble f or si g nifica nt d ose dela y) t o xicities 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 L T f oll o wi n g re vie w b y t he 
i n vesti gat ors a n d t he sp o ns or. All D L Ts nee d t o re prese nt a cli nicall y si g nifica n t s hift fr o m 
baseli ne.
T he f oll o wi n g A Es will n ot be a dj u dicate 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. Gra de 3 e n d ocri n o pat h y  n ot c o ntr olle d by h or m o nal 
re place me nt.
4. 3. 7. L ate T o xicit y Defi niti o n a n d M a n a ge me 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 t he c o nte xt of 
all a vaila ble safet y data . 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 2
T he details of t he p ote ntial late o nset t o xicit y  will be re vie we d d uri n g d ose le vel re vie w 
meeti n gs t o i nf or m decisi o ns a b o ut e nr oll me nt a n d d osi n g (e g, d ose le vel i ncre me nts, 
deter mi nati o n of t he d ose(s) use d be y o n d d ose escalati o n, re gi me n). 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, P hase 1 R D E
a n d/ or R P 2 D, as a p pr o priate.
T he o pti o n f or d ose re d ucti o n will be disc usse d wit h a n y  gi ve n partici pa nt t hat is 
o n -treat me nt at d ose le vels t hat are s u bse q ue ntly c o nsi dere d t o be a b o ve t he M T D. If a 
partici pa nt t olerate d t he a b o ve- M T D d ose le vel well a n d is be nefiti n g fr o m t hera p y, 
c o nti n uati o n of treat me nt at t he a b o ve -M T D d ose le vel will re q uire re -c o nse nti n g.
4. 3. 8. M a xi m u m T oler ate d D ose ( M T D) Defi niti o n
M T D is defi ne d as t he hi g hest d ose wit h tr ue D L T rate wit hi n t he tar get t o xicit y  i nterval. 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. 
T he safet y of eac h c o h ort will be assesse d b y a D ose Le vel Re vie w C o m mittee, w hic h is 
c o m p ose d of s p o ns or re prese ntati ves a n d t he I n vesti gat ors. T he C o m mittee will c o nsi der all 
rele va nt cli nical data, i ncl u di n g safet y, P K, efficac y, a n d P D i n ma ki n g decisi o ns s uc h as 
w het her t o d ose escalate, d ose de- escalate, d ose le vel i ncre me nts, e x pa n d 
c o h orts, a n d declare M T D.
4. 3. 9. Rec o m me n de d P h ase 2 D ose ( R P 2 D) Defi niti o n 
T he R P 2 D is t he d ose c h ose n f o r f urt her i n vesti gati o n base d o n P hase 1 st u d y res ults. T he 
R D E is t he d ose c h ose n f or f urt her i n vesti gati o n base d o n Part 1 d ose escalati o n res ults. If 
t he M T D pr o 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 n t his d ose bec o mes t he R D E . H o we ver, R D E mi g ht be l o wer t ha n t he 
M T D. Safet y, efficac y, a n d P K data as well as p ote ntial e x p os ure -res p o nse relati o ns hi ps will 
be c o nsi dere d i n i de ntif y i n g t he R D E . After e x pa nsi o n c o h orts wit h lar ger sa m ple size a n d 
s ufficie nt data, t he fi nal “ St u d y” R P 2 D will be deter mi ne d b y t he s p o ns or base d o n t he 
rec o m me n dati o n fr o m i n vesti gat ors a n d st u d y tea m. T he deter mi nati o n of “ St u d y” R P 2 D will 
be base d o n safet y, t olera bilit y  a n d earl y si g ns of cli nical efficac y a n d be nefit fr o m b ot h Part 
1 d ose escalati o n a n d Part 2 e x pa nsi o n.
T he d ose(s) selecte d f or use i n t he e x pa nsi o n c o h orts will be referre d t o as t he P hase 1 
E x pa nsi o n D ose(s).
4. 4. E n d of St u d y Defi niti o n
T he e n d of t he st u d y is defi ne d as 2 ye ars fr o m t he last partici pa nt’s first d ose u nless 
ot her wise n otifie d b y t he s p o ns or.
Accr ual ma y  be halte d a n d a t h or o u g h safet y a nalysis will be c o n d ucte d a n d s u b mitte d t o 
F D A i n t he e ve nt of si g nifica nt safet y c o ncer ns (e g, o ne Gra de 5 S A E or t w o Gra de 4 e ve nts 
c o nsi dere d at least p ossi bl y  relate d t o P F-0 7 2 6 0 4 3 7 ).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 3
A partici 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 peri o ds of 
t he st u d y, i ncl u di n g t he last sc he d ule d pr oce d ure s h o w n i n t he S O A w hic h f or Part 1 is t he 
4 -wee k f oll o w-u p visit a n d f or Part 2 is t he O S f oll o w - u p.
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 c o 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. 
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:  
A g e a n d Se x:
1.
Partici pa nts ≥1 8 y ears. 
a.
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.
T y pe of P artici p a nt a n d Dise ase C h ar acteristics:
2.
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.
3.
Pri mar y  disease:
P a rt 1: Hist ol o gical or c y t ol o gical dia g n osis of l ocall y a d va nce d or metastatic Br Ca , 
e n d o metrial ca ncer a n d O v Ca t hat is resista nt t o sta n dar d t hera py or f or w hic h n o 
sta n dar d t hera py is a vaila ble. Partici pa nts wit h ot her a d va nce d or metastatic s oli d 
t u m ors wit h hi g h B 7-H 4 e x pressi o n ma y  be c o nsi dere d after disc ussi o n wit h a n d 
a p pr o val b y sp o ns or. Si milarl y , t h ose partici pa nts wit h ot her a d va nce d or metastatic 
s oli d t u m ors s h o ul d be resista nt t o sta n dar d t hera p y or ha ve n o a vaila ble sta n dar d 
t hera py.
P art 2 A: 2 L + partici pa nts wit h hist ol o gical or c y t ol o gical dia g n osis of l ocall y 
a d va nce d or metastatic H R + H E R 2 - Br Ca s h o wi n g hi g h B 7-H 4 e x pressi o n (see 
Secti o n 8. 6. 2. 1 ) w h o ha ve pr o gresse d after at least 1 li ne of S O C C D K 4/ 6 i n hi bit or 
a n d 1 li ne of S O C e n d ocri ne treat me nt. De n o v o paire d pre - a n d o n -treat me nt 
bi o psies are ma n dat or y  f or a p pr o xi matel y 5 partici pa nts .
P art 2 B: 2 L + partici pa nts wit h hist ol o gical or c y t ol o gical dia g n osis of l ocall y 
a d va nce d or metastatic H R + H E R 2 - Br Ca w h o h a ve pr o gresse d after at least 1 li ne of 
S O C C D K 4/ 6 i n hi bit or a n d 1 L of S O C e n d ocri ne treat me nt, or 2 L + T N B C w h o ha ve 
pr o gresse d after at least 1 L of S O C s yste mic t hera p y (e g, 1 L  c he m ot hera p y i n 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 4
c o m bi nati o n wit h a c hec k p oi nt i n hi bit or if P D -L 1 p ositi ve or c he m ot hera p y al o ne if 
P D -L 1  ne gati ve/l o w). De n o v o paire d pre - a n d o n -treat me nt bi o psies are ma n dat or y 
f or a p pr o xi matel y 5 H R + H E R 2 - Br Ca a n d 5 T N B C partici pa nts. N o bi o mar ker 
selecti o n base d o n B 7- H 4 e x pressi o n is nee de d f or Part 2 B.
P art 2 C: 2 L + partici pa nts wit h hist ol o gical or c y t ol o gical dia g n osis of l ocall y 
a d va nce d or metastatic T N B C s h o wi n g hi g h B 7 -H 4 e x pressi o n (see Secti o n 8. 6. 2. 1 ) 
w h o ha ve pr o gresse d after at least 1 L of S O C c he m ot hera p y a n d 1 li ne of S O C 
s yste mic t hera p y (e g, c he m ot hera py i n c o m bi nati o n wit h a c hec k p oi nt i n hi bit or if P D-
L 1 p ositi ve or c he m ot hera p y  al o ne if P D-L 1 ne gati ve/l o w) . De no v o paire d pre - a n d 
o n -treat me nt bi o psies are ma n dat or y f or a p pr o xi matel y 5 partici pa nts . 
4.
Partici pa nts ha ve at least 1 meas ura ble lesi o n as defi ne d b y  R E CI S T versi o n 1. 1 t hat 
has n ot bee n pre vi o usl y  irra diate d. F or Part 1 d ose escalati o n, partici pa nts wit h 
metastatic H R + H E R 2 - breast ca ncer wit h n o n -meas ura ble b ut e val ua ble disease ma y  
be eli gi ble after disc ussi o n wit h a n d a p pr o val fr o m t he sp o ns or. 
5.
Partici pa nts m ust be a ble t o pr o vi de 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 uali t 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 fres h bi o ps y d uri n g scree ni n g. 1 0 partici pa nts e nr olli n g i n Part 2 B, a n d 
5 partici pa nts e nr olli n g i n eac h of Parts 2 A a n d 2 C m ust a gree t o paire d pre- a n d o n-
treat me nt bi o psies. A b ilit y of a partici pa nt t o u n der g o bi o psy safel y s h o ul d be 
deter mi ne d d uri n g scree ni n g. E xce pti o ns t hat bi o psies ca n n ot be o btai ne d d ue t o 
safety ris k s h o ul d be disc usse d a n d a p pr o ve d b y t he sp o ns or. 
6.
Partici pa nts wit h H R + H E R 2 - a d va nce d or m etastatic Br Ca m ust ha ve: 
a.
D oc u me ntati o n of E R or P R -p ositi ve t u m or ( ≥1 % p ositi ve stai ne d cells) base d o n 
m ost rece nt t u m or tiss ue utilizi n g a n assa y  c o nsiste nt wit h l ocal sta n dar ds a n d 
A S C O/ C A P g ui deli nes (Allis o n et al, 2 0 2 0 )
b.
D oc u me ntati o n t hat t u m or is H E R 2 -ne gati ve a s deter mi ne d b y  IH C sc ore of 0/ 1 + 
or ne gati ve b y i n sit u h ybri dizati o n ( FI S H/ CI S H/ SI S H/ DI S H) defi ne d as 
H E R 2/ C E P 1 7 rati o < 2 or f or si n gle pr o be assess me nt a H E R 2 c o p y n u m ber < 4 , 
c o nsiste nt wit h A S C O/ C A P g ui deli ne s (W olff et al, 2 0 1 8 ).
7.
Partici pa nts wit h T N B C m ust ha ve d oc u me ntati o n t hat t u m or tiss ue is ne gati ve 
( < 1 % cells wit h n uclear p ositi vit y) f or E R a n d P R as well as ne gati ve f or H E R 2 as 
deter mi ne d b y I H C sc ore of 0/ 1 + or ne gati ve b y I S H ( FI S H/ CIS H/ SI S H/ DI S H) 
defi ne d as a H E R 2/ C E P 1 7 rati o < 2 or f or si n gle pr o be assess me nt a H E R 2 c o p y  
n u m ber < 4 , c o nsiste nt wit h A S C O/ C A P g ui deli nes (W olff et al, 2 0 1 8 ; Allis o n et al, 
2 0 2 0 ).
I nf or me d C o nse nt: 
8.
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 IC D a n d i n 
t his pr ot oc ol.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 5
Ot her I ncl usi o n criteria:
9.
E C O G P S 0 or 1. 
1 0. A de q uate B o ne Marr o w F u ncti o n, defi ne d as:
a.
A N C ≥1, 5 0 0/ m m 3 or ≥1. 5 x 1 0 9/ L;
b.
Platelets ≥1 0 0, 0 0 0/ m m 3 or 1 0 0 x 1 0 9/ L;
c.
He m o gl o bi n ≥9 g/ d L.
1 1. A de q uate Re nal F u ncti o n, as f oll o ws:
a.
Ser u m creati ni ne ≤1. 5 x U L N) or esti mate d Cr Cl ≥5 0 m L / mi n as meas ure d or 
calc ulate d usi n g t he C oc kcr oft Ga ult f or m ula bel o w:

Fe male Cr Cl = [( 1 4 0 - a ge i n years) x wei g ht i n k g x 0. 8 5] / [7 2 x ser u m 
creati ni ne i n m g/ d L];

Male Cr Cl = [( 1 4 0 -
a ge i n years) x wei g ht i n k g x 1. 0 0] / [7 2 x ser u m 
creati ni ne i n m g/ d L];
b.
If a n esti mate d Cr Cl is belie ve d t o be i nacc urate f or a partici pa nt, 2 4-h o ur uri ne 
c ollecti o n wit h act ual assess me nt of Cr Cl is all o we d.
1 2. A de q uate Li ver F u ncti o n, defi ne d as:
a.
T otal 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 
s yn dr o me;
b.
A S T a n d A L T ≤2. 5 x U L N; ≤5. 0 x U L N if t here is li ver i n v ol ve me nt b y  t he 
t u m or; 
c.
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 or li ver metastasis).
1 3. Partici pa nts wit h brai n metastases m ust meet all t he f oll o wi n g c o n diti o ns:
a.
Ha ve c o m plete d t heir pla n ne d c o urse of treat me nt;
b.
Ha ve rec o vere d fr o m t he ac ute effects of ra diati o n t hera p y or s ur ger y pri or t o first 
d ose;  
c.
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;
d.
Ha ve bee n o n sta ble d oses of a nti-seiz ure me dicati o ns (if a p plica ble) f or at least 3 
m o nt hs. A ntiseiz ure me dicati o ns m ust meet a n y  eli gi bilit y criteria o utli ne d f or 
c o nc o mita nt me dicati o ns.
e.
Are ne ur ol o gicall y sta ble f or 3 m o nt hs si nce t he c o ncl usi o n of t hera p y, as 
d oc u me nte d b y b ot h ne ur ol o gic a n d M RI e xa mi nati o ns.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 6
f.
Partici pa nts w h o are dia g n ose d wit h a C N S metastasis d uri n g t he scree ni n g peri o d 
m ust als o meet t hese criteria.
1 4. Res ol uti o n of ac ute effects of a n y  pri or t hera p y t o eit her baseli ne se verity or C T C A E 
Gra de ≥1 (e xce pt f or A Es n ot c o nstit uti n g a safety ris k i n t he i n vesti gat or’s 
j u d g me nt).
1 5. T S H 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 
pa rtici pa nts wit h a b n or mal T S H if Free T 4 is W N L
a n d partici pa nt is cli nicall y 
e ut h yr oi d, partic i pa nt is eli gi ble.
1 6. Ne gati ve ser u m or uri ne pre g na nc y  test f or w o me n of c hil d beari n g p ote ntial at 
scree ni n g a n d at C 1 D 1 ( bef ore t he patie nt ma y recei ve t he i n vesti gati o nal pr o d uct).
1 7. Male patie nts w h o are a ble t o fat her c hil dre n, a n d fe male patie nts of c hil d beari n g 
p ote ntial a n d at ris k f or pre g na nc y  m ust a gree t o use 2 hi g hl y effecti ve met h o ds of 
c o ntrace pti o n t hr o u g h o ut t he st u d y a n d f or at least 5 m o nt hs after t he last d ose of 
assi g ne d treat me nt.
1 8. Fe male patie nts w h o are n ot of c hil d beari n g p ote ntial as def i ne d bel o w, are eli gi ble t o 
be i ncl u de d (ie, meet at least 1 of t he f oll o wi n g criteria):
a.
Ha ve u n der g o ne a d oc u me nte d h y sterect o m y a n d/ or bilateral o o p h orect o m y;
b.
Ha ve me dicall y  c o nfir me d o varia n fail ure; or
c.
Ac hie ve d p ost me n o pa usal stat us, defi ne d as f oll o ws : cessati o n of re g ular me nses 
f or at least 1 2 c o nsec uti ve m o nt hs wit h n o alter nati ve pat h ol o gical or 
p h y si ol o gical ca use; a ser u m F S H le vel wit hi n t he la b orat or y’s refere nce ra n ge 
f or p ost me n o pa usal w o me n.
d.
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, lifestyl e c o nsi derati o ns, a n d ot her st u d y  
pr oce d ures. 
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:
Me dic al C o n diti o ns:
1.
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 . 
Partici pa nts wit h sec o n dar y  mali g na nc y t hat ha d bee n a de q uately treate d, or i n d ole nt 
t u m ors t hat w o ul d n ot i nterfere wit h safety a n d efficac y asse ss me nts mi g ht be 
all o we d after disc ussi o n wit h a n d a p pr o val fr o m t he s p o ns or. 
2.
Partici pa nts wit h a d va nce d/ metastatic, s y m pt o matic, visceral s prea d, t hat are at ris k 
of life-t hreate ni n g c o m plicati o ns i n t he s h ort ter m (i ncl u di n g partici pa nts wit h 
massi ve u n c o ntr olle d eff usi o ns [ ple ural, pericar dial, perit o neal], p ul m o nar y  
l ym p ha n gitis, a n d o ver 5 0 % li ver i n v ol ve me nt). N ote: Partici pa nts wit h i n d welli n g 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 7
cat heter f or drai na ge, or re q uire me nt f or drai na ge n o m ore fre q ue ntl y  t ha n m o nt hl y 
will be all o we d.
3.
Cli nica ll y i m p orta nt (e g, 1 5 0 / 9 0 m m H g) h y perte nsi o n des pite o pti mal me dical 
t hera py. 
4.
K n o w n or s us pecte d h y p erse nsiti vit y t o P F-0 7 2 6 0 4 3 7 or e xci pie nts . 
5.
Hist or y  of Gra de ≥3 i m m u ne me diate d A E (i ncl u di n g A S T/ A L T ele vati o ns t hat 
w here c o nsi dere d dr u g relate d a n d c y t o ki ne release s yn 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 wit hi n 1 y ear of 
treat me nt. Partici pa nts wit h Gra de 2 h y p ot h y r oi dis m or h yp o pit uitaris m res ulti n g 
fr o m i m m u n ot hera py o n sta ble h or m o ne re place me nt t hera p y a n d partici pa nts wit h 
c hr o nic a dre nal i ns ufficie nc y  recei vi n g d oses < 1 0 m g/ da y of pre d nis o ne e q ui vale nts 
are eli gi ble.
6.
Pri or irra diati o n t o > 2 5 % of t he b o ne marr o w (see A p pe n di x 1 0 , B o ne Marr o w 
Reser ve i n A d ults) . 
7.
Ot her me dical or ps y c hiatric 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/ 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 
of st u d y  partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt 
i na p pr o priate f or t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
8.
C urre nt use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s) or t h ose u n willi n g/ u na ble t o 
use a per mitte d c o nc o mita nt me dicati o n(s). Refer t o Secti o n 6. 8 , C o nc o mita nt 
T hera p y. 
9.
T hera pe utic a ntic oa g ulati o n wit h hi g h blee di n g ris k or acti ve blee di n g.
1 0. S y ste mic a nti-ca ncer t hera p y c he m ot hera p y or e n docri ne t hera p y wit hi n 4 wee ks or 5 
half -li ves ( w hic he ver is s h orter) pri or t o first d ose ( 6 wee ks f or mit o m y ci n C or 
nitr os o ureas). If t he last i m me diate a ntica ncer treat me nt c o ntai ne d a n a nti b o d y -base d 
a ge nt(s) (a p pr o ve d or i n vesti gati o nal), t he n a n i nter val of 3 wee ks 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 
treat me nt is re q uire d. 
1 1. 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. 
1 2. Maj or s ur ger y  wit hi n 3 wee ks pri or t o first d ose or d uri n g t he st u d y. Mi n or s ur ger y 
ma y  be all o we d after c o ns ultati o n wit h a n d a p pr o val fr o m sp o ns or.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 8
1 3. Ra diati o n t hera py wit hi n 3 wee ks pri or t o first d ose or d uri n g t he st u d y. Palliati ve 
ra diati o n t o a li mite d fiel d ma y be all o we d after c o ns ultati o n wit h a n d a p pr o val fr o m 
sp o ns or . 
Bl o o d pr o d uct s u p p ort:
1 4. Re q uire me nt f or peri o dic bl o o d pr o d uct tra nsf usi o ns f or a c hr o nic c o n diti o n . Bl o o d 
pr o d uct tra nsf usi o ns f or tra nsie nt a n d re versi ble c y t o pe nias t hat are sec o n dar y t o pri or 
a nti-ca ncer treat me nt are all o we d after disc ussi o n wit h t he s p o ns or.
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
1 5. 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 3 wee ks or 5 
half -li ves ( w hic he ver is s h orter) pri or t o first d ose . A partici pa nt ma y  be eli gi ble e ve n 
if t he y are i n t he f oll o w-u p p hase of a n i n vesti gati o nal st u d y as l o n g as t he y  ha ve n’t 
recei ve d treat me nt i n t he st u d y f or 4 wee ks of 5 half-li ves pri or t o first d ose. 
Di a g n ostic Assess me nts:
1 6. 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.
1 7. 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 
( b ut n ot li mite d t o) H B V, H C V, C O VI D-1 9/ S A R S -C o V 2, a n d k n o w n HI V or AI D S -
relate d ill ness. C o m me nts re gar di n g s pecific circ u msta nces f oll o w: 
a.
C O VI D -1 9/ S A R S - C o V 2: T his pr ot oc ol e xcl u des patie 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 patie nt has a 
p ositi ve test res ult n ot fr o m pri or C O VI D vacci nati o n b ut fr o m S A R S -C o V 2 
acti ve i nfecti o n ( n ot fr o m pri or vacci nati o n b ut fr o m acti ve 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 is 
e xcl u de d. C O VI D-1 9 vacci ne a d mi nistrati o n relati ve t o t he d osi n g of st u d y dr u g 
o n pla n ne d C 1 D 1 is at t he discreti o n of t he i n vesti gat or alt h o u g h i t ma y be best t o 
a v oi d a d mi nistrati o n t he 7 da ys pri or t o C 1 D 1 a n d c o nsi der t he p ote ntial f or 
vacci ne -relate d a d verse e ve nts.
b.
HI V : 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 ot her wis e healt h y a n d at l o w ris k f or 
AI D S -relate d o utc o mes c o ul d be c o nsi dere d eli gi ble. P ote ntial eli gi bilit y f or a 
s pecific HI V p ositi ve pr ot oc ol ca n di date s h o ul d be e val uate d a n d disc usse d wit h 
t he s p o ns or pri or t o a ny s cree ni n g, 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 nfecti o ns), 
a n d stat us of HI V treat me nt. Healt h y HI V p ositi ve partici pa nts w h o are i ncl u de d 
s h o ul d be treate d usi n g t he sa me sta n dar ds as trial partici pa nts wit h ot her 
c o m or bi dities.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 9 9
c.
H B V/ H C V : Rele va nt la b orat or y  tests s h o ul d be perf or me d at scree ni n g, see ta ble 
i n A p pe n di x 2 . Refer t o C D C we bsite ( htt ps:// w w w.c dc. g o v/ he patitis/i n de x. ht m) 
f or f urt her details. 
d.
H B V: 

T his criteri o n e xcl u des partici pa nts wit h a p ositi ve H Bs A g (ie, eit her ac ute or 
c hr o nic acti ve he patitis). 

H o we ver, partici pa nts wit h H B V a nti b o d y p ositi vit y  i n dicati n g i m m u nit y, 
eit her d ue t o vacci nati o n or pri or nat ural i nfecti o n, are eli gi ble.

Patie nts wit h p ositi ve a nti -H Bc A b b ut n e gati ve H Bs A g a n d a nti -H Bs A b 
pr ofile ma y , de pe n di n g o n cli nical circ u msta nces, be eli gi ble. Disc ussi o n wit h 
t he s p o ns or is i n dicate d. Patie nts w h ose cli nical hist or y a n d pr ofile s u g gest 
eit her l o w le vel c hr o nic i nfecti o n or res ol vi n g ac ute i nfecti o n s h o ul d n ot be 
c o nsi dere d eli gi ble.
e.
H C V :

P ositi ve H C V a nti b o d y  is i n dicati ve of i nfecti o n b ut ma y n ot necessarily 
re n der a p ote ntial ca n di date i neli gi ble, de pe n di n g o n cli nical circ u msta nces. 
Disc ussi o n wit h t he s p o ns or is i n dicate d. If e x p os ure t o H C V is rece nt, H C V 
a nti b o d y ma y n ot ha ve yet t ur ne d p ositi ve. I n t his circ u msta nce it is 
rec o m me n de d t o test f or H C V R N A. Refer t o C D C we bsite f or f urt her details 
(htt ps:// w w w.c dc. g o v/ he patitis/ hc v/ p dfs/ hc v _ gra p h. p df ). 
1 8. Baseli ne sta n dar d 1 2 -lea d 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 
Q Tc F > 4 7 0 ms, c o m plete L B 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-T i nter val c ha n ges s u g gesti ve of acti ve m y oc ar dial isc he mia, sec o n d 
or -t hir d-de gree A V bl oc k, or seri o us bra d y arr h yt h mias or tac h yarr h yt h mias) . If t he 
baseli ne u nc orrecte d Q Tc F is > 4 7 0 ms, 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. Q Tc F e xcee ds 4 7 0 ms, or Q R S c o m ple x e xcee ds 1 2 0 ms, 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 F or Q R S c o m ple x val ues 
s h o ul d be use d t o deter mi ne t he partici pa nt’s eli gi bilit y. C o m p uter i nter prete d -E C Gs 
s h o ul d be o ver-rea d by a p h ysicia 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 t he s p o ns or t o j u d ge eli gi bilit y.
1 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, cli nicall y  i m p orta nt atrial or ve ntric ular arr h yt 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 yste m a b n or malities (e g, bifascic ular bl oc k [ defi ne d as ri g ht b u n dle 
bra nc h a n d left a nteri or or p osteri or he mi bl oc k], 3r d de gree A V 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 H F, Ne w Y or k Heart 
Ass ociati o n C lass III or I V, cere br o vasc ular acci de nt, tra nsie nt isc he mic attac k, 
s ym 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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 0
t hr o m b o-e m b olic disease . O n g oi n g car diac d ys r hyt h mias of N CI  C T C A E ≥ Gra de 2, 
atrial fi brillati o n of a n y gra de ( ≥ Gra de 2 i n t he case of as y 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 ms, t he partici pa nt ma y  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 t he s p o ns or t o j u d ge eli gi bilit y .
Ot her E xcl usi o ns :
2 0. I n vesti gat or site staff or Pfizer e m pl o yees directl y i n v ol ve d i n t he c o n d uct of t he 
st u d y, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d t heir res pecti ve fa mil y 
me m bers.
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 desi 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 , Secti o n 1 0. 4. 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 sc he d ule of acti vities ( 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 selecte d met h o ds of c o ntrace pti o n) c o nsi deri n g t hat t heir ris k f or 
pre g na nc y  m a y ha ve c ha n ge d si nce t he last visit. 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.
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nt s 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 nr olle d i n t he st u d y. A mi ni mal set of scree n fail ure i nf or mati o n is 
re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure partici pa nts t o meet t he C O N S O R T 
p u blis hi n g re q uire m e nts a n d t o res p o n d t o q ueries fr o m re g ulat or y  a ut h orities. Mi ni mal 
i nf or mati o n i ncl u des de m o gra p hy,  scree n fail ure details, eli gi bilit y criteria, a n d a n y S A E.
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 st u d y (scree n fail ure) ma y be
rescree ne d, u p t o a li mit of 1 ti me. 
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
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, me dical de vice(s), or st u d y  pr oce d ure(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, st u d y  i nter ve nti o n refers t o i n vesti gati o nal pr o d uct.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 1
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
I nter ve nti o n N a me
P F -0 7 2 6 0 4 3 7
A r m  N a me
( gr o u p of p artici p a nts recei vi n g a 
s pecific tre at me nt ( or n o tre at me nt)
All
T y pe
Bi ol o gic
D ose F or m ul ati o n
P o w der f or 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 5 m g/ vial
1 5 m g/ m L , 1 m L per vial
D os a ge Le vel(s)
D ose a m o u nt a n d fre q ue nc y – refere nce t he st u d y 
sc he me/fi g ure or te xt bel o w as a p pr o priate
R o ute of A d m i nistr ati o n
S C or I V
Use
E x peri me ntal
I M P or NI 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. Refere nce I P ma n ual f or 
s u p pl y distri b uti o n pr ocess details. 
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 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 o pe n -la bel pr o d uct.
C urre nt/ F or mer N a me(s) or Ali as(es)
P F -0 7 2 6 0 4 3 7, B 7 -H 4 bis pecific a nti b o d y
Eac h si n gle -use vial of li q ui d f or m ulati o n c o ntai ns 1 m L  of P F - 0 7 2 6 0 4 3 7 1 5 m g/ m L . T he 
vial is seale d wit h a c oate d st o p per a n d a n o verseal a n d is la bele d acc or di n g t o l ocal 
re g ulat or y re q uire me nts.
I n patie nt O bser vati o n
F or P F -0 7 2 6 0 4 3 7 a d mi nistrati o n wit h o ut a pri mi n g d ose, all partici pa nts 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 (or t he first I V d ose, as a p plica ble) 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 ( or t he sec o n d I V d ose, as a p plica ble)
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 o ut patie nt visits t o cl osel y 
ma na ge a n d m o nit or ac ute t o xicities .
F or P F - 0 7 2 6 0 4 3 7 a d mi nistrati o n wit h a pri mi n g d ose, 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 i nj ecti o n (or t he first I V d ose a d mi nistrati o n, 
as a p plica ble ) o n C 1 D 1 a n d f or at least 2 4 h o urs after t he sec o n d (f ull) S C d ose ( or t he 
sec o n d [f ull] I V d ose, as a p plica ble) o n C 1 D 1 5 t o cl osel y  ma na ge a n d m o nit or ac ute 
t o xicities. Partici pa nts s h o ul d be o bser ve d f or at least 1 h o ur p ost S C d ose f or all o ut patie nt 
visits starti n g wit h C 2 D 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 R S ( Ta ble 7 ). A d diti o nal i n patie nt o bser vati o n f or s u bse q ue nt 
c ycles of I V d osi n g b e y o n d C y cle 1 ma y be c o nsi dere d base d o n t he i n vesti gat or’s discreti o n 
a n d s h o ul d be disc usse d wit h t he s p o ns or.
I n a d diti o n, partici pa nts w h o e x perie nce ≥ Gra de 3 i nf usi o n -relate d a d verse e ve nts (I V 
a d mi nistrati o n) or cli nicall y  si g nifica nt C R S m ust be h os pitalize d f or at least 2 4 h o urs f or at 
least 4 s u bse q ue nt d oses (t w o c y cles).  
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 2
M o dificati o n of i n patie nt o bser vati o n peri o d m i ght be all o we d base d o n e mer gi n g safet y data 
a n d will re q uire disc ussi o n a n d a gree me nt bet wee n i n vesti gat or a n d s p o ns or.
6. 1. 1. A d mi nistr ati o n
6. 1. 1. 1. Pre me dic ati o n
Pr o p h y lactic pre me dicati o n f or i nf usi o n relate d reacti o n, aller gic reacti o n or C R S is n ot 
all o we d d uri n g t he D L T e val uati o n peri o d d uri n g i nitial d ose escalati o n . H o we ver, i f t he 
partici pa nt e x perie nces a n i nf usi o n relate d reacti o n (I V), si g nifica nt i njecti o n site reacti o n, 
C R S, fe ver/c hills, na usea/ v o miti n g, h yp ote nsi o n, or pai n, a p pr o priate treat me nt s h o ul d 
i nitiate a n d pre me dicati o n as pr o p hyl a xis ma y  be c o nsi dere d f or s u bse q ue nt c ycles 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 0 m g ( or e q ui vale nt), oral or I V
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 all o we d per h os pital or l ocal 
cli nical practice after 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.
Base d o n a re vie w of all acc u m ulate d safet y data (e g , > 5 0 % of partici pa nts e x perie nce d 
si g nifica nt aller gic reacti o n or C R S relate d s ym pt o ms a n d si g ns) , pr o p hyl actic pre me dicati o n 
ma y  be c o nsi dere d f or ne w partici pa nts after a gree me nt bet wee n i n vesti gat ors a n d t he 
s p o ns or t o deter mi ne t he M T D/ R D E wit h pr o p h yla xis.
I n a d diti o n, de pe n di n g o n acc u m ulate d safety data, pr o p h yl actic pre me dicati o n d uri n g c ycle 
1 after i de ntificati o n of t he ma xi m u m t olerate d d ose ( M T D)/rec o m me n de d d ose f or 
e x pa nsi o n ( R D E) ma y be all o we d.
T he pre -treat me nt me dicati o n will n ot be s u p plie d b y sp o ns or.
6. 1. 1. 2. S C A d mi nistr ati o n
Q ualifie d a n d trai ne d i n vesti gati o nal site pers o n nel will a d mi nister P F -0 7 2 6 0 4 3 7 t o 
partici pa nts b y S C i njecti o n. P F -0 7 2 6 0 4 3 7 will be a d mi nistere d at a flat d ose via S C 
i njecti o n Q 2 W at 2 8-da y  c ycles ( o n Da y 1 a n d Da y 1 5) u ntil t he partici pa nt meets o ne of t he 
st u d y i nter ve nti o n disc o nti n uati o n criteria ( See Secti o n 7. 1 ). 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 wit h prefere nce t o t he l o wer q ua dra nts w he n p ossi ble. F or 
partici pa nts recei vi n g 2 or m ore S C i njecti o ns, P F - 0 7 2 6 0 4 3 7 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. Refer t o A p pe n di x 1 4 , for details o n a d mi nistrati o n of 
m ulti ple i njecti o ns t o t he a b d o me n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 3
Eac h i njecti o n v ol u me ma y  be u p t o 2 ml i n v ol u me. If a n i nstit uti o nal p olic y sets a 
ma xi m u m v ol u me < 2 ml, t he n u m ber of i njecti o ns ma y  be i ncrease d t o e ns ure t hat t he c orrect 
v ol u me is a d mi nistere d. Refer t o t he I P Ma n ual f or s pe cific i nstr ucti o ns o n t he ha n dli n g a n d
pre parati o n of st u d y  treat me nt.
Refer t o Ta ble 7 f or re q uire d i n patie nt o bser vati o n sta ys f oll o wi n g P F-0 7 2 6 0 4 3 7 
a d mi nistrati o n.
6. 1. 1. 3. I V A d mi nistr ati o n
If IV r o ute is e val uate d. Q ualifie d a n d trai ne d i n vesti gati o nal site pers o n nel will a d mi nister 
P F -0 7 2 6 0 4 3 7 t o partici pa nts b y  IV i nf usi o n. P F -0 7 2 6 0 4 3 7 will be a d mi nistere d at a flat d os e
i ntra ve n o usl y o ver a p pr o xi matel y  6 0 mi n utes (± 1 5 mi n utes) Q 2 W at 2 8 -da y c y cles ( o n Da y 1 
a n d Da y 1 5) u ntil t he partici pa nt meets o ne of t he st u d y i nter ve nti o n disc onti n uati o n criteria 
(see Secti o n 7. 1 ).
If I V r o ute is e val uate d, a 1-h o ur i nf usi o n a n d i n patie nt m o nit ori n g i n a h os pital f or at least 
4 8 h o urs after t he first d ose i n C y cle 1 i n d ose escalati o n will be i m ple me nte d. A d diti o nal 
i n patie nt o bser vati o n f or s u bse q ue nt c ycles be yo n d C y cle 1 ma y be c o nsi dere d base d o n t he 
i n vesti gat or’s discreti o n a n d s h o ul d be disc usse d wit h t he sp o ns or as descri be d i n
Secti o n 6. 1 .
Details f or pre parati o n of P F -0 7 2 6 0 4 3 7 i nf usi o n are pr o vi de d i n t he I P Ma n ual.
6. 2. Pre p ar ati o n, H a n dli n g, St or a ge a n d Acc o u nt a bilit y
1.
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 
bee 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. 
2.
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 ntrolle 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 ons 
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 y s m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures 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.
3.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la b el st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h a ny acti o ns ta ke n . 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 i n 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. S pecific details re gar di n g t he defi niti o n of a n e xc ursi o n 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 4
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.
4.
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 la bel.
5.
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.
6.
See t he I P ma n ual 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. S pecific details of t he dil uti o n are pr o vi de d i n t he I P Ma n ual.
7.
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 bilit 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), s uc h as t he 
I P A L or s p o ns or-a p pr o ve d e q ui vale nt . 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. 
8.
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 IP ma n ual . All destr ucti o n m ust be a de q uatel y  
d oc u me nte d . 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.
U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y t he s p o ns o r wit hi n 1 b usi ness da y of 
disc o ver y  as descri be d i n t he IP ma n ual.
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
A q ualifie d staff me m ber will dis pe nse t he st u d y  i nter ve nti o n usi n g t he I RT s y ste m via 
u ni q ue c o ntai ner n u m bers i n t he vials pr o vi de d, i n q ua ntities a p pr o priate acc or di n g t o t he 
partici pa nt’s d ose . A sec o n d staff me m ber will verif y  t he dis pe nsi n g. 
See t he I P ma n ual f or i nstr ucti o ns 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 . St u d y  i nter ve nti o n 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 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. Vials are si n gle use.
O nl y  q ualifie d pers o n nel w h o are fa miliar wit h pr oce d ures t hat mi ni mize u n d ue e x p os ure t o 
t he msel ves a n d t o t he e n vir o n me nt s h o ul d u n derta ke t he pre parati o n, ha n dli n g, a n d safe 
dis p osal of P F -0 7 2 6 0 4 3 7. 
6. 3. 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. 3. 1. All oc ati o n t o St u d y I nter ve nti o n
F or Part 1: 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 5
St u d y  i nter ve nti o n will be dis pe nse d at t he st u d y visits 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 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 IR T refere nce ma n ual a n d I P 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 ys te m
D ose le vel all ocati o n i n Part 1 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 scree ni n g assess me nts. T he 
site staff will fa x/e mail a c o m plete Partici pa nt 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 sp 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.
N o partici pa nt s hall recei ve i n vesti gati o nal pr o d uct/st u d y  i nter ve nti o n 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 sp 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 partici 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.
I n Part 1, sites will use t he IR T f or dr u g s u p pl y a n d i n ve nt or y ma na ge me nt. 
F or Part 2:
All ocati o n of partici pa nts i n Part 2 of t he st u d y  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 R T s ys te m (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 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 user’s I D a n d 
pass w or d, t he pr ot oc ol n u m ber, a n d t he partici pa nt n u m ber. T he site pers o n nel will t he n be 
pr o vi de d wit h a treat me nt assi g n me nt, 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 
w he n st u d y  i nter ve nti o n is bei n g s u p plie d via t he I R T s ystem. T he I R T s ys te 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. 
St u d y  i nter ve nti o n will be dis pe nse d at t he st u dy visits 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 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 R T refere nce ma n ual a n d I P 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 h e I R T s ys te m.
6. 4. St u d y I nter ve nti o n C o m pli a nce
W he n partici pa nts are d ose d at t he site, t he y  will recei ve st u d y i nter ve nti o n directl y fr o m t he 
i n vesti gat or or desi g nee, u n der me dical s u per visi o n. T he date a n d ti me of eac h d ose 
a d mi nistere d i n t he cli nic will be rec or de d i n t he s o urce d oc u me nts a n d rec or de d i n t he C R F. 
T he d ose of st u d y i nter ve nti o n a n d st u d y partici pa nt i de ntificati o n will be c o nfir me d at t he 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 6
ti me of d osi n g by a me m ber of t he st u d y site staff ot her t ha n t he pers o n a d mi nisteri n g t he 
st u d y i nterve nti o n . 
T he site will c o m plete t he 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 c li nical site's 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 sp o ns or a n d/ or desi g nee.
6. 5. 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 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, or disc o nti n ue d as descri be d bel o w . I n 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. 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 n y a d verse sy m pt o m . I n a d diti o n t o d ose 
m o dificati o ns, i n vesti gat ors are e nc o ura ge d t o e m pl o y best s u p p orti ve care acc or di n g t o l ocal 
i nstit uti o nal cli nical practices.
T o xicities p ote ntiall y  relate d t o P F-0 7 2 6 0 4 3 7 s h o ul d be ma na ge d acc or di n g t o t he d ose 
m o dificati o ns descri be d i n Ta ble 1 0 a n d Ta ble 1 1 . 
Selecte d t o xicities t hat d o n ot res ol ve or w orse n f oll o wi n g s u p p orti ve care a n d d ose 
m o dific ati o ns a n d wit h a cli nical prese ntati o n c o nsiste nt wit h a p ote ntial ir A E wit h o ut a clear 
alter nati ve e x pla nati o n, ma y  re q uire treat me nt wit h c ortic oster oi ds or ot her 
i m m u n os u p pressa nts a n d s h o ul d be ma na ge d acc or di n g t o t he ma na ge me nt of ir A Es as 
descri be d i n Secti o n 1 0. 3. 5 .
C R S s h o ul d be ma na ge d acc or di n g t o t he C R S Miti gati o n a n d Ma na ge me nt g ui da nce as 
descri be d i n A p pe n di x 1 1 . 
6. 5. 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, 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 xicit y or i nt olera ble Gra de 2 t o xicit y  des pite s u p p orti ve treat me nt s h o ul d 
ha ve t heir treat me nt i nterr u pte d as i n dicate d i n Ta ble 1 0 a n d Ta ble 1 1 . 
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 
Secti o n 6. 5. 2 .
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 E 
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 s u bse q ue nt pla n ne d 
d oses wit hi n t hat sa me c y cle or t o dela y t he i nitiati o n of t he s u bse q ue nt c ycle as f oll o ws:
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 7

If t he pla n ne d Da y 1 d ose ( of a ny c ycle) ca n n ot be a d mi nistere d d ue t o a n A E, t he n 
D a y  1 d ose will be dela ye d u ntil t he A E has res ol ve d a n d t he st u dy dr u g ca n be 
a d mi nistere d. 

If t he pla n ne d Da y 1 5 d ose ( of a ny c ycle) is dela ye d f or ≤7 da y s, t he n t he pla nne d d a y  
1 5 d ose ca n be a d mi nistere d as t he dela ye d D a y  1 5 d ose . Da y 1 of t he s u bse q ue nt 
c ycle will be a d mi nistere d 2 wee ks after t he dela ye d Da y  1 5 d ose.

If t he pla n ne d Da y 1 5 d ose ( of a ny c ycle) is dela ye d f or > 7 da ys, t he n Da y 1 5 will be 
s ki p pe d. T he ne xt d ose will be a d mi nistere d w he n t he A E has res ol ve d a n d will be 
c o nsi dere d t he Da y 1 d ose of t he s u bse q ue nt 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 ose 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.
See A p pe n di x 8 , Secti o n 1 0. 8. 4 f or C O VI D-1 9 relate d d ose i nterr u pti o n. 
6. 5. 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 nicall y 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 2 6 0 4 3 7 ma y  be 
res u me d. Refer t o t he D ose Re d ucti o ns Secti o n 6. 5. 3 f or A Es 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 2 6 0 4 3 7 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 the sp o ns or. I n 
t his sit uati o n, if a treat me nt i nterr u pti o n c o nti n ues f or m ore t ha n 4 wee ks, 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. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 8
6. 5. 3. D ose 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 PF- 0 7 2 6 0 4 3 7 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 or 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 y s 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.
D ose re d ucti o n of P F- 0 7 2 6 0 4 3 7 b y  1 a n d, if nee de d, 2 d ose le vels ( See Ta ble 9 ) 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. 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. All d ose 
m o d ificati o ns/a dj ust me nts m ust be clearly 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.
T a ble 9 .  
A v ail a ble D ose Re d ucti o n Le vels Fr o m St arti n g D ose
D ose Le vel
P F -0 7 2 6 0 4 3 7 S C
P F -0 7 2 6 0 4 3 7 I V
Starti n g d ose
1 0 0 µ g Q 2 W
6 0 µ g Q 2 W
-1
6 0 u g Q 2 W ( o ne d ose le vel bel o w starti n g d ose)
N /A
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 
re d uce t he d ose t o 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. 
Rec o m me n de d d ose m o dificati o ns of P F- 0 7 2 6 0 4 3 7 f or n o n -i m m u ne relate d t o xicit y are 
descri be d i n Ta ble 1 0 . 
T a ble 1 0 .
D ose M o dific ati o ns f or St u d y f or N o n-I m m u ne-Rel ate d T o xicit y
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 
(e xce pt 
pa ncreatitis)
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 d ose b y  
1 le vel at t he discreti o n of t he 
i n vesti gat or.*
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 
d ose b y 1 le vel or 2 le vels, or 
per m a ne ntl y disc o nti n ue at 
t he discreti o n of t he 
i n vesti gat or.*
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 9
T a ble 1 0 .
D ose M o dific ati o ns f or St u d y f or N o n-I m m u ne-Rel ate d T o xicit y
T o xicit y
Gr a de 1  
Gr a de 2  
Gr a de 3
Gr a de 4
Pa ncreatitis
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 res ol ve d, 
t he n re d uce 
t he d ose b y 
1 le vel.
C o nsi der disc o nti n uati o n 
(c o nti n uati o n re q uires 
s p o ns or a p pr o val).
Per m a ne nt disc o nti n uati o n of 
st u d y dr u g f or relate d Gra de 
4 a d verse e ve nts of a n y 
d urati o n.
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 re d uce t he 
d ose b y 1 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 re d uce t he 
d ose b y 1 le vel or 2 le vels or 
per ma ne ntl y disc o nti n ue at 
t he discreti o n of t he 
i n vesti gat or.*
* 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.
Rec o m me n de d d ose m o dificati o ns of st u d y  i nter ve nti o n f or i m m u ne relate d t o xicit y are 
descri be d i n Ta ble 1 1 . Please refer t o Secti o n 1 0. 3. 5 f or detaile d d ose m o dificati o n a n d 
c o m pre he nsi ve ma na ge me nt of ir A Es.
T a ble 1 1 . D ose M o dific ati o ns f or I m m u ne -Rel ate d T o xicit y
Or ga n S yste m
Gra de 1
Gra de 2
Gra de 3
Gra 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 
i mpr o ves t o Gra de 
1, res u me treat me nt . 
If persists > 5-7 da ys 
or rec ur treat as 
G ra de 3 or 4 .
Wit h h ol d 
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 sa me 
d ose le vel or re d uce 
t he P F-0 7 2 6 0 4 3 7 
d ose b y 1 le vel 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 n.t
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.
C o nti n ue 
i n vesti gati o nal 
treat me nt. If persists 
> 1 -2 w ee 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 
i n vesti gati o nal 
treat me nt.
If i mpr o ves t o 
Gra de 1 after 
treat me nt, res u me 
i n vesti gati o nal 
t hera p y.
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.
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.
Wit h h ol d 
i n vesti gati o nal 
treat me nt; re-i ma ge. 
Disc o nti n ue  
Disc o nti n ue
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 0
T a ble 1 1 . D ose M o dific ati o ns f or I m m u ne -Rel ate d T o xicit y
Or ga n S yste m
Gra de 1
Gra de 2
Gra de 3
Gra de 4
M o nit or
If s y m pt o ms ret ur n 
t o baseli ne, t he n 
res u me 
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; i ncrease 
m o nit o ri n g of L F Ts; 
res u me 
i n vesti gati o nal 
t hera pe utic if la bs 
ret ur n t o baseli ne.
If ele vati o ns persist 
≥5 t o 7 da ys or 
w orse n, treat wit h 
c ortic oster oi ds, 
res u me 
i n vesti gati o nal 
treat me nt if la bs 
ret ur n t o Gra de 1 or 
baseli ne .
Disc o nti n ue  
Disc o nti n ue
E n d ocri n o pat hies 
( h y p ot h yr oi dis m, 
h y pert h yr oi dis m, 
a dre nal 
i ns ufficie nc y, t y pe 
1 dia betes 
mellit us)
C o nti n ue 
i n vesti gati o nal 
treat me nt.
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 
i mpr o ves t o Gra de 1 
after treat me nt, 
res u me 
i n vesti gati o nal 
t hera p y.
Disc o nti n ue
6. 6. C o nti n ue d Access t o St u d y 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 per pr ot oc ol t o st u d y  partici pa nts be yo n d t he e n d of t he 
st u d y. 
6. 7. 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 2 6 0 4 3 7 greater t ha n t he i nte n de d d ose le vel at a n y st u d y 
i nter ve nti o n a d mi nistrati o n ti me p oi nt 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 ician 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 1
2.
Cl osel y  m o nit or t he partici pa nt f or a ny 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 P F-0 7 2 6 0 4 3 7 ( w hic he ver 
is l o n ger). 
3.
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.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nl y w he n ass oci ate d wit h a n S A E .
5.
O btai n a bl o o d sa m ple f or P K a nal ys is wit hi n 2 wee ks fr o m t he date of t he last d ose 
of 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) . 
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 o f t he partici pa nt. 
6. 8. 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, 
par ace ntesis) recei ve d b y partici pa nts fr o m scree ni n g u ntil t he e n d of treat me nt visit will be 
rec or de d o n t he C R F.
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 u l 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 2 6 0 4 3 7 tra nsie ntl y i ncrease d ser u m c yt o ki ne le vels (e g, I L-6) i n m o n ke y s i n vi v o a n d 
li kel y i n patie nts (als o de m o nstrate d via i n vitr o h u ma n a n d m o n ke y P B M C assa ys) w hic h is 
e x pecte d wit h C D 3- tar gete d bis pecifics. Cyt o ki nes ha ve bee n s h o w n t o res ult i n d o w n -
re g ulati o n of s o me C Y P 4 5 0 e nz y mes. T heref ore, treat me nt wit h P F -0 7 2 6 0 4 3 7 has a 
t he oretical p ote ntial t o 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 nzy m es. 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 Y P 4 5 0 e nz y mes 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 y cle. Refer t o 
A p pe n di x 1 5 f or details o n t he list of dr u gs w hic h ma y  res ult i n a dr u g - dr u g i nteracti o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 2
6. 8. 1. Pr o hi bite d a n d/ or Li mite d use of A nti -t u m or/ A nti-C a ncer or E x peri me nt al 
Dr u gs, or Pr oce d ures
N o a d diti o nal a ntit u m or treat me nt will be per mitte d w hile partici pa nts are recei vi n g st u d y 
treat me nt.
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 2 6 0 4 3 7 wit h ra di ot hera py, 
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 ons 
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. 
P F - 0 7 2 6 0 4 3 7 treat me nt s h o ul d be i nterr u pte d d uri n g palliati ve ra diot hera p y , st o p pi n g 7 da ys 
bef ore a n d res u mi n g treat me nt after rec o ver y  t o baseli ne.
6. 8. 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  be 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 S C O g ui deli nes.
6. 8. 2. 1. S u p p ort i 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 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 ycar 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 s ym pt o ms occ ur . T he 
se verity of C R S will be assesse d acc or di n g t o t he m o difie d gra di n g descri be d b y  Lee et al 
(Lee et al, 2 0 1 9 ). A s u g geste d treat me nt al g orit h m f or t he ma na ge me nt of C R S is als o 
pr o vi de d i n A p pe n di x 1 1 ; h o we ver, if l ocal sta n dar d of care is a differe nt re gi me n t his s h o ul d 
be utilize d. 
T he decisi o n t o i nc or p orate pre -me dicati o n (ie, c ortic oster oi ds) 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 . 
T he pre -treat me nt me dicati o n will n ot be s u p plie d b y t he sp o ns or.
6. 8. 2. 2. S u p p ort i ve C are f or I m m u ne Effect or Cell -Ass oci ate d Ne ur ot o xicit y S y n dr o me 
(I C A N S)
I C A N S is defi ne d as dis or der c haracterize d by a pat h ol o gic pr ocess i n v ol vi n g t he ce ntral 
ner v o us s ys te m f oll o wi n g a ny i m m u ne t hera p y t hat res ults i n t he acti vati o n or e n ga ge me nt of 
e n d o ge n o us or i nf use d T cells a n d/ or ot her i m m u ne effect or cells. S y m pt o ms or si g ns ca n be 
pr o gressi ve a n d ma y  i ncl u de a p hasia, altere d le vel of c o nsci o us ness, i m pair me nt of c o g niti ve 
s kills, m ot or wea k ness, seiz ures, a n d cere bral e de ma. It has bee n o bser ve d f oll o wi n g 
a d mi nistrati o n of s o me C A R T cells a n d bis pecific a nti b o dies a n d ca n occ ur i n de pe n de ntl y of 
C R S. T he se verit y  of I CA N S s h o ul d be gra de d acc or di n g t o t he A S TC T c o nse ns us criteria
(Lee et al, 2 0 1 9 ). Ge n eral ma na ge me nt g ui deli nes ca n be f o u n d i n Neela p u et al (Neela p u et 
al, 2 0 1 8; Neela p u, 2 0 1 9 ) or per l ocal sta n dar d of care practice. T hese treat me nt g ui deli nes 
ma y  be m o difie d as nee de d b y t he res p o nsi ble i n vesti gat or acc or di n g t o t he best practices at 
t heir i nstit ute. Ma na ge me nt g ui deli nes are pr o vi de d i n A p pe n di x 1 1 , Secti o n 1 0. 1 1. 2 .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 3
6. 8. 2. 3. S u p p ort i ve C are f or I nf usi o n Rel ate d Re acti o ns (I V i nf usi o n o nl y)
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 partici 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 verity. I n t he e ve nt of I RRs, i n 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. 8. 2. 4. S u p p ort i ve C are f or I njecti o n Site R e acti o ns (I S R)
I S R is a ty pe of h y p erse nsiti vit y reacti o n t hat ma y be i m me diate, alt h o u g h it us uall y a p pears 
wit hi n 2 4 - 4 8 h o urs after i njecti o n. IS R, b y  defi niti o n, i ncl u des t he f oll o wi n g er yt he ma, 
pr urit us, pai n, i nfla m mati o n, ras h, i n d urati o n, itc hi n g a n d e de ma at t he i njecti o n site. T o 
e val uate I S Rs, site t olera bilit y assess me nts will be perf or me d per t he Sc he d ule of Acti vities .
I S R will n ot be c o nsi dere d D LTs b ut ma y  be a reas o n f or disc o nti n uati o n of S C d osi n g.
T o pical c ortic oster oi ds a n d t o pical or s y ste mic a nti hista mi nes ma y be a p plie d t o treat a ny 
ras h or pr uritis at t he i njecti o n site de pe n di n g o n t he se verit y a n d per i n vesti gat or’s 
assess me nt.
6. 8. 2. 5. S u p p ort i 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. I mm 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 kel y t o be dela 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 y m 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 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 y perse 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.
Detaile d g ui da nce o n treat me nt, d ose i nterr u pti o ns a n d p o te ntial re-treat me nt is pr o vi de d
Secti o n 6. 5 .
6. 8. 2. 6. 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 ir A Es is mai nl y  de pe n de nt u p o n se verity ( N CI 
C T C A E gra de versi o n 5. 0 (latest versi o n as a p plica ble). I n ge neral, Gra de 1 or 2 ir A Es are 
treate d sy m pt o maticall y wit h persiste nt Gra de 2, Gra de 3 , or Gra de 4 ir A Es ma na ge d wit h 
m o derate t o hi g h d ose c ortic oster oi ds.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 4
G ui deli nes o n t he treat me nt of ir A Es are pr o vi de d i n A p pe n di x 3 , Secti o n 1 0. 3. 5 .
A m ore detaile d s u m mar y of Ma na ge me nt of I m m u ne Relate d A Es is descr i be d i n Bra h mer 
et al (Bra h mer et al, 2 0 1 8 ).
6. 8. 3. He m at o p oietic Gr o wt h F act ors
Pri mar y  pr o p h ylactic use of c ol o n y sti m ulati n g fact ors is n ot per mitte d d uri n g t he D L T 
assess me nt peri o d i n Part 1, 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 by t he c urre nt A S C O g ui deli nes (S mit h et al, 2 0 0 6 ). D uri n g t he scree ni n g wi n d o w 
(ie, 1 4 da ys pri or t o Da y 1), Gra n ul oc yte c ol o n y sti m ulati n g fact ors are 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. 
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. 
If t he l ocal i n dicati o n a n d d osa ge of G- C S F c o m p o u n ds differs fr o m A S C O g ui deli nes, refer 
t o t he l ocal pr o d uct la bel or f oll o w t he c o u ntr y’s cli nical practice.
6. 8. 4. A nti di arr he al, A ntie metic T her a p y 
Pri mar y  pr o p h yla xis is n ot rec o m me n de d d uri n g t he i nitial d ose escalati o n. H o we ver, if t he 
partici pa nt e x perie nces na usea, v o miti n g or diarr hea, a p pr o priate treat me nt a n d s u p p orti ve 
care s h o ul d be i nitiated . P r o p h yla xis ma y  be c o nsi dere d f or s u bse q ue nt i njecti o ns as well as 
f or ne w partici pa nts at t he i n vesti gat or’s discreti o n . T he c h oice of t he pr o p h y lactic 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 ass u mi n g t he dr u g is n ot i ncl u de d 
Secti o n 6. 8 , C o nc o mita nt T hera p y.
Diarr hea is a p ossi ble a d verse e ve nt . As t here is n o pri or cli nical e x perie nce wit h 
P F -0 7 2 6 0 4 3 7, t he e xact nat ure of treat me nt relate d diarr hea i n h u ma ns is u n k n o w n . I n 
ge neral, ma na ge me nt of ca ncer treat me nt- i n d uce d diarr hea ha ve bee n descri be d (Be ns o n et 
al, 2 0 0 4). 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 irA Es f or 
diarr hea ( Secti o n 1 0. 3. 5 ) 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 y sf u ncti o n
6. 8. 5. C ortic oster oi ds 
C hr o n ic s yste 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. 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 5
6. 8. 6. 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 Secti o n 6. 8 , 
C o nc o mi ta nt T hera py. 
6. 8. 7. S ur ger y 
Ca uti o n is a d vise d 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 2 6 0 4 3 7 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 2 6 0 4 3 7 is rec o m me n de d at 
least 7 da ys pri or t o s ur ger y. P ost o perati vel y, t he decisi o n t o rei nitiate P F - 0 7 2 6 0 4 3 7 
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. P ost o perati vely, t he decisi o n t o rei nitiate P F-0 7 2 6 0 4 3 7 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. Palliati ve ra di ot hera p y t o s pecific sites of disease will be per mitte d if c o nsi dere d 
me dicall y  necessar y b y t he treati n g ph y sicia n. All atte m pts will be ma de t o r ule o ut 
pr o gressi ve disease i n t he e ve nt of i ncrease d l ocalize d pai n.
6. 8. 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 2 6 0 4 3 7; 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.
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
It ma y be necessar y f or a partici pa nt t o per ma ne ntl y disc o nti n ue st u d y i nter ve nti o n. Reas o ns 
f or per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n ma y i ncl u de t he f oll o wi n g:

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;

L ost t o f oll o w - u p;

Partici pa n t 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;
N ote t hat disc o nti n uati o n of st u d y  i nter ve nti o n d oes n ot re prese nt wit h dra wal fr o m t he st u d y. 
If st u d y i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt will re mai n i n t he st u d y t o 
be e val uate d f or safet y f oll o w -u p a n d s ur vi val f oll o w -u p ( Part 2) . See t he S O A f or data t o be 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 6
c ollecte d at t he ti me of disc o nti n uati o n of st u d y  i nter ve nti o n a n d f oll o w-u p 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.
I n t he e ve nt of disc o nti n uati o n of st u d y i nter ve nti o n, it m ust be d oc u me nte d o n t he 
a p pr o priate C R F/i n t he me dical rec or ds w het her t he partici pa nt is disc o nti n ui n g f urt her 
recei pt of st u dy i nter ve nti o n or als o fr o m st u d y  pr oce d ures, p osttreat me nt st u d y f oll o w- u p, 
an d/ or f ut ure c ollecti o n of a d diti o nal i nf or mati o n.
S afet y F oll o w -U p:
At least 2 8 cale n dar da ys, a n d n o m ore t ha n 3 5 cale n dar da ys after disc o nti n uati o n of st u d y 
i nter ve nti o n, partici pa nts will ret ur n t o u n der g o re vie w of c o nc o mita nt treat me nts, vital si g ns, 
a n d assess me nt f or res ol uti o n of a n y  treat me nt relate d A Es. Partici pa nts c o nti n ui n g t o 
e x perie nce A Es 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 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. If t he u nres ol ve d A E is c o nsi dere d 
b y  t he i n vesti gat or as p ossi bl y relate d t o or ass ociate d wit h A D A f or mati o n, t he partici pa nt 
will be as ke d t o ret ur n f or dr u g c o nce ntrati o n a n d A D A bl o o d sa m pli n g at u p t o 3 -m o nt h 
i nter vals, u ntil t he last f oll o w- u p of t he A E.
F or part 2 of t he st u d y, s ur vi val stat us will be c ollecte d b y tele p h o ne e ver y  3 m o nt hs u ntil 
deat h, or u p t o 2 4 m o nt hs after first d ose of t he last partici pa nt .
7. 1. 1. E C G C h a n ges 
A partici pa nt w h o meets eit her b ullete d criteri o n base d o n t he a vera ge of tri plicate E C G 
rea di n gs will be wit h dra w n fr o m t he st u dy i nter ve nti o n. 

Q Tc F > 5 0 0 msec.

C ha n ge fr o m baseli ne: Q Tc F > 6 0 msec a n d Q Tc F > 4 5 0 msec.
If a cli nicall y si g nifica nt fi n di n g is i de ntifie d (i ncl u di n g, b ut n ot li mite d t o, c ha n ges fr o m 
baseli ne i n Q Tc F after e nr oll me nt), t he i n vesti gat or or q ualifie d desi g nee will deter mi ne if 
t he partici pa nt ca n c o nti n ue i n t he st u d y a n d if a n y c ha n ge i n partici pa nt ma na ge me nt is 
nee de d . T his re vi e w of t he E C G pri nte d at t he ti me of c ollecti o n m ust be d oc u me nte d . A n y 
ne w cli nicall y rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
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 t heir o w n re q uest. Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  ma y i ncl u de:

Ref use d f urt her st u d y pr oce d ures;

L ost t o f oll o w - u p;

Deat h;

St u d y  ter mi nate d b y s p o ns or.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 7
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 ta ke n a n d n ot teste d, a n d 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 a n d n otif y t he s p o ns or acc or di n gl y.
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 Secti o n 7. 2. 1 ) 
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.
7. 2. 1.
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  i nter ve nti o n 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 nl y 
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 f urt 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 na ble t o be c o ntacte d by t he st u d y  site.
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt 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. 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 ascertai n w het her 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.

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. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 8
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 u res. 
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 all o we d.
Safet y  iss ues 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 w het her t he p artici 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 eli 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.
Pr oce d ures c o n d ucte d as part of t he partici pa nt’s r o uti ne cli nical ma na ge me nt (e g, bl o o d 
c o u nt) a n d o btai ne d bef ore si g ni n g of t he I C D ma y be utilize d f or scree ni n g or baseli ne 
p ur p oses pr o vi de d t he pr oce d ures met t he pr ot oc ol -s pecifie d criteria a n d were perf or me d 
wit hi n t he ti me fra me defi ne d i n t he S O A .
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. I n 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 o l-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 ta 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 a n 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 ud y .
8. 1. Effic ac y Assess me nts
8. 1. 1. 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 hea d, c hest, a b d o me n, a n d pel vis c o m p ute d t o m o gra p h y or M RI sca ns; 
brai n c o m p ute d t o m o gra p h y  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 P E T sca n f or all partici pa nts t o m o nit or p ote ntial b o ne 
metastases . F or partici pa nts wit h k n o w n c o m p ute d t o m o gra p h y c o ntrast aller g y, a n o n -
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 9
c o ntrast c o m p ute d t o m o gra p h y 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 ntit 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 e ver y  8 wee ks fr o m C 1 D 1 ( ± 7 d a y s) f or t he first 6 m o nt hs, e ver y  
1 2 wee ks ( ± 7 d a y s) 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 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 CIS T versi o n 1. 1 (see A p pe n di x 1 2 ) a n d ir R E CIS T 
( See A p pe n di x 1 3 ). C o nfir mati o n of res p o nse ( C R/ P R) wit h a sec o n d c o nsec uti ve sca n at 
least 4 wee ks later is preferre d.
All partici pa nts’ files a n d ra di ol o gic i ma ges 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. 
A nti t u m or acti vit y will be assesse 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 gr essi o n is s us pecte d (e g, s y 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).
If i ma gi n g is use d i n disease assess me nt, 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 p ost -baseli ne disease 
assess me nts. 
8. 2. 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 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 d y t o assess a n y 
percei ve d safet y  iss ues.
Safet y  assess me nts will i ncl u de c ollecti o n of A Es, S A Es, vital si g ns a n d p h ysical 
e xa mi nati o n, 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 m e nts.
8. 2. 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 scree ni n g o nl y . Refer t o 
A p pe n di x 1 6 f or E C O G perf or ma nce stat us gra di n g.
A c o m plete p h ys ical e xa mi nati o n will i ncl u de m ore c o m pre he nsi ve assess me nts of t he 
car di o vasc ular, res pirat or y, GI, ge nit o uri nar y  (if nee de d, m usc ul os keletal a n d ne ur ol o gical 
s yste ms i n a d diti o n t o t he assess me nts f or t he brief p h ysical e xa m liste d bel o w.
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 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). 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 0
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. 
P h y sical e xa mi nati o ns ma y be c o n d ucte d b y a p hysicia n, trai ne d p h ys icia n's assista nt, or 
n urse practiti o ner as acce pta ble acc or di n g t o l ocal re g ulati o n. 
Hei g ht a n d wei g ht will als o be meas ure d a n d rec or de d as per t he S O A . F or meas uri n g 
wei g ht, a scale wit h a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, 
flat s urface. Partici pa nts m ust re m o ve s h oes, b ul k y  l a yers of cl ot hi n g, a n d jac kets s o t hat 
o nl y  li g ht cl ot hi n g re mai ns. T he y m ust als o re m o ve t he c o nte nts of t heir p oc kets a n d re mai n 
still d uri n g meas ure me nt of wei g ht. 
P h y sical e xa mi nati o n fi n di n gs c ollecte d d uri n g 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. A n y u nt o war d p h ys ical 
e xa mi nati o n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d meet t he 
defi niti o n of a n A E or S A E ( A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he pr ocesses i n 
Secti o ns 8 . 3. 1 t o 8. 3. 3 .
W he n s h o ul d it be d o ne: 
P h y sical e xa mi nati o n s h o ul d be c o m plete d pri or t o d osi n g .
8. 2. 2. Vit al Si g ns
Oral te m perat ure, p ulse rate, res pirat or y  rate, a n d B P will be assesse d. B P a n d p ulse rate 
meas ure me nts will be assesse d i n a sitti n g or se mi -rec u m be nt p ositi o n (t he sa me p ositi o n 
s h o ul d be mai ntai ne d t hr o u g h o ut t he st u d y) wit h a c o m pletel y a ut o mate d de vice. Ma n ual 
tec h ni q ues will be use d o nl y if a n a ut o mate d de vice is n ot a vaila ble.
B P a n d p ulse rate meas ur e me nts s h o ul d be prece de d b y  at least 5 mi n utes of rest f or t he 
partici pa nt i n a q uiet setti n g wit h o ut distracti o ns (e g, tele visi o n, cell p h o nes).
Vital si g ns (t o be ta ke n bef ore bl o o d c ollecti o n f or la b orat or y  tests) will c o nsist of 1 p ulse 
rate a n d 2 B P meas ure me nts ( 2 c o nsec uti ve bl o o d press ure rea di n gs will be rec or de d at 
i nter vals of at least 1 mi n ute). T he a vera ge of t he 2 B P rea di n gs will be rec or de d o n t he C R F.
W he n s h o ul d it be d o ne: 
Vital si g n assess me nts s h o ul d be c o m plete d pri or t o d osi n g.
8. 2. 3. Electr oc ar di o gr a ms
A si n gle 1 2-lea d E C G will be utilize d as scree ni n g. A tri plicate 1 2-lea d E C Gs will be utilize d 
f or C ycles 1 t o 3 t o deter mi ne mea n QTc F i nter val. F or t he da ys of d ose a d mi nistrati o n, 
perf or m E C G u p t o 6 0 mi n utes pri or t o d osi n g ( S C or I V), a n d at t he e n d of i nf usi o n (I V 
o nl y ). 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 1
Fr o m C y cle 4 o n war ds: Tri plicate 1 2 -lea d E C G u p t o 6 0 mi n utes pri or t o d osi n g o n Da y 1 of 
e ver y 3 c ycles ( C 4 D1, C 7 D 1, etc.).
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 hyt h m stri p) s h o ul d be 
c ollecte d 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 an 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 (e g, Mas o n -Li kar) 
s h o ul d n ot be use 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 u le 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 5 mi n utes i n a s u pi ne p ositi o n. 
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 occ ur if a) t he mea n 
val ue fr o m t he tri plicate meas ure me nts f or a n y 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 
sc he d ule d E C G. If eit her of these 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 urly 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.
If t he Q Tc F i nter val re verts t o less t ha n t he t hres h ol d criteria liste d a b o ve, a n d i n t he 
j u d g me nt of t he i n vesti gat or(s) a n d s p o ns or, it is deter mi ne d t hat t he ca use(s) of Q Tc F 
pr ol o n gati o n is s o met hi n g ot her t ha n st u d y  i nter ve nti o n, treat me nt ma y be c o nti n ue d wit h 
re g ular E C G m o nit ori n g. If i n that ti mefra me t he Q Tc F i nter vals rise a b o ve t he t hres h ol d 
val ues, t he st u d y  i nter ve nti o n will be hel d u ntil t he Q Tc F i nter val decreases t o bel o w t he 
t hres h ol d val ues. Partici pa nts will t he n restart t he st u d y i nter ve nti o n at t he ne xt l o west d ose 
le vel. If the Q Tc F i nter val has still n ot decrease d t o < 4 8 0 msec after 2 wee ks, or if at a n y  
ti me a partici pa nt has a Q Tc F i nter val > 5 1 5 msec or bec o mes sy m pt o matic, t he partici pa nt 
will be re m o ve d fr o m t he st u d y . A d diti o nal tri plicate E C Gs ma y be perf or me d as cli nicall y 
i n dicate 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 
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.
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 .
W he n s h o ul d it be d o ne: 

E C G assess me nts s h o ul d prece de bl o o d c ollecti o n f or cli nical la b orat or y  tests if 
p ossi ble .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 2

At scree ni n g: si n gle 1 2-lea d E C G. 

C ycles 1 t o 3: tri plicate 1 2-lea d E C Gs t o deter mi ne mea n Q Tc F i nter val. F or t he da ys 
of d ose a d mi nistrati o n, perf or m E C G u p t o 6 0 mi n utes pri or t o d osi n g ( S C or I V), a n d 
at t he e n d of i nf usi o n (I V o nl y ). 

Fr o m C ycle 4 o n w ar ds: Tri plicate 1 2 -lea d E C G u p t o 6 0 mi n utes pri or t o d osi n g o n 
D a y 1 of e ver y  3r d c ycle.

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 or cl ose t o
t he ti me of t he e ve nt. 

E n d of Tre at me nt a n d 4 - wee k f oll o w-u p: tri plicate 1 2-lea d E C G.
8. 2. 4. 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. 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 la b orat or y ma n ual a n d 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 ned 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 iss ues . 
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 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.
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 2 8 da ys 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.
See A p pe n di x 6 f or s u g geste d acti o ns a n d f oll o w- u p assess me nts i n t he e ve nt of p ote ntial 
dr u g -i n d uce d li ver i nj ur y.
N o nee d t o re peat a cli nical la b orat or y assess me nt o n C y cle 1 Da y 1 if t he baseli ne 
assess me nt was perf or me d wit hi n 7 da ys pri or t o t hat date.
8. 2. 5. Pre g n a nc y T esti 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 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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 3
pri or t o t he partici pa nt’s recei vi n g t he st u d y i nter ve nti o n . Pre g na nc y  tests will als o be d o ne 
w he ne ver 1 me nstr ual c ycle is mi sse 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 ma y als o be 
re peate d if re q ueste d by I R Bs/ E Cs or if re q uire d b y l ocal re g ulati o ns. 
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, 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 mIU/ m L ma y  be use d b y t he partici 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 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.
8. 2. 6. I njecti o n Site T oler a bilit y Assess me nts
Asse ss 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 2 6 0 4 3 7 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 d y  dr u g 
a d mi nistrati o n i n C ycle 1 ( Da y s 1 a n d 1 5), as per t he Sc he d ule of Acti vities . 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 2 6 0 4 3 7 i njecti 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 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 ularly 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 y t he ma, i n d urati o n, ecc h ym osis, 
i njecti o n site pain, i njecti o n site pr urit us, or ot her o bser ve d c haracteristics after P F - 0 7 2 6 0 4 3 7 
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 C R F. A n y 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 d verse e ve nt . I S Rs s h o ul d be i m me diatel y p h ot o gra p he d i n 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 c o 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 .
If se vere I S R or u ne x pecte d l o w e x p os ure is e nc o untere d wit h S C d osi n g, alter nati ve I V 
i nf usi o n a d mi nistrati o n c o h orts ma y  be c o nsi dere d after disc ussi o n bet wee n i n vesti gat ors a n d 
s p o ns or a n d a p pr o val fr o m s p o ns or. 
8. 3. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her S afet y Re p orti n g
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 ma y  arise fr o m sy m pt o ms or ot her c o m plai nts re p orte d t o t he i n vesti gat or 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), or t he y  ma y arise fr o m cli nical fi n di n gs of t he I n vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, etc.). 
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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 4
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 t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca u se d t he partici pa nt t o disc o nti n ue 
t he st u d y i nter ve nti o n (see Secti o n 7. 1 ).
D uri n g t he acti ve c ollecti o n peri o d as descri be d i n Secti o n 8. 3. 1 , eac h partici pa nt/le gall y 
a ut h orize d re prese ntati ve will be q uesti o ne d a b o ut t he occ urre nce of A Es i n a n o nlea di n g 
ma n ner . 
I n a d diti o n, t he i n vesti gat or ma y be re q ueste d b y Pfizer Safety 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. 3. 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 ni m u m of 2 8 cale n dar da y s, 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 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.
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.
If a partici pa nt per ma ne ntl y disc o nti n ues or te m p orarily disc o nti n ues st u d y  i nter ve nti o n 
beca use of a n A E or S A E, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n 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 ny ti me after a partici pa nt has c o m plete d t he st u dy, 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, 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. 3. 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 as descri be d i n 
Secti o n 8. 3. 1 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 i m me diatel y  u p o n 
a ware ness 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 5
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. N ote t hat a s witc h t o a c o m merciall y a vaila ble versi o n of t he st u d y  i nter ve nti o n is 
c o nsi dere d as a ne w a ntica ncer t hera p y f or p ur p oses of S A E re p orti n g.
8. 3. 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
All n o nseri o us A Es a n d 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 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 3. 1 , will be rec or de d 
o n t he A E secti o n of t he C R F. 
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d a n d all s p o nta ne o usl y re p orte d 
A Es a n d S A Es re p orte d b y  t he partici pa nt.
Re p orti n g of A Es a n d S A Es f or partici pa nts w h o fail scree ni n g are s u bject t o t he C R F 
re q uire me nts as descri be d i n Secti o n 5. 4 .
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. N ote t hat a s witc h t o a 
c o m merciall y a vaila ble versi o n of t he s t u d y i nter ve nti o n is c o nsi dere d as a ne w a ntica ncer 
t hera py f or t he p ur p oses of S A E re p orti n g .
8. 3. 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. 3. 3. F oll o w -U p of A Es a n d S A Es
After t he i nitial A E or S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y  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 n til res ol uti o n, sta bilizati o n, t he e ve nt is ot her 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 ollo 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 ossi ble ca usalit y . A n y 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 n s 
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 p e n di x 3 .
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 6
8. 3. 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 d 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 on 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 o ut t he safety 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 co 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 R Bs/ E Cs, a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or 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 S U S A Rs or ot her s pecific safet y 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 S R S D(s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a ppr o priate acc or di n g t o l ocal re q uire me nts.
8. 3. 5. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal 
e x p os ure i ncl u de healt hcare pr o vi ders, fa mil y me m bers, a n d ot hers w h o ma y be e x p ose d. A n 
e n vir o n me ntal e x p o s ure ma y i ncl u de e x p os ure d uri n g pre g na nc y, e x p os ure d uri n g 
breastfee di n g, a n d occ u pati o nal e x p os ure.
A n y  s uc h 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 are re p orta ble t o Pfizer Safety 
wit hi n 2 4 h o urs of i n vesti gat or a ware ness.
8. 3. 5. 1. E x p os ure D uri n g Pre g n a n c y
A n E D P occ urs if:  

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n.

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d st u d y  i nter ve nti o n e x p oses a 
fe male part ner pri or t o or ar o u n d t he ti me of c o nce pti o n. 

A fe male is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o 
st u d y i nter ve nti o n d ue t o e n vir o n me ntal e x p os ure. Bel o w are e xa m ples of 
e n vir o n me ntal E D P:  

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt after 
ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n halati o n or s ki n c o ntact. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 7

A male fa mil y me m ber or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y 
i nter ve nti o n t he n ex p oses his fe male part ner pri or t o or ar o u n d t he ti me of 
c o nce pti o n. 
T he i n vesti gat or m ust re p ort E D P 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, irres pecti ve of w het her a n S A E has occ urre d . T he i nitial i nf or mati o n s u b mitte d 
s h o ul d incl u de t he a ntici pate d date 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). 

If E D P occ urs i n a partici pa nt or a partici pa nt’s part ner, 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 nd 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 . Details of t he 
pre g na nc y  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 wee ks 
after t he last d ose. 

If E D P occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he i n vesti gat or m ust re p ort 
i nf or mati o n t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m . Si nce t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he 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.
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  u ntil 
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 eve 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 ural test fi n di n gs are c o ncl usi ve f or a c on ge nital a n o mal y a n d t he fi n di n gs are 
re p orte d).
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es. 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 g e nital a n o mal y i n a li ve -b or n ba b y) , 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. 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 Safet y as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u di n g 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 deat 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. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 8
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 nts t o i de ntif y de v el o p me ntal dela ys). I n 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 hat 
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.
8. 3. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n e x p os ure d uri n g breastfee di n g occ urs if:

A fe male partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
disc o nti n ui n g st u d y  i nter ve nti o n.

A fe male is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o 
st u d y i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of e n vir o n me ntal 
e x p os ure d uri n g breastfee di n g is a fe male fa mil y  me m ber or healt hcare pr o vi der w h o 
re p orts t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n 
b y  a ny u n pla n ne d direct c o ntact wit h t he pr o d uct . 
T he i n vesti gat or m ust re p ort e x p os ure d uri n g breastfee di n g t o Pfizer Safet y  wit hi n 2 4 h o urs 
of t he i n vesti gat or’s a wa re ness, irres pecti ve of w het her a n S A E has occ urre d. T he 
i nf or mati o n m ust be re p orte d usi n g t he C T S A E Re p ort F or m. W he n e x p os ure d uri n g 
breastfee di n g occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he e x p os ure i nf or mati o n d oes 
n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y , s o 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.
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 nces a n S A E ass ociate d wit h s uc h a dr u g, 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. 3. 5. 3. Occ u p ati o n al E x p os ure
T he i n vesti gat or m ust re p ort a n y  i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety 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 a b o ut t he occ u pati o nal e x p os ure 
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 m ust be mai ntai ne d i n t he 
i n vesti gat or site file.
8. 3. 6. C ar di o v asc ul ar a n d De at h E ve nts
N ot a p plica ble
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 9
8. 3. 7. Dise ase -Rel ate d E ve nts a n d/ or Dise ase -Rel ate d O utc o mes N ot Q u alif yi n g as A Es 
or S A Es
T he f oll o wi n g D R Es are c o m m o n i n partici pa nts wit h a d va nce d or metastatic Br Ca, O v Ca or 
e n d o metrial ca ncer a n d ca n be seri o us/life t hreate ni n g:

Disease or ne o pla s m pr o gressi o n

Brai n metastases

Mali g na nt ple ural or perit o neal eff usi o n
Beca use t hese e ve nts are t y picall y ass ociate d wit h t he disease u n der st u d y, t he y will n ot be 
re p orte d acc or di n g t o t he sta n dar d pr ocess f or e x pe dite d re p orti n g of S A Es e ve n t h o u g h t he
e ve nt ma y meet t he defi niti o n of a n S A E. T hese e ve nts will be rec or de d o n t he A E pa ge i n 
t he partici pa nt’s C R F wit hi n t he a p pr o priate ti me fra me. T hese D R Es will be m o nit ore d b y a 
safety re vie w c o m mittee, safet y re vie w tea m o n a r o uti ne basis. 
N ote: H o we ver, if eit her of t he f oll o wi n g c o n diti o ns a p plies, t he n t he e ve nt m ust be rec or de d 
a n d re p orte d as a n S A E (i nstea d of a D R E):

T he e ve nt is, i n t he i n vesti gat or’s o pi ni o n, of greater i nte nsit y , fre q ue nc y, or d urati o n 
t ha n e x pecte d f or t he i n di vi d ual partici pa nt.
O R

T he i n vesti gat or c o nsi ders t hat t here is a reas o na ble p ossi bilit y  t hat t he e ve nt was 
relate d t o st u dy i nter ve nti o n.
8. 3. 8. A d verse E ve nts of S peci al I nterest
N ot a p plica ble.
8. 3. 8. 1. L ac k of Effic ac y
T his P hase 1 st u d y  is n ot desi g ne d t o i n vesti gate t he defi nitive cli nical efficac y  of 
P F - 0 7 2 6 0 4 3 7.
8. 3. 9.
Me dic al De vice Deficie ncies 
N ot a p plica ble.
8. 3. 1 0. 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 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 ng d osa ge stre n gt h. 
E x p os ures t o t he st u d y  i nter ve nti o n u n der st u d y ma y occ ur i n cli nical trial setti n gs, s uc h as 
me dicati o n err ors.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 0
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.

T he a d mi nistrati o n of e x pire d st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect st u d y  i nter ve nti o n;

T he a d mi nistrati o n of a n i nc orrect d osa ge;

T he a d mi nistrati o n of st u d y  i nter ve nti o n t hat has u n der g o ne te m perat ure e xc ursi o n 
fr o m t he s pecifie d st ora ge ra n ge, u nless it is deter mi ne d b y t he s p o ns or t hat t he st u d y 
i nter ve nti o n u n der q uesti o n is acce pta ble f or use.
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 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 t he 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. 4. P h ar m ac o ki netics 
Bl o o d sa m ples of a p pr o xi matel y  3 m L , t o pr o vi de a mi ni m u m of 1 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 2 6 0 4 3 7 as s pecifie d i n t he S O A . 
If C R S is s us pecte d, a n d if a P K sa m ple is n ot alrea d y sc he d ule d t o be ta ke n, a P K sa m ple 
s h o ul d als o be ta ke n. 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 la b orat or y  ma 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.
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 wit hi n t he sa m pli n g ti me wi n d o w s pecifie d i n t he P har mac o ki netic a n d 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 1
Bi o mar ker Sa m pli n g ta ble (see Secti o n 1. 3 ) 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 t he C R F . If a 
sc he d ule d bl o o d sa m ple c ollecti o n ca n n ot be c o m plete d f or a ny reas o n, t he missed sa m ple 
ti me ma y be re-sc he d ule d wit h a gree me nt of t he cli nical i n vesti gat or, partici pa nt, a n d 
sp o ns or. 
Sa m ples will be use d t o e val uate t he P K of P F -0 7 2 6 0 4 3 7 . Sa m ples c ollecte d f or a nal ys es of 
P F -0 7 2 6 0 4 3 7 ser u m c o nce ntrati o n ma y  als o be use d t o e val uate safety 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, f 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 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 c ollecte d f or meas ure me nt of ser u m c o nce ntrati o ns of P F- 0 7 2 6 0 4 3 7 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 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 
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 sp o ns or. 
O n a case -b y -case basis, t he s p o ns or ma y  deter mi ne 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 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 I RB/ 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. Ge netics
8. 5. 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. 5. 2. Ret ai ne d Rese arc h S a m ples 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 will be c ollecte d 
acc or di n g t o t he S O A , as l ocal re g ulati o ns a n d I R Bs/ E Cs all o w.. 
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o st u d y i nter ve nti o n(s) a n d 
ca ncer st u d y. Ge nes a n d ot her a nal yt es (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 retai ne d 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 o r 
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 t he La b orat or y M a n ual.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 2
8. 6. Bi o m ar kers
A ke y  ele me nt 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 c o ul d be m o difie d b y P F- 0 7 2 6 0 4 3 7. T he bi o mar ker st u dies will be use d t o e val uate t he 
i n vi v o M o A
of P F -0 7 2 6 0 4 3 7, as m o n ot hera p y, a n d p ote ntial i n c o m bi nati o n wit h ot her 
a ge nts, as well as e val uate p ote ntial mec ha nis ms of resista nce. 
Ta ble 1 2 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 he bi o mar ker sa m pli n g sc he d ule m a y  be m o difie d base d 
o n e mer gi n g P K a n d P D data.
T a ble 1 2 . 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 B 7 -H 4 e x pressi o n le vels a n d 
ot her t u m or a n d i m m u ne bi o mar kers
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
Ser u m
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
Meas ure me nt of t u m or m utati o nal c ha n ges
Plas ma pre - a n d p ost -treat me nt
Ger mli ne D N A
W h ole Bl o o d
Bi os peci me ns c ollecte d f or P D a n d ot her bi o mar ker asses s 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 a n d t u m or tiss ues a n d ma y be use d t o a nalyz e 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 
sc he d ule of acti vities f or sa m ple c ollecti o n ti me p oi nts a n d 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 peci 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 ncl 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 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 yna 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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 3
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 cel ls a n d ot her i m m u ne 
s u p pressi ve cells or pr otei ns). 
8. 6. 1. T u m or S a m ple C ollecti o n f or P art 1 
All partici pa nts i n Part 1 m ust pr o vi de a n arc hi val F F P E t u m or tiss ue sa m ple ( bl oc k 
preferre d) at scree ni n g. 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 ntly 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, c o ntai ni n g s ufficie nt 
t u m or tiss ue of dia g n ostic q ualit y a n d re prese ntati ve of t he dia g n ose d mali g na nc y. Tiss ue 
bl oc ks are prefera ble, b ut fres hl y c ut paraffi n secti o ns are a cce 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 ma n ual f or i nstr ucti o ns o n 
s u b mitti n g sli des. T u m or tiss ue fr o m c yt ol o gic sa m pli n g (e g, fi ne nee dle as pirati o n, 
i ncl u di n g F F P E cell pellet material) a n d b o ne bi o ps y s peci me ns are n ot a de q uate a n d s h o ul d 
n ot be s u b mitte d. 
If t he arc hi ve d sa m ple is ol der t ha n 1 2 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 t o e nr oll me nt.
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. If a 
bi o ps y  ca n n ot be perf or me d safely or i ns ufficie nt t u m or bi o ps y  material d ue t o safety ris k, 
t he partici pa nt ma y still be eli gi ble. H o we ver, s uc h e xce pti o ns s h o ul d be disc usse d wit h a n d 
a p pr o ve d b y t he s p o ns or. 
I n Part 1, 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 
pa rtici 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 ys of C ycle 2 Da y 
1 5 ( C 2 D 1 5 ± 7 da y s). 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.
8. 6. 2. T u m or S a m ple C ollecti o n f or P art 2
I n Part 2, arc hi val bi o psies s h o ul d be re q ueste d fr o m all pa rtici pa nts, 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. Arc hi val bi o psies s h o ul d 
meet t he criteria o utli ne d i n Secti o n 8. 6. 1. 
De n o v o pre -treat me nt bi o psies are als o re q ueste d fr o m all partici pa nts, u nless n ot me dicall y 
feasi ble, t o f urt her esta blis h t he 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 
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 5 partici pa nts i n Part 2 A a n d 2 C, a n d a p pr o xi matel y 5 H R + 
H E R 2 - Br Ca a n d 5 T N B C partici pa nts i n Part 2 B), ma n dat or y  pre -treat me nt a n d 
o n ‑treat me nt bi o ps y sa m ples will als o be c ollecte d i n or der t o c o nfir m t he M o A
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 . I n Part 2, 2 0 partici pa nts will be e nr olle d i n eac h 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 4
c o h ort. If 1 5 partici pa nts ha ve bee n e nr olle d i n Part 2 A or Part 2 C 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. If 5 partici pa nts wit h H R + 
H E R 2 - Br Ca or T N B C ha ve bee n e nr olle d i n Part 2 B 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 i n eac h hist ol o g y  a n d t he c o h ort ma y be e x pa n de d 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. 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 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 partici pa nts wit h a pre -treatme nt bi o ps y , a n a d diti o nal o pti o nal bi o ps y is als o e nc o ura ge d 
at disease pr o gress i o n t o e val uate s us pecte d ac q uire d resista nce t o t hera py. 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 acc or da nce 
wit h l oc al i nstit uti o nal practice 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  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 sec o n d 
d ose, wit hi n 7 da y s of C ycle 2 Da y 1 5 ( C 2 D 1 5 ± 7 da ys). If o n-treat me nt t u m or c ollecti o n 
ta kes place greater t ha n ± 3 da ys fr o m C 2 D 1 5, a d diti o nal u nsc he d ule d bl o o d sa m ple f or 
c yt 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 psy c ollecti o n.
8. 6. 2. 1. B 7 -H 4 e x pressi o n f or P art 2 eli gi bilit y 
Part 2 d ose will e val uate P F - 0 7 2 6 0 4 3 7 i n partici pa nts wit h a d va nce d or metastatic H R + 
H E R 2 - Br Ca ( Part 2 A) a n d T N B C ( Part 2 C) wit h hi g h B 7-H 4 e x pressi o n t o assess earl y  
si g ns of cli nical efficac y. Refere nce sets will be i m m u n ostai ne d at a C LI A -certifie d ce ntral 
la b orat or y wit h a B 7- H 4 L D T a n d t he res ulti n g H-sc ores will be ran ke d fr o m l o w t o hi g h a n d 
di vi de d i nt o 3 e q ual tertiles. Patie nt sa m ples wit h H -sc ores t hat fall wit hi n t he hi g hest tertile 
of t he refere nce set will be dee me d as hi g h B 7 -H 4 e x press ors. T he ar bitrar y  t hres h ol d f or 
hi g h B 7 -H 4 e x pressi o n ma y  be m o difie d based o n e mer gi n g cli nical data.   A n a d diti o nal
c o h ort of 2 0 partici pa nts wit h a d va nce d or metastatic H R + H E R 2 - Br Ca a n d T N B C will be 
e nr olle d i n Part 2 B.  T hese patie nts will n ot be e nr olle d base d o n B 7 -H 4 e x pressi o n .  
Sa m ples will be i m m u n ostai ne d a n d e val uate d retr os pecti vel y t o f urt her e x pl ore B 7 -H 4 
e x pressi o n le vels a n d cli nical efficac y . 
8. 6. 3. Peri p her al Bl o o d S a m ple C ollecti o n a n d 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 c yt o ki nes, cell free D N A, a n d ger mli ne D N A.
F or c y t o ki ne a n d circ ulati n g mar kers t o be a nalyz e d at a ce ntral la b orat or y, 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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 5
a n d circ ulati n g mar kers meas ure me nt will be c ollecte d as descri be d i n t he S O A . 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 y t o ki ne release 
s yn 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. 
T he c y t o ki nes t o be meas ure d m a y  i ncl u de, b ut n ot li mite d t o I F N-, T N F‑a, I L‑ 1 b, I L‑ 2, 
I L‑ 4, I L‑ 5, I L‑ 6, I L‑ 8, a n d I L‑ 1 0. A d diti o nal e x pl orat or y  circ ulati n g mar kers ma y 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.
F or a nal y sis of cell-free D N A, plas ma will be is olate d fr o m 1 0 ml bl o o d at C 1 D 1 a n d u p o n 
disease pr o gressi o n. A nal y sis of circ ulati n g t u m or D N A i n t hese sa m ples ma y be c orrelate d 
wit h partici pa nt res p o nse t o t hera p y.
A 2 ml w h ole bl o o d sa m ple will be c ollecte d at C 1 D 1 f or is olati o n of baseli ne ger mli ne 
D N A. T his sa m ple ma y  be use d t o e na ble s u btracti o n of ger mli ne D N A varia nts fr o m 
s o matic m utati o ns t hat ma y be i de ntifie d i n t u m or or cell-free D N A sa m ples.
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  ma n ual.
8. 6. 4. T Cell I m m u n o p he n ot y pi n g 
Bl o o d sa m ples of a p pr o xi matel y  5 m L  of w h ole bl o o d sa m ples will be c ollecte d f or 
e val uati o n of T , B, a n d N K cell i m m u n o p he n ot ypi n g as well as c haracterizati o n of T cells f or 
mar kers s uc h as b ut n ot li mite d t o K i 6 7, P D‑ 1, H L A‑ D R a n d ot her i n dicat ors of pr oliferati o n, 
acti vati o n, a n d e x ha usti 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 Sc he d ule of Acti vities. 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 ma n ual.
Sa m ples ma y  als o be use d f or fl o w c y t 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 me
fra me, will be destr oye d.
8. 6. 5. Ret ai ne d Rese arc h S a m ples f or Bi o m ar kers
N ot a p plica ble as Retai ne d Researc h Sa m ples f or Bi o mar kers are n ot c ollecte d i n t his st u d y .
8. 6. 6. S ol u ble B 7 -H 4 Assess me nt
W h ole bl o o d sa m ples (a p pr o xi matel y  3 m L) t o pr o vi de a mi ni m u m of 1 m L ser u m f or 
sol u ble B 7 -H 4 assess me nt will be c ollecte d at t he ti mes s pecifie d i n t he S O A . A n a d diti o nal 
s ol u ble B 7- H 4/ ot her fact or sa m ple s h o ul d als o be ta ke n if C R S is s us pecte d, a n d a sa m ple is 
n ot alrea d y sc he d ule d t o be ta ke n (e g, fr o m C ycle 4 o n war ds) . 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 ma n ual. 
S ol u ble B 7 -H 4 le vels will be deter mi ne d b y a li ga n d bi n di n g assa y, a n d sa m ples ma y be use d 
f or f urt her e val uati o n of t he bi oa nalyt ical met h o d, as well as f or ot her i nter nal e x pl orat or y 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 6
p ur p oses. Sa m ples c ollecte 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 me fra me, will be destr o ye d.
8. 7. I m m u n o ge nicit y Assess me nts
Bl o o d sa m ples of a p pr o xi matel y  5 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 deter mi nati o n of A D A a n d N A b 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 la b orat or y ma 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 va l 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 co 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 p les 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 
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 on of ti me p oi nts f or a n y pla n ne d st u d y 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 I R 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. 8. 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 t he S A P, w hic h will be mai ntai ne d b y  t he s p o ns or.
T he S A P ma y  m o dif y w hat is o utli ne d i n t he pr ot oc ol w here a p pr o priate; h o we ver, a n y maj or 
m o dificati o ns of t he pri mar y  e n d p oi nt defi niti o ns or t heir a nalys es will als o be reflecte d i n a 
pr ot oc ol a me n d me nt.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 7
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. 1. 1. Esti m a n ds
9. 1. 1. 1. Pri m ar y Esti m a n d/ C o -Pri m ar y Esti m a n ds
Pri mar y  Esti ma n d ( D L T) f or Part 1: 
D L T rate esti mate d base d o n data fr o m D L T-e val ua ble partici pa nts d uri n g t he D L T-
e val uati o n peri o d ( 2 8 da ys f or re gi me n wit h o ut pri mi n g ; pri m i n g d oses pl us 2 f ull d oses f or 
re gi me n wit h pri mi n g) i n Part 1.
Varia ble: Occ urre nce of D L Ts . D L Ts are defi ne d i n Secti o n 4. 3. 6
A nal y sis p o p ulati o n:
F or t he d ose escalati o n wit h o ut pri mi n g, D L T-e val ua ble partici pa nts defi ne d as partici pa nts: 

w h o recei ve at least 1 d ose of st u d y  treat me nt a n d e x perie nce D L T d uri n g t he D L T-
e val uati o n peri o d ( 2 8 da ys),
O R

w h o c o m plete t he D L T -e val uati o n peri o d wit h o ut D L T. Partici pa nts wit h o ut D L Ts 
w h o wit h dra w fr o m st u d y treat me nt bef ore recei vi n g at least 2 f ull d oses of st u d y  
dr u g f or reas o ns ot her t ha n treat me nt -relate d t o xicit y are n ot e val ua ble f or D LT. 
F or t he d ose escalati o n wit h pri mi n g, D L T -e val ua ble partici p a nts defi ne d as partici pa nts: 

w h o recei ve at least 1 d ose of st u d y  treat me nt a n d e x perie nce D L T d uri n g t he D L T-
e val uati o n peri o d ( pri mi n g d oses pl us 2 f ull d oses, e g, 4 2 da y s),
O R

w h o c o m plete t he D L T -e val uati o n peri o d wit h o ut D L T. Partici pa nts wit h o ut D L Ts 
w h o wit h dra w fr o m st u d y treat me nt bef ore recei vi n g at least t he pri mi n g d ose a n d 
2 f ull d oses of st u d y dr u g f or reas o ns ot her t ha n treat me nt-relate d t o xicit y are n ot 
e val ua ble f or D L T . 
P o p ulati o n -le vel s u m mar y meas ure: D L T rate defi ne d as t he n u m ber of D L T-e val ua ble 
partici pa nts wit h D L Ts i n t he D L T -e val uati o n peri o d di vi de d b y t he n u m ber of 
D L T- e val ua ble partici pa nts i n t he D LT-e val uati o n peri o d.
Pri mar y  Esti ma n d f or Parts 1 a n d 2: 
I nci de nce of A Es esti mate d i n t he a nalys is p o p ulati o n d uri n g t he A E-e val uati o n peri o d, 
defi ne d as t he ti me fr o m t he first d ose t o earliest of 2 8 d a y s p ost last d osi n g date a n d da y of 
ne w a nti -ca ncer t hera p y-1 da y .
Varia ble: Occ urre nce of A Es . A Es are defi ne d i n Secti o n 8. 3 . 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 8
A nal y sis p o p ulati o n:  Safet y a nalys is set defi ne d as partici pa nts w h o recei ve at least 1 d ose 
of st u d y treat me nt wit h o ut re gar d t o t olera bilit y or d urati o n of treat me nt. 
P o p ulati o n -le vel s u m mar y meas ure: I nci de nce of A Es defi ne d as t he n u m ber of partici pa nts 
wit h A Es i n t he A E -e val uati o n peri o d di vi de d b y  t he n u m ber of partici pa nts i n t he a nal ysis 
p o p ula ti o n. A Es will be s u m marize d b y ty 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 5), ti mi n g, seri o us ness, a n d relati o ns hi p t o treat me nt.
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nalys is sets are defi ne d. 
P artici p a nt A n al ysis Set
Des cri pti o n
F ull A nal ysis Set ( F A S)
All e nr olle d partici pa nts. 
Safet y A nal ysis Set ( S A S)
All e nr olle d partici pa nts w h o recei ve at least 1 d ose of st u d y 
i nter ve nti o n. U nless ot her wise s pecifie d t he safet y a nal ysis set will be 
t he defa ult a nal ysis set use d f or all a nal yses.
Per Pr ot oc ol A nal ysis Set
All e nr olle d partici pa nts w h o d o n ot ha ve maj or pr ot oc ol de viati o ns 
d uri n g t he c o urse of t he st u d y
D L T E val ua ble Set  
All e nr olle d partici pa nts w h o ha d at least 1 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 pr ot oc ol de viati o ns 
d uri n g t he D L T o bser vati o n peri o d.
mI T T P o p ulati o n 
All e nr olle d partici pa nts w h o ha ve recei ve d at least 1 d ose of st u d y 
me dicati o n; ha ve a baseli ne assess me nt a n d at least 1 p ost baseli ne 
assess me nt; 
P K Para meter Set 
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.
P K C o nce ntrati o n Set
All e nr olle d partici pa nts w h o are trea te d a n d ha ve at least 1 a nal yte 
c o nce ntrati o n a b o ve t he l o wer li mit of q ua ntitati o n.
Res p o nse E val ua ble Set 
All e nr olle d partici pa nts w h o recei ve d at least 1 d ose of st u d y 
treat me nt a n d ha d a de q uate baseli ne disease assess me nt. Partici pa nts 
w h o disc o nti n ue d earl y or die d will be i ncl u de d. 
P har mac o d y na mic/ 
Bi o mar ker A nal ysis Set(s)
T he P har mac o d y na mic/ 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 har mac o d y na mic/ 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 nicit y A nal ysis 
Set 
T he i m m u n o ge nicit y a nal ysis set i ncl u des all e nr olle d partici pa nts 
w h o recei ve d at least 1 d ose of st u d y treat me nt a n d ha ve at least 1 
sa m ple teste d f or A D A.
9. 3. St atistic al A n al yses
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nal ys 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 S A P, w hic h will be mai ntai ne d by 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 ur e me nts, safet y 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 9
9. 3. 1. Ge ner al C o nsi der ati o ns
U nless ot her wise s pecifie d, s u m maries will be prese nte d b y  d ose gr o u p a n d o verall. 
Descri pti ve statistics, s uc h as t he 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, a n d ma xi m u m val ues, will be pr o vi de d f or c o nti n u o us e n d p oi nts. T he rates of 
bi nar y  e n d p oi nts will be pr o vi de d al o n g wit h t he c orres p o n di n g 2-si de d 9 5 % CIs usi n g a n 
e xact met h o d. Ti me -t o-e ve nt e n d p oi nts will be s u m marize d usi n g t he Ka pla n -Meier met h o d 
a n d dis pla ye d gra p hicall y w he n a p pr o priate. Me dia n e ve nt ti mes a n d 2-si de d 9 5 % CIs f or 
eac h ti me-t o- e ve nt e n d p oi nt will be pr o vi de d.
F urt her details will be pr o vi de d i n t he S A P.
9. 3. 2. Pri m ar y E n d p oi nts/ Esti m a n ds/ A n al ysis
P art 1
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 ysis set (e val ua ble f or 
M T D) . T he d ose escalati o n i n Part 1 of t he st u d y  will be g ui de d by a Ba yesia n a nal ys is of 
D L T data f or P F -0 7 2 6 0 4 3 7. D ose t o xicit y  is m o delle d usi n g 2 -para meter l o gi stic 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 pecificall y 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. A mi xt ure of wea kl y  i nf or mati ve prior distri b uti o n base d o n 
n o ncli nical/e x pert o pi ni o n i nf or mati o n a n d a M A P pri or base d o n hist orical data will be use d 
t o defi ne t he pri or distri b uti o n f or t he P F-0 7 2 6 0 4 3 7 m o n ot hera p y  d ose escalati o n. 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 d y 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.
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 
partici pa nts at differe nt d oses of i nterest f or P F- 0 7 2 6 0 4 3 7 will be e val uate d se pa ratel 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; pri mi n g d oses pl us 2 f ull d oses 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]
D osi n g decisi o ns are g ui de d b y  t he E W O C pri nci pal (R o gat k o et al, 2 0 0 7 ). A d ose ma y  o nly 
be use d f or ne wl y e nr olle d partici pa nts if t he ris k of o ver d osi n g at t hat d ose is less t ha n 2 5 %. 
Rec o m me n dati o n fr o m t he B L R M, al o n g wit h safet y  ( A Es, S A Es), la b orat or y, P K, 
bi o mar ker, a n d ot her rele va nt data, will be use d at t he ti me of eac h d ose escalati o n a n d f or 
M T D/ R D E deter mi nati o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 0
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, see A p pe n di x 9 . 
A 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 wit h pri mi n g base d o n t he data c ollecte d i n Part 1 wit h o ut pri mi n g. 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 h e hist orical data (Ne ue nsc h wa n der et al, 2 0 1 0 ; Sc h mi dli et al, 2 0 1 4 ). 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 P F -0 7 2 6 0 4 3 7 m o del para meters is pr o vi de d i n A p pe n di x 9 . 
St arti n g d ose:
T he starti n g d ose f or t he m o n ot hera p y P F ‑ 0 7 2 6 0 4 3 7 is S C i njecti o n 1 0 0 µ g Q 2 W. T his d ose 
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 9 .
St o p pi n g criteri a:
T he s p o ns or esti mates t hat t he ma xi m u m n u m ber of partici pa nts i n t he Part 1 d ose escalati o n 
p orti o n of t he trial is 4 0 partici pa nts . H o we ver, t he act ual n u m ber ma y  be m ore or less base d 
o n o bser ve d P K a n d safet y . T he d ose escalati o n will st o p 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 or R D E .

T he d ose d f or P F- 0 7 2 6 0 4 3 7 satisfies 1 of t he f oll o wi n g c o n diti o ns f or t he m o n o-
escalati o n part:

T he pr o ba bilit y  of tar get t o xicit y at d ose d e xcee ds 5 0 %, ie, Pr ( 0. 1 6 ≤п d < 0. 3 3) 
≥5 0 %, or

A mi ni m u m of 1 5 partici pa nts ha ve bee n treate d i n Part 1.
Part 1 a n d Part 2
I nci de nce of A Es es ti mate d i n t he safety a nal ys is p o p ulati o n d uri n g t he A E-e val uati o n 
peri o d. defi ne d as t he ti me fr o m t he first d ose t o earliest of 2 8 da y s p ost last d osi n g date a n d 
da y  of ne w a nti-ca ncer t hera p y- 1 da y . 

V ari a ble: Occ urre nce of A Es . A Es are defi ne d i n Secti o n 8. 3 .

A n al ysis p o p ul ati o n:   Safet y a nal ysis set defi ne d as partici pa nts w h o recei ve at least 
1 d ose of st u d y  treat me nt wit h o ut re gar d t o t olera bilit y or d urati o n of treat me nt.

P o p ul ati o n -le vel s u m m ar y me as ure: I nci de nce of A Es defi ne d as t he n u m ber of 
partici pa nts wit h A Es i n t he A E -e val uati o n peri o d di vi de d b y t he n u m ber of 
partici pa nts i n t he a nal ys is p o p ulati o n. A Es will be s u m marize d b y ty pe, fre q ue nc y, 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 1
se verity (as gra de d b y 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 treat me nt.
9. 3. 3. Sec o n d ar y E n d p oi nt A n al ysis
Part 1 a n d Part 2
Si n gle -D ose a n d Ste a d y -St ate P F -0 7 2 6 0 4 3 7 P h ar m ac o ki netic A n al ysis
Ser u m c o nce ntrati o ns of P F -0 7 2 6 0 4 3 7 will be s u m marize d descri pti vel y ( 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, ge o metric mea n, a n d its 
ass ociate d c oefficie nt of variati o n) b y d ose, c ycle, da y , a n d n o mi nal ti me . 
I n di vi d ual partici pa nt ser u m c o nce ntrati o n -ti me data wit hi n a d ose i nter val after C ycle 1 
D a y 1 a n d C ycle 2 Da y  1 will be a nalyz e d usi n g n o nc o m part me ntal met h o ds t o deter mi ne 
si n gle a n d m ulti ple d ose P K para meters.
Si n gle d ose P K para meters t o be esti mate d will i ncl u de t he ser u m C ma x , T m a x a n d A U C last, 
a n d as data per mit, A U C fr o m ti me 0 e xtra p olate d t o i nfi nit y  (A U C i nf), t½ , cleara nce (C L / F
f or S C d osi n g a n d C L f or I V d osi n g) a n d v ol u me (V z/ F f or S C d osi n g a n d V ss f or I V d osi n g).
M ulti ple d ose
P K para meters t o be esti mate d will i ncl u de C ma x ,ss, T ma x ,ss, A U C ss,τ, Cmi n,ss , 
cleara nce ( C L ss/ F f or S C a n d C Lss f or I V) a n d as data per mit, v ol u me ( V z/ F f or S C or V ss f or 
I V), t½ , a n d R ac ( A U Css,τ/ A U Cs d,τ). T he si n gle d ose a n d stea dy- state P K para meters will be 
s u m marize d descri pti vel y ( 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, ge o metric mea n, a n d its ass ociate d c oefficie nt of variati o n) b y  d ose 
le vel a n d c ycle.
D ose n or malize d A U C i nf (A U C τ at stea d y state) a n d C ma x will be pl otte d a gai nst d ose ( usi n g a 
l o garit h mic scale) by c ycle. T hese pl ots will i ncl u de i n di vi d ual partici pa nt val ues a n d t he 
ge o metric mea ns f or eac h d ose. 
A n al ysis of I m m u n o ge nicit y D at a
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 a n d 
ne utralizi n g a nti b o dies eac h will be s u m marize d . F or partici pa nts wit h p ositi ve A D A or 
ne utralizi n g a nti b o dies, 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 
ne utralizi n g a nti b o dies res p o nse will als o be descri be d, if data per mit.
Part 2
Effic ac y A n al ysis
Res p o nse E val ua ble Set will be use d f or all res p o nse-relate d a nalys es i ncl u di n g O R R, D o R, 
P F S, a n d T T P ( R E CI S T) . 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, t u m or res p o nse at eac h visit, a n d best 
o verall res p o nse . O S will be re p orte d o n t he F ull A nal y sis Set as well as o n t he mIT T.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 2
Data will be s u m marize d (als o gra p hicall y  w here a p pr o priate) a n d liste d b y e x pa nsi o n 
c o h ort.
9. 3. 4. Te rti ar y/ E x pl or at or y E n d p oi nt(s)
Part 1
Effic ac y A n al ysis
Res p o nse E val ua ble Set will be use d f or O R R a n d P F S ( R E CI S T) . 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 ype, t u m or res p o nse at eac h visit, a n d best o verall res p o nse . 
Data will be s u m marize d (als o gra p hicall y  w here a p pr o priate) a n d liste d b y d ose le vel.
Part 1 a n d 2
A n al ysis of P h ar m ac o d y n a mics
Res ults of e x pl orat or y  e n d p oi nt a nal yses will be descri be d i n t he C S R t o t he e xte nt p ossi ble. 
D ue t o t he e x pl orat or y  nat ure of t he e n d p oi nts, t he ass ociate d data a nalys es ma y n ot be 
c o m plete at t he ti me of C S R pre parati o n. If res ults of e x pl orat or y  e n d p oi nt a nalys es ca n n ot 
be i ncl u de d i n t he C S R, t he y will be disse mi nate d t o t he scie ntifi c c o m m u nit y t o t he e xte nt 
p ossi ble t hr o u g h prese ntati o n at scie ntific meeti n gs a n d/ or p u blicati o n i n peer -re vie we d 
scie ntific j o ur nals.
9. 3. 5. Ot her 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.
A Es, E C Gs, B P, p ulse rate, car diac m o nit ori n g res ults, 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 R a b n or malities of p ote ntial cli nical 
c o ncer n will be descri b e 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 vel y , 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 i f t h ose fi n di n gs meet t he defi niti o n of a n A E. 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. 3. 5. 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 rate, Q Tc F, 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 3
T he n u m ber ( %) of partici pa nts wit h ma xi m u m p ost d ose Q Tc F 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 b y treat me nt: 
S afet y Q Tc F Assess me nt 
De gree of Pr ol o n gati o n
Mil d ( ms)
M o derate ( ms)
Se vere ( ms)
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
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. If a n y of t he 3 i n di vi d ual E C G traci n gs has a Q Tc F  val ue 
> 5 0 0 ms, b ut t he mea n of t he tri plicates is n ot > 5 0 0 ms, 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 C S R i n or der t o place t he 
> 5 0 0 m s 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 ms will n ot be i ncl u de d i n t he cate g orical 
a nal ys is u nless t he a vera ge fr o m t he tri plicate meas ure me nts is als o > 5 0 0 ms . C ha n ges fr o m 
baseli ne will be defi ne d as t he c ha n ge bet wee n t he p ost d ose Q Tc F 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 har mac o d y n a mics m o deli n g 
a p pr oac h . If a P K/ p har mac o dy na mics 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 safety a nal ysis set wit h 
baseli ne ( pre -d ose o n C ycle 1 Da y 1) a n d o n -treat me nt E C G data. 
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. A n 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 the o utlier 
a nal ys is (cate g orical a nal ysis) as i n di vi d ual val ues o btai ne d at u nsc he d ule d ti me p oi nts.
Q T i nter vals will be c orrecte d f or H R usi n g sta n dar d c orrecti o n fact ors (ie, Fri dericia’s 
( defa ult c orrecti o n), Bazett’s, 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, R R, 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), a n d b y  st u d y treat me nt (ie, m o n ot hera p y vers us c o m bi nati o n 
t hera py) 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 
treat me nt, 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 nalys 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 st u d y treat me nt, d ose, a n d ti me p oi nt. Details of 
a d diti o nal a nal ys is (if a n y) will be s pecifie d i n S A P. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 4
9. 3. 5. 2. A Es
A Es will be 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 a n d c o de d usi n g 
Me d D R A . A E data will be re p orte d i n ta bles a n d listi n gs . S u m maries of A E b y  a p pr o priate 
Me d D R A ter ms, t o xicit y  gra de, a n d seri o us ness an 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 Es 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 ycle 1 a n d C ycles be y o n d 1). Li sti n gs of D L Ts a n d deat hs will be pr o vi de d.
9. 3. 5. 3. L a b or at or y Test A b n or m alities
T he n u m be r 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. 3. 6. Ot her A n al ysis(es) 
P har mac o ge n o mic or bi o mar ker data fr o m Retai ne d Researc h Sa m ples ma y be c ollecte d 
d uri n g or after t he trial a n d retai ne d f or f ut ure a nal y ses; t he res ults of s uc h a nalys es are n ot 
pla n ne d t o be i ncl u de d i n t he C S R.
9. 3. 6. 1. 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 at baseli ne a n d p ost- treat me nt. F urt her a nal ys 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.
9. 3. 6. 2. P o p ul ati o n P h ar m ac o ki netic A n al ysis or P K/ P D M o deli n g 
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 c o m part me ntal 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 st u dies t o i n vesti gate a n y ass ociati o n bet wee n 
P F -0 7 2 6 0 4 3 7 e x p os ure a n d bi o mar kers or si g nifica nt safet y a n d/ or efficac y e n d p oi nts . T he 
res ults of t hese a nal yses, if perf or me d, m a y  be re p orte d se parately.
9. 4. 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 5
9. 5. S a m ple Size Deter mi n ati o n
T otal n u m ber of partici pa nts f or P art 1 a n d Part 2 c o m bi ne d, is esti mate d t o be a p pr o xi matel y  
1 0 0. 
9. 5. 1. P art 1 D ose Esc al ati o n
A p pr o xi matel y  3 5 partici pa nts are e x pecte d t o be e nr olle d i nt o 1 of 5 - 7 se q ue ntial d ose le vels 
i n Part 1 i ncl u di n g at least 6 partici pa nts treate d at t he M T D. 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 2 6 0 4 3 7 a n d t he n u m ber of d ose 
le vels t hat are re q uire d t o deter mi ne M T D/ R D E.
9. 5. 2. P art 2 D ose E x p a nsi o n
A p pr o xi matel y  6 0 partici pa nts are e x pecte d t o be e nr olle d i nt o 3 c o h orts i n Part 2: Part 2 A, 
Part 2 B a n d Part 2 C, wit h a p pr o xi matel y  n = 2 0 partici pa nts i n eac h c o h ort. T we nt y 
partici pa nts f or eac h c o h ort is cli nicall y  s ufficie nt t o el uate safet y si g nals.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 6
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 CI O M S I nter nati o nal Et hical G ui deli nes;

A p plic a ble I C H 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, S R S D(s), 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, 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 b y 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.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val pri or t o i nitiati o 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 vest i 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 R B/ 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 safet y 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 uct 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 F R, I C H G C P 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), E ur o pea n Me dical De vice Re g ulati o n 
2 0 1 7/ 7 4 5 f or cli nical de vice researc h (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 bi ti o n or restricti o n i m p ose d (ie, cli nical h ol d) by 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, Pfizer s h o ul d be i nf or me d i m me diatel y . 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 7
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 
of a n y seri o us breac hes of t his pr ot oc ol or of t he 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 bi 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 nvesti 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, i ncl u di n g t he 
ris ks a n d be nefits, t o t he partici pa nt a n d a ns wer all q uesti o ns re gar di n g t he st u d y. T he 
partici pa nt s h o ul d be gi ve n s ufficie nt ti me a n d o p p ort u nit y  t o as k q uesti o ns a n d t o deci de 
w het her or n ot t o partici pate i n t he trial.
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 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 uire me nts of 2 1 C F R 5 0, 
l ocal re g ulati o ns, I C H G C P g ui deli nes, pri vac y a n d data pr otecti o n 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  partici pa nt 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 acce ss 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 olle d i n t he st u d y  a n d t he date o n w hic h 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 8
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 .
A c o p y of t he I C D(s) m ust be pr o vi de d t o t he partici pa nt.
A partici pa nt w h o is rescree ne d is n ot re q uire d t o si g n a n ot her I C D if t he rescree ni n g occ urs 
wit hi n 2 8 da y s fr o m t he pre vi o us I C D si g nat ure date.
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 meas 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 ote cte 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 ha ve 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 will 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 partici pa nts 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 o t 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 a n d me dical rec or d I D. 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. C o m mittees Str uct ure
N o i n de pe n de nt o versi g ht c o m mittees will be utilize d i n t his st u d y .
1 0. 1. 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 D M C.
1 0. 1. 6. 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 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 S O Ps.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4 9
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 d y 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 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. T hese res ults are 
s u b mitte d f or p osti n g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.
E u dra C T
Pfizer p osts cli nical trial res ults o n E u dra C T f or Pfizer -s p o ns ore d i nter ve nti o nal st u dies i n 
acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y  E U re q uire me nts. 
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 
P fizer-s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he c orres p o n di n g st u d y res ults are 
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 ka 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 pu blicati o n of cli nical 
data t o t he 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, C S 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 nic al 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 n s 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 patie 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 utes t o t he scientific 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 data a vaila ble 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 y ses. 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 0
1 0. 1. 7. D at a Q u alit 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 
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.
G ui da nce o n c o m pleti o n of C R Fs will be pr o vi de d i n t he C R F C o m pleti o n Re q uire me nts 
d oc u me nt.
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 he st u d y site i n e ncr y pte d 
electr o nic a n d/ or pa per f or m a n d 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.
Q T L s are pre defi ne d para meters t hat are m o nit ore d d uri n g t he st u d y . I m p orta nt de viati o ns 
fr o m t he Q T Ls a n d a n y re me dial acti o ns ta ke n will be s u m marize d i n t he cli nical st u d y 
re p ort.
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 duri n g t he m o nit ori n g visits a n d p ossi ble a u dits 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 , i ncl u di n g t he defi niti o n of st u d y critical data ite ms 
a n d pr ocesses (e g, ris k -base d i nitiati ves i n o p erati 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 nal yt ical ris k-base d m o nit ori n g), met 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, virt ual, or o n-site mo nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n [a n d 
m o nit ori n g pla n] mai ntai ne d a n d utilize d b y  t he s p o ns or or desi g nee.
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.
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 urel y 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 1
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 mediatel 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 
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. 8. S o urce D oc u me nts
S o urce d oc u me 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 e C R F t hat are fr o m s o urce d oc u m e 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 a n d its ori gi n ca n be f o u n d i n t he cli nical 
m o nit ori n g pla n, w hic h is mai ntai ne d b y  t he s p o ns or.
Descri pti o n of t he use of t he c o m p uterize d s yste m is d oc u me nte d i n t he Data Ma na ge me nt 
Pla n, w hic h is mai ntai ne d b y  t he s p o ns or.
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.
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, t he I C H G C P g ui deli nes, a n d all a p plica ble re g ulat or y  re q uire me nts.
1 0. 1. 9. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date o n w hic h t he cli nical st u d y will be o pe n f or recr uit me nt of 
partici pa nts.
T he first act of recr uit me nt is t he date of t he first partic i pa nt’s first visit a n d will be t he st u d y 
start date.
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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 2
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he s p o ns or 
or desi g n ee/ C R O if re q ueste d t o d o s o b y  t he res p o nsi ble IR 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 or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti ga t 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 t he I C H 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 gat or;

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.
If t he st u dy is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y C R O(s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he i n vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w - u p.
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 ny 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. 1 0. P u blic 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 t he 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 
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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 3
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 wit 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 1. S p o ns or’s Q u alifie d Me dic al Pers o n nel
T he c o ntact i nf 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 hareP oi nt si te. 
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel f or 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 n E mer ge nc y  C o ntact Car d ( E C C) at 
t he ti me of i nf or me d c o nse nt. T he E C C c o ntai ns, at a mi ni m u m, (a) pr otoc ol a n d st u d y  
i nter ve nti o n i de ntifiers, ( b) partici pa nt’s st u dy i de ntificati o n n u m ber, (c) site e mer ge nc y 
p h o ne n u m ber acti ve 2 4 h o urs/ da y , 7 da ys per wee k, a n d ( d) Pfizer Call Ce nter n u m ber.
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c om m u nicati o n pat h wa y s 
bet wee n t he i n vesti gat or, site staff, a n d st u d y  tea m. T he E C C is t o be use d b y healt hcare 
pr ofessi o nals n ot i n v ol ve d i n t he researc h st u d y o nl y , as a mea ns of reac hi n g t he i n vesti gat or 
or site staff relate d t o t he care of a partici pa nt . T he Pfizer Call Ce nter n u m ber s h o ul d o nl y be 
use d w he n t he i n vesti gat or a n d site staff ca n n ot be reac he d. T he Pfizer Call Ce nter n u m ber is 
n ot i nte n de d f or use b y t he partici pa nt directl y ; if a partici pa nt calls t hat n u m ber directly, he 
or s he will be di recte d bac k t o t he i n vesti gat or site.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 4
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Assess me nts
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 porte 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 val ues. 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 ora t 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 iss ues. 
T a ble 1 3 . C ore L a b Tests
H e m at ol o g y
C he mistr y
Ser ol o g y
Pre g n a nc y Test
H e m o gl o bi n
A L T
H B V: H Bs A g, H Bc A b a
F or fe male partici pa nts
of c hil d beari n g p ote ntial, 
o n ser u m or uri ne (t o be 
s pecifie d i n t he pr ot oc ol)
Platelets
A S T
W B C
A L P
H C V a nti b o d y b
A bs ol ute Ne utr o p hils
Bicar b o nate or C O 2
A bs ol ute L y m p h oc ytes
S o di u m
A bs ol ute M o n oc ytes
P otassi u m
A bs ol ute E osi n o p hils
Ma g nesi u m
A bs ol ute Bas o p hils
C hl ori de
T otal Calci u m
C o a g ul ati o n
T otal Bilir u bi n c
Uri n al ysis
A d h oc L ocal La b 
C y t o ki ne A nal ysis d
P T or I N R
B U N or Urea
Uri ne di pstic k f or uri ne 
pr otei n: If p ositi ve 
c ollect 2 4 -h a n d 
micr osc o pic ( Refle x 
Testi n g)
P T T or a P T T
Creati ni ne
I L-6, I L -1 b, I L -1 0, 
I F N-, T N Fa-, ot her 
c yt o ki nes
Uric Aci d
Ot hers
Gl uc ose ( n o n -faste d)
A m ylase 
Al b u mi n
Li pase
P h os p h or us or P h os p hate
Uri ne di pstic k f or uri ne 
bl o o d: if p ositi ve c ollect 
micr osc o pic ( Refle x 
Testi n g)
T S H a n d free T 4
L D H
C R P
a.
He patitis B as cli nicall y i n dicate d: I g M a nti b o d y t o he patitis B c ore a nti ge n (I g M a nti -H Bc), H B V D N A.
b.
He patitis C as cli nicall y i n dicate d: H C V- P C R, H C V -R N A, He patitis C Viral L oa d.
c.
F or H y’s la w p ote ntial 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, P T/I N R, a n d al kali ne 
p h os p hatase.
d.
C y t 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.
N otes: Data base s h o ul d be c o nstr ucte d t o all o w ca pt ure of differe ntial c o u nts as perce nt a n d a bs ol ute val ues b ut o nl y o ne 
or t he ot her s h o ul d be use d b y t he site t o c ollect data. Res ults will be re p orte d as a bs ol ute val ues after c o n versi o n a n d 
gra de d acc or di n g t o t he C T C A E criteria
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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 5
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 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 patie 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 dy i nter ve nti o n.

N ote: 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 or at 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  i nter 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 ysis) 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 nically 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 . A n y a b n or mal la b orat or y test 
res ults t hat meet a ny of t he c o n diti o ns bel o w m ust be rec or de d as a n A E:

Is ass ociate d wit h acc o m pa n yi n g sy m pt o ms;

Re q uires a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n;

Lea ds t o a c ha n ge i n st u d y  d osi n g ( o utsi de of a n y pr ot oc ol-s pecifie d d ose 
a dj ust me nts) or disc o nti n uati o n fr o m t he st u d y , si g nifica nt a d diti o nal c o nc o mita nt 
dr u g treat me nt, or ot her t hera p y.

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 n 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 or 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/self-har 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 6
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 t hat 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 pital).

A ntici pate d da y -t o-d a y  fl uct uati o ns of pree xisti ng 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  
me as 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 a n S A E
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, meets 1 or 
m o re of t he criteri a liste d bel o w:
a.
Res ults i n de at h
b.
Is life-t hre ate 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 . It 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 p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati 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 for 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 7
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 or si g nific a nt dis a bilit y/i nc a p acit y

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), t hat 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 nit al a n o m al y/ birt h defect.
f.
Is a s us pecte d tr a ns missi o n vi a a Pfizer pr o d uct of a n i nfecti o us a ge nt, p at h o ge nic 
or n o n- p at 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 sy m 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 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.
g.
Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d b y  t he i n vesti gat or 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 si g nifica nt 
me dical e ve nts t hat 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 yscrasias 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 
pr 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 s y 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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 8
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 T C A E Gra de 5 (see t he Assess me nt of Se ver it y 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 D uri n g t he Acti ve 
C ollecti o n Peri o d
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 Es o n t he C R F a n d f or 
re p orti n g S A Es o n t he C T S A E Re p ort F or m t o Pfizer Safety t hr o u g h o ut t he acti ve 
c ollecti o n peri o d. T hese re q uire me nts are deli neate d f or 3 t y pes of e ve nts: ( 1) S A Es; ( 2) 
n o nseri o us 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 Pfize r 
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 
All A Es/ 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
N ote: I nsta nces of E D P or 
E D B n ot ass ociate d wit h a n 
A E or S A E are n ot ca pt ure d 
i n t he C R F.
All i nsta nces of E D P are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E) *
All i nsta nces of E D B are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E). * *
E n vir o n me ntal or 
occ u pati o nal e x p os ure t o 
t he pr o d uct u n der st u dy 
t o a n o n-partici pa nt ( n ot 
i n v ol vi n g E D P or E D B).
N o ne . E x p os ure t o a st u d y  
n o n - partici pa nt is n ot 
c ollecte d o n t he C R F.
T he e x p os ure ( w het her or 
n ot t here is a n ass ociate d 
A E or S A E) m ust be 
re p orte d.* * *
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5 9
* 
E D P ( wit h or wit h o ut a n ass ociate d A E or S A E): a n y pre g na nc y i nf or mati o n is 
re p orte d t o Pfizer Safety usi n g C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m; if t he E D P is ass ociate d wit h a n S A E, t he n t he S A E is re p orte d t o Pfizer 
Safet y  usi n g t he C T S A E Re p ort F or m. 
* * 
E D B is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m w hic h w o ul d 
als o i ncl u de details of a n y S A E t hat mi g ht be ass ociate d wit h t he E D B. 
* * * E n vir o n me nt al or Occ u p ati o n al e x p os ure: A Es or S A Es ass ociate d wit h 
occ u pati o nal e x p os ure are re p orte d t o Pfizer Safet y  usi n g t he C T S A E Re p ort 
F or m. 

W he n a n A E or 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 or 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 or 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 ueste d by Pfizer Safet y . I n 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 or S A E.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 0
Assess me nt of Se verit y
T he i n vesti gat or will ma ke a n assess me nt of se verit y  f or eac h A E re p orte d d uri n g t he st u dy 
a n d assi g n it t o 1 of t he cate g ories liste d bel o w (as defi ne d b y  t he N CI C T C A E s yste m). 
A n e ve nt is defi ne d as “seri o us” w he n it meets at least 1 of t he pre defi ne d o utc o mes as 
descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.
G R A D E
Cli nic al Descri pti o n of Se ver it y
1
MI L D A E
2
M O D E R A T E A E
3
S E V E R E A E
4
LI F E -T H R E A T E NI N G; 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 E
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 or S A E. 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.

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.

Alter nati ve ca uses, s uc h as u n derl yi n g disease(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 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 or 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 or 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 d at 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 1

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 g ulat 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 t he 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 sect i o n of t he C T S A E Re p ort F or m a n d i n acc or da 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 b y 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 o vi ders.

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  s u b mitte d 
d oc u me nts.

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 Ele ctr 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)  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 y ste 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 off -li 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 2

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 off-li 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 Safet 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 by 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.
1 0. 3. 5. G ui d a nce f or I m m u ne -Rel ate d A d verse E ve nts
M a n a ge me nt of I m m u ne- Rel ate d A d verse E ve nts
G astr oi ntesti n al ir A Es
Se verit y of
Di arr he a/ C olitis
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
Gr a de 1
Diarr hea: < 4 st o ols/ da y o ver baseli ne
C olitis: as y m pt o matic
-C o nti n ue st u d y treat me nt
-S y m pt o matic treat me nt
(e g, l o pera mi de)
-Cl ose m o nit ori n g f or w o rse ni n g 
s y m pt o ms.
-E d ucate partici pa nt t o re p ort 
w o rse ni n g i m me diatel y.
-If w orse ns: Treat as Gra de 2, 3 or 4.
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 treat me nt
- S y m pt o m atic treat me nt
-If i mpr o ves t o Gra de ≤1: Res u me 
st u d y treat me nt.
-If persists > 5 -7 da ys or rec urs: Treat
as Gra de 3 or 4.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 3
G astr oi ntesti n al ir A Es
Se verit y of
Di arr he a/ C olitis
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
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 h o urs; 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
Gra de 4: life-t hreate ni n g, perf orati o n
-Wit h h ol d
f or Gra de 3
-P er m a ne ntl y disc o nti n ue st u d y 
treat me nt f or Gra de 4 or rec urre nt 
Gra de 3
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne
I V or 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 l o wer e n d osc o p y
-If i mpr o ves: 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; res u me st u d y treat me nt
f oll o wi n g ster oi ds ta per (f or i nitial 
Gra de 3).
-If w o rse ns, persists > 3 t o 5 da ys, or
rec urs after i mpr o ve me nt.
-A d d 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 4
Der m at ol o gic al ir A Es
Gr a de of R as h 
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
Gr a de 1 t o 2
C o veri n g ≤3 0 % b o d y s urface area
-C o nti n ue st u d y treat me nt   
-S y m pt o m atic t hera p y (f or 
e xa m ple, a nti hista mi nes, t o pical
ster oi ds)
-If persists > 1 t o 2 w ee ks or rec urs: 
-Wit h h ol d
st u d y treat me nt
-C o nsi der s ki n bi o ps y
-C o nsi der 0. 5 -1. 0 m g/ k g/ da y 
pre d nis o ne or e q ui vale nt. O nce
i mpr 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 treat me nt f oll o wi n g ster oi ds 
ta per.
-If w orse n s: Treat as Gra de 3 t o 4.
Gr a de 3 t o 4
Gra de 3: C o veri n g > 3 0 % b o d y
s urface area;
Gra de 4: Life t hreate ni n g 
c o nse q ue nces
-Wit h h ol d
st u d y treat me nt f or
Gra de 3
-P er m a ne ntl y disc o nti n ue f or
Gra de 4 or rec urre nt Gra de 3
-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 pre d nis o ne
or 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
-If i mpr o ves t o Gra de ≤1: T a per
ster oi ds o ver at least 1 m o nt h; res u me
st u d y tr e at m e nt f oll o wi n g ster oi ds 
ta per (f or i nitial Gra de 3).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 5
P ul m o n ar y ir A Es
Gr a de of P ne u m o nitis
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
Gr a de 1
Ra di o gra p hic c ha n ges o nl y
-C o nsi der wit h h ol di n g st u d y 
treat me nt
-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 -assess at least e ver y 3 w ee ks.
-If w orse 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 treat me nt
-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 t o 2. 0 m g/ k g/ da y pre d nis o ne
or 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
-Re -assess e ver y 1 t o 3 da ys If
i mpr o ves:
-W he n
s y m pt o ms ret ur n t o Gra de
≤1, 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 
treat me nt f oll o wi n g ster oi ds ta per.
-If n ot i mpr o vi n g after 2 we e ks or
w orse ni n g: Treat as Gra de 3 t o 4.
Gr a de 3 t o 4
Gra de 3: Se vere ne w s y m pt o ms;
Ne w / worse ni n g h y p o xia;
Gra de 4: Life -t hreate ni n g
-P er m a ne ntl y disc o nti n ue st u d y 
treat me nt.
-H os pitalize
-P ul m o nar y a n d I nfecti o us Disease 
c o ns ults
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne
or 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 mpr o ves t o Gra de ≤1: Ta per
ster oi ds o ver at least 1 m o nt h.
-If n ot i m pr o vi n g after 4 8 h o urs or 
w o rse ni n g: A d d a d diti o nal
i m m u n os u p pressi o n (f or e xa m ple,
i nfli xi ma b, c ycl o p h os p ha mi de, I V 
i m m u n o gl o b uli n, or m yc o p he n olate
m o fetil).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 6
He p atic ir A Es
Gr a de of Li ver Test Ele v ati o n
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
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 treat me nt
-C o nti n ue li ver f u ncti o n m o nit ori n g
-If w orse ns: Treat as Gra de 2 or 3 – 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 treat me nt
-I ncrease fre q ue nc y of m o nit ori n g
t o e ver y 3 da ys
-If ret ur ns t o Gra de ≤1: Res u me r o uti ne 
m o nit ori n g; res u me st u d y tr e at m e nt .
-If ele vati o n persists > 5 t o 7 da ys or 
w orse ns: Treat as Gra de 3 t o 4.
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
-P er m a ne ntl y disc o nti n ue st u d y 
treat me nt
-I ncrease fre q ue nc y of m o nit ori n g
t o e ver y 1 t o 2 d a y s
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne
or 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/ 
he pat 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 ≤1: 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 o rse 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 7
Re n al ir A Es
Gr a de of Cre ati ni ne I ncre ase d
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p
M a n a ge m e nt
Gr a de 1
Creati ni ne i ncrease d > U L N t o 1. 5 x
U L N
-C o nti n ue st u d y treat me nt
-C o nti n ue re nal f u ncti o n
m o nit ori n g.
-If w orse ns: Treat as Gra de 2
t o 3 or 4.
Gr a de 2 t o 3
Creati ni ne i ncrease d > 1. 5 a n d ≤6 x
U L N
-Wit h h ol d st u d y treat me nt  
-I ncrease fre q ue nc y of m o nit ori n g t o
e ver y 3 da ys
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne or 
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 re nal bi o ps y
-If ret ur ns t o Gra de ≤1: T a per
ster oi ds o ver at least 1 m o nt h,
a n d res u me st u d y treat me nt
f oll o wi n g ster oi ds ta per.
-If w orse ns: Treat as Gra de 4.
Gr a de 4
Creati ni ne i ncrease d > 6 x U L N
-P er m a ne ntl y disc o nti n ue st u d y 
treat me nt 
-M o nit or creati ni ne dail y
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne or 
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 re nal bi o ps y
-Ne p hr ol o g y c o ns ult
-If ret ur ns t o Gra de ≤1: Ta per
ster oi ds o ver at least 1 m o nt h.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 8
C ar di ac ir A Es
M y oc ar ditis
I niti al M a n a ge m e nt
F oll o w -u p
M a n a ge m e nt
N e w o nset of car diac si g ns or 
s y m pt o ms a n d / or ne w la b orat or y
car diac bi o mar ker ele vati o ns (e g,
tr o p o ni n, C K -M B, B N P) or car diac 
i ma gi n g a b n or malities s u g gesti ve of
m y ocar ditis
-Wit h h ol d
st u d y treat me nt
- H os pitalize
-I n t he prese nce of life-t hreate ni n g car diac 
dec o m pe nsati o n, c o nsi der tra nsfer t o a 
facilit y e x perie nce d i n a d va nce d heart fail ure
a n d arr h yt h mia ma na ge me nt
-C o ns ult car di ol o gist t o esta blis h eti ol o g y a n d 
r ule-o ut i m m u ne-me diate d
m y ocar ditis
-G ui deli ne base d s u p p orti ve treat me nt as per 
car di ol o g y c o ns ult *
-C o nsi der m y ocar dial bi o ps y if rec o m me n de d 
per car di ol o g y c o ns ult
-If s y m pt o ms i mpr o ve a n d
i m m u ne-me diate d
eti ol o g y
is r ule d o ut, re-start st u d y 
treat me nt.
-If s y mpt o ms d o n ot 
i mpr o ve/ w orse n, viral 
m y ocar ditis is e xcl u de d, 
a n d i m m u ne-me diate d
eti ol o g y is s us pecte d or 
c o nfir me d f oll o wi n g
car di ol o g y c o ns ult, ma na ge 
as i m m u ne-me diate d
m y ocar ditis.
I m m u ne-me diate d m y ocar ditis
-P er m a ne ntl y disc o nti n ue st u d y treat me nt
-G ui deli ne base d s u p p orti ve treat me nt as
a p pr o priate as per car di ol o g y c o ns ult. * 1. 0 t o 
2. 0 m g/ k g/ da y pre d nis o ne or 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
-O nce  i m pr o vi n g,  
ta per  
ster oi ds o ver at least 1 
m o nt h.
-If n o i mpr o ve me nt or 
w o rse ni n g, c o nsi der 
a d diti o nal 
i m m u n os u p pressa nts (e g,
azat hi o pri ne, c ycl os p ori ne
A).
* L ocal g ui deli nes, or e g, E S C or A H A g ui deli nes
E S C g ui deli nes we bsite:  htt ps:// w w w.escar di o. or g/ G ui deli nes/ Cli nical -Practice - G ui deli nes A H A g ui deli nes we bsite:
htt p:// pr ofessi o nal. heart. or g/ pr ofessi o nal/ G ui deli nes State me nts/searc hres ult s.js p? q = & y = &t = 1 0 0 1
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6 9
E n d ocri ne ir A Es
E n d ocri ne Dis or der
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
Gra de 1 or Gra de 2 
e n d ocri n o pat hies
( h y p ot h yr oi dis m,
h y pert h yr oi dis m, a dre nal
i ns ufficie nc y, t ype I dia betes
mellit us)
-C o nti n ue st u d y treat me nt 
-E n d ocri n ol o g y c o ns ult if nee de d
-Start t h yr oi d h or m o ne re place me nt t hera p y
(f or h y p ot h yr oi dis m),
a nti -t h yr oi d treat me nt (f or h y pert h yr oi dis m),
c ortic oster oi ds (f or a dre nal i ns ufficie nc y) or 
i ns uli n (f or T y pe I dia betes mellit us) as 
a p pr o priate 
-R ule -o ut sec o n dar y e n d ocri n o pat hies (ie,
h y p o pit uitaris m / h y p o p h ysitis)
-C o nti n ue h or m o ne 
re place me nt/s u p pressi o n a n d 
m o nit ori n g of  e n d ocri ne
f u ncti o n as a p pr o priate.
Gr a de 3 or Gr a de 4
e n d ocri n o pat hies
( h y p ot h yr oi dis m,
h y pert h yr oi dis m, a dre nal
i ns ufficie nc y, t ype I dia betes
mellit us)
-Wit h h ol d
st u d y treat me nt
-C o nsi der h os pitalizati o n 
- E n d ocri n ol o g y c o ns ult
-Start t h yr oi d h or m o ne re place me nt t hera p y
(f or h y p ot h yr oi dis m),
a nti -t h yr oi d treat me nt (f or h y pert h yr oi dis m),
c ortic oster oi ds (f or a dre nal i ns ufficie nc y) or
i ns uli n (f or t y pe I dia betes mellit us) as 
a p pr o priate
-R ule -o ut sec o n dar y e n d ocri n o pat hies (ie,
h y p o pit uitaris m / h y p o p h ysitis)
-Res u me st u d y treat me nt o nce
s y m pt o ms a n d/ or la b orat or y 
tests i mpr o ve t o Gra de ≤1
( wit h or wit h o ut h or m o ne
re place me nt/s u p pressi o n).
-C o nti n ue h or m o ne 
re place me nt/s u p pressi o n a n d 
m o nit ori n g of  e n d ocri ne
f u ncti o n as a p pr o priate.
H y p o pit uitaris m/ H y p o p h ysitis
(sec o n dar y e n d ocri n o pat hies)
-If sec o n dar y t h yr oi d a n d/ or a dre nal 
i ns ufficie nc y is c o nfir me d (ie, s u b n ormal
ser u m free T 4 wit h i na p pr o priatel y l o w T S H
a n d/ or l o w ser u m c ortis ol wit h i na p pr o priatel y
l o w A C T H) :
-Refer t o e n d ocri n ol o gist f or d y na mic testi n g
as i n dicate d a n d meas ure me nt of ot her
h or m o nes ( F S H, L H, G H/I G F -1, P R L, 
test oster o ne i n me n, estr o ge ns i n w o me n)
-H or m o ne re place me nt/s u p pressi ve t hera p y as 
a p pr o priate
-Perf or m pit uitar y M RI a n d vis ual fiel d
e xa mi nati o n as i n dicate d
-If h y p o p h ysitis is c o nfir me d:
-C o nti n ue st u d y treat me nt if mil d s y m pt o ms
wit h n or mal M RI.
Re peat t he M RI i n 1 m o nt h
-Wit h h ol d
st u d y treat me nt if m o derate,
se vere,
or life -t hreate ni n g s y m pt o ms of h y p o p h ysitis
a n d/ or a b n or mal
M RI. C o nsi der 
h os pitalizati o n. I nitiate c ortic oster oi ds ( 1 t o 2 
m g/ k g/ da y pre d nis o ne or e q ui vale nt) f oll o we d
-Res u me st u d y treat me nt o nce
s y m pt o ms a n d h or m o ne tests
i m pr o ve t o Gra de ≤1 ( wit h or
wit h o ut h or m o ne
re place me nt).
-I n a d diti o n, f or h y p o p h ysitis 
wit h a b n or mal M RI,
res u me
st u d y treat me nt o nl y o nce
s hri n ka ge of t he pit uitar y
gla n d o n M RI/ C T
sca n is 
d oc u me nte d.
-C o nti n ue h or m o ne 
re place me nt/s u p pressi o n 
t hera p y as a p pr o priate.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 0
E n d ocri ne ir A Es
E n d ocri ne Dis or der
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
b y c ortic oster oi ds ta per d uri n g at least 1 
m o nt h
-A d d pr o p h ylactic a nti bi otics f or o p p ort u nistic 
i nfecti o ns
Ot her ir A Es ( n ot descri be d a b o ve)
Gr a de of ot her ir A Es 
( N CI-C T C A E v 5. 0)
I niti al M a n a ge m e nt
F oll o w -u p M a n a ge m e nt
Gr a de 2 or Gr a de 3 cli nic al
si g ns or s y mpt o m s
s u g gesti ve of a p ote nti al
ir A E
-Wit h h ol d st u d y treat me nt pe n di n g
cli nical i n vesti gati o n
-If ir A E is r ule d o ut, ma na ge as
a p pr o priate acc or di n g t o t he 
dia g n osis a n d c o nsi der re-
starti n g st u d y treat me nt
-If ir A E is c o nfir me d, treat as
Gra de 2 or 3 ir A E.
Gr a de 2 ir A E  or first 
occ urre nce of Gr a de 3 ir A E
-Wit h h ol d
st u d y treat me nt
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne 
or 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
-S pecialt y c o ns ult as a p pr o priate
-If i mpr o ves t o Gra de ≤1:
-Ta per ster oi ds o ver at least 
1 m o nt h a n d res u me st u d y 
treat me nt f oll o wi n g ster oi ds 
ta per.
Rec urre nce of s a m e Gr a de 3 
ir A Es
-Per ma ne ntl y disc o nti n ue st u d y 
treat me nt
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne or 
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
-S pecialt y c o ns ult as a p pr o priate
-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.
Gr a de 4
-Per ma ne ntl y disc o nti n ue st u d y 
treat me nt
-1. 0 t o 2. 0 m g/ k g/ da y pre d nis o ne or 
e q ui vale nt a n d/ or ot her 
i m m u n os u p pressa nt as nee de d
-A d d pr o p h ylactic a nti bi otics f or 
o p p ort u nistic i nfecti o ns
-S pecialt y c o ns ult
-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.
Re q uire me nt f or 1 0 m g per 
d a y or gre ater pre d nis o ne 
or e q ui v ale nt f or m ore t h a n 
1 2 wee ks f or re as o ns ot her 
t h a n h or mo n al re pl ace me nt 
f or a dre n al i ns ufficie nc y
Persiste nt Gr a de 2 or 3 ir A E 
l asti n g 1 2 wee ks or l o n ger
-Per ma ne ntl y disc o nti n ue st u d y 
treat me nt 
-S pecialt y c o ns ult
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 1
1 0. 4. A p pe n di x 4: C o ntr ace pti ve a n d B arrier G ui d a nce 
1 0. 4. 1. M ale P arti ci 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 6 5 da ys after t he last d ose of st u d y i nter ve nti o n, 
w hic h c orres p o n ds t o t he ti me nee de d t o eli mi nate re pr o d ucti ve safet y ris k of t he st u d y 
i nter ve nti o n(s) pl us a n a d diti o nal 9 0 da ys (a s per mat o ge nesis c ycle): 

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 as t heir preferre d a n d us ual lifest y le 
(a bsti ne nt o n a l o n g-ter 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 c o ntrace pti o n/ barrier as detaile d bel o w. 

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.

Male partici pa nts s h o ul d be a d vise d of t he be nefit f or a fe male part ner t o use a hi g hl y  
effecti ve met h o d of c o ntrace pti o n, as a c o n d o m ma y brea k or lea k w he n ha vi n g 
se x ual i nterc o urse wit h a W O C B P w h o is n ot c urre ntl y pre g na nt. 
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d uc ti 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 A p pe n di x 4 , 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 ye ar), prefera bl y wit h l o w user de pe n de nc y, 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 4 m o nt hs after t he last d ose of st u d y  
i nter ve nti o n, 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 re pr o d ucti ve 
safety ris k of t he st u d y i nt er ve nti o n(s) . As f or partici pa nts usi n g a hi g hl y effecti ve 
met h o d t hat is user de pe n de nt, t his c o ntrace pti o n met h o d m ust be use d t o get her wit h 
a sec o n d effecti ve met h o d of c o ntrace pti o n, as descri be d bel o w. 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 2
A W O C B P a grees n ot t o d o nate e g gs ( o va, o oc y tes) f or t he p ur p ose of re pr o d ucti o n d uri n g 
t his peri o d. T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of t h e 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 early u n detec te d 
pre g na nc y . 
1 0. 4. 3. W o m a n of C hil d be ari n g a n d N o n -C hil d be ari n g P ote nti al
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 discreti o n sh o ul d be 
a p plie d t o deter mi ni n g st u d y 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 u me 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 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 . I n a d diti o n, 

A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n u n der 6 0 ye ars of a ge a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 

A fe male 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 hly effecti ve c o ntrace pti o n met h o ds if t he y 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 3
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.
1 0. 4. 4. C o ntr ace pti o n Met h o ds
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
Hi g hl y Effecti ve Met h o ds T h at H a ve L o w User De pe n de nc y 
1.
I m pla nta ble pr o gest o ge n-o nl y  hor 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.
3.
I ntra uteri ne h or m o ne releasi n g sys te m.
4.
Bilateral t u bal occl usi o n. 
5.
Vasect o mize d part ner.

A 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 C B P 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 da ys.
Hi g hl y Effecti ve Met h o ds T h at Ar e User De pe n de nt 
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;

Tra ns der mal;
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;

I njecta ble.
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 n ce 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 4
O ne of t he f oll o wi n g effecti ve barrier met h o ds m ust be use d i n a d diti o n t o t he hi g hl y 
effecti ve met h o ds liste d a b o ve t hat are user de pe n de nt:

Male or fe male c o n d o m wit h or wit h o ut s per mici de;

Cer vical ca p, dia p hra g m, or s p o n ge wit h s per mici de;

A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m, or s p o n ge wit h 
s per mici de ( d o u ble-barrier met h o ds).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 5
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.

T he sc o pe of t he ge netic researc h ma y  be narr o w (e g, 1 or m ore ca n di date ge nes) or 
br oa d (e g, t he e ntire ge n o me), as a p pr o priate t o t he scie ntific q uesti o n u n der 
i n vesti gati o n.

T he sa m ples ma y  be a nal yze d as part of a m ultist 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 P F-0 7 2 6 0 4 3 7 or st u d y  i nter ve nti o ns of t his class t o 
u n dersta n d treat me nts f or t he 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 C S R or i n a se parate st u d y 
s u m mar y or m a 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 d icate d:

Retai ne d sa m ples f or ba n ki n g will be st ore d i n defi nitel y or f or a n 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 Retai ne d 
Sa m ples 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. 

Sa m ples f or ge netic researc h will be la bele d wit h a c o de. T he ke 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 sec urel y  at t he st u d y site. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 6
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 nl y referre d t o as 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 × 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 da pt ors” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n A S T a n d/ or A L T prece de 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 ypicall y occ urs w hile A S T/ A L T 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, b y 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 o cc 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 ue s 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 u es 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 7
T he partici pa n t 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 wit 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 repeati n g meas ure me nts of A S T a n d A L T a n d T Bili f or s us pecte d H y’s la w 
cases, a d diti o nal la b orat or y  tests s h o ul d i ncl u de al b u mi n, C K, direct a n d i n direct bilir u bi n, 
G G T, P T/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 
to 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 nal yses 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/ paraceta m ol (eit her b y itself or as a c of 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, or 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, 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 ples f or aceta mi n o p he n/ paraceta m ol 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 defi 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 L F T a b n or malities has yet 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 he res u lts 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 8
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 E

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 ms.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 ms (a bs ol ute) or b y ≥6 0 ms 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 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 E

Q Tc F pr ol o n gati o n > 5 0 0 ms.

Ne w S T -T c ha n ges s u g gesti ve of m y ocar 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 ms).

Ne w -o nset ri g ht b u n dle bra nc h bl oc k ( Q R S > 1 2 0 ms).

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 yt 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 ycar 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 h y t h m ( heart 
rate < 4 0 b p m), accelerate d i di o ve ntric ular r h yt h m ( H R > 4 0 b p m t o < 1 0 0 b p m), a n d 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7 9
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h y car dia ( H R > 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 S A E

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 u lar 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 0
1 0. 8. A p pe n di x 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. 
Use of t hese alter nati ve st u d y  meas ures are e x pecte d 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). 
1 0. 8. 1. 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 patie 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 # 1 7: 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 ( b ut n ot li mite d t o) H B V, H C V, C O VI D-1 9/ S A R S -C o V 2, a n d k n o w n 
HI V or AI D S -relate d ill ness. W he n t he i nfecti o n res ol ves, t he patie nt ma y be c o nsi dere d f or 
re-scree ni n g. 
1 0. 8. 2. 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 S O A 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 
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 to 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 si nce t he last c o ntact. Refer t o S O A a n d 
Secti o n 8. 3 .

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 n d Secti o n 1 0. 8. 3. 1 of t his a p pe n di x re gar di n g 
pre g na nc y  tests.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 1
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.
1 0. 8. 3. 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.
1 0. 8. 3. 1. 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. All 
pr ot oc ol -s pecifie d safet y la b orat or y e val uati o ns ma y be perf or me d 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 oc al 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 mIU/ m L ma y  be 
use d b y  t he partici pant 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  
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.
1 0. 8. 3. 2. I m a gi n g
If t he partici pa nt is u na ble t o visit t he st u d y site f or plan 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.
1 0. 8. 3. 3. Electr oc ar di o gr a ms
If t he partici pa nt is u na ble t o visit the 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. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 2
1 0. 8. 4. 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 c a 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 2 6 0 4 3 7 f or partici pa nts w h o 
ha ve acti ve C O VI D - 1 9 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:

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, P F-0 7 2 6 0 4 3 7 
s h o ul d be dela ye d f or at least 1 4 da ys fr o m t he start of s ym pt o ms. T his dela y  is 
i nte n 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 Secti o n 6. 8 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 SA R S -C o V 2 i nfecti o n
1 0. 8. 5. 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. 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 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. 3 . 

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 .
1 0. 8. 6. A d verse E ve nts a n d Seri o us A d verse E ve nts
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n A E or S A E a n d 
a p pr o priate me dical i nter ve nti o n pr o vi de d. St u d y  i nter ve nti o n s h o ul d co nti n ue u nless t he 
i n vesti gat or/treati n g p hys icia n is c o ncer ne d a b o ut t he safet y 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 t hat t he i n vesti gat or disc uss te m p orar y or per ma ne nt disc o nti n uatio 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. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 3
1 0. 8. 7. Effic ac y Assess me nts
T he use of alter nati ve meas ures f or efficac y  assess me nts m ust be e val uate d b y  t he s p o ns or 
f or t he i m pact o n data i nte grit y a n d i nter preta bilit y.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y Cli nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 4
1 0. 9. A p pe n di x 9: Det aile d D ose Esc al ati o n/ De- Esc al ati o n Sc he me f or B L R M Desi g n
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 decisi 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. 9. 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 2 6 0 4 3 7 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 g istic:
l o git π( ) = l o g( ) + β l o g  ∗T he para meter d * is t he refere nce d ose i n t he m o del a n d is use d t o scale t he d oses of 
P F -0 7 2 6 0 4 3 7. T he α, > 0 are t he para meters of t he m o del s uc h t hat  ( > 0) is t he 
P F -0 7 2 6 0 4 3 7 o d ds of a D L T at  ∗; a n d  ( > 0) is t he i ncrease i n t he l o g-o d ds of a D L T b y  a 
u nit i ncrease i n l o g -d ose.
1 0. 9. 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 l o g ( ) a n d l o g( ). 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 B V N distri b uti o n
                                                (l o g( α), l o g( β)) ~ N 2 (m, S)
wit h pri or mea ns m = ( m 1, m 2), a n d pri or c o varia nce matri x S c o m p ose d of sta n dar d 
de viati o ns s 1, s 2 a n d c orrelati o n ρ . 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 pa te d D LT rate at t he scali n g d ose d *. 
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 5 ).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 5
1 0. 1 0. A p pe n di x 1 0. B o ne M arr o w Reser ve i n A d ults 
A d a pte d fr o m R. E. E L LI S: T he Distri b uti o n of Active B o ne M arr o w i n t he A d ult, P hy. Me d. Bi ol . 5, 
2 5 5 -2 5 8, 1 9 6 1
M arr o w Distri b uti o n of t he A d ult
SI T E
M A R R O W
wt. ( g)
F R A C TI O N 
R E D 
M A R R O W
A G E 4 0
R E D 
M A R R O W
wt. ( g)
A G E 4 0
% T O T A L
R E D 
M A R R O W
C R A NI U M
Hea d:
1 3 6. 6
A N D
Cra ni u m
1 6 5. 8
0. 7 5
1 2 4. 3
1 3. 1
1 3. 1
M A N DI B L E
Ma n di ble
1 6. 4
0. 7 5
1 2. 3
U p per Li m b Gir dle:
8 6. 7
H U M E RI,
S C A P U L A E,
2 H u mer us , 
hea d & nec k
2 6. 5
0. 7 5
2 0. 0
8. 3 
8. 3
C L A VI C L E S
2 Sca p ulae 
6 7. 4
0. 7 5
5 0. 5
2 Cla vicles
2 1. 6
0. 7 5
1 6. 2
Ster n u m
3 9. 0
0. 6
2 3. 4
2. 3
Ri bs: 
8 2. 6
1 pair
1 0. 2
All 0. 4
4. 1
2 
1 2. 6
5. 0
3
1 6. 0
6. 4
S T E R N U M
4
1 8. 6
7. 4
A N D
5
2 3. 8
9. 5
7. 9
1 0. 2
RI B S
6
2 3. 6
9. 4
7
2 5. 0
1 0. 0
8
2 4. 0
9. 6
9
2 1. 2
8. 5
1 0
1 6. 0
6. 4
1 1
1 1. 2
4. 5
1 2
4. 6
1. 8
Sacr u m 
1 9 4. 0
0. 7 5
1 4 5. 6
1 3. 9
P E L VI C 
B O N E S
2 os c o xae
3 1 0. 6
0. 7 5
2 3 3. 0
2 2. 3
3 6. 2
F E M U R
2 Fe m oral hea d 
a n d nec k
5 3. 0
0. 7 5
4 0. 0
3. 8
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 6
M arr o w Distri b uti o n of t he A d ult (c o nt’ d)
SI T E
M A R R O W
wt. ( g)
F R A C TI O N R E D 
M A R R O W
A G E 4 0
R E D 
M A R R O W
wt. ( g)
A G E 4 0
% T O T A L
R E D M A R R O W
Verte brae
( Cer vical):
3 5. 8
1
6. 6
All 0. 7 5
5. 0
2
8. 4
6. 3
3
5. 4
4. 1
3. 4
4
5. 7
4. 3
5
5. 8
4. 4
6
7. 0
5. 3
7
8. 5
6. 4
Verte brae
( T h oracic):
1 4 7. 9
1 pair
1 0. 8
All 0. 7 5
8. 1
2
1 1. 7
8. 8
3
1 1. 4
8. 5
4
1 2. 2
9. 1
V E R T E B R A E
5
1 3. 4
1 0. 1
1 4. 1
2 8. 4
6
1 5. 3
1 1. 5
7
1 6. 1
1 2. 1
8
1 8. 5
1 3. 9
9
1 9. 7
1 4. 8
1 0
2 1. 2
1 5. 9
1 1
2 1. 7
1 6. 3
1 2
2 5. 0
1 8. 8
Verte brae
( L u m bar):
1 1 4. 1
1 pair
2 7. 8
All 0. 7 5
2 0. 8
2
2 9. 1
2 1. 8
1 0. 9
3
3 1. 8
2 3. 8
4
3 2. 1
2 4. 1
5
3 1. 4
2 3. 6
T O T A L
1 4 9 7. 7
1 0 4 5. 7
1 0 0. 0
1 0 0. 0
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 7
1 0. 1 1. A p pe n di x 1 1: C R S a n d I C A N S Gr a di n g , Miti g ati o n , a n d M a n a ge me nt
1 0. 1 1. 1. C yt o ki ne Rele ase S y n dr o me
C R S is a n o n -a nti ge n-s pecific c yt o ki ne-ass ociate d t o xicit y t hat occ urs as a res ult of hi g h-
le vel i m m u ne acti vati o n. C R S is a p ote ntiall y life-t hreate ni n g t o xicit y t hat has bee n o bser ve d 
f oll o wi n g a d mi nistrati o n of i m m u ne-base t hera pies f or ca ncer (a nti b o dies a n d a d o pti ve T cell 
t hera pies). C R S is li kel y t o be a c o m m o n t o xicit y t hat ca n be ma na ge d t hr o u g h s u p p orti ve 
care a n d a nti -c yt o ki ne i nter ve nti o ns.
I n cases of s us pecte d C R S, a ser u m sa m ple s h o ul d be pr o vi de d f or c y t o ki ne release assa y 
a nal ys is b y t he l ocal la b (see A p pe n di x 2 ) s o as l o n g as t he sa m pli n g d oes n ot i nterfere wit h 
t he me dical treat me nt of t he partici pa nt.
Earl y i nter ve nti o n s h o ul d be u n derta ke n at t he first si g n of C R S; si g ns ma y  i ncl u de pyre xia, 
tac hycar dia, tac h y p nea a n d/ or h y p ote nsi o n a n d are te m p orall y relate d t o P F - 0 7 2 6 0 4 3 7 i n t he 
a bse nce of alter nati ve eti ol o gies.
T he A S T C T C R S criteria pr o p ose d b y Lee et al (Lee et al, 2 0 1 9 ) as prese nte d i n Ta ble 1 4
will be use d f or t he assess me nt of t he C R S se verit y  gra de w hic h will be ca pt ure d o n t he A E 
C R F a n d o n t he C R S C R F.
T a ble 1 4 . A S T C T C R S Gr a di n g S yste m
C R S para meter:
Fe ver *
Wit h H y p ote nsi o n
A n d/ or † H y p o xia
Gra de 1
T e m p. ≥3 8° C
N o ne
N o ne
Gra de 2
T e m p. ≥3 8° C
N ot re q uiri n g vas o press ors
Re q uiri n g l o w -fl o w‡ nasal 
ca n n ula, l o w-fl o w ‡ face mas k or 
bl o w -b y
Gra de 3
T e m p. ≥3 8° C
Re q uiri n g a vas o press or wit h or 
wit h o ut vas o pressi n
Re q uiri n g hi g h -fl o w ‡ nasal 
ca n n ula, hi g h -fl o w‡ face mas k, 
n o nre breat her ma s k, or Ve nt uri 
mas k
Gra de 4
T e m p. ≥3 8° C
Re q uiri n g m ulti ple vas o press ors 
(e xcl u di n g vas o pressi n)
Re q uiri n g p ositi ve press ure (e g, 
C P A P, Bi P A P, i nt u bati o n a n d 
mec ha nical ve ntilati o n)
* Fe ver is defi ne d as te m perat ure ≥3 8° C a n d n ot attri b uta ble t o a n y ot her ca use. I n partici pa nts w h o ha ve C R S t he n 
recei ve a nti p yretic or a ntic yt o ki ne t hera p y s uc h as t ociliz u ma b or ster oi ds, fe ver is n o l o n ger re q uire d t o gra de 
s u bse q ue nt C R S se verit y. I n t his case, C R S gra di n g is dri ve n b y h yp ote nsi o n a n d/ or h y p o xia.
† C R S gra de is deter mi ne d b y t he m ore se vere e ve nt: h y p ote nsi o n or h y p o xia n ot attri b uta ble t o a n y ot her ca use. F or 
e xa m ple, a partici pa nt wit h te m perat ure of 3 9. 5° C h y p ote nsi o n re q uiri n g 1 vas o press or, a n d h y p o xia re q uiri n g l o w -fl o w 
nasal ca n n ula is classifie d as gra de 3 C R S.
‡ L o w -fl o w nasal ca n n ula or face mas k is defi ne d as o x y ge n deli vere d at ≤6 L/ mi n. L o w fl o w als o i ncl u des bl o w- b y 
o x y ge n deli ver y, s o meti mes use d i n pe diatrics. Hi g h -fl o w nasal ca n n ula or face mas k is defi ne d as o x y ge n deli vere d at > 6 
L/ mi n. T his is m o difie d fr o m ori gi nal A S T C T criteria t o differe ntiate bet wee n l o w -fl o w a n d hi g h-fl o w face mas k.
Or ga n t o xicities ass ociate d wit h C R S s h o ul d still be gra de d acc or di n g t o C T C A E v 5. 0 a n d d o n ot i nfl ue nce C R S gra di n g.
A da pte d fr o m Lee D W, et al ( Lee et al, 2 0 1 9 ).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 8
T he defi niti o ns f or hi g h d ose - vas o press ors are s h o w n i n Ta ble 1 5.
T a ble 1 5 .
Defi niti o n of Hi g h D ose V as o press or
Press or
Hi g h D ose
( d oses less t ha n t hese w o ul d be c o nsi dere d l o w)
N ore pi ne p hri ne m o n ot hera p y
≥2 0 µ g/ mi n
D o pa mi ne m o n ot hera p y
≥1 0 µ g/ k g/ mi n
P he n yle p hri ne m o n ot hera p y
≥2 0 0 µ g/ mi n
E pi ne p hri ne m o n ot hera p y
≥1 0 µ g/ mi n
If o n vas o pressi n
Vas o pressi n + n ore pi ne p hri ne
e q ui vale nt of ≥1 0 µ g/ mi n *
If o n c o m bi nati o n vas o press ors
( n ot vas o pressi n)
N ore pi ne p hri ne e q ui vale nt of
≥2 0 µ g/ mi n *
* V A S S T Trial vas o press or e q ui vale nt e q uati o n: n ore pi ne p hri ne e q ui vale nt d ose = [ n ore pi ne p hri ne ( µ g/ mi n)]
+ [ d o pa mi ne ( µ g/ k g/ mi n) ÷ 2] + [e pi ne p hri ne ( µ g/ mi n)] + [ p he n yle p hri ne ( µ g/ mi n) ÷ 1 0
C R S M a n a ge me nt G ui deli nes (Neela p u et al, 2 0 1 8 ; Neela p u, 2 0 1 9 ):
T hese ma y  be m o difie d as nee de d b y t he res p o nsi ble In ves ti gat or acc or di n g t o t he best 
practices at t heir i nstit ute.
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 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 ydrati o n.

S y m pt o matic ma na ge me nt of c o nstit uti o nal s ym 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8 9
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 ml 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.

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 C U, o btai n E C H O, a n d i nitiate ot her met h o ds of he m o d yna mic 
m o nit ori n g.

I n partici pa 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 h o urs.
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 pa rtici pa 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 d y.
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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 0

De xa met has o ne 1 0 m g I V e ver y 6 ho u rs; if refract or y, i ncrease t o 2 0 m g I V e ver y 
6 h o u rs.
H y p o xi a

S u p pl e 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 descri be d 
a b o ve.
A S T C T Gr a de 4 C R S:
M o nit or pa rtici pa 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 a lrea 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 ntila ti 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.
1 0. 1 1. 2. I m m u ne effect or cell-ass oci ate d ne ur ot o xicit y s y n dr o me (I C A N S)
Alt h o u g h less c o m m o nl y see n t ha n C R S, I C A N S has bee n o bser ve d wit h s o me T- cell 
directe d t hera pies a n d ma y  ma nifest as a p hasia, deliri u m, e nce p hal o pat h y, let har g y, diffic ulty 
c o nce ntrati n g, a gitati o n, tre m or, seiz ures, a n d cere bral e de ma (Lee et al, 2 0 1 9 ). If I C A N S is 
o bser ve d i n relati o n t o P F - 0 7 2 6 0 4 3 7, t he A S T C T criteria will be use d f or gra di n g (Lee et al, 
2 0 1 9 ) i n a n d p u blis he d g ui deli nes are rec o m me n de d f or ma n a ge me nt (Neela p u et al, 2 0 1 8 ; 
Lee et al, 2 0 1 9 ; Neela p u, 2 0 1 9 ).T hese treat me nt g ui deli nes ma y be m o difie d as nee de d b y 
t he res p o nsi ble i n vesti gat or acc or di n g t o t he best practices at t heir i nstit ute. See Ta ble 1 6 f or 
I C E sc ore deter mi nati o n a n d Ta ble 1 7 f or A S T C T IC A N S gra di n g.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 1
T a ble 1 6 . I m m u ne Effect or Cell -Ass oci ate d E nce p h al o p at h y (I C E) Sc ore
C ate g or y
T as k
P oi nts
Orie ntati o n
Orie ntati o n t o year, m o nt h, cit y, h os pital
4
N a m i n g
A bilit y t o na me 3 o bjects
3
F oll o w i n g c o m ma n ds
A bilit y t o f oll o w si m ple c o m ma n ds
1
Writi n g
A bilit y t o write a sta n dar d se nte nce
1
Atte nti o n
A bilit y t o c o u nt bac k war ds fr o m 1 0 0 b y 1 0
1
T a ble 1 7 . A S T C T I C A N S Gr a di n g
Ne ur ot o xicit y D o m ai n
Gr a de 1  
Gr a de 2  
Gr a de 3
Gr a de 4
I C E sc orea
7- 9
3- 6 
0- 2
0 ( u nar o usa ble a n d u na ble t o 
perf or m I C E)
De presse d le vel of 
c o nsci o us ness b
A wa ke ns 
s p o nta ne o usl y
A wa ke ns t o 
v oice
A wa ke ns o nl y t o 
tactile sti m ul us
U nar o usa ble or re q uires vi g or o us 
or re petiti ve tactile sti m uli t o 
ar o use. St u p or or c o ma
Seiz ure
N/ A  
N/ A
A n y cli nical 
seiz ure t hat 
res ol ves ra pi dl y or 
n o n- c o n v ulsi ve 
seiz ures o n E E G 
t hat res ol ve wit h 
i nter ve nti o n
Life -t hreate ni n g pr ol o n ge d 
seiz ure ( > 5 mi n); or re petiti ve 
cli nical or electrical seiz ures 
wit h o ut ret ur n t o baseli ne i n 
bet w e e n
M ot or fi n di n gs
c
N/ A  
N/ A  
N/ A
Dee p f ocal m ot or w ea k ness s uc h 
as he mi paresis or para paresis
Ele v ate d I C P/cere br al 
e de ma
N/ A  
N/ A
F ocal/l ocal e de ma 
o n ne ur oi ma gi n g d
Diff use cere bral e de ma o n 
ne ur oi ma gi n g; decere brate or 
dec orticate p ost uri n g; or cra nial 
ner ve VI (a b d uce ns ner ve ) pals y; 
or pa pille de ma; or C us hi n g’s 
tria d
a.
A partici pa nt wit h a n I C E sc ore of 0 ma y be classifie d as Gra de 3 I C A N S if a wa ke wit h gl o bal a p hasia, b ut a 
partici pa nt wit h a n I C E sc ore of 0 ma y be classifie d as Gra de 4 I C A N S if u nar o usa ble
b.  
De presse d le vel of c o nsci o us ness s h o ul d be attri b uta ble t o n o ot her ca use (e g, n o se dati n g me dicati o n).
c.
Tre m ors a n d m y ocl o n us a ss ociate d wit h i m m u ne effect or cell t hera pies ma y be gra de d acc or di n g t o C T C A E v 5. 0; 
t hese s y m pt o ms d o n ot i nfl ue nce I C A N S gra di n g.
d.
I ntracra nial he m orr ha ge wit h or wit h o ut ass ociate d e de ma is n ot c o nsi dere d a ne ur ot o xicit y feat ure a n d is e xcl u de d 
fr o m I C A N S gra di n g. It s h o ul d be gra de d acc or di n g t o C T C A E v 5. 0.
N ote : I C A N S gra de is deter mi ne d b y t he m ost se vere e ve nt (I C E sc ore, le vel of c o nsci o us ness, seiz ure, m ot or fi n di n gs, 
raise d I C P/cere bral e de ma) n ot attri b uta ble t o a n y ot her ca use; f or e xa m ple, a partici pa nt wit h a n I C E sc ore of 3 w h o has 
a ge neralize d seiz ure is classifie d as Gra de 3 I C A N S .
S o urce: (Lee et al, 2 0 1 9 ).
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 2
I C A N S M a n a ge me nt G ui deli nes Per A S T C T (Neela p u et al, 2 0 1 8 ; Neela p u, 2 0 1 9 )
I C A N S Gr a de 1:

Vi gi la nt s u p p orti ve care; as pirati o n preca uti o ns; I V h ydrati o n.

Wit h h ol d oral i nta ke of f o o d, me dici nes, a n d fl ui ds; assess s wall o wi n g.

C o n vert all oral me dicati o ns a n d/ or n utriti o n t o I V if s wall o wi n g is i m paire d.

A v oi d me dicati o ns t hat ca use C N S de pressi o n.

Ne ur ol o g y  c o ns ultati o n.

If s us pecte d, e val uate f or ele vate d I C P wit h f u n d osc o pic e xa m f or pa pille de ma a n d 
l u m bar p u nct ure f or C S F o pe ni n g press ure.

M RI  of t he brai n wit h a n d wit h o ut c o ntrast; C T sca n of t he brai n ca n be perf or me d if 
M RI  is n ot feasi ble. 

D ail y 3 0 mi n E E G u ntil s ym pt o ms res ol ve.

C o nsi der a nti -I L-6 t hera p y  wit h t ociliz u ma b 8 m g/ k g ( ma xi m u m 8 0 0 m g) I V or 
silt u xi ma b 1 1 m g/ k g I V i n case of c o nc urre nt C R S.
I C A N S Gr a de 2:

S u p p orti ve care a n d ne ur ol o gical w or k -u p as descri be d f or Gra de 1 I CA N S.

A nt i-I L-6 t hera p y  if ass ociate d wit h c o nc urre nt C R S, as descri be d f or Gra de 1 
I C A N S a n d if n ot a d mi nistere d pre vi o usly.

De xa met has o ne 1 0 m g I V e ver y 6 h o urs or met h yl pre d nis ol o ne 1 m g/ k g I V e ver y 1 2 
h o urs if refract or y  t o a nti-I L-6 t hera p y , or f or I C A N S wit h out c o nc urre nt C R S.

C o nsi der tra nsferri n g partici pa nt t o I C U if I C A N S ass ociate d wit h Gra de ≥2 C R S.
I C A N S Gr a de 3:

S u p p orti ve care a n d ne ur ol o gical w or k -u p as i n dicate d f or Gra de 1 I C A N S.

I C U tra nsfer is rec o m me n de d.

If E E G s h o ws n o n-c o n v ulsi ve stat us e pile ptic us:

Assess air wa y , breat hi n g, a n d circ ulati o n; c hec k bl o o d gl uc ose.

L oraze pa m 0. 5 m g I V, wit h a d diti o nal 0. 5 m g I V e ver y  5 mi n, as nee de d, u p t o a 
t otal of 2 m g t o c o ntr ol electr o gra p hical seiz ures.

Le vetiraceta m 5 0 0 m g I V b ol us, as well as mai nte na nce d oses.

If seiz ures persist, tra nsfer t o I CU, a n d treat wit h p he n o bar bital l oa di n g d ose of 
6 0 m g I V.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 3

Rec o m me n de d mai nte na nce t hera p y after res ol uti o n of n o n -c o n v ulsi ve stat us 
e pile ptic us are as f oll o ws: 

l oraze pa m 0. 5 m g I V e ver y 8 h o urs f or 3 d oses; 

le vetiraceta m 1, 0 0 0 m g I V e ver y 1 2 h o urs; d urati o n of t hera p y per 
i n vesti gat or/treati n g p hys icia n’s discreti o n;

p he n o bar bital 3 0 m g I V e ver y  1 2 h o urs; d urati o n of t hera py per 
i n vesti gat or/treati n g p hys icia n’s discreti o n.

Lac osa mi de ma y  als o be c o nsi dere d f or treat me nt of seiz ures s h o ul d t he seiz ures 
persist. Lac osa mi de s h o ul d n ot be use d i n partici pa nts wit h c o nc urre nt C R S i n 
or der t o a v oi d arr h yt h mias a n d h y p ote nsi o n.

F or c o n v ulsi ve stat us e pile ptic us:

Assess air wa y , breat hi n g, a n d circ ulati o n; c hec k bl o o d gluc ose.

Tra nsfer t o I C U.

L oraze pa m 2 m g I V, wit h a d diti o nal 2 m g I V t o a t otal of 4 m g t o c o ntr ol 
seiz ures.

Le vetiraceta m 5 0 0 m g I V b ol us, as well as mai nte na nce d oses.

If seiz ures persist, a d d p he n o bar bital at a l oa di n g d ose of 1 5 m g/ k g I V.

Mai nte na nce d oses after res ol uti o n of c o n v ulsi ve stat us e pile ptic us: 

l oraze pa m 0. 5 m g I V e ver y 8 h o urs f or 3 d oses; 

le vetiraceta m 1, 0 0 0 m g I V e ver y 1 2 h o urs; d urati o n of t hera p y per 
i n vesti gat or/treati n g p hys icia n’s discreti o n; 

p he n o bar bital 1 -3 m g/ k g I V e ver y  1 2 h o urs; d urati o n of t hera py per 
i n vesti gat or/treati n g p hys icia n’s discreti o n.

Lac osa mi de ma y  als o be c o nsi dere d f or treat me nt of seiz ures s h o ul d t he seiz ures 
persist. Lac osa mi de s h o ul d n ot be use d i n partici pa nts wit h c o nc urre nt C R S i n 
or der t o a v oi d arr h y t h mias a n d hy p ote nsi o n.

C o nti n u o us E E G m o nit ori n g s h o ul d be perf or me d if seiz ures are refract or y t o 
treat me nt.

Hi g h -d ose met h y l pre d nis ol o ne I V 1 g/ da y f or f ocal/l ocal e de ma.

A nti- I L-6 t hera p y  if ass ociate d wit h c o nc urre nt C R S, as descri be d f or Gra de 1 
I C A N S a n d if n ot a d mi nistere d pre vi o usly.

C ortic oster oi ds as o utli ne d f or Gra de 2 I C A N S if s y m pt o ms w orse n des pite a nti -I L- 6 
t hera py, or f or I C A N S wit h o ut c o nc urre nt C R S; c o nti n ue c ortic oster oi ds u ntil 
i m pr o ve me nt t o Gra de 1 I C A N S a n d t he n ta per.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 4
I C AN S Gr a de 4:

S u p p orti ve care a n d ne ur ol o gical w or k -u p as o utli ne d f or Gra de 1 I C A N S.

I C U m o nit ori n g; c o nsi der mec ha nical ve ntilati o n f or air wa y pr otecti o n.

A nti- I L-6 t hera p y  a n d re peat ne ur oi ma gi n g as descri be d f or Gra de 3 I C A N S.

Hi g h -d ose c ortic oster oi ds c o nti n ue d u ntil i m pr o ve me nt t o Gra de 1 I CA N S a n d t he n 
ta per; f or e xa m ple, met h yl pre d nis ol o ne I V 1 g/ da y f or 3 d a y s, f oll o we d by ra pi d ta per 
at 2 5 0 m g e ver y 1 2 h o urs f or 2 da ys, 1 2 5 m g e ver y 1 2 h o urs f or 2 da ys, a n d 6 0 m g 
e ver y 1 2 h o urs f or 2 da ys.

F or c o n v u lsi ve stat us e pile ptic us, treat as descri be d f or Gra de 3 I C A N S.

M RI  of t he s pi ne s h o ul d be o btai ne d f or f ocal m ot or wea k ness.

T o ma na ge ele vate d I C P:

Ele vate hea d of t he partici pa nt's be d t o a n a n gle of 3 0 de grees.

H y per ve ntilati o n t o ac hie ve tar get partia l press ure of arterial car b o n di o xi de 
( Pa C O2) of 2 8– 3 0 m m H g, b ut mai ntai ne d f or n o l o n ger t ha n 2 4 h o u rs. 

H y per os m olar t hera p y  wit h eit her ma n nit ol ( 2 0 g/ dl s ol uti o n) or h ypert o nic sali ne 
( 3 % or 2 3. 4 %, as detaile d bel o w):

Ma n nit ol: i nitial d ose 0. 5 – 1 g/ k g; mai nte na nce at 0. 2 5 – 1 g/ k g e ver y  6 ho u rs 
w hile m o nit ori n g meta b olic pr ofile a n d ser u m os m olalit y  e ver y 6 h o urs, a n d 
wit h h ol d ma n nit ol if ser u m os m olalit y  is ≥3 2 0 m Os m/ k g, or t he os m olalit y  
ga p is ≥4 0.

H y pert o nic sali ne: i nitial 2 5 0 ml of 3 % h y pert o nic sal i ne; mai nte na nce at 
5 0 -7 5 ml/ h o ur w hile m o nit ori n g electr ol yt es e ver y 4 ho u rs, a n d wit h h ol d 
i nf usi o n if ser u m Na le vels reac h ≥1 5 5 m E q/l.

F or partici pa nts wit h i m mi ne nt her niati o n: i nitial 3 0 ml of 2 3. 4 % h y pert o nic 
sali ne; re peat after 1 5 mi n, if nee de d.

If patie nt has O m ma ya reser v oir, drai n C S F t o tar get o pe ni n g press ure of < 2 0 m m H g

C o nsi der ne ur os ur ger y  c o ns ultati o n f or ve ntric ul o perit o neal s h u nt i n partici pa nts wit h 
cere bral e de ma, a n d I V a nest hetics f or b urst-s u p pressi o n patter n o n E E G.

Meta b olic pr ofi li n g e ver y 6 h o urs a n d daily C T sca n of hea d, wit h a dj ust me nts i n 
usa ge of t he af ore me nti o ne d me dicati o ns t o pre ve nt re b o u n d cere bral oe de ma, re nal 
fail ure, electr olyt e a b n or malities, h yp o v ole mia, a n d h y p ote nsi o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 5
1 0. 1 2. A p pe n di x 1 2: 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 da pte d fr o m E. A. Eise n ha uer, et al (Eise n ha uer et al, 2 0 0 9 ): 
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 1 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 greater 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 di n g 
n o des wit h s h ort a xi s 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 ym 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 ysical 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 dise ase: 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 by C T or M RI  a n d meet the defi niti o n of meas ura bilit y  at baseli ne.
Pre vi o us l oc al tre at me nt: A pre vi o usl y  irra diate d lesi o n ( or lesi o n partici pa nt li 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 y stic 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 defi niti o n a b o ve. If n o n -c ystic 
lesi o ns are als o prese nt, t hese are preferre d as tar get lesi o ns.
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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 6
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 nerally s h o ul d be 
i n deter mi nate. 
N ote: F or t he pa rtici pa nt p o p ulati o n bei n g e val uate d i n t his pr ot oc ol, t he baseli ne assess me nt 
ma y  be c o m plete d wit hi n 6 wee ks pri or t o ra n d o mizati 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 uita bilit 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 dal 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 2 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 v al ue of 5 m m s h o ul d be rec or de d.
N O T E: W he n n o dal lesi o ns decrease t o < 1 0 m m ( n or mal), t he act ual meas 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 1 or ga n ma y  be rec or de d as a 
si n gle ite m o n t he case rep ort f or m (e g, ‘ m ulti ple e nlar ge d pel vic l y m p h n o des’ or ‘ m ulti ple 
li ver metastases’).
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 m i 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 . If n ot, s u bse q ue nt 
o bjecti ve stat uses are i n deter mi nate. 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 7
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.
P arti al 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. 
St a ble: D oes n ot q ualif y  f or C R, P R, or Pr o gr essi o n. All tar get lesi o ns m ust be 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 p y), wit h a mi ni m u m a bs ol ute i ncrease of 5 m m. 
I n deter mi n ate: 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 ns 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 1 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 1 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 si ze ( < 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. 
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 py. 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 n ate: Pr o gressi o n has n ot bee n deter mi ne d a n d 1 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.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 8
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 og 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 or de 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 pletel y, 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 natio 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 ma 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
Pa rtici pa 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 eve n after 
disc o nti n uati o n of treat me nt. 
T a ble 1 8 . 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9 9
T a ble 1 9 .
O bjecti ve Res p o nse St at us at E ac h E v al u ati o n f or P artici p a n ts 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 0
1 0. 1 3. A p pe n di x 1 3: 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 he ir R E CI S T t u m or assess me nt s y ste m has bee n de vel o pe d t o i nc or p orate dela ye d or flare 
t ype- res p o nses i nt o t he R E CIS T v 1. 1 (Nis hi n o et al, 2 0 1 4 ). 
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 meter 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: 

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 l y 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. 

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 %. 

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 pa re 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). 

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 date 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 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 1
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 ni n de x, a n d ne w lesi o ns are o utli ne d i n 
Ta ble 2 0 .
T a ble 2 0 . 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
Meas ura ble Res p o nse
N o n meas ura ble - Res p o nse
O verall Res p o nse Usi n g 
ir R E CI S Tb
I n de x a n d Ne w 
Meas ura ble Lesi o ns 
( T u m or B ur de n)a
N o nI n de x - Lesi o ns
Meas ura 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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 2
1 0. 1 4. A p pe n di x 1 4: 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. L ocati o n 
1 is pr o xi mal t o t he u m bilic us a n d Locati o n 2 is distal t o t he u m bilic us.
A d mi nister t he re q uire d n u m ber of i njecti o ns i n t he f oll o wi n g or der:
1.
L o wer Left Q ua dra nt L ocati o n 1;
2.
L o wer Ri g ht Q ua dra nt L ocati o n 1;
3.
L o wer Left Q ua dra nt L ocati o n 2;
4.
L o wer Ri g ht Q ua dra nt L ocati o n 2;
5.
U p per Ri g ht Q ua dra nt L ocati o n 1;
6.
U p per Left Q ua dra nt L ocati o n 1;
7.
U p per Ri g ht Q ua dra nt L ocati o n 2;
8.
U p per Left Q ua dra nt L ocati o n 2.
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 njec ti 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. 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.
Trac k t he pa rtici pant’s i njecti o n site(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 patie nt’s a b d o me n acc or di n g t o y o ur cli nic’s sta n dar d practice.
Rec or d t he l ocati o n, ti me of eac h i njecti o n a n d a n y I S Rs i n t he pa rtici pa nt’s s o urce rec or ds 
a n d st u d y C R F. C o m plete 1 C R F per i njecti o n.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 3
1 0. 1 5. A p pe n di x 1 5 . C a uti o nar y Use of C o nc o mit a nt Me dic ati o ns wit h N arr o w 
T her a pe utic I n de x D ue t o Dr u g -Dr u g I nter acti o n ( D DI) P ote nti al .
M e dicati o ns liste d bel o w ha ve narr o w t hera pe utic i n de x a n d s h o ul d be use d wit h ca uti o n as
c o nc o mita nt treat me nt wit h P F - 0 7 2 6 0 4 3 7. It has bee n k n o w n t hat C R S is m ostl y li kely t o 
occ ur wit hi n t he first fe w da y s after t he first d ose, a n d t he i ncrease d c yt o ki ne le vel c o ul d 
p ote ntiall y  d o w n-re g ulate C Y P 4 5 0 e nz ymes a n d alter t he e x p os ure of dr u gs t hat are 
s u bstrates of t hese e nz y mes. T he P fizer st u d y tea m s h o ul d be n otifie d of a n y  liste d 
me dicati o ns ta ke n d uri n g t he st u d y f or c o ns ultati o n . 
T his list of dr u gs f or p ote ntial D DI c o ncer ns wit h t he P F -0 7 2 6 0 4 3 7 ma y  be re vise d d uri n g 
t he c o urse of t he st u d y wit h writte n n otificati o n fr o m s p o ns or, t o i ncl u de or e xcl u de s pecific 
dr u gs or dr u g cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI res ults f or P F - 0 7 2 6 0 4 3 7, 
ne w i nf or mati o n i n literat ures o n t he D DI p ote ntial of ot her dr u gs). 
T his is n ot a n all -i ncl usi ve list. S hare d s u bstrate s f or m ulti ple C Y P 4 5 0 e nz y mes are liste d 
o ne ti me t o a v oi d d u plicati o n. Site staff s h o ul d c o ns ult wit h t he s p o ns or or desi g nee wit h a n y 
q uesti o ns re gar di n g p ote ntial D DI.
Dr u g C ate g or y
Dr u gs
C Y P 3 A 4 S u bstrate
alfe nta nil
a mi o dar o ne
ar gatr o ba n
car ba maze pi ne
c ycl os p ori ne
di h y dr oer g ota mi ne
er g ota mi ne
e ver oli m us
fe nta nyl
pi m ozi de
q ui ni di ne
rifa m pi n
sir oli m us
tacr oli m us 
val pr oate
C Y P 2 C 9 S u bstrate
ace n oc o u mar ol
is otreti n oi n
p he n y t oi n
P he n o bar bital
p he n pr oc o u m o n
warfari n
C Y P 2 C 1 9 S u bstrate
me p he n yt oi n
C Y P 1 A 2 S u bstrate
the o p h y lli ne
tiza ni di ne
C Y P 2 B 6 S u bstrate
car ba maze pi ne
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 4
Dr u g C ate g or y
Dr u gs
c yc l o p h os p ha mi de
I n vesti gat ors s h o ul d c o ns ult t he pr o d uct la bel f or a n y ot her me dicati o n use d d uri n g t he st u d y
f or i nf or mati o n re gar di n g me dicati o n t hat is pr o hi bite d f or c o nc o mita nt use.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 5
1 0. 1 6. A p pe n di x 1 6 : E C O G Perf or m a nce St at us
Gr a de
E C O G Perf or m a nce St at us
0
F ull y  acti ve, a ble t o carr y o n all pre-disease perf or ma nce wit h o ut restricti o n.
1
Restricte d i n p h y sicall y stre n u o us acti vit y b ut a m b ulat or y a n d a ble t o carr y o ut 
w or k of a li g ht or se de ntar y  nat ure, e g, li g ht h o use w or k , office w or k.
2
A m b ulat or y  a n d ca pa ble of all self-care b ut u na ble t o carr y o ut a ny w or k 
acti vities. U p a n d a b o ut m or e t ha n 5 0 % of wa ki n g h o urs.
3
Ca pa ble of o nl y li mite d self -care, c o nfi ne d t o be d or c hair m ore t ha n 5 0 % of 
wa ki n g h o urs.
4
C o m pletel y  disa ble d. Ca n n ot carr y o n a n y self-care. T otall y c o nfi ne d t o be d or 
c hair.
5
Dea d.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 6
1 0. 1 7. A p pe n di x 1 7 : 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
2 L +
after first li ne sta n dar d of care
A C T H
a dre n oc ortic otr o pic h or m o ne
A D A
a nti dr u g a nti b o dies
A D L
acti vities of dail y li vi n g
A E
a d verse e ve nt
A H A
A m erica n Heart Ass ociati o n
AI D S
ac q uire d i m m u n o deficie nc y  sy n dr o me
A L P
al kali ne p h os p hatase
A L T
ala ni ne a mi n otra nsferase
A N C
a bs ol ute ne utr o p hil c o u nt
a P T T
acti vate d partial t hr o m b o plasti n ti me
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 T
ami n otra nsferases
A U C
area u n der t he c ur ve
A U C i nf
area u n der t he c o nce ntrati o n -ti me vers us ti me c ur ve fr o m ti me 0 t o 
i nfi nit y
A U C last
area u n der t he c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o ti me of last 
meas ura ble c o nce ntrati o n
A U C s d,τ
area u n der t he c o nce ntrati o n -ti me c ur ve after si n gle d ose o ver 
d osi n g i nter val τ
A U C ss,τ
area u n der t he c o nce ntrati o n -ti me c ur ve at stea dy state o ver d osi n g 
i nter val τ
A V
atri o ve ntric ul ar
B
B cells
B B S
Bi os peci me n Ba n ki n g S yste m
Bi P A P
bile vel p ositi ve air wa y  press ure
B L R M
Ba yesia n l o gistic re gressi o n m o del
B N P
brai n natri uretic pe pti de
B P
bl o o d press ure
B p m
beats per mi n ute
Br Ca
breast ca ncer 
B U N
bl o o d urea nitr o ge n
B V N
bi variate n or mal
C
c ycle
C A R
c hi meric a nti b o d y rece pt or
C D 3
Cl uster -Defi ne d 3
C D C
T he Ce nters f or Disease C o ntr ol a n d Pre ve nti o n
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 7
A b bre vi ati o n
Ter m
C D K
c ycli n-de pe n de nt ki nase
C F R
C o de of Fe deral Re g ulati o ns
C H F
c o n gesti ve heart fail ure
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
CI S H
c hr o m o ge nic i n sit u h ybri dizati o n
C K
creati ne ki nase
C K -M B
creati ne ki nase -m uscle t y pe, m y ocar dial ba n d
C L
cleara nce
C L / F
a p pare nt cleara nce
C L S S / F
a p pare nt cleara nce at stea d y state
C L I A
Cli nical L a b orat or y Im pr o ve me nt A me n d me nts
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C ma x ,ss
ma xi m u m c o nce ntrati o n at stea d y state
C mi n ,ss
mi ni m u m c o nce ntrati o n at stea d y state
C N S
ce ntral ner v o us s ys te m
C O 2
car b o n di o xi de
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 O VI D -1 9
c or o na vir us disease 2 0 1 9
C P A P
c o nti n u o us p ositi ve air wa y press ure
C R
c o m plete res p o nse
Cr Cl
creati ni ne cleara nce
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 S F
cere bral s pi nal fl ui d
C S R
cli nical st u d y re p ort
C T
cli nical trial/ c o m p ute d t o m o gra p h y
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C T L s
C y t ot o xic T l ym p h oc y tes
C Y P
c yt oc hr o me P-4 5 0 e nz y mes;
D
da y
D DI
dr u g -dr u g i nteracti o n
DI LI
dr u g -i n d uce d li ver i nj ur y
DI S H
d ual i n sit u h y bri dizati 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 nts
D U
dis pe nsa ble u nit
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 8
A b bre vi ati o n
Ter m
E C
et hics c o m mittee
E C 5 0
half ma xi mal effecti ve c o nce ntrati o n
E C C
e mer ge nc y c o ntact car d
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 B
e x p os ure d uri n g breastfee di n g
E D P
e x p os ure d uri n g pre g na nc y
E E G
electr oe nce p hal o gra m
E M A
E ur o pea n Me dici nes A ge nc y
E O T
e n d of treat me nt
E R
estr o ge n rece pt or
E S C
E ur o pea n S ociet y of Car di ol o g y
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 A S
f ull a nal ysis set
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 S H
fl u oresce nce 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 S F
gra n ul oc y te-c ol o n y sti m ulati n g fact or
G C P
G o o d Cli nical Practice
G G T
ga m ma gl uta m yl  tra nsferase
G H
gr o wt h h or m o ne
GI
gastr oi ntesti nal
G L P
G o o d La b orat or y  Practice
H Bc
he patitis B c ore
H Bc A b
he patitis B c ore a nti b o d y
H Bs A b
he patitis B s urface 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 E R 2 -
h u ma n e pi der mal gr o wt h fact or rece pt or 2 ne gati ve
H E R +
h u ma n e pi der mal gr o wt h fact or rece pt or p ositi ve
HI V
h u ma n i m m u n o deficie nc y vir us
H L A -D R
h u ma n le u k oc y te a nti ge n-a nti ge n D relate d
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 +
h or m o ne rece pt or p ositi ve
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0 9
A b bre vi ati o n
Ter m
H R T
h or m o ne re place me nt t hera p y
I B
i n vesti gat or’s br oc h ure
I C A N S
I m m u ne Effect or Cell-Ass ociate d Ne ur ot o xicit y  S yn dr o me
I C D
i nf or me d c o nse nt d oc u me nt
I C E
i m m u ne effect or cell-ass ociate d e nce p hal o pat h y
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n
I C P
i ntracra nial press ure
I C U
i nte nsi ve care u nit
I D
i de ntificati o n
I F N-
i nterfer o n-ga m ma
I GF -1
i ns uli n-li ke gr o wt h fact or 1
I g G
i m m u n o gl o b uli n G
I g G 2
i m m u n o gl o b uli n G 2
I g M
i m m u n o gl o b uli n M
I H C
i m m u n o hist oc he mistr y 
I L
i nterle u ki n
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
I N R
i nter nati o nal n or malize d rati o
I P ma n ual
i n vesti gati o nal pr o d uct ma n ual
I P A L
I n vesti gati o nal Pr o d uct Acc o u nta bilit y L o g
ir
i m m u ne-relate d
ir A E
i m m u ne-relate d a d verse e ve nts
I RB
i nstit uti o nal re vie w b oar d
ir C R
i m m u ne-relate d c o m plete res p o nse
ir P D
i m m u ne-relate d pr o gressi ve disease
ir P R
i m m u ne-relate d partial res p o nse
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 deri ve d fr o m R E CI S T 1. 1
ir S D
i m m u ne-relate d sta ble disease
I R T
i nteracti ve res p o nse tec h n ol o g y
I S H
i n sit u h y bri dizati o n
I S R
i njecti o n site reacti o n
I V
i ntra ve n o us
I W R
i nteracti ve We b-base d res p o nse
K 2 E D T A
di p otassi u m et h yle ne dia mi netetraacetic aci d
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 D T
La b orat or y  De vel o pe d Test
L F T
li ver f u ncti o n test
L H
l utei nizi n g h or m o ne
m A b 
m o n ocl o nal a nti b o d y
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1 0
A b bre vi ati o n
Ter m
M A B E L
mi ni m u m a ntici pate d bi ol o gical effect le vel
M A P
meta -a nal yt ic-pre dicti ve
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 I
mea n fl u oresce nce i nte nsit y
M H C
Maj or Hist oc o m pati bilit y  C o m ple x
mI T T
m o difie d i nte nt t o treat
M o A
mec ha nis m of acti o n
M RI
ma g netic res o na nce i ma gi n g
M T D
ma xi m u m t olerate d d ose
m T N B C
metastatic tri ple ne gati ve Br Ca
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 cells
N O A E L
n o -o bser ve d -a d verse-effect le vel
N S AI Ds
n o n -ster oi dal a nti-i nfla m mat or y dr u gs
O R
o bjecti ve res p o nse
O R R
o bjecti ve res p o nse rate
O S
o verall s ur vi val
O v Ca
o varia n ca ncer
Pa C O 2
partial press ure of car b o n di o xi de
P B M C
peri p heral bl o o d m o n o n uclear cell
P C R
p ol y merase c hai n reacti o n
P D
p har mac o d y n a mics(s)/ pr o gressi ve disease
P D -1
pr o gra m me d deat h -1
P D -L 1
pr o gra m me d deat h -Li ga n d 1
P E
p h y sical e xa mi nati o n
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
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic(s)
P R
partial res p o nse/ pr o gester o ne rece pt or/ p ulse rate
P R L
pr olacti n
P S
perf or ma nce stat us
P T
pr ot hr o m bi n ti me
P T T
partial t hr o m b o plasti n ti me
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q 1 W
e ver y 1 wee k
Q 2 W
e ver y 2 wee ks
Q 3 W
e ver y 3 wee ks
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1 1
A b bre vi ati o n
Ter m
Q 4 W
e ver y 4 wee ks
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)
Q T L
q ualit y  t olera nce li mit
R ac
acc u m ulati o n rati o
R D E
rec o m me n de d d ose f or e x pa nsi o n
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 N A
ri b o n ucleic aci d
R P 2 D
rec o m me n de d p hase 2 d ose
R R
res pirat or y rate
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S A R S -C o V 2
se vere ac ute res pirat or y s yn dr o me c or o na vir us 2
S A S
safety a nal ysis set
S C
s u bc uta ne o us
S D
si n gle d ose/sta ble disease/sta n dar d de viati o n
SI S H
sil ver e n ha nce d i n sit u h y bri dizati o n
S O A
sc he d ule of acti vities
S O C
sta n dar d of care
S O P
sta n dar d o perati n g pr oce d ure
S R S D
si n gle refere nce safety d oc u me nt
ss
stea d y state
S U S A R
s us pecte d u ne x pecte d seri o us a d verse reacti o n
T
T cell
t½
ter mi nal eli mi nati o n half-life
T 4
t h yr o xi ne
T Bili
t otal bilir u bi n
T C R
T cell rece pt or
TI L
t u m or i nfiltrati n g l ym p h oc y tes
T ma x
ti me t o ma xi m u m c o nce ntrati o n
T ma x,ss
ti me t o ma xi m u m c o nce ntrati o n at stea d y state
T M E
t u m or micr oe n vir o n me nt
T N B C
tri ple ne gati ve Br Ca
T N F
t u m or necr osis fact or
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 L N
u p per li mit of n or mal
U S
U nite d States
V ss
v ol u me at stea d y -state
V A A S T
Vas o pressi n a n d Se ptic S h oc k Trial
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)
C CI

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1 2
A b bre vi ati o n
Ter m
V z/ F
a p pare nt v ol u me of distri b uti o n d uri n g ter mi nal p hase
W B C
w hite bl o o d cell
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 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1 3
1 1. R E F E R E N C E S
Allis o n K H, Ha m m o n d M E H, D o wsett M, et al. Estr o ge n a n d Pr o gester o ne Rece pt or Testi n g 
i n Breast Ca ncer: A S C O/ C A P G ui deli ne U p date. J Cli n O nc ol. 2 0 2 0; 3 8( 1 2): 1 3 4 6- 6 6.
Be ns o n A B, 3r 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.
B LI N C Y T O ( bli nat u m o ma b). B LI N C Y T O ( bli nat u m o ma b) U S Prescri bi n g I nf or mati o n 
( U S PI); 1 7 Marc h 2 0 2 1 2 0 2 1, T h o usa n Oa ks, C A. A vaila ble fr o m: 
htt ps:// dail y me d. nl m. ni h. g o v/ dail y m e d/ dr u gI nf o.cf m?seti d = 3 8 b 4 8 2a 8 - 9 6 0 b- 4 5 9 1- 9 8 5 7-
5 0 3 1ec b 8 3 0aa . Accesse d o n: 0 5 Ma y 2 0 2 1.
Bra h mer J R, L acc hetti C, Sc h nei der BJ, et al. Ma na ge me nt of i m m u ne- relate d a d verse e ve nts 
i n patie nts treate d wit h i m m u ne c hec k p oi nt i n hi bit or t hera py:  A merica n S ociet y of Cli nical 
O nc ol o g y  Cli nical Practice G ui deli ne. 2 0 18; 3 6( 1 7): 1 7 1 4.
C osta L J, W o n g S W, Ber m u dez A, et al. First cli nical st u d y of t he B-cell mat urati o n a nti ge n 
( B C M A) 2 + 1 T cell e n ga ger ( T C E) C C-9 3 2 6 9 i n patie nts ( Pts) wit h rela pse d/refract or y  
m ulti ple m y el o ma ( R R M M): i nteri m res ults of a p hase 1 m ultice nte r trial. A merica n S ociety 
of He mat ol o g y  Was hi n gt o n, D C; 2 0 1 9.
Eise n ha uer E A, T herasse P, B o gaerts J, et al. Ne w res p o nse e val uati o n criteria i n s oli d 
t u m o urs: re vise d R E CIS T g ui deli ne ( versi o n 1. 1). E ur J Ca ncer. 2 0 0 9; 4 5( 2): 2 2 8 - 4 7.
Garfall A, e dit or U p date d P hase 1 Res ults of Teclista ma b, a B- Cell Mat urati o n A nti ge n 
( B C M A) x C D 3 Bis pecific A nti b o d y, i n Rela pse d a n d/ or Refract or y M ulti ple M yel o ma 
( R R M M). 6 2 n d A S H A n n ual Meeti n g a n d E x p ositi o n; 2 0 2 0: A S H.
He n dri k x J, Haa ne n J, V oest E E, et al. Fi xe d D osi n g of M o n ocl o nal A nti b o dies i n O nc ol o g y . 
O nc ol o gist. 2 0 1 7; 2 2( 1 0): 1 2 1 2- 2 1.
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 yt o ki ne release sy n dr o me. Bl o o d. 2 0 1 4; 1 2 4( 2): 1 8 8 - 9 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. Bi ol Bl o o d 
Marr o w Tra ns pla nt. 2 0 1 9; 2 5( 4): 6 2 5- 3 8.
Le o n g S R, Lia n g W - C, W u Y, et al. A n a nti-B 7 -H 4 a nti b o d y – dr u g c o nj u gate f or t he 
treat me nt of breast ca ncer. 2 0 1 5; 1 2( 6): 1 7 1 7- 2 9.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1 4
Ma d d uri D, R os k o A, Bra y er J, et al., e dit ors. R E G N 5 4 5 8, a B C M A × C D 3 bis pecific 
m o n ocl o nal a nti b o d y , i n d uces dee p a n d d ura ble res p o nses i n patie nts wit h rela pse d/refract or y 
m ulti ple m y el o ma ( R R M M). Pr ocee di n gs of t he 6 2 n d A S H A n n ual Meeti n g a n d E x p ositi o n, 
Virt ual O nli ne, Sa n Die g o, C A, U S A; 2 0 2 0.
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. 2 0 1 8; 1 5( 1): 4 7.
Neela p u S SJ H o. Ma na gi n g t he t o xicities o f car T‐cell t hera py. 2 0 1 9; 3 7: 4 8 - 5 2.
Ne ue nsc h wa n der B, Ca p k u n - Ni g gli G, Bra ns o n M, et al. 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. 2 0 1 0; 7( 1): 5 - 1 8.
Ne ue nsc h wa n der B, Mata n o A, Ta n g Z, et al. 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 . 2 0 1 5; 6: 9 5- 1 3 5.
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 
patie nts treate d wit h i pili m u ma b? 2 0 1 4; 2( 1): 1- 1 2.
R o gat k o A, Sc h oe nec k D, J o nas W, et al. Tra nslati o n of i n n o vati ve desi g ns i nt o p hase I 
trials. 2 0 0 7; 2 5( 3 1): 4 9 8 2- 8 6.
Sc h mi dli H, Gstei ger S, R o y c h o u d h ur y S, et al. R o b ust meta‐a nalyt 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. 2 0 1 4; 7 0( 4): 1 0 2 3 - 3 2.
S har ma PJ T o. Bi ol o g y  a n d ma na ge me nt of patie nts wit h tri ple-ne gati ve breast ca ncer. 
2 0 1 6; 2 1( 9): 1 0 5 0.
S mit h TJ, K hatc heressia n J, L y ma n G H, et al. 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 Cli n 
O nc ol. 2 0 0 6; 2 4( 1 9): 3 1 8 7 - 2 0 5.
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.
Wa n g D D, Z ha n g S, Z ha o H, et al. Fi xe d d osi n g ve rs us b o dy 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. 2 0 0 9; 4 9( 9): 1 0 1 2- 2 4.
W olff A C, Ha m m o n d M E H, Allis o n K H, et al. H u ma n E pi der mal Gr o wt h Fact or Rece pt or 2 
Testi n g i n Breast Ca ncer: A merica n S ociet y of Cli nical O nc ol o g y / C olle ge of A merica n 
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)

P F -0 7 2 6 0 4 3 7
Pr ot oc ol C 4 4 3 1 0 0 1
Fi nal Pr ot oc ol, A me n d me nt 1, 0 9 A u g ust 2 0 2 1
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P O nc ol o g y C li nical Pr ot oc ol Te m plate ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1 5
Pat h ol o gists Cli nical Practice G ui deli ne F oc use d U p date. J Cli n O nc ol. 2 0 1 8; 3 6( 2 0): 2 1 0 5 -
2 2.
Z ha n g S, S hi R, L i 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. 2 0 1 2; 5 2( 1): 1 8- 2 8.
0 9 0 1 7 7 e 1 9 7 c 4 5 5 b d\ A p pr o v e d\ A p pr o v e d O n: 0 9- A u g- 2 0 2 1 2 2: 0 8 ( G M T)