Clinical trial NCT05067972
Conditions: Ovarian Neoplasms Endometrial Neoplasms Breast Neoplasms
Keywords: Cancer of Endometrium Cancer of the Endometrium Carcinoma of Endometrium Endometrial Cancer Endometrial Carcinoma Endometrium Cancer Neoplasms, Endometrial Cancer of Ovary Cancer of the Ovary Neoplasms, Ovarian Ovarian Cancer Ovary Cancer Ovary Neoplasms Breast Cancer Breast Carcinoma Breast Tumors Cancer of Breast Cancer of the Breast Human Mammary Carcinoma Malignant Neoplasm of Breast Malignant Tumor of Breast
Sponsor: Pfizer
Start date: 2021-10-07; Completion date: 2023-10-17
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
A study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-07260437, a B7-H4 x CD3 bispecific mAb, in participants aged ≥18 years of age with advanced or metastatic breast cancer, ovarian cancer or endometrial cancer. Adult participants with other advanced or metastatic high B7-H4 expressing tumors may be considered after discussion with and approval from sponsor.

Detailed description:

Arms: arm 1: Participants will receive PF-07260437 arm 2: Participants will receive PF-07260437 arm 3: Participants will receive PF-07260437 arm 4: Participants will receive PF07260437
Interventions: intervention 1: PF-07260437 intervention 2: B7-H4 IHC
Intervention descriptions: intervention 1: B7-H4 x CD3 bi-specific mAb intervention 2: B7-H4 expression

Protocol documents:
Prot_000.pdf: 
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)

SAP_001.pdf: 
Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 1 
 
 
Pr ot oc ol C 4 4 3 1 0 0 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 atistic al A n al ysis Pl a n  
( S A P) 
 
 
 
 
 
 
 
Versi o n:  
1   
 
D ate:  
0 4 Oct o ber 2 0 2 1  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 2 
 
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..................................................................................................................... 3
LI S T O F FI G U R E S ................................................................................................................... 4
1. V E R SI O N HI S T O R Y............................................................................................................ 4
2. I N T R O D U C TI O N................................................................................................................. 4
2. 1. St u d y O bjecti ves, E n d p oi nts a n d Esti ma n ds ............................................................. 4
2. 1. 1 Pri mar y Esti ma n d(s)...................................................................................... 4
2. 2. St u d y Desi g n............................................................................................................. 5
2. 3. Sc he ma ...................................................................................................................... 9
3.  E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S................................................................................................................ 1 1
3. 1  
P RI M A R Y E N D P OI N T( S)....................................................................................... 1 1
3. 2 
Sec o n dar y E n d p oi nt(s)..................................................................................... 1 2
3. 3 
Tertiar y/ E x pl orat or y E n d p oi nt(s)..................................................................... 1 3
3. 4 
Baseli n e Varia bl es ........................................................................................... 1 4
3. 5 
Safet y E n d p oi nts.............................................................................................. 1 4
3. 5. 1  
A d verse E v e nts .................................................................................. 1 4
3. 5. 2 
La b orat or y D ata................................................................................. 1 4
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S)................................................... 1 4
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S ..................................................... 1 5
5. 1  
H y p ot heses a n d D ecisi o n R ules ....................................................................... 1 5
5. 2  
Ge n eral Met h o ds.............................................................................................. 1 5
5. 2. 1  
A nal yses f or Bi nar y E n d p oi nts.......................................................... 1 6
5. 2. 2  
A nal yses f or C o nti n u o us E n d p oi nts.................................................. 1 6
5. 2. 3  
A nal yses f or Cat e g orical E n d p oi nts.................................................. 1 6
5. 2. 4 A nal yses f or Ti me-t o- E ve nt E n d p oi nts ....................................................... 1 6
5. 3  
Met h o ds t o Ma na ge Missi n g Data................................................................... 1 6
5. 3. 1  
Missi n g Dates .................................................................................... 1 6
5. 3. 2 
Efficac y A nal ysis............................................................................... 1 7
5. 3. 3 
P har mac o ki n etics ............................................................................... 1 7
5. 3. 3. 1
C o nce ntrati o ns Bel o w t he Li mit of Q ua ntificati o n ................. 1 7
5. 3. 3. 2
De viati o ns, Missi n g C o nce ntrati o ns a n d A n o m al o us 
Val u es ................................................................................................ 1 7
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 3 
 
5. 3. 4 
P har mac o ki n etic Para met ers ............................................................. 1 7
5. 3. 5 
P har mac o d y na mic Para meters........................................................... 1 8
5. 3. 6  
Q Tc.................................................................................................... 1 8
5. 4 
Statisti cal C o nsi derati o ns of C O VI D- 1 9 I m p acte d Data ................................. 1 8
6. A N A L Y S E S A N D S U M M A RI E S...................................................................................... 1 9
6. 1 
Pri mar y E n d p oi nt(s)......................................................................................... 1 9
6. 1. 2  
A d verse E v e nts ( Part 1 a n d Part 2).................................................... 1 9
6. 1. 3 
La b orat or y a b n or malities ( Part 1 a n d Part 2).................................... 1 9
6. 2 
Sec o n dar y E n d p oi nts ....................................................................................... 2 0
6. 2. 1 
ir A Es.................................................................................................. 2 0
6. 2. 2 
Si n gle- D ose a n d St ea d y- State P F- 0 7 2 6 0 4 3 7 P har mac o ki n etic 
A nal ysis 2 0  
6. 2. 3 A nal ysis of I m m u n o ge nicit y Data ............................................................... 2 1
6. 2. 4 
Efficac y A nal ysis............................................................................... 2 1
6. 3 
Tertiar y/ E x pl orat or y E n d p oi nt(s)..................................................................... 2 6
6. 5 
Baseli n e a n d Ot her S u m maries a n d A n al yses ................................................. 2 6
6. 5. 1 
Baseli n e S u m maries .......................................................................... 2 6
6. 5. 2 
St u d y C o n d uct a n d Partici pa nt Dis p ositi o n ....................................... 2 6
6. 5. 3 
St u d y Treat me nt E x p os ure ................................................................ 2 7
6. 5. 4 
C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts......................... 2 8
6. 6 
Safet y S u m maries a n d A nal yses ...................................................................... 2 8
6. 6. 1  
A d verse E v e nts .................................................................................. 2 9
6. 6. 2 
Cli nical Safet y La b orat or y Ass ess me nts........................................... 2 9
6. 6. 3  
Vit al Si g ns......................................................................................... 2 9
6. 6. 4 
Electr ocar di o gra ms............................................................................ 2 9
6. 6. 5 
P h ysical E xa mi n ati o n........................................................................ 3 0
7.  I N T E RI M A N A L Y S E S ...................................................................................................... 3 1
8. R E F E R E N C E S .................................................................................................................... 3 1
9. A P P E N DI C E S ..................................................................................................................... 3 1
LI S T O F T A B L E S 
Ta ble 1.  
A nal ysis Sets............................................................................................. 1 4
Ta ble 2  
P F S a n d D O R O utc o me a n d E ve nt Dates................................................. 2 4
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 4 
 
Ta ble 3  
P F S Ce ns ori n g Reas o ns a n d Hieararc h y .................................................. 2 5
Ta ble 4  
O S O utc o me a n d E ve nt D ates .................................................................. 3 1
LI S T O F FI G U R E S 
Fi g ure 1. 
St u d y Sc he ma........................................................................................... 1 0
1.  V E R SI O N HI S T O R Y 
T his is t he first versi o n. 
2.  I N T R O D U C TI O N 
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 m ai n t h at rec o g niz es 
, e x press e d o n T cells, wit h m o derate affi nit y. C o-e n ga g e 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 u ces 
s ystemic  
 tar g eti n g a n d t o xicit y. T his m ec ha nis m circ u m ve nts t he nee d f or T cells t o 
rec o g niz e s p ecifi c a nti ge nic pe pti des i n t he c o nte xt of 
 o n m ali g na nt cells. 
C yt ot o xicit y is m e 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 dress es 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 m aj orit y of Br Cas acr oss all m olec ular s u bt y pes. 
T his statistical a nal ysis pla n ( S A P) pr o vi des t he d etaile d met h o d ol o g y f or s u m mar y a n d 
statisti cal a nal yses of t he data c ollecte d i n St u d y P F- 0 7 2 6 0 4 3 7.  T his d oc u me nt pr o vi des 
a d diti o nal details f or t he pla n ne d a nal yses t h at are o utli ne d i n t he pr ot oc ol. T his S A P was 
writte n i n refere n ce t o t h e pr ot oc ol date d J u n e 2 3, 2 0 2 1.  A n y maj or m o dificati o ns of t he 
e n d p oi nts or a nal yses will be reflecte d i n f urt her a m e n d me nts t o t he pr ot oc ol a n d S A P. 
2. 1.  St u d y O bjecti ves, E n d p oi nts a n d Esti m a n ds 
2. 1. 1 Pri m ar y Esti m a n d(s) 
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 d a ys f or re gi me n wit h o ut pri mi n g; 4 2 da ys f or t he re gi me n wit h 
pri mi n g ( pri mi n g d oses pl us 2 f ull d oses)) i n Part 1. 
Vari a ble: O cc urre nce of D L Ts.  
A nal ysis 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 parti ci pa nts d efi ne d as parti ci pa nts: 
 w h o recei ve at least 1 d ose of st u d y treat m e nt a n d e x perie n ce D L T d uri n g t he D L T-
e val uati o n peri o d ( 2 8 d a ys), 
O R
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 
C CI
C CI
C CI
C CI
C CI


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 5 
 
 w h o c o m plete t h e 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 h a n treat me nt-relate d t o xi cit y are n ot e v al ua ble f or D L T.  
F or t he d ose escalati o n wit h pri mi n g, D L T-e val ua ble partici pa nts defi n e d as partici pa nts:  
 w h o recei ve at least 1 d ose of st u d y treat m e nt a n d e x perie n ce 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 ys), 
O R
 w h o c o m plete t h e 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 h a n tr eat m e 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 d efi ne d as t he n u m ber of D L T-e val ua bl e 
partici pa nts wit h D L Ts i n t he D L T-e v al uati o n peri o d di vi de d b y t he n u m ber of 
D L T-e val u a ble partici pa nts i n t he D L T-e val uati o n peri o d. 
Pri mar y Esti ma n d f or Parts 1 a n d 2:  
I n ci de nce of A Es esti mate d i n t he a nal ysis p o p ulati o n d uri n g t he A E-e v al u ati 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 ys p ost last d osi n g date a n d da y of 
ne w a nti-ca ncer t h era p y- 1 da y.
Vari a ble: O cc urre nce of A Es. 
A nal ysis p o p ulati o n:  S afet y a nal ysis set d efi n e d as p artici pa nts w h o recei v e 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 n ci de nce of A Es defi n e d as t h e n u m ber of partici pa nts 
wit h A Es i n t h e 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 ulati o n. A Es will be s u m m arize d b y t y pe, fre q ue nc y, se verit y (as gra de d b y N CI C T C A E 
versi o n 5), ti mi n g, seri o us ness, a n d relati o ns hi p t o treat m e nt.
2. 2.  St u d y Desi g n 
T his is a n o pe n la bel, m ulti-ce nter, first-i n- h u m a 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 u ate t he safet y, t olera bilit y, P K, P D, a n d preli mi n ar 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 v a nce d or m etastatic select e d 
s oli d t u m ors ( Br Ca, O v C a a n d e n d o metri al 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 n cer t hat is resista nt or i nt olera nt t o sta n dar d t h era p y or f or w h o m n o 
sta n dar d t h era p y is a vaila ble, t o deter mi ne t he M T D a n d select t he R D E. P artici pa nts wit h 
ot her a d va n ce d or m etastatic 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 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 6 
 
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 select e d, eit her wit h or wit h o ut pri mi n g, Part 2 
d ose e x p a nsi o n c o h orts m a y be i niti ate d t o f urt her e val uate t h e s afet 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 h era p y i n a d va nce d or m etastatic 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 ns electe d H R + H E R 2- Br Ca or T N B C ( Part 2 B).
  
Part 1 D ose Escal ati o n
Partici pa nts will recei v e 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 n ci ple will be use d t o g ui d e t he d ose escalati o n pr ocess a n d 
deter mi n e t h e 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 h a 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 v ati 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 assess e d d uri n g t he first 2 8 da ys. F or m o n ot hera p y wit h 
pri mi n g, t h e D L T assess m e 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 n cl u de a p pr o xi matel y 3 partici p a nts, wit h at 
least 1 D L T e val u a ble p artici pa nt per c o h ort i n t h e first 2 c o h orts a n d at le ast 2 D L T 
e val ua ble p artici 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 pa n di n g a d diti o nal p artici 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 h e preferre d r o ute d ue t o se vere s ki n t o xicities, l o w P K 
e x p os ure or ot h er 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 h e hi g hest S C d ose l e vel t hat is d ee me d t olera bl e (e g, st arti 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 s afet y dat a.
A pri mi n g d ose a p pr oac h i n t h e ne xt d ose le vel ma y be i nitiate d if a d ose le vel i n d u
Gra de 2 C R S (lasti n g f or > 2 4 h o urs) occ urs i n > 1 parti ci pa nt des pite treat me nt wit h 
t ociliz u ma b a n d/ or vas o press ors. If t h e d ose es calati o n has reac h e 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 t he d ose re gi m e n, a pri mi n g d ose escal ati o n 
c o h ort t o mi ni mi ze C ma x ma y be i nitiate d base d o n cli nical safet y, P K/ P D, a n d cli nical 
effic ac 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 ys. T he D L T p eri 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 h e 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 h e t otal 
D L T o bser vati o n peri o d will be 4 2 da ys). A tra diti o nal 2- para m eter 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 n creas e will be 2 0 0 % ( d ose tri pli n g fr o m t he pre vi o us d ose le vel).
Part 2 D ose E x pa nsi o n  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 7 
 
T he Part 2 d ose e x p a 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 o cri n e 
treat me nt. De n o v o p aire d pre- a n d o n-treat m e nt bi o psies are ma n d at 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 parti ci 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 n e 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 h e m ot h era 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 h era p y al o ne 
if P D- L 1 ne gati v e/l o w). A p pr o xi m atel 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. D e n o v o p aire d pre- a n d o n-treat m e nt bi o psies 
are m a n d at 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 v e pr o gresse d aft er at least 1 li ne of S O C 
s yste mic t hera p y (e g, 1 L c he m ot h era 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 p ositi ve or c he m ot h era 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 m e nt bi o psies will b e 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 nic al c o m bi n ati o n i n vi v o efficac y data, e mer gi n g cli nical 
m o n ot h era p y safet y a n d effic ac 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, 
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 h era pies i n H R + H E R 2-
Br Ca a n d c o m bi nati o n wit h c hec 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 h e n recei ve st u d y i nter v e 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 d ecisi o n b y t he parti ci 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 p artici pa nt is classifie d as h a 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 m ati o n of P D b y a sec o n d s ca n i n t he a bse n ce of ra pi d cli nical 
deteri orati o n is re q uire d per ir R E CI S T. 
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 m ate 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 pect e 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 parti ci 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 h e n u m ber of d os e 
le vels t hat are re q uire d t o deter mi ne M T D/ R D E.  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 8 
 
A p pr o xi matel y 6 0 partici pa nts are e x pect e 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 e val uate safet y si g nals.
I nter ve nti o n Gr o u ps a n d D ur ati o n 
T he t otal d urati o n of t he st u d y fr o m t he be gi n ni n g of scree ni n g t o t he safet y f oll o w- u p visit is 
a p pr o xi matel y 2 years. 
S afet y Re vie w C o m mittee 
T his st u d y will use a n S R C. T he S R C will be c o m prise d of partici pati n g i n vesti gat ors or 
t heir me dicall y q ualifie d desi g nee(s) w h o ha ve at least 1 parti ci pa nt e nr olle d i n t he st u d y a n d 
t he Pfizer m e dic al m o nit or or d esi g nee. T he S R C me m bers will ha ve v oti n g ri g hts f or d ose 
escalati o n decisi o ns.  
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 m ea n, sta n d ar d d e viati o n, c oefficie nt of v ariati 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 v e nt e n d p oi nts will be s u m m arize d usi n g t he Ka pl a n- Meier m et h o d 
a n d dis pla ye d gra p hi call y w he n a p pr o priate. Me dia n e ve nt ti m es a n d 2-si d e 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 d e d b y a Ba yesia n a nal ysis of D L T d ata 
f or P F- 0 7 2 6 0 4 3 7. D os e 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 h e 
pr o ba bilit y of a p arti ci pa nt e x perie nci n g a D L T at t h e gi v e 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 n e 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 parat el 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 v ati o n peri o ds 
( 2 8 da ys f or t he re gi m e 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 h e 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 d e t he p osteri or 
pr o ba bilit y t hat t he ris k of D L T li es 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 p al ( R o gat k o et al, 2 0 0 7 ). A d ose ma y o nl y 
be use d f or n e 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 os e is less t ha n 2 5 %.
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 9 
 
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 h er rele va nt data, will be use d at t h e ti m e of eac h d os e escalati o n a n d f or 
M T D/ R D E deter mi n ati o n.
A wea kl y i nf or mati v e pri or was use d as t here wer e n o rele va nt h u ma n hist orical D L T d ata 
a vaila ble.. F or d etails, pl ease se e C 4 4 3 1 0 0 1 Tec h nical S u p ple me nt t o A p pe n di x 1 0. 9.  
F or Part 2, t he e x pa nsi o n ar ms will be c o n d ucte d t o assess effi cac y as well as safet y a n d 
t olera bilit y of P F- 0 7 2 6 0 4 3 7.
I n Part 2, t h e sec o n d ar y e n d p oi nt of o verall res p o nse b y R E CI S T versi o n 1. 1 a n d b y 
ir R E CI S T will be s u m marize d a n d liste d b y e x p a nsi o n c o h ort a n d disease t y pe. T he 
sec o n dar y e n d p oi nts of D O R ( R E CI S T versi o n 1. 1, ir R E CI S T) , P F S ( R E CI S T versi o n 1. 1, 
ir R E CI S T), T T P ( R E CI S T versi o n 1. 1, ir R E CI S T), a n d O S will be s u m marize d ( gra p hicall y 
w here a p pr o priat e) a n d liste d b y e x pa nsi o n c o h ort a n d disease t y pe.
A Es will be gra de d b y t h e i n vesti gat or acc or di n g t o t he N CI C T C A E v ersi o n 5. 0 a n d c o de d 
usi n g t h e Me d D R A.  T he n u m ber a n d perce nt a ge of partici pa nts w h o e x p erie nce d a n y A E, 
S A E, treat m e nt-relate d A E, a n d treat m e 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 o n t he e ntire st u d y peri o d. 
2. 3.  Sc he m a 
A dia gra m of t h e st u d y d esi g n is dis pla ye d i n  
Fi g ure 1 . 
 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot oc ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n
 
 
P FI Z E R C O N FI D E N TI A L 
Pa g e 1 0 
 
Fi g ure 1. 
St u d y S c he m a 
P art 1 - D os e Esc al ati o n  
Ba yesi a n desi g n B 7- H 4 x C D 3 m o n ot hera p y d os e escal ati 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 a n 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 ni cal efficac y 
* A pri mi n g d ose es calati o n ma y be i nitiate d if crit eria is m et.
D ose L e vel 1, S C, Q 2 W, 
Br Ca, O v Ca or e n d o metri al ca ncer, 
n o bi o m ar ker selecti o n
D ose L e vel 2, S C
D ose L e vel 3 + 
Part 2 B –  N ot 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 h era p y, N = 2 0, a p pr o xi matel y 5 
ma n dat or y paire d bi o psies 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 h era 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 m ar ker selecti o n, hi g h B 7- H 4, 
T N B C, 2 L +
M o n ot h era p y, N = 2 0, a p pr o xi matel y 5 
ma n dat or y paire d bi o psies
Base d o n e mer gi n g dat a, c o nsi der 
c o m bi n ati 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 h ec k p oi nt i n hi bit or i n T N B C.
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 1 1 
 
3.  
E N D P OI N T S A N D B A S E LI N E V A RI A B L E S:  D E FI NI TI O N S A N D 
C O N V E N TI O N S 
3. 1 
P RI M A R Y E N D P OI N T( S) 
Part 1 
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 d e 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 m eter l o gistic re gressi o n 
f or t h e pr o ba bilit y of a p arti ci 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 v el 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 wea kl y i nf or m ati ve pri or 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 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 h era p y d ose escal ati o n.  
D osi n g decisi o ns are g ui de d b y t he E W O C pri nci p al ( R o gat k o et al, 2 0 0 7 ). A d ose ma y o nl y 
be use d f or n e 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 os e 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 h er rele va nt data, will be use d at t h e ti m e of eac h d os e escalati o n a n d f or 
M T D/ R D E deter mi n ati o n. 
Pri or distri b uti o ns: 
Wea kl y i nf or mati v e pri or distri b uti o ns base d o n pre-cli nical/e x p ert o pi ni o n i nf or mati o n will 
be c h ose n f or t he l o gistic para meters f or pri or distri b uti o n i n Part 1.  
A M A P a p pr oac h will be use d t o deri v e t h e pri or distri b uti o n f or m o del para meters us e 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 gisti c 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 ( 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 n ces bet wee n t he 
st u dies.  
St arti n g d ose: 
satisfies t he E W O C criteri o n.  
St o p pi n g criteri a: 
T he s p o ns or esti mates t h at t he ma xi m u m n u m b er 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 p a nts. H o w e ver, t he act ual n u m b er ma y b e m ore or less bas e d 
o n o bser ve d P K a n d s afet y. T he d ose es calati o n will st o p w he n t h e f oll o wi n g criteria are met:
 At least 6 parti ci pa nts ha ve bee n tr eate d at t h e rec o m m e 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 h e f oll o wi n g c o n diti o ns f or t h e m o n o- 
escalati o n part: 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 1 2 
 
 
 
 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 n ci 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, defi ne d as t h e ti m e fr o m t he first d ose t o earliest of  2 8 da ys p ost last d osi n g date a n d 
da y of ne w a nti-ca n cer t h era p y- 1 d a 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 n al ysis set defi ne d as parti ci pa nts w h o recei ve at least 
1 d ose of st u d y treat m e nt wit h o ut re gar d t o t olera bilit y or d urati o n of treat m e nt. 
 P o p ul ati o n-le vel s u m m ar y me as ure:  I nci d e 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 v al 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 ulati o n. A Es will be s u m marize d b y t y pe, fre q ue nc y, 
se verit y (as gra de d b y N CI C T C A E versi o n 5), ti mi n g, seri o us ness, a n d relati o ns hi p 
t o treat m e nt. 
3. 2 
Sec o n d ar y E n d p oi nt(s) 
Part 1 a n d Part 2
ir A Es 
ir A Es as c haract eriz e d b y t y pe, fre q u e nc y, se v erit y (as gra d e 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. 
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 a r m ac o ki netic A n al ysis 
Ser u m c o nce ntr ati 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 n al ti m e.  
I n di vi d ual partici pa nt ser u m c o nce ntrati o n-ti m e d ata wit hi n a d ose i nter val after C ycle 1 
Da y 1 a n d C y cle 2 Da y 1 will be a nal yze d usi n g n o nc o m part m e 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 m ate d will i n cl u de t he ser u m C ma x , Tma x a n d A U C last, 
a n d as data p er 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 n ce ( 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 Vss f or I V 
d osi n g).
M ulti ple d ose P K para meters t o be esti m ate d will i ncl u de C
ma x,ss , Tma x,ss , A U C
, 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 d ata per mit, v ol u me ( V z/ F f or S C or Vss f or 
I V), t½ , a n d Rac ( A U C
/ A U C
). T he si n gle d ose a n d stea d y-state P K para meters will be 
s u m marize d descri pti vel y ( n, mea n, sta n d ar d d e vi ati o n, c oeffi cie nt of variati o n, me dia n, 
mi ni m u m, ma xi m u m, ge o m etric mea n, a n d its ass ociate d c o efficie nt of variati o n) b y d ose 
le vel a n d c y cle.
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


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Pa g e 1 3 
 
D ose n or malize d A U C i nf ( A U C at stea d y state) a n d C ma x will b e pl otte d a gai nst d ose ( usi n g 
a l o garit h mic scale) b y c y cle. T hese pl ots will i ncl u de i n di vi d ual partici pa nt val ues a n d t h e 
ge o metric m ea 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 g e of p artici 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 (tit er), ti m e 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 b e d, if data per mit. 
Part 2 
Effic ac y A n al ysis
Res p o nse E val ua ble Set will b e use d f or all res p o nse-relat e d a nal ys 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, ir 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 ysis Set as well as o n t h e 
mI T T. 
Data will be s u m mariz e d (als o gra p hic all 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. 
 
3. 3 
Terti a r 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 b e use d f or O R R a n d P F S ( R E CI S T, ir R E CI S T). T u m or 
res p o nse will be prese nte d i n t h e f or m of partici p a 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.  
Data will be s u m mariz e d (als o gra p hic all 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 a r 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 b e 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 dat a a nal yses m a y n ot b e 
c o m plete at t he ti m e 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 nal yses ca n n ot 
be i ncl u de d i n t he C S R, t h e y will be disse mi n ate d t o t h e scie ntific 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.
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 1 4 
 
3. 4 
B aseli n e V ari a bl es
Baseli ne c haracteristi cs will be c ollect e d acc or di n g t o Sc he d ule of Acti vities  as s p ecifie d i n 
t he pr ot oc ol.  F or t h e pri mar y a nal yses, n o b aseli n e varia bl e will be use d f or stratificati o n or 
as c o v ari ates i n t he statisti cal a nal ysis.  U nless ot h er wise s pecifie d, t he b aseli ne val ue is 
defi ne d as t he v al ue c ollecte d at t he ti m e cl osest t o, b ut pri or t o, starti n g t he st u d y 
i nter ve nti o n a d mi nistrati o n i n t he first c ycle.  
La b orat or y b aseli ne will be t he last pre d ose m eas ure me nt ta ke n b ef ore t he first d ose of a n y 
c o m p o ne nt of t h e st u d y i nter ve nti o n.
3. 5 
S afet y E n d p oi nts 
T he o n-treat me nt peri o d will be use d f or all safet y assess me nts. T he o n-treat me nt peri o d is 
defi ne d as t he p eri o d t hat starts wit h t he first d ose of st u d y treat m e nt a n d e n ds at mi ni m u m 
(last d ose of st u d y treat m e nt + 3 0 da ys, start of n e w a nti-ca n cer t h era p y - 1 da y). 
3. 5. 1 
A d verse E v e nts 
A Es will be gra de d b y t h e i n vesti gat or acc or di n g t o t he 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 ort e 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 s eri o us ness a n d relati o ns hi p t o st u d y treat me nt will be 
prese nte d, as well as s u m maries of A 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 m e nt. T he n u m b er a n d perce nt a ge of p artici pa nts w h o e x p erie n ce 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 y cle 
( C ycle 1 a n d C y cles b e y o n d 1). W he n a pri mi n g d ose is use d, t h e f ull 4 2 da y peri o d will be 
re p orte d se p aratel y, i nstea d of C y cle 1. Listi n gs of D L Ts a n d deat hs will be pr o vi de d. 
A si mil ar a p pr oac h will be use d f or ir A Es.  
3. 5. 2 
L a b or at or y D at a 
Details of t he la b orat or y tests ca n be f o u n d i n A p p e n di x 1 0. 2 of t h e pr ot oc ol . 
 
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S) 
Data f or all parti ci pa nts will be assesse d t o deter mi n e if partici pa nts meet t h e criteria f or 
i ncl usi o n i n eac h a nal ysis p o p ulati o n pri or t o u n bli n di n g a n d releasi n g t he data base a n d 
classificati o ns will be d o c u me nt e d per st a n d ar d o perati n g pr oce d ures.
T a bl e 1. 
A n al ysis S ets 
P artici p a nt A n al ysis Set
Descri pti o n  
F ull A nal ysis Set ( F A S) 
All e nr olle d parti ci pa nts. 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
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P artici p a nt A n al ysis Set
Descri pti o n
Safet y A nal ysis Set ( S A S)
All e nr olle d parti ci 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 pecifi e d t h e safet y a nal ysis set 
will b e t h e defa ult a nal ysis set use d f or all a nal ys es.
Per Pr ot oc ol A nal ysis Set
All e nr olle d parti ci pa nts w h o d o n ot ha ve m aj or pr ot oc ol 
de viati o ns d uri n g t h e c o urse of t h e st u d y
D L T E val ua ble Set
All e nr olle d parti ci 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 vi ati o ns d uri n g t h e D L T o bser vati o n peri o d a n d 
recei v e d eit her 1 0 0 % of d osi n g i n c ycle 1 ( n o pri mi n g re gi m e n) 
or 1 0 0 % of d osi n g i n c ycle 1 a n d c ycl e 2 ( pri mi n g re gi me n).. 
mI T T P o p ulati o n 
All e nr olle d parti ci pa nts w h o ha ve recei v e d at least 1 d ose of 
st u d y me dicati o n; ha ve a baseli ne assess m e nt a n d at least 1 p ost 
baseli n e assess me nt;  
Res p o nse E val ua ble set 
T he res p o nse e val ua bl e p o p ulati o n will i ncl u de all partici pa nts 
w h o recei ve d at least o ne d ose of st u d y treat m e nt a n d ha d 
meas ura ble disease at baseli ne a n d at least o n e p ost baseli ne 
disease assess me nt. 
P K Para meter Set 
All e nr olle d parti ci pa nts treate d w h o d o n ot ha v e pr ot oc ol 
de viati o ns i nfl ue nci n g P K assess m e nt a n d ha v e s uffi cie nt 
i nf or mati o n t o esti mate at least 1 of t h e P K para m eters of 
i nterest. 
P K C o nce ntrati o n Set
All e nr olle d parti ci pa nts w h o are tr eate d a n d ha v e at least 1 
a nal yte c o n ce ntrati o n a b o ve t he l o wer li mit of q u a ntitati o n. 
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S
5. 1 
H y p ot heses a n d Decisi o n R ules 
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. 
5. 2 
Ge ner al Met h o ds
T he data are s u m m ariz e d b y d ose le vel c o h ort, d efi ne d b y t he i nitial d ose of t h e st u d y 
i nter ve nti o n a d mi nistere d t o partici pa nts. D L T rates at t he st u d y d ose le vels will be 
prese nte d via m ea n a n d me dia ns a n d a Ba y esia n cre di ble i nter v al base d o n t he p osteri or 
de nsit y fr o m t he f ull pr o ba bilit y m o del. T his i nf or mati o n will als o be use d f or t he d ose 
escalati o n decisi o n meeti n gs. U nless ot her wise s p ecifie d, all ot h er s u m maries will be 
prese nte d b y d os e le vel c o h ort a n d o verall. A d diti o nall y, s u m mar y ta bles will i ncl u de t he 
t otal sa m ple size a n d n u m b er missi n g/ n ot re p orte d. Lastl y, missi n g data ma y be i m p ute d 
acc or di n g t o secti o n 0 a n d u nless ot her wis e s p ecifie d missi n g val ues t hat are n ot i m p ute d will 
be e xcl u de d fr o m t he a n al ysis. 
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5. 2. 1 A n al yses f or Bi n a r y E n d p oi nts 
Bi n ar y data will be s u m marize d usi n g n u m ber of u ni q ue p atie nt i nci de nce, a n d c o nfi de n ce 
i nter val f or bi n o mial pr o p orti o ns will be prese nte d if warra nte d usi n g Cl o p per- Pears o n e xact 
met h o d.
Bi n ar y e n d p oi nts i n t his st u d y i ncl u de c o m plete res p o nse ( C R), partial res p o nse ( P R), sta ble 
disease ( S D), pr o gressi ve disease ( P D), dis ease c o ntr ol rate ( D C R) , o bjecti ve res p o nse rate
( O R R) base d o n R E CI S T v 1. 1, a n d ir C R, ir P R, ir S D, ir P D a n d ir D C R base d o n ir R E CI S T.
Descri pti ve statistics al o n g wit h t he c orres p o n di n g 2-si d e d 9 5 % c o nfi d e nce i nter vals ( CI)
usi n g Cl o p per- Pears o n e xact met h o d will b e pr o vi de d f or t hese e n d p oi nts if t he s a m ple size 
per c o h ort p er mits. 
5. 2. 2 A n al yses f or C o nti n u o us E n d p oi nts
C o nti n u o us data will be s u m marize d wit h t he mea n, me dia n, mi ni m u m, ma xi m u m,
c oeffi cie nt of v ariati o n, sta n dar d de viati o n, a n d 2-si de d 9 5 % c o nfi de n ce i nt er vals if t he 
sa m ple size per mits.   
5. 2. 3 A n al yses f or C ate g o ric al E n d p oi nts 
Cate g orical data will be s u m marize d b y n u m ber of u ni q ue patie nt i nci de nce.   
5. 2. 4 A n al yses f or Ti me-t o- E ve nt E n d p oi nts
T he ti me-t o-e v e nt d ata will be prese nte d f or i n di vi d ual p atie nt, b y d ose l e vel c o h ort, a n d 
o verall w he n a p plica ble. Ti me-t o-e ve nt e n d p oi nts will b e s u m m arize d usi n g t he Ka pla n-
Meier met h o d a n d esti m ate d s ur vi val c ur v es will be dis pla ye d gra p hi call y w he n a p pr o priate.  
Gra p hs will descri b e t he n u m b er of partici p a nts at ris k o ver ti me.  T he me dia n, q uartiles, a n d 
pr o ba bilities of a n e ve nt at partic ul ar p oi nts i n ti me will be esti m ate d b y t he Ka pla n- Meier 
met h o d, w he n p ossi ble base d o n t he n u m ber of o bser ve d e v e nts.  C o nfi de n ce i nter vals f or 
me dia ns a n d q uartil es are base d o n t he Br o o k me yer- Cr o wle y m et h o d.  C o nfi de nce i nter v als 
f or t h e esti mate d pr o b a bilit y of a n e ve nt at a p artic ular ti me p oi nt will b e ge nerate d usi n g t he 
Gree n w o o d f or m ula.  
5. 3 
Met h o ds t o M a n a ge Missi n g D at a 
F or t he a nal ysis of safet y e n d p oi nts, t h e s p o ns or data sta n dar d r ules f or i m p utati o n will be 
a p plie d. See Cli nical D ata I nterc ha n ge Sta n d ar ds C o ns orti u m ( C DI S C) a n d Pfizer data 
sta n dar d ( P D S) Safet y R ule b o o ks f or details. 
5. 3. 1 
Missi n g D ates 
I n c o m plia nce wit h Pfizer sta n dar ds, if t he d a y of t he m o nt h is missi n g f or a n y date use d i n a 
calc ulati o n, t he 1st of t he m o nt h will be use d t o re place t h e missi n g date u nless t he 
calc ulati o n res ults i n a ne gati ve ti me d urati o n (e g, d ate of o nset ca n n ot be pri or t o da y o ne 
date).  I n t his case, t he date res ulti n g i n 0 ti me d urati o n will be use d.  Pfizer sta n dar ds are 
als o use d if b ot h m o nt h a n d da y are missi n g (Ja n 1 u nless ne gati ve ti m e d urati o n).  T his 
e xcl u des t he p har mac o ki netic a n d E C G a nal yses, w hic h will o nl y use t he act ual date 
c ollecte d or if d ate n ot a v aila ble d ee m t h e d ata missi n g. 
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5. 3. 2 
Effic ac y A n al ysis
N o i m p utati o n will be perf or me d f or t u m or assess m e nts t hat will be use d f or t h e bi n ar y 
effic ac y e n d p oi nts. E ver y eff ort will be ma d e t o retrie ve data i n t h e C R F, h o we ver 
missi n g data will be left as is. T he reas o ns f or missi n g t u m or assess m e nts will be 
c ollecte d.
F or t he ti me-t o-e ve nt e n d p oi nts, t he missi n g data ha n dli n g met h o d will be ce ns ori n g.  
5. 3. 3 
P h a r m ac o ki netics  
5. 3. 3. 1 C o nce ntr ati o ns Bel o w t he Li mit of Q u a ntific ati o n 
I n all data prese ntati o ns (e xce pt listi n gs), c o nce ntrati o ns bel o w t he li mit of q ua ntificati o n 
will b e re place d wit h t he val ue f or t h e l o w er li mit of q ua ntificati o n.) 
5. 3. 3. 2 De vi ati o ns, Missi n g C o nce ntr ati o ns a n d A n o m al o us V al ues 
I n s u m m ar y ta bles a n d pl ots of m e dia n pr ofiles, st atistics will be cal c ulate d ha vi n g set 
c o nce ntr ati o ns t o missi n g if 1 of t h e f oll o wi n g cas es is tr ue: 
1.  A c o n ce ntr ati o n has bee n c ollecte d as N D (i.e., n ot d o ne) or N S (i.e., n o s a m ple), 
2.  A de vi ati o n i n sa m pli n g ti m e is of s ufficie nt c o ncer n or a c o n ce ntr ati o n has bee n 
fla g ge d a n o mal o us b y t h e p har mac o ki neticist. 
N ote t hat s u m mar y statistics will n ot be prese nt e d at a partic ular ti me p oi nt if m ore t ha n 
5 0 % of t he data are missi n g. 
A n a n o mal o us c o nce ntrati o n val ue is o ne t hat, after verificati o n of bi oa nal ytical vali dit y, 
is gr ossl y i nc o nsiste nt wit h ot her c o nce ntrati o n data fr o m t he s a me i n di vi d ual or fr o m 
ot her partici pa nts. F or e xa m ple, a B L Q c o nce ntrati o n t hat is bet w ee n q ua ntifia ble val u es 
fr o m t he sa me d os e is c o nsi dere d as a n o mal o us.
A n o mal o us c o nce ntr ati o n val ues ma y 
be e xcl u de d fr o m P K a nal ysis at t he discreti o n of t he P K a nal yst. 
 
5. 3. 4 
P h a r m ac o ki netic P ar a meters
Act u al P K sa m pli n g ti m es will be use d i n t h e deri vati o n of P K para meters. 
If a P K para meter ca n n ot be deri ve d fr o m a s u bje ct’s c o nce ntrati o n data, t h e para meter will 
be c o de d as N C (i.e., n ot calc ulate d). ( N ote t hat N C val ues will n ot be ge nerate d be y o n d t he 
da y t hat a s u bject dis c o nti n ues.) 
I n s u m m ar y ta bles, statistics will be calc ulate d b y setti n g N C val u es t o missi n g; a n d statisti cs 
 
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If a n i n di vi d ual s u bject h as a k n o w n biase d esti mate of a P K para meter ( d u e f or e x a m ple t o 
d osi n g err or), t his will be f o ot n ote d i n s u m mar y ta bles a n d will n ot be i n cl u de d i n t he 
calc ulati o n of s u m mar y statistics or statistical a nal yses. 
5. 3. 5 
P h a r m ac o d y n a mic P ar a meters
Missi n g data f or t he p h ar mac o d y na mic para meters will be treate d as s uc h a n d n o i m p ute d
val ues will be deri ve d.
5. 3. 6 
Q T c 
F or t he c orre cte d Q T ( Q Tc) a n al yses, n o val ues will be i m p ute d f or missi n g data. 
5. 4 
St atistic al C o nsi der ati o ns of C O VI D- 1 9 I m p acte d D at a 
I n M arc h 2 0 2 0, t h e W orl d Healt h Or ga nizati o n ( W H O) a n n o u nce d a gl o b al pa n de mic of t h e 
vir us S A R S- C o V- 2 a n d t h e res ulti n g disease C O VI D- 1 9. D uri n g t he c o n d u ct of t his trial, if 
a n y parti ci pa nt’s d ata is i m pacte d b y t his pa n de mi c, t he f oll o wi n g c o nsi derati o ns will be 
gi ve n i n t he data a n al yses: 
a) If a partici pa nt dr o p pe d o ut of t he st u d y d uri n g t he D L T e val uati o n wi n d o w i n 
Part 1 d ue t o C O VI D- 1 9, a re place me nt partici pa nt ma y be a d de d. 
b)
Deat h ca use d b y C O VI D-
P F S a n d O S. If dee m e d n ecessar y, a se nsiti vit y a nal ysis m a y be perf or me d w here 
C O VI D- 1 9 dri ve n d eat h is ce ns ore d at t h e d eat h d ate.  
c) If a sc h e d ule d t u m or ra di o gra p hic s ca n is dela ye d o ut of t he Sc he d ule of A cti vit y  
all o wa ble wi n d o w, or is missi n g (i.e. parti ci pa nt s ki p pe d a sc he d ule d t u m or 
ra di o gra p hic s ca n) d u e t o a n y reas o ns relate d t o t h e pa n d e mic, t his dela y or 
missi n g ness d oes n ot alter t he ce ns ori n g r ules f or P F S or T T P as descri be d i n 
A p pe n di x 1 . A ce ns ori n g reas o n of “ C O VI D-
s u m mar y if t he s pecific reas o n of t u m or sca n dela y or missi n g ca n be attri b ute d t o 
C O VI D- 1 9. If dee m e d necessar y, a se nsiti vit y a nal ysis ma y b e perf or me d w here 
partici pa nts w o ul d be c e ns ore d at t h e dat e of t h eir last sca n pri or t o t heir C O VI D-
1 9 dia g n osis.  
I n t he c o nfir me d O R R a nal ysis, if a res p o nse ca n’t be c o nfir me d b y a s u bse q ue nt 
t u m or sca n beca use of t h e pa n de mic (i. e., t he s u bs e q ue nt t u m or sca n w as n’t 
perf or me d), t he n t he i nitial res p o nse will be c o nsi dere d as u n c o nfir me d. N o 
se nsiti vit y a nal ysis will be p erf or me d.  
d)  A n y C O VI D- 1 9 relate d s y m pt o ms are t o be ca pt ure d as a d verse e v e nts i n t h e case 
re p ort f or m. T h os e a d verse e ve nts will be s u m marize d i n t he sa me ma n n er as 
ot her a d verse e ve nts. If a la bel of C O VI D- 1 9 ca n be i de ntifie d i n t he i n vesti gat or 
pr o vi de d a d verse e ve nt ter m, t he n a se p arat e A E listi n g ma y be pr o vi d e d f or j ust 
t he C O VI D- 1 9 relate d e v e nts. 
e) If i d e ntifia ble, t he C O VI D- 1 9 relat e d data p oi nts, i n cl u di n g missi n g data w here 
t he reas o n of missi n g is i de ntifie d as C O VI D- 1 9 relate d (sit e cl os ure he n ce data 
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c o ul d n ot ca pt ure d; parti ci pa nts s ki p pe d a visit beca use of c o n cer n o ver t he 
pa n de mic), pr ot o c ol de vi ati o ns dri ve n b y C O VI D- 1 9, safet y e v e nts ca use d b y 
C O VI D- 1 9 ma y b e se paratel y liste d. 
6. A N A L Y S E S A N D S U M M A RI E S
6. 1 
Pri m ar y E n d p oi nt(s) 
6. 1. 1  
D L Ts ( Part 1) 
Dete
M T D) as des cri be d a b o v e i n Secti o n 3 .  
6. 1. 2 
A d verse E v e nts ( Part 1 a n d Part 2)
 A nal ysis set: Safet y a nal ysis set.    
 A nal ysis met h o d ol o g y:  
A Es will be c haract erize d b y t y pe, fre q u e nc y, se v erit y (as gra de d b y N CI C T C A E 
versi o n 5. 0, e xce pt C R S, w hic h will be gra de d b y A S T C T criteria ( L ee et al., 
2 0 1 9)) 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. F urt h er d escri pti o n 
is gi v e n i n Secti o n 0. T he pri mar y f oc us will be o n T E A Es. T E A Es is defi n e d as 
a n y A E t h at occ urs d uri n g t h e o n-treat me nt p eri o d. A Es t hat occ ur after t h e o n-
treat me nt peri o d ma y still be rec or de d i n t he cli nical data base a n d will be 
i ncl u de d i n t he A E listi n gs, b ut will n ot be i ncl u de d i n t he o n-treat me nt e mer ge nt 
A E s u m maries.
See Secti o n 0 f or det ails o n t he s pecific A E s u m m aries t o be pr o vi de d.
 Missi n g data: If a n A E st art or st o p date is missi n g, i m p utati o n will be perf or me d. 
T he i m p ute d dates will be use d t o deter mi n e w het her t h e A E is t o be i ncl u d e d i n 
t he T E A E s u m mar y. T he missi n g A E start or st o p dates will be list e d as is i n A E 
listi n gs. W he n t he C T C A E gra de is missi n g f or a n A E, t he A E will be e x cl u de d 
fr o m t he C T C A E gra d e s u m m ar y ta ble.  
6. 1. 3 
L a b or at or y a b n o r m alities ( Part 1 a n d Part 2) 
 A nal ysis met h o d ol o g y:  
La b orat or y a b n or maliti es will be prese nte d as ta bles a n d 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 ersi o n 5. 0), a n d ti mi n g. 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 hi g h/l o w, or n ot d o ne. T he n u m ber a n d perce nta ge of 
partici pa nts w h o e x p erie 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 ass a y. S hift ta bles 
of baseli n e gra de t o w orst p ost- baseli ne gra de will be pr o vi de d. Q ua ntitati ve 
s u m maries f or c h a n ge fr o m baseli ne a n d perce nt c ha n ge fr o m baseli ne f or t he 
la b orat or y tests ma y be pr o vi de d, if d ee m e d necess ar y. T hese s u m maries will be 
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prese nte d f or t h e e ntire o n-treat m e nt p eri o d a n d f or t he vari o us s u b gr o u ps of t he 
st u d y ( b y d ose le vel f or Part 1 a n d b y e x pa nsi o n c o h ort f or Part 2).  
He mat ol o g y, ser ol o g y a n d c oa g ulati o n la b res ults ca n be c o m bi ne d i nt o o ne 
s u m mar y o ut p ut. Se parat e s u m maries will be create d f or c h e mistr y tests. 
Uri nal ysis a n d pre g n a nc y tests will n ot be s u m marize d a n d will o nl y be liste d.  
 Missi n g data: Missi n g la b val ues will n ot be i m p ute d. 
6. 2 
Sec o n d ar y E n d p oi nts
Part 1 a n d Part 2
6. 2. 1
ir A Es
A nal ysis met h o d ol o g y: 
ir A Es will be c haracterize d b y t y pe, fre q ue nc y, s e verit y (as gra de d b y N CI 
C T C A E versi o n 5. 0, e xce pt C R S, w hic h will be gra de d b y A S T C T criteria ( Lee et 
al., 2 0 1 9)) ti mi n g, seri o us ness, a n d relati o ns hi p t o st u d y t h era p y. F urt her 
descri pti o n is gi ve n i n Secti o n 0. ir A Es t hat occ ur after t he o n-treat me nt peri o d 
ma y still be rec or de d i n t he cli nical data b ase a n d will be i ncl u de d i n t he ir A E 
listi n gs, b ut will n ot be i ncl u de d i n t he o n-treat m e nt e mer ge nt A E s u m mari es.
 Missi n g data: If a n ir A E start or st o p date is missi n g, i m p utati o n will be 
perf or me d. T he i m p ute d dates will be use d t o deter mi n e w het her t h e ir A E is t o be 
i ncl u de d i n t he ir T E A E s u m mar y. T he missi n g ir A E st art or st o p dates will be 
liste d as is i n ir A E listi n gs. W he n t he C T C A E gra de is missi n g f or a n ir A E, t h e 
ir A E will be e xcl u de d fr o m t h e C T C A E gra de s u m mar y ta ble.  
6. 2. 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 
 A nal ysis set: P K a nal ysis set
Ser u m c o nce ntr ati o ns of P F- 0 7 2 6 0 4 3 7 will be s u m marize d des cri 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 n al ti m e.  
I n di vi d ual partici pa nt ser u m c o nce ntrati o n-ti m e d ata wit hi n a d ose i nter val after C ycle 1 
Da y 1 a n d C y cle 2 Da y 1 will be a nal yze d usi n g n o nc o m part m e 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 m ate d will i n cl u de t he ser u m C ma x , Tma x a n d A U C last, 
a n d as data p er 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 n ce ( 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 Vss f or I V 
d osi n g).
M ulti ple d ose P K para meters t o be esti m ate d will i ncl u de C
ma x,ss , Tma x,ss , A U C
, 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 d ata per mit, v ol u me ( V z/ F f or S C or Vss f or 
I V), t½ , a n d Rac ( A U C
/ A U C
). T he si n gle d ose a n d stea d y-state P K para meters will be 
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s u m marize d descri pti vel y ( n, mea n, sta n d ar d d e vi ati o n, c oeffi cie nt of variati o n, me dia n, 
mi ni m u m, ma xi m u m, ge o m etric mea n, a n d its ass ociate d c o efficie nt of variati o n) b y d ose 
le vel a n d c y cle.
D ose n or malize d A U C i nf ( A U C at stea d y state) a n d C ma x will b e pl otte d a gai nst d ose ( usi n g 
a l o garit h mic scale) b y c y cle. T hese pl ots will i ncl u de i n di vi d ual partici pa nt val ues a n d t h e 
ge o metric m ea ns f or eac h d ose.  
6. 2. 3 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 g e of p artici 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 (tit er), ti m e 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 b e d, if data per mit. 
Part 2
6. 2. 4 Effic ac y A n al ysis 
Res p o nse E val ua ble Set will b e use d f or all res p o nse-relat e d a nal ys 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, ir 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. I m m u ne relat e d res p o nse b y ir R E CI S T will be calc ul ate d a n d 
re p orte d si mil arl y t o R E CI S T res p o ns e. O S will be re p orte d o n t he F ull A nal ysis Set as well 
as o n t he mI T T. 
Data will be s u m mariz e d (als o gra p hic all 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.  
 O ver all Res p o nse R ate ( O R R )   
 O verall res p o nse r ate ( O R R) is defi ne d as t he pr o p orti o n of patie nts wit h a B O R 
of c o nfir me d C R or c o nfir me d P R b y I n v esti gat or assess me nt i n i ntracra nial 
metastasis a n d e xtracra ni al lesi o ns per m R E CI S T v 1. 1 ( or R A N O f or 
gli o blast o mas) a n d R E CI S T v 1. 1, res pecti vel y. 
  
 D ur ati o n of Res p o nse ( D O R) 
 D urati o n of res p o ns e is defi n e d as t he ti me fr o m start date ( w hic h is t he date of 
first d oc u me nt ati o n of P R or C R) t o date of first d oc u me ntati o n of o bjecti ve 
pr o gressi o n or deat h.  B ot h c o nfir me d D O R a n d u n c o nfir me d D O R ( u D O R) will 
be deter mi ne d a n d re p orte d s e paratel y f or t h e s u bset of p arti ci pa nts wit h a 
c o nfir me d a n d u n c o nfir m e d o bjecti v e res p o nse of C R or P R ( defi ne d bel o w). 
D O R will be deri ve d f or I ntracra ni al/ R A N O res p o nse rate, e xtracra nial res p o nse 
rate a n d O R R. 
 Best O ver all Res p o nse ( B O R) 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 2 2 
 
 C o m plete R es p o nse ( C R) :  T w o o bjecti v e st at us es of C R a mi ni m u m of 4 wee ks 
a part d oc u me nt e d bef ore P D.
 P arti al Res p o nse ( P R) :  T w o o bjecti ve stat uses of P R or better ( P R f oll o we d b y 
P R or P R f oll o we d b y C R) a mi ni m u m of 4 wee ks a part d oc u me nt e d bef ore P D, 
b ut n ot q ualif yi n g as C R.  Se q ue nces of P R- Sta bl e- P R are c o nsi d ere d P Rs as 
l o n g as t he t w o P R res p o nses are o bs er ve d at a mi ni m u m of 4 wee ks a part. 
 St a bl e Dise ase ( S D) (a p pli ca ble o nl y t o patie nts wit h meas ura ble dis ease at 
baseli n e):  At least o ne o bjecti v e stat us of sta ble disease or b etter d oc u me nt e d at 
least 6 wee ks after start of treat m e nt a n d b ef ore P D b ut n ot q ualif yi n g as C R or 
P R.   
 N o n- C R/ n o n- P D  (a p plica ble o nl y t o patie nts wit h n o n- meas ura ble disease at 
baseli n e): at least o n e n o n- C R/ n o n- P D assess me nt ( or better) d o c u me nte d at least 
5 wee ks after start of treat me nt a n d bef ore first d o c u me ntati o n of P D (a n d n ot 
q ualif yi n g f or C R or P R).   
 Pr o gressi v e Dise ase ( P D):   Pr o gressi o n d oc u m e nte d wit hi n 1 2 wee ks aft er ‘start 
date’ a n d n ot q ualif yi n g as C R, P R or S D.   
 N ot E v al u a bl e ( N E):   All ot h er cases.  N ote t hat reas o ns f or N E s h o ul d be 
s u m marize d a n d t h e f oll o wi n g reas o ns c o ul d b e use d:  
 N o a de q uate baseli n e assess me nt  
 N o e vi de nce of disease at baseli ne 
 N o p ost- baseli ne ass ess me nts d ue t o earl y d eat h, i. e., deat h pri or t o 6 w ee ks 
after ‘st art date’.  
 N o p ost- baseli ne ass ess me nts d ue t o ot her reas o ns 
 All p ost- baseli ne assess m e nts ha ve o verall res p o nse N E 
 Ne w a nti-ca ncer t h era p y starte d bef ore first p ost- baseli ne assess me nt 
 
rt date’ wit h o ut f urt her 
e val ua ble t u m or ass ess m e nts) 
 P D t o o late ( > 1 2 wee ks after st art of tr eat m e nt) 
 S pecial a n d rare cases w h ere B O R is N E d ue t o b ot h S D of i ns ufficie nt 
d urati o n (‘t o o earl y’) a n d late P D will be classifie d as ‘ S D of i ns ufficie nt 
d urati o n. 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


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Pa g e 2 3 
 
 U nc o nfir me d C R ( u C R) is defi n e d as o n e o bjecti v e stat us of C R d oc u me nte d 
bef ore P D.  
 U nc o nfir me d P R ( u P R) is defi ne d as o n e o bjecti v e stat us of P R d oc u me nte d 
bef ore P D b ut n ot q ualif yi n g as u C R. 
N ote: A n o bjecti ve stat us of P R, S D, or N o n- C R/ N o n- P D ca n n ot f oll o w o ne of C R.  
S D ca n f oll o w P R o nl y i n t he rare cas e t hat t u m or 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 fr o m bas eli n e n o 
l o n ger h ol ds.  If t his occ urs t he se q ue nce P R –  S D –  P R is c o nsi dere d a c o nfir me d 
P R.  A se q ue nce of P R –  S D –  S D –  P D w o ul d be a best res p o nse of S D if t he 
wi n d o w f or S D defi niti o n has bee n met. 
s u m marize d b y reas o n f or ha vi n g u n k n o w n stat us. T he f oll o wi n g reas o ns will b e use d:
 
N o a de q uate baseli n e assess me nt. 
 
N o p ost- baseli ne ass ess me nts d ue t o earl y d eat h . 
 
N o p ost- baseli ne ass ess me nts d ue t o C O VI D- 1 9 (ie, patie nts miss t u m or 
assess me nt visits d ue t o C O VI D- 1 9 pa n d e mic). 
 
N o p ost- baseli ne ass ess me nts d ue t o ot her reas o ns. 
 
All p ost- baseli ne assess m e nts ha ve o verall res p o nse N E. 
 
Ne w a ntica ncer t h era p y starte d bef ore first p ost- b aseli ne assess me nt.
 
 
e val ua ble t u m or ass ess m e nts).
 
P D > 1 2 wee ks after d ate of t he first d ose (ie, t u m or assess me nt of P D was > 1 2 
wee ks after dat e of t h e first d ose a n d t here was n o t u m or ass ess me nt i n bet wee n).
S pecial a n d rare cases w h ere B O R
wee ks after dat e of t h e first d ose) a n d late P D ( P D > 1 2 wee ks after date of t he first d ose) will 
 T u m or res p o nse will be prese nte d i n t he f or m of p artici pa nts data listi n gs t hat i ncl u de, b ut 
are n ot li mit e d t o: t u m or t y pe, act ual recei v e d da y 1 d ose, t u m or res p o nse at eac h 
assess me nt, a n d best o verall res p o nse.  Pr o gressi o n date, deat h d ate, date of first res p o nse, 
last assess me nt date, a n d date of last c o nta ct will als o be liste d. A d diti o nall y, a gra p hical 
re pres e ntati o n (s wi m mer pl ot) will be pr o vi d e d t o dis pla y t u m or res p o nse o verti m e a n d a 
waterfall pl ot dis pla yi n g t he best perce nta ge c ha n ge i n t u m or size will be pr o vi de d. 
 Missi n g data: Data after t h e st u d y i nter ve nti o n is dis c o nti n ue d a n d resc u e will b e 
e xcl u de d; i nter me diate missi n g val ues (ie, val ues c ollecte d bet wee n baseli n e a n d t h e last 
st u d y meas ure me nt) will n ot be i m p ute d. 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 2 4 
 
Pr o gressi o n-free S u r vi v al ( P F S)
 
A nal ysis set: Res p o nse E val ua ble 
Pr o gressi o n-free s ur vi val ( P F S) is defi ne d as t h e ti m e fr o m date of t h e first d ose of st u d y 
treat me nt t o t he earliest d oc u me nte d disease pr o gressi o n b y I n v esti gat or assess me nt, or deat h 
d ue t o a n y ca us e, w hic he ver occ urs first. If a patie nt has n ot ha d a P F S e ve nt at t h e ti m e of
t he a nal ysis c ut off or at t he start of a n y n e w a ntic a ncer t h era p y, P F S is ce ns ore d at t h e dat e of
last a de q u ate t u m or assess me nt. 
P F S will be calc ulate d as f oll o ws: 
P F S ( m o nt hs) = ( date of e ve nt or ce ns ori n g – date of first d ose + 1)/ 3 0. 4 3 7 5
T he ce ns ori n g a n d e ve nt d ate o pti o ns t o be c o nsi dere d f or P F S a nal ysis are prese nte d i n 
Ta ble 2.
P F S ti me will be esti mate d usi n g t he Ka pla n- M eier m et h o d. T he P F S rate at 3, 6, 9, 1 2, 1 5 
a n d 1 8 m o nt hs will be esti m ate d wit h c orres p o n di n g 2-si d e d 9 5 % CIs. 
Fre q u e nc y ( n u m b er a n d perce nt a ge) of partici pa nts wit h eac h e ve nt t y pe ( P D or deat h) a n d
ce ns ori n g reas o ns will be prese nt e d al o n g wit h t h e o verall e ve nt a n d ce ns or rates. Reas o ns
f or ce ns ori n g will be s u m m arize d acc or di n g t o t h e cate g ories i n T a ble 3 . I n a d diti o n, ti me t o 
pr o gressi o n/ce ns ori n g, e v e nt, a n d ce ns ori n g reas o ns will be liste d. 
T a bl e 2  
P F S a n d D O R O utc o me a n d E ve nt D ates 
 
Sit u ati o n
D ate of 
Pr o gressi o n/ Ce ns ori n g  
O utc o m e
N o a de q uate baseli n e assess me nt
a 
Date of first d os e a
Ce ns ore d a
P D or deat h
- after at m ost o ne missi n g or 
i na de q uate p ost bas eli n e t u m or 
assess me nt, or
-
- da y wi n d o w) after 
date of first d ose 
Date of P D or d eat h 
E ve nt
P D or deat h
- after > = 2 missi n g or i na de q uate 
p ost baseli ne t u m or ass ess me nt 
Date of last a d e q uate 
t u m or assess me ntb 
d oc u me nti n g n o P D 
pri or t o ne w a ntica ncer
t hera p y, or miss e d 
t u m or assess me nts 
Ce ns ore d
N o P D
Ne w a ntica ncer t h era p y gi ve n 
pri or t o P D or deat h 
a 
6 wee ks after d ate of first d ose a n d a n d 
di d n ot i nitiate n e w a ntica ncer t h era p y, t h e d eat h is a n e v e nt wit h d ate o n d eat h d ate ( 6 wee ks is 2 ti m es t h e 
le n gt h of t h e first 2 t u m or assess me nt i nter v als). 
 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
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Pa g e 2 5 
 
b If t h ere are n o a d e q u ate p ost- baseli n e assess m e nts pri or t o t h e P D or d eat h, t h e n t h e ti me wit h o ut a d e q u ate 
assess m e nt s h o ul d b e meas ure d fr o m t he d ate of first d ose; if t he criteria is met, t h e ce ns ori n g will be o n t h e 
d ate of first d ose.
T a bl e 3  
P F S Ce ns o ri n g Re as o ns a n d Hie arc h y  
Hier arc h y
C o n diti o n
Ce ns ori n g Re as o n
1  
N o a de q uate baseli n e assess me nt
N o a de q uat e baseli ne
assess me nt
2  
Start of ne w a nti ca ncer t h era p y bef ore e ve nt 
Start of ne w a ntica ncer
t hera p y 
3
E ve nt aft er 2 or m ore missi n g or i na de q u ate 
p ost baseli ne t u m or ass ess me nt/start date 
E ve nt after missi n g or
i na de q uate ass ess me nts
4
date of first d ose O R E n d of st u d y ( E O S) = 
S u bject ref us e d f urt her f oll o w- u p] 
Wit h dra w al of c o nse nt
5  
N o e ve nt a n d l ost t o f oll o w- u p i n a n y 
dis p ositi o n pa ge 
L ost t o f oll o w- u p 
6  
N o e ve nt a n d l ost t o f oll o w- u p i n a n y 
dis p ositi o n pa ge 
N o a de q uate p ost- baseli n e
t u m or assess me nt 
7  
N o e ve nt a n d n o n e of t he c o n diti o ns i n t he 
pri or hierarc h y are met 
O n g oi n g wit h o ut a n e ve nt
Ti m e t o Pr o gressi o n ( T T P) 
Ti me t o pr o gressi o n ( T T P) is defi ne d as t he ti me fr o m date of t he first d ose of st u d y 
treat me nt t o t he earliest d oc u me nte d disease pr o gressi o n b y I n v esti gat or assess me nt.
T T P will b e calc ulate d i n m o nt hs as f oll o ws: 
T T P ( m o nt hs) = ( date of pr o gressi o n or ce ns ori n g – date of first d ose + 1)/ 3 0. 4 3 7 5 
T T P will b e esti mate d usi n g t he Ka pla n- Mei er m et h o d. T he T T P rate at 3, 6, 9, 1 2, 1 5 a n d 1 8 
m o nt hs will be esti m ate d wit h c orres p o n di n g 2-si d e d 9 5 % CIs. 
 
O ver all S ur vi v al ( O S) 
 
A nal ysis set: F ull A nal ysis Set  
O S will be calc ul ate d i n m o nt hs as f oll o ws: 
O S ( m o nt hs) = ( date of d eat h or ce ns ori n g –  date of first d ose + 1)/ 3 0. 4 3 7 5 
 
O S ti m e will be esti mate d usi n g t he sa me Ka pla n- Meier met h o d. T he O S rate at 6, 1 2, 1 8, 2 4, 
3 0 a n d 3 6 m o nt hs will be esti m ate d wit h c orres p o n di n g 2-si de d 9 5 % CIs. 
 
Fre q u e nc y ( n u m b er a n d perce nt a ge) of patie nts wit h deat h e ve nts a n d ce ns ori n g reas o ns will 
be prese nt e d b y c o h ort al o n g wit h t he o verall e ve nt a n d ce ns or rates. T he e v e nt a n d e ns ori n g 
reas o ns are as f oll o ws: 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 2 6 
 
 Deat h:
Deat h d ue t o C O VI D- 1 9.
O n g oi n g a n d n o deat h.
Wit h dra w al of c o nse nt.
L ost t o f oll o w- u p.
 T he O S ti me or ce ns ori n g ti me a n d t he reas o ns f or ce ns ori n g will als o be prese nte d i n a 
patie nt listi n g.
P he n ot y pes, a n d q u a ntit y of TI L bef ore a n d after P F- 0 7 2 6 0 4 3 7 tre at me nt (e g, C D 3, 
C D 8, Gr a n z y me B, Ki 6 7 I H C)
6. 3 
Terti a r 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 b e use d f or O R R a n d P F S ( R E CI S T, ir R E CI S T). T u m or 
res p o nse will be prese nte d i n t h e f or m of partici p a 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.  
Data will be s u m mariz e d (als o gra p hic all 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 a r 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 b e d i n t he b S A P a n d C S R t o t he e xte nt 
p ossi ble. D ue t o t h e e x pl orat or y nat ure of t h e e n d p oi nts, t he ass ociate d data a nal yses ma y n ot 
be c o m plete at t he ti m e 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 nal yses 
ca n n ot be i n cl u de d i n t he C S R, t he y will be disse mi nate d t o t he scie ntific c o m m u nit y t o t he 
e xte nt p ossi ble t hr o u g h pres e 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 s cie ntific j o ur n als. 
6. 5 
B aseli n e a n d Ot her S u m m aries a n d A n al yses
6. 5. 1 
B aseli n e S u m m aries
Baseli ne c haracteristi cs s u c h as de m o gra p hics, pri or me dicati o n, a n d pri mar y dia g n osis will 
be ta b ulate d a n d liste d. T he Safet y A nal ysis Set will be use d. 
6. 5. 2 
St u d y C o n d uct a n d P arti ci p a nt Dis p ositi o n 
A n acc o u nti n g of t he st u d y partici pa nts will be ta b ulate d. T he partici pa nt d ose le vel c o h ort 
will b e liste d.  T he F ull A nal ysis Set will be use d.  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
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Pa g e 2 7 
 
Partici pa nt disc o nti n uati o n fr o m treat m e nt a n d st u d y will be ta b ulate d a n d liste d f or eac h 
partici pa nt se paratel y wit h t h eir reas o n f or disc o nti n uati o n.  T he Safet y A n al ysis Set will b e 
use d. 
6. 5. 3 
St u d y Tre at me nt E x p os u re
T he Safet y A n al ysis Set will be use d. 
D ose m o dificati o ns are d escri be d i n t he pr ot o c ol.  T he f oll o wi n g will be s u m marize d b y 
treat me nt d ose le v el a n d o verall:
 N u m ber of s u bjects;  
 Me dia n a n d ra n ge of n u m ber of treat me nt c ycles starte d;  
 N u m ber ( %) of s u bjects starti n g a treat m e nt c y cle ( 1, 2, 3 …);  
 N u m ber ( %) of d ose i nterr u pti o ns (i ncl u de b ot h k n o w n a n d u n k n o w n dates). D os e 
i nterr u pti o ns is defi ne d as as a pla n n e d d osi n g da y wit h 0 m g t otal d ose a d mi nistere d. 
Missi n g d oses o n u n k n o w n dates will be i n cl u de d i n t h e s u m m ar y. N ote: D ose 
i nterr u pti o ns a p pl y t o u ne x pecte d d os e i nterr u pti o ns a n d n ot t he o ne- w ee k treat m e nt 
h oli d a y gi v e n i n eac h treat me nt c ycle; 
 N u m ber ( %) of d ose i nterr u pti o ns relate d t o A Es, defi n e d as “ Was t he Act u al D ose 
 
a n d “ L atest Acti o n T a ke n wit h 
“ D O S E 
; 
 N u m ber ( %) of s u bjects wit h d ose re d ucti o ns. A d ose re d ucti o n is defi n e d as a d a y 
w he n t he a ct ual d ose is less t ha n t he pla n ne d d ose at e nr oll me nt a n d t he a c utal d ose is 
greater t h a n 0 m g (i. e., misse d d oses are n ot c o u nte d as a re d ucti o n);  
 N u m ber ( %) of d ose re d u cti o ns relate d t o A Es, defi ne d as “ Was t he Act u al D ose 
R E D U C E D
 N u m ber ( %) of parti ci pa nts wit h d ose re d ucti o ns or i nterr u pti o ns f or eac h reas o n ( A E 
vs i ns ufficie nt cli nical res p o nse vs Ot her);  
 Da ys o n treat m e nt ( me dia n, ra n ge). 
 N u m ber of  treat me nt c y cles recei v e d p er s u bject ( me dia n, ra n g e);  
 N u m ber of treat me nt c ycles recei ve d b ef ore 1st re d ucti o n ( me dia n, ra n g e);  
 N u m ber of treat me nt c ycles recei ve d b ef ore 1st i nterr u pti o n ( me dia n, ra n ge).  
T he f oll o wi n g will be s u m marize d f or c u m ulati ve d ose b y d ose le vel:  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 2 8 
 
 S u m mar y statistics ( mea n, m e dia n, sta n dar d d e viati o n a n d ra n ge) of c u m ulati ve d ose 
a n d c u m ulati ve perce nt of a d mi nistere d d ose (c o m pare d t o pla n ne d d os e);
 Act u al d ose i nte nsit y ( m g/ da y): Defi ne d as c u m ul ati v e act ual d ose recei ve d ( m g) 
di vi d e d b y t h e n u m b er of d oses sc he d ule d p er pr ot oc ol d uri n g treat m e nt peri o d;
 Rati o of act ual d ose i nte nsit y t o pla n ne d d ose i nte nsit y.
W here pla n n e d d ose i nte nsit y 
is defi ne d as a p artici pa nt’s pla n ne d starti n g d ose. 
Listi n gs b y s u bject ( or dere d b y d ose le v el): start d ate a n d st o p date of d osi n g peri o d wit hi n 
eac h c ycle (i n cl u di n g rec or ds wit h 0 m g), t otal dail y d ose rec ei ve d f or eac h d osi n g peri o d, 
a n y misse d d oses wit h u n k n o w n dates ( yes/ n o), n u m ber of miss e d d oses wit h u n k n o w n dates,  
reas o n f or a n y d osi n g c h a n ges, a n d c ycle n u m ber relati ve t o t he d osi n g peri o d.  
Listi n gs b y s u bject a n d c ycle ( or dere d b y d os e le vel): c ycle le n gt h, t otal pla n ne d d ose, t otal 
act ual d ose recei ve d, perce nta ge of pla n ne d d os e, d ose re d ucti o n ( y es/ n o), a n d d ose 
i nterr u pti o n ( yes/ n o). 
6. 5. 4 
C o nc o mit a nt Me dic ati o ns a n d N o n dr u g Tre at me nts 
Pri or, c o nc o mita nt, a n d f urt her t hera pies ( dr u g a n d n o n- dr u g treat m e nts) will be c o de d b y t he 
W orl d Healt h Or ga nizati o n ( W H O) m e dical dicti o nar y. Listi n gs of pri or, c o nc o mita nt, a n d 
f urt h er t h era pies will be pr o vi de d s e paratel y. 
 
6. 6 
S afet y S u m m aries a n d A n al yses
All safet y a nal yses will be perf or me d o n t he Safet y A nal ysis Set. 
S u m maries a n d a nal yses of safet y para m eters will i n cl u de all partici pa nts i n t he safet y 
a nal ysis set. 
A Es, E C Gs, bl o o d press ure ( B P), p uls e rat e, o p ht h al mi c e xa mi nati o ns a n d s afet y la b orat or y 
data will be re vie we d a n d s u m m arize d o n a n o n g oi n g basis d uri n g t he st u d y t o e val uate t he 
safet y of partici pa nts.  A n y cli nical la b orat or y, E C G, B P, a n d p ulse rate a b n or malities of 
p ote ntial cli nical c o ncer n will be descri be d.  Safet y data will b e pres e 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 des cri pti vel y, w here a p pr o priat e. 
Me dical hist or y a n d p h ysical e xa mi n ati 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 oll ecte 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 b e re p orte d, u nless ot her wise n ote d.  H o w e ver, a n y u nt o war d fi n di n gs 
i de ntifie d o n p h ysical/ or ne ur ol o gical e x a mi n ati o ns e xa mi nati o ns c o n d ucte d d uri n g t h e 
acti v e c ollecti o n peri o d will be ca pt ure d as A Es, if t h ose fi n di n gs meet t h e defi niti o n of a n 
A E.  Data c ollecte d at s cree ni n g t hat are use d f or i ncl usi o n/e xcl usi o n crit eri a, s uc h as 
la b orat or y dat a, 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 wis e n ote d. D e m o gra p hic data c oll ect e d at scree ni n g will 
be re p ort e d.  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 2 9 
 
6. 6. 1 A d verse E v e nts 
A Es will be gra de d b y t h e i n vesti gat or acc or di n g t o t he C T C A E versi o n 5. 0 a n d c o de d usi n g 
t he Me dical Dicti o nar y f or Re g ulat or y A cti vities ( Me d D R A, versi o n 2 3. 1).  A d v erse e ve nt 
data will be re p orte d i n ta bles a n d listi n gs.  S u m maries of a d v erse e ve nt b y s yste m or ga n 
class a n d preferre d t er ms, t o xicit y gra de, a n d seri o us ness a n d relati o ns hi p t o st u d y treat me nt 
will b e prese nte d, as well as s u m maries of a d v erse e ve nts lea di n g t o deat h a n d pre mat ure 
wit h dra wal fr o m st u d y treat m e nt.  T he n u m b er a n d perce nt a ge of p arti ci pa nts w h o 
e x perie n ce d a n y A E, S A E, treat m e nt rel ate d A E, a n d treat m e 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 h e s u m m aries will prese nt A Es acr oss t he 
e ntire st u d y peri o d.  A ta ble s u m marizi n g 
Fr o m Last D ose of St u d y Treat me nt) or off st u d y treat me nt (i.e., d eat h > 3 0 Da ys Fr o m L ast 
D ose of St u d y Treat me nt) will be pr o vi de d. A d diti o nall y, listi n gs of D L Ts a n d deat hs will be 
pr o vi de d. Deat h a n d S A E i nf or mati o n will be bas e d o n t he d ata ca pt ure d fr o m t h e C R F.
A si mil ar a p pr oac h will be use d f or ir A Es. 
6. 6. 2 Cli ni c al S afet y L a b or at or y Assess me nts
Safet y la b orat or y t ests will be perf or me d as descri be d i n t he pr ot o c ol. 
T o deter mi ne if t h ere are a n y cli nicall y si g nifica nt la b orat or y a b n or malities, t h e 
he mat ol o gical, cli nical c h e mistr y a n d uri nal ysis safet y tests will be assesse d a gai nst t he 
criteria s pecifie d i n t he s p o ns or re p orti n g sta n dar ds.  T he assess me nt will ta ke i nt o acc o u nt 
w het h er eac h s u bject’s b aseli ne test res ult is wit hi n or o utsi de t he l a b orat or y refere nce ra n ge 
f or t h e p artic ul ar la b orat or y p ara m eter.
T he data ma y b e s u m marize d wit h res p ect t o de m o gra p hic a n d b aseli ne c haract eristi cs, 
effic ac y o bser vati o ns a n d meas ure me nts, safet y o bser vati o ns a n d meas ure m e nts, 
p har mac o ki n etic a n d bi o mar ker meas ure m e nts. 
6. 6. 3 Vit al Si g ns 
Vital si g ns will c o nsist of s yst olic a n d diast olic bl o o d press ure, a n d p ulse rate meas ure me nts. 
Criteria f or cli nic all y rele va nt a b n or mal fi n di n gs are pr o vi d e d i n A p p e n di x 2 . Meas ure me nts 
t hat meet t hese criteria will b e liste d. 
 
6. 6. 4 Electr oc a r di o gr a ms 
T he a nal ysis of E C G res ults will be base d o n partici pa nts i n t he Safet y A n al ysis Set wit h 
baseli n e a n d o n-treat me nt E C G data. Baseli n e is defi n e d as meas ure me nts ta ke n at C y cle 1 
Da y 1 pre- d ose (s ee S o A i n pr ot oc ol  f or details).
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 T c i nter val, p ulse 
rate i nter v al, a n d Q R S c o m ple x will be s u m marize d b y treat m e nt a n d ti me. 
T he n u m ber ( %) of p artici pa nts wit h m a xi m u m p ost d ose Q Tc F v al ues a n d ma xi m u m 
i ncreas es fr o m baseli ne i n t h e f oll o wi n g cate g ories will be ta b ulate d b y treat me nt c o h ort:  
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 3 0 
 
S afet y Q Tc F Ass ess me nt
 
De gree of P r ol o n g ati o n  
Mil d ( msec)  
M o der ate ( msec) 
Se v ere ( msec)
A bs ol ute v al ue
> 4 5 0- 4 8 0
> 4 8 0- 5 0 0
> 5 0 0 
I ncrease fr o m b aseli ne 
N A 
3 0- 6 0 
> 6 0
I n a d diti o n, t h e n u m b er of partici pa nts wit h Q Tc F val ues > 5 0 0 msec will be s u m m arize d.
Electr ocar di o gra m ( E C G) meas ure m e nts (a n a v era ge of t he tri plicate meas ure me nts) will be 
use d f or t he statistical a n al ysis a n d all data pres e ntati o ns.  
If m ore t h a 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 x a m ple, 
tri plicate E C Gs), t he mea n of t he re pli cate 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 h e 3 i n di vi d ual E C G traci n gs h as a Q Tc F val u e 
> 5 0 0 msec, b ut t he mea n of t he tri plicates is n ot > 5 0 0 msec, t he d ata fr o m t he p arti ci pa nt’s 
i n di vi d ual traci n g will be descri be d i n a s afet y secti o n of t h e C S R i n or der t o place t he 
> 5 0 0- msec v al ue i n a p pr o priate cli nical c o nt e 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 mse c will n ot be i ncl u de d i n t he cate g orical 
a nal ysis u nless t he a vera ge fr o m t he tri pli cate m eas ure m e nts is als o > 5 0 0 msec.  C h a n ges 
fr o m baseli ne will b e defi n e d as t he c ha n g e bet w ee n t he p ost d ose Q Tc F val u e a n d t he 
a vera g e of t h e pre d ose tri plicate val ues o n D a y 1.   
I n a d diti o n, a n atte m pt will be m a de t o e x pl ore a n d c haracteri ze t h e relati o ns hi p bet wee n 
plas ma c o n ce 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 mic m o deli n g 
a p pr oac h.  If a P K/ p h ar mac o d y na mic relati o ns hi p is f o u n d, t h e i m pact of partici pa nt fact ors 
(c o v ari ates) o n t he relati o ns hi p will be e xa mi ne d. 
T he a nal ysis of E C G res ults will be base d o n partici pa nts i n t he Safet y A n al ysis Set wit h 
baseli n e 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 h e tri plicate m eas ure m e nts) will be use d f or t he 
statisti cal a nal ysis a n d all data prese ntati o ns.  A n y data o btai n e d fr o m E C Gs re p eat e d f or 
safet y reas o ns aft er 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 v al m eas ure me nts fr o m re peat e d E C Gs will be i ncl u de d i n t he o utlier 
a nal ysis (cate g orical a nal ysis) as i n di vi d ual val ues o btai n e 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 heart rate ( H R) ( Q Tc) usi n g t he st a n d ar d c orrecti o n fact or 
of Fri dericia.  D ata will be s u m marize d a n d liste d f or Q T, H R, R R, p uls e rate, Q R S, Q Tc F, 
ti m e a n d d ose.  Descri pti ve statistics ( n, mea n, m e dia n, sta n d ar d de vi ati o n, mi ni m u m, a n d 
ma xi m u m) will be use d t o s u m m arize t h e a bs ol ute c orrecte d Q T i nter val a n d c ha n ges fr o m 
baseli n e i n c orrecte d Q T aft er tr eat m e nt, b y d ose a n d ti me p oi nt. 
6. 6. 5 P h ysic al E x a mi n ati o n 
Partici pa nts will ha ve a p h ysical e xa mi nati o n t o i n cl u de wei g ht, vital si g ns, assess me nt of 
E C O G perf or ma nce stat us a n d hei g ht; hei g ht will be meas ure d at baseli n e o nl y.  
 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 3 1 
 
7.  
I N T E RI M A N A L Y S E S
N o f or mal i nteri m a nal ysis 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 d y, 
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 h e st u d y f or t he p ur p ose of 
safet y assess me nt, facilit ati n g d ose-escalati o n decisi o ns, facilitati n g P K m o deli n g, a n d/ or 
s u p p orti n g cli nical de vel o p me nt.
8. R E F E R E N C E S 
Ne ue nsc h wa n der B, Mata n o A, Ta n g Z, R o yc h o u d h ur y S, Wa n del S a n d B aile y S.  A 
Ba yesia n I n d ustr y A p pr oac h t o P hase I C o m bi nati o n Trials i n O nc ol o g y.  I n St atistic al 
Met h o ds i n Dr u g C o m bi n ati o n St u dies .  Z ha o W a n d Ya n g H (e ds), C h a p ma n & Hall/ C R C, 
2 0 1 4. 
R o gat k o A 1, Sc h oe nec k D, J o nas W, Ti g hi o uart M, K h uri F R, P orter A. Tra nsl ati o n of 
i n n o vati ve desi g ns i nt o p hase I trials. J Cli n O nc ol. 2 0 0 7 N o v 1; 2 5( 3 1): 4 9 8 2- 6. 
9. A P P E N DI C E S 
A p pe n di x 1 
Ti m e t o E ve nt D at a A n al ysis Ce ns ori n g R ules 
T a bl e 4  
O S O utc o m e a n d E ve nt D ates 
Sit u ati o n
D ate of De at h/ Ce ns ori n g
O utc o m e
Ali v e
Date of L ast C o ntact 
Ce ns ore d
Deat h d ue t o a n y ca use
Date of Deat h 
E ve nt
A p pe n di x 2
C ate g oric al Cl asses f or E C G a n d Vit al Si g ns 
 
Cli ni c all y Rele v a nt C ate g ories f o r Q T c F 
Q Tc F ( msec) 
ma x. 
4 5 0 
ma x. 
4 8 0
ma x. 
5 0 0
ma x. > 5 0 0 
Q Tc F ( msec) 
i ncreas e fr o m 
baseli n e
 
 
Cli ni c all y Rele v a nt C ate g ories f o r P ulse R ate a n d Q R S
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 3 2 
 
P uls e Rate 
( msec)
ma x.
P uls e R ate
( msec) 
i ncreas e fr o m 
baseli n e
Baseli ne 
> 2 0 0 a n d 
i ncreas e
a n d ma x. 
Q R S ( msec) 
ma x.
 
Q R S ( msec) 
i ncreas e fr o m 
baseli n e
Baseli ne 
> 1 0 0 a n d 
i ncreas e
a n d ma x. 
Cli ni c all y Rele v a nt C ate g ories f o r Vit al Si g ns
S yst olic B P ( m m H g) 
1 6 0 ma x. 
S yst olic B P ( m m H g) 
c ha n ge fr o m baseli n e
ma x. decreas e 
 
ma x. i ncreas e 
 
Diast olic B P ( m m H g)
 
Diast olic B P ( m m H g) 
c ha n ge fr o m baseli n e
ma x. decreas e 
 
ma x. i ncreas e 
 
S u pi n e p uls e rate ( b p m)  
ma x. > 1 2 0
Meas ure me nts t hat f ulfil t hese criteria are t o be liste d i n t he st u d y re p ort. 
A p pe n di x 3
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 b e use d i n t h e S A P. 
A b bre vi ati o n  
Ter m
A E 
a d vers e e ve nt
A S T C T 
A merica n s o ciet y f or tra ns pla ntati o n a n d cell ular t hera p y 
A U C 
area u n d er t he c o nce ntrati o n-ti me c ur ve 
A U C i nf
area u n d er t he c o nce ntrati o n-ti me v ers us ti me c ur ve fr o m ti m e 0 t o 
i nfi nit y 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 3 3 
 
A b bre vi ati o n 
Ter m
A U C last
area u n d er t he c o nce ntrati o n-ti me c ur ve fr o m ti me 0 t o ti m e of last 
meas ura ble c o nce ntrati o n
A U C ta u,ss 
area u n d er t he ste a d y stat e d ose c o nce ntrati o n-ti m e c ur v e o v er 
d osi n g i nter val ta u
B L Q 
bel o w t he li mit of q ua ntificati o n 
B L R M
Ba yesi a n l o gistic re gressi o n m o del
B O R 
best o verall res p o ns e 
B P
bl o o d press ure
b p m 
beats per mi n ute
b S A P
bi o mar ker statistical a nal ysis pla n
C DI S C 
cli nical data i nterc ha n ge sta n dar ds c o ns orti u m 
CI
c o nfi de nce i nter val
C L 
t otal cleara nce of dr u g fr o m e g, plas ma 
C ma x  
m a xi m u m o bser ve d c o nce ntrati o n
C O VI D 
c or o na vir us disease
C R 
c o m plete res p o nse
C R F 
case re p ort f or m
C R S 
c yt o ki ne release s y n dr o m e
C S R 
cli nical st u d y re p ort 
C T 
c o m p ute d t o m o gra p h y/cli nical trial
C T C A E
c o m m o n ter mi n ol o g y crit eria f or a d verse e v e nts 
ct D N A
circ ulati n g t u m or D N A 
D C 
disease c o ntr ol
D C R 
disease c o ntr ol rate
D DI 
dr u g- dr u g i nteracti o n
D L R M
d ose le vel re vi e w meeti n g
D L T 
d ose-li miti n g t o xicit y 
D O R 
d urati o n of res p o ns e
E C G
electr ocar di o gra m
E W O C
escalati o n wit h o ver d os e c o ntr ol
FI H 
first i n h u ma n
H R 
heart rate
I T T 
i nte nti o n t o treat
L L Q 
l o wer li mit of q ua ntificati o n 
M A P 
meta-a nal ytic- pre dicti ve 
Me d D R A
me dical dicti o nar y f or re g ulat or y acti vities
m g 
milli gra ms 
mI T T
m o difie d-i nte nt-t o-treat 
m m 
milli meters
M RI 
m a g netic res o n a nce i m a gi n g 
msec 
millisec o n d
M T D 
ma xi m u m t olerate d d ose 
N C 
n ot cal c ulate d 
N CI 
nati o nal Ca ncer I nstit ute 
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)
 


Pr ot o c ol C 4 4 3 1 0 0 1 ( P F- 0 7 2 6 0 4 3 7)  Statistical A nal ysis Pla n 
 
P FI Z E R C O N FI D E N TI A L  
Pa g e 3 4 
 
A b bre vi ati o n 
Ter m
N D
n ot d o ne
N E 
n ot e val ua ble
N S
n o sa m ple
N S C L C
n o n-s mall cell l u n g ca n cer 
O R
o verall res p o ns e
O R R 
o bjecti v e res p o nse rate
O S
o verall s ur vi val
P D 
p har mac o d y n a mics(s)/ pr o gressi v e dis eas e
P D S 
Pfizer data sta n d ar d 
P F S 
pr o gressi o n-free s ur vi val
P K 
p har mac o ki n etic(s)
P R
partial res p o nse
Q Tc 
c orrecte d Q T
Q Tc F
Q Tc c orrecte d Q T ( Fri dericia met h o d) usi n g Fri dericia’s f or m ula
R ac
acc u m ulati o n rati o base d o n A U C ( o bser ve d) 
R E CI S T 
res p o nse e v al uati o n criteria i n s oli d t u m ors 
R P 2 D
rec o m m e n de d P has e 2 d ose 
S A E 
seri o us a d verse e v e nt
S A P 
statisti cal a nal ysis pla n
S D 
sta ble disease
t½  
ter mi nal p hase half-life 
T E A E
treat me nt e mer ge nt a d verse e ve nts
T ma x  
ti me t o reac h Cma x  
T T P 
ti me t o pr o gressi o n
W H O
w orl d healt h or ga ni zati o n
0 9 0 1 7 7 e 1 a 0 6 5 e 9 a 8\ A p pr o v e d\ A p pr o v e d O n: 1 0- A pr- 2 0 2 4 0 6: 1 1 ( G M T)