An Open-Label Phase 2 Study of Itacitinib (INCB039110) in Combination With Low-Dose Ruxolitinib or Itacitinib Alone Following Ruxolitinib in Subjects With Myelofibrosis
Phase: PHASE2
Conditions: MPN (Myeloproliferative Neoplasms)
Sponsor: Incyte Corporation

 
Offici al Titl e:  
A n O p e n -L a b el P h as e 2 St u d y of It aciti ni b (I N C B 0 3 9 1 1 0) i n C o m bi n ati o n 
Wit h  L o w -D os e  R u x oliti ni b  or  It aciti ni b  Al o n e  F oll o wi n g  R u x oliti ni b  i n  
S u bj ects Wit h M y el ofi br osis  
N C T N u m b er:  
N C T 0 3 1 4 4 6 8 7  
 
D oc u m e nt  D at e : 
 
Cli nic al St u dy Pr ot oc ol : 1 4  A u g ust 2 0 1 7  
 
 
 
 
 
 
 
 

I nc yte C or p orati o n 
P a ge 1 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
 
Cli nic al St u d y Pr ot oc ol 
 
I N C B 3 9 1 1 0 -2 0 9  
A n O pe n - L a bel P h ase 2 St u d y of It aciti ni b (I N CB 0 3 9 1 1 0 ) i n 
C o m bi n ati o n Wit h L o w -D ose R u x oliti ni b or It aciti ni b Al o ne 
F oll o wi n g R u x oliti ni b i n S u bje cts Wit h M yel ofi b r osis  
 
 
 
 
 
P r o d uct:  
It aciti ni b (I N C B 03 9 1 1 0) 
I N D N um ber:  
 
P h ase of S t u d y: 
2 
S p o ns or:  
I nc yte C or p or ati o n 
1 8 0 1 A u g usti ne C ut - Off 
Wil mi n gt o n, D E 1 9 8 0 3 
D ate of P r ot oc ol:  
2 2 M A R 2 0 1 7 
D ate of A me n de me nt  1:  
1 4 A U G 2 0 1 7 
 
 
 
T his  st u d y will be perf or me d i n acc or da nce wit h et hical pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n of 
Helsi n ki a n d c o n d ucte d i n a d here nce t o t he st u d y Pr ot oc ol , G o o d Cli nical Practices  as defi ne d i n Title 2 1 of t he 
U S  C o de of Fe deral Re g ulati o ns P arts 1 1, 5 0, 5 4 , 5 6, a n d 3 1 2 , as well as I C H G C P c o ns oli date d g ui deli nes ( E 6) a n d 
a p plica ble re g ulat or y re q uire me nts. 
 
T he i nf or mati o n i n t his d oc u me nt is  c o nfi de ntial.  N o part of t his i nf or mati o n ma y be d u plicate d, refere nce d, or 
tra ns mitte d i n a n y f or m or b y a n y mea ns (electr o nic, mec ha nical, p h ot oc o p y, rec or di n g, or ot her wise) wi t h o ut t he pri or 
writte n c o nse nt of I nc yte C or p orati o n.  

I nc yte C or p orati o n 
P a ge 2 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
I N V E S TI G A T O R'S A G R E E M E N T  
I h a ve r ea d t he I N C B 3 9 1 1 0- 2 0 9 Pr ot oc ol A me n d me nt 1 ( date d 1 4 A U G  2 0 1 7) a n d a gree t o 
c o n d uct t he st u d y as o utli ne d.  I a gr ee t o mai ntai n t he c o nfi de ntialit y of all i nf or mati o n recei ve d 
or de vel o pe d i n c o n n ecti o n wit h t his Pr ot oc ol. 
 
 
 
 
 
( Pri nte d Na me of I n vesti gat or) 
 
 
 
 
 
 
 
 
( Si g nat ur e of I n v esti gat or) 
 
( Date) 

I nc yte C or p orati o n 
P a ge 3 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
S Y N O P SI S  
N a me of I n vesti g ati o n al Pr o d uct:   Itaciti ni b (I N C B 0 3 9 1 1 0) 
Title of St u d y:   A n O pe n -La bel  P hase 2 St u d y of Itaciti ni b (I N CB 0 3 9 1 1 0) i n C o m bi nati o n Wit h 
L o w - D ose R u x oliti ni b or Itaciti ni b Al o ne F oll o wi n g R u x oliti ni b i n S u bjects Wit h M yel ofi br osis  
P r ot oc ol N u m ber:   I N CB 3 9 1 1 0 - 2 0 9 
St u d y P h ase:   2 
I n dic ati o n:  Pri mar y a n d sec o n dar y m yel ofi br osis ( M F) 
 
Pri m ar y O bjecti ve  
Pri m ar y E n d p oi nt  
T o e val uate preli mi nar y effica c y of itaciti ni b 
(I N C B 0 3 9 1 1 0) o n s plee n v ol u me re d ucti o n ( S V R) 
fr o m baseli ne at W ee k 2 4 i n t he 2 f oll o wi n g c o h orts 
of M F  s u bj ects: 
•  C o h ort A :  i n c o m bi nati o n i n s u bj ects wit h 
r u x oliti ni b l o w d ose (less t ha n 2 0 m g dail y). 
•  C o h ort B :  as m o n ot hera p y i n s u bj ects w h o 
pr o gresse d ( per re vise d E ur o pea n Le u ke mia Net 
[E L N ] 2 0 1 3 res p o nse criteria f or M F) after i nitial 
re d ucti o n i n s plee n o n r u x oliti ni b or disc o nti n ue d 
f or he mat ol o gic t o xicities. 
C ha n ge a n d p erce ntage c ha n ge  i n S V R as meas ure d b y 
ma g netic res o na nce i ma gi n g [ M RI] (c o m p ute d 
t o m o gra p h y [ C T] sca n i n s u bj ects w h o are n ot ca n di dates 
f or M RI or w he n M RI is n ot r ea dil y a vaila ble) at 
W ee k 2 4 w he n c o m pare d wit h  baseli ne.  
Sec o n d ar y O bjecti ve s ( C o h orts A a n d B) 
Sec o n d ar y E n d p oi nt s 
T o e val uate preli mi nar y safet y a n d t olera bilit y of 
itaciti ni b al o ne. 
Safet y a n d t olera bilit y t hr o u g h assess me nt of fre q ue nc y, 
se verit y, a n d d urati o n of a d verse e ve nts ( A Es ); c ha n ges 
i n cli nical safet y assess me nts; a n d c ha n ges i n cli nical 
la b orat or y para meters. 
T o e val uate preli mi nar y safet y a n d t olera bilit y of 
itaciti ni b i n c o m bi nati o n wit h r u x oliti ni b. 
T o e val uate preli mi nar y effica c y of itaciti ni b al o ne or 
i n c o m bi nati o n wit h r u x oliti ni b o n S V R  fr o m 
baseli ne at W ee k 1 2.  
C ha n ge a n d  perce nta ge i n S V R fr o m baseli ne t hr o u g h 
W ee k 1 2 as meas ure d b y M RI ( or C T sca n i n a p plica ble 
s u bj ects). 
T o e val uate preli mi nar y effica c y of itaciti ni b al o ne or 
i n c o m bi nati o n wit h r u x oliti ni b o n s plee n le n gt h 
re d ucti o n fr o m baseli ne at W e e k 1 2 a n d W ee k 24.  
C ha n ge  a n d perce nta ge c ha n ge o n s plee n le n gt h 
re d ucti o n fr o m baseli ne t hr o u g h W ee k 1 2 a n d W ee k 2 4 
as meas ure d b y pal pati o n.  
T o e val uate preli mi nar y effica c y of itaciti ni b al o ne or 
i n c o m bi nati o n wit h r u x oliti ni b wit h res pect t o M F 
s y m pt o ms at W ee k 1 2 an d W ee k 2 4.  
C ha n ge a n d perce nta ge c ha n ge i n T otal S y m pt o m Sc ore 
(T S S ) fr o m baseli ne t hr o u g h W ee k 1 2 a n d W ee k 2 4 as 
meas ure d b y t he M yel ofi br osis S y m pt o m Assess me nt 
F or m versi o n 2. 0 ( M F S A F v 2. 0) s y m pt o m diar y a n d b y 
t he M yel o pr oliferati ve Ne o plas ms S y m pt o m Assess me nt 
F or m ( M P N -S A F).  
P atie nt Gl o bal I m pressi o n of C ha n ge sc ore at eac h visit 
w here t he varia ble is meas ure d.  
T o e val uate preli mi nar y effica c y of itaciti ni b usi n g 
I nter nati o nal W or ki n g Gr o u p-M yel o pr oliferati ve 
Ne o plas ms Researc h a n d Treat me nt (I W G-M R T)  
criteria.  
N u m ber of s u bj ects wit h res p o nses acc or di n g t o t he 2 0 1 3 
I W G-M R T c o nse ns us c riteria f or treat me nt res p o nse. 
 

I nc yte C or p orati o n 
P a ge 4 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
 
Sec o n d ar y O bjecti ve s ( C o h orts A a n d B) ( C o nt' d) 
Sec o n d ar y E n d p oi nts ( C o nt' d)  
T o assess t he p har mac o ki netics ( P K) of itaciti ni b a n d  
r u x oliti ni b. 
Calc ulati o n of t he P K para met ers s uc h as A U C, C L/ F, 
C ma x , a n d tma x  al o n g wit h s u m marizati o n of t he o bser ve d 
c o nce ntrati o n data b y ti me p oi nt will be perf or me d f or 
b ot h r u x oliti ni b a n d itaciti ni b. 
 
O ver all S t u d y Desi g n: 
T his is a n o pe n-la bel P hase 2 st u d y wit h 2 c o h orts: 
•  C o h ort A :  M F  s u bjects w h o are t olerati n g a r u x oliti ni b d ose of less t ha n 2 0 m g dail y will recei ve a  
c o m bi nati o n of t he J A K 1 i n hi bit or itaciti ni b at t he d ose of 2 0 0 m g o nce dail y ( Q D ) a n d t he J A K 1/ 2 
i n hi bit or r u x oliti ni b. 
•  C o h ort B :  M F  s u bjects w h o pr o gresse d after i nitial re d ucti o n i n s plee n wit h  r u x oliti ni b treat me nt or 
disc o nti n ue d f or he mat ol o gic t o x icities will recei ve treat me nt wit h J A K 1 i n hi bit or itaciti ni b  al o ne at t he 
d ose of 6 0 0 m g Q D.  
S u bj ects will c o nti n ue st u d y treat me nt u ntil disease pr o gressi o n, u nacce pta ble t o xicit y, wit h dra wal of 
c o nse nt, or ot her Pr ot oc ol -s pecifie d criteria t o st o p treatme nt are met.  S u bj ects w h o are recei vi n g be nefit 
will c o nti n ue recei vi n g st u d y treat me nt u ntil wit h dra wal criteria are met . 
All s u bj ects will be f oll o we d f or safet y (e g, re p orti n g of A Es a n d seri o us A Es) 3 0 t o 3 5 da ys after last 
d ose of st u d y treat me nt. 
St u d y P o p ul ati o n:   
Male or fe male s u bjects a ge d 1 8 years or ol der w h o ha ve bee n dia g n ose d wit h M F (eit her pri mar y 
m yel ofi br osis [ P M F ] or sec o n dar y M F [ p ost –p ol yc yt he mia vera m yel ofi br osis { P P V -M F } or p ost –
esse ntial t hr o m b oc yt he mia m yel ofi br osis { P E T -M F }] ) a n d w h o ca n t olerate o nl y less t ha n 2 0 m g dail y 
d ose of r u x oliti ni b or s u bjects w h o eit her disc o nti n ue d f or he mat ol o gical t o xicities or pr o gresse d o n 
r u x oliti ni b after i nitial re d ucti o n i n s plee n. 

I nc yte C or p orati o n 
P a ge 5 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
Ke y I ncl usi o n Criteri a: 
C o h ort A o nl y 
•  Recei vi n g r u x oliti nib d ose of less t ha n 2 0  m g dail y wit h n o d ose i ncrease or n o d ose m o dificati o n i n t he 
last 8 wee ks bef ore scree ni n g visit. 
C o h ort B o nl y  
•  M ust ha ve ha d i nitial re d ucti o n i n s plee n o n r u x oliti ni b treat me nt ( res p o nse is defi ne d b y a n y s plee n 
le n gt h or v ol u me re d ucti o n, b y pal pati o n or M RI/ C T assess me nt, fr o m baseli ne w hile o n pre vi o us 
r u x oliti ni b treat me nt per I W G-M R T E L N 2 0 1 3 g ui deli nes): 
-  F oll o we d b y d oc u me nte d e vi de nce of pr o gressi o n i n s plee n le n gt h or v ol u me O R  
-  Disc o nti n ue d r u x oliti ni b f or he mat ol o gic t o xic ities, after t he i nitial re d ucti o n i n s plee n le n gt h or 
v ol u me. 
All s u bj ects  
•  Me n a n d w o me n, a ge d 1 8 years or ol der. 
•  C o nfir me d dia g n osis of P M F, P P V -M F, or P E T -M F  acc or di n g t o re vise d W H O 2 0 1 6 criteria . 
•  M ust ha ve pal pa ble s plee n of ≥ 5 c m bel o w t he left s u bc ostal mar gi n o n p h ysical e xa mi nati o n at t he 
scree ni n g visit.  (If s plee n is n ot pal pa ble d ue t o b o d y ha bit us, s plee n e nlar ge me nt m ust be d oc u me nte d 
b y ot her mea ns [ e g, ultras o u n d or M RI ] a n d st u d y s p o ns or me dical m o nit or be c o ntacte d f or 
acce pta nce). 
•  E C O G perf or ma nce stat us of 0, 1, or 2.  
•  Scree ni n g b o ne marr o w bi o ps y s peci me n a vaila ble or willi n g ness t o u n der g o a b o ne marr o w bi o ps y at 
scree ni n g/ baseli ne; willi n g ness t o u n der g o b o ne marr o w bi o ps y at Wee k 2 4. 
•  Life e x pecta nc y of at least 2 4 wee ks.  
•  Willi n g ness t o a v oi d pre g na nc y or fat heri n g c hil dre n base d o n t he f oll o wi n g criteria : 
-  W o ma n of n o nc hil d beari n g p ote ntial (ie, s ur gicall y sterile wit h a h ysterect o m y a n d/ or bilateral 
o o p h orect o m y O R ≥ 1 2 m o nt hs of a me n orr hea a n d at least 5 0 years of a ge). 
-  W o ma n of c hil d beari n g p ote ntial w h o has a ne gati ve ser u m pre g na nc y test at scree ni n g a n d ne gati ve 
uri nar y test bef ore t he first d ose o n Da y 1 a n d w h o a grees t o ta ke a p pr o priate preca uti o ns t o a v oi d 
pre g na nc y ( wit h at least 9 9 % certai nt y) fr o m scree ni n g t hr o u g h safet y f oll o w - u p.  Per mitte d met h o ds 
t hat are at least 9 9 % effecti ve i n pre ve nti n g pre g na nc y s h o ul d be c o m m u nicate d t o t he s u bject a n d 
t heir u n dersta n di n g c o nfir me d. 
-  Ma n w h o a grees t o ta ke a p pr o priate preca uti o ns t o a v oi d fat heri n g c hil dre n ( wit h at least 9 9 % 
certai nt y) fr o m scree ni n g t hr o u g h safet y f oll o w- u p.  Per mitte d met h o ds t hat are at least 9 9 % effecti ve 
i n pre ve nti n g pre g na nc y s h o ul d be c o m m u nicate d t o t he s u bject a n d t heir u n dersta n di n g c o nfir me d. 
Ke y E xcl usi o n Criteri a:  
All s u bj ects  
•  L ac k of rec o ver y fr o m a ll t o xicities fr o m pre vi o us t hera p y (e xce pt r u x oliti ni b) t o Gra de 1 or better. 
•  Pre vi o us treat me nt wit h itaciti ni b or J A K 1 i n hi bit ors (J A K 1/J A K 2 i n hi bit or r u x oliti ni b is per mitte d). 
•  I na bilit y t o s wall o w f o o d or a n y c o n diti o n of t he u p per gastr oi ntesti nal tract t hat precl u des 
a d mi nistrati o n of oral me dicati o ns. 
•  U n willi n g ness t o be tra nsf use d wit h bl o o d c o m p o ne nts. 
•  Rece nt hist or y of i na de q uate b o ne marr o w reser ve as de m o nstrate d b y t he f oll o wi n g:  
-  Platelet c o u nt < 5 0 × 1 0 9/ L i n t he 4 wee ks bef ore scree ni n g or platelet tra nsf usi o n wit hi n 8 wee ks 
bef ore scree ni n g.  
-  A bs ol ute ne utr o p hil c o u nt le vels < 0. 5 × 1 0 9/ L i n t he 4 wee ks bef ore scree ni n g. 
-  Peri p heral bl o o d blast c o u nt of > 1 0 % at t he scree ni n g or baseli ne he mat ol o g y assess me nts.  

I nc yte C or p orati o n 
P a ge 6 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
•  I na de q uate li ver f u ncti o n at scree ni n g a n d baseli ne visits as  de m o nstrate d b y t he f oll o wi n g:  
-  Direct bilir u bi n ≥ 2. 0 × t he u p per li mit of la b orat or y n or mal ( U L N).  ( N O T E:  direct bilir u bi n ma y be 
ass u me d t o be wit hi n li mits if t otal bilir u bi n is ≤ 2. 0 × U L N).  
-  Ala ni ne a mi n otra nsferase  or as partate a mi n otra nsferase > 2. 5 × U L N. 
•  I na de q uate re nal f u ncti o n at scree ni n g a n d baseli ne visits as de m o nstrate d b y creati ni ne cleara nce 
< 4 0 m L/ mi n meas ure d or calc ulate d b y C oc kr oft - Ga ult e q uati o n, or gl o mer ular filtrati o n rate 
< 4 0 m L/ mi n/ 1. 7 3 m 2 as calc ulate d usi n g t he M o dificati o n of Diet i n Re nal Disease f or m ula. 
•  Acti ve bacterial, f u n gal, parasitic, or viral i nfecti o n t hat re q uires t hera p y.  S u bjects wit h ac ute 
i nfecti o ns re q uiri n g treat me nt s h o ul d dela y scree ni n g/e nr oll me nt u ntil t he c o urse of t hera p y has bee n 
c o m plete d a n d t he e ve nt is c o nsi dere d res ol ve d.  Pr o p h ylactic a nti bi otics will be per mitte d.  
•  E vi de nce of he patitis B vir us ( H B V) or he patitis C vir us ( H C V) i nfecti o n or ris k of reacti vati o n:  H B V 
D N A a n d H C V R N A m ust be u n detecta ble.  S u bjects ca n n ot be p ositi ve f or he patitis B s urface a nti ge n 
or a nti – he patitis B c ore a nti b o dies.  S u bjects w h o ha ve p ositi ve a nti- H Bs as t he o nl y e vi de nce of pri or 
e x p os ure ma y partici pate i n t he st u d y pr o vi de d t hat t here is b ot h 1) n o k n o w n hist or y of H B V i nfecti o n 
a n d 2) verifie d recei pt of he patitis B vacci ne.  
•  K n o w n h u ma n i m m u n o deficie nc y vir us i nfecti o n. 
•  Cli nicall y si g nifica nt or u nc o ntr olle d car diac disease , i ncl u di n g u nsta ble a n gi na; ac ute m y ocar dial 
i nfarcti o n wit hi n 6 m o nt hs of Da y 1 of st u d y dr u g a d mi nistrati o n; Ne w Y or k Heart Ass ociati o n 
Class  III or I V c o n gesti ve heart fail ure; a n d arr h yt h mia re q uiri n g t hera p y u nless a p pr o ve d b y me dical 
m o nit or/s p o ns or. 
•  Acti ve i n vasi ve mali g na nc y o ver t he pre vi o us 2 years e xce pt treate d basal or s q ua m o us carci n o mas of 
t he s ki n, c o m pletel y resecte d i ntrae pit helial carci n o ma of t he cer vi x, a n d c o m pletel y resecte d pa pillar y 
t h yr oi d a n d f ollic ular t h yr oi d ca ncers.  S u bjects wit h mali g na ncies wit h i n d ole nt be ha vi or s uc h as 
pr ostate ca ncer treate d wit h ra diati o n or s ur ger y ma y be  e nr olle d as l o n g as t he y ha ve a reas o na ble 
e x pectati o n t o ha ve bee n c ure d wit h t he treat me nt m o dalit y recei ve d.  
•  S ple nic irra diati o n wit hi n 6 m o nt hs bef ore recei vi n g t he first d ose of itaciti ni b . 
•  Use of a n y pr o hi bite d c o nc o mita nt me dicati o ns. 
•  Acti ve alc o h o l or dr u g a d dicti o n t hat w o ul d i nterfere wit h t heir a bilit y t o c o m pl y wit h t he st u d y 
re q uire me nts. 
•  Use of a n y p ote nt/str o n g c yt oc hr o me P 4 5 0 3 A 4 i n hi bit ors wit hi n 1 4 da ys or 5 half- li ves ( w hic he ver is 
l o n ger) bef ore t he first d ose of itaciti ni b or a ntici pat e d d uri n g t he st u d y. 
•  Use of c o nc o mita nt treat me nt of fl uc o naz ole at a d ose >  2 0 0 m g (f or r u x oliti ni b s u bj ects treate d i n 
C o h ort A o nl y) . 
•  I na de q uate rec o ver y fr o m t o xicit y a n d/ or c o m plicati o ns fr o m a maj or s ur ger y bef ore starti n g t hera p y. 
•  C urre ntl y breastfe e di n g or pre g na nt. 
•  I na bilit y t o c o m pre he n d or u n willi n g t o si g n t he i nf or me d c o nse nt f or m. 
•  A n y c o n diti o n t hat w o ul d, i n t he i n vesti gat or's j u d g me nt, i nterfere wit h f ull partici pati o n i n t he st u d y, 
i ncl u di n g a d mi nistrati o n of st u d y dr u g a n d atte n di n g re q uire d st u d y visits; p ose a si g nifica nt ris k t o t he 
s u bj ect; or i nterfere wit h i nter pretati o n of st u d y data. 
It aciti ni b/ St u d y Dr u g, D os a ge, a n d M o de of A d mi nistr ati o n:  
Itaciti ni b is f or m ulate d as 1 0 0 m g s ustai ne d-release ta blet.  Itaciti ni b will be a d mi niste re d orall y Q D  i n 
t he m or ni n g o n a n o ut patie nt basis as f oll o ws: 
•  C o h ort A o nl y :  2 0 0 m g Q D, wit h o ut re gar d t o f o o d, f or t he c o m bi nati o n treat me nt wit h r u x oliti ni b.  
•  C o h ort B o nl y :  6 0 0 m g Q D, wit h o ut re gar d t o f o o d, f or t he m o n ot hera p y treat me nt. 

I nc yte C or p orati o n 
P a ge 7 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
Ref ere nce  T her a p y, D os a ge , a n d M o de of A d mi nistr ati o n:   
•  C o h ort A o nl y :  R u x oliti ni b will be a d mi nistere d orall y, t wice dail y  ( BI D), a p pr o xi matel y 1 2 h o urs 
a part usi n g t he sta ble d ose of less t ha n 2 0 m g dail y esta blis he d bef ore e nteri n g t he st u d y. 
•  C o h ort B o nl y :  N o t a p plica ble. 
St u d y Sc he d ule/ P r oce d ures:  
S u bj ects will ha ve a re g ularl y sc he d ule d st u d y visit at scree ni n g, baseli ne, Da y 1, Wee k 2, Wee k 4, 
Wee k  8, Wee k 1 2, Wee k 1 6, Wee k 2 0, a n d Wee k 2 4 a n d e ver y 1 2 wee ks t hereafter if c o nti n ui n g o n 
treat me nt, w here assess me nts, i ncl u di n g bl o o d sa m ples a n d s plee n meas ure me nts, will be o btai ne d.  All 
la b orat or y para meters (ser ol o g y, li pi d pr ofile, uri nal ysis, bl o o d c he mistr y, he mat ol o g y, a n d c oa g ulati o n) 
will be assesse d usi n g l ocal la b orat ories.  Bl o o d 
 P K sa m ples will be c ollecte d a n d 
a nal yze d b y t he s p o ns or or s p o ns or' s desi g nee.  
A d diti o nal la b orat or y assess me nts ma y be perf or me d at i n vesti gat or 's discreti o n, i ncl u di n g f oll o wi n g 
c ha n ges i n d ose, or if la b orat or y para meters are at Gra de 3 or Gra de 4 le vels base d o n t he C T C A E v 4. 0 3.  
S u bj ects will ha ve a n M RI of t he u p per a n d l o wer a b d o me n a n d pel vis t o deter mi ne t he s plee n v ol u me at 
baseli ne, at Wee k 1 2 a n d Wee k 2 4, a n d e ver y 1 2 wee ks t hereafter.   C o m p ute d t o m o gra p h y sca n will be 
s u bstit ute d f or s u bj ects w h o are n ot ca n di dates f or M RI or w he n M RI is n ot rea dil y a vaila ble.  Patie nt 
Gl o bal I m pressi o n of C ha n ge q uesti o n naire will be c o m plete d at eac h st u d y visit fr o m Wee k 4.  
Deter mi nati o n of s plee n le n gt h bel o w t he left c ostal mar gi n will be meas ure d b y p al pati o n at eac h st u d y 
visit usi n g a fle xi ble r uler.  
S u bj ects will c o m plete a n electr o nic s y m pt o m diar y ( M F S A F v 2. 0) dail y fr o m baseli ne t hr o u g h t he 
Wee k  2 4 visit (t otal of 2 5 wee ks).  
S u bj ects will c o m plete t he M P N -S A F at baseli ne; at Wee ks 1 2 a n d 2 4; a n d e ver y 1 2 wee ks t hereafter.  
Esti m ate d D ur ati o n of P artici p ati o n:  
Scree ni n g :  U p t o 2 1 da ys.  
B aseli ne :  7 da ys bef ore first d ose of itaciti ni b.  
Tre at me nt :  Be gi ns wit h t he first d ose of itaciti ni b ( Da y 1).  Treat me nt will c o nti n ue as l o n g as t he 
re gi me n is t olerate d a n d t he s u bject d oes n ot meet disc o nti n uati o n criteria.  
S af et y f oll o w -u p :  3 0 da ys t o 3 5 da ys after t he last d ose of me dicati o n is ta ke n.  
It is esti mate d t hat a n i n di vi d ual s u bject will partici pate f or a p pr o xi matel y 3 2 wee ks . 
Esti m ate d  N u m ber of S u bjects:   
A p pr o xi matel y 2 1 s u bjects will be i ncl u de d i n eac h d ose c o h ort f or a t otal of 4 2 s u bj ects.  A p pr o xi matel y 
2 0 cli nical sites will be use d.  
P ri nci p al C o or di n ati n g I n vesti g at or:   T B D  
St atistic al Met h o ds:  
T he pri mar y e n d p oi nt of c ha n ge a n d perce nta ge c ha n ge of S V R  (as meas ure d b y M RI or C T ) fr o m 
baseli ne at Wee k 2 4  will be s u m marize d b y c o h ort.  Wit hi n eac h c o h ort, t he si g n test will be use d t o 
e val uate me dia n perce nta ge of S V R a n d a 9 0 % c o nfi de nce i nter val f or t he me dia n perce nta ge S V R will  
be calc ulate d usi n g t he e xact bi n o mi al c o nfi de nce i nter val met h o d .  If t he perce nta ge of S V R at Wee k 2 4  
is n or mall y distri b ute d wit h mea n 1 1. 4 a n d sta n dar d de viati o n 1 4. 5, t he test has 8 5 % p o wer t o i n dicate 
a d diti o nal de vel o p me nt is warra nte d wit h a sa m ple size of 2 1 s u bjects per c o h ort.  T he perce nta ge of  S V R  
will be s u m marize d descri pti vel y at Wee k 1 2 b y c o h ort. 
Safet y data, i ncl u di n g la b orat or y val ues, A E s, a n d vital si g ns, will be s u m marize d. A d verse e ve nts  of 
s pecial i nterest i ncl u de Gra de 4 t hr o m b oc yt o pe nia, Gra de 2 or hi g her a ne mia, a n d Gra de 2 or hi g her 
he m orr ha gic e ve n ts, as meas ure d b y C T C A E v 4. 0 3. 
Sec o n dar y efficac y e n d p oi nts f or perce nt a ge c ha n ge fr o m baseli ne i n 7 - da y M F S A F T S S a n d M P N -S A F 
T S S will be s u m marize d at Wee k 1 2 a n d Wee k 2 4 b y c o h ort , a n d 9 0 % c o nfi de nce i nter vals f or t he 

I nc yte C or p orati o n 
P a ge 9 of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
T A B L E O F C O N T E N T S  
S Y N O P SI S  ...................................................................................................................................... 3 
LI S T O F A B B R E VI A TI O N S ........................................................................................................ 1 6  
1.  
I N T R O D U C TI O N ...................................................................................................... 1 9 
1. 1.  
Bac k gr o u n d a n d O v er vie w o n M yel ofi br osis ............................................................. 1 9  
1. 2.  
R ole of J A K Pat h wa y i n M yel ofi br osis ...................................................................... 2 0  
1. 3.  
Pr o d uct I nf or mati o n a n d O ver vie w of Itaciti ni b  ........................................................ 2 1 
1. 3. 1.  
P har mac ol o g y  ............................................................................................................. 2 1 
1. 3. 2.  
N o ncli nical Dr u g Met a b olis m a n d P har mac o ki netics  ................................................ 2 2 
1. 3. 3.  
Itaciti ni b Cli nical Safet y S u m mar y ............................................................................ 2 2 
1. 3. 3. 1.  
Cli nical St u dies i n Patie nts  ......................................................................................... 2 2 
1. 3. 4.  
R u x oliti ni b Cli nical Safet y S u m mar y  ......................................................................... 2 3 
1. 3. 4. 1.  
Cli nical Safet y D ata  .................................................................................................... 2 3 
1. 3. 4. 2.  
R u x oliti ni b I n dicati o ns ............................................................................................... 2 4  
1. 4.  
St u d y R ati o nale  ........................................................................................................... 2 4 
1. 5.  
P ote ntial Ris ks a n d Be nefits of t he Treat me nt Re gi me n  ............................................ 2 5 
1. 5. 1.  
Ris ks Relate d t o Itaciti ni b  ........................................................................................... 2 5 
1. 5. 2.  
Ris ks Relate d t o R u x oliti ni b  ....................................................................................... 2 6 
1. 5. 3.  
Ris ks f or t he C o m bi nati o n of It aciti ni b a n d R u x oliti ni b ............................................ 2 6 
1. 5. 4.  
P ote ntial Be nefits of It aciti ni b a n d R u x oliti ni b  .......................................................... 2 6 
1. 5. 4. 1.  
Itaciti ni b P ote ntial Be nefits ........................................................................................ 2 6 
1. 5. 4. 2.  
R u x oliti ni b P ote ntial Be nefit  ...................................................................................... 2 6 
2.  
S T U D Y O BJ E C TI V E S A N D  E N D P OI N T S  .............................................................. 2 7 
3.  
S U BJ E C T E LI GI BI LI T Y  ........................................................................................... 2 8 
3. 1.  
S u bject I n cl usi o n Criteria  ........................................................................................... 2 8 
3. 2.  
S u bject E x cl usi o n Criteria  .......................................................................................... 2 9 
3. 3.  
S u bjects W h o Fail t o Meet Scree ni n g Criteri a  ........................................................... 3 1 
4.  
I N V E S TI G A TI O N A L P L A N ..................................................................................... 3 2 
4. 1.  
O verall St u d y Desi g n  .................................................................................................. 3 2 
4. 2.  
Meas ures T a ke n t o A v oi d Bias ................................................................................... 3 3  
4. 3.  
N u m ber of S u bjects .................................................................................................... 3 3  
4. 4.  
D urati o n of Tr eat me nt a n d S u bject Partici pati o n  ....................................................... 3 3 

I nc yte C or p orati o n 
P a ge 1 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
4. 5.  
O verall St u d y D urati o n  ............................................................................................... 3 3 
4. 6.  
St u d y Ter mi nati o n  ...................................................................................................... 3 3 
5.  
T R E A T M E N T  ............................................................................................................ 3 4 
5. 1.  
Treat me nt Assi g n me nt  ................................................................................................ 3 4 
5. 1. 1.  
S u bject N u m beri n g a n d Treat me nt Assi g n me nt ......................................................... 3 4  
5. 1. 2.  
Ra n d o mizati o n a n d Bli n di n g ...................................................................................... 3 4  
5. 2.  
St u d y Dr u g  .................................................................................................................. 3 4 
5. 2. 1.  
Itaciti ni b ...................................................................................................................... 3 4 
5. 2. 1. 1.  
Descri pti o n a n d A d mi nistrati o n  .................................................................................. 3 4 
5. 2. 1. 2.  
S u p pl y, Pac ka gi n g, a n d La b eli n g ............................................................................... 3 5  
5. 2. 2.  
R u x oliti ni b  .................................................................................................................. 3 5 
5. 2. 2. 1.  
Descri pti o n a n d A d mi nistra ti o n .................................................................................. 3 5 
5. 2. 2. 2.  
S u p pl y, Pac ka gi n g, a n d La b elli n g .............................................................................. 3 5  
5. 2. 3.  
St ora ge  ........................................................................................................................ 3 5 
5. 3.  
Treat me nt C o m plia nce  ................................................................................................ 3 6 
5. 4.  
Treat me nt M o dificati o ns:  I ncreases, Decreases, a n d I nterr u pti o ns ........................... 3 6  
5. 4. 1.  
D ose I ncreas es f or I n a de q uate Efficac y  ..................................................................... 3 6 
5. 4. 2.  
D ose M o dificati o n f or T o xici t y .................................................................................. 3 6 
5. 4. 2. 1.  
La b orat or y Fi n di n gs T h at Re q uire D ose M o dificati o n .............................................. 3 6  
5. 4. 2. 2.  
Per mitte d D ose Le vels  ................................................................................................ 3 7 
5. 4. 2. 3.  
D ose A dj ust me nt G ui deli nes a n d Ma na gi n g T o xicit y ................................................ 3 7  
5. 4. 2. 4.  
G ui deli nes f or D ose R estart or Re- escalati o n  ............................................................. 3 9 
5. 4. 3.  
I nterr u pti o n of R u x oliti ni b ( C o h ort A O nl y) .............................................................. 3 9 
5. 5.  
Wit h dra wal of S u bjects Fr o m St u d y Treat me nt  ......................................................... 3 9 
5. 5. 1.  
Wit h dra wal Criteria  .................................................................................................... 3 9 
5. 5. 2.  
Wit h dra wal Pr oce d ures  ............................................................................................... 4 0 
5. 6.  
C o nc o mita nt Me dicati o ns ........................................................................................... 4 1  
5. 6. 1.  
Per mitte d Me dicati o ns  ................................................................................................ 4 1 
5. 6. 2.  
Restricte d Me dicati o ns  ............................................................................................... 4 1 
5. 6. 3.  
Pr o hi bite d Me dicati o ns ............................................................................................... 4 2  
6.  
S T U D Y A S S E S S M E N T S  .......................................................................................... 4 2 
6. 1.  
Scree ni n g  .................................................................................................................... 4 8 
6. 2.  
Baseli ne  ....................................................................................................................... 4 9 

I nc yte C or p orati o n 
P a ge 1 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
6. 3.  
Treat me nt  .................................................................................................................... 5 0 
6. 4.  
E n d of Treat me nt ........................................................................................................ 5 0  
6. 5.  
F oll o w- U p  ................................................................................................................... 5 1 
6. 5. 1.  
Safet y F oll o w -U p  ........................................................................................................ 5 1 
6. 6.  
E n d of St u d y ............................................................................................................... 5 1  
6. 7.  
U nsc he d ule d Visits ..................................................................................................... 5 1  
7.  
C O N D U C T O F 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  ........................... 5 1 
7. 1.  
A d mi nistrati o n of I nf or m e d C o nse nt F or m ................................................................ 5 1  
7. 2.  
I nteracti ve Res p o nse Tec h n ol o g y Pr oce d ure .............................................................. 5 1 
7. 3.  
De m o gra p h y a n d Me dical Hist or y .............................................................................. 5 2  
7. 4.  
Pri or a n d C o nc o mita nt Me dicati o ns a n d Pr oce d ures .................................................. 5 2  
7. 5.  
Safet y Assess me nts  ..................................................................................................... 5 2 
7. 5. 1.  
Re vie w I ncl usi o n a n d E x cl usi o n Criteria  ................................................................... 5 2 
7. 5. 2.  
A d verse E v e nts  ........................................................................................................... 5 2 
7. 5. 3.  
P h ysical E x a mi nati o ns  ................................................................................................ 5 2 
7. 5. 3. 1.  
C o m pre he nsi ve P h ysical E x a mi nati o n  ....................................................................... 5 2 
7. 5. 3. 2.  
Tar gete d P h ysical E x a mi nati o ns  ................................................................................. 5 3 
7. 5. 4.  
Vital Si g ns  .................................................................................................................. 5 3 
7. 5. 5.  
Electr ocar di o gra ms  ..................................................................................................... 5 3 
7. 5. 6.  
La b orat or y Ass ess me nts  ............................................................................................. 5 3 
7. 5. 6. 1.  
Pre g n a nc y T esti n g  ...................................................................................................... 5 3 
7. 6.  
Efficac y Assess me nts  ................................................................................................. 5 4 
7. 6. 1.  
B o ne Marr o w Bi o ps y .................................................................................................. 5 4  
7. 6. 2.  
S plee n a n d Li v er Pal pati o n  ......................................................................................... 5 4 
7. 6. 3.  
I ma gi n g ....................................................................................................................... 5 4 
7. 6. 4.  
S y m pt o m Diar y  ........................................................................................................... 5 5 
7. 7.  
Perf or ma nce a n d Q ualit y - of-Life Assess me nts  .......................................................... 5 5 
7. 7. 1.  
Easter n C o o per ati ve O nc ol o g y Gr o u p Perf or ma n ce Stat us ........................................ 5 5  
7. 7. 2.  
Patie nt Gl o bal I m pr essi o n of C ha n ge ......................................................................... 5 5  
7. 7. 3.  
M yel o pr olif erati ve Ne o plas ms S y m pt o m Assess m e nt F or m  ..................................... 5 5 
7. 8.  
I W G-M R T Assess me nt  .............................................................................................. 5 5 
7. 9.  
P har mac o ki netic Assess me nts  .................................................................................... 5 6 
7. 9. 1.  
Bl o o d Sa m ple C ollecti o n  ............................................................................................ 5 6 

I nc yte C or p orati o n 
P a ge 1 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
7. 9. 2.  
Bi oa nal ytical M et h o d ol o g y a n d A nal ysis ................................................................... 5 6  
 
5 6  
 
5 6  
 
5 6  
 
5 7  
7. 1 1.  
Ot her St u d y Pr oce d ur es .............................................................................................. 5 7  
7. 1 1. 1.  
A d mi nistrati o n of St u d y Treat me nt  ............................................................................ 5 7 
7. 1 1. 2.  
Dis pe nsati o n of St u d y Tr eat me nt ............................................................................... 5 7  
7. 1 1. 3.  
Assess me nt of C o m plia nce Wit h St u d y Dr u g  ............................................................ 5 7 
7. 1 1. 4.  
Distri b uti o n of S u bject Re mi n der Car ds ..................................................................... 5 7  
8.  
S A F E T Y M O NI T O RI N G A N D R E P O R TI N G  ......................................................... 5 8 
8. 1.  
A d verse E v e nts  ........................................................................................................... 5 8 
8. 1. 1.  
Defi niti o ns  .................................................................................................................. 5 8 
8. 1. 2.  
Re p orti n g .................................................................................................................... 5 8  
8. 2.  
La b orat or y T est A b n or m alities  ................................................................................... 5 9 
8. 3.  
Seri o us A d verse E v e nts .............................................................................................. 6 0  
8. 3. 1.  
Defi niti o ns  .................................................................................................................. 6 0 
8. 3. 2.  
Re p orti n g .................................................................................................................... 6 0  
8. 4.  
E mer ge nc y U n bli n di n g of Treat me nt Assi g n me nt ..................................................... 6 1  
8. 5.  
Pre g n a nc y  ................................................................................................................... 6 1 
8. 6.  
War ni n gs a n d Pr eca uti o ns .......................................................................................... 6 2  
8. 7.  
Data M o nit ori n g C o m mittee  ....................................................................................... 6 2 
8. 8.  
A d verse E v e nts of S peci al I nt erest  ............................................................................. 6 2 
8. 9.  
Pr o d uct C o m plai nts .................................................................................................... 6 2  
9.  
S T A TI S TI C S  .............................................................................................................. 6 3 
9. 1.  
St u d y P o p ulati o ns ....................................................................................................... 6 3  
9. 2.  
Selecti o n of Sa m ple Size  ............................................................................................ 6 3 
9. 3.  
Le v el of Si g nifi ca nce  .................................................................................................. 6 3 
9. 4.  
Statistical A nal yses  ..................................................................................................... 6 3 
9. 4. 1.  
Efficac y A nal yses  ....................................................................................................... 6 3 
9. 4. 1. 1.  
Pri mar y Efficac y A nal ys es  ......................................................................................... 6 3 
9. 4. 1. 2.  
Sec o n dar y Efficac y A nal ys es  ..................................................................................... 6 4 
9. 4. 2.  
Safet y A nal yses  .......................................................................................................... 6 4 

I nc yte C or p orati o n 
P a ge 1 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
9. 4. 2. 1.  
A d verse E v e nts  ........................................................................................................... 6 5 
9. 4. 2. 2.  
Cli nical La b or at or y Tests  ........................................................................................... 6 5 
9. 4. 2. 3.  
Vital Si g n s .................................................................................................................. 6 5 
9. 4. 2. 4.  
Electr ocar di o gra ms  ..................................................................................................... 6 5 
9. 4. 2. 5.  
A d verse E v e nts of S peci al I nt erest  ............................................................................. 6 6 
9. 4. 3.  
P har mac o ki netic A n al ys es  .......................................................................................... 6 6 
 
6 6  
9. 5.  
A nal ys es f or t he Data M o nit ori n g C o m mittee  ............................................................ 6 6 
9. 6.  
I nteri m A nal ysis .......................................................................................................... 6 6 
1 0.  
E T HI C A L C O N SI D E R A TI O N S A N D A D MI NI S T R A TI V E 
P R O C E D U R E S  .......................................................................................................... 6 7 
1 0. 1.  
I n v esti gat or Res p o nsi bilities ....................................................................................... 6 7 
1 0. 2.  
Acc o u nta bilit y, Ha n dli n g, a n d Dis p osal of St u d y Dr u g ............................................. 6 8  
1 0. 3.  
Data Ma na ge me nt  ....................................................................................................... 6 9 
1 0. 3. 1.  
Data C ollecti o n  ........................................................................................................... 6 9 
1 0. 3. 2.  
Data Ma na ge me nt  ....................................................................................................... 6 9 
1 0. 4.  
St u d y M o nit ori n g ........................................................................................................ 6 9  
1 0. 5.  
Pr ot oc ol A d here n ce .................................................................................................... 7 0  
1 0. 6.  
Data Pri vac y a n d C o nfi de ntialit y of St u d y R ec or ds ................................................... 7 0  
1 0. 7.  
Fi na ncial Discl os ur e  ................................................................................................... 7 1 
1 0. 8.  
Q ualit y C o ntr ol a n d Q u alit y Ass ura n ce  ...................................................................... 7 1 
1 0. 8. 1.  
S p o ns or A u dits............................................................................................................ 7 1  
1 0. 8. 2.  
I ns p ecti o n b y Re g ulat or y A ut h orities ......................................................................... 7 1 
1 0. 9.  
Data Ha n dli n g a n d Rec or d kee pi n g ............................................................................. 7 2  
1 0. 9. 1.  
I ns p ecti o n of Rec or ds ................................................................................................. 7 2 
1 0. 9. 2.  
Rete nti o n of Rec or ds .................................................................................................. 7 2  
1 0. 9. 3.  
C o nfi de ntialit y  ............................................................................................................ 7 2 
1 0. 1 0.  
P u blicati o n P olic y  ....................................................................................................... 7 3 
1 1.  
R E F E R E N C E S  ........................................................................................................... 7 4 
A P P E N DI X  A. R E VI S E D W H O 2 0 1 6 C RI T E RI A F O R M Y E L O FI B R O SI S  .......................... 7 6 
A P P E N DI X  B.  I N T E R N A TI O N A L W O R KI NG G R O U P – M Y E L O P R O LI F E R A TI V E 
N E O P L A S M S R E S E A R C H A N D T R E A T M E N T C RI T E RI A  ................................ 7 8 

I nc yte C or p orati o n 
P a ge 1 4  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  C.  E A S T E R N C O O P E R A TI V E O N C O L O G Y G R O U P 
P E R F O R M A N C E S T A T U S  ....................................................................................... 8 0 
A P P E N DI X  D.  M O DI FI E D M Y E L O FI B R O S I S S Y M P T O M A S S E S S M E NT S F O R M 
V E R SI O N 2. 0  ............................................................................................................. 8 1 
A P P E N DI X  E.  M Y E L O P R O LI F E R A TI V E N E O P L A S M S S Y M P T O M 
A S S E S S M E N T F O R M  .............................................................................................. 8 2 
A P P E N DI X  F.  P A TI E N T G L O B A L I M P R E S SI O N O F C H A N G E  ......................................... 8 3 
A P P E N DI X  G.  I N F O R M A TI O N R E G A R DI N G E F F E C TI V E N E S S O F 
C O N T R A C E P TI V E M E T H O D S ............................................................................... 8 4  
A P P E N DI X  H.  C Y T O C H R O M E P 4 5 0 A N D P- G L Y C O P R O T EI N I N HI BI T O R S 
A N D C Y T O C H R O M E P 4 5 0 I N D U C E R S  ................................................................ 8 5 
 

I nc yte C or p orati o n 
P a ge 1 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
LI S T O F T A B L E S  
Ta ble  1: 
Ris k Cate g ories  ........................................................................................................... 2 0 
Ta ble  2: 
St u d y O bjecti ves a n d E n d p oi nts  ................................................................................. 2 7 
Ta ble  3: 
Per m itte d D ose Le vels b y C o h ort ............................................................................... 3 7 
Ta ble  4: 
D ose I nterr u pti o ns or Re d ucti o ns f or T o xicit y ........................................................... 3 8  
Ta ble  5: 
Sc he d ule of Assess me nts f or C o h ort A a n d B ( Scree ni n g T hr o u g h Wee k 1 2) .......... 4 3  
Ta ble  6: 
Sc he d ule of Assess me nts f or C o h ort A a n d B ( Wee k 1 6 T hr o u g h 
F oll o w- U p)  ................................................................................................................. 4 4 
Ta ble  7: 
Sc he d ule of La b orat or y Assess me nts f or C o h ort A a n d B ( Scree ni n g 
T hr o u g h Wee k 1 2) ...................................................................................................... 4 5  
Ta ble  8: 
Sc he d ule of La b orat or y Assess me nts f or C o h ort A a n d B ( Wee k 1 6 T hr o u g h 
F oll o w- U p)  ................................................................................................................. 4 6 
Ta ble  9: 
L ocal La b or at or y Tests:  Re q uire d A n al ytes  .............................................................. 4 7 
Ta ble  1 0: Sc he d ule of P har mac o ki netic Sa m pli n g f or C o h ort A (It aciti ni b a n d 
R u x oliti ni b) ................................................................................................................. 4 8  
Ta ble  1 1: Sc he d ule of P har mac o ki netic Sa m pli n g f or C o h ort B (Itaciti ni b Al o ne) ................... 4 8  
Ta ble  1 2: Criteria f or Cli nicall y N ota ble Vital Si g n A b n or m alities  ........................................... 6 5 
Ta ble  1 3: W H O Pre – Pri mar y M yel ofi br osis Criteria  ................................................................. 7 6 
Ta bl e 1 4:  W H O O vert Pri mar y M yel ofi br osis Criteria  .............................................................. 7 6 
Ta ble  1 5: M yel ofi br osis Gra di n g  ................................................................................................ 7 7 
 
LI S T O F FI G U R E S  
Fi g ure  1: 
St u d y Desi g n  ............................................................................................................... 3 2 
 

I nc yte C or p orati o n 
P a ge 1 6  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
LI S T O F A B B R E VI A TI O N S 
T he f oll o wi n g a b bre vi ati o ns a n d s pecial ter ms are use d i n t his cli nical st u d y Pr ot oc ol. 
A b bre vi ati o n  
Defi niti o n  
A E  
ad verse  eve nt  
A L T  
ala ni ne a mi n otra nsferase 
A N C  
abs ol ute  ne utr o p hil c o u nt  
A S T  
as partate a mi n otra nsferase 
A U C  
area u n der t he c ur ve 
B A T  
best  a vaila ble t hera p y 
BI D  
twice  dail y  
 
 
C F R  
C o de of Fe deral Re g ulati o ns 
CI  
cli nical i m pr o ve me nt  
C ma x  
ma xi m u m  plas ma c o nce ntrati o n  
C M L  
c hr o nic m yel oi d le u ke mia 
C R  
c o m plete re missi o n 
C T  
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 T er mi n ol o g y Criteria f o r A d verse E ve nts 
C Y P  
c yt oc hr o me P 4 5 0 
DI P S S  
D y na mic I nter nati o nal Pr o g n ostic Sc ori n g S yste m  
D N A  
de o x yri b o n ucleic aci d 
E C G  
electr 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 L N  
E ur o pea n Le u ke mia Net 
E O T  
e n d of treat me nt 
E T  
esse ntial thr o m b oc yt h e mia 
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 
F S H  
f ollicle-sti m ulati n g h or m o ne 
G C P  
G o o d Cli nical Practice  
 
 
H B V  
he patitis  B vir us  
H C V  
he patitis  C vir us  
H D L  
hi g h - de nsit y li p o pr otei n 
HI P A A 
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act  of 1 9 9 6 

I nc yte C or p orati o n 
P a ge 1 7  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
A b bre vi ati o n  
Defi niti o n  
H U  
h y dr o x y urea 
I B 
I n vesti gat or's Br oc h ure 
I C F 
inf or me d  co nse nt f or m  
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I E C 
in de pe n de nt et hics co m mittee  
 
 
I N 
I n vesti gat or N otificati o n 
I NR 
i nter nati o nal n or malize d rati o 
I P S S 
I nter nati o nal Pr o g n ostic Sc ori n g S yste m 
I R B 
i nstit uti o nal re vie w b oar d  
I W G-M R T  
I nter nati o nal W or ki n g Gr o u p-M yel o pr oliferati ve Ne o plas ms Researc h a n d 
Treat me nt  
I X R S 
interacti ve  v oice/ we b res p o nse s yste m  
J A K 
Ja n us ki nase 
L D L  
l o w- de nsit y li p o pr otei n 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M F  
m yel ofi br osis 
M F S A F v 2. 0  
M yel ofi br osis S y m pt o m Assess me nt F or m versi o n 2. 0  
M P N  
m yel o pr oliferati ve  ne o plas m 
M P N -S A F  
M yel o p r oliferati ve Ne o plas m– S y m pt o m Assess me nt F or m  
M RI  
ma g netic res o na nce i ma gi n g  
N A  
n ot a p plica ble 
N CI  
Nati o nal Ca ncer I nstit ute  
N S AI D  
n o nster oi dal a nti-i nfla m mat or y dr u g 
 
  
P E T -M F  
p ost –esse ntial t hr o m b oc yt he mia m yel ofi br osis 
P GI C  
P atient G l o bal Im pressi o n of C ha n ge  
P K  
p har mac o ki netic  
P M F  
pri mar y  m yel ofi br osis 
P P V -M F  
p ost – p ol yc yt he mia vera m yel ofi br osis 
P R  
partial  res p o nse 
P R B C  
pac ke d re d bl o o d cell 
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  
p ol yc yt he mia  vera  
Q D  
o nce dail y  

I nc yte C or p orati o n 
P a ge 1 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
A b bre vi ati o n  
Defi niti o n  
R A  
r he u mat oi d art hritis 
R B C  
re d bl o o d cell 
R N A  
ri b o n ucleic aci d 
S A E  
seri o us a d verse eve nt  
S A P  
Statistical A nal ysis Pla n  
S T A T  
si g nal tra ns d ucer a n d acti vat or of tra nscri pti o n 
S U S A R  
s us pecte d u ne x pecte d seri o us a d verse reacti o n  
S V R  
s plee n v ol u me re d ucti o n 
T E A E  
treat me nt-e mer ge nt  a d verse e ve nt 
 
 
 
 
T P O  
t hr o m b o p oieti n 
T S S  
T otal S y m pt o m Sc ore 
T Y K 2 
t yr osi ne ki nase 2  
U L N  
u p per li mit of n or mal 
W B C  
w hite  bl o o d cells 

I nc yte C or p orati o n 
P a ge 1 9  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
1.  
I N T R O D U C TI O N 
Itaciti ni b (I N C B 0 3 9 1 1 0) re pres e nts a n o vel, p ote nt, a n d selecti ve i n hi bit or of t he J A Ks wit h 
selecti vit y f or J A K 1 wit h l o w i n vitr o affi nit y f or J A K 2 a n d is pr o p ose d f or i n vesti gati o n a n d 
de vel o p me nt f or t he tr eat me nt of M F .  F or a t h or o u g h disc ussi o n of t he p h ar mac ol o g y of 
itaciti ni b, refer t o t he I n v esti gat or's Br o c h ure (I B). 
R u x oliti ni b, a p ote nt a n d selecti ve i n hi bit or of t he J A K fa mil y of pr otei n t yr osi ne ki nases, J A K 1 
a n d J A K 2, is a p pr o ve d i n m ulti ple j uris dicti o ns f or M F, wit h variati o ns o n t he s pecific i n dicati o n 
la n g u a ge, a n d is c urre ntl y i n de v el o p me nt f or t he treat me nt of M P Ns , he m at ol o gic mali g na n cies, 
a n d s oli d t u m ors.  F or a t h or o u g h disc ussi o n of t h e p har mac ol o g y of r u x oliti ni b (I N C B 0 1 8 4 2 4), 
refer t o t he r u x oliti ni b prescri bi n g i nf or mati o n. 
1. 1.  
B ac k gr o u n d  a n d O ver vie w o n M yel ofi br osis  
T he classic M P Ns i ncl u d e C M L, P V , E T, a n d P M F.  M yel ofi br osis ca n prese nt as a de n o v o  
dis or der ( P M F) or e v ol ve sec o n daril y fr o m pre vi o us P V or E T ( P P V -M F or P E T -M F).  
Re gar dless of w h et her M F is a pri mar y or sec o n d ar y dis or d er, it is c haracterize d b y a cl o nal ste m 
cell pr olifer ati o n ass ociat e d wit h pr o d ucti o n of ele vate d ser u m le v els of m ulti ple i nfla m mat or y 
a n d pr oa n gi o ge nic c yt o ki nes, a c haracteristic b o ne marr o w str o mal patter n t hat i ncl u des var yi n g 
de grees of c olla ge n fi br osis, oste oscler osis a n d a n gi o ge n esis , a n d a peri p heral bl o o d s mear 
s h o wi n g a l e u k oer yt hr o bl astic patter n wit h var yi n g de grees of circ ulati n g pr o ge nit or cells.  
Cli nicall y, M F is c haracterize d b y pr o gressi ve a ne mia , le u k o pe nia or le u k o c yt osis, 
t hr o m b oc yt o pe ni a or t hr o m b oc yt he mia, a n d m ulti or ga n e xtra me d ullar y he mat o p oiesis m ost 
pr o mi ne ntl y i n v ol vi n g t h e li ver a n d s plee n.  Patie nts ma y e x perie n ce de bilitati n g s y m pt o ms 
(Mesa  et al 2 0 0 7 , M esa  et al 2 0 1 3a), se q uel ae of massi ve s ple n o me gal y ( p ai n, li mitati o ns of 
m o ve me nt, earl y satiet y a n d s h ort ness of breat h, he patic o bstr ucti o n, a n d s ple nic i nfarcti o n), a 
h y per meta b olic state wit h cac h e xia, pr o gre ssi ve h e mat o p oietic fail ure, pr o gressi o n t o le u ke mia, 
a n d pre mat ur e deat h. 
T he me dia n a ge at dia g n osis of M F is a p pr o xi matel y 6 0 t o 6 5 years, a n d t h e i nci de nce of P M F 
has bee n esti mate d at 4 t o 6 cases per 1 0 0, 0 0 0 pe o ple i n t he U nite d States  (Stei n  et al 2 0 1 5).  
S ur vi val i n M F varies wit h t he prese nce or a bs e nce of s pecifi c ris k fact ors.  A nal ysis of ris k 
fact ors o ver t he past 2 0 years has res ulte d i n a n u m ber of pr o g n ostic sc ori n g s yste ms (f or a 
re vie w, r efer t o B os e  a n d Verst o vse k 2 0 1 5).  A pr o g n ostic sc ori n g s yste m base d o n a 
ti me- de pe n de nt ris k e v al uati o n has bee n de v el o pe d:  t he DI P S S f or P M F (Passa m o nti  et al 
2 0 1 0 ).  A ge of great er t h a n 6 5 years, prese n ce of c o nstit uti o nal s y m pt o ms, a ne mia ( he m o gl o bi n 
less t ha n 1 0 0 g/ L), l e u k o c yt osis ( W B C c o u nt > 2 5 × 1 09/ L), a n d a circ ulati n g blast perce nt a ge of 
1 % or hi g h er w ere assess e d f or t heir i m pact o n s ur vi val w he n a nal yze d as ti me- de pe n d e nt 
c o variates i n a m ulti variate C o x pr o p orti o nal hazar ds m o del.  T he a p pr o ac h s h o we d t hat 
ac q uisiti o n of a ne mia o v er ti me aff ects s ur vi val wit h a hazar d rati o r o u g hl y d o u ble t hat of ot her 
para meters, a n d t heref ore a ne mia was assi g n e d a s c ore of 2, w hile t he ot her 4 fact ors w ere 
assi g ne d s c ores of 1.  F o ur ris k cate g ories wit h n o n o verla p pi n g s ur vi val c ur ves ha ve b ee n 
descri be d  (Ta ble  1). 

I nc yte C or p orati o n 
P a ge 2 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
T a ble 1: 
Ris k C ate g ories  
T ot al Ris k Sc ore 
Ris k C a te g or y 
Me di a n S ur vi v al ( ye ars ) 
0 
L o w  
n ot reac he d 
1 or 2 
I nter me diate- 1 
1 4. 2 
3 or 4 
I nter me diate- 2 
4 
5 or 6 
Hi g h  
1. 4 
Alt h o u g h n ot i ncl u de d i n t he DI P S S, c yt o ge n etic a b n or malities i n P M F, J A K V 6 1 7 F allele 
b ur de n, m utati o ns i n e x o n 9 of t he ge ne e nc o di n g C A L R a n d m utati o ns i n t he ge ne e nc o di n g t he 
T P O  rece pt or ( M P L) ha v e bee n e x a mi ne d f or i m pact o n DI P S S sc ore, t hr o m b otic ris k, a n d 
o verall s ur vi val a n d t o get her ar e gr o u pe d as " dri ver" m utat i o ns.  T hese m ut ati o ns ofte n c oe xist 
wit h se veral s o matic m ut ati o n s:  ge nes f or t he e pi ge n etic re g ul at ors E Z H 2 (e n ha ncer of zeste 2 
p ol yc o m b r e pressi ve c o m ple x 2 s u b u nit), A S X L 1 (a d diti o nal se x c o m bs- li ke 1 tra nscri pti o nal 
re g ulat or, t he s plici n g ge ne S R S F 2 (seri ne/ar gi ni ne-ric h s plici n g fact or), a n d t he ge nes e n c o di n g 
the Kre bs c ycle e nz y mes is ocitrate de h y dr o ge nase 1 a n d 2 (I D H 1 a n d I D H 2).  T hese fact ors are 
c o m bi ne d i nt o t he ne west pr o g n ostic sc ori n g s yste m, t he ge n etics- bas e d pr o g n ostic sc ori n g 
s yste m, w hic h is c urre ntl y bei n g v ali date d.  
F or t he s u bset of p atie nts w h o are y o u n ger ( ge nerall y < 6 5 years), ot her wise healt h y, a n d ha v e a 
hist oc o m pati ble d o n or, all o ge n eic ste m cell tra ns pl a ntati o n ma y pr o vi de a c urati ve o pti o n, 
alt h o u g h wit h s u bsta ntial ( 1 0 %- 2 0 %) ris ks of m ortalit y ( Dee g  et al 2 0 0 3 ).  Dr u g t hera pi es use d 
i n M F, i ncl u di n g H U , b us ulfa n, 6- mer ca pt o p uri ne, a na greli de, t h ali d o mi de, le nali d o mi de, 
i nterfer o n, c ortic oster oi ds, a n d er yt hr o p oiesis-sti m ulati n g a ge nts or gr o wt h fact ors, ha v e n ot 
bee n s h o w n t o i m pr o ve s ur vi val.  S o me c a n i ncrease t he ris k of le u ke mic tra nsf or mati o n, ca n b e 
p o orl y t oler ate d, a n d all ha ve li mite d effecti ve ness i n i m pr o vi n g s ple n o me gal y a n d c o nstit uti o nal 
s y m pt o ms.  S ple nic irra diati o n is als o e m pl o ye d t o re d uce s y m pt o ms sec o n dar y t o s ple n o me gal y, 
b ut s y m pt o matic i m pr o ve me nt is varia ble a n d s h ort-li ve d; m ore o ver, tra nsi e nt a n d 
life-t hreat e ni n g p a nc yt o p e nia a n d a n a p pr o xi mate 2 0 % treat me nt-relate d m ortalit y ha v e bee n 
n ote d.  S ple nect o m y, p erf or me d i n a p pr o xi matel y 1 0 % of t he patie nt c o h ort re p orte d b y 
Cer va ntes  et al (2 0 0 9 ), is ass ociate d wit h si g nifica nt m or bi dit y a n d m ortalit y. 
1. 2.  
R ole of J A K P at h w a y i n M yel ofi br osis  
Wit hi n t he rece nt years , it was disc o vere d t hat a p pr o xi matel y 9 5 % of patie nts wit h P V a n d 
a p pr o xi matel y 5 0 % of p atie nts wit h P M F a n d E T ha ve a s o matic gai n- of-f u ncti o n m utati o n i n 
t he J A K 2 ge ne res ulti n g i n s u bstit uti o n of p he n yl ala ni ne f or v ali ne at p ositi o n 6 1 7 (J A K 2 
V 6 1 7 F) wit hi n t he pse u d o ki nase d o mai n of t he e n c o de d pr otei n.  J a n us ki nase 2 is o ne of 
4 me m bers of t he J A K fa mil y al o n g wit h J A K 1, J A K3, a n d T Y K 2.  T h e J A Ks are res p o nsi ble 
f or tra ns d ucti o n of cell si g nali n g fr o m T y p e I a n d II c yt o ki ne rece pt ors fa milies, beca use t hes e 
rece pt ors d o n ot p ossess i ntri nsic ki nase acti vit y t o acti vate d o w nstrea m si g nal tra ns d ucti o n.  
U n der p h ysi ol o gi c c o n diti o ns, t he J A Ks ass ociate wit h t he i ntracell ular d o mai n of t he c yt o ki ne 
rece pt ors i n res p o nse t o c yt o ki ne bi n di n g.  T he y t h e n u n der g o a ut o p h os p h or yl ati o n, res ulti n g i n 
c o nf or mati o nal c h a n ges t hat e na ble t he m t o  tra ns d uce i ntracell ular si g nali n g b y p h os p h or ylati n g 
a n d acti vati n g tra ns cri pti o n fact ors calle d S T A T pr otei ns.  T he acti vat e d S T A Ts tra nsl ocate t o 
t he n ucle us w here t he y r e g ulate tr a nscri pti o n of a n u m ber of ge n es i n v ol ve d i n cell ular 

I nc yte C or p orati o n 
P a ge 2 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
•  Itaciti ni b i n c o m bi nati o n wit h I N C B 0 5 0 4 6 5 f or t h e treat me nt of s oli d t u m ors. 
•  Itaciti ni b i n c o m bi nati o n wit h pe m br oliz u ma b f or t he treat me nt of s oli d t u m ors. 
•  Itaciti ni b i n c o m bi nati o n wit h e paca d ostat f or t he treat me nt of s oli d t u m ors. 
•  Itaciti ni b i n c o m bi nati o n wit h c ortic oster oi ds f or t he treat me nt of ac ute G V H D. 
Of t he s u bjects e x p ose d t o itaciti ni b, 4 9 3 s u bjects ha ve bee n e x p ose d t o itaciti ni b m o n ot hera p y:  
2 8 4 of t hese s u bjects w er e healt h y v ol u nteers a n d 2 0 9 s u bjects ha d u n derl yi n g diseas e, s uc h as 
R A ( St u d y I N C B 3 9 1 1 0- 2 0 1), c hr o nic pla q u e ps oriasis ( St u d y I N C B 3 9 1 1 0- 2 5 0), or M F ( St u d y 
I N C B 3 9 1 1 0- 2 3 0).  Ni ne  P hase 1 , 3 P hase 1/ 2, a n d 5 P hase 2 cli nical st u dies wit h itaciti ni b , 
i ncl u di n g st u dies of itaciti ni b i n c o m bi nati o n wit h PI 3 K δ i n hi bit ors I N C B 0 4 0 0 9 3 a n d 
I N C B 0 5 0 4 6 5, ha v e eit her bee n c o m plet e d or are o n g oi n g.  A d diti o nal details re gar di n g t he st u d y 
desi g ns a n d pri mar y e n d p oi nts of t hese st u dies are s u m marize d i n t he itaciti ni b I B. 
I n t he o p e n -la b el P hase 2 st u d y I N C B 3 9 1 1 0- 2 3 0 , t he efficac y a n d safet y of 3 d ose le vels of 
itaciti ni b, a p ote nt a n d selecti ve oral J A K 1 i n hi bit or, were e val u ate d i n pati e nts wit h 
i nter me diate- or hi g h-ris k M F a n d a pl atelet c o u nt ≥ 5 0 × 1 09/ L.  Of 1 0, 4 5, a n d 3 2 s u bjects 
e nr olle d i n t he 1 0 0 m g BI D , 2 0 0 m g BI D , a n d 6 0 0 m g Q D  c o h orts, res p ecti vel y, 5 0. 0 %, 6 4. 4 %, 
a n d 6 8. 8 % c o m plete d W ee k 2 4.  A ≥ 5 0 % re d ucti o n i n T S S  was ac hie ve d b y 3 5. 7 % a n d 2 8. 6 % 
of s u bjects i n t he 2 0 0 m g BI D  c o h ort a n d 3 2. 3 % a n d 3 5. 5 % i n t he 6 0 0 m g Q D  c o h ort at Wee k 1 2 
( pri mar y e n dp oi nt) a n d Wee k 2 4, res pecti vel y.  B y c o ntrast, 2 s u bjects ( 2 0 %) i n t he 1 0 0 m g BI D  
c o h ort ha d ≥ 5 0 % T S S  re d ucti o n at Wee ks 1 2 a n d 2 4.  F or t he 2 0 0 m g BI D  a n d 6 0 0 m g Q D  
c o h orts, t he me dia n S V R  at Wee k 1 2 were 1 4. 2 % a n d 1 7. 4 %, res p ecti vel y. F urt her m ore, 2 1 of 
3 9 s u bjects ( 5 3. 8 %) w h o re q uire d R B C  tra nsf usi o ns d uri n g t he 1 2 w ee ks prece di n g treat me nt 
i nitiati o n ac hie ve d a ≥ 5 0 % re d ucti o n i n t he n u m b er of R B C u nits tra nsf us e d d uri n g st u d y 
W ee ks 1 t hr o u g h 2 4.  O nl y 1 s u bject disc o nti n ue d f or Gra de 3 t hr o m b oc yt o pe nia.  
N o n he mat ol o gi c A Es  were lar gel y Gra d e 1 or 2; t he m ost c o m m o n was fati g ue.  Treat me nt wit h 
itaciti ni b res ulte d i n cli nicall y m ea ni n gf ul s y m pt o m relief, m o dest S V R , a n d li mite d 
m yel os u p pr essi o n ( Mascare n has  et al 2 0 1 6).  Alt h o u g h t he pri mar y efficac y e n d p oi nts w ere at 
1 2 a n d 2 4 wee ks p oste nr oll me nt, s u bjects were all o we d t o c o nti n ue i n t he st u d y as l o n g as t he y 
are e x perie n ci n g cli nical be nefit i n t he i n vesti gat or 's o pi ni o n.  As of t he d at a c ut off, 1 4 s u bjects 
are still recei vi n g t he st u d y dr u g.  
1. 3. 4.  
R u x oliti ni b Cli nic al S afet y  S u m m ar y  
1. 3. 4. 1.  
Cli nic al S af et y D at a  
Base d o n t h e ra n d o mize d P hase 3 C O M F O R T  I a n d II a n d R E S P O N S E st u dies, ru x oliti ni b is 
i n dicate d f or t he tr eat me nt of i nter me diate or hi g h-ris k M F , i ncl u di n g P M F, P P V -M F , P E T-M F,  
a n d P V patie nts. 
T he m ost c o m m o n he mat ol o gical a d vers e reacti o ns base d o n t hese st u dies are m yel os u p pressi o n 
(t hr o m b oc yt o p e nia, a n e mia , a n d ne utr o pe nia) a n d i ncreas e of A L T/ A S T, h y perc h olester ole mia 
a n d h y p ertri gl yceri de mia.  N o n he mat ol o gi c a d verse reacti o ns are br uisi n g, dizzi ness, hea dac h e, 
uri nar y tract i nfecti o n , a n d wei g ht gai n. 
T he A E pr ofile of t he c o m p o u n d has bee n ass esse d i n m ore t ha n 3 7 0 healt h y v ol u nteers, i n 
s u bjects wit h vari o us de grees of re nal ( n = 3 2) or he patic ( n = 2 4) i m pair m e nt, a n d i n s u bjects 

I nc yte C or p orati o n 
P a ge 2 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
efficac y o n S V R  a n d so me de gree of s y m pt o ms i m pr o ve me nt wit h li mite d he mat ol o gical a n d 
n o n he mat ol o gical A E  r ate, alt h o u g h t his d ose w as n ot ma xi mall y effecti ve.  
S o me patie nts treate d wit h r u x olit i ni b ha ve re q uire d i nterr u pti o ns i n t hera p y f or eit her 
he mat ol o gical t o xicities o r ha ve e x perie n ce d a n o n d ura ble s plee n res p o nse a n d disc o nti n ue d 
r u x oliti ni b d ue t o disease pr o gressi o n.  Itaciti ni b ma y re prese nt a sec o n d -li ne t hera p y o pti o n f or 
t hese patie nts wit h g o o d perf or ma n ce stat us .  It aciti ni b at t he d ose of 6 0 0 m g Q D m a y 
de m o ns trate g o o d t olera bilit y a n d efficac y o n s y m pt o ms i m pr o ve me nt a n d s o me S V R  f or t hese 
patie nts.  
T h us, t his st u d y is pr o p osi n g t o a d mi nister itaciti ni b i n 2 disti nct c o h orts:  
− C o h ort A s u bjects will recei ve a c o m bi nati o n of t he J A K 1 i n hi bit or itaciti ni b at 
t he d ose of 2 0 0 m g Q D a n d t he J A K 1/ 2 i n hi bit or r u x oliti ni b, a n d 
− C o h ort B s u bjects will recei ve t he J A K 1 i n hi bit or itaciti ni b as m o n ot hera p y at t he 
d ose of 6 0 0 m g Q D. 
T he st u d y will t h us e val u ate t he effects of selecti v e J A K 1 i n hi biti o n i n M F , i n c o m bi nati o n wit h 
a l o w d ose of r u x oliti ni b (less t ha n 2 0 m g d ail y ) or as a m o n ot hera p y aft er r u x oliti ni b treat me nt  
i n s u bjects w h o i nitiall y ha d s o me re d u cti o n i n s plee n f oll o we d b y pr o gressi o n or disc o nti n ue d 
f or he mat ol o gic t o xicities.  T he  i m pact o n s plee n size a nd M F s y m pt o m s (usi n g pal pati o n a n d 
M RI  or C T a n d usi n g s y m pt o m diar y, res pecti vel y) al o n g wit h t he p ossi ble be nefits of l o w ere d 
a ne mia a n d t hr o m b oc yt o pe nia i nci de nce will be assesse d. 
1. 5.  
P ote nti al Ris ks a n d Be nefits of t he Tre at me nt Re gi me n  
1. 5. 1.  
Ris ks R el ate d t o It aciti ni b 
Cli nical e x perie nce wit h itaciti ni b as of 1 3 D E C 2 0 1 6 is base d o n a d mi nistrati o n t o 7 7 7 safet y 
e val ua ble s u bjects.  T his p o p ulati o n i ncl u des 4 9 3 s u bjects w h o recei ve d itaciti ni b as 
m o n ot hera p y, i ncl u di n g healt h y s u bjects ( n = 2 8 4) a n d s u bjects wit h M F ( n = 8 7), c hr o ni c pla q ue 
ps oriasis ( n = 3 8), a n d R A ( n = 8 4).  Als o, 6 4 s u bjects wit h s oli d t u m ors recei ve d itaciti ni b i n 
c o m bi nati o n wit h c he m ot hera p y; 7 8 s u bjects wit h l y m p h oi d mali g n a ncies recei ve d itaciti ni b i n 
c o m bi nati o n wit h t he PI 3 K δ i n hi bit o r, I N C B 0 4 0 0 9 3; 3 8 s u bjects wit h s oli d t u m ors or l y m p h oi d 
mali g na n cies recei ve d itaciti ni b i n c o m bi nati o n wit h pe m br oliz u ma b ; 4 0 s u bjects wit h s oli d 
t u m ors recei ve d itaciti ni b i n c o m bi nati o n wit h e paca d ostat; a n d 2 9 s u bjects wit h a G V H D disease 
recei v e d itaciti ni b i n c o m bi nati o n wit h c ortic oster oi ds.  A d diti o nal details o n eac h of t h ese 
st u dies ca n be f o u n d i n t he itaciti ni b I B. 
A d verse e ve nts t hat ha ve bee n re p orte d b y m ore t ha n 5 % of healt h y s u bjects recei vi n g itaciti ni b 
i n a n i n di vi d ual st u d y i n cl u de d fati g u e, hea dac h e, ne utr o pe nia, na us ea, c o ntact der matitis, 
ecc h y m osis, retic ul oc yt e c o u nt decr ease d, e x c oriati o n, a n d nasal c o n gesti o n . 
Beca use of t h e p ote ntial f or m yel os u p pressi o n, s u bjects will ha ve he mat ol o gic p ara met ers  
cl osel y m o nit ore d d uri n g cli nical st u dies.  If t here are cli nicall y rele va nt d ecli nes i n he mat ol o g y 
para meters, t he n t her a p y ma y b e i nterr u pte d u ntil res ol uti o n or disc o nti n uati o n.  As itaciti ni b 
als o has t he p ote ntial t o ca use W B C mar gi nati o n (ie, a tra n sie nt decrease i n A N C), assess me nt of 
he mat ol o g y p ara met ers s h o ul d be perf or me d bef ore st u d y dr u g a d mi nistrati o n a n d at all 
a p plica ble st u d y visits.  

I nc yte C or p orati o n 
P a ge 2 6  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
A d verse e ve nts re p orte d b y m ore t h a n 1 0 % of s u bjects i n t he M F st u d y i n cl u de d a ne mia, fati g u e, 
t hr o m b oc yt o pe ni a/ platelet c o u nt decrease d , u p p er res pirat or y tract i nfecti o n, na usea, 
c o nsti pati o n, diarr hea, c o u g h, peri p heral e de ma, p yre xia, d ys p nea, dizzi ness, pai n i n e xtre mit y, 
ni g ht s weats, a b d o mi nal pai n, art hral gia, c o nt usi o n, hea dac he, pr urit us, a n d v o miti n g.  T he o nl y 
a d verse e ve nt r e p orte d b y m ore t h a n 1 0 % of itaciti ni b-treate d s u bjects wit h a n i nfla m mat or y 
c o n diti o n was nas o p har y n gitis i n a ps oriasis st u d y ; t here were n o T E A Es re p orte d b y m ore t ha n 
1 0 % of s u bjects wit h R A. 
1. 5. 2.  
Ris ks R el ate d t o R u x oliti ni b  
T he safet y of r u x oliti ni b was assesse d i n 6 1 7 s u bj ects i n 6 cli nical st u dies wit h a me dia n d urati o n 
of f oll o w- u p of 1 0. 9 m o nt hs, i ncl u di n g 3 0 1 s u bjects wit h M F  i n 2 P hase 3 st u dies.  I n a 
d o u ble- bli n d ra n d o mize d, place b o c o ntr olle d st u d y of r u x oliti ni b, a m o n g t he 1 5 5 s u bjects treat e d 
wit h r u x oliti ni b, t he m ost fre q ue nt a d vers e dr u g reacti o ns were t hr o m b oc yt o pe nia a n d a n e mia.  
T hr o m b oc yt o p e nia, a n e mia, a n d ne utr o pe nia are d ose-relat e d effects.  T h e m ost fre q ue nt 
n o n he mat ol o gic a d vers e reacti o ns w ere br uisi n g, di zzi ness, a n d hea dac he.  
S o me s y m pt o ms s uc h as i nfecti o ns wit h her pes z oster or m ultif ocal le u k oe nce p hal o pat h y ( P M L), 
s y m pt o m e x acer b ati o n f oll o wi n g i nterr u pti o n or disc o nti n uati o n of treat me nt wit h r u x oliti ni b, 
a n d n o nmela n o ma s ki n ca ncer  h a ve o cc urre d.  
F or  a d escri pti o n of t he f ull ris ks of r u x oliti ni b, refer t o t he prescri bi n g i nf or mati o n. 
1. 5. 3.  
Ris ks f or t he C o m bi n ati o n of I t aciti ni b a n d R u x oliti ni b  
I n hi biti o n of J A K 1 a n d J A K 2 b y r u x oliti ni b is ass ociate d wit h a p ote ntial ris k of de vel o pi n g 
seri o us bacterial, myc o bacterial, f u n gal, a n d viral i nfecti o ns.  It is n ot k n o w n w het her  i n hi biti o n 
pri maril y of J A K 1, s uc h as wit h itaciti ni b, will be ass ociate d wit h i ncrease d ris k of i nfecti o ns.  
S u bjects wit h acti ve seri o us i nfecti o ns will n ot be all o we d t o e nr oll i n t he st u d y.  I n v esti gat ors 
s h o ul d caref ull y o bser ve s u bjects recei vi n g itaciti ni b f or si g ns a n d s y m pt o ms of i nfecti o ns a n d 
i nitiate a p pr o priate tr eat me nt. 
1. 5. 4.  
P ot e nti al B e nefits  of It aciti ni b a n d R u x oliti ni b  
1. 5. 4. 1.  
It aciti ni b P ote nti al B e n efits 
J a n us ki nase i n hi biti o n b y itaciti ni b ma y res ult i n re d ucti o ns i n s plee n size a n d s y m pt o ms.   
1. 5. 4. 2.  
R u x oliti ni b P ote nti al B e nefit 
T he cli nical efficac y res ults of r u x oliti ni b t hat ha ve e mer ge d fr o m t he o n g oi n g st u dies a n d 
P hase  3 st u dies are n ota ble, i ncl u di n g mar k e d re d ucti o n i n s ple n o me gal y, i m pr o ve me nt i n 
s y m pt o ms, perf or ma nce stat us a n d acti vit y le v el, a n d re d ucti o n i n plas ma l e vels of 
i nfla m mat or y, pr ot hr o m b otic, a n d a n gi o ge nic c yt o ki nes.  I n t h os e s u bjects wit h pr ol o n ge d 
e x p os ure t o r u x oliti ni b ( me dia n of 5 years t hera p y), t hes e p osi ti ve effects ha ve bee n mai ntai ne d, 
gi ve n t he cl osel y rel ate d pat h o p h ysi ol o g y of M P Ns. 

I nc yte C or p orati o n 
P a ge 2 7  of 8 5 
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
2.  
S T U D Y O B J E C TI V E S A N D  E N D P OI N T S  
St u d y o bj ecti ves a n d e n d p oi nts are pres e nte d i n T a ble  2. 
T a ble 2: 
St u d y O bjecti ves a n d E n d p oi nts  
Pri m ar y O bjecti ve  
Pri m ar y E n d p oi nt  
T o e val uate preli mi nar y effica c y of itaciti ni b o n S V R 
fr o m baseli ne at W ee k 2 4 i n t he 2 f oll o wi n g c o h orts of 
M F  s u bj ects: 
•  C o h ort A :  i n c o m bi nati o n i n s u bj ects wit h 
r u x oliti ni b l o w dose (less t ha n 2 0 m g dail y) . 
•  C o h ort B :  as m o n ot hera p y i n s u bj ects w h o 
pr o gresse d ( per re vise d E L N 2 0 1 3 res p o nse criteria 
f or M F) after i nitial re d u cti o n i n s plee n o n 
r u x oliti ni b or disc o nti n ue d f or he mat ol o gic 
t o xicities. 
C ha n ge a n d p erce nta ge c ha n ge  i n S V R as meas ure d b y 
M RI ( C T sca n i n s u bj ects w h o are n ot ca n di dates f or M RI 
or w he n M RI is n ot rea dil y a vaila ble) at W ee k  2 4 w he n 
c o m pare d wit h  baseli ne.  
Sec o n d ar y O bjecti ve s ( C o h orts A a n d B) 
Sec o n d ar y E n d p oi nt s 
T o e val uate preli mi nar y safet y a n d t olera bil it y of 
itaciti ni b al o ne.  
Safet y a n d t olera bilit y t hr o u g h assess me nt of fre q ue nc y, 
se verit y, a n d d urati o n of A Es; c ha n ges i n cli nical safet y 
assess me nts; a n d c ha n ges i n cl i nical la b orat or y 
para meters.  
T o e val uate preli mi nar y safet y a n d t olera bilit y of 
itaciti ni b i n c o m bi nati o n wit h r u x oliti ni b. 
T o e val uate preli mi nar y effica c y of itaciti ni b al o ne or 
i n c o m bi nati o n wit h r u x oliti ni b o n S V R  fr o m baseli ne 
at W ee k 1 2. 
C ha n ge a n d p erce nta ge i n S V R fr o m baseli ne t hr o u g h 
W ee k 1 2 as meas ure d b y M RI ( or C T sca n i n a p plica ble 
s u bj ects).  
T o e val uate preli mi nar y effica c y of itaciti ni b al o ne or 
i n c o m bi nati o n wit h r u x oliti ni b o n s plee n le n gt h 
re d ucti o n fr o m baseli ne at W e e k 1 2 a n d W ee k 2 4.  
C ha n ge a n d p erce nta ge c ha n ge o n s plee n le n gt h re d ucti o n 
fr o m baseli ne t hr o u g h Wee k 1 2 a n d W ee k 2 4 as meas ure d 
b y pal pati o n.  
T o e val uate preli mi nar y effica c y of itaciti ni b al o ne or 
i n c o m bi nati o n wit h r u x oliti ni b wit h res pect t o M F 
s y m pt o ms at W ee k 1 2 a n d W ee k 2 4. 
C ha n ge a n d perce nta ge c ha n ge i n T S S  fr o m baseli ne 
t hr o u g h W ee k 1 2 a n d W ee k 2 4 as meas ure d b y t he 
M F S A F v 2. 0 s y m pt o m diar y a n d b y t he M P N -S A F.  
P GI C  sc ore at eac h visit w her e t he varia ble is meas ure d. 
T o e val uate preli mi nar y effica c y of itaciti ni b usi n g 
I W G-M R T  criteria.  
N u m ber of s u bj ects wit h res p o nses acc or di n g t o t he 
2 0 1 3  I W G-M R T  c o nse ns us criteria f or treat me nt res p o nse.  
T o assess t he P K of itaciti ni b a n d r u x oliti ni b.  
Calc ulati o n of t he P K para met ers s uc h as A U C, C L/ F, 
C ma x , a n d tma x  al o n g wit h s u m marizati o n of t he o bser ve d 
c o nce ntrati o n data b y ti me p oi nt will be perf o r me d f or b ot h 
r u x oliti ni b a n d itaciti ni b. 

I nc yte C or p orati o n 
P a ge 2 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
T a ble 2: 
St u d y O bjecti ves a n d E n d p oi nts ( C o nti n ue d)  
3.  
S U B J E C T E LI GI BI LI T Y  
De viati o ns fr o m eli gi bilit y criteria are n ot all o w e d beca use t h e y ca n p ot e ntiall y je o p ar dize t he 
scie ntific i nte grit y of t he st u d y, re g ul at or y acce pta bilit y, a n d/ or s u bject safet y.  T heref ore, 
a d here n ce t o t he criteria as s pecifie d i n t he P r ot oc ol is esse ntial. 
3. 1.  
S u bject I ncl usi o n Criteri a  
A s u bject  w h o meet s all of t he f oll o wi n g criteri a ma y b e i ncl u de d i n t he st u d y:  
C o h ort A o nl y  
1.  Recei vi n g  r u x oliti ni b d ose of less t ha n 2 0 m g dail y wit h n o d ose i ncreas e or n o d ose 
m o difica ti o n i n t he last 8 wee ks bef ore s cree ni n g visit. 
C o h ort B o nl y  
2.  M ust ha ve ha d i nitial re d ucti o n i n s plee n o n r u x oliti ni b treat me nt (res p o nse is defi ne d b y 
a n y s plee n le n gt h or v ol u me re d ucti o n, b y pal pati o n or M RI/ C T assess me nt, fr o m 
baseli ne w hile o n pr e vi o us r u x oliti ni b treat me nt per I W G-M R T E L N 2 0 1 3 g ui deli nes, 
A p pe n di x B ): 
a. F oll o we d b y d oc u me nt e d e vi de nce of pr o gressi o n i n s plee n le n gt h or v ol u me O R   
b.  Disc o nti n ue d r u x oliti ni b f or he mat ol o gic t o xicities, after t he i nitial re d u ct i o n i n 
s plee n le n gt h or v ol u me. 
All s u bjects  
3.  Me n a n d w o me n, a ge d 1 8 years or ol d er.  
4.  C o nfir me d dia g n osis of P M F, P P V- M F, or P E T- M F acc or di n g t o re vise d W H O 2 0 1 6 
criteria (A p pe n di x A ). 

I nc yte C or p orati o n 
P a ge 2 9  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
5.  M ust ha ve pal pa ble s plee n of ≥ 5 c m bel o w t h e left s u bc ostal mar gi n o n p h ysical 
e x a mi nati o n at t he scree ni n g visit  (if s plee n is n ot pal pa ble d ue t o b o d y ha bit us, s plee n 
e nlar ge me nt m ust be d o c u me nte d b y ot h er mea ns [e g, ultras o u n d or M RI] a n d st u dy 
s p o ns or me dical m o nit or be c o ntact e d f or acce pta n ce). 
6.  E C O G perf or ma nce stat us of 0, 1, or 2.  
7.  Scree ni n g b o ne marr o w bi o ps y s peci me n a vaila bl e or willi n g ness t o u n der g o a b o n e 
marr o w bi o ps y at scree ni n g/ baseli ne; willi n g ness t o u n der g o b o ne marr o w bi o ps y at 
Wee k 2 4. 
8.  Lif e e x pecta nc y of at least 2 4 wee ks.  
9.  Willi n g ness t o a v oi d pre g na n c y or fat heri n g c hil dre n base d o n t h e f oll o wi n g criteria 
(A p pe n di x G ): 
a. W o ma n of n o nc hil d beari n g p ote ntial (ie, s ur gicall y sterile wit h a h yst erect o m y a n d/ or 
bilateral o o p h orect o m y O R ≥ 1 2 m o nt hs of a me n orr hea a n d at least 5 0 years of a ge). 
b.  W o ma n of c hil d beari n g p ote ntial w h o has a ne gati ve ser u m pre g n a nc y test at 
scree ni n g a n d ne gati ve uri nar y test bef ore t he first d ose o n Da y 1 a n d w h o a grees t o 
ta ke a p pr o priate pr eca uti o ns t o a v oi d preg na nc y ( wit h at least 9 9 % certai nt y) fr o m 
scree ni n g t hr o u g h s afet y f oll o w-u p.  Per mitte d met h o ds t hat are at least 9 9 % effecti ve 
i n pre ve nti n g pre g n a nc y s h o ul d be c o m m u nicate d t o t he s u bject a n d t heir 
u n dersta n di n g c o nfir m e d. 
c. Ma n w h o a gr ees t o ta ke a p pr o pr iate preca uti o ns t o a v oi d fat heri n g c hil dre n ( wit h at 
least 9 9 % certai nt y) fr o m scree ni n g t hr o u g h s afet y f oll o w- u p.  Per mitte d met h o ds t hat 
are at least 9 9 % effecti ve i n pre ve nti n g pre g n a nc y s h o ul d be c o m m u nicate d t o t he 
s u bject a n d t heir u n dersta n di n g c o nfir me d. 
3. 2.  
S u bject E xcl usi o n Criteri a  
A s u bject  w h o meet s a n y of t he f oll o wi n g criteri a will be e x cl u de d fr o m t he st u d y: 
1.  Lac k of r ec o v er y fr o m all t o xicities fr o m pre vi o us t hera p y (e x ce pt r u x oliti ni b) t o Gra de 1 
or better.  
2.  Pre vi o us treat me nt wit h itaciti ni b  or J A K 1 i n hi bit ors (J A K 1/J A K 2 i n hi bit or r u x oliti ni b is 
per mitte d ). 
3.  I n a bilit y t o s wall o w f o o d or a n y c o n diti o n of t he u p per gastr oi ntesti nal tract t hat 
precl u des a d mi nistrati o n of oral me dicati o ns.  
4.  U n willi n g ness t o be tra nsf use d wit h bl o o d c o m p o ne nts. 
5.  Rece nt hist or y of i na de q uate b o ne marr o w reser v e as de m o nstrate d b y t h e f oll o wi n g:  
a. Platelet c o u nt < 5 0 × 1 0 9/ L i n t he 4 w ee ks bef ore s cree ni n g or platelet tra nsf usi o n 
wit hi n 8 wee ks bef ore scree ni n g.  
b.  A N C  le vels < 0. 5 × 1 09/ L i n t he 4 w ee ks bef ore s cree ni n g.  
c. Peri p heral bl o o d blast c o u nt of > 1 0 % at t he scree ni n g or b aseli ne he mat ol o g y 
assess me nts.  

I nc yte C or p orati o n 
P a ge 3 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
6.  I n a de q uat e li ver f u n cti o n at scree ni n g a n d baseli n e visits as de m o nstrate d b y t he 
f oll o wi n g:  
a. Direct bilir u bi n ≥ 2. 0 × U L N.  ( N O T E:  direct bilir u bi n ma y be ass u me d  t o be wit hi n 
li mits if t otal bilir u bi n is ≤ 2. 0 × U L N).  
b.  A L T or A S T > 2. 5 × U L N.  
7.  I n a de q uat e re n al f u ncti o n at scree ni n g a n d baseli n e visits as de m o nstrate d b y creati ni ne 
clear a nce < 4 0 m L/ mi n meas ure d or calc ul ate d b y C oc kr oft -Ga ult e q u ati o n , or 
gl o mer ula r filtrati o n rat e < 4 0 m L/ mi n/ 1. 7 3 m2 as calc ulate d usi n g t he M o dificati o n of 
Diet i n Re nal Disease f or m ula . 
8.  Acti ve bact erial, f u n gal, parasitic, or viral i nfecti o n t hat re q uires t hera p y.  S u bjects wit h 
ac ute i nfecti o ns re q uiri n g treat me nt s h o ul d dela y s cr ee ni n g/e nr oll me nt u ntil t he c o urse of 
t hera p y has b ee n c o m plet e d a n d t he e v e nt is c o nsi dere d res ol ve d.  Pr o p h ylactic 
a nti bi otics will be per mitte d.  
9.  E vi de nce of H B V or H C V i nfecti o n or ris k of reacti vati o n:  H B V D N A a n d H C V R N A 
m ust be u n detecta ble.  S u bjects ca n n ot be p ositi v e f or he p atitis B s urface a nti ge n or  
a nti– he patitis B c or e a nti b o dies.  S u bjects w h o ha ve p ositi ve a nti- H Bs as t he o nl y 
e vi de nce of pri or e x p os ure ma y partici pate i n t he st u d y pr o vi de d t hat t here is b ot h 1) n o 
k n o w n hist or y of H B V i nfe cti o n a n d 2) v erifie d recei pt of he patitis B v acci ne.  
1 0.  K n o w n h u ma n i m m u n o deficie nc y vir us i nfecti o n. 
1 1.  Cli nicall y si g nifica nt or  u nc o ntr olle d car diac disease, i ncl u di n g u nst a ble a n gi na; ac ute 
m y ocar dial i nfarcti o n wit hi n 6 m o nt hs of Da y 1 of st u d y dr u g a d mi ni strati o n; Ne w Y or k 
Heart Ass o ciati o n Class III or I V c o n gesti ve h eart fail ure; a n d arr h yt h mia re q uiri n g 
t hera p y u nless a p pr o ve d b y me dical m o nit or/s p o ns or.   
1 2.  Acti ve i n vasi ve mali g na n c y o v er t he pre vi o us 2 years e x ce pt treat e d basal or s q ua m o us 
carci n o mas of t he s ki n, c o m pletel y resecte d i ntrae pit helial carci n o ma of t h e cer vi x, a n d 
c o m pletel y resecte d pa pillar y t h yr oi d a n d f ollic ular t h yr oi d ca ncers.  S u bjects wit h 
mali g na n cies wit h i n d ole nt be ha vi or s uc h as pr ostate ca n cer treate d wit h ra diati o n or 
s ur ger y ma y b e e nr olle d as l o n g as t h e y ha ve a reas o na ble e x pectati o n t o ha ve bee n c ure d 
wit h t he treat me nt m o dalit y recei ve d . 
1 3.  S ple nic irra diati o n wit hi n 6 m o nt hs bef ore recei vi n g t he first d ose of itaciti ni b. 
1 4.  Use of a n y pr o hi bite d c o nc o mita nt  me dicati o ns . 
1 5.  Acti ve alc o h ol or dr u g a d dicti o n t hat w o ul d i nterfere wit h t heir a bilit y t o c o m pl y wit h t he 
st u d y re q uire me nts. 
1 6.  Use of a n y p ote nt /str o n g c yt o c hr o me P 4 5 0 3 A 4 i n hi bit ors wit hi n 1 4 da ys or 5 half -li ves 
( w hic he ver is l o n ger) b ef ore t he first d ose of itaciti ni b or a ntici pate d d uri n g t he st u d y. 
1 7.  Use of c o n c o mita nt treat me nt of fl uc o naz ole at a d ose >  2 0 0 m g ( o nl y f or s u bjects treate d 
i n C o h ort A wit h r u x oliti ni b ). 
1 8.  I n a de q uat e rec o ver y fr o m t o xicit y a n d/ or c o m pli cati o ns fr o m a maj or s ur ger y bef ore 
starti n g t her a p y. 
1 9.  C urre nt l y breastf ee di n g or pre g na nt. 

I nc yte C or p orati o n 
P a ge 3 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
2 0.  I n a bilit y t o c o m pr e he n d or u n willi n g t o si g n t he I C F. 
2 1.  Hist or y or prese n ce of a n a b n or mal E C G  t hat, i n t he i n vesti gat or's o pi ni o n, is cli nicall y 
mea ni n gf ul. 
2 2.  A n y c o n diti o n t hat w o ul d, i n t he i n vesti gat or' s j u d g me nt, i nterfere wit h f ull partici pati o n 
i n t he st u d y, i ncl u di n g a d mi nistrati o n of st u d y dr u g a n d atte n di n g re q uire d st u d y visits; 
p ose a si g nifica nt ris k t o t he s u bject; or i nterfere wit h i nter pretati o n of st u d y dat a.  
3. 3.  
S u bjects W h o F ail t o Meet Scree ni n g Criteri a  
A s u bject w h o has a l a b orat or y test res ult, vital si g n assess me nt , or E C G fi n di n g t hat d oes n ot 
satisf y t he e ntra n ce criteria ma y h a ve t he tests re p eate d o nce.  T hes e tests ma y b e re p eate d as 
s o o n as t he i n vesti gat or b elie ves t hat t he ret est res ult is li kel y t o be wit hi n t he acce pta ble ra n ge t o 
satisf y t he e ntra n ce criteria, b ut t he y m ust be c o m plete d wit hi n t he 3- wee k scree ni n g p eri o d  
( Da ys - 2 8 t o - 8).  I n t his case, t he s u bject will n ot be re q uire d t o si g n a n ot h er I C F, a n d t he 
ori gi nal s u bject i de ntificati o n n u m ber will be use d.  If t he la b orat or y tests ca n n ot be perf or m e d 
wit hi n t he scree ni n g peri o d, if t he retests d o n ot meet t he e ntra nce criteri a, or if t he s u bject's 
me dical c o n diti o n has c h a n ge d si g nifica ntl y d uri n g t he scree ni n g p eri o d  s u c h t hat 
i ncl usi o n/e x cl usi o n criteria are n o l o n ger met, t he s u bject will be c o nsi dere d a scree n fail ure a n d 
m ust be wit h dra w n fr o m t he st u d y.  T heref ore, sites s h o ul d c o nsi der t he testi n g sc he d ule 
caref ull y s o t hat a n y p ote ntial retests are acc o m plis he d wit h i n t he 3-wee k ti me fra me.  If t he 
s u bject a n d i n vesti gat or a gr ee t o r escr ee ni n g, t he n t he s u bject m ust si g n a n e w I C F, a ne w 
s u bject i de ntificati o n n u m ber will be assi g n e d, a n d all re q uire d scree ni n g acti vities m ust be 
perf or me d w he n t he s u bj ect is re scree n e d f or p arti ci pati o n in t he st u d y (e x ce pt b o ne marr o w 
bi o ps y if alr ea d y perf or m e d at scr ee ni n g).  A n  i n di vi d ual s u bject ma y o nl y rescree n o nce f or t he 
st u d y. 
If all scr ee ni n g acti vities ca n n ot be c o m plet e d d uri n g t he scree ni n g p eri o d  b eca use of a n e ve nt 
u nrelate d t o a me di cal fi n di n g (f or e x a m ple, sc he d uli n g diffic ulties f or M RI), t he n t he 2 1-da y 
scree ni n g p eri o d ma y be e xte n de d t o as m uc h as 4 2 da ys, wit h t he s u bject retai ni n g t he ori gi n al 
s u bject n u m ber.  A r e peat of scree ni n g  tests f or he mat ol o g y a n d bl o o d c h e mistr y ma y be 
ne cessar y t o deter mi ne eli gi bilit y. 

I nc yte C or p orati o n 
P a ge 3 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
4.  
I N V E S TI G A TI O N A L P L A N  
4. 1.  
O ver all St u d y Desi g n  
T his is a n o pe n-la bel P hase 2 st u d y wit h 2 c o h orts: 
•  C o h ort A :  M F  s u bjects w h o are t olerati n g a r u x oliti ni b d ose of less t ha n 2 0 m g dail y 
wit h n o d ose i ncreas e or n o d ose m o dificat i o n i n t he last 8 wee ks b ef ore scree ni n g 
visit  will recei ve a c o m bi nati o n of t he J A K 1 i n hi bit or itaciti ni b at t he d ose of 2 0 0 m g 
Q D a n d t he J A K 1/ 2 i n hi bit or r u x oliti ni b. 
•  C o h ort B :  M F  s u bjects w h o, after a n i nitial re d u cti o n i n s plee n wit h r u x oliti ni b 
treat me nt, pr o gr esse d or disc o nti n ue d f or he mat ol o gic t o xicities, will recei ve 
treat me nt wit h J A K 1 i n hi bit or itaciti ni b al o ne at t he d ose of 6 0 0 m g Q D.  
S u bjects will c o nti n ue st u d y treat me nt u ntil disease pr o gressi o n, u nacce pta ble t o xicit y, 
wit h dra wal of c o nse nt, or ot her Pr ot oc ol- s pecifi e d criteria t o st o p treat me nt are met.  S u bjects 
w h o are recei vi n g b e nefit fr o m t he t hera p y will c o nti n ue recei vi n g st u d y treat me nt u ntil 
wit h dra wal criteria are m et . 
All s u bjects will be f oll o we d f or s afet y 3 0 t o 3 5 d a ys afte r t h e last d ose of st u d y treat me nt (e g, 
re p orti n g of A Es a n d S A Es). 
T he o ver all st u d y desi g n is s h o w n i n Fi g ure  1. 
Fi g ure  1: 
St u d y Desi g n   
 

I nc yte C or p orati o n 
P a ge 3 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
4. 2.  
Me as ures T a ke n t o A v oi d Bi as  
T his is a n o pe n-la bel st u d y; n o c o m paris o ns will be ma de bet w ee n s u bjects or a gai nst hist orical 
c o ntr ols.  Meas ur e me nts of safet y a n d effi cac y are o bjecti ve meas ure me nts, a n d o nl y 
c o m paris o ns t o pretreat me nt c o n diti o ns will be ma de. 
4. 3.  
N u m ber of S u bjects  
A p pr o xi ma tel y 2 1 s u bj ects will be i ncl u de d i n eac h d ose c o h ort f or a t otal of 4 2 s u bjects. 
4. 4.  
D ur ati o n of Tre at me nt a n d S u bject P artici p ati o n  
After si g ni n g t he I C F, s u bject st u d y partici pati o n is esti mate d t o a vera ge a p pr o xi matel y 
3 2 wee ks  per i n di vi d ual s u bject, e x clusi ve of l o n g- ter m f oll o w- u p peri o d:  
•  Scree ni n g  peri o d  ( Da y - 2 8 t o Da y - 8):  U p t o 2 1 da ys.  
•  B aseli ne ( p retre at me nt) peri o d  ( Da y - 7 t o Da y -1):  7 da ys b ef ore t he  first d ose of 
itaciti ni b (re q uired f or all eli gi ble s u bjects t o c o m plete t he dail y s y m pt o m di a r y f or 
7 da ys b ef or e t he  first d ose of st u d y m e dicati o n). 
•  Tre at me nt peri o d  (starts at Da y 1 t hr o u g h E O T ):  Be gi ns wit h t he first d ose of 
itaciti ni b ( Da y 1).  Tr eat me nt will c o nti n ue as l o n g as t he re gi me n is t olerate d a n d t he 
s u bject d oes n ot meet disc o nti n uati o n criteria.  
•  S af et y f oll o w -u p  peri o d :  3 0 t o 3 5 da ys after t he l ast d ose of itaciti ni b is ta ke n. 
4. 5.  
O ver all St u d y D ur ati o n  
T he st u d y will be gi n w h e n t he first s u bject e nters s cree ni n g, a n d t he  e n d of t he st u d y will occ ur  
w he n all s u bjects ha v e c o m plete d treat me nt or disc o nti n ue d st u d y dr u g a n d ha ve c o m plete d 
a p plica ble f oll o w- u p assess me nts .  I n di vi d ual s u bj ect partici pati o n is e x pecte d t o a vera ge 
3 2 wee ks per i n di vi d ual s u bject. 
4. 6.  
St u d y Ter mi n ati o n  
T he in vesti gat or ret ai ns t he ri g ht t o ter mi nate st u d y partici pati o n at a n y ti me, acc or di n g t o t he 
ter ms s pecifie d i n t he st u d y c o ntr act.  T h e i n vesti gat or is t o n otif y t he i nstit uti o nal re vie w b oar d 
(I R B)/i n de p e n de nt et hics c o m mittee (I E C) i n writi n g of t he st u d y's c o m pleti o n or earl y 
ter mi nati o n, se n d a c o p y of t he n otificati o n t o t he s p o ns or or s p o ns or's desi g nee, a n d retai n 
1 c o p y f or t he site st u d y r e g ul at or y file.  
T he s p o ns or ma y ter mi nate t he st u d y el ecti vel y, if re q uire d b y re g ulat or y d ecisi o n.  If t he st u d y 
is ter mi nate d pre mat ur el y, t he n t he s p o ns or will n otif y t he i n vesti gat ors, t h e I R Bs a n d IE C s, a n d 
re g ulat or y b o dies of t h e decisi o n a n d reas o n f or t er mi nati o n of t he st u d y. 

I nc yte C or p orati o n 
P a ge 3 4  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
5.  
T R E A T M E N T  
5. 1.  
Tre at me nt Assi g n me nt  
5. 1. 1.  
S u bject N u m beri n g a n d Tre at me nt Assi g n me nt  
Eac h s u bject will be i de ntifie d i n t he st u d y b y a s u bject I D n u m ber, w hic h is a c o m bi nati o n of 
the site I D a n d s u bject n u m ber (see Secti o n 7. 2 ). 
E nr oll me nt will be c o ntr olle d b y a n I X R S .   
St u d y sites will re gister st u d y s u bjects i n t he I X R S i n or der t o recei ve a s u bject n u m ber a n d 
treat me nt all ocati o n. 
All s u bject n u m bers will be 6 di gits; t he first 3 di gits will be t he site n u m ber , a n d t he last 3 di gits 
will be t he s u bject 's n u m ber.  T his s u bject n u m ber will be mai ntai ne d t hr o u g h o ut t he st u d y a n d 
will n ot be reassi g n e d .  S u bjects w h o wit h dra w c o nse nt or disc o nti n ue fr o m t he st u d y aft er bei n g 
assi g ne d a s u bject n u m ber will retai n t heir i nitial n u m ber.  
Site staff will c o ntact t he I X R S t o o btai n t he i nitial st u d y dr u g assi g n me nt.  Refer t o t he I X R S 
ma n ual f or det aile d i nf o r mati o n. 
If a s u bject is mista ke nl y gi ve n a b ottle of st u d y dr u g t hat is n ot t he b ottle assi g ne d b y t he I X R S, 
t he n t he I X R S hel p des k m ust be n otifie d i m me diatel y.  T h e reas o n f or t h e misall ocati o n of t he 
st u d y dr u g m ust be d oc u me nte d b y t h e st u d y site a n d re p ort e d t o t he I R B/I E C. 
F or s u bjects w h o si g ne d a n I C F b ut are n ot all ocat e d a n d f or s u bj ects w h o are all ocat e d b ut were 
n ot treate d, r efer t o t he e C R F C o m pleti o n G ui deli nes f or i nstr ucti o n o n w hic h e C R Fs t o 
c o m plete.  
5. 1. 2.  
R a n d o miz ati o n a n d Bli n di n g  
N ot a p plica ble.  
5. 2.  
St u d y Dr u g   
5. 2. 1.  
It aciti ni b 
5. 2. 1. 1.  
Descri pti o n a n d A d mi nistr ati o n   
5. 2. 1. 1. 1.  C o h ort A s u bjects  
Itaciti ni b will be self-a d mi nistere d  as a 2 0 0 m g Q D oral treat me nt i n t he f or m of 1 0 0 m g ta blets , 
i n a d diti o n t o t heir c urre nt r u x oliti ni b treat me nt.  D oses of itaciti ni b s h o uld be self -a d mi nistere d 
wit h o ut re gar ds t o f o o d.  N ote t hat s u bjects m ust be i nstr u cte d t o wit h h ol d t he m or ni n g d os e of 
itaciti ni b u ntil reac hi n g t he cli nic f or eac h st u d y visit w here d ose a d mi nistrati o n  will occ ur.   

I nc yte C or p orati o n 
P a ge 3 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
5. 2. 1. 1. 2.  C o h ort B s u bjects  
Itaciti ni b will be self-a d mi nistere d  as a 6 0 0 m g Q D oral treat me nt i n t he f or m of 1 0 0 m g ta blets .  
N ote t hat s u bjects m ust be i nstr u cte d t o wit h h ol d t he m or ni n g d os e of itaciti ni b u ntil reac hi n g t he 
cli nic f or eac h st u d y visit w here d os e a d mi nistrati o n  will occ ur.   
5. 2. 1. 2.  
S u p pl y, P a c k a gi n g, a n d L a beli n g  
Itaciti ni b will be pr o vi de d as 1 0 0 m g S R  ta blets p acka ge d i n hi g h -d e nsit y p ol yet h yle n e  b ottles.   
All I nc yt e i n vesti gati o nal pr o d uct la bels will be i n t he l ocal la n g ua ge a n d will c o m pl y wit h t he 
le gal re q uir e me nts of eac h c o u ntr y. 
5. 2. 2.  
R u x o liti ni b 
5. 2. 2. 1.  
Descri pti o n a n d A d mi nistr ati o n  
5. 2. 2. 1. 1.  C o h ort A s u bjects  
R u x oliti ni b will be self-a d mi nistere d  as a n oral treat me nt at t he sta ble d ose of less t ha n 2 0 m g  
dail y esta blis he d b ef or e e nteri n g t he st u d y. 
D oses of r u x oliti ni b s h o ul d be self- a d mi nistere d a p pr o xi m atel y 1 2 h o urs a part wit h o ut re gar d t o 
f o o d. 
N ote t hat s u bjects m ust be i nstr ucte d t o wit h h ol d t he m or ni n g d os e of r u x oliti ni b u ntil reac hi n g 
t he cli nic f or eac h st u d y visit w here d ose a d mi nistrati o n will occ ur (see Secti o n  6. 3 ). 
5. 2. 2. 1. 2.  C o h ort B s u bjects 
N ot a p plica ble.  
5. 2. 2. 2.  
S u p pl y, P ac k a gi n g, a n d L a belli n g  
Refer t o t h e r u x oliti ni b prescri bi n g i nf or mati o n  f or s u p pl y, pac ka gi n g, a n d la beli n g i nf or mati o n.  
5. 2. 3.  
 St or a ge 
T he b ottles of ta blets s h o ul d be st ore d at r o o m te m perat ure, 1 5° C t o 3 0° C ( 5 9° F t o 8 6° F). 
T he s u bject m ust be i nstr ucte d i n t he ha n dli n g of st u d y dr u gs as f oll o ws: 
•  T o st ore s t u d y dr u gs at r o o m te m perat ure. 
•  T o o nl y r e m o ve fr o m t he b ottle of itaciti ni b or r u x oliti ni b t he n u m ber of ta blets 
nee de d at t he ti me of a d mi nistrati o n.  
•  N ot t o re m o ve d oses i n a d va nce of t h e ne xt sc he d ule d a d mi nistrati o n. 
•  T o ma ke e ver y e ff ort t o ta ke d oses o n sc h e d ule. 
•  T o re p ort a n y misse d d os es at t he ne xt st u d y visit.  
•  If t he s u bject v o mits after ta ki n g st u d y dr u g(s), t h e n t he s u bject s h o ul d n ot ta ke 
a n ot her d os e.  

I nc yte C or p orati o n 
P a ge 3 6  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
•  If a d ose of st u d y dr u g itaciti ni b is misse d b y m ore t ha n 8 h o urs, t he n t hat d ose s h o ul d 
be s ki p pe d, a n d t he ne xt sc he d ule d d ose ta k e n at t he us ual ti me, e x ce pt o n Wee k 2 
Da y 8 f or P K sa m ple m a na ge me nt.  ( F or C o h ort A s u bjects, r u x oliti ni b s h o ul d be 
ta ke n BI D  e v er y 1 2 h o urs b ut n o less t ha n 8 h o urs a part). 
•  T o  kee p st u d y dr u g i n a s afe place a n d o ut of reac h of c hil dre n. 
•  T o bri n g all use d a n d u n use d st u d y dr u g kits t o t he site at eac h visit. 
5. 3.  
Tre at me nt C o m pli a nce  
C o m plia nce wit h all st u d y -r elate d tr eat me nts s h o ul d be e m p hasize d t o t he s u bject b y t h e site 
pers o n nel, a n d a p pr o priat e ste ps s h o ul d be ta ke n t o o pti mize c o m plia nce d uri n g t he st u d y.  
C o m plia nce wit h itaciti ni b  will be calc ulate d b y t h e s p o ns or base d o n t he dr u g acc o u nta bilit y 
d oc u me nte d b y t he site st aff a n d m o nit ore d b y t h e s p o ns or/ desi g nee (ta blet c o u nts).  S u bjects 
will be i nstr ucte d t o bri n g all st u d y  dr u gs  wit h t he m t o t he st u d y visits i n or der f or site p ers o n nel 
t o c o n d uct ta blet c o u nts t o assess st u d y dr u g acc o u nta bilit y.  T h e dr u g acc o u nta bilit y 
d oc u me ntati o n will be use d b y t h e s p o ns or t o calc ulate treat me nt c o m plia n ce.   
5. 4.  
Tre at me nt M o dific ati o ns :  I ncre ases, Decre ases , a n d I nterr u pti o ns  
5. 4. 1.  
D ose Incre as es f or In a de q u ate E ffic ac y  
F or C o h ort A a n d C o h ort B, itaciti ni b will be gi ve n at a fi x e d starti n g d ose ( 2 0 0  m g or 6 0 0 m g 
Q D) , a n d n o i ncreas e will be all o we d f or i n a de q uate efficac y . 
5. 4. 2.  
D os e M o dific ati o n f or T o xicit y 
A d verse e ve nt data a n d l a b orat or y d ata s h o ul d be re vie we d b y t h e i n vesti gat or wit h t he s u bject 
(eit her i n pers o n or b y tel e p h o ne or em ail) at least wee kl y.  Dat a will als o be m o nit ore d b y t h e 
s p o ns or o n a n o n g oi n g b asis i n or der t o o bser v e a n y e m er gi n g tre n ds.  La b orat or y data s h o ul d be 
use d t o g ui de d os e m o dificati o ns f or i n di vi d ual s u bjects as descri be d i n t his secti o n.  
5. 4. 2. 1.  
L a b or at or y Fi n di n gs T h at Re q uire D ose M o dific ati o n  
T he g o al of t he d ose titr ati o n is t o a d mi nister t he hi g hest d ose t hat ca n be t olerate d w hile 
mai ntai ni n g t he f oll o wi n g s pecific safet y para met ers: 
1.  Platelet c o u nts s h o ul d re mai n a b o ve 3 5 ×  1 0 9/ L ( 5 0 × 1 0 9/ L is desira ble). 
2.  A N C s h o ul d re mai n ≥ 0. 5 × 1 0 9/ L. 
3.  A L T, A S T, bilir u bi n, a n d creati ni ne v al ues s h o ul d n ot e x cee d Gra d e 3 . 
4.  T he s u bject s h o ul d n ot e x perie nce ne w or w orse ni n g a n e mia.  F or t h e p ur p oses of t his 
Pr ot oc ol, ne w or w ors e ni n g a n e mia is defi ne d as f oll o ws: 
a. F or s u bj ects w h o are tra nsf usi o n - de pe n de nt * at baseli ne:  
− R ecei ve d t he s a me t otal n u m ber of pac ke d R B C ( P R B C ) u nits tra nsf use d b et wee n 
st u d y start Da y 1 t hr o u g h Da y 4 2 as w as o bser ve d d uri n g t he 1 2 wee ks b ef ore 
st u d y start; O R 

I nc yte C or p orati o n 
P a ge 3 7  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
− A n i ncreas e b y m ore t ha n 5 0 % i n t otal n u m ber of P R B C  u nits c o m pare d wit h t he 
1 2 wee ks bef ore t h e st u d y start. 
b.  F or s u bjects w h o are tra nsf usi o n-i n de pe n de nt * * at b aseli ne: 
− A decli ne i n he m o gl o bi n of at least 2 g/ d L t o a le v el < 8. 0 g/ d L ( n ot res ulti n g 
fr o m a blee d ca use d b y ac ute tra u ma), if c o nfir m e d b y a re peat la b orat or y 
assess me nt wit hi n 7 da ys wit h o ut i nter ve ni n g c h a n ge i n d os e, use of a n 
er yt hr o p oiesis sti m ula nt , or recei pt of a tra nsf usi o n. 
* B aseli ne tra nsf usi o n -de pe n d e n t is defi ne d as tra nsf usi o ns of at least 6 u nits of P R B Cs  i n t he 1 2 wee ks 
bef ore  st u d y e nr oll me nt, or a he m o gl o bi n le vel of < 8.5 g/ d L, i n t he a bse nce of blee di n g or treat me nt -
i n d uce d a ne mia.  I n a d diti o n, t he m ost rece nt tra nsf usi o n e pis o de m ust ha ve occ urre d i n t he 2 8 da ys 
bef ore  st u d y e nr oll me nt. 
* *  S u bj ects n ot meeti n g t he defi niti o n of tra nsf usi o n -de pe n de nt at baseli ne are c o nsi dere d tra nsf usi o n -
i n de pe n de nt. 
5.  A d diti o nall y, si g nifi ca nt A Es  or la b orat or y a b n or malities ot her t ha n t h ose s pecifie d ma y 
preci pitate a d os e a dj ust me nt or i nterr u pti o n if j u d ge d b y t h e i n vesti gat or t o be at least 
p ossi bl y relate d t o st u d y dr u g.  
5. 4. 2. 2.  
Per mitte d D ose Le v els  
Per mitte d d ose le vels ar e o nl y t h ose s h o w n i n Ta ble  3.  
T a ble 3: 
Per mitte d D ose Le v els b y C o h ort  
 
D ose Le v el 1 
D ose Le vel 2  
D ose Le vel 3  
D ose Le vel 4  
C o h ort A 
2 0 0 m g Q D 
1 0 0 m g Q D 
I nterr u pt 
N/ A  
C o h ort B 
6 0 0 m g Q D 
3 0 0 m g Q D 
2 0 0 m g Q D 
I nterr u pt 
5. 4. 2. 3.  
D ose A dj ust me nt G ui deli nes a n d M a n a gi n g T o xicit y  
He mat ol o gi c or bl o o d c h e mistr y fi n di n gs ma y res ult i n ma n dat or y re d ucti o ns or i nterr u pti o ns i n 
itaciti ni b a d mi nistrati o n as s h o w n i n Ta ble  4.  G ui deli nes are pr o vi d e d f or d ose re d ucti o ns, 
i nterr u pti o ns, restarts, a n d re-es calati o ns i n or der t o pr o vi de c o nsiste nc y i n t he d ose titrati o n 
strate g y; h o we ver, n ot all p ossi ble cases ma y be a ntici pate d b y t h ese g ui deli nes.  T he  
i n vesti gat or ma y us e a m ore ca uti o us a p pr oac h t o d ose i nterr u pti o n, restart, or re-escal ati o n if 
dee me d i n t he s u bject 's b est i nterest, b ut ma y n ot use d oses t hat e x cee d t he g ui deli nes des cri be d 
here u nless a p pr o ve d b y t he me dical m o nit or. 
I n ge ner al, t o xicities are t o be ma na ge d b y d os e re d ucti o ns or i nterr u pti o ns.  Me dicati o ns ma y be 
use d t o ma na ge e m er gi n g t o xicities if nee de d ; h o we ver , please see Secti o ns  5. 6. 2  a n d 5. 6. 3  f or 
restricte d a n d pr o hi bite d me dicati o ns.  Er yt hr o p oi eti n is n ot all o we d d uri n g t he st u d y.  
Gra n ul oc yte gr o wt h fact ors are n ot all o w e d w hile st u d y me di cati o n is bei n g  a d mi nistere d b ut 
ma y b e use d f or se vere n e utr o pe nia at t he i n v esti gat or' s dis creti o n w hile st u d y me dicati o n is 
i nterr u pte d. 
D ose decisi o ns s h o ul d be ma de i n c o nj u ncti o n wit h t he s p o ns or' s me di cal m o nit or w he n s pecial 
cases e xist.  T hese g ui deli nes c o ul d be re vise d b as e d o n e mer gi n g safet y data.  T he s p o ns or will 
pr o vi de a n y r ele va nt safet y u p dates t o t he i n vesti gat or. 

I nc yte C or p orati o n 
P a ge 3 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
T a ble 4: 
D ose I nterr u pti o ns or Re d ucti o ns f or T o xicit y  
L a b or at or y Fi n di n g or 
A d verse E ve nt  
Act i o n T a ke n wit h It aciti ni b D ose 
Re q uire d D ur ati o n of  
D ose Re d ucti o n or I nterr u pti o n  
C O H O R T A  
Restart or re -escalati o n is per mitte d after 
≥ 2 wee ks I F:   
 
St art:  D ose Le vel 1  
First Re d ucti o n:   D ose Le vel 2  
↓ 
P latelet c o u nt  
2 5 t o <  3 5 × 1 0 9/ L 
Re d uce t o or mai ntai n D ose Le vel 2 . 
Platelets rec o ver t o ≥ 5 0  × 1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part . 
Platelet c o u nt  
< 2 5  × 1 0 9/ L 
I nterr u pt d ose. 
Platelets sta bilize at ≥ 3 5 -5 0 × 1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part  
(restart all o we d o nl y at D ose Le vel 2) 
O R  
Platelets rec o ver t o 5 0 × 1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part . 
A N C < 0. 5 × 1 0 9/L 
I nterr u pt d ose.  
A N C rec o vers t o  ≥ 0. 5 × 1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part . 
Pr ot oc ol -defi ne d a ne mia  
Re d uce 1 le vel fr o m c urre nt d ose. 
H e m o gl o bi n sta bilize d f or at l east 4 wee ks 
at ≥ 9 g/ d L . 
C o nfir me d Gra de 4 a 
i ncrease i n A L T, A S T, 
bilir u bi n, or creati ni ne  
I nterr u pt d ose. 
La b orat or y a b n or malit y res ol ves t o Gra de 2 
or  better . 
Ot her n o n he mat ol o gic 
t o xicities 
St u d y dr u g ma y be i nterr u pte d at t he 
discreti o n of t he i n vesti gat or.  
C o ns ult s p o ns or 's me dical m o nit or bef ore 
restarti n g. 
C O H O R T B  
Restart or re -escalati o n is per mitte d after 
≥ 2 wee ks I F:   
 
St art:  D ose Le vel 1  
First Re d ucti o n:  D ose Le vel 2  
Sec o n d Re d ucti o n:  D ose Le vel 3  
↓ 
P latelet c o u nt  
2 5 t o <  3 5 × 1 0 9/ L 
Re d uce 1 le vel fr o m c urre nt d ose 
O R mai ntai n d ose if at D ose L e vel 3. 
Platelets rec o ver t o ≥ 5 0 ×  1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part . 
Platelet c o u nt  
< 2 5 × 1 0 9/ L 
I nterr u pt d ose. 
Platelets sta bilize at ≥ 3 5 -5 0 × 1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part  
(restart per mitte d o nl y at Dose L e vel 3)  
O R  
Platelets  rec o ver t o ≥ 5 0 ×  1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part . 
A N C < 0. 5 × 1 0 9/L 
I nterr u pt d ose. 
A N C rec o vers t o ≥ 0. 5 ×  1 0 9/ L o n 
2 c o nsec uti ve meas ures ≥ 7 da ys a part . 
Pr ot oc ol -defi ne d a ne mia  
Re d uce 1 le vel fr o m c urre nt d ose. 
H e m o gl o bi n sta bilize d f or at l east 4 wee ks at 
≥ 9 g/ d L.  
C o nfir me d Gra de 4 a 
i ncrease i n A L T, A S T, 
bilir u bi n, or creati ni ne  
I nterr u pt d ose. 
La b orat or y a b n or malit y res ol ves t o Gra de 2 or 
better . 
Ot her n o n he mat ol o gic 
t o xicities 
St u d y dr u g ma y be i nterr u pte d at t he 
discreti o n of t he i n vesti gat or.   
C o ns ult s p o ns or 's me dical m o nit or bef ore 
restarti n g. 
a Ac c or di n g t o t h e C T C A E v 4. 0 3.  

I nc yte C or p orati o n 
P a ge 3 9  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
5. 4. 2. 4.  
G ui deli nes f or D ose Rest art o r Re-esc al ati o n 
It is rec o m me n de d t hat a n y la b or at or y fi n di n gs or A Es preci pitati n g a d ose decrease or 
i nterr u pti o n be m o nit ore d at least t wice w ee kl y u ntil rec o vere d.  T he d ose i nterr u pti o n or 
re d ucti o n s h o ul d be at least 2 wee ks i n d urati o n, after w hic h st u d y dr u g ma y be rec h alle n ge d 
(ie, restarte d or r e-es calat e d) I F t he criteri o n s h o w n i n Ta ble  4 has bee n met.  
T he rec halle n ge ma y  utli ze t he d ose t hat preci pitat e d t he re d u cti o n or i nterr u pti o n, u nless 
ot her wise specifie d  i n Ta ble  4.  If rec o ver y is pr ol o n ge d or t he a b n or malit y is ver y pr o n o u nce d, 
c o nsi der rec halle n gi n g at t he ne xt l o wer d ose , if o ne is a vaila ble.  T h e decisi o n t o rec halle n ge at 
t he d ose preci pitati n g t he e ve nt or at a l o w er a vail a ble d ose le vel  s h o ul d de pe n d o n t he d urati o n 
a n d se verit y of t he a b n or malit y; disc ussi o n wit h t he me dical m o nit or is rec o m me n de d.  I n t he 
case t hat r ec h alle n ge is c o n d ucte d at a d ecrease d d ose, t he d ose ma y be re -escalate d 
s u bse q ue ntl y (after ≥ 2 w ee ks) if safet y para meters per mit. 
A n y  gi ve n  d os e ma y be r ec halle n ge d a ma xi m u m of t wice.  S u bse q ue ntl y, a n y rec h alle n ge m ust 
utilize t he ne xt l o wer d ose f or t hat c o h ort ( Ta ble  3).   (E x ce pti o n s ma y b e gra nte d b y t he 
s p o ns or's me dical m o nit or if t he preci pitati n g e v e nts are se parate d b y l o n g p eri o ds of sta ble 
c o u nts.)  If t he l o w est all o wa ble d ose h as bee n rec halle n ge d t wice a n d is f o u n d t o be n ot 
t olerate d, O R if t he st u d y dr u g ca n n ot safel y be resta rte d at t he l o west a v aila ble d ose le vel wit hi n 
2 1 da ys, t h e s u bject s h o ul d be wit h dra w n fr o m t he st u d y ( see Secti o n  5. 5. 1 )  
5. 4. 3.  
I nterr u pti o n of R u x oliti ni b  ( C o h ort A O nl y ) 
D ose re d u cti o ns of r u x oliti ni b t o dail y d ose s b el o w 5 m g BI D are n ot p er mitte d a n d will res ult i n 
t he disc o nti n uati o n of t he s u bject fr o m t he st u d y.  All c ha n ges i n d ose s h o ul d be rec or de d i n t he 
e C R F, a n d t he s u bject s h o ul d be n otifie d b y p h o n e wit h writte n f oll o w- u p i n cases w here 
la b orat or y dat a s u bse q ue nt t o a st u d y visit i n dicate t hat a d ose c h a n ge is re q uire d.  
D ose m o dificati o n or te m p orar y i nterr u pti o n (f or n o m ore t ha n 8 wee ks) of r u x oliti ni b f or safet y 
reas o ns is at t he discr eti o n of t he i n vesti gat or wit h a p pr o val fr o m t he m e dical m o nit or. 
5. 5.  
W it h dr a w al of S u bjects Fr o m St u d y Tre at me nt  
5. 5. 1.  
Wit h dr a w al Criteri a  
S u bjects m ust  be wit h dr a w n fr o m st u d y treat me nt f or t he f oll o wi n g reas o ns: 
•  If t o xicit y r e q uiri n g itaciti ni b interr u pti o n is n ot res ol ve d s ufficie ntl y t o per mit st u d y 
dr u g a d mi nistrati o n t o res ume wit h 2 1 da ys.  
•  Treat me nt wit h itaciti ni b is i nterr u pte d f or m ore t ha n 2 1  da ys f or a n y reas o n ot her 
t ha n t o xicit y. 
•  If t he l o west all o wa bl e d ose ( base d o n c o h ort) h as been rec halle n ge d t wice a n d was 
n ot t olerate d. 
•  C o h ort A:  Treat me nt wit h r u x oliti ni b is i nterr u pte d f or ≥ 8 wee ks, u nless a p pr o ve d 
b y t he me di cal m o nit or, or if r u x oliti ni b is re d uce d t o a d ose bel o w 5 m g Q D.  
•  T he s u bject re q uires s ple nic irra diati o n. 

I nc yte C or p orati o n 
P a ge 4 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
•  T he s u bject e x hi bits le u ke mic tra nsf or m ati o n (as e vi de nce d b y b o ne m arr o w blast 
c o u nts of at least 2 0 %, or peri p heral blast c o u nts of at least 2 0 %, lasti n g at l east 
8 c o nsec uti ve w ee ks ). 
•  T he s u bject bec o mes pre g na nt ( p ositi ve uri n e pre g na n c y test, c o nfir m e d b y p ositi ve 
ser u m pre g na nc y [ser u m h u ma n c h ori o nic g o na d otr o pi n] test res ults). 
•  C o nse nt is wit h dra w n. 
•  F urt her p artici pati o n w o ul d be i nj uri o us t o t he s u bject' s healt h or w ell- bei n g, i n t he 
i n vesti gat or's me dical j u d g me nt. 
•  T he st u d y is t er mi nat e d  b y t he s p o ns or. 
•  T he st u d y is t er mi nat e d  b y t he l o cal healt h a ut h orit y, I R B, or I E C. 
A s u bject  m a y  be disc o nti n ue d fr o m st u d y treat me nt as f oll o ws: 
•  S u bjects ma y c h o os e t o wit h dra w fr o m t he st u d y at a n y ti me wit h o ut pe nalt y of 
je o par dizi n g t heir h ealt h care or l oss of be n efits t o w hic h t he s u bject is ot her wise 
e ntitle d.  E ver y reas o na bl e eff ort s h o ul d be ma d e t o deter mi ne t he reas o n  t h at a 
s u bject wit h dra ws pr e mat urel y, a n d t his i nf or mati o n s h o ul d be rec or de d i n t he e C R F.  
•  If, d uri n g t he c o urse of t h e st u d y, a s u bject is f o u n d n ot t o ha ve met eli gi bilit y 
criteria, t he n t he m e dical m o nit or, i n c olla b orati o n wit h t he i n vesti gat or, will 
deter mi ne w het h er t he s u bject s h o ul d be wit h dra w n fr o m t he st u d y (see Secti o n 1 0. 5 , 
Pr ot oc ol A d here n ce).  
•  A s u bject ma y be wit h dr a w n fr o m t he st u d y if, i n t he i n vesti gat or' s e x pert me dical 
j u d g me nt, t he s u bject is n o nc o m plia nt wit h t he st u d y re q uire me nts.  T h e s p o ns or 
s h o ul d be c o ns ulte d f or i nstr ucti o n o n ha n dli n g t h e s u bject.  S u bjects ma y be 
wit h dra w n at t he discr eti o n of t he h ealt h a ut h oriti es  or t he i n vesti gat or. 
5. 5. 2.  
Wit h dr a w al Pr oce d ures  
I n t he e ve nt t hat t he d ecisi o n is ma de t o per ma ne ntl y disc o nti n ue t he st u d y treat me nt (itaciti ni b) 
t he E O T visit s h o ul d be c o n d ucte d.  Reas o na bl e eff orts s h o ul d be ma de t o h a ve t he s u bject ret ur n 
f or a f oll o w- u p visit.   T h ese visits are des cri be d i n Secti o n 6 .  T he last date of t he last d ose of 
st u d y treat me nt a n d t he r eas o n f or s u bject wit h dra wal will be rec or de d i n t he eC R F . 
If a s u bject is wit h dr a w n f r o m t he st u d y tre at me nts: 
•  T he st u d y m o nit or or s p o ns or m ust be n otifie d. 
•  T he reas o n(s) f or wit h dra wal m ust be d oc u me nte d i n t he s u bject's me di cal rec or d a n d 
i n t he eC R F.  
•  T he E O T  visit s h o ul d be perf or me d, i n cl u di n g diar y c o m pleti o n. 
•  T he date of t h e E O T visit s h o ul d be rec or de d i n t he I X R S. 
•  I n t he e ve nt t hat a d ecisi o n is ma de t o per ma ne ntl y disc o nti n ue t he st u d y treat me nt, 
reas o na bl e eff orts s h o ul d be ma de t o ha v e t he su bject  ret ur n f or a f oll o w- u p visit f or 
safet y a n d, if p ossi ble, s h o ul d be f oll o we d u ntil st u d y treat me nt -relate d t o xicities 
res ol ve, ret ur n t o baseli n e , or are dee me d irre versi ble, w hic he ver is l o n gest. 

I nc yte C or p orati o n 
P a ge 4 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
5. 6.  
C o nc o mit a nt Me dic ati o ns  
5. 6. 1.  
Per mitte d Me dic ati o ns  
All c o nc o mita nt me dicati o ns a n d treat me nts m ust be rec or de d i n t he e C R F.  A n y pri or 
me dicati o n recei ve d u p t o 3 0 da ys b ef ore e nr ol me nt will be rec or d e d i n t he e C R F.  C o nc o mita nt 
treat me nts or pr o ce d ur es t hat are r e q uire d t o ma n a ge a s u bject's me dical c o n diti o n d uri n g t he 
st u d y will als o be rec or d e d i n t he e C R F. 
A nti bi otic pr o p h yla xis f or c hr o nic tr eat me nt is per mitte d; s u bjects re q uiri n g ac ute a nti bi otic 
treat me nt at t he ti me of s cree ni n g m ust dela y s cree ni n g/e nr oll me nt u ntil t he c o urse of a nti bi otic 
t hera p y is c o m plete d.  
T he s u bject nee ds t o n otif y t he i n v esti gati o nal site a b o ut a n y ne w me di cati o ns he/s he ta kes after 
t he start of t he st u d y dr u g.  All me dicati o ns ( ot her t ha n st u d y dr u g) a n d si g nifica nt n o n dr u g 
t hera pies (i ncl u di n g p h ysical t hera p y a n d bl o o d tra nsf usi o ns) a d mi nistere d after t he s u bject starts 
treat me nt wit h st u d y dr u g m ust be liste d o n t he C o nc o mita nt Me dicati o ns/ Si g nifica nt N o n dr u g 
T hera pies A fter Start of St u d y Dr u g e C R F.   
5. 6. 2.  
Restricte d Me dic ati o ns  
T he f oll o wi n g m e dicati o ns are pr o hi bite d d uri n g t he st u d y: 
1.  As piri n i n d oses e x cee di n g 8 1 m g per da y i n t he U nite d States, 1 2 5 m g i n E ur o pe or 
sta n dar d d ose f or pr o p h yla xis is n ot per mitte d.  L o w- d ose as piri n is per mitte d.  
2.  Aceta mi n o p he n a n d N S AI Ds  (e g, i b u pr ofe n) m a y be us e d at o ver-t he-c o u nter d oses.  
S u bjects recei vi n g o ver -t he-c o u nter N S AI Ds s h o ul d n ot e x cee d t he rec o m me n de d d ose 
a n d s h o ul d be e nc o ura ge d t o use gastr o pr otecti ve a ge nts (a ntaci ds, H 2 a nta g o nists, or 
pr ot o n p u m p i n hi bit ors). 
3.  I n d u cers of C Y P 3 A 4 (A p pe n di x H ) ma y be us e d wit h ca uti o n, a n d i n vesti gat ors s h o ul d 
see k ot her o pti o ns if a v aila ble. 
4.  Mil d/ m o derate C Y P 3 A 4 i n hi bit ors ( A p pe n di x H ) ma y b e use d wit h ca uti o n.  Differe nces 
i n i n di vi d ual se nsiti vit y a n d variati o n i n p ote nc y of i n hi biti o n of vari o us C Y P e nz y m es 
ma y r es ult i n t he nee d f or a re d u ce d d ose of r u x oliti ni b / or itaciti ni b d uri n g a peri o d of 
c o nc o m ita nt me dicati o n use.  If re q uire d f or safet y,  r u x oliti ni b d ose ma y be re d uce d 
fr o m BI D  t o Q D  i n t hese circ u msta nces.  T he s p o ns or's me di cal m o nit or ma y be 
c o ns ulte d f or a d vice w he n usi n g t hese a ge nts. 
5.  If c o nc o mita nt a d mi nistr ati o n of a n a ntic oa g ul a nt/a nti platelet me dicati o n is i n dicate d, 
t he n ca uti o n a n d e n h a nce d m o nit ori n g is re q uire d.  Hist or y of t hr o m b o c yt o p e nia a n d a n y 
c o nc urr e nt r u x oliti ni b-relate d t hr o m b oc yt o pe nia s h o ul d be a fact or i n t he c h oice of 
a ntic oa g ula nt a n d d ose.   
6.  Gra n ul oc yte gr o wt h fact o rs are n ot all o w e d w hile st u d y me dicati o n is bei n g a d mi nistere d 
b ut ma y be us e d f or s e vere ne utr o p e nia at t he i n vesti gat or's discreti o n w hile st u d y 
me dicati o n is i nterr u pte d  
7.  If a s u bject re q uires ster oi ds f or a c o m or bi d c o n diti o n d uri n g st u d y partici p ati o n, t he n 
c o nti n uati o n i n t he st u d y will be c o nsi dere d o n a n i n di vi d ual basis b y t he s p o ns or a n d t he 
i n vesti gat or. 

I nc yte C or p orati o n 
P a ge 4 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4  A U G 2 0 1 7  
C O N FI D E N TI A L  
5. 6. 3.  
Pr o hi bite d Me dic ati o ns  
1.  A n y i n vesti gati o nal me di cati o n ( a dr u g t h at is n ot a p pr o ve d f or a n y i n dicati o n) ot her t ha n 
t he st u d y dr u g is pr o hi bit e d.  Use of s u c h me dicati o ns wit hi n 3 0 da ys or 5 h alf-li ves, 
w hic he ver is l o n ger, bef ore t he first d ose of st u d y dr u g a n d d uri n g t he st u d y t hr o u g h t he 
safet y f oll o w- u p visit is pr o hi bite d.  
2.  Use of a n y me di cati o n use d t o treat M F ( e g, H U , i nterfer o n, t h ali d o mi de, b us ulfa n, 
le nali d o mi de, a na gr eli de, ot her c yt ot o xics or i m m u ne m o d ulat ors, ot her J A K 1 i n hi bit ors, 
or a n y i n vesti gati o nal a ge nt) is n ot per mitte d at a n y ti me be gi n ni n g at D a y 1 u p u ntil t he 
ti me t hat itaciti ni b t hera p y is per m a ne ntl y disc o nti n ue d.  I n vesti gat ors m ust deter mi ne 
t hat t he s u bject is a ble t o wit h dra w c urre nt t hera p y wit h o ut it bei n g li kel y t o lea d t o 
si g nifica nt d eteri or ati o n of t he s u bject's c o n diti o n i n or der f or t h e s u bject t o q ualif y f or 
t he st u d y. 
3.  Use of T P O  rece pt or a g o nists (r o mi pl osti m, eltr o m b o pa g) is n ot per mitte d fr o m scree ni n g 
t o t he safet y foll o w- u p visit. 
4.  Us e of er yt hr o p oieti n  is n ot per mitte d fr o m scree ni n g. 
5.  Use of rif a m pi n a n d St J o h n' s W ort, is n ot per mitte d at a n y ti me d uri n g partici pati o n i n 
t he st u d y fr o m scree ni n g t o safet y foll o w- u p visit. 
6.  Use of p ote nt /str o n g C Y P 3 A 4 i n hi bit ors ( b oce pre vir, clarit hr o m yci n, c o ni v a pta n, 
i n di na vir, itrac o naz ole, k et oc o naz ole, l o pi na vir/rit o na vir, rit o na vir, mi befra dil, 
nefaz o d o ne, nelfi n a vir, p osac o naz ole, sa q ui na vir, tela pre vir, telit hr o m yc i n, v oric o naz ole) 
is pr o hi bite d.  Base d o n t he l o w o verall bi oa v aila bilit y of t o pical ket oc o n az ole, t here are 
n o restricti o ns o n t o pical ket oc o naz ole i n t he st u d y. 
See A p pe n di x H  f or a list of C Y P  i n hi bit ors a n d i n d ucers. 
6.  
S T U D Y A S S E S S M E N T S  
All st u d y assess me nts will be perf or me d as i n dicat e d i n t he sc he d ule of assess me nts (see Ta ble  5 
a n d Ta ble  6), a n d all la b orat or y assess me nts will b e perf or me d as i n dicate d i n Ta ble  7 a n d 
Ta ble  8.  Re q uire d la b orat or y a n al yt es are liste d i n Ta ble  9.  T he or d er of assess me nts is 
s u g geste d b y t h e or der of me nti o n wit hi n t he sc he d ule.  See Secti o n 7  f or i nstr ucti o ns o n eac h 
assess me nt.  F urt h er details of st u d y pr oce d ures a n d assess me nts ca n b e f o u n d i n t he st u d y 
refere nce ma n ual.

I nc yte C or p orati o n 
P a ge 4 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
 
C O N FI D E N TI A L  
T a ble 5: 
Sc he d ule of Assess me nts  f or C o h ort A a n d B ( Scree ni n g T hr o u g h Wee k 1 2) 
Visit D a y ( R a n g e)  
Secti o n  
Scree ni n g  
D a y -2 8 t o 
D a y - 8 
B aseli ne  
D a y -7 t o  
D a y - 1 
D 1  
W 2 
( D 8) 
W 4 ( D 2 9), 
W 8 ( D 5 7)  
W 1 2 
( D 8 5) 
N otes  
± 5 d  
± 5 d  
I nf or me d c o nse nt 
7. 1  
X 
 
 
 
 
 
 
C o ntact I X R S  
7. 1  
X 
 
X 
 
X 
X 
 
I ncl usi o n/e xcl usi o n criteria 
3  
X 
X 
 
 
 
 
 
Pri or me dical a n d  me dica ti o n hist or y  
7. 3  
X 
X 
 
 
 
 
 
C o nc o mita nt me dicati o n re vie w  
7. 4  
 
X 
X 
 
X 
X 
 
Tra nsf usi o n hist or y/stat us  
7. 3  
X 
X 
X 
 
X 
X 
 
Rec or d  A Es  
7. 5. 2  
X 
X 
X 
X 
X 
X 
 
C o m pre he nsi ve p h ysic al e xa mi n ati o n  
7. 5. 3. 1  
X * 
 
X 
 
 
 
*I ncl u des hei g ht (scree ni n g o nl y).  
Tar gete d p h ysical e xa mi n ati o n  
7. 5. 3. 2  
 
 
 
 
X 
X 
 
S plee n pal pati o n a n d meas ure /li v er 
pal pati o n  
7. 6. 2  
X 
X 
 
 
X 
X 
 
Vital si g ns  
7. 5. 4  
X 
X 
X 
X 
X 
X 
 
1 2 -lea d E C G 
 7. 5. 5   
X 
 
 
 
 
 
 
M RI/ C T of t he u p p er a n d l o wer 
a b d o me n a n d pel vis  
7. 6. 3  
 
X 
 
 
 
X 
 
E C O G stat us  
7. 7. 1  
X 
 
 
 
 
 
 
P GI C ( A p pe n di x  F) 
7. 7. 2  
 
 
 
 
X 
X 
 
I W G-M R T assess me nt * 
7. 8  
 
 
 
 
 
 
* R es p o nse assess me nt starts at Wee k 2 4  
Dis pe nse a n d/ or bri n g M F S A F v 2. 0 
diar y t o visit  
7. 6. 4  
 
X 
X 
X 
X 
X 
 
M o difie d M F S A F v 2. 0 diar y 
(A p pe n di x  D) 
7. 6. 4  
 
C o m plete d e ver y e ve ni n g fr o m b aseli n e t hr o u g h Wee k 2 4 
( 2 5 wee k s i n t otal) 
 
M P N -S A F ( A p p e n di x  E) 
7. 7. 3  
 
X 
 
 
 
X 
 
La b orat or y assess me nts *  
7. 5. 6  
X 
X 
X 
X 
X 
X 
* S ee Ta ble  7 a n d Ta ble  8. 
Dis pe nse re mi n d er car d  
7. 1 1. 4  
 
X 
X 
 
X 
X 
 
A d mi nister st u d y dr u g d uri n g visit  
7. 1 1. 1  
 
 
X 
X 
X 
X 
 
Di s pe nse st u d y dr u g 
7. 1 1. 2  
 
 
X 
 
X 
X 
 
Dr u g acc o u nta bilit y assess me nt  
7. 1 1. 3  
 
 
 
X 
X 
X 
 

I nc yte C or p orati o n 
P a ge 4 4  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
 
C O N FI D E N TI A L  
T a ble 6: 
Sc he d ule of Assess me nts  f or C o h ort A a n d B  (Wee k 1 6  T hr o u g h F oll o w-U p)  
Visit D a y ( R a n g e)  
Secti o n  
W 1 6 ( D 1 1 3), 
W 2 0 ( D 1 4 1)  
W 2 4 ( D 1 6 9)  
E xte nsi o n 
Visits ( Q 1 2 W 
A fter W 2 4) 
E O T /E arl y 
Ter m i n. Visit  
+ 7 d  of disc o n.  
S afet y F oll o w -U p  
3 0 -3 5 d After L ast 
D ose of It aciti ni b 
N otes  
± 5 d  
± 5 d  
± 7 d  
I nf or me d c o nse nt 
7. 1  
 
 
 
 
 
 
C o ntact I X R S  
7. 1  
X 
X 
X 
X 
 
 
I ncl usi o n/e xcl usi o n criteria 
3  
 
 
 
 
 
 
Pri or me dical a n d me dicati o n hist o r y  
7. 3  
 
 
 
 
 
 
C o nc o mita nt me dicati o n re vie w  
7. 4  
X  
X  
X  
X  
X  
 
Tra nsf usi o n hist or y/stat us  
7. 3  
X  
X  
X  
X  
X  
 
Rec or d A Es  
7. 5. 2  
X  
X  
X  
X  
X  
 
C o m pre he nsi ve p h ysic al e xa mi n ati o n  
7. 5. 3. 1  
 
X 
 
 
X 
 
Tar gete d p h ysical e xa mi n ati o n  
7. 5. 3. 2  
X 
 
X 
X 
 
 
S plee n pal pati o n a n d meas ure /li v er 
pal pati o n  
7. 6. 2  
X 
X 
X 
X 
X 
 
Vital si g ns  
7. 5. 4  
X 
X 
X 
X 
X 
 
1 2 -lea d E C G 
7. 5. 5  
 
 
 
X 
 
 
M RI/ C T of t he u p p er a n d l o wer 
a b d o me n a n d pel vis  
7. 6. 3  
 
X 
X 
 
 
 
E C O G stat us  
7. 7. 1  
 
X  
 
 
X  
 
P GI C ( A p pe n di x  F ) 
7. 7. 2  
X  
X  
X  
X  
 
 
I W G-M R T assess me nt  
7. 8  
 
X *  
X *  
 
 
* Q 2 4 W   
Dis pe nse a n d/ or bri n g M F S A F v 2. 0 
diar y t o visit  
7. 6. 4  
X 
X 
 
 
 
 
M o difie d M F S A F v 2. 0 diar y 
(A p pe n di x  D) 
7. 6. 4  
C o m plete d e ver y e ve ni n g fr o m 
b aseli n e t hr o u g h Wee k  2 4 
( 2 5 wee k s i n t otal) 
 
 
 
 
M P N -S A F ( A p p e n di x  E) 
7. 7. 3  
 
X 
X * 
 
 
* Q 1 2 W  
La b orat or y assess me nts *  
7. 5. 6  
X 
X 
X 
X 
X 
* S ee Ta ble  7 a n d Ta ble  8. 
Dis pe nse re mi n d e r car d 
7. 1 1. 4  
X  
X  
X  
 
 
 
A d mi nister st u d y dr u g d uri n g visit  
7. 1 1. 1  
X 
X 
 
 
 
 
Dis pe nse st u d y dr u g  
7. 1 1. 2  
X  
X  
X  
 
 
 
Dr u g acc o u nt a bilit y assess me nt  
7. 1 1. 3  
X  
X  
X  
X  
 
 

I nc yte C or p orati o n 
P a ge 4 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
 
C O N FI D E N TI A L  
T a ble 7: 
Sc he d ule of L a b or at or y Assess me nts  f or C o h ort A a n d B ( Scree ni n g T hr o u g h Wee k 1 2) 
 
Secti o n  
Scree ni n g  
D a y -2 8 t o 
D a y - 8 
B aseli ne  
D a y -7 t o 
D a y - 1 
D 1  
W 2 
( D 8) 
W 4 ( D 2 9), 
W 8 ( D 5 7)  
W 1 2 
( D 8 5) 
N otes  
Wi n d o w  
 
T he wi n d o w f or l a b or at or y visits is ± 3 d a ys  
 
L oc al L a b or at or y Assess me nts  
 
Bl o o d c he mistries  
7. 5. 6  
X  
X *  
X *  
 
X  
X  
* S h o ul d be ta k e n as cl ose as p ossi ble t o Da y 1 b ut ma y be 
dra w n u p t o 3 da ys bef ore first d ose.  O nl y 1 sa m ple f or 
b aseli ne/ Da y 1 is re q uire d.  
He mat ol o g y  
7. 5. 6  
X  
X *  
X *  
 
X  
X  
* S h o ul d be ta ke n as cl ose as p ossi ble t o Da y  1 b ut m a y be 
dra w n u p t o 3 da ys bef ore first d ose.  O nl y 1 sa m ple f or 
b aseli ne/ Da y 1 is re q uire d.  
C oa g ulati o n pa nel  
7. 5. 6  
X  
 
 
 
 
X  
 
Uri ne pre g na nc y test *  
7. 5. 6. 1  
 
 
X * *  
 
 
 
* Al l fe male s u bjects of c hil d beari n g p ote ntial. 
* * Pre g na nc y tests s h o ul d be c o n d ucte d m ore ofte n if 
re q uire d b y l ocal re g ulati o ns. 
B o ne marr o w bi o ps y/as pirate  
a n d a nal ysis  
7. 5. 6  
 
X *  
 
 
 
 
* R e q uire me nt f or baseli ne bi o ps y/as pirate ma y be f ulfille d 
b y pri or sta n dar d -of -care assess me nt wit hi n 2 m o nt hs of 
D a y 1 if data are ma de a vaila ble t o t he i n vesti gat or a n d 
s p o ns or. 
Li pi d pa nel (re q uires 
o ver ni g ht fast)  
7. 5. 6  
X  
 
 
 
 
X  
 
Ser o l o g y - he patitis *  
7. 5. 6  
X  
 
 
 
 
 
* H B V, H C V  
Uri nal ysis  
7. 5. 6  
X  
 
 
 
 
X  
 
Ser u m pre g na nc y *  
7. 5. 6. 1  
X  
 
 
 
 
 
* All fe male s u bjects of  c hil d beari n g p ote ntial. 
F S H *  
7. 5. 6. 1  
X  
 
 
 
 
 
* T o d oc u me nt h or m o nal me n o pa use.  
Ce ntr al L a b or at or y Assess me nts *  
* T he ce ntral la b orat or y is t he s p o ns or or s p o ns or's desi g nee.  
C o h ort A a n d B *  
P K sa m ples  
7. 9  
 
 
 
X * *  
X * * *  
 
* C o h ort A, see Ta ble  1 0 .  C o h ort B, see Ta ble  1 1 . 
* * F or C o h ort A , itaciti ni b s h o ul d be a d mi nistere d  after last 
P K c ollecti o n ; see Ta ble  1 0 . 
* * * We e k 4 o nl y.  
C orrelati ve p las ma 
7. 1 0. 2  
 
 
X  
X  
X *  
X  
* We e k 4 o nl y  

I nc yte C or p orati o n 
P a ge 4 6  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
 
C O N FI D E N TI A L  
T a ble 8: 
Sc he d ule of L a b or at or y Assess me nts  f or C o h ort A a n d B ( Wee k 1 6 T hr o u g h F oll o w-U p ) 
 
Secti o n  
W 1 6 
( D1 1 3) , 
W 2 0 
( D 1 4 1) 
W 2 4 
( D 1 6 9) 
E xte nsi o n 
Visits ( Q 1 2 W 
After W 2 4)  
E O T /E arl y 
Ter m i n. Visit  
+ 7 d  of disc o n.  
S afet y F oll o w -U p  
3 0 -3 5 d After L ast 
D ose of It aciti ni b 
N otes  
Wi n d o w  
 
T he wi n d o w f or l a b or at or y visits is ± 3 d a ys  
 
L oc al L a b or at or y Assess me nts  
 
Bl o o d c he mistries  
7. 5. 6  
X 
X 
X 
X 
X 
 
He mat ol o g y  
7. 5. 6  
X 
X 
X 
X 
X 
 
C oa g ulati o n pa nel  
7. 5. 6  
 
X 
X 
X 
X 
 
Uri ne pre g na nc y test *  
7. 5. 6. 1  
 
 
 
 
 
* All fe male s u bjects of c hil d beari n g p o te ntial. 
B o ne marr o w 
bi o ps y/as pirate, a n d a n al ysis  
7. 5. 6  
 
X 
X *  
 
 
* R e q uire d Q 2 4 W.  
Li pi d pa nel (re q uires 
o ver ni g ht fast)  
7. 5. 6  
 
X 
X *  
X 
X 
* R e q uire d Q 1 2 W.  
Ser ol o g y * - he p atitis  
7. 5. 6  
 
 
 
 
 
* H B V, H C V  
Uri nal ysis  
7. 5. 6  
 
X 
X *  
 
X 
* R e q uire d Q 1 2 W.  
Ser u m pre g na nc y *  
7. 5. 6. 1  
 
 
 
X 
 
* All fe male s u bject s of c hil d beari n g p ote ntial. 
F S H *  
7. 5. 6. 1  
 
 
 
 
 
* T o d oc u me nt h or m o nal me n o pa use.  
Ce ntr al L a b or at or y * Assess me nts  
* T he ce ntral la b orat or y is t he s p o ns or or s p o ns or 's 
desi g nee.  
C o h ort A a n d B *  
P K sa m ples  
7. 9  
 
 
 
 
 
* C o h ort A, see Ta ble  1 0 .  C o h ort B, see Ta ble  1 1 . 
C orrelati ve plas ma  
7. 1 0. 2  
 
X 
X * *  
 
 
* * Wee k 3 6 a n d 4 8 o nl y  
 

I nc yte C or p orati o n 
P a ge 4 7  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
 
C O N FI D E N TI A L  
T a ble 9:  
L oc al L a b or at or y Tests:  Re q uire d A n al ytes 
Bl o o d C he mistr y  
He m at ol o g y  
Uri n al ysis  Wit h 
Micr osc o pic E x a mi n ati o n  
He p atitis Scree ni n g  
C o a g ul ati o n  
Al b u mi n  
Al kali ne p h os p hatase  
A L T  
A S T  
Bicar b o nate  
Bl o o d urea nitr o ge n  
Calci u m  
C hl ori de  
Creati ni ne  
Ferriti n  
Gl uc ose  
Lactate de h y dr o ge nase  
P h os p hate  
P otassi u m  
S o di u m  
T otal bilir u bi n  
Direct bilir u bi n (if t otal bilir u bi n is 
ele vate d a b o ve U L N)  
T otal pr otei n  
Uric aci d  
C o m plete bl o o d c o u nt , 
i ncl u di n g re p orti n g of % 
blasts  
He m o gl o bi n  
He mat ocrit  
Platelet c o u nt  
R B C  c o u nt  
W B C  c o u nt  
 
Differe ntial c o u nt, i ncl u di n g:  
B as o p hils  
E osi n o p hils  
L y m p h oc ytes  
M o n oc y tes 
Ne utr o p hils  
 
A bs ol ute val ues m ust be 
pr o vi de d f or:  
W B C differe ntial la b orat or y 
res ults: 
L y m p h oc ytes  
Ne utr o p hils  
 
C ol or a n d a p peara nce  
p H a n d s pecific gra vit y  
Bilir u bi n  
Gl uc ose  
Ket o nes  
Le u k oc ytes  
Nitrite  
Occ ult bl o o d  
Pr otei n  
Ur o bili n o ge n  
He patitis B s u rface a nti ge n 
He patitis  B s urface a nti ge n 
a nti b o d y 
He patitis A , B c ore a nti b o d y  
H B V -D N A  
H C V a nti b o d y  
H C V -R N A  
P T  
P T T  
I N R 
Li pi d P a nel  
Pre g n a nc y Testi n g  
T otal ch olester ol  
Tri gl yceri des  
L D L  
H D L  
Fe male s u bj ects of 
c hil d beari n g p ote ntial 
o nl y re q uire a ser u m test 
at scree ni n g a n d E O T a n d 
a uri ne pre g na nc y test 
bef ore t he first d ose o n 
C ycle 1 Da y  1.  
Pre g na nc y tests (ser u m or 
uri ne) s h o ul d be re peate d 
if re q uire d b y l ocal 
re g ulati o ns. 
F S H  
H D L = hi g h -de nsit y li p o pr otei n; I N R = i nter n ati o nal n or malize d rati o; L D L = l o w -d e nsit y li p o pr otei n ; 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. 
N ote:  A d diti o nal tests ma y b e re q uire d, as a gree d b y i n vesti g at or a n d s p o ns or, b ase d o n e mer gi n g safet y d ata . 

I nc yte C or p orati o n 
P a ge 4 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
T a ble 1 0: 
Sc he d ule of P h ar m a c o ki netic S a m pli n g f or C o h ort A ( It a citi ni b a n d 
R u x oliti ni b)  
Wee k 2  ( D a y 8) 
Wee k 4 
S u bj ect arri ves ha vi n g wit h hel d b ot h itaciti ni b a n d 
r u x oliti ni b 
Pre d ose sa m ple = Ti me 0 sa m ple  
A d mi nister ru x oliti ni b  
Ti me d sa m ples:  
1 h o ur p ost d ose  ( ± 1 5  mi n) 
2 h o ur s p ost d ose  ( ± 3 0  mi n)  
5 h o ur s p ost d ose  ( ± 6 0  mi n)  
8 h o ur s p ost d ose ( ±  6 0  mi n) a 
A d mi nister itaciti ni b  
S u bj ect arri ves ha vi n g wit h hel d b ot h itaciti ni b a n d 
r u x oliti ni b 
Pre d ose sa m ple = Ti me 0 sa m ple  
A d mi nis ter itaciti ni b pl us r u x oliti ni b  
Ti me d sa m ples:  
1 h o ur p ost d ose  ( ± 1 5  mi n)  
2 h o ur s p ost d ose  ( ± 3 0  mi n)  
5 h o ur s p ost d ose  ( ± 6 0  mi n)  
8 h o ur s p ost d ose ( ±  6 0  mi n)  
a Ei g ht -h o ur p ost d ose sa m ples o n Wee k 2 s h o ul d o nl y b e c ollecte d if t h e s u bject is still i n cli nic at t h e sc h e d ule d ti me of 
c ollecti o n (ie,  at least 7 h p ost d ose).  If t h e s u bject will b e release d b ef ore t h e start of t h e c ollecti o n wi n d o w ( 7 h p ost d ose) , t he 
sa m ple is n ot re q uire d.  T h e s u bject s h o ul d recei ve itaciti ni b Wee k 2 after c ollecti o n of t h e last P K sa m ple at eit h er 5 or 8  h o urs 
p ost d ose.  T he Wee k 4 ei g ht -h o ur p ost d ose sa m ple is re q uire d.  
T a ble 1 1: 
Sc he d ule of P h ar m a c o ki netic S a m pli n g f or C o h o rt B (It aciti ni b Al o ne) 
Wee k 2 ( D a y 8)  
Wee k 4  
S u bj ect arri ves ha vi n g wit h hel d  itaciti ni b  
Pre d ose sa m ple = Ti me 0 sa m ple  
A d mi nister itaciti ni b  
Ti me d sa m ples:  
1 h o ur p ost d ose  ( ± 1 5  mi n)  
2 h o ur s p ost d ose  ( ± 3 0  mi n)  
5 h o ur s p ost d ose  ( ± 6 0  mi n)  
8 h o ur s p ost d o se ( ± 6 0  mi n) a 
S u bj ect arri ves ha vi n g wit h hel d itaciti ni b  
Pre d ose sa m ple = Ti me 0 sa m ple  
A d mi nister itaciti ni b   
Ti me d sa m ples:  
1 h o ur p ost d ose  ( ± 1 5 mi n)  
2 h o ur s p ost d ose  ( ± 3 0 mi n)  
5 h o ur s p ost d ose  ( ± 6 0 mi n)  
8 h o u rs p ost d ose ( ±  6 0 mi n)  
a Ei g ht -h o ur p ost d ose sa m ples o n Wee k 2 s h o ul d o nl y b e c ollecte d if t h e s u bject is still i n cli nic at t h e sch e d ule d ti me of 
c ollecti o n (ie,  at least 7 h p ost d ose).  If t h e s u bject will b e release d b ef ore  t h e start of t h e c ollecti o n wi n d o w ( 7 h p ost d ose) , t he 
sa m ple is n ot re q uire d.  T h e Wee k 4 ei g ht-h o ur p ost d ose sa m ple is re q uire d.  
6. 1.  
Scree ni n g  
Scree ni n g is t he i nter val bet wee n si g ni n g t he I C F a n d t he be gi n ni n g of t he 7- da y ba seli ne p eri o d 
(ie, Da y - 2 8 t o D a y - 7).  Scree ni n g ma y n ot e x cee d 2 1 da ys.  Assess me nts t hat are re q uire d t o 
de m o nstrate eli gi bilit y ma y b e perf or me d o v er t he c o urse of 1 or m ore d a ys d uri n g t he s cree ni n g 
pr ocess.  
S u bjects s h o ul d arri ve f or t he scree ni n g visit after a n o ver ni g ht fast of at least 8 h o urs or si nce 
mi d ni g ht.  A s u bject w h o has n ot faste d s h o ul d be sc he d ule d f or t h e scree ni n g ass ess me nt bl o o d 
dra ws o n a m or ni n g w h e n he/s he ca n arri ve after a n o ver ni g ht fast of at least 8 h o urs or si nce 
mi d ni g ht.  
Pr oce d ures  c o n d ucte d as part of t he s u bject's r o uti ne cli nical ma na ge me nt (e g, bl o o d c o u nt, b o ne 
marr o w bi o ps y) a n d o bt ai ne d bef or e si g ni n g of i nf or me d c o nse nt ma y b e us e d f or scree ni n g 
p ur p oses pr o vi de d t hat t h e pr oce d ure meets t he Pr ot oc ol- defi ne d crite ria a n d has bee n perf or m e d 

I nc yte C or p orati o n 
P a ge 4 9  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
i n t he ti mefra me of t he st u d y (ie, wit hi n 2 8 da ys  of C ycl e 1 Da y 1) .  All i nf or mati o n ass ociate d 
wit h eli gi bilit y re q uir e me nts  m ust be e ntere d i nt o t he a p pr o pri ate eC R F p a ges.  
B o ne marr o w bi o ps y ( a n d a d diti o nal as pirate c oll ecti o n) f or c o nfir mati o n of M F dia g n osis a n d 
de gree of fi br osis m ust be perf or me d at t he s cree ni n g or bas eli ne visit i nter vals.  N O T E:  
S u bjects wit h o ut circ ulati n g blasts at t he scree ni n g he mat ol o g y assess me nt ma y use a hist orical 
bi o ps y o btai ne d wit hi n 2 m o nt hs bef ore scree ni n g if all data a n d re p orts are a vaila ble f or 
i n vesti gat or's r e vie w.  S u bjects wit h o ut a pri or bi o ps y re p ort as i n dicat e d a b o ve m ust ha ve a 
bi o ps y at scree ni n g or b aseli ne or will n ot be a ble t o e nr oll i n t he st u d y.  T h e pri or data will nee d 
t o be e ntere d i nt o t he e C R F f or t his st u d y, wit h e x pla nati o n as t o t he ori gi n of t he data ( d ate of 
bi o ps y/as pirate). 
Res ults fr o m t he scree ni n g v isit e val uati o ns will be re vie w e d t o c o nfir m s u bject eli gi bilit y b ef ore  
e nr oll me nt.   
6. 2.  
B aseli ne  
S u bjects w h o h a ve si g ne d t he I C F a n d meet all t he e ntr y criteria (s ee Secti o n  3 ) ma y be eli gi ble 
in t he st u d y a n d will be c o ntacte d b y cli nical site staff t o sc he d ule t h e baseli ne visit.  T he 
baseli ne i nter val c orres p o n ds t o t he 7 da ys b ef ore i nitiati n g treat me nt wit h itaciti ni b  a n d d uri n g 
w hic h t he baseli ne M RI ( or C T sca n i n a p plica bl e s u bjects) a n d s y m pt o m diar y will be i nitiate d. 
•  S u bjects w h o meet all eli gi bilit y criteria ma y b e gi n t he baseli ne peri o d of t his st u d y 
( 7 da ys bef ore D a y 1 st u d y start).  D uri n g t he bas eli ne peri o d, all eli gi ble s u bjects 
will be iss ue d a ha n d hel d de vice (e Diar y) o n w hic h t o rec or d s y m pt o ms of M F  i n t he 
M F -S A F diar y (see A p pe n di x D ).  S u bjects will recei ve trai ni n g o n t he d e vice b y 
st u d y site staff b ef or e lea vi n g t he site.  T he i n v esti gati ve site staff m ust e ns ure t hat 
t he diar y is c o m plete d eac h ni g ht be gi n ni n g o n at least Da y - 7 i n or d er t o pr o vi de 
1 c o m plete wee k  of data e ntries bef ore t he D a y 1 visit.   S u bjects will bri n g t he de vice 
al o n g t o t he D a y 1 visit t o c o nfir m t hat at t he diar y e ntri es ha ve b ee n c o m plete d.  T he 
Da y 1 visit s h o ul d n ot be sc he d ule d f or a n y s u bject w h o has n ot c o m plete d at least 
4 da ys of diar y e ntries.  T he s u bjects will als o bri n g t he d e vice al o n g t o e v er y st u d y 
visit t o verif y t he de vi ce c har gi n g a n d t o d o w nl oa d acc u m ulate d d ata.  T he de vice 
will t he n be ret ur ne d t o t he s u bject u p o n visit c o m pleti o n f or c o nti n ue d use eac h 
ni g ht.  S u bjects will ret ur n t he de vice a n d its d oc ki n g s tati o n f or t he fi nal ti me at t he 
E O T visit s o t hat all data ca n be arc hi ve d.  N O T E:   T he diar y ma y b e distri b ute d as 
earl y as t he s cree ni n g visit i n or der t o acc o m m o date s u bject visit sc he d ules d uri n g t he 
baseli ne peri o d. 
•  T he M RI ( or C T sca n i n a p plica ble s u bjects) s h o ul d be c o n d ucte d o n t he first or 
sec o n d da y of t h e baseli n e i nter val t o all o w a m ple ti me t o verif y s ca n q ualit y.   
•  Bl o o d sa m ples f or h e mat ol o g y a n d c he mistr y a nal ys es s h o ul d be t a ke n as cl ose as 
p ossi ble t o Da y 1 b ut ma y be dra w n u p t o 3 d a ys bef ore t h e first d ose of it aciti ni b.  
T his bl o o d sa m ple will ser ve as t h e pre -itaciti ni b baseli ne sa m ple; a D a y 1 sa m ple is 
n ot re q uire d if t he b aseli ne sa m ple is wit hi n 3 da ys of t he first d ose of itaciti ni b. 

I nc yte C or p orati o n 
P a ge 5 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
6. 3.  
Tre at me nt  
T he treat me nt peri o d be gi ns wit h t he first d ose of itaciti ni b ( Da y 1) t hr o u g h t he p oi nt at w hic h 
t he i n vesti gat or d eter mi n es t he s u bject will be per ma ne ntl y disc o nti n ue d fr o m st u d y dr u g. 
T here will be st u d y visits wit h  la b orat or y assess m e nts  i n t he st u d y.  Ta ble  5, Ta ble  6, Ta ble  7, 
a n d Ta ble  8 pr o vi d e t he s c he d ule d a ss ess me nts f or eac h st u d y visit. 
S u bjects will ha ve a re g ularl y s c he d ule d st u d y visit at scree ni n g , b aseli ne, Da y 1, Wee k 4, 
Wee k  8, Wee k 1 2, Wee k 1 6, Wee k 2 0, a n d Wee k 2 4 a n d e ver y 1 2 wee ks t hereafter if c o nti n ui n g 
o n treat me nt, w here bl o o d sa m ples, s plee n meas ure me nts, a n d ot her assess me nts will be 
o btai ne d.  T her e is als o a st u d y visit at Wee k 2  f or P K sa m pli n g, A E assess me nt, a n d he mat ol o g y 
bl o o d dra ws.  T he visit wi n d o w is ± 5 da ys f or visits t hr o u g h Wee k 2 4 a n d ± 7 da ys f or visits 
t hereafter.  T h e ti mi n g f or st u d y visits will be base d o n t he date of t he D a y 1 visit w he n treat me nt 
wit h itaciti ni b  is i nitiate d. 
Bl o o d 
 P K sa m ples will be c ollecte d a n d a nal yz e d b y t he s p o ns or or 
s p o ns or's desi g n ee.  S u bjects will arri ve f or all st u d y visits ha vi n g wit h hel d t he m or ni n g d ose of 
itaciti ni b a n d r u x oliti nib if a p plica ble  a n d i n t he faste d state; a d mi nistrati o n will occ ur i n t he 
cli nic.  S u bjects s h o ul d be t ol d t o bri n g a s n ac k or s mall meal t o t he st u d y visits, as t he y will 
arri ve f or t he visits i n t he faste d state.  
S u bjects will ha ve la b orat or y ass ess me nt s perf or m e d d uri n g st u d y visits t o c ollect he mat ol o g y 
la b sa m ples as n ote d i n T a ble  7 a n d Ta bl e  8.  T he wi n d o w f or la b orat or y visits is ± 3 da ys.  
A d diti o nal la b orat or y ass es s me nts ma y b e perf or me d at t he i n vesti gat or's discreti o n, i ncl u di n g 
f oll o wi n g c h a n ges i n d os e, or if la b or at or y para meters are at Gra de 3 or Gra de 4 le vels base d o n 
t he C T C A E v 4. 0 3. 
S u bjects will c o m plete a n el ectr o nic s y m pt o m diar y ( M F S A F v 2. 0) dail y fr o m baseli ne t hr o u g h 
t he Wee k 2 4 visit (t otal of 2 5 wee ks; A p p e n di x D ). 
S u bjects will c o m plete t he M P N -S A F  i n a e-diar y  (A p pe n di x E ) at visits n ote d i n Ta ble  5 a n d 
Ta ble  6. 
6. 4.  
E n d of Tre at me nt 
T here is n ot a pr e defi n e d E O T.  If a d ecisi o n is ma de t hat t he s u bject will wit h dra w fr o m st u d y 
partici pati o n, t he n a n E O T visit s h o ul d be c o n d ucte d wit hi n 7 da ys after t h e last d ose of st u d y 
treat me nt.  If t he E O T visit c oi nci des wit h a re g ul ar st u d y visit, t he n t he E O T e val uati o ns will 
s u perse de t h ose of t hat sc he d ule d visit, a n d t he dat a s h o ul d be e ntere d i n t he E O T visit i n t he 
e C R F.  T he s u bject s h o ul d be e nc o ur a ge d t o ret ur n f or t he f oll o w- u p visit.   
If a st u d y wit h dra w al occ urs, or if t he s u bject fails t o ret ur n f or visits, t he n t he i n vesti gat or m ust 
deter mi ne t he pri mar y reas o n f or a s u bject's pre m at ure wit h dra wal fr o m t h e st u d y a n d rec or d t his 
i nf ormati o n i n t he e C R F.  
T he i n vesti gat or m ust c o ntact t he I X R S s yste m t o re gister t he s u bject's disc o nti n uati o n. 

I nc yte C or p orati o n 
P a ge 5 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
6. 5.  
F oll o w - U p 
6. 5. 1.  
S af et y F oll o w- U p  
T he safet y f oll o w- u p peri o d is t he i nter val bet wee n t he E O T visit a n d t he sc he d ule d f oll o w- u p 
visit, w hic h s h o ul d occ ur 3 0 t o 3 5 da ys after t he E O T visit ( or after t h e last d ose of st u d y 
treat me nt if t he E O T visit was n ot perf or m e d).  A d verse e v e nts a n d S A Es m ust be re p orte d u p 
u ntil 3 0 da ys aft er t he last d ose of st u d y treat me nt, t he date of t he f oll o w- u p visit, or u ntil st u d y 
treat me nt– relat e d t o xicities res ol ve, r et ur n t o baseli ne, or are dee m e d irre v ersi ble, w hic he ver is 
l o n ger.  R eas o na ble eff orts s h o ul d be ma de t o ha v e t he s u bject ret ur n f or t h e f oll o w- u p visit a n d 
re p ort a n y A Es t h at ma y occ ur d uri n g t his peri o d.  If t he s u bject ca n n ot ret ur n t o t he site f or t he 
safet y f oll o w- u p visit (e g, li ves far a w a y), t he n t h e s u bject s h o ul d be c o ntacte d b y tel e p h o ne f or 
assessi n g A Es a n d S A Es.  Sites s h o ul d d oc u me nt t his c o ntact i n t he s o urce. 
6. 6.  
E n d o f St u d y 
T he e n d of st u d y f or eac h s u bject is c o nsi dere d t o ha ve occ urre d w he n t he s u bject is decease d, 
w he n t he st u d y is c o m plete d, or w he n t he s u bject is per ma ne ntl y l ost t o f oll o w u p.   
6. 7.  
U nsc he d ule d Visits  
U nsc he d ule d st u d y visits ma y o cc ur at a n y ti me if me dicall y warra nte d.  A n y ass ess me nts 
perf or me d (e g, la b orat or y or cli nical assess me nts) at t h ose visits s h o ul d be rec or d e d i n t he eC R F.  
7.  
C O N D U C T O F 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  
Pr os pecti ve partici pa nts will be sc he d ule d f or a scree ni n g visit b y site staff.  A s u bject n u m ber 
will b e assi g ne d b y a n I X R S.  All pr oce d ures f or s cree ni n g a n d baseli ne m ust be c o m plete d 
wit hi n t he 2 1- da y s cree ni n g + 7 -da y b aseli ne peri o d , e x ce pt as n ote d i n Secti o n  6. 1 ).  T he 
pr oce d ur es i n t his secti o n will be perf or me d. 
7. 1.  
A d mi nistr ati o n of I nf or me d C o nse nt F or m  
Vali d i nf or me d c o nse nt m ust be o btai ne d fr o m t he st u d y s u bject bef ore c o n d ucti n g a n y 
st u d y-s pecific pr o ce d ur es usi n g a n I C F a p pr o v e d b y t he l ocal I R B/I E C t hat c o ntai ns all ele me nts 
re q uire d b y I C H E 6 a n d descri bes t he n at ure, sc o pe, a n d p os si ble c o nse q u e nces of t h e st u d y i n a 
f or m u n dersta n d a ble t o t he st u d y s u bject.  L o cal a n d i nstit uti o nal g ui deli nes f or I C F c o nte nt a n d 
a d mi nistrati o n m ust be f oll o we d; t he ori gi nal si g ne d I C F m ust be retai ne d b y t he i n vestigat or , 
a n d a c o p y of t h e si g n e d I C F m ust be pr o vi de d t o t he st u d y s u bject.  T h e i nf or me d c o nse nt 
pr ocess f or eac h s u bject m ust be d oc u me nte d i n writi n g wit hi n t he s u bject s o urce d oc u me nt ati o n. 
7. 2.  
I nter acti ve Res p o nse Tec h n ol o g y Pr oce d ure  
T he I X R S will be c o ntact e d t o o btai n a s u bject I D n u m ber w he n a s u bject e nters t he scree ni n g 
peri o d.  U p o n deter mi ni n g t hat t he s u bject is eli gi ble , t he I X R S will be c o ntacte d t o o btai n  t he 
treat me nt c o h ort assi g n m e nt.   A d diti o nall y, t he I X R S will be c o ntacte d at eac h re g ul ar st u d y v isit 
t o u p date t he st u d y tr eat me nt s u p pl y a n d at t he E O T visit t o rec or d s u bject disc o nti n uati o n fr o m 
t he st u d y treat me nt (see Secti o n  5. 1. 1 ). 

I nc yte C or p orati o n 
P a ge 5 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
7. 3.  
De m o gr a p h y a n d Me di cal Hist or y  
De m o gra p hic d ata a n d a c o m plete  me dical a n d m e dicati o n hist or y will be c ollecte d at scree ni n g.  
T he s u bject 's date of birt h, race, et h nicit y, m e dical a n d s ur gi cal hist or y, a n d c o nc urrent ill nesses 
assesse d usi n g C T C A E v 4. 0 3 ( N CI  2 0 1 0) will be rec or de d .  D oc u me ntati o n of disease hist or y, 
i ncl u di n g details of M F  dia g n osis, a n d pri or b o ne marr o w bi o ps y data wit h res pect  t o fi br osis 
sta ge will be rec or de d.  All treat me nts f or M F, i n cl u di n g a c o m plete hist or y of r u x oliti ni b usa ge, 
p hle b ot o m y hist or y, a n d all tra nsf usi o ns of R B C pr o d ucts or platelets fr o m at least 1 2 wee ks 
bef ore t h e scr ee ni n g visit will als o be c ollecte d . 
7. 4.  
Pri or  a n d C o nc o mit a nt Me dic ati o n s a n d Pr oce d ures  
Pri or  a n d c o nc o mita nt m e dicati o ns a n d pr o ce d ures will be re vie we d t o d eter mi ne s u bject 
eli gi bilit y.  All c o nc o mit a nt me dicati o ns a n d meas ures  m ust be rec or de d i n t he eC R F , a n d an y 
me dicati o n recei ve d  or pr oce d ur e perf or me d wit hi n 3 0 da ys b ef ore  e nr ollm e nt  a n d u p t o t he 
safet y f oll o w- u p ( 3 0-3 5 da ys after E O T ) will be rec or de d i n t he eC R F.  T h e me dicati o n rec or d 
will be mai ntai ne d  after si g ni n g t he I C F t o d o c u me nt c o nc o mita nt me dicati o ns, i ncl u di n g a n y 
c ha n ges t o t he d ose or re gi me n.  C o nc o mita nt me dicati o ns i ncl u de a n y prescri pti o n, 
o ver-t he- c o u nter, or nat ural/ her bal pr e parati o ns ta ke n or a d mi nistere d d uri n g t he st u d y peri o d.  
C o nc o mita nt treat me nts  a n d/ or pr oce d ures t hat are re q uire d t o ma na ge a s u bject's me di cal 
c o n diti o n d uri n g t he st u d y will als o be rec or d e d i n t he eC R F.   Tra nsf usi o ns of PR B Cs , platelets, 
or ot her bl o o d pr o d uct m ust be rec or d e d i n t he e C R F.   
7. 5.  
S afet y Assess me nts  
Safet y e x a mi nati o ns m ust be perf or m e d b y a s uita bl y trai ne d, m e dicall y q u alifie d i n di vi d ual s uc h 
as a lice nse d p h ysici a n, p h ysicia n 's assista nt, or a n a d va nce d r e gistere d n urs e p ractiti o ner, as 
l ocal la w per mits. 
7. 5. 1.  
Re vie w I ncl usi o n a n d E xcl usi o n C riteri a 
All safet y data a n d ot her eli gi bilit y ass ess me nts m ust be re vie w e d d uri n g t he scree ni n g peri o d t o 
c o nfir m t he s u bject's eli gi bilit y.  
7. 5. 2.  
A d verse E ve nts  
A d verse e ve nts will be m o nit ore d fr o m t he ti me t he s u bject si g ns t he I C F.  S u bjects will be 
i nstr ucte d t o re p ort all A Es d uri n g t he st u d y a n d will be assesse d f or t h e o cc urre nce of A Es 
t hr o u g h o ut t he st u d y.  I n or der t o a v oi d bias i n eliciti n g A Es, s u bjects will be as ke d ge n eral, 
n o nlea di n g q u esti o ns s uc h as "H o w ar e y o u feeli n g? "  All A Es (seri o us a n d n o nseri o us) m ust be 
rec or d e d o n t he s o ur ce d oc u me nts a n d eC R Fs  re gar dless of t he ass u m pti o n of a ca us al 
relati o ns hi p wit h t he st u d y treat me nt.  T he d efi niti o n, re p orti n g, a n d rec or di n g re q uire me nts f or 
A Es are d escri be d i n Secti o n  8 . 
7. 5. 3.  
P h ysic al E x a mi n ati o ns 
7. 5. 3. 1.  
C o m pre he nsi ve P h ysic al E x a mi n ati o n 
T he c o m pre h e nsi ve p h ysical e x a mi nati o n will i ncl u de hei g ht (at scree ni n g) a n d b o d y wei g ht, a n d 
assess me nt(s) of t he f oll o wi n g or ga n or b o d y s yste ms:  s ki n; hea d, e yes, ears, n ose, a n d t hr oat; 

I nc yte C or p orati o n 
P a ge 5 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
t h yr oi d; l u n gs; car di o vas c ular s yste m; a b d o me n (li ver, s plee n); e xtre mities; a n d l y m p h n o des, as 
well as a brief ne ur ol o gical e x a mi nati o n.   T he c o m pre he nsi ve p h ysical e x a mi nati o n s h o ul d als o 
i ncl u de a n assess me nt of b o d y fl ui d a b n or malities , i ncl u di n g ascites a n d e d e ma. 
7. 5. 3. 2.  
 T ar gete d P h ysic al E x a mi n ati o ns 
A tar gete d p h ysical e x a mi nati o n will be a s y m pt o m - directe d e val uati o n a n d will i ncl u de 
assess me nt(s) of t he b o d y s yste ms or or ga ns, as i n dicate d b y s u bject s y m pt o ms, A Es, or ot her 
fi n di n gs as d eter mi ne d b y t he i n vesti gat or or desi g nee.  A tar gete d p h ysical e x a mi nati o n m ust 
i ncl u de a meas ure me nt of t he s u bject's b o d y wei g ht ( wit hi n 1 l b. or 0. 5 k g), a n assess me nt of 
b o d y fl ui d a b n or malities of e de ma a n d ascites, a n d a n e v al uati o n of a n y A Es or s y m pt o ms t hat 
t he s u bject has ha d pr e vi o usl y.  
7. 5. 4.  
Vit al Si g ns  
Vital si g n meas ur e me nts i ncl u de bl o o d press ure, p ulse, res pirat or y rate, a n d b o d y te m perat ure.  
Bl o o d press ur e a n d p ulse will be ta ke n wit h t he s u bject i n t he rec u m b e nt, se mi rec u m be nt, or 
sitti n g p ositi o n after 5 mi n utes of rest.   Cli nicall y n ota ble a b n or malities t hat are c o nsi dere d 
cli nicall y si g nifica nt i n t he j u d g me nt of t h e i n vesti gat or are t o b e re p orte d as A Es . 
7. 5. 5.  
Electr oc a r di o gr a ms  
All 1 2 -lea d E C Gs will be perf or me d wit h the s u bject i n a rec u m be nt or se mirec u m be nt p ositi o n 
after 5 mi n utes of r est.  
T he 1 2- lea d E C Gs will be i nter pret e d b y t he in vesti gat or at t he site  t o be us e d f or i m me diate 
s u bject ma na ge me nt.  T h e decisi o n t o i ncl u de or e x cl u de a s u bject or wit h dra w a s u bje ct fr o m 
t he st u d y bas e d o n a n E C G fla g ge d as "A b n or mal, Cli nicall y Si g nifica nt " is t he res p o nsi bilit y of 
t he i n vesti gat or, i n c o ns ultati o n wit h t he s p o ns or's m e dical m o nit or, as a p pr o priate.  C li nicall y 
n ota ble a b n or malities t hat are c o nsi dere d cli nicall y si g nifica nt i n t he j u d g me nt of t he i n vesti gat or 
are t o be re p orte d as A E s. 
7. 5. 6.  
L a b or at or y Assess me nts 
All he mat ol o g y la b or at or y ass ess me nt s, bl o o d c he mistries , c oa g ul ati o n , li pi d pa nel, ser ol o g y, 
a n d uri nal ysis para m eters will be a nal yze d b y l o cal la b orat ories .  Sa m ples f or he mat ol o g y, bl o o d 
c he mistr y, s er ol o g y, c o a g ulati o n tests, pre g n a nc y, a n d F S H tests a n d uri n al ysis  will be pre p are d 
usi n g sta n dar d pr oce d ures.  A c o m plete list of la b orat or y assess me nts is s h o w n i n Ta ble  7 a n d 
Ta ble  8.  Refer t o t he La b orat or y Ma n u al f or f urt her details a n d s pecificati o ns f or sa m ple 
ha n dli n g, pr o cessi n g, a n d s hi p pi n g.  A d diti o nal la b orat or y assess me nts ma y be c o n d ucte d at 
i n vesti gat or's discr eti on t o u n dersta n d safet y fi n di n gs or t o s u p p ort d ose m o dificati o ns   
7. 5. 6. 1.  
Pre g n a nc y Testi n g  
A ser u m pre g n a nc y test will be re q uire d f or all w o me n  of c hil d beari n g p ot e ntial at scree ni n g  a n d 
at t he E O T  visit .  A n F S H test will be perf or m e d o n fe males w h o h a ve bee n a me n orr h eic f or 
≥ 1 year.  If F S H le v els are ele v ate d t o p ost me n o p a usal ra n ge, n o pre g n a nc y testi n g is re q uire d 
f or t hese f e male s u bjects.  Uri ne pre g n a nc y tests will be c o n d ucte d  as o utli ne d i n Ta ble  7, as 
me dicall y i n dicate d , or p er c o u ntr y-s p ecific re q uire me nt.  Uri ne pre g na n c y tests will be 
perf or me d  l o call y. 

I nc yte C or p orati o n 
P a ge 5 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A n M RI is t he pr eferre d met h o d f or o btai ni n g s pl ee n v ol u me data.  H o we v er, C T sca ns ma y b e 
perf or me d at t he visits w here M RI is desi g nate d if t he s u bject is n ot a ca n di date f or M RI (e g, 
beca use of t he pr ese nce of metal cli ps i n t he b o d y, beca use of cla ustr o p h o bi a) or if M RI is n ot 
rea dil y a vaila bl e.  C o m p ute d t o m o gra p h y s ca ns will be si milarl y pr ocess e d b y t he sa m e ce ntral 
la b orat or y as us e d f or M RIs.  Pr oce d ure-s pecifi c trai ni n g f or sca n ni n g a n d i ma ge ca pt ure will be 
pr o vi de d b y t he ve n d or.  N O T E:  T he sa me m et h o d ( M RI vs C T) m ust be use d f or all visits f or a 
gi ve n s u bject u nless a ne w c o ntrai n dicati o n t o t he use of M RI occ urs (e g, p ace ma k er i nserti o n). 
7. 6. 4.  
S y m pt o m Di a r y  
S y m pt o ms of M F will be assesse d usi n g a s y m pt o m diar y ( m o difie d M F S A F v 2. 0 diar y; 
A p pe n di x D ).  S u bjects will be iss ue d a ha n d- hel d de vice o n w hic h t o rec or d a ns wers t o q ueries 
re gar di n g M F s y m pt o ms.  S y m pt o ms ass esse d will i ncl u de filli n g u p q uic kl y/ earl y satiet y, 
a b d o mi nal disc o mf ort, a b d o mi nal pai n, i nacti vit y, ni g ht s weats, itc hi n g, a n d b o ne/ m us cle pai n.  
T he m o di fie d M F S A F v 2. 0 diar y will be c o m plete d b y s u bjects eac h ni g ht be gi n ni n g at D a y - 7 
(first da y of b aseli ne) a n d c o nti n ui n g t o t he Wee k 2 4 visit ( 2 5 wee ks t otal).  S u bjects will bri n g 
t he de vice t o t he st u d y site at st u d y visits as o utli ne d i n Ta ble  5 a n d T a ble  6 s o t hat t he de vice 
c har gi n g ca n be verifie d a n d t he acc u m ulate d data ca n be d o w nl o a de d.  N O T E:  S u bjects w h o 
will ha ve o ver ni g ht sta ys ass ociate d wit h t heir st u d y visit  m ust als o bri n g t heir d oc ki n g stati o n s o 
t hat t heir de vice ca n be f ull y c har ge d at all ti mes a n d s o t hat t he y ca n c o m plete t he e ve ni n g diar y 
e ntries.  T he de vi ce will t he n be ret ur ne d t o t he s u bject at t hese sa m e visits f or c o nti n ue d use 
eac h ni g ht.  T he s u bject will ret ur n t he de vice a n d t he d oc ki n g stati o n f or t he fi nal ti me at t he 
Wee k 2 4 visit s o t hat t he data ca n b e ar c hi ve d.  D etaile d directi o ns f or t he a d mi nistrati o n of t he 
m o difie d M F S A F v 2. 0 di ar y will be pr o vi de d i n a refere nce ma n ual.  Fre nc h a n d S pa nis h 
tra nslati o ns of t he m o difie d M F S A F v 2. 0 di ar y will be a vaila ble. 
7. 7.  
Perf or m a nce a n d Q u alit y -of -Life  Assess me nts  
7. 7. 1.  
E aster n C o o per ati ve O nc ol o g y Gr o u p Perf or m a nce St at us  
T he E C O G perf or ma n ce stat us will be assesse d as s h o w n i n Ta ble  5 a n d Ta ble  6 (A p pe n di x C ).   
7. 7. 2.  
P ati e nt Gl o b al I m pressi o n of C h a n ge 
S u bjects will c o m plete t he 1 - q uesti o n assess me nt f or m (A p pe n di x F ) at st u d y visits s h o w n i n  
Ta ble  5 a n d T a ble  6.  I nstr ucti o ns will be pro vi de d as a se parate d o c u me nt.  
7. 7. 3.  
M yel o pr olif er ati ve Ne o pl as ms S y m pt o m Assess me n t F or m  
T he M P N -S A F q uesti o n naire (see A p pe n di x E ) will be c o m plete d at b aseli ne; at Wee ks 1 2 a n d 
2 4 ; a n d at e ver y 1 2- wee k visit t hereafter  s o t hat t h e o verall s y m pt o ms res p o nse assess me nt ca n 
be deter mi ne d a n d re p orte d. 
7. 8.  
I W G-M R T Assess me nt  
O verall r es p o nse assess m e nt will be gr a de d acc or di n g t o t he I W G c o nse ns us criteria f or 
treat me nt res p o ns e i n P M F a n d P P V/ E T -M F ( A p pe n di x B , Tefferi  et al 2 0 1 3). 

I nc yte C or p orati o n 
P a ge 5 7  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
7. 1 1.  
Ot her St u d y Pr oce d ures  
7. 1 1. 1.  
A d mi nistr ati o n of St u d y T re at me nt  
C o h ort A a n d B :  S u bjects will ta ke t heir d ose of  itaciti ni b i n t he m or ni n g. 
C o h ort A o nl y :  Ru x oliti ni b will be a d mi nistere d orall y as direct e d b y t he l ocal pres cri bi n g 
i nf or mati o n.  I n t h e U nite d States, u p date d i nf or m ati o n ca n be f o u n d at 
htt p:// dail y me d. nl m. ni h. g o v/ dail y me d/a b o ut.cf m. 
7. 1 1. 2.  
Dis pe ns ati o n of S t u d y T re at me nt  
Site staff will c o ntact t he I X R S t o o btai n t he i nitial s u bject st u d y treat me nt assi g n me nt, as well 
as f or s u bse q u e nt dis pe nsati o ns of st u d y treat me nt.  T he i n vesti gat or or desi g nee will select t he 
assi g ne d st u d y dr u g b ottl es fr o m t heir st oc k t hat c orres p o n d wit h  t he n u m b er pr o vi de d b y I X R S 
a n d dis pe nse t he me dicati o n.  T he i n vesti gat or will e nter t he b ottle n u m bers i n t he e C R F.  F ull 
details will be pr o vi de d i n t he I X R S Ma n ual.  
7. 1 1. 3.  
Assess me nt of C o m pli a nce Wit h St u d y Dr u g  
C o m plia nce will be calc ulate d b y t h e s p o ns or base d o n t he dr u g acc o u nta bilit y d oc u me nte d b y 
t he site staff a n d m o nit or e d b y t h e s p o ns or/ desi g n ee (ta blet c o u nts).  T he o bjecti ve is 1 0 0 % 
c o m plia nce, a n d i n v esti gat ors a n d t heir staff s h o ul d e val uate c o m plia nce at eac h visit a n d ta ke 
a p pr o priate ste ps t o o pti mize c o m plia n ce. 
7. 1 1. 4.  
Distri b uti o n of  S u bject Re mi n der C ar ds  
S u bjects will be pr o vi de d wit h re mi n der car ds at eac h visit.  T he s u bject re mi n der car ds will 
i n dicate t he date/ti me of t he ne xt visit a n d i ncl u de a n y s p ecial i nstr ucti o ns f or t hat visit.  T his 
car d will ha ve a n area f or t he s u bject t o rec or d  t he date a n d ti me of t he last d ose ta ke n bef ore  t he 
st u d y visit a n d t he ti me of t heir last m eal (re q uire d f or P K visits).   O n da ys w he n st u d y dr u g is 
N O T t o be ta ke n at h o me i n a d va nce of t he st u d y cli nic, re mi n der car ds will i n dicate t his.  

I nc yte C or p orati o n 
P a ge 5 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
8.  
S A F E T Y M O NI T O RI N G A N D R E P O R TI N G  
8. 1.  
A d verse E ve nts  
8. 1. 1.  
Defi niti o ns  
F or t he p ur p os es of t his Pr ot oc ol, a n a d vers e e ve nt ( A E) is defi ne d as a n y u nt o war d me dical 
occ urr e nce ass ociat e d wit h t he use of a dr u g i n h u ma ns, w het her or n ot c o nsi dere d dr u g r elate d, 
t hat occ urs after a s u bject pr o vi des i nf or me d c o ns e nt.  A b n or mal la b orat or y val ues or test res ults 
occ urri n g after i nf or me d c o nse nt c o nstit ute A Es o nl y if t he y i n d uce cli nical si g ns or s y m pt o ms, 
are c o nsi d ere d cli nicall y mea ni n gf ul, re q uire t hera p y  (e g, he mat ol o gic a b n or malit y t hat re q uires 
tra nsf usi o n), or r e q uire c ha n ges i n t he st u d y dr u g(s). 
8. 1. 2.  
Re p orti n g  
A d verse e ve nts t hat be gi n or w orse n after i nf or me d c o nse nt s h o ul d be rec or de d o n t he A d verse 
E ve nts f or m of t he e C R F.  C o n diti o ns t hat were alrea d y prese nt at t he ti me of i nf or me d c o ns e nt 
s h o ul d be rec or de d o n t h e Me dical Hist or y f or m i n t he e C R F.  M o nit ori n g f or t he occ urre nce of 
ne w A Es s h o ul d be c o nti n ue d f or at least 3 0 da ys after t he l ast d ose of st u d y dr u g  A d vers e 
e ve nts (i ncl u di n g la b orat or y a b n or malities t hat c o nstit ute A Es) s h o ul d be descri be d usi n g a 
dia g n osis w he n e ver p ossi ble rat her t h a n b y i n di vi d ual u n derl yi n g si g ns a n d s y m pt o ms.  W he n a 
clear dia g n osis ca n n ot be i de ntifie d, eac h si g n or s y m pt o m s h o ul d be re p ort e d as a se p arat e A E. 
T he ter m "disease pr o gressi o n " s h o ul d be rec or de d as a n A E/ S A E o nl y if t here are n o ot her 
i de ntifia ble A Es/ S A Es ass ociate d wit h t he disease pr o gressi o n at t he ti me of re p orti n g.  F or 
e ve nts ass ociate d wit h disease pr o gressi o n, t he rele va nt si g ns a n d s y m pt o ms s h o ul d be re p orte d 
usi n g a dia g n osis w h e ne ver p ossi ble rat her t ha n i n di vi d ual u n derl yi n g si g ns a n d s y m pt o ms.  
W he n a clear di a g n osis ca n n ot be i de ntifie d, eac h si g n or s y m pt o m s h o ul d be re p ort e d as a 
se parat e A E.  If t h e e ve nts res ulti n g fr o m disease pr o gressi o n meet t he criteria f or a n S A E (e g, 
res ulte d i n h os pitalizati o n, a life-t hreate ni n g e v e nt, or deat h), t he s pecific e ve nt(s) s h o ul d be 
re p orte d as a n S A E(s) as descri be d i n Secti o n 8. 3. 2 .  I n b ot h cases (i e, AEs or S A Es relate d t o 
disease pr o gr essi o n), it s h o ul d be i n dicate d t hat eac h e v e nt (re p orte d as a dia g n osis or as si g ns 
a n d s y m pt o ms) is relat e d t o disease pr o gressi o n o n t he A d verse E ve nts f or m of t he e C R F. 
T he se verit y of A Es will be assesse d usi n g C T C A E  v 4. 0 3 Gra des 1 t hr o u g h 5.  If a n e v e nt is n ot 
classifie d b y C T C A E, t he se verit y of t he A E will be gra de d acc or di n g t o t he scale b el o w t o 
esti mate t he gra de of se v erit y:  
Gr a de  1 
Mil d; as y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y;  
i nter ve nti o n n ot i n dicate d. 
Gr a de 2  
M o derate; mi ni mal, l ocal, or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g 
a ge -a p pr o priate acti vities of dail y li vi n g.  
Gr a de 3  
Se vere or me dical l y si g nifica nt b ut n ot i m me diatel y life-t hreate ni n g; h os pitalizati o n 
or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; li miti n g self -care acti vities of 
dail y li vi n g.  
Gr a de 4  
Life -t hreate ni n g c o nse q ue nces; ur ge nt i nter ve nti o n i n dicate d. 
Gr a de 5  
Deat h d ue t o A E. 

I nc yte C or p orati o n 
P a ge 5 9  of 8 5 
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
T he occ urre n ce of A Es s h o ul d be s o u g ht b y n o n directi ve q uesti o ni n g of t he s u bject d uri n g t h e 
scree ni n g pr o cess after si g ni n g t he I C F a n d at eac h visit d uri n g t he st u d y.  A d verse e ve nts ma y 
als o be detect e d w he n t h e y are v ol u nteere d b y t he s u bject d uri n g t h e scree ni n g pr ocess or 
bet wee n visits, or t hr o u g h p h ysical e x a mi nati o n, la b orat or y test, or ot h er assess me nts.  T o t he 
e xte nt p ossi ble, eac h A E s h o ul d be e val uate d t o deter mi ne: 
•  T he se verit y gr a de ( C T C A E Gra d e  1 t o 5). 
•  W het her t here is at least a reas o n a ble p ossi bilit y t hat t he A E is relate d t o t h e st u d y 
treat me nt:  s us pecte d ( yes) or n ot s us pecte d ( n o). 
•  T he start a n d e n d d ates, u nless u nres ol ve d at fi nal f oll o w- u p. 
•  T he acti o n ta ke n wit h re gar d t o st u d y dr u g. 
•  T he e ve nt o utc o me (e g, n ot rec o vere d/ n ot res ol ve d, rec o vere d/res ol ve d, 
rec o veri n g/res ol vi n g, rec o vere d/res ol ve d wit h se q uelae, fatal, u n k n o w n). 
•  T he seri o us ness, as p er s eri o us a d vers e e v e nt ( S A E) defi niti o n pr o vi de d i n 
Secti o n  8. 3. 1 . 
U nli ke r o uti ne safet y assess me nts, S A Es are m o nit ore d c o nti n u o usl y a n d h a ve s peci al re p orti n g 
re q uire me nts (s ee Secti o n  8. 3. 2 ). 
All A Es s h o ul d be treate d a p pr o priatel y.  If a n A E is treate d wit h a c o n c o mita nt me dicati o n or 
n o n dr u g t h era p y, t his acti o n s h o ul d be rec or de d o n A d verse E v e nt f or m a n d t he treat me nt s h o ul d 
be s pecifie d o n t h e Pri or/ C o nc o mita nt Me dicati o ns or Pr oce d ures a n d N o n- Dr u g T hera p y f or m 
i n t he e C R F. 
O nce a n A E is detect e d, it s h o ul d be f oll o we d u ntil it has res ol ve d or u ntil it is j u d ge d t o be 
per ma ne nt; assess me nt s h o ul d be ma de at eac h visit ( or m ore fre q ue ntl y if necessar y) of a n y 
c ha n ges i n se v erit y, t h e s us pecte d r elati o ns hi p t o t he st u d y dr u g, t h e i nter ve nti o ns re q uire d t o 
treat t he e v e nt, a n d t he o utc o me. 
W he n t he se verit y of a n A E c ha n ges o v er ti me f or a re p orti n g p eri o d ( e g, bet wee n visits), eac h 
c ha n ge i n se v erit y will be re p ort e d as a s e parate A E u ntil t he e ve nt res ol v es.  F or e x a m ple, 
2 se parat e A Es will be re p orte d if a s u bject h as Gra de 1 diarr hea, m eeti n g t he defi niti o n of a n A E 
t hat lasts f or 3 da ys bef or e w orse ni n g t o a Gra d e 3 se verit y.  T he Gra de  1 e ve nt will be re p orte d 
as a n A E wit h a start date e q ual t o t he da y t he e ve nt met t he Gra de  1 A E defi niti o n a n d a st o p 
date e q ual t o t he d a y t hat t he e ve nt i ncrease d i n se verit y fr o m Gra de  1 t o Gra de 3.  T h e Gra d e  3 
e ve nt will als o be re p orte d as a n A E, wit h t he start date e q ual t o t he d a y t he e ve nt c ha n ge d i n 
i nte nsit y fr o m Gr a de 1 t o Gra de 3 a n d a st o p date e q ual t o t he da y t hat t he e ve nt eit her c ha n ge d 
se verit y a gai n or res ol ve d. 
8. 2.  
L a b or at or y Test A b n or m alities  
La b orat or y a b n or malities t hat c o nstit ute a n A E i n t heir o w n ri g ht (c o nsi dere d cli nicall y 
mea ni n gf ul, i n d uce cli nical si g ns or s y m pt o ms, re q uire c o nc o mita nt t hera p y, or re q uire c ha n ges 
i n st u d y dr u g) s h o ul d be rec or d e d o n t he A d v erse E ve nt f or m i n t he e C R F.  W he ne ver p ossi ble, a 
dia g n osis r at her t ha n a s y m pt o m s h o ul d be pr o vi de d (e g, " a n e mia" i nstea d of "l o w h e m o gl o bi n").  
La b orat or y a b n or malities t hat meet t he criteri a f or A Es s h o ul d be f oll o we d u ntil t he y ha ve 
ret ur ne d t o n or mal or a n a de q uate e x pla nati o n of t he a b n or malit y is f o u n d.  W he n a n a b n or mal 

I nc yte C or p orati o n 
P a ge 6 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
la b orat or y test r es ult c orr es p o n ds t o a si g n or s y m pt o m of a pre vi o usl y re p orte d A E, it is n ot 
necessar y t o se par atel y r ec or d t he la b orat or y test res ult as a n a d diti o nal e v e nt.  
La b orat or y a b n or malities t hat d o n ot meet t he defi niti o n of a n A E s h o ul d n ot be re p orte d as A Es.  
A Gra d e  3 a n d Gr a de 4  A E d oes n ot a ut o maticall y i n dicat e a n S A E u nless it meets t he defi niti o n 
of seri o us, as defi ne d i n Secti o n  8. 3. 1 .  A d ose m o dificati o n f or t he la b orat or y a b n or malit y m a y 
be re q uir e d (see Secti o n  5. 4 ) a n d s h o ul d n ot c o ntri b ute t o t he desi g nati o n of a la b orat or y test 
a b n or malit y as a n S A E.  
8. 3.  
Seri o us A d verse E ve nts  
8. 3. 1.  
Defi niti o ns  
A n S A E is defi ne d as a n e ve nt t hat meets at least 1 of t he f oll o wi n g criteri a:  
•  Is fatal or life-t hreate ni n g. 
•  Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n, u nless 
h os pitalizati o n is a res ult of:  
− A r o uti ne treat me nt or m o nit ori n g of t he st u die d i n dicati o n n ot ass ociate d wit h 
a n y d eteri or ati o n i n c o n diti o n. 
− A n electi ve s ur ger y or pre pla n ne d treat me nt f or a pre- e xisti n g c o n diti o n t hat is 
u nrelate d t o t he i n dicati o n u n der st u d y a n d has n ot w orse ne d si nce si g ni n g t he 
I C F. 
− A treat me nt o n a n e mer ge nc y o ut patie nt basis f or a n e ve nt n ot f ulfilli n g a n y of t he 
defi niti o ns of a S A E a n d n ot res ulti n g i n h os pital a d missi o n. 
− A n y s o cial reas o ns a n d res pite care, i n t he a bse n ce of a n y det eri orati o n i n t he 
s u bject's ge ner al c o n diti o n. 
•  Res ults i n persiste nt or si g nifica nt disa bilit y, i nca p acit y, or 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. 
•  C o nstit utes a c o n ge nital a n o mal y or birt h defect. 
•  Is c o nsi dere d t o b e a n i m p orta nt me dical e v e nt or a me dicall y si g nifica nt e ve nt t hat 
ma y n ot r es ult i n deat h, b e i m me diatel y life -t hreat e ni n g, or re q uire h os pitalizati o n b ut 
ma y b e c o nsi der e d seri o us w he n, base d o n a p pr o priate me dical j u d g me nt, t he e ve nt 
ma y je o p ar dize t he s u bject or ma y re q uire me dical or s ur gi cal i nter ve nti o n t o pre ve nt 
1 of t he o utc o mes liste d a b o ve. 
8. 3. 2.  
Re p orti n g  
E ver y S A E, re gar dless of s us pecte d ca usalit y (e g, relati o ns hi p t o st u d y dr u g(s) or st u d y 
pr oce d ur e or disease pr o gr essi o n), occ urri n g after t he s u bject has si g n e d t h e I C F t hr o u g h t he last 
st u d y visit ( or 3 0 da ys after t he last d ose of st u d y dr u g, w hic he ver is later) m ust be re p orte d t o 
t he s p o ns or ( or desi g nee) wit hi n 2 4 h o urs  of lear ni n g of its occ urre n ce, u nl ess ot her wise 
s pecifie d b y t he Pr ot oc ol.  A n y S A Es occ urri n g m ore t ha n 3 0 da ys after t h e last d ose of st u d y 
dr u g s h o ul d be re p ort e d t o t he s p o ns or or its desi g nee o nl y if t he i n vesti gat or s us pects a ca usal 
relati o ns hi p t o t he st u d y dr u g.   

I nc yte C or p orati o n 
P a ge 6 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
I nf or mati o n a b o ut all S A Es is c ollecte d a n d rec or de d o n t he A d verse E ve nt f or m of t he e C R F.  
T he i n vesti gat or m ust assess a n d rec or d t he ca usal relati o ns hi p of eac h S A E t o t he st u d y 
treat me nt.  
T he i n vesti gat or m ust als o c o m plete t he I nc yt e Seri o us A d verse E ve nt Re p ort F or m, i n E n glis h, 
a n d se n d t he c o m plete d a n d si g ne d f or m t o t he s p o ns or or desi g nee wit hi n 2 4 h o urs of bec o mi n g 
a war e of t he S A E.  T h e i n vesti gat or m ust pr o vi de a ca usalit y assess me nt, t h at is, assess w het her 
t here is at least a reas o n a ble p ossi bilit y t hat t he S A E is relate d t o t he st u d y treat me nt:  s us pecte d 
( yes) or n ot s us pecte d ( n o).  Refer t o t he I nc yte R efere nce G ui de f or C o m pleti n g t he Seri o us 
A d verse E v e nt Re p ort F or m. 
T he c o ntact i nf or mati o n of t he s p o ns or' s st u d y-s p ecific re pres e ntati ves is liste d i n t he 
i n vesti gat or ma n u al pr o vi de d t o eac h site.  T h e ori gi nal c o p y of t he S A E Re p ort F or m a n d t he 
c o nfir mati o n s heet m ust be ke pt at t he st u d y site. 
I n v esti gati o nal site pers o n nel m ust re p ort a n y ne w i nf or mati o n re gar di n g t h e S A E wit hi n 
2 4 h o urs of bec o mi n g a w are of t h e i nf or mati o n i n t he sa me ma n ner t hat t he i nitial S A E Re p ort 
F or m was s e nt.  F oll o w- u p i nf or mati o n is rec or d e d o n a n a me n de d or ne w S A E Re p ort F or m, 
wit h a n i n dicati o n t hat it is f oll o w - u p t o t he pre vi o usl y re p orte d S A E a n d t h e date of t he ori gi nal 
re p ort.  T he f oll o w- u p re p ort s h o ul d i ncl u de i nf or mati o n t hat was n ot pr o vi de d o n t he pre vi o us 
S A E Re p ort F or m, s uc h as t he o utc o me of t he e ve nt (e g, res ol ve d or o n g oi n g), treat me nt 
pr o vi de d, acti o n ta ke n wit h st u d y dr u g beca use of t he S A E (e g, d ose re d uce d, i nterr u pte d, or 
disc o nti n ue d), or s u bject dis p ositi o n (e g, c o nti n ue d or wit h dre w fr o m st u d y partici pati o n).  Eac h 
rec urre nce, c o m plicati o n, or pr o gressi o n of t he ori gi nal e v e nt s h o ul d be re p orte d as f oll o w- u p t o 
t hat e ve nt, re gar dless of w he n it occ urs. 
If t he S A E is n ot d oc u me nte d i n t he I B f or t he st u d y dr u g ( ne w o cc urre nce) a n d is t h o u g ht t o be 
relate d t o t he s p o ns or's st u d y dr u g, t h e s p o ns or or its desi g nee m a y ur ge ntl y re q uire f urt her 
i nf or mati o n fr o m t he i n v esti gat or f or re p orti n g t o healt h a ut h orities.  T he s p o ns or or its desi g n ee 
ma y n ee d t o iss ue a n I n v esti gat or N otificati o n (I N) t o i nf or m all i n ve sti gat ors i n v ol ve d i n a n y 
st u d y wit h t he sa me dr u g t hat t his S A E has bee n re p orte d.  S us pecte d U ne x pecte d Seri o us 
A d verse Reacti o ns ( S U S A Rs) will be c ollecte d a n d re p orte d t o t he c o m pete nt a ut h orities a n d 
rele va nt et hics c o m mittees i n acc or da nce wit h Directi ve 2 0 0 1/ 2 0/ E C, or as per nati o nal 
re g ulat or y r e q uire me nts i n partici pati n g c o u ntries. 
8. 4.  
E mer ge nc y U n bli n di n g of Tre at me nt Assi g n me nt  
N ot a p plica ble.  
8. 5.  
Pre g n a nc y  
Pre g n a nc y, i n a n d of itself, is n ot re gar d e d as a n A E u nless t here is s us pici o n t hat st u d y dr u g m a y 
ha ve i nterf ere d wit h t he effecti ve n ess of a c o ntrace pti ve me dicati o n or met h o d.  W he n a 
pre g na nc y h as bee n c o nfir me d i n a s u bject d uri n g mater nal or p ater nal e x p os ure t o st u d y dr u g, 
t he f oll o wi n g pr o ce d ur es s h o ul d be f oll o we d i n or der t o e ns ure s u bj ect safet y: 
•  T he st u d y dr u g m ust be disc o nti n ue d i m me diatel y (fe male s u bjects o nl y; see 
Secti o n  5. 5. 1  f or t he ma xi m u m per mitte d d urati o n of st u d y dr u g i nterr u pti o n). 
•  T he i n vesti gat or m ust c o m plete a n d s u b mit t he I n c yt e Cli nical Trial Pre g n a nc y f or m 
t o t he s p o ns or or its desi g nee wit hi n 2 4 h o urs  of lear ni n g of t he pre g na n c y. 

I nc yte C or p orati o n 
P a ge 6 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
Data o n fet al o utc o me a n d breastfee di n g are c ollecte d f or re g ulat or y re p orti n g a n d dr u g safet y 
e val uati o n.  F oll o w- u p s h o ul d be c o n d ucte d f or eac h pre g na n c y t o deter mi ne o utc o me, i ncl u di n g 
s p o nta ne o us or v ol u ntar y ter mi nati o n, details of t he birt h, a n d t he prese nce or a bse nce of a n y 
birt h defects, c o n ge nital a b n or malities, or mater n al a n d/ or ne w b or n c o m plicati o ns, b y f oll o wi n g 
u ntil t he first well - ba b y visit.  Pre g na nc y s h o ul d b e rec or de d o n a Cli nical Trial Pre g na nc y f or m 
a n d re p ort e d b y t he i n vesti gat or t o t he s p o ns or or its desi g nee.  Pre g na n c y f oll o w- u p i nf or mati o n 
s h o ul d be rec or de d o n t h e sa me f or m a n d s h o ul d i ncl u de a n ass ess me nt of t he p ossi ble ca usal 
relati o ns hi p t o t he s p o ns or's st u d y dr u g t o a n y pre g na n c y o utc o me, as well as f oll o w- u p t o t he 
first well- ba b y visit or t he d urati o n s pecifi e d i n l ocal re g ulati o ns, w hic h e ver is later.  Refer t o t he 
I n c yt e Ref ere n ce G ui d e f or C o m pleti n g t he Cli nical Trial Pre g na n c y F or m.  
A n y S A E occ urri n g d uri n g pre g n a nc y m ust be rec o r de d o n t he S A E re p ort f or m a n d 
s u b mitte d t o t he s p o ns o r or desi g nee. 
8. 6.  
W ar ni n gs a n d Prec a uti o ns  
S pecial war ni n gs or preca uti o ns f or t he st u d y dr u g, deri ve d fr o m s afet y i nf or mati o n c olle cte d b y 
t he s p o ns or or its desi g n ee, are prese nt e d i n t he itaciti ni b I n vesti gat or's Br o c h ure (I B) a n d 
r u x oliti ni b prescri bi n g i nf or mati o n.  A d diti o nal safet y i nf or mati o n c ollect e d bet wee n I B u p d ates 
will be c o m m u nicate d i n t he f or m of I n v esti gat or N otificati o ns (I Ns).  A n y i m p orta nt ne w safet y 
i nf or mati o n s h o ul d be disc usse d wit h t he s u bject d uri n g t he st u d y, as n ecessar y.  If n e w 
si g nifica nt ris ks are i de ntifie d, t he y will be a d de d t o t he I C F. 
8. 7.  
D at a M o nit ori n g C o m mittee  
N o t a p plica ble. 
8. 8.  
A d verse E ve nts of S peci al I nterest  
All re p orte d A Es will be c ollecte d.  T he i n ci de nce of s pecific s afet y  e v e nts i ncl u di n g maj or 
t hr o m b osis, he m orr ha gic e ve nts, le u ke mia, or m yel oi d tra nsf or mati o n will be ta b ulate d.  
8. 9.  
Pr o d uct C o m pl ai nts  
T he s p o ns or c ollects pr o d uct c o m plai nts o n st u d y dr u gs a n d dr u g deli ver y s yste ms use d i n 
cli nical st u dies i n or der t o e ns ure t he s afet y of st u d y partici pa nts, m o nit or q ualit y, a n d facilitate 
pr ocess a n d pr o d uct i m pr o ve me nts. 
All pr o d uct c o m plai nts ass ociate d wit h  material p ac ka ge d, la bele d, a n d rel ease d b y t he s p o ns or 
or its desi g nee will be re p orte d t o t he s p o ns or.  All pr o d uct c o m plai nts ass ociate d wit h ot her 
st u d y materi al will be re p orte d directl y t o t he res pecti ve ma n ufact urer. 
T he i n vesti gat or or his/ her desi g nee is res p o nsi ble f or re p orti n g a c o m plet e descri pti o n of t he 
pr o d uct c o m plai nt via e mail or ot her writte n c o m m u nicati o n t o t he s p o ns or c o ntact or res pecti ve 
ma n ufact ur er as n ot e d i n t he pac ka gi n g i nf or mati o n.  A n y A E ass ociat e d wit h a pr o d uct 
c o m plai nt s h o ul d be re p orte d as descri be d i n Secti o n 8. 1. 2  of t his Pr ot oc ol. 
If t he i n vesti gat or is as ke d t o ret ur n t he pr o d uct f or i n vesti gati o n, he/s he will ret ur n a c o p y of t h e 
pr o d uct c o m plai nt c o m m u nicati o n wit h t he pr o d uct. 

I nc yte C or p orati o n 
P a ge 6 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
9.  
S T A TI S TI C S  
9. 1.  
St u d y P o p ul ati o n s 
T he F A S i ncl u des all s u bjects e nr olle d i n t h e st u d y w h o recei ve d at least 1  d ose of st u d y dr u g 
(itaciti ni b).  T he F A S  will be use d i n t he a nal yses of de m o gra p hic, b aseli ne, a n d effi cac y d ata.  
T he safet y p o p ulati o n i ncl u des all e nr olle d  s u bjects w h o recei ve d at least 1 d ose of st u d y dr u g.   
T he per pr ot o c ol p o p ulati o n i ncl u des all e nr olle d s u bjects w h o were s uffi cie ntl y c o m plia nt wit h 
t he Pr ot oc ol.  S pecific criteria f or t his p o p ulati o n will be defi ne d i n t he S A P.  
T he P K /P D  e val ua ble p o p ulati o n i ncl u des all s u bjects w h o recei ve d at least 1 d ose of st u d y dr u g 
a n d pr o vi de d at least 1 sa m ple f or P K /P D .   
9. 2.  
Selecti o n of S a m ple S ize 
U p t o 2 1 s u bjects will be e nr olle d i n eac h of t he 2 d ose c o h orts ( C o h ort A a n d C o h ort B) f or a 
t otal of 4 2 s u bjects o verall.  T he si g n test will be use d t o e val uate p erce nt a ge c ha n ge fr o m 
baseli ne i n s plee n v ol u m e b y M RI or C T at Wee k 2 4 i n a p plica ble s u bjects  wit h a 1-si de d T y pe I 
err or of 0. 0 5.  If 1 5 or m ore o ut of 2 1 s u bjects o bser ve a > 0 % S V R at Wee k 2 4, t he n f urt her 
de vel o p me nt of itaciti ni b as m o n ot hera p y or i n c o m bi nati o n wit h r u x oliti ni b ma y b e c o nsi dere d.  
If t he per ce nta ge of S V R at Wee k 2 4 is n or mall y distri b ute d wit h mea n 1 1. 4 a n d sta n dar d 
de viati o n 1 4. 5, t he test has 8 5 % p o wer t o i n dicat e t hat a d diti o nal de vel o p me nt is warra nt e d.   
9. 3.  
Le vel of Si g nific a nce  
T he le vel of si g nifica nce f or detecti n g a differe nce  fr o m a 0 % me dia n p erce nta ge S V R i n eac h 
c o h ort is 5 % ( 1-si de d).  I n ot her w or ds, u n der t he n ull h y p ot hesis of s u bjects recei vi n g itaciti ni b 
ha vi n g a tr ue me dia n p er ce nta ge S V R of 0 %, t here is a 5 % c h a nce of decl ari n g a gi v e n c o h ort as 
ha vi n g a me dia n perce nt a ge S V R > 0 %.  N ote t h at t his le vel of si g nifica n ce d oes n ot acc o u nt f or 
testi n g of m ulti ple c o h orts. 
9. 4.  
St atistic al A n al yses  
A f ull descri pti o n of all a nal yses will be i ncl u de d i n t he S A P d oc u me nt. 
9. 4. 1.  
Effic ac y A n al yses 
9. 4. 1. 1.  
Pri m ar y Effic ac y A n al yses  
T he pri mar y e n d p oi nt of c ha n ge a n d perce nt a ge of S V R (as meas ure d b y M RI or C T ) at 
Wee k  2 4 will be s u m marize d b y c o h ort.  Wit hi n eac h c o h ort, t he si gn test will be use d t o 
e val uate me dia n p er ce nta ge of S V R , a n d a 9 0 % c o nfi de nce i nter val f or t h e me dia n perce nta ge 
S V R will be calc ulate d  usi n g t he e x act bi n o mial c o nfi de nce i nter val met h o d.  Perce nta ge S V R 
will be s u m marize d descri pti vel y at Wee k 1 2 b y c o h ort.  

I nc yte C or p orati o n 
P a ge 6 4  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
9. 4. 1. 2.  
Sec o n d ar y Effic ac y A n al yses 
Sec o n dar y efficac y a n al yses will be c o n d ucte d f or t he F A S  p o p ulati o n.  C ha n ge a n d p erce nta ge 
c ha n ge fr o m baseli ne i n q ua ntitati ve varia bles will be s u m marize d  b y c o h ort usi n g des cri pti ve 
statistics.  Fre q ue n cies a n d perce nt a ges f or cat e g orical varia bles will be pr o vi de d b y c o h ort.  
C ha n ge a n d perce nt a ge c ha n ge i n s plee n le n gt h fr o m baseli ne as meas ure d b y pal p ati o n at eac h 
visit w here t he par a meter is assesse d t hr o u g h Wee k 2 4 will be ta b ulate d b y c o h ort wit h s u m mar y 
statistics.  
Perce nt a ge c ha n ge fr o m baseli ne i n 7 -da y M F S A F T S S a n d M P N -S A F T S S will be s u m marize d 
at Wee k 1 2 a n d Wee k 2 4 b y c o h ort, a n d 9 0 % c o nfi de nce i nter v al s f or t he m e dia n perce nta ge 
c ha n ge will be esti mate d.  
Patie nt Gl o bal I m pr essi o n of C ha n ge will be s u m mari ze d b y visit.  S u bject data will be 
s u m marize d b y c o h ort a n d fi nal titrate d d ose of itaciti ni b. 
T he n u m ber of s u bjects wit h res p o nses acc or di n g t o t he 2 0 1 3 I W G c o ns e ns us criteria will be 
ta b ulate d. 
9. 4. 1. 2. 1.  Deri v ati o n of M F S A F T S S  
T he T S S f or t he M F S A F v 2. 0 diar y w ill be deter mi ne d as f oll o ws ( N O T E:  sc ores f or i nacti vit y 
a n d fati g ue will n ot be i n cl u de d i n T S S  deter mi nati o ns):  
•  T he Dail y T otal Sc ore will be defi ne d as t he s u m of 6 i n di vi d ual s y m pt o m sc ores 
( ni g hts s weats, itc hi ness, a b d o mi nal disc o mf ort, pai n u n der left ri bs, earl y s atiet y, 
b o ne/ m uscle pai n, eac h wit h a 0 t o 1 0 p oi nt scale) c ollecte d o n t he s a me d a y; t he 
sc ore will be missi n g if t here are a n y missi n g i n di vi d ual sc ores.  N ote t hat t he diar y is 
c o m plete d at t he e n d of eac h da y.  
•  T he Baseli ne T otal Sc or e will be defi ne d as t he a v era ge of Dail y T otal Sc ores fr o m 
t he baseli ne peri o d.  If t h ere are m ore t ha n 7 da ys of b aseli ne s y m pt o m data rec or de d 
( beca us e of a d ela y i n treat me nt start), t he last 7 d a ys b ef ore e nr oll me nt will be use d.  
T he Baseli ne T otal S c or e will be missi n g if t here are fe wer t ha n 4 d a ys of Baseli ne 
Dail y T otal Sc ore s. 
•  T he Wee k 1 2 ( 2 4) T ot al Sc ore will be defi n e d as t he a vera ge of Dail y T otal Sc ores 
fr o m t he last 7 da ys of s y m pt o m sc ores bef ore t he Wee k 1 2 ( 2 4) visits.  T he Wee k 1 2 
( 2 4) Total Sc ore will be missi n g if t here are fe w er t ha n 4 da ys of Wee k 1 2 ( 2 4) Dail y 
T otal Sc ores.  
•  T he per ce nt a ge c ha n ge will be calc ulate d as f oll o ws:   
% C ha n ge = 1 0 0 × ( Wee k 1 2 T otal Sc ore – Baseli ne T otal Sc ore) / Bas eli ne T otal 
Sc ore  
9. 4. 2.  
S af et y A n al yses 
T he sa fet y a nal yses will be c o n d ucte d f or t he safet y e v al ua ble p o p ulati o n. 

I nc yte C or p orati o n 
P a ge 6 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
9. 4. 2. 1.  
A d verse E ve nts  
A T E A E is a n y A E eit her re p orte d f or t he first ti me or w orse ni n g of a pre- e xisti n g e ve nt after 
first d ose of st u d y dr u g.  A nal ysis of A Es will be li mite d t o T E A Es, b ut data listi n gs will i ncl u de 
all A Es re gar dless of t heir ti mi n g t o st u d y dr u g a d mi nistrati o n.  A d verse e v e nts will be ta b ulate d 
b y t he M e d D R A preferre d ter m a n d s yste m or ga n class.  Se verit y of A Es will be base d o n t he 
N CI C T C A E v 4. 0 3 usi n g Gra des 1 t hr o u g h 5. 
T he s u bset of A Es c o nsi d ere d b y t he i n vesti gat or t o ha ve a relati o ns hi p t o st u d y dr u g will be 
c o nsi dere d t o be tr eat me nt-relate d A Es.  If t he i n v esti gat or d o es n ot s pecif y t he relati o ns hi p of 
t he A E t o st u d y dr u g, t he n t he A E will be c o nsi dere d treat me nt-relate d.  T h e i nci de nce of A Es 
a n d treat me nt -relate d A Es will be ta b ulate d. 
9. 4. 2. 2.  
Cli nic al L a b or at or y Tests 
La b orat or y test v al ues o utsi de t he n or mal ra n ge will be assesse d f or s e verit y base d o n t he n or mal 
ra n ges f or t he cli nical r ef ere nce la b or at or y.  T he i nci de nce of a b n or m al la b orat or y val ues a n d 
s hift ta bles relati ve t o bas eli ne will be ta b ulate d. 
La b orat or y d ata will be classifie d i nt o G ra des 1 t hr o u g h 5 usi n g C T C A E v 4. 0 3 or si milar criteria 
w here cli nical i nter ve nti o n is re q uire d f or C T C A E gra di n g.  S hift ta bles fr o m baseli ne t o t he 
w orst p ost baseli ne C T C A E gra de will be pr o vi de d f or la b orat ories usi n g C T C A E gra di n g 
criteria.  F or la b orat or y p ara meters w here C T C A E gra des are n ot defi ne d, s hift ta bles t o t he 
w orst p ost baseli ne val ue usi n g t he l o w/ n or mal/ hi g h cl assificati o ns base d o n la b orat or y refere nce 
ra n ges will be pr o vi de d.  
9. 4. 2. 3.  
Vit al Si g ns  
Descri pti ve statistics a n d mea n c ha n ge fr o m b aseli ne will be deter mi ne d f or vital si g ns ( bl o o d 
press ure, p ulse , res pirat or y rate, a n d b o d y te m perat ure) at eac h assess me nt ti me.  Vital si g n 
res ults will be re vie w e d f or cli nicall y n ot a ble a b n or malities (see Ta bl e  1 2), a n d s u bjects 
e x hi biti n g cli nicall y n ota ble vital si g n a b n or m alities will be liste d.  A val ue will be c o nsi dere d a n 
"alert" v al ue if it is o utsi de t he esta blis he d ra n ge a n d s h o ws a > 2 5 % c ha n ge fr o m baseli ne.  
T a ble 1 2: 
Criteri a f or Cli nic all y N ot a ble Vit al Si g n A b n or m alities  
P ar a meter  
Hi g h T hres h ol d  
L o w T hres h ol d  
S yst olic bl o o d press ure  
> 1 5 5  m m H g  
< 8 5 m m H g  
Diast olic bl o o d press ure  
> 1 0 0 m m H g  
< 4 0 m m H g  
P ulse  
> 1 0 0 b p m  
< 4 0 b p m  
T e m perat ure  
> 3 8º C  
< 3 5. 5º C  
Res pirat or y rate  
> 2 4/ mi n  
< 8/ mi n  
9. 4. 2. 4.  
Electr oc a r di o gr a ms  
Electr ocar di o gra m a b n or malities, b ot h at baseli ne a n d p ost baseli ne visits, wil l be ta b ulate d b y 
treat me nt gr o u p.  S u bjects e x hi biti n g cli nicall y n ota ble E C G a b n or malities will be liste d.  

I nc yte C or p orati o n 
P a ge 6 7  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
1 0.  
E T HI C A L C O N SI D E R A TI O N S A N D A D MI NI S T R A TI V E 
P R O C E D U R E S  
1 0. 1.  
I n vesti g at or Res p o nsi bilities 
T his st u d y will be perf or me d i n acc or d a nce wit h et hical pri nci ples t hat ori gi nate i n t he 
Declar ati o n of Helsi n ki a n d c o n d ucte d i n a d h ere n ce t o t he st u d y Pr ot o c ol; G C Ps as defi ne d i n 
Title  2 1 of t he U S C F R Parts 1 1, 5 0, 5 4, 5 6, a n d 3 1 2; I C H E 6 G C P c o ns oli date d g ui deli nes; a n d 
l ocal re g ulat or y re q uir e me nts as a p plica ble t o t he st u d y l ocati o ns. 
T he i n vesti gat or will be r es p o nsi ble f or: 
•  P er mitti n g st u d y-related m o nit ori n g , s p o ns or a u dits, I R B/I E C re vie w, a n d re g ul at or y 
i ns pecti o ns b y pr o vi di n g direct access t o s o urce data a n d ot her rele va nt cli ni cal st u d y 
d oc u me nts. 
− M o nit ori n g:  Q ualifie d r e prese ntati ves of t h e s p o ns or or its desi g n ee , st u d y 
m o nit ors, will m o ni t or t he st u d y acc or di n g t o a pre deter mi ne d pla n.  T he 
i n vesti gat or m ust all o w t he st u d y m o nit ors t o re vi e w a n y st u d y materi als a n d 
s u bject rec or ds at eac h m o nit ori n g visit. 
− A u diti n g:  Q ualifie d r e prese ntati ves of t he s p o ns or or its desi g n ee ma y a u dit t he 
cli nical st u d y site a n d st u d y dat a t o e val uat e c o m plia nce wit h t he Pr ot oc ol, 
a p plica ble l ocal cli nical st u d y re g ul ati o ns, a n d o verall st u d y c o n d u ct.  T he 
i n vesti gat or m ust all o w t he a u dit ors t o re vie w ori gi nal s o urce rec or ds a n d st u d y 
d oc u me ntati o n f or all s u bjects. 
− Re g ulat or y i ns pecti o n:  Re g ulat or y a ut h orities ma y c o n d uct a n i ns pecti o n of t he 
st u d y a n d t he site at a n y ti me d uri n g t he d e vel o p m e nt of a n i n vesti gati o nal 
pr o d uct .  T he i n vesti gat or a n d staff are e x pecte d t o c o o perat e wit h t he i ns pect ors 
a n d allo w access t o all s o urce d oc u m e nts s u p p orti n g t he e C R Fs a n d ot her 
st u d y-r elate d d oc u m e nts.  T he i n vesti gat or m ust i m me diatel y n otif y t he s p o ns or 
w he n c o ntacte d b y a n y re g ulat or y a ut h orit y f or t he p ur p oses of c o n d u cti n g a n 
i ns pecti o n. 
•  O btai ni n g i nf or m e d c o ns e nt a n d e ns uri n g t hat t he st u d y s u bjects' q uesti o ns ha ve bee n 
a ns wer e d a n d t he s u bjects f ull y u n dersta n d st u d y pr oce d ures: 
− I nf or me d c o ns e nt m ust be o btai ne d bef ore  a n y st u d y-relate d pr oce d ures are 
c o n d ucte d, u nless ot her wise s pecifie d b y t he Pr ot o c ol. 
− I nf or me d c o ns e nt m ust be o btai ne d usi n g t h e I R B/I E C-a p pr o ve d versi o n i n a 
la n g u a ge t hat is nati ve a n d u n dersta n da ble t o t he s u bject.  A te m plate will be 
pr o vi de d b y t he s p o ns or or its desi g nee.  T he s p o ns or or its desi g n ee m ust re vie w 
a n d ac k n o wl e d ge t he site-s pecific c ha n ges t o t he I C F te m plate.  T he I C F m ust 
i ncl u de a state me nt t hat t he s p o ns or or its desi g n ee a n d re g ul at or y a ut h oriti es ha ve 
direct access t o s u bject rec or ds.  

I nc yte C or p orati o n 
P a ge 6 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
•  O btai ni n g a p pr o val fr o m t he I R B/I E C bef ore t he  st art of t he st u d y a n d f or a n y 
c ha n ges  t o t he cli nical st u d y Pr ot oc ol, i m p orta nt Pr ot oc ol de viati o ns, r o uti ne u p dates, 
a n d safet y i nf or mati o n i n acc or d a nce wit h i nstit uti o nal re q uire m e nts a n d l ocal la w. 
− T he  i n vesti gat or is res p o nsi ble f or e ns uri n g t hat t he safet y re p orts pr o vi de d b y t he 
s p o ns or are re vie w e d a n d pr ocesse d i n acc or da nce wit h re g ul at or y re q uire m e nts 
a n d wit h t he p olicies a n d pr oce d ures esta blis he d b y t he I R B /I E C. 
•  A d heri n g t o t he Pr ot oc ol as descri be d i n t his d oc u me nt a n d a gree i n g t hat c ha n ges t o 
t he Pr ot oc ol pr oce d ur es, wit h t he e x ce pti o n of me dical e mer ge ncies, m ust be 
disc usse d a n d a p pr o v e d, first, b y t he s p o ns or or its desi g nee a n d, s ec o n d, b y t he 
I R B/IE C.  Eac h i n v esti gat or is res p o nsi ble f or e nr olli n g s u bjects w h o ha v e met t he 
s pecifie d eli gi bilit y criteria. 
T he I R B/I E C t hat g r a nte d ori gi nal a p pr o val, or t h e I R B/I E C c urre ntl y res p o nsi ble f or 
o verseei n g t he c o n d uct of t he st u d y, m ust be n otifie d of all c ha n ges i n a n d de viati o ns 
fr o m t he P r ot oc ol t hat ma y i n crease ris k t o t he s u bject a n d/ or t hat ma y a d v ersel y 
affect t he ri g hts of  t he s u bject or vali dit y of t he i n vesti gati o n.  T he i n v esti gat or m ust 
se n d a c o p y of t h e a p pr o val letter fr o m t he I R B/I E C t o t he s p o ns or or C R O a n d retai n 
t he ori gi nal i n t he site st u d y re g ulat or y file. 
Maj or eli gi bilit y d e viati o ns m ust be re p orte d t o t h e I R B/I E C i n acc or d a nce wit h t he 
I R B/I E C re q uir e me nts.  D uri n g t h e c o urs e of t he st u d y, t he m o nit or m ust n otif y t he 
s p o ns or of s u bjects f o u n d n ot t o ha ve met eli gi bilit y criteria.  T he me di cal m o nit or, i n 
c olla b orati o n wit h t he i n vesti gat or, will deter mi ne w het her  t h e s u bject s h o ul d be 
wit h dra w n fr o m t he st u d y. 
•  Retai n i n g r ec or ds i n acc or da nce wit h all l ocal, nati o nal, a n d re g ulat or y la ws, b ut f or a 
mi ni m u m peri o d of at least 2  years aft er t he last m ar keti n g a p plicati o n a p pr o val i n a n 
I C H re gi o n a n d u ntil t her e are n o p e n di n g or c o nt e m plate d mar keti n g a p plicati o ns i n 
a n I C H re gi o n, or if n ot a p pr o ve d, 2 years aft er t he ter mi nati o n of t he test article f or 
i n vesti gati o n t o e ns ure t h at t he a vaila bilit y of st u d y d oc u m e ntati o n s h o ul d it bec o me 
necessar y f or t he s p o ns or or a re g ul at or y a ut h orit y t o re vie w. 
− T he i n vesti gat or m ust n ot destr o y a n y rec or ds ass ociate d wit h t he st u d y wit h o ut 
recei vi n g a p pr o val fr o m t he s p o ns or.  T he i n vesti gat or m ust n otif y t he s p o ns or or 
its desi g nee i n t he e ve nt of acci d e ntal l oss or destructi o n of a n y st u d y rec or ds.  If 
t he i n vesti gat or l ea ves t h e i nstit uti o n w here t he st u d y w as c o n d uct e d, t he s p o ns or 
or its desi g nee m ust be c o ntacte d t o arra n ge alter n ati ve rec or d st ora ge o pti o ns. 
− All eC R F data e ntere d b y t he site (i ncl u di n g a u dit trail), as well as c o m p uter 
har d ware a n d s oft war e (f or accessi n g t h e data), will be mai ntai ne d or ma de 
a vaila ble at t he site i n c o m plia nce wit h a p plica ble rec or d rete nti o n re g ulati o ns.  
T he s p o ns or will retai n t he ori gi n al e C R F data a n d a u dit trail.  
1 0. 2.  
Acc o u nt a bilit y , H a n dli n g, a n d Dis p os al of St u d y Dr u g 
T he i n vesti gat or is res p o nsi ble f or dr u g acc o u nta bilit y at t he st u d y site; h o we ver, t he i n v esti gat or 
ma y assi g n s o me of t he dr u g acc o u nt a bilit y d uties t o a n a p pr o priat e p har macist or desi g n ee.  
I n v e nt or y a n d acc o u nt a bilit y rec or ds m ust be mai ntai ne d a n d rea dil y a vaila ble f or i ns pecti o n b y 
t he st u d y m o nit or a n d are o pe n t o i ns pecti o n at a n y ti me b y a n y a p plica ble re g ulat or y a ut h orities. 

I nc yte C or p orati o n 
P a ge 6 9  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
T he i n vesti gat or or desi g nee will be e x pecte d t o c ollect a n d retai n all use d, u n use d, a n d partiall y 
use d c o ntai ners of st u d y dr u g u ntil t he e n d of t he st u d y.  T he i n vesti gat or or desi g n ee m ust 
mai ntai n rec or ds t hat d o c u me nt: 
•  I n v esti gati o nal pr o d uct d eli ver y t o t he st u d y site 
•  T he i n ve nt or y at t he site 
•  Use b y eac h s u bject i ncl u di n g pill/ u ni t c o u nts fr o m eac h s u p pl y dis pe nse d 
•  Ret ur n t o t he i n vesti gat or or desi g n ee  
T hese rec or ds s h o ul d i ncl u de dates, q ua ntities, bat c h/serial n u m bers (if a vaila ble), a n d t he u ni q ue 
c o de n u m bers (if a vaila bl e) assi g ne d t o t he i n vesti gati o nal pr o d u ct a n d st u d y s u b jects. 
T he i n vesti gati o nal pr o d uct m ust be use d o nl y i n acc or d a nce wit h t he pr ot oc ol.  T he i n vesti gat or 
will als o mai ntai n rec or ds a de q uatel y d oc u m e nti n g t hat t he s u bjects were pr o vi de d t he c orrect 
st u d y dr u g s pecifie d. 
C o m plete d acc o u nta bilit y r ec or ds wil l be arc hi v e d b y t he site.  At t he c o m pleti o n of t he st u d y, 
t he i n vesti gat or or desi g n ee will o versee s hi p me nt of a n y re m ai ni n g st u d y dr u g b ac k t o t he 
s p o ns or or s p o ns or's desi g nee f or d estr ucti o n acc or di n g t o i nstit uti o nal sta n dar d o perati n g 
pr oce d ur es.  If l ocal pr oce d ures ma n d ate site destr ucti o n of i n vesti gati o nal s u p pl y, pri or writte n 
a p pr o val m ust be o btai ne d fr o m t he s p o ns or. 
1 0. 3.  
D at a M a n a ge me nt  
1 0. 3. 1.  
D at a C ollecti o n 
T he i n vesti gat or will be pr o vi de d wit h a n e C R F f or eac h s u bj ect.  E ntries ma de i n t he e C R F m us t 
be verifia bl e a gai nst s o ur ce d oc u me nts; a n y discre pa ncies s h o ul d be e x plai ne d a n d d oc u me nt e d.  
T he i n vesti gat or will be r es p o nsi ble f or re vie wi n g all data a n d e C R F e ntries a n d will si g n a n d 
date t he desi g nate d p a ges i n eac h s u bject 's e C R F, verif yi n g t hat t he i nf or m ati o n is tr ue a n d 
c orrect.  T he i n vesti gat or is res p o nsi ble f or t he re vie w a n d a p pr o val of all res p o nses.   
1 0. 3. 2.  
D at a M a n a ge me nt 
Data ma na ge me nt will be perf or me d i n a vali dat e d data base via a n Electr o nic Data Ca pt ure 
( E D C) s yst e m.  All data e ntr y, verificati o n, a n d v ali dati o n will be perf or m e d i n acc or da nce wit h 
t he c urr e nt sta n dar d o p er ati n g pr o ce d ures of t he D ata Ma na ge me nt De p art me nt at t he s p o ns or or 
its desi g nee.  T h e data b ase will be a ut h orize d f or l oc k o nce all defi ne d pr o ce d ures are c o m plete d. 
1 0. 4.  
St u d y M o nit ori n g  
Q ualifie d re prese nt ati ves of t he s p o ns or or s p o ns or desi g n ees, "st u d y m o nit ors," will m o nit or t he 
st u d y acc or di n g t o a pr e d eter mi ne d m o nit ori n g pla n.  M o nit ori n g visits pr o vi de t he s p o ns or wit h 
t he o p p ort u nit y t o: 
•  E val uate t he pr o gress of t he st u d y  
•  Verif y t he acc urac y a n d c o m plete ness of e C R Fs  

I nc yte C or p orati o n 
P a ge 7 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
•  Ass ure t hat all pr ot oc ol r e q uire me nts, a p plica ble la ws a n d/ or re g ulati o ns, a n d 
i n vesti gat or's o bli gati o ns are bei n g f ulfille d 
•  Res ol ve a n y i nc o nsiste ncies i n t he st u d y rec or ds. 
T he i n vesti gat or m ust all o w t he st u d y m o nit ors t o peri o dicall y re vie w, at m ut uall y c o n v e nie nt 
ti mes, d uri n g t he st u d y a n d after t he st u d y has b ee n c o m plete d, all e C R Fs a n d office, h os pital, 
a n d la b orat or y rec or ds s u p p orti n g t he partici pati o n of eac h s u bj ect i n t he st u d y.  T he e C R Fs a n d 
ot her d oc u me ntati o n s u p p orti n g t he st u d y m ust be ke pt u p- t o-date b y t he i n vesti gat or a n d t he 
researc h staff at t he i n vesti gati ve site.  T hes e st u d y materials m ust be a vaila ble f or re vi e w b y t he 
st u d y m o nit or, a n d/ or ot h er q ualifie d r e prese ntati v es of t he s p o ns or, at eac h m o nit ori n g visit. 
T he st u d y m o nit or will re vie w t he vari o us rec or ds of t he st u d y (e C R Fs, s u bj ect me dical a n d 
la b orat or y r ec or ds, a n d ot her perti ne nt data).  T he st u d y m o nit or will verif y t he e C R F data 
a gai nst ori gi n al s o urce d oc u me ntati o n f or acc urac y a n d c o m plete ness.  T h e st u d y m o nit or will 
i de ntif y dat a discre p a nci es a n d c olla b orate wit h t he i n vesti gat or a n d researc h staff t o res ol ve t he 
discre pa n cies i n a ti mel y ma n ner.  Pr ot oc ol de viati o ns will als o be i de ntifie d a n d rec or de d o n a 
" Pr ot oc ol De vi ati o n L o g."  T he st u d y m o nit or will f oll o w a n "Iss ue Escalati o n" pla n i n or d er t o 
e ns ure t hat eac h iss ue i de ntifie d d uri n g a m o nit ori n g visit is a p pr o priatel y d oc u me nte d, re p orte d, 
a n d res ol ve d i n a ti mel y ma n ner i n acc or d a nce wit h t he pla n 's re q uire me nts. 
1 0. 5.  
Pr ot oc ol A d here nce  
T he Pri nci pal I n vesti gat or m ust o btai n I R B a p pr o v al f or t he i n vesti gati o n.  I nitial I R B a p pr o val, 
a n d all materials a p pr o ve d b y t he I R B f or t his st u d y i ncl u di n g t he s u bject I C F a n d recr uit me nt 
materials m ust be mai nta i ne d b y t he i n v esti gat or a n d ma de a vaila ble f or i ns pecti o n. 
Eac h i n vesti gat or m ust a d here t o t he pr ot o c ol as d escri be d i n t his d oc u me nt a n d a gree t hat 
c ha n ges t o t he pr ot o c ol, wit h t he e x ce pti o n of me dical e mer ge ncies, m ust be disc usse d a n d 
a p pr o ve d, firstl y, b y t he s p o ns or a n d, sec o n dl y, b y t he I R B/I E C.  Eac h i n vesti gat or is res p o nsi ble 
f or e nr olli n g s u bjects w h o ha ve met t he pr ot oc ol i ncl usi o n a n d e x cl usi o n criteria.  T he I R B/I E C 
t hat gr a nte d ori gi nal a p pr o val, or t he I R B/I E C c urre ntl y res p o nsi ble f or o verseei n g t he c o n d u ct 
of t he st u d y m ust be n otifie d of all c h a n ges i n a n d de viati o ns fr o m t he pr ot oc ol t hat ma y i n crease 
ris k t o t he s u bject, a n d/ or t hat ma y a d vers el y affect t he ri g hts of t he s u bject or vali dit y of t he 
i n vesti gati o n.  T he i n vesti gat or m ust se n d a c o p y of t he a p pr o v al letter fr o m t he I R B/I E C t o t he 
s p o ns or or C R O a n d retai n t he ori gi nal i n t he site st u d y re g ul at or y file. 
Maj or eli gi bilit y d e viati o ns m ust be re p orte d t o t h e I R B/I E C i n acc or d a nce wit h t he I R B/I E C 
re q uire me nts.  D uri n g t h e c o urse of t he st u d y, t he m o nit or m ust n otif y t he s p o ns or of s u bjects 
f o u n d n ot t o ha ve met eli gi bilit y criteria.  T h e me dical m o nit or, i n c olla b orati o n wit h t he 
i n vesti gat or, will deter mi ne if t he s u bject s h o ul d b e wit h dra w n fr o m t he st u d y. 
1 0. 6.  
D at a Pri v ac y a n d C o n fi de nti alit y of St u d y Rec or ds  
T he i n vesti gat or a n d t he s p o ns or or its desi g nee m ust a d here t o a p plica ble d ata pri vac y l a ws a n d 
re g ulati o ns.  T he i n vesti gat or a n d t he s p o ns or or its desi g nee are res p o nsi ble f or e ns uri n g t h at 
se nsiti ve i nf or mati o n is ha n dle d i n acc or da n ce wit h l ocal re q uire me nts (e g, HI P A A).  
A p pr o priate c o nse nt a n d a ut h orizati o ns f or use a n d discl os ure a n d/ or tra nsfer (if a p plica ble) of 
pr otecte d i nf or m ati o n m ust be o btai ne d. 

I nc yte C or p orati o n 
P a ge 7 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
S u bject na mes will n ot be s u p plie d t o t he s p o ns or or its desi g nee, if a p plica ble.  O nl y t he s u bject 
n u m ber a n d s u bject' s i nitials (s u bject's i nitials will o nl y be rec or de d if all o wa ble b y l ocal 
re g ulati o ns) will be rec or de d i n t he eC R F , w here p er mitte d; if t he s u bject 's na me a p pears o n a n y 
ot her d oc u me nt ( e g, la b orat or y re p ort), it m ust be o bliterate d o n t he c o p y of t he d oc u me nt t o be 
s u p plie d t o t he s p o ns or or its desi g nee.  St u d y fi n di n gs st ore d o n a c o m p uter will be st ore d i n 
acc or d a nce wit h l ocal dat a pr otecti o n la ws.  T h e s u bjects will be i nf or me d t hat re pres e ntati ve s of 
t he s p o ns or or its desi g n ee, I R B or I E C, or re g ulat or y a ut h orities ma y i ns pect t heir me dical 
rec or ds t o verif y t he i nf or mati o n c ollecte d, a n d t h at all pers o nal i nf or m ati o n ma de a vaila ble f or 
i ns pecti o n will be ha n dle d i n strictest c o nfi de nce a n d i n acc or d a nce wit h l ocal data pr ot ecti o n 
la ws. 
1 0. 7.  
Fi n a nci al Discl os ure  
All cli nical i n vesti gat ors partici pati n g i n cli nical st u dies s u bject t o F D A Re g ulati o n Title 2 1 
C o de of Fe d er al Re g ul ati o ns ( C F R) Part 5 4 – Fi na ncial Discl os ure b y Cli nical I n vesti gat ors, are 
re q uire d pri or t o st u d y i nitiati o n t o s u b mit a c o m plete d Cli nical I n v esti gat or Fi na nci al Discl os ure 
Re q uest F or m t hat s uffi cie ntl y det ails a n y fi na ncial i nterests a n d arra n ge me nts t hat a p pl y.  F or 
t he p ur p ose of t his re g ulati o n, cli nical i n vesti gat or is defi ne d as a n y i n vesti gat or or 
s u bi n vesti gat or w h o is directl y i n v ol ve d i n t he treat me nt or e val uati o n of researc h s u bjects, 
i ncl u di n g t he s p o use a n d eac h d e pe n de nt c hil d of t he cli nical i n vesti gat or.  T hese re q uire me nts 
a p pl y t o b ot h U S a n d f or ei g n cli nical i n vesti gat ors c o n d ucti n g c o vere d cli nical st u dies. 
A n y n e w i n vesti gat ors or s u b- i n vesti gat ors a d de d t o t he c o vere d cli nical st u d y d uri n g its c o n d uct 
m ust als o s u b mit a c o m plete d Cli nical I n vesti gat or Fi na ncial Discl os ure Re q uest F or m.  D uri n g a 
c o vere d cli nical st u d y, a n y c h a n ges t o t he fi n a ncial i nf or mati o n pre vi o usl y re p orte d b y a cli nical 
i n vesti gat or m ust be r e p orte d t o t he s p o ns or/ desi g nee.  At t he c o n cl usi o n of t he c o vere d cli nical 
st u d y, t he cli nical i n vesti gat ors will be re mi n de d of t heir o bli gati o n t o re p ort t o t he 
s p o ns or/ desi g nee a n y c ha n ges t o t he fi na ncial i nf or mati o n pre vi o usl y re p ort e d.  T he cli nical 
i n vesti gat ors will als o be re mi n de d t hat t he y m ust re p ort a n y c ha n ges i n t heir fi na ncial 
i nf or mati o n f or a p eri o d of 1 year after c o m pleti o n of t he c o vere d cli nical st u d y. 
1 0. 8.  
Q u alit y C o ntr ol a n d Q u alit y Ass ur a nce  
1 0. 8. 1.  
S p o ns or A u dits  
At s o me p oi nt d uri n g t he st u d y, i n di vi d uals fr o m t he s p o ns or' s Q ualit y Ass ura nce d e part me nt 
a n d/ or t heir a ut h orize d r e prese ntati ve ma y visit t he i n vesti gat or 's site t o c o n d uct a n a u dit of t he 
st u d y.  T he p ur p ose of t his visit will be t o deter mi ne t he i n vesti gat or's a d here nce t o t he pr ot oc ol, 
a p plica ble r e g ulati o ns, a n d t he s p o ns or' s pr oce d ures, i n a d diti o n t o assessi n g t he acc urac y of t he 
st u d y data.  Bef ore i nitiati n g t his a u dit, t he i n vesti gat or will be c o ntact e d b y t he s p o ns or t o 
arra n ge a c o n ve nie nt ti me f or t his visit.  T he i n vesti gat or a n d st aff are e x pecte d t o c o o perate wit h 
t he a u dit ors a n d all o w access t o all s u bject rec or ds s u p p orti n g t he e C R Fs a n d ot her st u d y-relat e d 
d oc u me nts. 
1 0. 8. 2.  
I ns pecti o n b y Re g ul at or y A ut h orities 
At s o me p oi nt d uri n g t he i n vesti gati o nal pr o d u ct's de vel o p me nt pr o gra m, a re g ulat or y a ut h orit y 
ma y visit t he i n vesti gat or t o c o n d uct a n i ns pecti o n of t he st u d y a n d t he site.  T he i n vesti gat or a n d 

I nc yte C or p orati o n 
P a ge 7 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
staff ar e e x pecte d t o c o o perate wit h t he i ns pect ors a n d all o w access t o all s o urce d oc u m e nts 
s u p p orti n g t he e C R Fs a n d ot her st u d y-relat e d d oc u me nts.  T he i n vesti gat or m ust i m me diatel y 
n otif y t he s p o ns or w h e n c o ntacte d b y a n y re g ulat or y a ut h orit y f or p ur p os es of c o n d uct i n g a n 
i ns pecti o n. 
1 0. 9.  
D at a H a n dli n g a n d Rec or d kee pi n g  
1 0. 9. 1.  
I ns pecti o n of Rec or ds 
T he s p o ns or will be all o we d t o c o n d uct site visits t o t he i n vesti gati o n facilities f or t he p ur p ose of 
m o nit ori n g a n y as p ect of t he st u d y.  T he i n v esti gat or a grees t o all o w t he m o nit or  t o i ns pect t he 
dr u g st or a ge area, st u d y dr u g st oc ks, dr u g acc o u nta bilit y rec or ds, s u bject c harts a n d st u d y s o urce 
d oc u me nts, a n d ot her r ec or ds relati ve t o st u d y c o n d uct. 
T he i n vesti gat or m ust e ns ure t hat all rec or ds pertai ni n g t o t he c o n d uct of t h e cli nic al st u d y (as 
liste d a b o ve) ar e a d e q uat el y mai ntai ne d f or a peri o d of 2 years after t he last a p pr o val of a 
mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o p e n di n g or c o nte m plate d mar keti n g 
a p plicati o ns i n a n I C H re gi o n, or at least 2 years h a v e ela ps e d si nce t he f or mal ter mi nati o n of 
cli nical de vel o p me nt of t he i n vesti gati o nal pr o d uct. 
1 0. 9. 2.  
Rete nti o n of Rec or ds  
T he Pri nci pal I n vesti gat or m ust mai ntai n all d oc u me ntati o n relati n g t o t he st u d y f or a peri o d of 
2 years after t he l ast mar keti n g a p plicati o n a p pr o v al, or if n ot a p pr o ve d, 2 years after t he 
ter mi nati o n of t he test article f or i n vesti gati o n.  If it bec o mes necessar y f or t he s p o ns or or t he 
Re g ulat or y A ut h orit y t o r e vie w a n y d o c u me ntati o n relati n g t o t he st u d y, t h e i n vesti gat or m ust 
per mit access  t o s uc h rec or ds. 
T he i n vesti gat or m ust n ot destr o y a n y rec or ds ass ociate d wit h t he st u d y wit h o ut recei vi n g 
a p pr o val fr o m t he s p o ns or.  T he i n vesti gat or m ust n otif y t he s p o ns or i n t he e ve nt of acci de ntal 
l oss or destr ucti o n of a n y st u d y rec or ds.  If t he i nv esti gat or l ea ves t he i nstit uti o n w here t he st u d y 
was c o n d ucte d, t he s p o ns or m ust be c o ntacte d t o arra n ge alter nati ve rec or d st ora ge o pti o ns. 
W he ne ver p ossi ble, a n ori gi nal rec or di n g of a n o bser vati o n m ust be retai n e d as t he s o urce 
d oc u me nt.  H o we v er, a p h ot oc o p y of a rec or d is acce pta bl e, pr o vi de d it is le gi ble a n d is a 
verifie d c o p y of t he ori gi nal d oc u me nt. 
All e C R F data e ntere d b y t he site (i ncl u di n g a u dit trail), as well as c o m p uter har d w are a n d 
s oft ware (f or accessi n g t he data), will be mai ntai n e d or ma de a vaila ble at t he site i n c o m plia nce 
wit h a p plica ble rec or d r ete nti o n re g ul ati o ns.  T he s p o ns or will retai n t he ori gi nal e C R F d ata a n d 
a u dit trail. 
1 0. 9. 3.  
C o nfi de nti alit y  
S u bject na mes will n ot be s u p plie d t o t he s p o ns or.  O nl y t he s u bject n u m ber a n d s u bject i nitials 
will be rec or d e d i n t he e C R F, a n d if t he s u bject n a me a p pears o n a n y ot h er d oc u me nt (e g, 
la b orat or y r e p ort), it m ust be o bliterate d o n t he c o p y of t he d oc u me nt t o be s u p plie d t o t he 
s p o ns or.  St u d y fi n di n gs st ore d o n a c o m p uter will be st ore d i n acc or da n ce wit h l ocal data 
pr otecti o n la ws.  T he s u bjects will be i nf or me d t hat re prese nt ati ves of t he s p o ns or, I R B/I E C, or 
re g ulat or y a ut h orities ma y i ns pect t heir me dical rec or ds t o verif y t he i nf or mati o n c ollecte d, a n d 

I nc yte C or p orati o n 
P a ge 7 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
t hat all pers o nal i nf or mati o n ma de a vaila ble f or i ns pecti o n will be ha n dle d i n strictest c o nfi de nce 
a n d i n acc or da nce wit h l ocal data pr ot ecti o n la ws.  
1 0. 1 0.  
P u blic ati o n P olic y  
B y si g ni n g t he st u d y Pr ot oc ol, t he i n vesti gat or a n d his or her i nstit uti o n a gree t hat t he res ults of 
t he st u d y ma y be us e d b y t he s p o ns or, I nc yte C or p orati o n (I nc yte), f or t h e p ur p oses of nati o nal 
a n d i nter nati o nal r e gistrati o n, p u blicati o n, a n d i nf or mati o n f or me dical a n d p har mace utical 
pr ofessi o nals.  St u d y r es ults will be p u blis he d i n acc or d a nce wit h a p plica ble l ocal a n d nati o nal 
re g ulati o ns.  If necessar y, t he a ut h orities will be n otifie d of t he i n vesti gat or's na m e, a d dress, 
q ualificati o ns, a n d e xte nt of i n v ol ve me nt.  T he ter ms re gar di n g t he p u blicati o n of st u d y res ults 
are c o nt ai ned i n t he a gree me nt si g ne d wit h t he s p o ns or or its desi g n ee.  A si g ne d a gree me nt will 
be retai ne d b y t h e s p o ns or or its desi g n ee. 

I nc yte C or p orati o n 
P a ge 7 4  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
1 1.  
R E F E R E N C E S  
Ar ber D A, Or azi A, Hasserjia n R, et al . T he 2 0 1 6 re visi o n t o t he W orl d Healt h Or ga nizati o n 
classificati o n of m yel oi d ne o plas ms a n d ac ut e le u ke mia . Bl o o d 2 0 1 6; 1 2 7: 2 3 9 1- 2 4 0 5. 
B ose P , Verst o vse k S. T he e v ol uti o n a n d cli nical rele va nce of pr o g n ostic classificati o n s yste ms 
i n m yel ofi br osis. Ca ncer 2 0 1 6; 1 2 2: 6 8 1- 6 9 2. 
Cer va ntes  F,  D u preiz B, Pereira A , et al. N e w pr o g n ostic sc ori n g s yste m f or pri mar y 
m yel ofi br osis bas e d o n a st u d y of t he I nter nati o nal w or ki n g Gr o u p f or M yel ofi br osis Researc h 
a n d Treat me nt.  Bl o o d 2 0 0 9; 1 1 3: 2 8 9 5- 2 9 0 1. 
Cer va ntes  F, Va n n u cc hi A M, Kila djia n JJ, et al. T hree-year effi cac y, s afet y, a n d s ur vi val 
fi n di n gs fr o m C O M F O R T-II, a p h ase 3 st u d y c o m pari n g r u x oliti ni b wit h best a vaila ble t hera p y 
f or m yel ofi br osis. Bl o o d 2 0 1 3; 1 2 2: 4 0 4 7- 4 0 5 3. 
Cli nical Trial  Facilitati o n Gr o u p ( C T F G) . Rec o m me n dati o ns relate d t o c o ntrace pti o n a n d 
pre g na nc y t esti n g i n cli ni cal trials. 2 0 1 4. htt p:// w w w. h ma.e u/ctf g. ht ml . Accesse d J ul y 1 5, 2 0 1 6. 
Dee g HJ, G o ole y T A, Fl o wers M E , et al. All o ge nic he mat o p oietic ste m cell tra ns pla ntati o n f or 
m yel ofi br osis. Bl o o d 2 0 0 3; 1 0 2: 3 9 1 2- 3 9 1 8. 
Harris o n C, Kila djia n JJ, Al- Ali H K, et al. J A K i n hi biti o n wit h r u x oliti ni b vers us best a vaila bl e 
t hera p y f or m yel ofi br osis. N E n gl J Me d 2 0 1 2; 3 6 6: 7 8 7- 7 9 8. 
I N C 4 2 4 (I N C B 0 1 8 4 2 4) R u x oliti ni b I n vesti gat or's Br oc h ure (I B). Basel, S witzerla n d : N o vartis. 
I N C B 0 3 9 1 1 0 I n v esti gat or's Br o c h ure (I B). Wil mi n gt o n, D E: I n c yt e C or p orati o n. 
Mascar e n has J O, Tal paz M, G u pta V, e t al. Pri mar y a n al ysis of a p has e II o pe n -la bel trial of 
I N C B0 3 9 1 1 0, a s electi ve J A K 1 i n hi bit or, i n patie nts wit h m yel ofi br osis, H ae mat ol o gica 
2 0 1 6; 1 5 1 1 2 6. 
Mesa R A, Ni blac k J, Wa dlei g h M, et al. T h e b ur d e n of fati g ue a n d q ualit y of life i n 
m yel o pr olif erati ve dis or d ers ( M P Ds): a n i nter n ati o nal I nt er net- b ase d s ur v e y of 1 1 7 9 M P D 
patie nts. Ca ncer 2 0 0 7; 1 0 9: 6 8- 7 6. 
Mesa R A, G otli b J, G u pta V, et al. Effect of r u x oliti ni b t hera p y o n m yel ofi br osis- relate d 
s y m pt o ms a n d ot her pati e nt-re p ort e d o utc o mes i n C O M F O R T-I: a ra n d o mize d, d o u ble bli n d, 
place b o -c o ntr olle d trial.  J Cli n O nc ol 2 0 1 3a; 3 1: 1 2 8 5- 1 2 9 2. 
Mesa R A, S hiel ds A, Har e T, et al . Pr o gressi ve b ur de n of m yel ofi br osis i n u ntreate d patie nts: 
assess me nt of patie nt -r e p orte d o utc o mes i n patie nts ra n d o mize d t o place b o i n t he C O M F O R T- 1 
st u d y. Le u k Res 2 0 1 3 b; 3 7: 9 1 1- 9 1 6. 
Nati o nal Ca ncer I nstit ute ( N CI) . C o m m o n Ter mi n ol o g y Criteria f or A d vers e E ve nts versi o n 
4. 0 3. 2 0 1 0. htt p://cte p.ca ncer. g o v/r e p orti n g/ ctc. ht ml. Accesse d J ul y 1 5, 2 0 1 6. 
O ke n M M, Creec h R H, T or me y D C. T o xicit y a n d res p o nse criteria of t h e Easter n C o o perati ve 
O nc ol o g y Gr o u p.  J Cli n O nc ol 1 9 8 2; 5: 6 4 9- 6 5 5. 
Passa m o nti F, Cer va ntes F, Va n n u c hi A M, et al. A d y na mic pr o g n ostic m o del t o pre dict s ur vi val 
i n pri mar y m yel ofi br osis: a st u d y b y t he I W G-M R T. Bl o o d 2 0 1 0; 1 1 5: 2 7 0 3- 1 7 0 8. 

I nc yte C or p orati o n 
P a ge 7 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
Stei n B L, G otli b J, Arcas o y M, et al. Hist orical vie ws, c o n ve nti o nal a p pr oac hes, a n d e v ol vi n g 
ma na ge me nt strat e gies f or m yel o pr oliferati ve ne o plas ms.  J Natl C o m pr Ca nc  Net w  
2 0 1 5; 1 3: 4 2 4- 4 3 4. 
Tefferi A, Cer v a ntes F, Mesa R , et al. Re vise d res p o nse criteria f or m yel ofi br osis: I nter nati o nal 
W or ki n g Gr o u p- M yel o pr oliferati ve N e o plas ms R esearc h a n d T reat me nt (I W G- M R T) a n d 
E ur o pea n Le u ke mia N et ( E L N) c o nse ns us re p ort. Bl o o d 2 0 1 3; 1 2 2: 1 3 9 5- 1 3 9 8. 
T hiele J, K vas nic ka H M, Facc hetti F , Fra n c o V, v a n der Walt J, Ora zi A. E ur o pea n c o ns e ns us o n 
gr a di n g b o ne marr o w fi br osis a n d assess me nt of cell ularit y. H ae mat ol o gica 2 0 0 5; 9 0: 1 1 2 8- 1 1 3 2. 
Va n n ucc hi A M, Ka ntarji a n H M, Kila djia n JJ, et al. A p o ole d a nal ysis of o verall s ur vi val i n 
C O M F O R T - 1 a n d C O M F O R T-II, 2 ra n d o mize d p hase III trials of r u x oliti ni b f or t he treat me nt of 
m yel ofi br osis. H ae mat ol o gica 2 0 1 5; 1 0 0: 1 1 3 9- 1 1 4 5. 
Verst o vse k S, Mesa R A, G otli b J, et al. A d o u ble- bli n d, place b o-c o ntr olle d trial of r u x oliti ni b f or 
m yel ofi br osis. N E n gl J Me d 2 0 1 2; 3 6 6: 7 9 9- 8 0 7. 
Verst o vse k S, Mesa R A, G otli b J, et al. T he cli nical be nefit of r u x oliti ni b acr oss patie nt 
s u b gr o u ps: a n al ysis of a place b o- c o ntr olle d, P has e III st u d y i n patie nts wit h m yel ofi br osis. Br J 
Hae mat ol 2 0 1 3; 1 6 1: 5 0 8- 5 1 6. 
Verst o vse k S, Mesa R A, G otli b J, et al. Efficac y, safet y , a n d s ur vi val wit h r u x oliti ni b i n patie nts 
wit h m yel ofi br osis: res ults of a me dia n 3 -year f oll o w - u p of C O M F O R T -I. Hae mat ol o gica 
2 0 1 5; 1 0 0: 4 7 9- 4 8 8. 

I nc yte C or p orati o n 
P a ge 7 6  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  A.  R E VI S E D W H O 2 0 1 6 C RI T E RI A F O R M Y E L O FI B R O SI S 
T a ble 1 3: 
W H O Pre – Pri m a r y M y el ofi br osis Criteri a  
M aj or Criteri a  
1.  Me ga kar y oc ytic pr oliferati o n a n d at y pia, wit h o ut retic uli n fi br osis > gra de 1
a, acc o m pa nie d b y i ncrease d 
a ge-a dj uste d B M cell ularit y, gra n ul oc ytic pr oliferati o n, a n d ofte n decrease d er yt hr o p oiesis  
2.  N ot meeti n g t he W H O criteria f or B C R -A B L 1 +  C M L, P V, E T, m yel o d ys plastic s y n dr o mes, or ot her m yel oi d 
ne o plas ms  
3.  Prese nce of J A K 2 , C A L R , or M P L  m utati o n or i n t he a bse nce of t hese m utati o ns, prese nc e of a n ot her cl o nal 
mar ker, b or a bse nce of mi n or reacti ve B M retic uli n fi br osis c 
Mi n or Criteri a  
Prese nce of at least 1 of t he f oll o wi n g, c o nfir me d i n 2 c o nse c uti ve deter mi nati o ns:  
a. A ne mia n ot attri b ute d t o a c o m or bi d c o n diti o n  
b.  Le u k oc yt osis ≥1 1 × 1 0 9/ L 
c. P al pa ble s ple n o me gal y  
d.  L D H i ncrease d t o a b o ve u p per n or mal li mit of i nstit uti o nal r efere nce ra n ge  
Dia g n osis of pre P M F re q uires meeti n g all 3 maj or criteria, a n d at least 1 mi n or criteri o n  
a See Ta ble  1 5 . 
b I n t he a bse nce of a n y of t h e 3 maj or cl o n al m utati o ns, t h e searc h f or t h e m ost fre q u e nt acc o m p a n yi n g m utati o ns (e g, A S X L 1, 
E Z H 2, T E T 2, I D H 1/I D H 2, S R S F 2, S F 3 B 1) are of h el p i n d eter mi ni n g t h e cl o n al n at ure of t h e disease.  
c B M fi br osis sec o n d ar y t o i nfecti o n, a ut oi m m u n e dis or d er, or ot h er c hr o nic  i nfla m mat or y c o n diti o ns, h air y cell le u ke mi a or 
ot her l y m p h oi d n e o plas m, metast atic mali g n a n c y, or t o xic (c hr o nic) m yel o p at hies.  
T a ble 1 4: 
W H O O vert Pri m ar y M yel ofi br osis Criteri a  
M aj or Criteri a  
1. Prese nce of me ga k ar y oc ytic pr oliferati o n a n d at y pia, acc o m pa nie d b y eit her retic uli n a n d/ or c olla ge n fi br osis 
gra des 2 or 3 a 
2. N ot meeti n g W H O criteria f or E T, P V, B C R -A B L 1 + C M L, m yel o d ys plastic s y n dr o mes, or ot her m yel oi d 
ne o pla s ms 
3. Prese nce of J A K 2, C A L R, or M P L m utati o n or i n t he a bs e nce of t hese m utati o ns, prese nce of a n ot her cl o nal 
mar ker, b or a bse nce of reacti ve m yel ofi br osis c 
Mi n or Criteri a  
Prese nce of at least 1 of t he f oll o wi n g, c o nfir me d i n 2 c o nse c uti ve deter mi nati o ns:  
 a. A ne mia n ot attri b ute d t o a c o m or bi d c o n diti o n  
 b. Le u k oc yt osis ≥1 1 × 1 0 9/ L 
 c. P al pa ble s ple n o me gal y  
 d. L D H i ncrease d t o a b o ve u p per n or mal li mit of i nstit uti o nal refere nce ra n ge  
 e. Le u k oer yt hr o blast osis  
Dia g n osis of o vert P M F re q uires meeti n g all 3  maj or criteria, a n d at least 1 mi n or criteri o n  
a See Ta ble  1 5 . 
b I n t he a bse nce of a n y of t h e 3 maj or cl o n al m utati o ns, t h e searc h f or t h e m ost fre q u e nt acc o m p a n yi n g m utati o ns (e g, A S X L 1, 
E Z H 2, T E T 2, I D H 1/I D H 2, S R S F 2, S F 3 B 1) are of h el p i n d eter mi ni n g t h e cl o n al n at ure of t h e disease.  
c B M fi br osis sec o n d ar y t o i nfecti o n, a ut oi m m u n e dis or d er, or ot h er c hr o nic i nfla m mat or y c o n diti o ns, h air y cell le u ke mi a or 
ot her l y m p h oi d n e o plas m, metast atic mali g n a n c y, or t o xic (c hr o nic) m yel o p at hies.  

I nc yte C or p orati o n 
P a ge 7 7  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
T a ble 1 5: 
M y el ofi br osis Gr a di n g  
M yel ofi br osis Gr a di n g  
M F - 0 
Scattere d li near retic uli n wit h n o i ntersecti o ns (cr oss o vers) c orres p o n di n g t o n or mal B M  
M F - 1 
L o ose net w or k of retic uli n wit h ma n y i ntersecti o ns, es peciall y i n peri vasc ular areas  
M F - 2 
Diff use a n d de nse i ncrease i n retic uli n wit h e xte nsi ve i nters ecti o ns, occasi o nall y wit h f oc al b u n dles of 
t hic k fi bers m ostl y c o nsiste nt wit h c olla ge n, a n d/ or f ocal oste oscler osisa 
M F - 3 
Diff use a n d de nse i ncrease i n retic uli n wit h e xte nsi ve i nters ecti o ns a n d c oarse b u n dles of t hic k fi bers 
c o nsiste nt wit h c olla ge n, us uall y ass ociate d wit h oste oscler osis a 
a I n gra des M F -2 or M F -3 a n a d diti o n al tric hr o me stai n is rec o m me n d e d.  
S o urce:  Ar ber  et al 2 0 1 6 . 

I nc yte C or p orati o n 
P a ge 7 8  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  B. I N T E R N A TI O N A L W O R KI NG G R O U P –
M Y E L O P R O LI F E R A TI V E N E O P L A S M S R E S E A R C H 
A N D T R E A T M E N T C RI T E R I A 
Res p o nse 
C ate g ories  
Re q uire d Criteri a (f or All Res p o nse C ate g ories, B e nefit M ust L ast f or ≥ 1 2 Wee ks t o 
Q u alif y as a Res p o nse)  
C R  
B o ne marr o w a:  A ge -a dj uste d n or m ocell ularit y; < 5 % blasts; ≤ Gra de 1 M F b a n d  
P eri p heral bl o o d:  He m o gl o bi n ≥ 1 0 0 g/ L a n d < U N L; ne utr o p hil c o u nt ≥ 1 × 1 0 9/ L a n d 
< U N L;  
Platelet c o u nt ≥ 1 0 0 × 1 0 9/ L a n d < U N L; < 2 % i m mat ure m yel oi d cellsc a n d  
Cli nical:  Res ol uti o n of diseas e s y m pt o ms; s plee n a n d li ver n o t pal pa ble; n o e vi de nce of 
E M H  
P R  
P eri p heral bl o o d:   He m o gl o bi n ≥ 1 0 0 g/ L a n d <  U N L; ne utr o p hil c o u nt ≥ 1 × 1 0 9/ L a n d 
< U N L; platelet c o u nt ≥ 1 0 0 × 1 0 9/ L a n d < U N L; <  2 % i m mat ure m yel oi d cells c a n d  
Cli nical:  Res ol uti o n of diseas e s y m pt o ms; s plee n a n d li ver n ot pal pa ble; n o e vi de nce of 
E M H or  
B o ne marr o w: a  A ge -a dj uste d n or m ocell ularit y; <  5 % blasts; ≤ Gra de 1 M Fb; a n d peri p heral 
bl o o d:  he m o gl o bi n ≥ 8 5 g/ L b ut <  1 0 0 g/ L a n d <  U N L; ne utr o p hil c o u nt ≥ 1 × 1 0 9/ L a n d 
< U N L; platelet c o u nt ≥ 5 0  × 1 0 9/ L b ut < 1 0 0 × 1 0 9/ L a n d < U N L; <  2 % i m mat ure m yel oi d 
cells c a n d  
Cli nical:  Res ol uti o n of diseas e s y m pt o ms; s plee n a n d li ver n ot pal pa ble; n o e vi de nce of 
E M H  
CI  
T he ac hie ve me nt of a ne mia, s plee n or s y m pt o ms res p o nse wit h o ut pr o gressi ve disease or 
i ncrease i n se verit y of a ne mia, t hr o m b oc yt o pe nia, or ne utr o pe nia d 
A ne mia res p o nse  
Tra nsf usi o n -i n de pe n de nt patie nts:  a ≥ 2 0 g/ L i ncrease i n he m o gl o bi n le vel e 
Tra nsf usi o n -de pe n de nt patie nts:   bec o mi n g tra nsf usi o n -i n de pe n de ntf 
S plee n res p o nse g 
A basel i ne s ple n o me gal y t hat is pal pa ble at 5-1 0 c m, bel o w t he L C M, bec o mes n ot pal pa ble h 
or  
A baseli ne s ple n o me gal y t hat is pal pa ble at >  1 0 c m, bel o w t he L C M, decreases b y ≥ 5 0 % h 
A baseli ne s ple n o me gal y t hat is pal pa ble at <  5 c m, bel o w t he L C M, is n ot eli gi ble f or s pl ee n 
res p o nse 
A s plee n res p o nse re q uires c o nfir mati o n b y M RI or C T  s h o wi n g ≥ 3 5 % s plee n v ol u me 
re d ucti o n 
S y m pt o ms 
res p o nse 
A ≥ 5 0 % re d ucti o n i n t he M P N-S A F T S S i 
Pr o gressi ve disease j 
A p peara nce of a ne w s ple n o me gal y t hat is pal pa ble at least 5 c m bel o w t he L C M or  
A ≥ 1 0 0 % i ncrease i n pal pa bl e dista nce, bel o w L C M, f or baseli ne s ple n o me gal y of 5 -1 0 c m 
or  
A 5 0 % i ncrease i n pal pa ble dista nce, bel o w L C M, f or baseli ne s ple n o me gal y of >  1 0 c m or  
Le u ke mic tra nsf or mati o n c o nfir me d b y a b o ne marr o w blast c o u nt of ≥ 2 0 % or  

I nc yte C or p orati o n 
P a ge 7 9  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
Res p o nse 
C ate g ories  
Re q uire d Criteri a (f or All Res p o nse C ate g ories, B e nefit M ust L ast f or ≥ 1 2 Wee ks t o 
Q u alif y as a Res p o nse)  
A peri p heral bl o o d blast c o nte nt of ≥ 2 0 % ass oc iate d wit h a n a bs ol ute blast c o u nt of 
≥ 1 × 1 0 9/ L t hat lasts f or at least 2 wee ks 
Sta ble disease  
B el o n gi n g t o n o ne of t he a b o ve -liste d res p o nse cate g ories 
Rela pse  
N o l o n ger meeti n g criteria f or at least CI after ac hie vi n g C R, P R, or CI, or  
L oss of a ne m ia res p o nse persisti n g f or at least 1 m o nt h or 
L oss of s plee n res p o nse persisti n g f or at least 1 m o nt h  
CI = cli nical i m pr o ve me nt; C R = c o m plete res p o nse; C T = c o m p ute d t o m o gra p h y; E M H = e xtra me d ullar y h e mat o p oiesis ; L C M 
= left c ostal mar gi n; M F = m yel of i br osis; M P N-S A F T S S = M yel o pr oliferati ve Ne o plas m S y m pt o m Assess me nt F or m T otal 
S y m pt o m Sc ore; M RI = ma g n etic res o n a n ce i ma gi n g; P R = p artial res p o nse; P R B C = p ac ke d re d bl o o d cell; U N L = u p per 
n or mal li mit.  
a Baseli ne a n d p ost -treat me nt b o n e marr o w sli d es are t o b e i nter prete d at 1 sitti n g b y a ce ntral re vie w pr o cess.  
 
 
b Gra di n g of M F is acc or di n g t o t he E ur o p ea n classificati o n ( T hiele  et al 2 0 0 5 ).  It is u n d ersc ore d t h at t h e c o nse ns us d efi niti o n 
of a C R b o ne marr o w is t o b e use d o nl y i n t h ose p atie nts i n w hic h all ot h er criter ia are met, i n cl u di n g res ol uti o n of 
le u k oer yt hr o blast osis.  It s h o ul d als o b e n ote d t h at it was a p artic ularl y diffic ult tas k f or t h e w or ki n g gr o u p t o reac h a c onse ns us 
re gar di n g w hat re prese nts a c o m plete hist ol o gic re missi o n. 
c I m mat ure m yel oi d cells c o nstit ute blasts + pr o m yel o c ytes + m yel o c yt es + meta m yel o c ytes + n u cleate d re d bl o o d cells.  I n 
s ple nect o mize d p atie nts, < 5 % i m mat ure m yel oi d cells is all o we d.  
d See a b o ve f or d efi niti o ns of a n e mia res p o nse, s plee n res p o nse, a n d pr o gressi ve disease.  I n crease i n se verit y of a n e mia 
c o nstit utes t he o cc urre n ce of n e w tra nsf usi o n d e p e n d e n c y or a ≥ 2 0 g/ L d ecre ase i n h e m o gl o bi n le vel fr o m pret reat me nt 
baseli ne t hat lasts f or at least 1 2 we e ks.  I n creas e i n se verit y of t hr o m b o c yt o p e nia or n e utr o p e nia is d efi n e d as a 2-gra d e 
decli ne, fr o m pretreat me nt b aseli n e, i n platelet c o u nt or a bs ol ute ne utr o p hil c o u nt, acc or di n g t o t h e C T C A E versi o n 4. 0.  In 
a d diti o n, assi g n me nt t o CI re q uires a mi ni m u m platelet c o u nt of ≥ 2 5 ,0 0 0 × 1 0 9/ L a n d a bs ol ute n e utr o p hil c o u nt of 
≥ 0. 5  × 1 0 9/ L. 
e A p plica ble o nl y t o p atie nts wit h baseli n e h e m o gl o bi n of <  1 0 0 g/ L.   I n p atie nts n ot meeti n g t h e strict criteria f or tra nsf usi o n 
de pe n de nc y at t h e ti me of st u d y e nr oll me nt (see as f oll o ws), b ut h a ve recei ve d tra nsf usi o ns wit hi n t he pre vi o us m o nt h, t he 
pretra nsf usi o n h e m o gl o bi n le vel s h o ul d b e use d as t h e b aseli n e.  
f Tra nsf usi o n de p e n d e n c y b ef ore st u d y e nr oll me nt is d efi n e d as tra nsf usi o ns of at least 6 u nits of P R B C s, i n t h e 1 2 wee ks pri or 
t o st u d y e nr oll me nt, f or a h e m o gl o bi n le vel of < 8 5 g/ L, i n t h e a bse n c e of blee di n g or treat me nt -i n d uce d a n e mia.  I n a d diti o n, 
t he m ost rece nt tra nsf usi o n e pis o d e m ust h a ve o cc urre d i n t h e 2 8 da ys pri or t o st u d y e nr oll me nt.  Res p o nse i n 
tra nsf usi o n-de p e n d e nt p atie nts re q uires a bse n ce of a n y P R B C tra nsf usi o ns d uri n g a n y c o nse c uti ve "r olli n g" 1 2 -wee k i nter val 
d uri n g t he treat me nt p h ase, ca p p e d b y a h e m o gl o bi n le vel of ≥ 8 5 g/ L.  
g I n s ple nect o mize d p atie nts, p al p a ble h e p at o me g al y is s u bstit ute d wit h t h e sa me meas ure me nt strate g y. 
h S plee n or li ver res p o nses m ust b e c o nfir me d b y i ma gi n g st u dies w h ere a ≥ 3 5 % re d u cti o n i n s plee n v ol u me, as assesse d b y 
M RI or C T, is re q uire d.  F urt h er m ore, a ≥ 3 5 % v ol u me re d u cti o n i n t h e s plee n or li ver, b y M RI or C T, c o nstit utes a res p o nse 
re gar dless of w h at is re p orte d wit h p h ysical e xa mi n ati o n. 
i S y m pt o ms are e val u ate d b y t h e M P N -S A F T S S.   T h e M P N -S A F T S S is assesse d b y t h e p atie nts t he msel v es a n d t his i n cl u des 
fati g ue, c o nce ntrati o n, earl y s atiet y, i n acti vit y, ni g ht s we ats, itc hi n g, b o n e p ai n, a b d o mi n al disc o mf ort, wei g ht l oss, a n d fe vers.  
Sc ori n g is fr o m 0 (a bse nt/as g o o d as it ca n b e) t o 1 0 ( w orst i ma gi n a ble/as b a d as it ca n b e) f or eac h ite m. T h e M P N -S A F T S S 
is t he s u m mati o n of all t h e i n di vi d u al sc ores ( 0-1 0 0 scale).   S y m pt o ms res p o nse re q uires ≥ 5 0 % re d u cti o n i n t h e M P N -S A F 
T S S.  
j Pr o gressi ve disease assi g n me nt f or s pl en o me gal y re q uires c o nfir mati o n b y M RI or C T s h o wi n g a ≥ 2 5 % i n crease i n s plee n 
v ol u me fr o m b aseli n e.   Baseli n e val u es f or b ot h p h ysical e xa mi n ati o n a n d i ma gi n g st u dies refer t o pretreat me nt b aseli n e a n d 
n ot t o p osttreat me nt me as ure me nts.  
S o urce:  Tefferi   et al 2 0 1 3 . 

I nc yte C or p orati o n 
P a ge 8 0  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  C.  E A S T E R N C O O P E R A TI V E O N C O L O G Y G R O U P  
P E R F O R M A N C E S T A T U S  
Gr a de  
P erf or m a nce St at us  
0 
F ull y a cti 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 ysicall 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 n y w or k acti vities .  U p 
a n d a b o ut m ore 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 hai r 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.  
S o urce :  O ke n  et al 1 9 8 2 . 

I nc yte C or p orati o n 
P a ge 8 1  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  D.  M O DI FI E D M Y E L O FI B R O SI S  S Y M P T O M 
A S S E S S M E N T S F O R M V E R SI O N 2 . 0 
Please c o m plete t his diar y at ni g ht bef ore b e dti me.  T he diar y as ks a b o ut y o ur M F s y m pt o ms 
d uri n g t he p ast 2 4 h o urs.  T here is n o ri g ht or wr o n g a ns wer.  Pleas e gi ve t he a ns wer t hat best 
reflects y o ur o pi ni o n. 
1. D uri n g t he past 2 4 h o urs, h o w se vere 
were y o ur w orst ni g ht s weats ( or feeli n g 
h ot or fl us he d) d ue t o M F?  
0 ( A bse nt)  1    2    3    4    5    6    7    8    9    1 0 ( W orst I ma gi na ble)  
2. D uri n g t he past 2 4 h o urs , h o w se vere 
was y o ur w orst itc hi n ess d ue t o M F?  
0 ( A bse nt)  1    2    3    4    5    6    7    8    9    1 0 ( W orst I ma gi na ble)  
3. D uri n g t he past 2 4 h o urs , h o w se vere 
was y o ur w orst a b d o mi nal dis c o mf ort 
(feel u nc o mf orta ble, press ure or 
bl oati n g) d ue t o M F?  
0 ( A bse nt)  1    2    3    4    5    6    7    8    9    1 0 ( W orst I ma gi na ble)  
4. D uri n g t he past 2 4 h o urs , h o w se vere 
was y o ur w orst pai n u n der t he ri bs o n 
t he left si de d ue t o M F? 
0 ( A bse nt)  1    2    3    4    5    6    7    8    9   1 0 ( W orst I ma gi na ble)  
5. D uri n g t he past 2 4 h o u rs, w hat was 
t he w orst feeli n g of f ull ness (e arl y 
satiet y) y o u ha d after be gi n ni n g t o eat, 
d ue t o M F?  
0 ( A bse nt)  1    2    3    4    5    6    7    8    9   1 0 ( W orst I ma gi na ble)  
6. D uri n g t he past 2 4 h o urs , h o w se vere 
was y o ur w orst b o ne or m uscl e pai n d ue 
t o M F ( diff use, n ot  j oi nt or art hritis 
pai n)?  
0 ( A bse nt)  1    2    3    4    5    6    7    8    9   1 0 ( W orst I ma gi na ble)  
7. D uri n g t he past 2 4 h o urs , w hat was 
t he w orst de gree of i nacti vit y (i ncl u di n g 
w or k a n d s ocial acti vities) y o u ha d d ue 
t o M F? 
0 ( A bse nt)  1    2     3    4    5    6    7    8    9   1 0 ( W orst I ma gi na ble)  
 

I nc yte C or p orati o n 
P a ge 8 2  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  E. M Y E L O P R O LI F E R A TI V E N E O P L A S M S S Y M P T O M 
A S S E S S M E N T F O R M  
S u bj ect 
N u m ber 
 
 
 
 
 
S y m pt o m  
1 t o 1 0 ( 0 if a bse nt) r a n ki n g - 1 is m ost  
 f a v or a ble a n d 1 0 le ast f a v or a ble 
Please rate y o ur fati g ue ( weari ness, tire d ness) b y 
circli n g t he o ne n u m ber t hat best descri bes y o ur 
W O R S T le vel of fati g ue d uri n g t he past 2 4 h o urs.  
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
Circle t he o ne n u m ber t h at descri bes, d uri n g t he p ast we e k, h o w m uc h diffic ult y y o u h a d wit h e ac h 
of t he f oll o wi n g s y m pt o ms  
Ni g ht s weats  
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
Itc hi n g ( pr urit us) 
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
B o ne pai n ( diff use, n ot  j oi nt pai n or art hritis) 
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
Fe ver ( > 1 0 0° F)  
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
U ni nte nti o nal wei g ht l oss i n t he last 6 m o nt hs  
0 ( A bse nt)   1  2  3  4  5  6  7  8   9     1 0 ( W orst I ma gi na ble)  
Filli n g u p q uic kl y w he n y o u e at (earl y satiet y)  
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
A b d o mi nal disc o mf ort  
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
I nacti vit y 
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
Pr o ble ms wit h c o nce ntrati o n - 
 c o m pare d t o pri or t o m y M P D  
0 ( A bse nt)   1  2  3  4  5  6  7  8  9     1 0 ( W orst I ma gi na ble)  
 
 
 
 
 
T S S:    _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
M D Si g nat ure/ Date  
P er I W G -M R T 2 0 1 3 Criteri a: T S S t o i ncl u de fati g ue, 
c o nce ntrati o n, earl y satiet y, i nacti vit y, ni g ht s weats, 
itc hi n g, b o ne pai n, a b d o mi nal disc o mf ort, wei g ht l oss, a n d 
fe vers. 
 
Staff Si g nat ure/ Date  
 
 
 
 

I nc yte C or p orati o n 
P a ge 8 3  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  F.  P A TI E N T G L O B A L I M P R E S SI O N O F C H A N G E  
I nstr ucti o ns:  C ircle t he a ns w er t h at is m ost a p pr o pri ate. 
Si nce t he start of t he tr eat me nt y o u ' ve recei ve d i n t his st u d y, y o ur m yel ofi br osis s y m pt o ms are: 
1.  Ver y m uc h i m pr o ve d 
2.  M uc h i m pr o ve d 
3.  Mi ni mall y i m pr o v e d  
4.  N o c ha n ge  
5.  Mi ni mall y w orse  
6.  M uc h w orse 
7.  Ver y m uc h w orse  

I nc yte C or p orati o n 
P a ge 8 4  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  G. I N F O R M A TI O N R E G A R DI NG E F F E C TI V E N E S S O F 
C O N T R A C E P TI V E M E T H O D S 
F or S u bjects P arti ci p ati n g i n t he St u d y:  
T he f oll o wi n g m et h o ds t hat ca n ac hie ve a fail ure rate of less t ha n 1 % per year w h e n use d 
c o nsiste ntl y a n d c orr ectl y are c o nsi d ere d as hi g hl y effecti ve birt h c o ntr ol met h o ds.  
S uc h met h o ds i ncl u de: 
•  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 1 
− oral  
− i ntra va gi nal 
− tra ns der mal 
•  Pr o gest o ge n - o nl y 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 n1 
− oral  
− i njectable 
− i m pla nta ble2 
•  I ntr a uteri ne d e vice (I U D)2 
•  I ntr a uteri ne h or m o ne-rel easi n g s yst e m (I U S)2 
•  Bilater al t u bal occl usi o n 2 
•  Vasect o mise d  part ner2, 3 
•  Se x ual a bsti ne nce 4 
 
1  H or m o nal  c o ntrace pti o n ma y be s usce pti ble t o i nteracti o n wit h t he I M P, w hic h ma y re d uce t he efficac y of t he 
c o ntrace pti o n met h o d.  
2  C o ntrace pti o n  met h o ds t hat i n t he c o nte xt of t his g ui da nce are  c o nsi dere d t o ha ve l o w us er de pe n de nc y.  
3  Vasect o mise d  part ner is a hi g hl y effecti ve met h o d pr o vi de d of a v oi di n g pre g na nc y  t hat p art ner is t he s ole se x ual 
part ner of t he W O C B P trial partici pa nt a n d t hat t he vasect o mise d  part ner has recei ve d me di cal assess me nt of t he 
s ur gical s uccess.  
4  I n t he c o nte xt of t his g ui da nce, se x ual a bsti ne nce is c o nsi d ere d a hi g hl y effecti ve met h o d o nl y if defi ne d as 
refrai ni ng 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 treat me nts.  T he 
relia bilit y of se x ual a bsti ne nce nee ds t o be e val uate d i n relati o n t o t he d urati o n of t he cli nic al trial a n d t he 
preferre d a n d us ual lifest yle of t he s u bj ect.  
S o urce :  C T F G  2 0 1 4 . 

I nc yte C or p orati o n 
P a ge 8 5  of 8 5  
Pr ot oc ol I N C B  3 9 1 1 0 -2 0 9 A me n d me nt 1  
1 4 A U G 2 0 1 7  
C O N FI D E N TI A L  
A P P E N DI X  H. C Y T O C H R O M E P 4 5 0 A N D P- G L Y C O P R O T EI N 
I N HI BI T O R S A N D C Y T O C H R O M E P 4 5 0 I N D U C E R S 
I n cli nical st u dies wit h C Y P 3 A 4 i n hi bit ors, ele vate d le vels of I N C B 0 1 8 4 2 4 of a p pr o xi matel y 
2-f ol d ha ve b ee n o bser ve d a fter or al a d mi nistrati o n.  A d diti o nall y, si m ulati o ns usi n g 
p h ysi ol o gicall y base d p h ar mac o ki netic m o d els s u g geste d t h at fl uc o naz ole (a d ual C Y P 3 A 4 a n d 
C Y P 2 C 9 i n hi bit or) i ncreases stea d y- st ate r u x oliti ni b A U C b y a p pr o xi matel y 1- t o 3-f ol d after 
oral a d mi nist rati o n.  T h us, t hese c o nc o mita nt me dicati o ns s h o ul d n ot be ta ke n b y s u bj ects 
be gi n ni n g 2 w ee ks or 5 h alf-li ves ( w hic h e ver is l o n ger) bef ore t h e first a p plicati o n of st u d y dr u g 
u ntil t he last a d mi nistrati o n (eit her Wee k 2 4 or W ee k 4 8); h o we ver, t o pical use of t hese a ge nts if 
t he s yste mic bi oa v aila bilit y is l o w ma y be per mitte d o n a case-b y -case b asis.  T he f oll o wi n g is a 
list of p ote nt C Y P 3 A 4 i n hi bit ors a n d fl uc o naz ole.  T he s p o ns or s h o ul d be c o ntacte d wit h a n y 
q uesti o ns re gar di n g c o n c o mita nt me dicati o ns t hat mi g ht be c o nsi dere d p ote nt C Y P 3 A 4 i n hi bit ors 
b ut are n ot o n t his list. 
b oce pre vir 
clarit hr o m yci n  
c o bicistat  
c o ni va pta n 
da n o pre vir 
el vite gr a vir  
fl uc o naz ole 
gr a pefr uit j uice  
i delalisi b 
i n di na vir 
itrac o naz ole 
ket oc o naz ole 
L C L 1 6 1  
l o pi na vir 
mi befra dil  
nefaz o d o ne 
nelfi na vir 
p osac o naz ole 
rit o na vir 
sa q ui na vir