A Phase 1/2, Open-Label, Multicenter Study of INCB000928 Administered as a Monotherapy in Participants With Anemia Due to Myelodysplastic Syndromes or Multiple Myeloma
Phase: PHASE1
Conditions: Myelodysplastic Syndromes, Multiple Myeloma, Anemia
Sponsor: Incyte Corporation

Offici al Title:  
A P hase 1/ 2, O pe n -La bel, M ultice nter St u d y of I N C B 0 0 0 9 2 8  
A d mi nistere d as a M o n ot hera p y i n Partici pa nts Wit h A ne mia D ue t o  
M yel o d ys plastic S y n dr o mes or M ulti ple M yel o ma  
N C T N u m ber:  
N C T 0 4 5 8 2 5 3 9  
D oc u me nt D ate:  
Pr ot oc ol I N C B 0 0 9 2 8 -1 0 5 A m 5 Versi o n 6 0 6 D E C 2 0 2 3  
 
 
 

I nc yte C orp orati o n  
Pa ge 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
TI T L E P A G E  
Cli nic al St u d y Pr ot oc ol  
 
 
I N CB  0 0 9 2 8 -1 0 5  
A P hase 1/ 2 , O pe n -La bel, M ultice nter St u d y of I N C B 0 0 0 9 2 8 
A d mi nistere d as a M o n ot hera p y i n Partici pa nts W it h A ne mia D ue t o 
M yel o d ys plastic S y n dr o mes or M ulti ple M yel o ma  
 
Pr o d uct:  
I N C B 0 0 0 9 2 8 
I N D N u m ber: 
1 4 7, 4 9 5  
E u dr a C T  N u m ber :  
2 0 2 0 -0 0 2 7 7 1 -3 5  
P h ase of St u d y : 
1 / 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  
Ori gi n al  Pr ot oc ol:  
1 0 J U N  2 0 2 0  
Pr ot oc ol A me n d me nt 1 : 
1 7 N O V 2 0 2 0  
Pr ot oc ol A me n d me nt 2 : 
0 8  A P R 2 0 2 1  
Pr ot oc ol A me n d me nt 3:  
2 2  D E C  2 0 2 1  
Pr ot oc ol A me n d me nt 4 : 
2 0  D E C 2 0 2 2  
Pr ot oc ol A me n d me nt 5:  
0 6  D E C  2 0 2 3  
 
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 ( Brazil 2 0 1 3) 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, a p plica ble G o o d Cli nical Practices, a n d 
a p plica ble la ws a n d c o u ntr y -s pecific re g ulati o ns, i ncl u di n g W M O ( Me dical Researc h I n v ol vi n g H u ma n Partici pa nts 
Act) a n d Cli nical Trials Re g ulati o n ( E U) N o. 5 3 6/ 2 0 1 4, i n w hic h t he st u d y is bei n g c o n d ucte d.  
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) wit h o ut pri or 
writte n c o nse nt.  

I nc yte C orp orati o n  
Pa ge 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
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 rea d t he I N C B 0 0 9 2 8 -1 0 5  Pr ot oc ol  (A me n d me nt 5  date d 0 6  D E C  2 0 2 3 ) 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 gree 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 ure of I n v esti gat or) 
 
( Date) 

I nc yte C orp orati o n  
Pa ge 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
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  
TI T L E P A G E  ...................................................................................................................................1  
I N V E S TI G A T O R' S A G R E E M E N T ................................................................................................2  
T A B L E O F C O N T E N T S  .................................................................................................................3  
LI S T O F A B B R E VI A TI O N S  ..........................................................................................................9  
1.  
P R O T O C O L S U M M A R Y  ..........................................................................................1 3  
2.  
I N T R O D U C TI O N ......................................................................................................2 1  
2. 1.  
Bac k gr o u n d  .................................................................................................................2 1  
2. 1. 1.  
O ver vie w of M yel o d ys plastic S y n dr o mes  ..................................................................2 1  
2. 1. 2.  
O ver vie w of M ulti ple M yel o ma  .................................................................................2 2  
2. 1. 3.  
A ne mia i n Patie nts Wit h M yel o d ys plastic S y n dr o mes a n d M ulti ple 
M yel o ma  .....................................................................................................................2 2  
2. 1. 3. 1.  
Patie nts Wit h M yel o d ys plastic S y n dr o mes  ................................................................2 2  
2. 1. 3. 2.  
Patie nts Wit h M ulti ple M yel o ma  ................................................................................2 3  
2. 2.  
O ver vie w of I N C B 0 0 0 9 2 8  ..........................................................................................2 3  
2. 2. 1.  
I N C B 0 0 0 9 2 8 Mec ha nis m of Acti o n ...........................................................................2 3  
2. 2. 2.  
I N C B 0 0 0 9 2 8 Safet y P har mac ol o g y ...........................................................................2 4  
2. 2. 3.  
I N C B 0 0 0 9 2 8 P har mac ol o g y S u m mar y ......................................................................2 4  
2. 3.  
St u d y Rati o nale  ...........................................................................................................2 5  
2. 3. 1.  
R ole of Acti vi n Rece pt or -Li ke Ki nase -2 Re g ulati n g t he B o ne 
M or p h o ge netic Pr otei n Pat h wa y  .................................................................................2 5  
2. 3. 2.  
R ole of He pci di n i n M yel o d ys plastic S y n dr o me –  a n d M ulti ple M yel o ma –
Relate d A ne mia  ..........................................................................................................2 5  
2. 3. 3.  
Scie ntific Rati o nale f or St u d y Desi g n  ........................................................................2 6  
2. 3. 4.  
J ustificati o n f or Starti n g D ose ....................................................................................2 6  
2. 3. 5.  
U p date d Dat a Fr o m O n g oi n g Cli nical Trials ..............................................................2 7  
2. 4.  
Be nefit/ Ris k Assess me nt  ............................................................................................2 8  
2. 4. 1.  
P ote ntial Ris ks of I N C B 0 0 0 9 2 8 Base d o n Precli nical T o xic ol o g y  ............................2 8  
2. 4. 2.  
P ote ntial Be nefit  .........................................................................................................3 0  
2. 5.  
E x p os ure Mar gi ns  .......................................................................................................3 0  
3.  
O BJ E C TI V E S A N D E N D P OI N T S  ............................................................................3 2  
4.  
S T U D Y D E SI G N  .......................................................................................................3 4  
4. 1.  
O verall  Desi g n  ............................................................................................................3 4  

I nc yte C orp orati o n  
Pa ge 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
4. 1. 1.  
D ose Escalati o n a n d De -Escalati o n Al g orit h m  ..........................................................3 4  
4. 1. 2.  
E x pl orati o n of Alter nati v e A d mi nistrati o n Sc he d ules  ................................................3 5  
4. 1. 3.  
E x pa nsi o n Sta ges  ........................................................................................................3 5  
4. 2.  
O verall St u d y D urati o n  ...............................................................................................3 5  
4. 3.  
St u d y Ter mi nati o n  ......................................................................................................3 6  
5.  
S T U D Y P O P U L A TI O N  .............................................................................................3 7  
5. 1.  
I n cl usi o n Criteria ........................................................................................................3 7  
5. 2.  
E xcl usi o n Criteria  .......................................................................................................3 8  
5. 3.  
Lifest yle C o nsi derati o ns  .............................................................................................4 1  
5. 3. 1.  
Meals a n d Dietar y Restri cti o ns  ...................................................................................4 1  
5. 4.  
Scree n Fail ures  ............................................................................................................4 1  
5. 5.  
Re place me nt of Partici pa nts  .......................................................................................4 2  
5. 6.  
Data M o nit ori n g C o m mittee  .......................................................................................4 2  
6.  
S T U D Y T R E A T M E N T  ..............................................................................................4 3  
6. 1.  
St u d y  Treat me nt A d mi nistere d  ...................................................................................4 3  
6. 2.  
Pre parati o n, H a n dli n g, a n d Acc o u nta bilit y  ................................................................4 4  
6. 3.  
Meas ures t o Mi ni mize Bias:  Ra n d o mizati o n a n d Bli n di n g  .......................................4 5  
6. 4.  
St u d y Treat me nt C o m plia nce  .....................................................................................4 5  
6. 5.  
D ose -Li miti n g T o xicit y a n d Deter mi nati o n of Ma xi m u m T olerate d D ose 
a n d/ or P har mac ol o gicall y Acti ve D ose  ......................................................................4 5  
6. 5. 1.  
Defi niti o n of a D ose -Li miti n g T o xicit y  ......................................................................4 5  
6. 5. 2.  
Pr oce d ures f or C o h ort Re vie w a n d D os e Escalati o n  ..................................................4 7  
6. 5. 2. 1.  
Assess me nt of Safet y a n d P har mac o ki netic Res ults  ..................................................4 7  
6. 5. 2. 2.  
I nterc o h ort D ose I n creas e Al g orit h m .........................................................................4 7  
6. 5. 3.  
Defi niti o n of t he Ma xi m u m T olerate d D ose  ..............................................................4 7  
6. 5. 4.  
Defi niti o n of t he Rec o m me n de d D ose f or E x pa nsi o n  ................................................4 8  
6. 6.  
D ose M o dificati o ns  .....................................................................................................4 8  
6. 6. 1.  
Ma na ge me nt of D ose -Li miti n g T o xicities or Ot her Ur ge nt Sit uati o ns  ......................4 8  
6. 6. 2.  
F oll o w -U p of D os e -Li miti n g T o xicities  .....................................................................4 8  
6. 6. 3.  
Criteria a n d Pr oce d ures f or D ose I nterr u pti o ns a n d A dj ust me nts of St u d y 
Dr u g  ............................................................................................................................4 8  
6. 6. 3. 1.  
D ose Re d ucti o ns of St u d y Dr u g f or C o nc o mita nt Use of I n d u cers or 
I n hi bit ors of C Y P 3 A 4/ 5 ..............................................................................................5 2  

I nc yte C orp orati o n  
Pa ge 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
6. 6. 4.  
Criteria f or Per m a ne nt Disc o nti n uati o n of St u d y Dr u g  ..............................................5 3  
6. 6. 5.  
Criteria a n d Pr oce d ures f or D ose I n creases of St u d y Dr u g  ........................................5 3  
6. 6. 6.  
Treat me nt Aft er I nitial Ra di ol o gic E vi de nce of Disease Pr o gressi o n  ........................5 4  
6. 7.  
C o nc o mita nt Me dicati o ns a n d Pr oce d ures  .................................................................5 4  
6. 7. 1.  
Per mitte d Me dicati o ns a n d Pr oce d ures  ......................................................................5 4  
6. 7. 2.  
Restricte d Me dicati o ns a n d Pr oce d ures  ......................................................................5 4  
6. 7. 3.  
Pr o hi bite d Me dicati o ns a n d Pr oce d ures  .....................................................................5 5  
6. 8.  
Treat me nt Aft er t he E n d of t he St u d y  .........................................................................5 5  
7.  
DI S C O N TI N U A TI O N O F S T U D Y T R E A T M E N T A N D P A R TI CI P A N T 
WI T H D R A W A L  ........................................................................................................5 6  
7. 1.  
Disc o nti n uati o n of St u d y Treat me nt  ...........................................................................5 6  
7. 1. 1.  
Reas o ns f or Disc o nti n uati o n  .......................................................................................5 6  
7. 1. 2.  
Disc o nti n uati o n Pr oce d ures  ........................................................................................5 7  
7. 2.  
Partici pa nt Wit h dra w al Fr o m t he St u d y  .....................................................................5 8  
7. 3.  
L ost t o F oll o w -U p .......................................................................................................5 8  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ......................................................5 9  
8. 1.  
A d mi nistrati ve a n d Ge neral Pr oce d ures  .....................................................................5 9  
8. 1. 1.  
I nf or me d C o nse nt Pr ocess ..........................................................................................5 9  
8. 1. 2.  
Scree ni n g Pr oce d ures  ..................................................................................................6 0  
8. 1. 3.  
I nteracti ve Res p o nse Tec h n ol o g y Pr oce d ure ..............................................................6 0  
8. 1. 4.  
De m o gra p h y a n d Me dical Hist or y  ..............................................................................6 0  
8. 1. 4. 1.  
De m o gra p hics a n d Ge n eral Me dical Hist or y  .............................................................6 0  
8. 1. 4. 2.  
Disease C haracteristics a n d Treat me nt Hist or y  ..........................................................6 0  
8. 2.  
Efficac y Assess me nts  .................................................................................................6 1  
8. 2. 1.  
Efficac y Assess me nts f or All Disease Gr o u ps  ...........................................................6 1  
8. 2. 2.  
Me dical Res o urce Utilizati o n a n d Healt h Ec o n o mi cs  ................................................6 2  
8. 3.  
Safet y Assess me nts  .....................................................................................................6 2  
8. 3. 1.  
A d verse E v e nts  ...........................................................................................................6 2  
8. 3. 2.  
P h ysical E xa mi nati o ns  ................................................................................................6 2  
8. 3. 3.  
Easter n C o o perati ve O nc ol o g y Gr o u p Perf or ma n ce Stat us  ........................................6 3  
8. 3. 4.  
Vital Si g ns  ..................................................................................................................6 3  
8. 3. 5.  
Car diac F u ncti o n Assess me nts  ...................................................................................6 4  

I nc yte C orp orati o n  
Pa ge 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8. 3. 5. 1.  
1 2 -Lea d Electr ocar di o gra ms a n d Car diac Ec h o gra p h y or M ulti g ate d 
Ac q uisiti o n  ..................................................................................................................6 4  
8. 3. 5. 2.  
Tri plicate 1 2 -le a d E C Gs .............................................................................................6 4  
8. 3. 6.  
Ir o n O verl oa d Assess me nt ..........................................................................................6 5  
8. 4.  
La b orat or y Ass ess me nts  .............................................................................................6 6  
8. 4. 1.  
Pre g na nc y T esti n g  ......................................................................................................6 9  
8. 4. 2.  
Ser ol o g y  ......................................................................................................................6 9  
8. 5.  
P har mac o ki netic Assess me nts  ....................................................................................6 9  
8. 5. 1.  
Bl o o d Sa m ple C ollecti o n  ............................................................................................6 9  
8. 6.  
P har mac o d y na mic a n d Tra nslati o nal Assess me nts  ....................................................7 0  
8. 6. 1.  
Bl o o d a n d B o ne Marr o w Sa m ple C ollecti o n  ..............................................................7 0  
8. 6. 2.  
P har mac o d y na mic a n d Tra nslati o nal Researc h Para meters  .......................................7 0  
8. 7.  
U nsc he d ule d Visits  .....................................................................................................7 1  
8. 8.  
E n d of Treat me nt a n d/ or Earl y Ter mi nati o n  ..............................................................7 1  
8. 9.  
F oll o w -U p  ...................................................................................................................7 1  
8. 9. 1.  
Safet y F oll o w -U p  ........................................................................................................7 1  
8. 9. 2.  
P ost -Treat me nt F oll o w -U p  .........................................................................................7 1  
9.  
A D V E R S E E V E N T S:  D E FI NI TI O N S A N D P R O C E D U R E S F O R 
R E C O R DI N G, E V A L U A TI N G, F O L L O W -U P, A N D R E P O R TI N G  ......................7 3  
9. 1.  
Defi niti o n of A d vers e E v e nt  .......................................................................................7 3  
9. 2.  
Defi niti o n of Seri o us A d verse E ve nt  ..........................................................................7 4  
9. 3.  
Rec or di n g a n d F oll o w -U p of A d verse E ve nts a n d/ or Seri o us A d verse E ve nts  .........7 5  
9. 4.  
Re p orti n g of Seri o us A d verse E ve nts  .........................................................................7 7  
9. 5.  
E mer ge nc y U n bli n di n g of Treat me nt Assi g n me nt  .....................................................7 8  
9. 6.  
Pre g na nc y  ...................................................................................................................7 9  
9. 7.  
War ni n gs a n d Preca uti o ns  ..........................................................................................7 9  
9. 8.  
Pr o d uct C o m plai nts  ....................................................................................................7 9  
9. 9.  
Treat me nt of O v er d ose  ...............................................................................................8 0  
1 0 . 
S T A TI S TI C S  ..............................................................................................................8 1  
1 0. 1.  
Sa m ple Size Deter mi nati o n  ........................................................................................8 1  
1 0. 1. 1.  
D ose Escalati o n  ..........................................................................................................8 1  
1 0. 1. 2.  
D ose E x pa nsi o n  ..........................................................................................................8 1  
1 0. 2.  
P o p ulati o ns f or A nal yses  ............................................................................................8 1  

I nc yte C orp orati o n  
Pa ge 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 0. 3.  
Le vel of Si g nifica nce  ..................................................................................................8 1  
1 0. 4.  
Statistical A nal yses  .....................................................................................................8 2  
1 0. 4. 1.  
Pri mar y A nal ysis:  Safet y  ...........................................................................................8 2  
1 0. 4. 2.  
Sec o n dar y A n al yses  ....................................................................................................8 2  
1 0 . 4. 2. 1. 
Efficac y  .......................................................................................................................8 2  
1 0. 4. 2. 2.  
P har mac o ki netics  ........................................................................................................8 3  
1 0. 4. 2. 3.  
P har mac o d y na mics  .....................................................................................................8 3  
1 0 . 4. 3. 
Safet y A nal yses  ..........................................................................................................8 3  
1 0. 4. 4.  
E x pl orat or y A nal yses  ..................................................................................................8 4  
1 0. 5.  
I nteri m A nal ysis ..........................................................................................................8 5  
1 1.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S  ..................................................................................................8 6  
1 1. 1.  
I n v esti gat or Res p o nsi bilities .......................................................................................8 6  
1 1. 1. 1.  
I d e ntificati o n of t he C o or di nati n g Pri nci pal I n v esti gat or ...........................................8 7  
1 1. 2.  
Data Ma na g e me nt  .......................................................................................................8 7  
1 1. 3.  
Data Q ualit y Ass ur a nce  ..............................................................................................8 9  
1 1. 4.  
Data Pri vac y a n d C o nfi de ntialit y of St u d y Rec or ds  ...................................................8 9  
1 1. 5.  
Fi na ncial Discl os ur e  ...................................................................................................9 0  
1 1. 6.  
P u blicati o n P olic y  .......................................................................................................9 0  
1 1. 7.  
St u d y a n d Site Cl os ure ................................................................................................9 1  
1 2.  
R E F E R E N C E S  ...........................................................................................................9 2  
A P P E N DI X  A.  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 A N D D E FI NI TI O N S  ............................................9 7  
A P P E N D I X B.  I N S T R U C TI O N T O P A R TI CI P A N T S F O R H A N D LI N G S T U D Y 
D R U G (I N C B 0 0 0 9 2 8)  ................................................................................................9 9  
A P P E N DI X  C.  M A N A G E M E N T O F P O T E N TI A L H Y' S L A W C A S E S  ..............................1 0 0  
A P P E N DI X  D.  C O VI D -1 9 P A N D E MI C MI TI G A TI O N S T R A T E GI E S A N D 
I N S T R U C TI O N S .....................................................................................................1 0 4  
A P P E N DI X  E.  P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S  ..........................1 0 6  
 
LI S T O F  T A B L E S  
Ta ble  1:  
Pri mar y a n d Sec o n dar y O bjecti ves a n d E n d p oi nts  .....................................................1 3  
Ta ble  2:  
Ke y St u d y Desi g n Ele me nts  .......................................................................................1 4  
Ta ble  3:  
Sc he d ule of A cti vities  .................................................................................................1 7  

I nc yte C orp orati o n  
Pa ge 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Ta ble  4:  
Sc he d ule of La b orat or y Assess me nts  .........................................................................2 0  
Ta ble  5:  
S u m mar y of Preli mi nar y Stea d y -State P har mac o ki netic Para meters f or 
I N C B 0 0 0 9 2 8 o n Da y 1 0 ( St u d y I N C B  0 0 9 2 8 -1 0 2)  ...................................................2 8  
Ta ble  6:  
A U C 0 -t a n d C ma x  Val ues ( T otal) f or I N C B 0 0 0 9 2 8 Ass ociate d Wit h D oses 
T hat D o N ot Ca use A d v erse Effects i n 2 8 -Da y St u di es i n Rats a n d D o gs  ................3 0  
Ta ble  7:  
E x p os ure Mar gi ns f or 5 0 m g a n d 1 0 0 m g Q D D os e Relati ve t o D oses T hat 
D o N ot Ca use A d verse Effects i n 2 8 -Da y St u dies i n Rats a n d D o gs  .........................3 1  
Ta ble  8:  
O bjecti ves a n d E n d p oi nts  ...........................................................................................3 2  
Ta ble  9:  
Decisi o n B o u n daries  ...................................................................................................3 4  
Ta ble  1 0:  E xcl usi o nar y La b orat or y Val ues  ................................................................................4 1  
Ta ble  1 1:  St u d y Treat me nt I nf or mati o n  .....................................................................................4 3  
Ta ble  1 2:  Defi niti o n of D ose -Li miti n g T o xicit y  ........................................................................4 6  
Ta ble  1 3:  G ui deli nes f or I nterr u pti o n a n d Restarti n g of St u d y Dr u g  .........................................4 9  
Ta ble  1 4:  Easter n C o o perati ve O nc ol o g y Gr o u p Perf or ma n ce Stat us  ........................................6 3  
Ta ble  1 5:  Sc he d ule of Car diac F u n cti o n Assess me nts  ...............................................................6 5  
Ta ble  1 6:  Re q uire d La b orat or y A n al ytes  ....................................................................................6 8  
Ta ble  1 7:  P har mac o ki netic Bl o o d Sa m ple Ti mi n g  .....................................................................7 0  
Ta ble  1 8:  P o p ulati o ns f or A nal yses  ............................................................................................8 1  
Ta ble  1 9:  Criteria f or Cli nicall y N ota ble Vital Si g n A b n or malities  ...........................................8 4  
Ta ble  2 0:  Criteria f or Cli nicall y N ota ble Electr ocar di o gra m A b n or malities  .............................8 4  
 
LI S T O F FI G U R E S  
Fi g ure  1:  
St u d y Desi g n Sc he ma  .................................................................................................1 6  
 

I nc yte C orp orati o n  
Pa ge 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
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  
A b bre vi ati o n s a n d 
S peci al Ter ms  
Defi nit i o n 
A E  
a d verse e ve nt  
A L K  
acti vi n rece pt or -li ke ki nase 
A L P  
al kali ne p h os p hatase  
A L T  
ala ni ne a mi n otra nsferase  
A N C  
a bs ol ute ne utr o p hil c o u nt  
A N S M  
Nati o nal Sec urit y A ge nc y of Me dici nes a n d Healt h Pr o d ucts  
a nti-H Bc  
he patitis B c ore a nti b o d y  
a nti-H Bs  
he patitis B s urface a nti b o d y  
A S T  
as partate a mi n otra nsferase  
A U C  
area u n der t he plas ma/ uri ne c o nce ntrati o n c ur ve 
A U C 0 -2 4 h 
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o ti me 2 4 h o urs 
A U C 0 -t 
area u n der t he  plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o t he last 
q ua ntifia ble meas ura ble plas ma c o nce ntrati o n  
A U C ∞ 
area u n der t he c o nce ntrati o n -ti me c ur ve e xtra p olate d t o ti me of i nfi nit y 
B A P  
b o ne al kali ne p h os p hatase  
B C R P  
breast ca ncer resista nce pr otei n  
BI D  
t wice dail y 
B M  
b o ne marr o w  
B M P  
b o ne m or p h o ge netic pr otei n  
B OI N  
Ba yesia n o pti mal i nter val  
C 1 D 1  
C ycle 1 Da y 1  
C F R  
C o de of Fe deral Re g ulati o ns  
CI  
c o nfi de nce i nter val  
C L/ F o bs 
o bser ve d oral d ose cleara nce  
C ma x  
ma xi m u m c o nce ntrati o n 
C mi n  
mi ni m u m c o nce ntrati o n  
C M M L  
c hr o nic m yel o m o n oc ytic le u ke mia  
C N S  
ce ntral ner v o us s yste m  
C O VI D -1 9  
c or o na vir us d isease 2 0 1 9  
C R  
c o m plete res p o nse  
C R P  
C -reacti ve pr otei n 
C S R  
Cli nical St u d y Re p ort  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
C Y P  
c yt oc hr o me 

I nc yte C orp orati o n  
Pa ge 1 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A b bre vi ati o n s a n d 
S peci al Ter ms  
Defi nit i o n 
D L T  
d ose -li miti n g t o xicit y 
D M C  
data m o nit ori n g c o m mittee  
D N A  
de o x yri b o n ucleic aci d  
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 D C  
electr o nic data ca pt ure 
E O T  
e n d of treat me nt  
E P O  
er yt hr o p oieti n 
E R F E  
er yt hr oferr o ne  
E S A  
er yt hr o p oieti n -sti m ulati n g a ge nt 
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 Practices  
G D P R  
Ge neral Data Pr otecti o n Re g ulati o n   
GI  
gastr oi ntesti nal  
H A M P  
he pci di n a nti micr o bial pe pti de  
H b A 1c 
gl ycate d he m o gl o bi n  
H Bs A g  
he patitis B s urface a nti ge n  
H B V  
he patitis B vir us  
Hct  
he mat ocrit  
H C V  
he patitis C vir us  
H g b  
he m o gl o bi 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  
HI V  
h u ma n i m m u n o deficie nc y vir us  
H R T  
h or m o nal re place me nt t hera p y  
I B 
I n vesti gat or's Br oc h ure 
I C5 0 
half ma xi mal i n hi bit or y c o nce ntrati o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts f or 
P har mace uticals f or H u ma n Use  
I E C 
i n de pe n de nt et hics c o m mittee  
I L-6  
i nterle u ki n-6  
I R B 
i nstit uti o nal re vie w b oar d 
I R T 
i nteracti ve res p o nse tec h n ol o g y 

I nc yte C orp orati o n  
Pa ge 1 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A b bre vi ati o n s a n d 
S peci al Ter ms  
Defi nit i o n 
J Tc 
c orrecte d J T i nter val  
L F S  
le u ke mia-free s ur vi val 
L F T  
li ver f u ncti o n test 
M C H  
mea n c or p usc ular he m o gl o bi n  
M C H C  
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n  
M C V  
mea n c or p usc ular v ol u me  
M D R 1  
m ulti dr u g resista nt ge ne 1  
M D S  
m yel o d ys plastic s y n dr o mes  
M D S -R S  
m yel o d ys plastic s y n dr o me wit h ri n g si der o blasts 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
M M  
m ulti ple m yel o ma  
M M A  
met h yl mal o nic aci d  
M P N  
m yel o pr oliferati ve ne o plas m  
M RI  
ma g netic res o na nce i ma gi n g  
m R N A  
messe n ger ri b o n ucleic aci d  
M R P 2  
m ulti dr u g resista nce-ass ociate d pr otei n 2  
M T D  
ma xi m u m t olerate d d ose  
M U G A  
m ulti gate d ac q uisiti o n  
N CI  
Nati o nal Ca ncer I nstit ute  
N O A E L  
n o o bser ve d a d verse effect le vel  
N R B C  
n ucleate d re d bl o o d cell  
N T BI  
n o n – tra nsferri n-b o u n d ser u m ir o n  
P B M C  
pe ri p heral bl o o d m o n o n uclear cell  
P D  
p har mac o d y na mic  
P F S  
pr o gressi o n -free s ur vi val 
P -g p  
P -gl yc o pr otei n  
P H L  
p ote ntial H y 's la w 
P h V  
p har mac o vi gila nce  
P K  
p har mac o ki netic  
P R  
partial res p o nse  
Q D  
o nce dail y  
Q Tc  
c orrecte d Q T i nter val  
Q Tc F  
Q T i nter val c orrecte d usi n g Fri dericia 's f or m ula 
R A R S  
refract or y a ne mia wit h ri n ge d si der o blasts 
R B C  
re d bl o o d cell 
R B C -TI  
re d bl o o d cell tra nsf usi o n i n de pe n de nce 

I nc yte C orp orati o n  
Pa ge 1 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A b bre vi ati o n s a n d 
S peci al Ter ms  
Defi nit i o n 
R C  
retic ul oc yte c o u nt 
R D E  
rec o m me n de d d ose f or e x pa nsi o n 
R D W  
re d bl o o d cell distri b uti o n wi dt h  
R N A  
ri b o n ucleic aci d 
R SI  
refere nce safet y i nf or mati o n  
S A E  
seri o us a d verse e ve nt 
S A P  
Statistical A nal ysis Pla n  
S A R S -C o V -2  
se vere ac ute res pirat or y s y n dr o me c or o na vir us 2 
S o A  
sc he d ule of acti vities 
S O P  
sta n dar d o perati n g pr oce d ure 
S Tf R  
s ol u ble tra nsferri n rece pt or  
St u d y dr u g  
t his ter m refers t o I nc yte me dici nal i n vesti gati o nal pr o d uct I N C B 0 0 0 9 2 8 
t½  
half -life 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
TI B C  
t otal ir o n-bi n di n g ca pacit y  
tma x  
ti me t o ma xi m u m plas ma c o nce ntrati o n  
T R Ac P 5 b  
tartrate-resista nt aci d p h os p hatase t y pe 5 b  
T S A T  
tra nsferri n sat urati o n 
T SI  
t otal ser u m ir o n 
UI B C  
u nsat urate d ir o n -bi n di n g ca pacit y  
U L N  
u p per li mit of n or mal  
V z/ Fo bs 
o bser ve d oral d ose v ol u me of distri b uti o n  
W H O  
W orl d Healt h Or ga nizati o n  
W O C B P  
w o me n of c hil d beari n g p ote ntial  

I nc yte C orp orati o n  
Pa ge 1 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1.  
P R O T O C O L S U M M A R Y  
Pr ot oc ol Title:  
A P hase 1/ 2 , O pe n -L a bel, M ultice nter St u d y of I N C B 0 0 0 9 2 8 A d mi nistere d as a M o n ot hera p y i n 
Partici pa nts W it h A ne mia D ue t o M yel o d ys plastic Sy n dr o mes or M ulti ple M yel o ma  
Pr ot oc ol N u m ber:   I N CB  0 0 9 2 8 -1 0 5  
O bjecti ves a n d E n d p oi nts : 
Ta ble  1  pres e nts t he pri mar y a n d maj or/ k e y sec o n dar y o bjecti ves a n d e n d p oi nts.  
T a ble  1 : 
Pri m ar y a n d Sec o n d ar y O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
T o deter mi ne t he safet y a n d t olera bilit y of 
I N C B 0 0 0 9 2 8 m o n ot hera p y i n partici pa nts wit h M D S 
or M M . 
•  Fre q ue nc y a n d se verit y of A Es a n d S A Es, i ncl u di n g 
c ha n ges i n vital si g ns, E C Gs, p h ysical e xa mi nati o ns, 
a n d cli nical bl o o d a n d uri ne la b orat or y para meters.  
•  I de ntificati o n of t he D L Ts, M T D, a n d R D E(s). 
Sec o n d ar y  
T o deter mi ne t he efficac y of I N C B 0 0 0 9 2 8 i n 
partici pa nts wit h M D S or M M.  
F or b ot h M D S a n d M M dise ase gr o u ps:  
•  F or tra nsf usi o n -i n de pe n de nt partici pa nts at baseli ne:  
− T he pr o p orti o n of partici pa nts wit h a ne mia 
res p o nse, defi ne d as a n H g b i ncrease of at least 
1. 5 g/ d L relati ve t o baseli ne f or a n y 8 -wee k 
peri o d ( wit h eac h assess me nt meeti n g t his 
re q uire me nt) d uri n g t he first 2 4 wee ks of 
treat me nt.  
− D urati o n of a ne mia res p o nse , defi ne d as t he 
i nter val fr o m t he first o nset of a ne mia res p o nse 
t o t he earliest date of l oss of a ne mia res p o nse 
t hat persists f or at least 4 wee ks or deat h fr o m 
a n y ca use. 
•  F or tra nsf usi o n -de pe n de nt partici pa nts at baseli ne:  
− T he pr o p orti o n of partici pa nts wit h R B C -TI , 
defi ne d as t he a bse nce of a n y R B C  tra nsf usi o n 
f or at least 8 c o nsec uti ve wee ks d uri n g t he first 
2 4  wee ks of treat me nt.  
− D urati o n of R B C -TI peri o d f or partici pa nts 
ac hie vi n g R B C -TI f or at least 8 c o nsec uti ve 
wee ks d uri n g t he first 2 4 wee ks of treat me nt.  
•  Rate of R B C tra nsf usi o n t hr o u g h Wee ks  1 2 a n d 2 4, 
defi ne d as t he a vera ge n u m ber of R B C u nits per 
partici pa nt -m o nt h d uri n g t he treat me nt peri o d.  
•  T he lar gest i ncrease fr o m baseli ne i n t he mea n H g b 
val ues o ver a n y r olli n g 8 -wee k treat me nt peri o d 
d uri n g t he first 2 4 wee ks of treat me nt.  

I nc yte C orp orati o n  
Pa ge 1 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 : 
Pri m ar y a n d Sec o n d ar y O bjecti ves a n d E n d p oi nts ( C o nti n ue d)  
O bjecti ves  
E n d p oi nts  
T o deter mi ne t he efficac y of I N C B 0 0 0 9 2 8 i n 
partici pa nts wit h M D S or M M (c o nti n ue d).  
F or M D S p artici p a nts o nl y:  
•  O verall res p o nse  rate, defi ne d as t he pr o p orti o n of 
partici pa nts wit h C R or P R as per  C hes o n et al  
(2 0 0 6 ) defi niti o ns f or M D S a n d as per Sa v o na et al  
(2 0 1 5 ) defi niti o ns f or M D S/ M P N o verla p 
s y n dr o mes, as a p plica ble. 
•  P F S , defi ne d as t he i nter val fr o m t he first d ose of 
st u d y dr u g u ntil t he first d oc u me nte d pr o gressi o n or 
deat h as per C hes o n et al  (2 0 0 6 ) defi niti o ns f or M D S 
a n d  as per  Sa v o na et al  (2 0 1 5 ) defi niti o ns f or 
M D S/ M P N o verla p s y n dr o mes.  
•  L F S , defi ne d as t he i nter val fr o m t he first d ose of 
st u d y dr u g u ntil t he first d oc u me nte d le u ke mia 
tra nsf or mati o n or deat h fr o m a n y ca use.  
F or M M p artici p a nts o nl y:  
•  O verall res p o nse rate , defi ne d as t he pr o p orti o n of 
partici pa nts wit h stri n ge nt C R , C R , ver y g o o d P R , 
a n d P R  as per K u mar et al (2 0 1 6 ).   
•  P F S , defi ne d as t he i nter val fr o m t he first d ose of 
st u d y dr u g u ntil t he first d ocu me nte d pr o gressi o n or 
deat h as per K u mar et al ( 2 0 1 6 ). 
T o e v al uate t he P K of I N C B 0 0 0 9 2 8 i n partici pa nts 
wit h M D S or M M .  
P K para meters:  C ma x , tma x , a n d A U C 0 -t.  
T o e v al uate t he effect of I N C B 0 0 0 9 2 8 o n t he ir o n 
h o me ostasis a n d t he er yt hr o p oiesis para meters i n 
partici pa nts wit h M D S or M M.  
•  Bl o o d le vels of he pc i di n. 
•  Ir o n h o me ostasis para meters. 
•  Er yt hr o p oiesis para meters.  
O ver all Desi g n:  
Ta ble  2  pres e nts t he ke y st u d y desi g n ele me nts.  F urt her st u d y details are prese nte d after t he 
ta ble. 
T a ble  2 : 
Ke y St u d y Desi g n Ele me nts  
St u d y P h ase  
1/ 2  
Cli nic al I n dic ati o n  
P artici pa nts w h o are tra nsf usi o n-de pe n de nt  or  prese nt wit h s y m pt o matic 
a ne mia d ue t o:  
•  
M D S  or M D S/ M P N o verla p s y n dr o mes  O R  
•  
M M  
P o p ul ati o n  
Male a n d fe male partici pa nts at least 1 8 years of a ge w h o ha ve n ot u n der g o ne 
a n y ste m cell tra ns pla ntati o n,  w h o are n ot ca n di d ates f or s uc h a 
tra ns pla ntati o n, a n d w h o are tra nsf usi o n-de pe n de nt or prese nt wit h 
s y m pt o matic a ne mia d ue t o M D S or M M. 
N u m ber of 
P artici p a nts  
De pe n di n g o n t he n u m ber of partici pa nts i ncl u de d i n t he d ose -escalati o n sta ge, 
a p pr o xi matel y 1 2 0 partici pa nts will be i ncl u de d.  

I nc yte C orp orati o n  
Pa ge 1 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  2 : 
Ke y St u d y Desi g n Ele me nts ( C o nti n ue d)  
St u d y Desi g n  
D ose escalati o n  
D ose escalati o n utilizi n g B OI N desi g n ( Li u a n d Y ua n  2 0 1 5 ) will pr ocee d b y 
i ncl u di n g partici pa nts fr o m b ot h disease gr o u p s u ntil t he M T D is reac he d 
a n d/ or t he R D E (s) are deter mi ne d . 
E x pa nsi o n  
A n a d diti o nal 1 5 e val ua ble partici pa nts i n eac h of t he disease gr o u ps will be 
i ncl u de d i n t he e x pa nsi o n sta ges at eac h R D E  as a p plica ble . 
Esti m ate d D ur ati o n 
of St u d y 
P artici p ati o n  
U p t o 2 8 da ys f or scree ni n g, c o nti n u o us st u d y dr u g treat me nt i n c o nsec uti ve 
2 8 -da y treat me nt c ycles u p t o 6 m o nt hs , as l o n g as partici pa nts are recei vi n g 
be nefit fr o m st u d y dr u g a n d ha ve n ot met a n y criteria f or st u d y dr u g 
disc o nti n uati o n, a n d 3 0 da ys f or safet y f oll o w-u p.   
Treat me nt d urati o n will var y bet wee n partici pa nts b ut is e x pecte d t o a vera ge 
a p pr o xi matel y 6 m o n t hs. 
D M C  
Yes (i nter nal)  
C o or di n ati n g 
Pri nci p al 
I n vesti g at or 
T o be deter mi ne d  
Tre at me nt  Gr o u ps a n d D ur ati o n:  
O ne treat me nt m o dalit y :  
•  I N C B 0 0 0 9 2 8 a d mi nistere d as a m o n ot hera p y i n p artici pa nts w h o are 
tra nsf usi o n-de p e n de nt  or prese nt wit h s y m pt o matic a ne mia d u e t o M D S or M M. 
T he st u d y has 2 disease gr o u ps:  
•  Partici pa nts wit h M D S  or M D S/ M P N o verla p s y n dr o mes, c ollecti vel y r eferre d t o as 
M D S partici pa nts . 
•  Partici pa nts wit h r ela pse d/refract or y M M .  
Fi g ure  1  prese nts a s c he matic re pr ese ntati o n of t he st u d y desi g n.  
A d here n ce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uir e d f or st u d y c o n d uct.  All st u d y assess me nts will be perf or m e d as i n dicate d i n t he S o A  
(see Ta bl e  3 ), a n d all la b orat or y assess me nts will be perf or me d as i n dicate d i n Ta ble  4 . 
F urt her details of st u d y pr oce d ures a n d ass ess me nts ca n be f o u n d i n t he i n v esti gat or site file. 

I nc yte C orp orati o n  
Pa ge 1 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Fi g ure  1 : 
St u d y Desi g n Sc he m a  
 
D os e es c al ati o n 
I N C B 0 0 9 2 8
St arti n g d o s e: 5 0 m g Q D 
B ot h M D S a n d M M p arti ci p a nts 
m a y b e i n cl u d e d i n t h e s a m e c o h ort 
I d e ntifi c ati o n of t h e R D E(s)
A d diti o n al 1 5 e v al u a bl e 
p arti ci p a nts at t h e 
R D E _ 1
A d diti o n al 1 5 e v al u a bl e 
p arti ci p a nts at t h e 
R D E _ 2 – as a p pli c a bl e -
M D S di s e a s e gr o u p : M D S p arti ci p a nts w h o ar e tr a nsf usi o n-d e p e n d e nt or pr es e nt wit h s y m pt o m ati c a n e mi a 
M M di s e a s e gr o u p: R el a ps e d/r efr a ct or y M M p arti ci p a nts w h o ar e tr a nsf usi o n -d e p e n d e nt or pr es e nt wit h 
s y m pt o m ati c a n e mi a
I n e a c h di s e a s e gr o u p a s a p pli c a bl e 

I nc yte C orp orati o n  
Pa ge 1 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities  
Visit D a y ( R a n ge)  
Scr ee ni n g  
Tre at me nt P eri o d 
F oll o w -U p  
N otes / Pr ot oc ol Secti o n 
D a y −2 8 
t o Da y 0  
C ycle 1 ( ± 1 d a y f or t he 
visits fr o m C 1 D 1  as 
refere nc e)  
C ycle 2  
( ± 1 d a y) 
≥ C ycle 3  
( ± 3 d a ys) 
E O T  
( ± 7 
d a ys)  
S afet y  
( 3 0 +  5  
d a ys ) 
S ur vi v al  
(e ver y 1 8 0  
± 1 4 d a ys)  
D a y 
1  
D a y 
8  
D a y 
1 5  
D a y 
2 2  
D a y 
1  
D a y 
1 5  
D a y 
1  
D a y 
1 5  
A d mi nistr ati ve P r oce d ures  
I nf or me d c o nse nt si g ne d  
X  
 
 
 
 
 
 
 
 
 
 
 
 
C o ntact I R T  
X  
X  
 
 
 
X  
 
X  
 
X  
 
 
 
I ncl usi o n/e xcl usi o n criteria 
X  
X  
 
 
 
 
 
 
 
 
 
 
Secti o n  5  
De m o gra p h y/ g e neral a n d disease 
hist or y  
X  
 
 
 
 
 
 
 
 
 
 
 
 
Dis pe nse/ ad mi nister st u d y dr u g  
 
X  
 
 
 
X  
 
X  
 
 
 
 
Secti o n  6. 1  
Pri or/c o nc o mita nt me dicati o ns  
  Fr o m 3 0 da ys b ef ore C 1 D 1 u ntil 3 0 da ys after t he last d ose of st u d y dr u g or start of a 
ne w a ntica ncer t h era p y, w hic he ver occ urs first  → 
 
Secti o n  6. 7  
S afet y A ssess me nts 
A E assess m e nt  
 Fr o m si g nat ure of t h e I C F u ntil  at least 3 0 da ys after t he last d ose of st u d y dr u g or start 
of a ne w a ntica ncer t h era p y, w hic he ver occ urs first  → 
 
Secti o n  8. 3. 1  a n d Secti o n 9  
P h ysical e xa mi n ati o n/ E C O G 
perf or ma nce stat us 
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
 
Secti o n  8. 3. 2  a n d 
Secti o n  8. 3. 3  
Hei g ht  
X  
 
 
 
 
 
 
 
 
 
 
 
 
Vital si g ns/ b o d y wei g ht  
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
 
Secti o n  8. 3. 4  
1 2 -lea d E C G 
X  
X  
 
 
 
X  
 
X *  
 
X  
X  
 
* Will be perf or me d pre d ose 
o n Da y 1 of e ver y t hir d c ycle  
( C ycles 3, 6, 9, etc). 
Secti o n  8. 3. 5. 1  
Ec h ocar di o gra p h y  or M U G A sca n  
X  
 
 
 
 
 
 
X *  
 
X  
 
 
* E v er y si xt h c ycle.  
Secti o n  8. 3. 5. 1  

I nc yte C orp orati o n  
Pa ge 1 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities ( C o nti n ue d)  
Visit D a y ( R a n ge)  
Scree ni n g  
Tre at me nt Peri o d  
F oll o w -U p  
N otes/ Pr ot oc ol Secti o n  
D a y −2 8 
t o D a y 0 
C ycle 1 ( ± 1 d a y f or t he 
visits fr o m C 1 D 1 as 
refere nc e)  
C ycle 2  
( ± 1 d a y) 
≥ C ycle 3  
( ± 3 d a ys) 
E O T  
( ± 7 
d a ys)  
S afet y  
( 3 0 + 5 
d a ys)  
S ur vi v al  
(e ver y 1 8 0  
± 1 4 d a ys)  
D a y 
1  
D a y 
8  
D a y 
1 5  
D a y 
2 2  
D a y 
1  
D a y 
1 5  
D a y 
1  
D a y 
1 5  
S afet y Assess me nts (c o nti n ue d)  
Ti me d tri plicate 1 2 -lea d E C Gs 
ali g ne d wit h P K/ P D sa m pli n g as 
a p plica ble 
X *  
X  
 
X  
 
 
 
 
 
 
 
 
* At scree ni n g a n d wit hi n 
7  da ys pri or t o C 1 D 1.  
E C Gs fr o m C ycle 2 a n d 
be y o n d o nl y nee d t o be 
perf or me d i n tri plicate if t here 
has bee n a Q T pr ol o n gati o n 
o n st u d y or t h e E C G s h o ws a 
cli nicall y si g nifica nt 
a b n or malit y n ot prese nt at 
baseli ne . 
Secti o n  8. 3. 5. 2  
Li ver M RI  
 
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 3. 6  
Partici p a nts wit h scree ni n g 
ferriti n le vel of 
<  1 0 0 0  n g/ m L *  
 
 
 
 
 
 
 
 
 
 
 
 
* W h e n o n -treat me nt ferriti n 
le vel is > 1. 5 × scree ni n g 
ferriti n le vel A N D 
 1 0 0 0  n g/ m L, e ver y 3 c ycles 
t h ereafter a n d at E O T. 
Partici p a nts wit h scree ni n g 
ferriti n le vel of 
≥ 1 0 0 0  n g/ m L *  
X †  
 
 
 
 
 
 
X *  
 
X  
 
 
* E v er y 6 c ycles.  W h e n 
o n -treat me nt ferriti n le vel is 
>  1. 5 × scree ni n g le vel , e ver y 
3 c ycles t h ereafter a n d E O T. 
† Ma y be perf or me d wit hi n 
3  m o nt hs pri or t o scree ni n g . 

I nc yte C orp orati o n  
Pa ge 1 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  3 : 
Sc he d ule of Acti vities ( C o nti n ue d)  
Visit D a y ( R a n ge)  
Scree ni n g  
Tre at me nt Peri o d  
F oll o w -U p  
N otes/ Pr ot oc ol Secti o n  
D a y −2 8 
t o D a y 0 
C ycle 1 ( ± 1 d a y f or t he 
visits fr o m C 1 D 1 as 
refere nc e)  
C ycle 2  
( ± 1 d a y) 
≥ C ycle 3  
( ± 3 d a ys) 
E O T  
( ± 7 
d a ys)  
S afet y  
( 3 0 + 5 
d a ys)  
S ur vi v al  
(e ver y 1 8 0  
± 1 4 d a ys)  
D a y 
1  
D a y 
8  
D a y 
1 5  
D a y 
2 2  
D a y 
1  
D a y 
1 5  
D a y 
1  
D a y 
1 5  
Effic ac y Assess me nts  
F o r All P artici p a nts  
R B C tra nsf usi o n rec or d  
 D uri n g a mi ni m u m of 8 wee ks b ef ore C 1 D 1, t hr o u g h o ut st u d y dr u g treat me nt, a n d u ntil 
3 0  da ys after t he last d ose of st u d y dr u g → 
 
Secti o n  8. 2. 1   
H g b  
 D uri n g a mi ni m u m of 8  wee ks b ef ore C 1 D 1, wee kl y f or C ycle 1, e ver y 2 wee ks f or 
C ycles 2 –  6 , o n Da y 1 of eac h c ycle t hereafter, at E O T, a n d at safet y f oll o w -u p → 
 
B M as pirate/ bi o ps y 
X *  
 T o c o nfir m a res p o nse ( C R or P R f or M D S a n d C R f or M M) i n case of 
s us pecte d disease pr o gressi o n a n d as cli nicall y i n dicate d as p er i nstit uti o nal 
sta n dar ds → 
 
* Arc hi v al tiss ue all o we d f or 
M M partici pa nts.  M a y be 
perf or me d wit hi n 3  m o nt hs 
pri or t o scree ni n g . 
Secti o n  8. 2. 1   
Disease res p o nse assess me nt  
 
 
 
 
 
 
 
X *  
 
 
 
 
* E v er y si xt h c ycle.  
F o r M M P artici p a nts O nl y  
S keletal s ur ve y:  x -ra y of t he s k ull, 
l o n g b o nes, s pi n e, pel vis, a n d ribs  
X *  
 As cli nicall y i n dicate d at t he discreti o n of t h e i n vesti g at or  → 
 
 
* U nless perf or me d wit hi n 
8  wee ks pri or t o C 1 D 1 . 
Ser u m free li g ht c hai n,  
ser u m a n d  uri n e (s p ot) pr otei n 
electr o p h oresis, 
q ua ntitati ve i m m u n o gl o b uli ns,  
beta 2-macr o gl o b uli n  
X  
 
 
 
 
 
 
X *  
 
X  
 
 
* E v er y si xt h c ycle. 
Secti o n  8. 2. 1   
P ost -Tre at me nt Assess me nts  
Le u ke mia pr o gressi o n/ d isease 
pr o gressi o n/ n e w a ntica ncer t h era p y 
 
 
 
 
 
 
 
 
 
 
 
X  
Secti o n  8. 9. 2   

I nc yte C orp orati o n  
Pa ge 2 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  4 : 
Sc he d ule of L a b or at or y Assess m e nts  
Pr oce d ure  
Scr ee ni n g  
Tre at me nt P eri o d 
F oll o w -U p  
N otes/ Pr ot oc ol Secti o n  
D a y −2 8 
t o Da y 0  
C ycle 1 ( ± 1 d a y f or t he visits 
fr o m C 1 D 1 as refere nce) 
C ycle 2  
( ± 1 d a y) 
≥ C ycle 3  
( ± 3 d a ys) 
E O T  
( ± 7 
d a ys)  
S afet y  
( 3 0 +  5 
d a ys ) 
S ur vi v al  
(e ver y 1 8 0  
± 1 4 d a ys)  
D a y 1  D a y 8  D a y 1 5  D a y 2 2  D a y 1  D a y 1 5  D a y 1  D a y 1 5  
L a b or at or y A ssess me nts  
Pre g na nc y  testi n g  
X *  
 
 
 
 
X  
 
X  
 
X  
X  
 
* Wit hi n 3 da ys of C 1 D 1.  
Secti o n  8. 4. 1  
He mat ol o g y  
X  
X  
X  
X  
X  
X  
 
X  
 
X  
X  
 
Secti o n  8. 4  a n d Ta ble  1 6  
H g b o nl y  
 
 
 
 
 
 
X  
 
X *  
 
 
 
* Fr o m C ycles 3 t o 6 o nl y.  
Secti o n  8. 2  a n d Secti o n  8. 4  
Bl o o d  c he mistr y 
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
 
Secti o n  8. 4  a n d Ta ble  1 6  
H b A 1c, v ita mi n B1 2, a n d M M A  
X  
 
 
 
 
 
 
X *  
 
X  
 
 
* E v er y t hir d c ycle.  
Secti o n  8. 4  
Ser ol o g y scree ni n g  
X  
 
 
 
 
 
 
 
 
 
 
 
Secti o n  8. 4. 2  a n d Ta ble  1 6  
Li pi d pa nel  
X  
X  
 
 
 
X  
 
X  
 
X  
X  
 
* C 3 D 1 o nl y.  
Secti o n  8. 4  a n d Ta ble  1 6  
C oa g ulati o n pa nel  
X  
X  
 
 
 
X  
 
X *  
 
X  
X  
 
Uri nal ysis  
X  
 
 
 
 
 
 
 
 
X  
 
 
P K S a m pli n g S c he d ule 
Bl o o d P K sa m ple  
 
X  
 
X  
 
 
 
 
 
 
 
 
Secti o n  8. 5  
P D S a m pli n g Sc he d ule  
As of Pr ot o c ol A me n d me nt 5, n o f urt h er P D /tra nslati o nal assess me nt  sa m ples will be c ollecte d. 

I nc yte C orp orati o n  
Pa ge 2 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
2.  
I N T R O D U C TI O N 
2. 1.  
B ac k gr o u n d  
2. 1. 1.  
O ver vie w of M yel o d ys pl astic S y n dr o mes  
M yel o d ys plastic s y n dr o mes are cl o nal ste m dis or ders c haract erize d b y i neffecti ve h e mat o p oiesis, 
m or p h ol o gical d ys plasia, peri p heral bl o o d c yt o pe nias, a n d a hi g h ris k of pr o gressi o n t o ac ute 
m yel o ge n o us le u ke mia.  
Rece nt  e pi de mi ol o gical st u dies of M D S i n Asia, E ur o pe, a n d t he U nite d States ha ve re p orte d 
di ver ge nt i nci de nce rat es of M D S ra n gi n g fr o m <  2 t o m ore t ha n 6 8 per 1 0 0, 0 0 0 pe o ple  (C hi hara  
et al 2 0 1 4, C o gle 2 0 1 5 , Di n m o ha me d  et al 2 0 1 4, Mc Q uilte n et al 2 0 1 3 ), wit h a hi g her i nci de nce 
a m o n g me n  a n d a me di a n s ur vi val of < 3 years or 3‐ year s ur vi val of <  6 0 %  (Ga n g at et al 2 0 1 6 , 
G ol d ber g et al 2 0 1 0 , Ma et al 2 0 0 7 , R ollis o n et al 2 0 0 8 ).  I n West er n c o u ntries, a m o n g 
i n di vi d uals ol der t ha n 7 0 years,  t he i nci d e nce is r e p orte d t o be bet wee n 2 2 a n d 4 5 per 1 0 0, 0 0 0 
pe o ple, a n d t his i nci de nce f urt her i n creases wit h a ge (Di n m o ha me d et al 2 0 1 4 , Ma 2 0 1 2 ).  
T he maj orit y of patie nts wit h M D S prese nt wit h l o w or i nter me diate  ris k, as defi ne d b y t he 
I nter nati o nal Pr o g n ostic Sc ori n g S yste m criteria.  Peri p heral bl o o d c yt o pe nias e x perie n ce d b y 
t hese patie nts i ncl u de a n e mia, ne utr o pe nia, a n d t hr o m b oc yt o pe nia ( Fe n a u x a n d A dès  2 0 1 3 ).  
A ne mia is t he m ost c o m m o n c yt o pe nia a n d a m aj or t hera p e utic c halle n g e i n patie nts wit h M D S 
beca use  it affects >  5 0 % of patie nts at pres e ntati o n ( B o we n a n d Hellstr o m -Li n d ber g 2 0 0 1 ) a n d 
u p t o 9 0 % of patie nts at s o me p oi nt d uri n g t he c o urse of t he dise ase , a n d it e ve nt uall y re q uir es 
R B C  tra nsf usi o ns i n >  8 0 % of patie nts  (Casa d e vall  1 9 9 8 , Kelai di et al 2 0 1 0 ).  A ne mia is t he 
mai n ca use of s y m pt o ms  of M D S,  i ncl u di n g fati g ue a n d d ys p nea, w hic h res ult i n a de gra dati o n 
of q ualit y of life a n d i ncrease d m or bi di t y s uc h as car diac c o m plicati o ns (S a nti ni 2 0 1 1 a). 
T he pat h o p h ysi ol o g y of a ne mia i n M D S ma y o verla p wit h t he pat h o p h ysi ol o g y of a ne mia of 
i nfla m mati o n, partic ularl y i n earl y-sta ge (ie, l o wer-ris k) M D S.  I n ma n y patie nts wit h M D S, 
le vels of pr oi nfla m mat or y c yt o ki nes (e g, i n I L-6 ) ha ve bee n s h o w n t o be ass ociate d wit h hi g h 
le vels of he pci di n.  F or t h ose patie nts, t he sta n dar d of care pri maril y c o m prises s u p p orti ve care 
f or t heir s y m pt o ms:  R B C tra nsf usi o ns a n d E S As f or a ne mia as well as  ma na ge me nt of ris k of 
blee di n g a n d i nfecti o ns.  C hr o nic a ne mia a n d R B C tra nsf usi o ns are i n de pe n de nt ris k fact ors 
affecti n g s ur vi val a n d are ass ociate d wit h ir o n o verl oa d, fati g ue, i m pair e d q ualit y of life, a n d 
i ncreas e d car di o vasc ular risks.  Er yt hr o p oieti n -sti m ulati n g a ge nts ca n pr o vi de cli nical be nefit t o 
s o me patie nts wit h M D S.  H o we ver, o nl y a p pr o xi matel y 3 0 % of patie nts treate d wit h E S As 
ac hie ve i m pr o ve me nt.  T he be nefit is us uall y li mite d t o t h ose patie nts w h o  ha ve a l o w E P O le vel 
at baseli ne.  T he m aj orit y of patie nts wit h M D S ha ve ele vat e d ser u m E P O c o nce ntrati o ns, w hic h 
i n dicates t hat a ne mia i n M D S is d ue t o i neffecti v e er yt hr o p oiesis t hat ofte n ca n n ot be c orrecte d 
b y e x o ge n o us E S A a d mi nistrati o n.  Treat me nt of a ne mia a n d re d ucti o n  of tra nsf usi o n b ur de n are 
t he maj or t hera p e utic g oals i n patie nts wit h l o w- or i nter me diate -ris k M D S.  T here are fe w 
treat me nt o pti o ns f or t hese patie nts, partic ularl y after fail ure of E S As. 

I nc yte C orp orati o n  
Pa ge 2 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
2. 1. 2.  
O ver vie w of M ulti ple M yel o m a  
M ulti ple m yel o ma is a mali g na nt plas ma cell d yscrasia c h aracterize d b y m o n ocl o nal 
pr oliferati o n of plas ma cells t o get her wit h o ver pr o d ucti o n of a m o n ocl o nal a nti b o d y 
(Va n der ker ke n et al 2 0 0 3 ) t hat is ofte n acc o m pa ni e d b y a ne mia, h y p ercalce mia, re nal 
i ns ufficie nc y, or b o n e lesi o ns (K yle a n d Raj k u mar 2 0 0 4 ).  Fati g ue is r e p ort e d b y ma n y patie nts 
a n d ma y be ca use d b y b ot h p h ysical a n d ps yc h ol o gical fact ors relate d t o t h e disease a n d its 
treat me nt , b ut a ne mia h as bee n s h o w n t o be a n i m p orta nt c o ntri b ut or y fact or ( Cella et al 2 0 0 4 ).   
M ulti ple m yel o ma acc o u nts f or a p pr o xi matel y 1. 8 % of all ca n cers a n d sli g htl y m ore t ha n 1 7 % of 
he mat ol o gic mali g na ncies i n t h e U nite d States (Sie gel et al 2 0 1 7 ).  It is m ost fre q ue ntl y 
dia g n ose d i n pe o ple a g e d 6 5 t o 7 4 years, wit h a m e dia n a ge of  6 9 years ( Sie gel et al 2 0 1 7 ).  T h e 
A merica n Ca n cer S oci et y esti mate d t hat 3 2, 1 1 0 ne w cas es of M M w o ul d b e dia g n ose d i n t he 
U nite d States i n 2 0 1 9, wit h a n esti mate d 1 2, 9 6 0 deat hs ( Sie gel et al 2 0 1 7 ).   
I n E ur o pe, M M affects a p pr o xi matel y 4 of  e very 1 0 0 ,0 0 0 pe o ple  (Ferla y et al 2 0 1 3 , Pal u m b o a n d 
A n ders o n 2 0 1 1 ).  A E ur o pea n p o p ulati o n‐ bas e d st u d y re p orte d a n i ncrease i n 5‐ year s ur vi v al i n 
patie nts wit h M M/ plas mac yt o ma fr o m 2 9. 8 % i n 1 9 9 7‐ 1 9 9 9 t o 3 9. 6 % i n 2 0 0 6‐ 2 0 0 8  (Sa nt 
et al 2 0 1 4 ).  
Nearl y all patie nts wit h M M will be affecte d b y a ne mia d uri n g t he c o urse of t heir disease.  A 
retr os pecti ve st u d y of 1 0 2 7 patie nts wit h M M fr o m t he U nite d States  de m o nstrate d t hat a ne mia 
( H g b c o nce ntrati o n <  1 2 g/ d L) was pres e nt at dia g n osis i n 7 3 % of pati e nts (K yle et al 2 0 0 3 ).  A 
E ur o pea n -wi de s ur v e y of  7 2 0 patie nts wit h M M s h o we d t hat 2 9. 7 % of patie nts prese nt e d wit h 
H g b le vels of ≤ 9. 9 g/ d L at t he ti me of dia g n osis, a n d 8 5. 3 % of t hes e patie nts were a n e mic at a n y 
ti me duri n g t he s ur ve y ( Bir ge g år d et al 2 0 0 6 ).  A p pr o xi matel y 1 0 % of patie nts wit h M M ha ve a n 
H g b le vel < 8  g/ d L ( V a n der Wall et al 2 0 1 3 ).  N o nres p o n ders a n d rel a psi n g M M patie nts ofte n 
c o nti n ue t o ha ve  a n e mia.   
F urt her m ore, c yt or e d ucti ve treat me nts a g ai nst M M c o ntri b ute t o t he de vel o p me nt of a ne mia, a n d 
o verall 4 5 % t o 9 0 % of p atie nts wit h M M recei vi n g c he m ot hera p y will re q uire R B C  tra nsfusi o ns 
d uri n g t he c o urse of t heir treat me nt (D a m macc o et al 1 9 9 8 , Oster b or g et al 1 9 9 6 ).  
A ne mia is a c o m m o n c o m plicati o n of M M t hat ca n ne gati vel y affect  t he pr o gressi o n of a n d 
s ur vi val fr o m t he diseas e (K yle a n d Raj k u mar  2 0 0 8 ).  T he mec h a nis m of a n e mia of c hr o ni c 
disease i n w hic h ir o n h o me ostasis is i m paire d u n derlies t hat of M M -relate d a ne mia.  The m ost 
c o m m o n f or m of a ne mia i n M M is a ne mia of c hr o nic disease (als o referre d as a ne mia of 
i nfla m mati o n), c haracteri ze d b y i na de q u ate pr o d u cti o n a n d bl u nte d res p o nse t o E P O , i n hi biti o n 
of re d cell pr o ge nit ors, re d uce d re d cell s ur vi val a n d i m pair me nt of ir o n meta b olis m, a n d, 
c o nse q ue n tl y, ir o n-restricte d er yt hr o p oiesis, w hic h is i n d uce d b y t he ke y ir o n re g ulat or he p ci di n 
(G o o d n o u g h 2 0 0 7 , Weiss a n d G o o d n o u g h 2 0 0 5 ). 
2. 1. 3.  
A ne mi a i n P atie nts  Wit h M yel o d ys pl astic  S y n dr o me s a n d M ulti ple M yel o m a  
2. 1. 3. 1.  
P atie nts  Wit h M yel o d ys pl astic S y n dr o me s 
T he m ost fre q ue nt cli nical pr o ble m o bser ve d i n p atie nts wit h M D S  is a ne mia (Malc o vati 
et al 2 0 0 8 ).  A ne mia ca n us uall y be i m pr o ve d b y E S As  a n d/ or R B C  tra nsf usi o ns (Par k 
et al 2 0 0 8 ).  T he o bje cti ves of tra nsf usi o n t hera p y are t o mai ntai n q ualit y of life a n d pre v e nt 
a ne mia-relate d m or bi dit y a n d m ortalit y.  H o we ver, reg ular tr a nsf usi o ns ca n lea d t o ir o n 

I nc yte C orp orati o n  
Pa ge 2 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
o verl oa d, w hic h is fre q ue ntl y e nc o u ntere d i n M D S a n d affects  b ot h t he o verall s ur vi val a n d L F S  
(Malc o vati et al  2 0 0 5 ) a n d ca n ha v e p ote ntiall y seri o us cli nical c o nse q ue n ces. 
Pr ol o n ge d R B C  tra nsf usi o n t hera p y a p p ears t o be t he mai n c o ntri b ut or of ir o n o verl oa d, b ut 
ma n y patie nts a p pear t o de vel o p it at a n earl y sta ge of t he diseas e, bef ore t he o nset of 
tra nsf usi o ns (C ortelezzi et al 2 0 0 0 ).  P ullar kat ( 2 0 0 9 ) h y p ot hesize d t hat a n altere d pr od u cti o n of 
he pci di n, t he ke y h or m o n e re g ulati n g ir o n  h o me ostasis  (Ga nz a n d Ne met h  2 0 1 1 ), ma y pla y a 
r ole i n t his re gar d. 
2. 1. 3. 2.  
P atie nts  Wit h M ulti ple M yel o m a  
T he a ne mia i n patie nts wit h M M is us uall y n or m oc ytic/ n or m oc hr o mic (K yl e et al 2 0 0 3 ), wit h 
n or mal t o l o w ser u m ir o n le vels, ele vate d s er u m ferriti n le vels, a n d pr o mi ne nt he m osi deri n i n 
B M  macr o p ha ges ( Oz k urt et al 2 0 1 0 ).  T his s u g gests t ha n ir o n release fr o m retic ul oe n d ot helial 
macr o p ha g es is i m paire d, c o nsiste nt wit h a ne mia of i nfla m mati o n (Ar ma n d et al 2 0 0 7 ).  T he 
mai n me diat or of a n e mia of i nfla m mati o n is t he ir o n -re g ulat or y h or m one h e pci di n .  Rece nt 
st u dies ha ve i n dicate d t h at t he pr o xi mal ca us e of d ysre g ulate d ir o n meta b olis m a n d a ne mia i n 
t hese patie nts is c yt o ki ne-i n d uce d u pre g ulati o n of he pci di n e x pressi o n.  Pat h ol o gic i n d ucti o n of 
he pci di n b y i nfla m mati o n ca uses h y p oferriti ne mi a, restricts t he ir o n s u p pl y f or er yt hr o p oi esis, 
a n d e ve nt uall y c a uses a n e mia ( Ga n z 2 0 1 9 ).  
T he ma na ge m e nt of a n e mia i n M M i ncl u des t he c o ntr ol of t he pri mar y dis ease a n d t h e utilizati o n 
of E S A al o ne or i n c o m bi nati o n wit h i ntra ve n o us ir o n or R B C  tra nsf usi o ns.  
•  R B C tra nsf usi o ns pr o d uce ra pi d i m pr o ve me nt of t he patie nt 's a ne mic c o n diti o n.  
U nf ort u natel y, t he effects of R B C tra nsf usi o ns are o nl y tra nsie nt a n d ca n be 
ass ociate d wit h se veral ris ks, i ncl u di n g i nfecti o ns a n d mil d t o e ve n life -t hreate ni n g 
i m m u n ol o gic reacti o ns.   
•  Alt h o u g h E S As s uc h as dar be p oeti n alfa a n d e p oeti n alfa were o nce rec o m me n de d f or 
t he ma na ge me nt of a ne mia i n patie nts wit h ca ncer, st u dies ha ve de m o nstrat e d a n 
i ncreas e d ris k of t hr o m b oe m b olic e ve nts (T o nia et al 2 0 1 2 ).  I n a d diti o n, 
a p pr o xi matel y o ne -t hir d of patie nts d o n ot res p o n d t o E S As, mai nl y d ue t o t he 
i m paire d ir o n utilit y a n d t he de vel o p me nt of ir o n-restricte d er yt hr o p oiesis occ urri n g 
eit her at dia g n osis or d uri n g treat me nt wit h E S As (G o o d n o u g h 2 0 0 7 ).  F urt her m ore, 
re p orts ha ve als o s u g gest e d decreas e d s ur vi val a n d i ncreas e d ris k of ca ncer 
pr o gressi o n or rec urre nce wit h t he use of E S As i n patie nts wit h ca ncer 
(Le yla n d -J o n es et al 2 0 0 5, Le yla n d -J o nes et al 2 0 1 6, T h o mas et al 2 0 0 8 , U ntc h 
et al 2 0 1 1 ). 
Alt h o u g h a ne mia is c o m m o n i n patie nts wit h M M, n o clear c o nse ns us e xists as t o t he use a n d 
i m pact of E S As o n o utc o me i n M M, a n d ra n d o mize d st u dies i n patie nts wit h M M are still 
li mite d (Ter p o s et al 2 0 1 5 ). 
2. 2.  
O ver vie w of I N C B 0 0 0 9 2 8 
2. 2. 1.  
I N C B 0 0 0 9 2 8 Mec h a nis m of Acti o n  
I N C B 0 0 0 9 2 8 re pres e nts a selecti ve i n hi bit or of A L K 2.  Cell -base d pr ofili n g i n dica te d t hat 
I N C B 0 0 0 9 2 8 i n hi bite d A L K 2, wit h a 1 2 -f ol d selecti vit y o ver A L K 1 a n d a n 1 8-f ol d selecti vit y 

I nc yte C orp orati o n  
Pa ge 2 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
a gai nst A L K 3 i n cell -b as e d assa ys.   I N C B 0 0 0 9 2 8 de m o nstrate d wea k I C5 0 p ote nc y a gai nst 
A L K 5 a n d A L K 6 bi o c he micall y .  I n h u ma n li ver cells, I N C B 0 0 0 9 2 8 i n hi bite d t he B M P -i n d uce d 
pr o d ucti o n of he pci di n i n b ot h H u h 7 cells  a n d h u ma n pri mar y he p at oc ytes (refer t o t he 
I N C B 0 0 0 9 2 8 I B f or f urt her details). 
2. 2. 2.  
I N C B 0 0 0 9 2 8 S afet y P h ar m ac ol o g y  
I N C B 0 0 0 9 2 8 ha d n o effect o n t he C N S or res pirati o n i n rats after a si n gle d ose; t he 
n o -o bser ve d -effect le v el was 1 0 0  m g/ k g, t he hi g hest d ose e val uat e d.  T he I C 5 0 f or h E R G 
i n hi biti o n was esti mate d t o be >  1 0 0  µ M, a n d a d mi nistrati o n of I N C B 0 0 0 9 2 8 t o d o gs as a si n gle 
oral d ose of 1 5  a n d 5 0 m g/ k g r es ulte d i n d ose -de p e n de nt i ncreases i n mea n heart rate ( mea n 
differe n ces of u p t o 1 7  a n d 7 0 beats/ mi n , res pecti vel y, o ver ti me-matc h e d c o ntr ols), wit h 
c o nc o mita nt decreases i n P R  i nter val, R R i nter val, a n d Q Tc ( Va n de Water) a n d bl o o d press ure 
at 5 0 m g/ k g  per da y.  T h e N O A E L was 1 5  m g/ k g base d o n t he s mall ma g nit u de of t he effects at 
t his d ose.  T he ca use of t he i ncrease d heart rate is u ncertai n.  
Gi ve n t he a bilit y t o m o nit or vital si g ns i n cli nical st u dies, t he ris k ass ociate d wit h I N C B 0 0 0 9 2 8 
a d mi nistrati o n  is e x pecte d t o be l o w. 
2. 2. 3.  
I N C B 0 0 0 9 2 8 P h ar m ac ol o g y S u m m ar y  
I n a ne mia m o use m o dels, t he li ver-s pecific deleti o n of eit her A L K 2 or A L K 3 ca n bl oc k t he 
i n d ucti o n of he pci di n pr o d ucti o n a n d i n d uce ir o n o verl oa d  (Stei n bic ker  et al  2 0 1 1 a).  B M P 
si g nali n g pla ys a ce ntral r ole i n dri vi n g he pci di n tra nscri pti o nal i n d ucti o n b y acti vati n g S M A D 
si g nali n g. 
I n st u dies usi n g naï ve C 5 7 B L/ 6 mice, I N C B 0 0 0 9 2 8 e x hi bite d c o nsiste nt P K  wit h e x p os ures t hat 
were i n li ne wit h t he d os es use d.  Tar get e n ga g e m e nt of I N C B 0 0 0 9 2 8 was pr o ve n b y st u dies 
s h o wi n g d ose-de pe n d e nt decreases i n t he dir ect tar gets of A L K 2  a n d p S M A D 1/ 5, a n d t hese 
decreases c orres p o n d e d t o plas ma c o nce ntrati o ns e xcee di n g t he i n vi v o p S M A D I C 5 0.  Li ke wise, 
he pci di n, t he d o w nstrea m tar get of p S M A D si g nali n g, was als o s u p presse d i n a d ose -de p e n de nt 
ma n ner b y I N C B 0 0 0 9 2 8. 
I N C B 0 0 0 9 2 8 is efficaci o us i n 2  m o use m o dels of he pci di n -dri ve n a ne mia.  I n t he 
B 1 6 F 1 0 -i n d uce d a ne mia m o del, I N C B 0 00 9 2 8  was a ble t o re d uce t he a n e mia br o u g ht o n b y 
i ntra perit o neal gr o wt h of B 1 6 F 1 0 cells i n a d ose-d e pe n de nt ma n n er, as i n di cate d b y i m pr o ve d 
R B C  c o u nts, H g b  le vels, a n d Hct le vels .  D os es of I N C B 0 0 0 9 2 8 t hat gi ve I C5 0 e x p os ure f or 
a p pr o xi matel y 9 h o urs are li kel y t o res ult i n i m pr o ve me nt i n s y m pt o ms of a ne mia.  Li ke wise , 
I N C B 0 0 0 9 2 8 als o was efficaci o us i n t he t ur pe nti n e -i n d uce d a ne mia m o del, w here mice d ose d 
wit h I N C B 0 0 0 9 2 8 ha d R B C  c o u nts , H g b le vels, a n d Hct  le vels si milar t o t h ose of n o na ne mic 
mice.  
T h e res ults fr o m t he i n vitr o a n d i n vi v o p har mac ol o g y st u dies (refer t o t he  I N C B 0 0 0 9 2 8 I B) 
i n dicate t hat I N C B 0 0 0 9 2 8 is a p ote nt, orall y bi oa vaila ble, a n d hi g hl y selecti ve s mall m olec ule 
i n hi bit or of A L K 2.  D ysr e g ulati o n of the ir o n h o m e ostasis re g ulat or he p ci di n ca n res ult i n ir o n 
deficie nc y a n d a n e mia.  He pci di n le vels ha v e bee n f o u n d t o be ele vat e d i n patie nts wit h  a ne mias 
br o u g ht o n b y n u mer o us pri mar y diseases , i ncl u di n g ca ncer.  Acti vi n r ece pt or -li ke ki nase-2  
si g nali n g thr o u g h t he S M A D pat h wa y lea ds t o tra nscri pti o nal acti vati o n of he patic he p ci di n 
( H A M P ge ne), m a ki n g A L K 2 i n hi biti o n a p ote ntial t hera pe utic i nter ve nti o n p oint f or 
he pci di n -i n d uce d a ne mia. 

I nc yte C orp orati o n  
Pa ge 2 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
2. 3.  
St u d y R ati o n ale  
2. 3. 1.  
R ole of Acti vi n Rece pt or -Li ke Ki n ase -2  Re g ul ati n g t h e B o ne M or p h o ge netic 
Pr otei n P at h w a y  
B o ne m or p h o ge netic pr ot ei n bel o n gs t o t he tra nsf or mi n g gr o wt h fact or β  s u perfa mil y, a n d t he 
bi n di n g of B M P li ga n ds t o B M P rece pt or s lea ds t o t he asse m bl y of tetra m eric rece pt or 
c o m ple xes c o m p ose d of t y pe II rece pt ors ( B M P RII, A C T RII A, or A C T RII B) a n d t y pe I 
rece pt ors ( A L K 1, A L K 2, A L K 3, or A L K 6).  T he acti vate d B M P rece pt or c o m ple x 
p h os p h or ylates S M A D pr otei ns s uc h as S M A D1/ 5/ 8 , w hic h t he n ass ociate wit h c o -S M A D s a n d 
tra nsl ocate t o t he n u cle us t o re g ulate ge n e tra nscri pti o n (Bl o be et  al 2 0 0 0 , R oss et al  2 0 1 2 ). 
Acti vi n rece pt or -li ke ki n ase-2  has b ee n re p orte d t o me dia te m ulti ple h u ma n diseases, i ncl u di n g 
fi br o d ys plasia ossifica ns pr o gressi v a, diff us e i ntri nsic p o nti ne gli o ma, a n d ca ncer ( Mass a g u é a n d 
W ott o n  2 0 0 0 , Ta yl or et al 2 0 1 4 ).  I m p orta ntl y, A L K 2 has  bee n s h o w n t o pl a y a n esse ntial r ol e i n 
re g ulati n g he pci di n le vels a n d ma y c o ntri b ute t o a ne mia of c hr o ni c diseases a n d a ne mia d ue t o 
he mat ol o gic mali g na ncies i n w hic h ele vati o n of h e pci di n le vels has bee n o bser ve d 
(A n dri o p o ul os et  al 2 0 0 9 , Gallitz et al 2 0 1 8 , Me y nar d et al 2 0 0 9 , Stei n bic ker et al 2 0 1 1a , 
Stei n bic ker et  al 2 0 1 1 b ). 
2. 3. 2.  
R ole of He pci di n i n M yel o d ys pl astic S y n dr o me –  a n d M ulti ple M yel o m a – Rel ate d 
A ne mi a  
He pci di n is a s mall pe pti de h or m o ne pri maril y s y nt hesize d i n he pat oc yt es t hat re d uces b ot h 
d u o de nal ir o n a bs or pti o n a n d ir o n e x p ort fr o m m o n oc ytes a n d macr o p ha g es b y bi n di n g t o a n d 
i n d uci n g t he i nter nalizati o n a n d de gra d ati o n of t he ir o n e x p orter ferr o p orti n (Ne met h et  al 2 0 0 4 , 
T he url et al 2 0 1 1 , Weiss  a n d G o o d n o u g h  2 0 0 5 , Z ha o et al 2 0 1 3 ).  T h e ele vate d ser u m he p ci di n 
le vels e n ha nce st ora g e of ir o n wit hi n t he retic ul oe n d ot helial s yste m a n d res ult i n re duce d ir o n 
a vaila bilit y an d ir o n -restricte d er yt hr o p oiesis.  I n a p pr o priatel y i ncrease d h e pci di n e x pressi o n 
ca uses se v ere f u ncti o nal ir o n deficie n c y a ne mia i n h u ma ns a n d is ce ntral t o t he pat h o p h ysi ol o g y 
of a ne mia of c hr o nic dise ase  (Weiss a n d G o o d n o u g h 2 0 0 5 ). 
I n vi v o, tar get e n g a ge me nt of I N C B 0 0 0 9 2 8 was s h o w n b y d ose -de p e n de nt p S M A D 1/ 5 re d ucti o n 
i n t he m o use li ver, wit h a c orres p o n di n g d ecrease i n plas ma he pci di n le vels (I C5 0 ≈ 2 0 0 n M at 
4  h o urs after a si n gle oral d ose).   
H o me ostatic c o ntr o l of h e pci di n b y ir o n was o bser ve d t o be disr u pte d i n m ost M D S s u bt y pes a n d 
al m ost c o m pletel y l ost i n c o n diti o ns wit h pr o mi ne nt d ys m yel o p oiesis s uc h as refract or y a ne mia 
wit h e xcess blasts  a n d i n C M M L  (Sa nti ni et al  2 0 1 1 b ).  I n c o ntrast, p atie nts wit h R A R S  were 
f o u n d t o ha ve l o wer he pci di n le vels.  T his fi n di n g was c orr o b orate d b y t h e o bser vati o n t hat 
he pci di n e x pressi o n is s u p presse d b y a v aria nt of E R F E , w hic h is restrict e d t o S F 3 B 1 s plici n g 
fact or g e ne m utate d R A R S (B o n d u et al 2 0 1 9 ). 
T he ca us e of a n e mia i n patie nts wit h M M is m ultifact orial :  B M i nfiltrati o n b y t he m yel o ma 
itself lea ds t o re d uce d n u m bers of er yt hr oi d prec urs ors, E P O deficie nc y (i n patie nts wit h re nal 
i m pair me nt), decrease d res p o nsi ve ness of t he pr o-er yt hr o blasts a n d c ol o n y-f or mi n g 
u nit – er yt hr oi d cells t o E P O , i m paire d ir o n utilizati o n d ue t o i ncreas e d pr o d ucti o n of he pci di n 
beca use of c hr o ni c i nfla m ma ti o n, a n d para pr ot ei n-i n d uce d i ncrease of t he plas ma v ol u me (K ö ni g 
et al 2 0 1 3). 

I nc yte C orp orati o n  
Pa ge 2 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Ser u m he pci di n le vels ha ve bee n s h o w n t o b e si g nifica ntl y hi g her i n patie nts wit h M M c o m pare d 
wit h  healt h y i n di vi d uals a n d a ge -m atc he d c o ntr ols ( I brice vi c-Balic et al 2 0 1 6 , Maes  et al 2 0 1 0 , 
Vict or et al 2 0 1 7 ).  Patie nts wit h sta ge III M M  at dia g n osis ha d hi g her uri n ar y he pci di n le vels 
t ha n n or mal c o ntr ols.  He pci di n ser u m le vels are i n versel y c orrelat e d wit h H g b c o nce ntr ati o ns i n 
patie nts wit h M M ( Kat o drit o u et al 2 0 0 8 ) a n d i n p atie nts wit h M M w h o ha ve  n or mal re n al 
f u ncti on , i n dicati n g a p ossi ble c o ntri b uti o n of i ncrease d he p ci di n le vels t o t he pat h o ge nesis of 
a ne mia i n M M (Maes  et al 2 0 1 0 ).  F urt h er m ore, i n patie nts wit h M M w h o ha ve  n or mal r e nal 
f u ncti o n, uri nar y he p ci di n le vel was i n vers el y c orrelate d wit h H g b le vel at dia g n osis, a n d a  
str o n g ass ociati o n bet wee n u pre g ulate d h e pci di n e x pressi o n a n d a ne mia h as bee n de m o nstr ate d 
i n patie nts wit h a d va nce d -sta ge M M, s u g gesti n g a ca usal r elati o ns hi p bet wee n u pre g ulate d 
he pci di n e x pressi o n a n d a ne mia.  Uri nar y he p ci di n le vels als o si g nifica ntl y c orrel ate d wit h 
ser u m ferriti n a n d C R P  le vels (S har ma et al 2 0 0 8 ). 
H A M P (t he ge ne c o di n g f or he pci di n) m R N A e x pressi o n i n P B M Cs  a n d plas ma he pci di n le vels 
i n patie nts wit h M M are all si g nifica ntl y i ncrease d w he n  c o m pa re d wit h  t h ose i n c o ntr ol 
s u bjects.  I n patie nts wit h M M, t he e x pressi o n of H A M P m R N A s h o we d a p ositi ve c orrelati o n 
wit h ser u m ferriti n le vel a n d a ne g ati ve c orrelati o n wit h H g b le vel.  O vere x pressi o n of H A M P 
m R N A i n P B M Cs si g nifica ntl y c orrelate d wit h i nc rease d pl as ma he pci di n l e vel a n d ma y b e 
i n v ol ve d i n t he pat h o ge n esis of M M-relat e d a ne mia (Mei et al 2 0 1 4 ). 
I n hi biti o n of A L K 2, a n u pstrea m re g ulat or of he p ci di n, s h o ul d i ncrease cir c ulati n g ir o n le vels 
a n d i m pr o ve a ne mia.   I N C B 0 0 0 9 2 8 has p ote nt acti vit y a gai nst t he A L K 2 ki nase a n d i n hi bits 
B M P -i n d uce d he pci di n pr o d ucti o n.  I n s u m mar y, I N C B 0 0 0 9 2 8 s h o ul d re d uce he p ci di n le vels, 
i ncreas e ir o n a vaila bilit y, a n d i m pr o ve a ne mia i n p artici pa nts wit h M D S a n d M M. 
2. 3. 3.  
Scie ntific R ati o n a le f or St u d y Desi g n 
T his is a P hase 1/ 2 , o pe n -la bel st u d y t o e val uate t he safet y, P K, P D, a n d efficac y (a ntia ne mic 
acti vit y) of I N C B 0 0 0 9 2 8 a d mi nistere d as a m o n ot hera p y i n partici pa nts wit h M D S or M M w h o 
are tr a nsf usi o n -de p e n de nt or prese nt wit h s y m pt o matic a ne mia . 
I N C B 0 0 0 9 2 8 ta blets will be a d mi nistere d orall y at a starti n g d ose of 5 0  m g Q D.  O ne c y cle will 
be defi ne d as 2 8 c o nsec uti ve da ys; treat me nt will c o nsist of re peati n g 2 8 -da y c ycles.  
T he prese nt st u d y will e v al uate i ncreasi n g d oses of I N C B 0 0 0 9 2 8 a d mi nistere d as a si n gle a ge nt 
i n t he d ose-escalati o n sta ge.  T he d ose -escalati o n/ de -escalati o n sta ges will use a n o pe n -l a bel 
B OI N al g orit h m.  
O nce a n a p pr o pri ate d ose has bee n det er mi ne d t o be safe a n d t olera bl e i n t he d ose -es calati o n 
sta ge ( R D E[s]), t he d ose e x pa nsi o n will start a n d partici pa nts w it h M D S a n d M M w h o are 
tra nsf usi o n-de p e n de nt or prese nt wit h s y m pt o matic a ne mia will recei ve I N C B 0 0 0 9 2 8 at eac h 
R D E.  T he e x pa nsi o n sta ges will ai m t o f urt her assess t he safet y a n d t olera bilit y of I N C B 0 0 0 9 2 8, 
assess its  P K a n d P D,  a n d deter mi n e its a ntia nemi c acti vit y i n partici pa nts  w h o are 
tra nsf usi o n-de p e n de nt or prese nt wit h s y m pt o matic a ne mia d u e t o M D S or M M  i n a parallel a n d 
i n de pe n de nt fas hi o n i n e ac h diseas e gr o u p (see Secti o n 4. 1 ). 
2. 3. 4.  
J ustific ati o n f or St arti n g D ose  
A P hase 1, d o u ble -bli n d, ra n d o mize d, place b o -c o ntr olle d, si n gle -d ose, d ose -escal ati o n a n d 
f o o d-effect st u d y is bei n g c o n d ucte d wit h I N C B 0 0 0 9 2 8 t o assess t he safet y, t olera bilit y, a n d P K 

I nc yte C orp orati o n  
Pa ge 2 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
of I N C B 0 0 0 9 2 8 w he n a d mi nistere d orall y as a si n gle d ose t o healt h y a d ult partici pa nts 
( St u d y I N C B 0 0 9 2 8 -1 0 1).  
Refer t o t he I N C B 0 0 0 9 2 8 I B.  
F oll o wi n g  si n gle oral d os e a d mi nistrati o n, I N C B 0 0 0 9 2 8 was ra pi dl y a bs or be d, wit h me dia n t ma x  
o bser ve d at 2. 0 t o 4. 1  h o urs p ost d ose i n plas ma a n d acr oss t he d ose ra n g e of 1 0 t o 5 0 0  m g.  A 
hi g h -fat meal dela ye d I N C B 0 0 0 9 2 8 me dia n tma x  b y 1  h o ur; h o we ver, it di d n ot statisticall y 
si g nifica ntl y c ha n ge C ma x  or A U C ( p  =  0. 2 7 8 8).  T he ge o metric mea n rati os ( 9 0 % CIs) f or C ma x  
a n d A U C ∞ were 0. 9 7 7 ( 0. 9 0 5, 1. 0 5 5) a n d 1. 0 3 1 ( 0. 9 6 8, 1. 0 9 8), res pecti vel y; b ot h 9 0 % CIs were 
wit hi n t he " n o effect li mits" of 0. 8 0 t o 1. 2 5, s u g gesti n g I N C B 0 0 0 9 2 8 ca n b e a d mi nistere d 
wit h o ut re gar d t o f o o d . 
T he pr o p ose d starti n g d ose f or St u d y  I N C B 0 0 9 2 8 -1 0 5  is 5 0 m g Q D as a m o n ot hera p y.  I n 
a gree m e nt  wit h t he pri nci ples o utli ne d i n I C H S 9 ( 2 0 1 0 ) f or selecti n g t he starti n g d ose f or 
cli nical trials i n patie nts wit h ca ncer a n d F D A G ui da nce f or I n d ustr y : Se verel y De bilitati n g or 
Life -T hreate ni n g H e mat ol o gic Dis or ders:  N o ncli nical De vel o p me nt of P h ar mace uticals ( 2 0 1 9 ), 
the pr o p ose d starti n g d os e f or I N C B  0 0 9 2 8 -1 0 5  is 5 0 m g Q D, w hic h was s electe d base d o n 
a vaila ble cli nical e x p os ur e data fr o m I N C B  0 0 9 2 8 -1 0 1 t o pr o vi de a d ose t h at is a ntici pate d t o be 
b ot h p har mac ol o gicall y acti ve a n d reas o na bl y safe f or use.  Base d o n t h e P K data fr o m t he 
healt h y partici pa nts i n St u d y I N C B  0 0 9 2 8 -1 0 1, t he A U C t (t otal) at 5 0 m g Q D is 3. 7 7 μ M ∙h (t he 
A U C i nf is 3. 8 6 μ M ∙h) a n d t he C ma x (t otal) is 0. 1 8 4 μ M.   T his C ma x  val ue a p pr o xi mates t he i n vi v o 
I C5 0 o btai ne d i n a ca ncer -i n d uce d m o use a n e mia m o del ( 2 0 0 n M) a n d is t h us a ntici pate d t o be 
p har mac ol o gicall y acti ve.   T he A U C a n d C ma x  val ues at 5 0 m g Q D are ≥ 3. 2 -f ol d a n d ≥ 1 1. 3-f ol d 
l o wer, res p ecti vel y, t ha n e x p os ures ass o ciate d wit h t he N O A E Ls i n 2 8-da y pi v otal t o xic ol o g y 
st u dies i n rats a nd d o gs;  t h us, t his d ose is a ntici pate d t o be reas o na bl y safe f or use. 
D ose escalati o n will pr ocee d f oll o wi n g re vi e w of s afet y i nf or mati o n a n d P K data c ollecte d as t he 
st u d y pr o gresses, as d escri be d i n Secti o n  4. 1  a n d Secti o n  6. 5 . 
T he decisi o n o n t he R D E (s) a n d f ut ur e de v el o p me nt will i nc or p orate safet y, P K, a n d P D data, as 
a vaila ble, o btai ne d d uri n g t his st u d y.  
2. 3. 5.  
U p d ate d D at a F r o m O n g oi n g Cli nic al Tri als   
St u d y I N C B  0 0 9 2 8 -1 0 2 is a si n gle -ce nter, ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, 
s p o ns or-u n bli n de d,  m ulti ple -d ose, P hase 1 st u d y d esi g ne d t o e val uate t h e safet y, t olera bilit y, P K, 
a n d P D of escalati n g oral d oses of I N C B 0 0 0 9 2 8  i n healt h y a d ult partici pa nts. 
Refer t o t he I N C B 0 0 0 9 2 8 I B. 
At t he ti me of data c ut off ( 2 9 O C T 2 0 2 1), 6 0  parti ci pa nts ha ve recei ve d at l east 1  d ose of bli n de d 
st u d y dr u g ( u p t o 4 0 0 m g I N C B 0 0 0 9 2 8 or place b o).  
T here h a ve bee n n o deat hs, ot her seri o us T E A Es, or T E A Es lea di n g t o disc o nti n uati o n fr o m 
st u d y dr u g.  T we nt y -t w o partici pa nts ( 3 6. 7 %) re p orte d at  least 1 T E A E.  T h e m ost fre q ue ntl y 
re p orte d T E A Es were me dical de vice site reacti o n (re p orte d t er m: "c o ntact der matitis at 
electr o de site(s)" fr o m t h e lea ds of t he E C G m o nit or) i n 9  partici pa nts ( 1 5. 0 %), c o nsti pati o n i n 
3  partici pa nts ( 5. 0 %), a n d hea dac he  i n 2 partici p a nts ( 3. 3 %). All ot her T E A Es occ urre d i n 
1  partici pa nt eac h . 

I nc yte C orp orati o n  
Pa ge 2 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Preli mi nar y P K data a n d a nal ysis fr o m t his m ulti ple asce n di n g d ose st u d y are a vaila bl e f or 
4 4  healt h y partici pa nts w h o ha ve recei ve d 5 0, 1 0 0, 1 5 0, 2 0 0, or 4 0 0  m g I N C B 0 0 0 9 2 8 Q D orall y 
f or 1 0 da ys.   I N C B 0 0 0 9 2 8 ac hie ve d Cma x  at a me dia n t ma x  of 2 t o 4  h o urs p ost d ose a n d was 
eli mi nate d i n a bie x p o ne ntial fas hi o n, wit h a mea n t ½  ra n gi n g fr o m 2 4. 2 t o 2 6. 7 h o urs (see  
Ta ble  5 ).  T he m ea n acc u m ulati o n rati o was 2. 0 1 - t o 2. 1 6-f ol d acr oss t he d ose ra n ge. 
I N C B 0 0 0 9 2 8 reac h e d stea d y state ar o u n d Da y 5 t o Da y  7.  S u pra pr o p orti o nalit y was o bser ve d 
fr o m 5 0 t o 4 0 0 m g Q D; h o we ver, I N C B 0 0 0 9 2 8 plas ma e x p os ures see me d t o i ncreas e 
pr o p orti o nal t o d ose as t h e d ose i ncrease d fr o m 1 5 0 t o 4 0 0  m g Q D . 
T a ble  5 : 
S u m m ar y of Preli mi n ar y Ste a d y -St ate P h ar m ac o ki netic P ar a meters f or 
I N C B 0 0 0 9 2 8 o n D a y 1 0 ( St u d y I N C B  0 0 9 2 8 -1 0 2)  
P a r a meter  
D ose ( m g)  
5 0  
( N = 9) 
1 0 0  
( N = 8a) 
1 5 0  
( N = 9) 
2 0 0  
( N = 9) 
4 0 0  
( N = 9) 
C ma x  ( n M) 
3 9 1 ± 1 1 6  
( 3 7 5, 3 1. 0 %) 
6 3 5 ± 1 8 9  
( 6 0 5, 3 6. 0 %) 
1 4 7 0 ± 2 8 8  
( 1 4 5 0, 1 8. 5 %) 
1 8 5 0 ± 3 9 3  
( 1 8 1 0, 2 4. 4 %) 
4 4 0 0 ± 1 1 7 0  
( 4 2 7 0, 2 5. 6 %) 
tma x  ( h) 
2. 0 ( 2. 0, 4. 0)  
4. 0 ( 2. 0, 4. 0) 
2. 0 ( 1. 0, 4. 0)  
2. 0 ( 1. 0, 4. 0)  
4. 0 ( 2. 0, 4. 0)  
C mi n  ( n M) 
1 4 1 ± 2 6. 4  
( 1 3 9, 1 8. 8 %) 
2 4 1 ± 8 9. 9  
( 2 2 1, 5 3. 2 %) 
4 7 7 ± 9 0. 9  
( 4 6 8, 2 0. 3 %) 
6 8 6 ± 2 0 8  
( 6 5 9, 3 0. 5 %) 
1 8 9 0 ± 6 5 5  
( 1 8 0 0, 3 2. 5 %) 
A U C  ( h· n M) 
5 5 4 0 ± 1 1 5 0  
( 5 4 3 0, 2 1. 3 %) 
9 3 3 0 ± 2 9 4 0  
( 8 8 8 0, 3 5. 9 %)  
1 9, 6 0 0 ± 2 2 6 0  
( 1 9, 5 0 0, 1 2. 0 %) 
2 7, 2 0 0 ± 6 5 6 0  
( 2 6, 5 0 0, 2 5. 3 %) 
7 0, 2 0 0 ± 1 9, 7 0 0  
( 6 8 1 0 0, 2 5. 9 %) 
t½  ( h) 
2 6. 7 ± 2. 8 8  
( 2 6. 6, 1 0. 7 %) 
2 6. 4 ± 2. 8 4  
( 2 6. 3, 1 1. 3 %) 
2 4. 2 ± 2. 5 6  
( 2 4. 0, 1 0. 6 %) 
2 5. 9 ± 4. 0 0  
( 2 5. 6, 1 5. 4 %) 
2 6. 2 ± 2. 9 6  
( 2 6. 1, 1 0. 9 %) 
C L ss/ F ( L/ h) 
1 8. 7 ± 3. 9 5  
( 1 8. 3, 2 1. 3 %) 
2 3. 7 ± 9. 5 8  
( 2 2. 4, 3 5. 9 %) 
1 5. 4 ± 1. 9 1  
( 1 5. 3, 1 2. 0 %) 
1 5. 5 ± 4. 0 0  
( 1 5. 0, 2 5. 3 %) 
1 2. 0 ± 2. 7 9  
( 1 1. 7, 2 5. 9 %) 
V z/ F ( L) 
7 2 1 ± 1 7 5  
( 7 0 2, 2 4. 0 %) 
9 2 0 ± 4 4 5  
( 8 4 9, 4 2. 8 %) 
5 3 8 ± 9 5. 2  
( 5 3 0, 1 8. 5 %) 
5 6 7 ± 1 2 2  
( 5 5 6, 2 0. 9 %) 
4 5 5 ± 1 2 3  
( 4 4 0, 2 8. 6 %)  
Acc u m ulati o n 
i n de x 
2. 1 6 ± 0. 1 6 8  
( 2. 1 5, 7. 7 3 %) 
2. 1 4 ± 0. 1 6 5  
( 2. 1 3, 7. 9 5 %) 
2. 0 1 ± 0. 1 4 8  
( 2. 0 0, 7. 3 7 %) 
2. 1 1 ± 0. 2 3 3  
( 2. 1 0, 1 0. 9 %) 
2. 1 3 ± 0. 1 7 2  
( 2. 1 2, 7. 8 6 %) 
N ote: Val u es are prese nte d as mea n ± S T D ( ge o metric mea n, ge o metric perce nt c oefficie nt of variati o n) e xce pt f or t ma x , w hic h is 
re p orte d as me dia n ( mi n, ma x). 
a O ne partici p a nt was e xcl u de d fr o m t h e s u m mar y d ue t o si g nifica ntl y l o w e x p os ure le vels o n Da y 1 0 t h at a wait f urt her 
i n vesti gati o n. 
2. 4.  
Be nefit/ Ris k Assess me nt  
2. 4. 1.  
P ote nti al Ris ks of I N C B 0 0 0 9 2 8 B ase d o n Precli nic al T o xic ol o g y  
T he t o xic ol o gic a n d t o xic o ki netic pr ofile of I N C B 0 0 0 9 2 8 was c haracterize d i n a si n gle -d ose d o g 
st u d y a n d i n re peat or al d ose st u dies of u p t o 2 8 da ys i n d urati o n i n rats a n d d o gs.  P ote ntial 
ge netic t o xicit y was e v al uate d i n a bacterial m uta ge nicit y assa y, a n i n vitr o micr o n ucle us assa y, 
a n i n vi v o micr o n ucle us a n d c o met assa y, a n d a micr o n uclei assess me nt i n t he 2 8 -da y G o o d 
La b orat or y Practice s rat st u d y.  P h ot ot o xicit y was eval uate d i n vitr o a n d i n vi v o.  
Tar get tiss ues i de ntifie d i n 2 8 -da y t o xicit y st u dies i n b ot h rats a n d d o gs i ncl u de t he GI tr act, 
li ver, s plee n, s ki n ( hair f ollicles), a n d B M .  Effects o n t he li ver i ncl u de d i n creas e d ir o n le vels a n d 
i nfla m mat or y c ha n g es a n d, at hi g h d oses, sec o n dar y he pat ocell ular effects a n d i ncrease d 
A L T/ A S T le vels.  I ncrease d he mat o p oiesis was o bser ve d i n t he B M  i n b ot h s pecies, a n d 
e xtra me d ullar y h e mat o p oiesis was o bser ve d i n t h e s plee n a n d li ver of rats.  Effects o n t he GI 
tract were pri maril y m uc osal h y pertr o p h y/ h y per pl asia, wit h sec o n dar y i nfla m mat or y fi n di n gs 

I nc yte C orp orati o n  
Pa ge 2 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
a n d c ha n g es i n t he drai ni n g mese nteric l y m p h n o d e.  S ki n c ha n ges w ere rel ate d t o effects o n hair 
f ollicles (arrest i n t he a na ge n p hase). 
T hese fi n di n gs were c o nsiste nt wit h I N C B 0 0 0 9 2 8 i n hi biti o n of A L K 2 at l o wer d oses a n d A L K 3 
at hi g her d oses.  A cti vi n rece pt or -li ke ki nase-2 , a t y pe I rece pt or f or B M Ps, pla ys a n i m p orta nt 
r ole i n t he d o w nstrea m si g nali n g of m ulti ple B M Ps.  B o ne m or p h o ge netic pr otei n  si g nali n g 
t hr o u g h A L K 2 has bee n de m o nstrate d t o pla y a cr ucial r ole i n ir o n re g ul ati o n (Stei n bic ker 
et al 2 0 1 1 b ).  A d diti o nall y, B M P si g nali n g t hr o u g h A L K 3, a relate d B M P t y pe I rece pt or, is 
i n v ol ve d i n ir o n re g ulati o n (Stei n bic ker et al 2 0 1 1 a) b ut is als o i n v ol ve d i n t he pr oliferati o n of 
t he i ntesti nal m uc osa (Va n u ytsel et al 2 0 1 3 ) a n d h air f ollicle gr o wt h a n d differe ntiati o n 
(A n dl  et al 2 0 0 4 , Mi n g  K wa n et  al 2 0 0 4 ), a m o n g ot her effects.  I N C B 0 0 0 9 2 8 is a p ote nt i n hi bit or 
of A L K 2 (I C 5 0  = 2 0 n M) , wit h 5 8 -f ol d selecti vit y o ver A L K 3 i n bi oc h e mical assa ys.  T he ref ore, 
alterati o ns i n ir o n meta b olis m are li kel y relate d t o A L K 2 i n hi biti o n at l o wer d oses a n d b ot h 
A L K 2 a n d A L K 3 at hi g her d oses, w hile fi n di n gs r elate d t o hair a n d t h e GI  tract are li kel y rel ate d 
t o AL K 3 i n hi biti o n at hi g her d oses.  
I n t he d o g st u dies, d ose-relate d i ncreases i n heart rate, decreas es i n l y m p h oi d cell ularit y i n t he 
l y m p h oretic ular s yste m, h y pertr o p h y/ h y per plasi a i n t he gall bla d der, a n d, i n 1 a ni mal, decrease d 
re d cell mass w ere als o o bser ve d.  I n t h e 1 4-da y st u d y at hi g h d oses, p at h ol o gic effects i n t he 
heart a n d v asc ulat ure were c o nsi dere d p ote ntiall y sec o n dar y t o t he effects o n heart rate 
(J o nes et al 2 0 1 3 ).  I n t he 2 8-da y st u d y i n d o gs, t he N O A E L was 5 m g/ k g  per da y bas e d o n a n 
i ncreas e i n i nfla m mat or y c ha n ges i n t he li ver at 1 5 m g/ k g per da y.  
I n rats, a d diti o nal fi n di n gs i ncl u de d decrease d re d cell mass, decreas e d cell ularit y of t he 
l y m p h oretic ular s yste m, a dre nal c ortical h y pertr o p h y, i ncreas e d heart wei g hts wit h o ut 
micr osc o pic c orrelates, m i ni mal t o sli g ht al ve olar i nfla m mati o n a n d mi ni mal al ve olar 
macr o p ha g es i n t he l u n g, a n d c ha n g es i n t he u p per a n d l o wer i ncis ors.  T h e i ncis or fi n di n gs were 
li kel y a res ult of i n hi biti o n of A L K 2 a n d A L K 3, b ot h of w hic h are i m p orta nt i n de vel o p me nt a n d 
gr o w t h of teet h ( A n dl et  al 2 0 0 4 , Wa n g et al 2 0 1 2 ).  I n rats, i ncis ors gr o w a n d differe ntiat e 
t hr o u g h o ut t he life of t he a ni mal a n d are re n e we d e ver y 4 0 t o 5 0 da ys (K uij pers et al 1 9 9 6 ).  T h e 
fi n di n gs o bser ve d i n t he rat i ncis ors were s pecifi c t o acti vel y gr o wi n g teet h, a n d n o fi n di n gs were 
o bser ve d i n t he rat m olar, w hic h are p er ma n e nt n o n gr o wi n g str uct ures.  Gi v e n t hat a d ult h u ma n 
teet h are f ull y f or med b y t he mi d -tee n years, rat i n cis or fi n di n gs are n ot c o nsi dere d rel e va nt to 
a d ult h u ma n ris k assess me nt.  
I n rats, m ost of t he treat me nt-relate d fi n di n gs were re v ersi ble, alt h o u g h effects o n ir o n st ora g e i n 
t he li ver a n d s plee n p ersiste d w hile c ha n ges i n t he i ncis or teet h i nc o m pletel y re verse d or ha d 
pr o gresse d at t he e n d of t he rec o v er y p hase.  I n d o g s, m ost of t hese fi n di n gs als o re verse d wit h 
t he e xce pti o n of t he s ki n a n d li ver fi n di n gs, i ncl u di n g A S T a n d A L T acti vities, w hic h re mai n e d 
ge nera ll y t he s a me or pr o gresse d d uri n g t he rec o v er y p hase. 
I N C B 0 0 0 9 2 8 is n ot m uta ge nic, base d o n t he res ults of a  bact erial m uta ge ni cit y assa y.  
Alt h o u g h I N C B 0 0 0 9 2 8 i n d uce d micr o n ucl ei i n a n i n vitr o h u ma n l y m p h oc yte micr o n ucle us 
assa y, t he i n vi v o rat micr o n ucl e us a n d c o met assa y de m o nstrate d t hat I N C B 0 0 0 9 2 8 is n ot 
clast o ge nic or a ne u ge ni c.  A d diti o nall y, n o i n d ucti o n of micr o n uclei w as o bser ve d i n t he 2 8 -d a y 
oral t o xicit y st u d y i n rats.  Base d o n t hese c ollecti ve fi n di n gs, I N C B 0 0 0 9 2 8 is n ot c o nsi dere d t o 
be ge n ot o xic.  
De vel o p me ntal a n d re pr o d ucti ve t o xicit y st u dies ha ve n ot bee n p erf or me d wit h I N C B 0 0 0 9 2 8. 

I nc yte C orp orati o n  
Pa ge 3 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
I N C B 0 0 0 9 2 8 is wea kl y p h ot ot o xic i n t he 3 T 3 m o use fi br o blast assa y, a n d i n vi v o, 3 0 0 m g/ k g  
per da y w as t he p h ot ot o xic N O A E L i n Bal b/c mice.  
All a d verse fi n di n gs i n n o ncli nical t o xic ol o g y st u dies were ass ociate d wit h e x p os ures t hat e x cee d 
t he a ntici pate d e x p os ures i n partici pa nts o ver t he pla n ne d d ose ra n ge.   
M ore detaile d i nf or mati o n a b o ut t he k n o w n e x pecte d be nefits a n d ris ks of I N C B 0 0 0 9 2 8 ma y be 
f o u n d i n t he I B.   
T he st u d y desi g n will ma xi mize partici pa nt safet y w hile i m p orta nt P K , P D, safet y, a n d efficac y 
i nf or mati o n is c ollecte d.  All A Es , i ncl u di n g he mat ol o g y, bl o o d c he mistr y, a n d L F T  
a b n or malities , a n d GI-ass ociate d A Es will be m o nit ore d i n all partici pa nts t o i de ntif y 
occ urre nces of a n y safet y c o ncer ns. 
2. 4. 2.  
P ote nti al Be nefit  
Ser u m he pci di n le vels are si g nifica ntl y i ncrease d i n patie nts wit h M D S a n d M M.  I n hi biti o n of 
A L K 2, a n u pstrea m re g ul at or of he p ci di n , s h o ul d i ncreas e cir c ulati n g ir o n le vels a n d i m pr o ve 
a ne mia.  I N C B 0 0 0 9 2 8 has p ote nt acti vit y a gai nst t he A L K 2 ki nase a n d i n hi bits B M P -i n d uce d 
he pci d i n pr o d ucti o n.   
St u d y  I N C B 0 0 9 2 8 -1 0 5 will i ncl u de o nl y partici pa nts wit h M D S or M M w h o are 
tra nsf usi o n-de p e n de nt or prese nt wit h s y m pt o matic a ne mia.   
Partici pa nts wit h M D S m ust be i neli gi ble t o recei v e or ha ve n ot res p o n de d t o a vaila ble t hera pies 
f or a ne mia, a n d partici p a nts wit h M M m ust ha ve faile d t o res p o n d t o sta n dar d treat me nts.   
I n s u m mar y, I N C B 0 0 0 9 2 8 m o n ot hera p y s h o ul d re d uce he p ci di n le vels, i ncrease ir o n a vaila bilit y, 
a n d i m pr o ve a ne mia i n p artici pa nts wit h M D S a n d M M .  
2. 5.  
E x p os ure  M ar gi ns  
T he A U C 0 -t a n d C ma x  val ues o btai ne d at t he N O A E L i n t he pi v otal 2 8 -da y rat a n d d o g st u dies are 
prese nte d i n Ta bl e  6 , a n d e x p os ure mar gi ns f or a 5 0 m g a n d 1 0 0 m g Q D d ose relati ve t o t he 
N O A E Ls i n t he 2 8 -da y st u dies are s u m mari ze d i n Ta ble  7 . 
T a ble  6 : 
A U C 0 -t a n d C m a x  V al ues ( T ot al ) f or I N C B 0 0 0 9 2 8 Ass oci ate d Wit h D oses T h at 
D o N ot C a use A d ve rse Effects i n 2 8 -D a y St u dies i n R ats a n d D o gs  
N O A E L  
R at  
D o gs  
1 0 m g/ k g/ d a y ( m ale ) a n d 3 0 m g/ k g/ d a y (fe m ale) 
5 m g/ k g/ d a y  
M ale  
Fe m ale  
M ale a n d Fe m ale ( A ver a ge)  
A U C 0 -t ( μ M∙h) 
1 8. 8  
2 1. 5  
1 1. 9  
C ma x  ( μ M) 
2. 1  
3. 8  
2. 1  

I nc yte C orp orati o n  
Pa ge 3 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  7 : 
E x p os ure M ar gi ns f or 5 0 m g a n d 1 0 0 m g Q D D ose Rel ati ve t o D oses T h at D o 
N ot C a use A d vers e Effects  i n 2 8 -D a y St u dies i n R ats a n d D o gs  
N O A E L  
R at  
D o gs  
1 0 m g/ k g/ d a y ( m ale) a n d 3 0 m g/ k g/ d a y (fe m ale)  
5 m g/ k g/ d a y  
M ale  
Fe m ale  
M ale a n d Fe m ale ( A ver a ge)  
5 0 m g Q D a 
A U C 0 -t 
5. 0  
5. 7  
3. 2  
C ma x  
1 1. 3  
2 0. 7  
1 1. 4  
1 0 0 m g Q D b 
A U C 0 -t 
2. 2  
2. 5  
1. 4  
C ma x  
4. 8  
8. 9  
4. 9  
N ote:  A U C 0 -t a n d C ma x  fr o m P K d ata o btai ne d fr o m healt h y partici pa nts (I N C B 0 0 9 2 8-1 0 1).  
a A U C (t otal) = 3. 7 7 μ M∙h, A U C ( u n b o u n d) = 0. 5 6 μ M∙h, C ma x  (t otal) = 0. 1 8 4 μ M, Cma x  ( u n b o u n d) = 0. 0 3 μ M. 
b A U C (t otal) = 8. 6 7 μ M∙h, A U C ( u n b o u n d) = 1. 2 8 μ M∙h, C ma x  (t otal) = 0. 4 2 9 μ M, Cma x  ( u n b o u n d) = 0. 0 6 μ M. 

I nc yte C orp orati o n  
Pa ge 3 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
3.  
O B J E C TI V E S A N D E N D P OI N T S  
Ta ble  8  pres e nts t he  detaile d  o bjecti ves a n d e n d p oi nts.  
T a ble  8 : 
O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
T o deter mi ne t he safet y a n d t olera bilit y of 
I N C B 0 0 0 9 2 8 m o n ot hera p y i n partici pa nts wit h M D S 
or M M . 
•  Fre q ue nc y a n d se verit y of A Es a n d S A Es, i ncl u di n g 
c ha n ges i n vital si g ns, E C Gs, p h ysical e xa mi nati o ns, 
a n d cli nical bl o o d a n d uri ne la b orat or y para meters.  
•  I de ntificati o n of t he D L Ts, M TD, a n d R D E (s). 
Sec o n d ar y  
T o deter mi ne t he efficac y of I N C B 0 0 0 9 2 8 i n 
partici pa nts wit h M D S or M M . 
F or b ot h M D S a n d M M dise ase gr o u ps:  
•  F or tra nsf usi o n-i n de pe n de nt partici pa nts at baseli ne:  
− T he pr o p orti o n of partici pa nts wit h a ne mia 
res p o nse, defi ne d as a n  H g b i ncrease of at least 
1. 5 g/ d L relati ve t o baseli ne f or a n y 8 -wee k 
peri o d ( wit h eac h assess me nt meeti n g t his 
re q uire me nt) d uri n g t he first 2 4 wee ks of 
treat me nt. 
− D urati o n of a ne mia res p o nse , defi ne d as t he 
i nter val fr o m t he first o nset of a ne mia res p o nse 
t o t he earliest date of l oss of a ne mia res p o nse 
t hat persists f or at least 4 wee ks or deat h fr o m 
a n y ca use. 
•  F or tra nsf usi o n-de pe n de nt  partici pa nts at baseli ne:  
− T he pr o p orti o n of partici pa nts wit h R B C -TI , 
defi ne d as t he a bse nce of a n y R B C  tra nsf usi o n 
f or at least 8 c o nsec uti ve wee ks d uri n g t he first 
2 4  wee ks of treat me nt.  
− D urati o n of R B C -TI peri o d f or partici pa nts 
ac hie vi n g R B C -TI f or at least 8 c o nsec uti ve 
wee ks d uri n g t he first 2 4 wee ks of treat me nt. 
•  Rate of R B C tra nsf usi o n t hr o u g h Wee ks 1 2  a n d 2 4 , 
defi ne d as t he a vera ge n u m ber of R B C u nits per 
partici pa nt -m o nt h d uri n g t he treat me nt peri o d.  
•  T he lar gest i ncrease fr o m baseli ne i n t he mea n H g b 
val ues o ver a n y r olli n g 8 -wee k treat me nt peri o d 
d ur i n g t he first 2 4 wee ks of treat me nt. 

I nc yte C orp orati o n  
Pa ge 3 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  8 : 
O bjecti ves a n d E n d p oi nts ( C o nti n ue d)  
O bjecti ves  
E n d p oi nts  
T o deter mi ne t he efficac y of I N C B 0 0 0 9 2 8 i n 
partici pa nts wit h M D S or M M (c o nti n ue d). 
F or M D S p artici p a nts o nl y:  
•  O verall res p o nse rate, defi ne d as t he pr o p orti o n of 
partici pa nts wit h C R or P R as per C hes o n et al  
(2 0 0 6 ) defi niti o ns f or M D S a n d as per Sa v o na et al  
(2 0 1 5 ) defi niti o ns f or M D S/ M P N o verla p 
s y n dr o mes, as a p plica ble. 
•  P F S, defi ne d as t he i nter val fr o m t he first d ose of 
st u d y dr u g u ntil t he first d oc u me nte d pr o gressi o n or 
deat h as per C hes o n et al  (2 0 0 6 ) defi niti o ns f or M D S 
a n d as per Sa v o na et al  (2 0 1 5 ) defi niti o ns f or 
M D S/ M P N o verla p s y n dr o mes.  
•  L F S, defi ne d as t he i nter val fr o m t he first d ose of 
st u d y dr u g u ntil t he first d oc u me nte d le u ke mia 
tra nsf or mati o n or deat h fr o m a n y ca use. 
F or M M p artici p a nts o nl y:  
•  O verall res p o nse rate , defi ne d as t he pr o p orti o n of 
partici pa nts wit h stri n ge nt C R , C R , ver y g o o d P R , 
a n d P R  as per K u mar et al (2 0 1 6 ).   
•  P F S , defi ne d as t he i nter val fr o m t he first d ose of 
st u d y dr u g u ntil t he first d oc u me nte d pr o gressi o n or 
deat h as per K u mar et al (2 0 1 6 ). 
T o e v al uate t he P K of I N C B 0 0 0 9 2 8 i n partici pa nts 
wit h M D S or M M .  
P K para meters:  C ma x, tma x , a n d A U C 0 -t.  
T o e v al uate t he effect of I N C B 0 0 0 9 2 8 o n t he ir o n 
h o me ostasis a n d t he er yt hr o p oiesis para meters i n 
partici pa nts wit h M D S or M M.  
•  Bl o o d le vels of he pci di n .  
•  Ir o n h o me ostasis para meters.  
•  Er yt hr o p oiesis para meters .  
E x pl or at or y  

I nc yte C orp orati o n  
Pa ge 3 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
4.  
S T U D Y D E SI G N  
4. 1.  
O ver all Desi g n  
T his P hase 1/ 2, o pe n -la b el, m ultice nter, d ose-fi n di n g st u d y is i nte n de d t o e val uate t he safet y a n d 
t olera bilit y, P K, P D, a n d preli mi nar y efficac y of I N C B 0 0 0 9 2 8 a d mi nistere d as a m o n ot hera p y i n 
partici pa nts wit h M D S or M M w h o are tr a nsf usi o n -de pe n de nt or pres e nt wit h s y m pt o matic 
a ne mia. 
4. 1. 1.  
D ose Esc al ati o n a n d De -Esc al ati o n Al g orit h m  
I n t he d os e-es calati o n sta ge, a B OI N desi g n (Li u a n d Y ua n 2 0 1 5 ) will be us e d t o deter mi ne t he 
M T D.  I n eac h d ose -escalati o n c o h ort, data fr o m b ot h partici pa nts wit h M D S a n d partici pa nts 
wit h M M will be e val uate d t o get her .   
T he c o h ort size will be 3.  A p pr o xi matel y 2 4 e val u a ble partici pa nts ma y b e treate d i n t he 
d ose -escalati o n sta ges, a n d t he d ose-es calati o n pr oce d ure m a y be st o p pe d if t he n u m ber of 
e val ua ble p artici pa nts treate d at a n y d ose l e vel is >  9.  T he val ue of 0. 6  × 0. 2 8 is t he hi g hest D L T 
rate t hat is dee me d s u bt hera pe utic.  T he l o west D L T rate dee me d o verl y t o xic is 1. 4  × 0. 2 8, 
mea ni n g t hat if t he partici pa nts ha ve a D L T(s) rate of  ≤ 0. 6  × 0. 2 8, d ose es calati o n is re q uire d; if 
t he partici pa nts ha v e a D L T(s) rat e of ≥ 1. 4 × 0. 2 8, d ose de -es calati o n is re q uire d.  A n e q u al 
pri or pr o ba bilit y of h y p ot hesis bei n g tr ue is assi g ne d t o eac h of t he h y p ot heses.  T he val ue of 
0. 9 5 is selecte d f or t h e c ut off t o eli mi nate a n o verl y t o xic d ose f or safet y.  
Ta ble  9  wi ll be use d t o g ui de d ose escalati o n/ de-escalati o n decisi o ns.  
T a ble  9 : 
Decisi o n B o u n d aries  
N u m ber of partici pa nts treate d at 
c urre nt d ose  
1  
2  
3  
4  
5  
6  
7  
8  
9  
Escalate if n u m ber of partici pa nts 
wit h D L T(s) is ≤ 
0  
0  
0  
0  
1  
1  
1  
1  
1  
De -escalate if n u m ber of 
partici pa nts wit h D L T(s) is ≥ 
1  
1  
2  
2  
2  
3  
3  
3  
4  
U nacce pta ble t o xicit y if n u m ber of 
partici pa nts wit h D L T(s) is ≥ 
N A  
N A  
3  
3  
4  
4  
4  
5  
5  
N A = n ot a p plica ble.  
If t he n u m ber of partici p a nts wit h D L T(s) s pecifie d i n t he last r o w is reac h e d, t hat d ose le vel a n d 
a b o ve d ose le v els will be eli mi nate d.  If t he n u m b er of partici pa nts wit h D L T(s) is bet wee n t he 
escalati o n a n d d e -es calati o n b o u n daries s pecifie d i n t he sec o n d a n d t hir d r o ws i n Ta ble  9 , 
a n ot her 3 e v al ua ble partici pa nts will be e nr olle d i n t he c urre nt d ose le vel c o h ort.  
T he e xact n u m ber of p artici pa nts treate d i n t he d os e -escalati o n sta ge will de pe n d u p o n t he 
n u m ber of partici p a nts re q uire d per d ose le vel a n d u p o n t he n u m ber of d ose le vels st u die d.  
O ne or m ore R D E(s) ma y be defi ne d i n eac h tr eat me nt gr o u p – as a p plica bl e-.  T he d efi niti o n of 
t he R D E(s) are as f oll o ws: 
•  Defi ne d R D E d oses are p har mac o d y n a micall y acti ve,  
•  R D E d oses will n ot e xcee d t he M T D defi ne d i n eac h treat me nt gr o u p.  

I nc yte C orp orati o n  
Pa ge 3 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
4. 1. 2.  
E x pl or ati o n of Alter n ati ve A d mi nistr ati o n Sc he d ules  
T he s p o ns or, i n c o ns ultati o n wit h partici pati n g i n vesti gat ors, ma y elect t o e x pl ore alter nati ve 
a d mi nistrati o n sc he d ules or e x pa n d d ose c o h orts d ee me d t olera ble  i n or der t o o btai n 
s u p ple me ntal P K, p har m ac o d y na mic, a n d safet y data. 
A lter nati ve d ose le v els or a d mi nistrati o n sc he d ules (s uc h as BI D) m a y be e x pl ore d.  I n t hat 
sit uati o n, t he t otal dail y d ose of t he alter n ati ve a d mi nistrati o n sc he d ule(s) e x pl ore d will n ot 
e xcee d 2 -f ol d of t he pri or t otal dail y d ose or t he M T D, as a p plica bl e. Alter n ati ve d ose sc he d ul es 
f or d ose-escalati o n c o h orts will be c o m m u nicate d t o sites pri or t o c o h ort e nr oll me nt.  
4. 1. 3.  
E x p a nsi o n St a ge s 
T he R D E (s) i de ntifie d i n t he d ose-escalati o n sta ges will be ta ke n f or war d a n d a d mi nistere d t o a n 
a d diti o nal 1 5 e val ua ble p artici pa nts i n eac h  of t he disease gr o u ps  a n d at eac h of t he i de ntifie d 
R D E(s) , a n d f urt her e v al uati o n of t he safet y, efficac y, P K, a nd P D of t he R D E (s) will be 
perf or me d i n a parallel a n d i n de pe n de nt fas hi o n i n eac h dise ase gr o u p.  I n t he e ve nt t hat m ore 
t ha n o ne R D E is e x pl ore d i n a disease gr o u p, t he partici pa nts i n t his disease gr o u p will be 
ra n d o ml y all ocate d t o o n e of t he R D Es. 
A d d iti o nal partici pa nts ma y be i ncl u de d at t he sp o ns or 's discreti o n i n eac h disease gr o u p t o 
e ns ure t hat at least 3 0 % or 1 0 tra nsf usi o n -de p e n d e nt partici pa nts are i ncl u de d i n eac h e x pa nsi o n 
c o h ort. 
Fiftee n  p artici pa nt s per R D E c o h ort will pr o vi de a > 7 5 % c h a nce of i de ntif yi n g a t o xicit y  wit h a 
tr ue e ve nt r ate of 9 %. 
Defi niti o ns:  
•  M T D:  as per t he B OI N desi g n, M T D is defi ne d as t he d ose at w hic h t he o bser ve d 
D L T rate is cl osest t o t he tar get D L T rate of 2 8 % usi n g t he is ot o nical met h o d, w hic h 
ta kes t he ass u m pti o n of a m o n ot o nic d ose-t o xicit y relati o ns hi p i nt o acc o u nt. 
•  R D E:  t he R D E(s) will be deter mi ne d b y e val uati o n of all a vaila ble data (i e, safet y, 
P D , a n d P K data) fr o m t he d ose -es calati o n sta ge of t he st u d y , w hic h i ncl u d es data 
fr o m partici pa nts fr o m b ot h disease gr o u p s, f or f urt her i n vesti gati o n i n t he e x pa nsi o n 
c o h orts, i ncl u di n g l o w -gra de b ut c hr o nic t o xicities, d ose re d ucti o ns, d ose 
i nterr u pti o ns, or misse d d oses of I N C B 0 0 0 9 2 8.  T he R D E (s) will ne ver e xcee d t he 
M T D.  
4. 2.  
O ver all St u d y D ur ati o n  
T he st u d y be gi ns w he n t he first partici pa nt si g ns t he I C F.  T h e e n d of t he st u d y will occ ur w he n 
all partici pa nts ha ve c o m plete d u p t o 6  m o nt hs  of treat me nt or ha v e disc o nti n ue d treat me nt 
earlier a n d c o m plete d a p plica ble safet y f oll o w -u p assess me nts or w he n t he s p o ns or ter mi nates 
t he st u d y.  T he partici pa nts w h o are still recei vi n g I N C B 0 0 0 9 2 8, w h o are d eri vi n g cli nical 
be nefit , a n d w h o d o n ot h a ve a n y e vi de nce of pr o gressi ve diseas e at t he ti me of st u d y cl os ure 
ma y  ha ve t he o pti o n t o c o nti n ue recei vi n g tr eat me nt wit h I N C B 0 0 0 9 2 8 u n d er t his trial or a 
r oll o ver pr ot oc ol. 
A partici pa nt is c o nsi dere d t o ha ve c o m plet e d t he st u d y if he/s he has c o m plete d all sta ges of t he 
st u d y, i ncl u di n g t he safet y f oll o w-u p visit.  

I nc yte C orp orati o n  
Pa ge 3 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
F or eac h partici pa nt, t he st u d y will c o m prise t he f oll o wi n g: 
•  U p t o 2 8 da ys f or scree ni n g . 
•  C o nti n u o us st u d y dr u g treat me nt i n c o nsec uti ve 2 8-da y treat me nt c ycles u p t o 
6  m o nt hs as l o n g as partici pa nts are d eri vi n g be nefit fr o m st u d y dr u g  a n d h a ve n ot 
met a n y criteria f or st u d y dr u g  disc o nti n uati o n  (see Secti o n  7. 1 ). 
•  A n a d diti o nal 3 0 da ys f or t he safet y f oll o w -u p p eri o d . 
•  P ost -treat me nt f oll o w-u p  e ver y 6 m o nt hs.  
4. 3.  
St u d y Ter mi n ati o n  
T he i n 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 ntract.  T h e i n vesti gat or is t o n otif y t he I R B /I E C 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 h e 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 re g ulat or y file.  
After e nr oll me nt has be g u n i n e x pa nsi o n at t he R D E (s) i n disease gr o u ps M D S a n d M M, f urt her 
e nr oll m e nt of partici pa nts will be s us pe n de d if 1) m ore t ha n 1 partici p a nt i n t he first 
5  partici pa nts e nr olle d i n a s pecific dise ase gr o u p ha ve a n A E ≥ Gra d e 3 t hat is attri b uta ble t o t he 
i n vesti gati o nal a ge nt, or 2) at least 4 0 % of 5 or m ore partici p a nts e nr olle d i n a s pecific dise ase 
gr o u p ha ve a n A E ≥ Gra de 3 t hat is attri b uta ble t o t he i n vesti gati o nal a ge nt.   E nr oll me nt of 
partici pa nts will be s us pe n de d i n t he disease gr o u p u ntil t he s p o ns or, i n vesti gat ors, a n d D M C 
ha ve deter mi ne d t he a p pr o priate c o urs e of acti o n a n d o nl y after re g ulat or y a ut h orit y a p pr o val of 
t he restart. 
T he s p o ns or ma y ter mi nate t he st u d y electi ve l y, if re q uire d b y re g ulat or y d ecisi o n , or u p o n 
a d vice of t he D M C.  If t h e st u d y is ter mi nate d pre mat urel y, t he s p o ns or will n otif y t he 
i n vesti gat ors, t he I R Bs/I ECs , a n d re g ulat or y b o di es of t he decisi o n a n d reas o n f or ter mi nati o n of 
t he st u d y.  T he D M C ma y rec o m me n d ter mi nati o n of t he st u d y if warra nte d, as descri be d i n 
Secti o n  5. 6 . 
T he st u d y will be c o nsi dere d cl os e d f or d ata c ollecti o n f or pri mar y a na l ysis w he n all partici pa nts 
ha ve c o m plete d 6 m o nt hs of st u d y dr u g treat me nt or disc o nti n ue d pre mat urel y.  

I nc yte C orp orati o n  
Pa ge 3 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
5.  
S T U D Y P O P U L A TI O N  
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 par dize t h e 
scie ntific i nte grit y of t he st u d y, reg ulat or y acce pta bilit y, a n d/ or partici pa nt  safet y.  T heref ore, 
a d here n ce t o t he criteria as s pecifie d i n t he Pr ot oc ol is esse ntial .  Pr os pecti ve a p pr o val of 
P r ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as P r ot oc ol wai vers or 
e xe m pti o ns, are n ot per mitte d.  
5. 1.  
I ncl usi o n Criteri a 
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:  
1.  A bilit y t o c o m pre he n d a n d willi n g ness t o si g n a writte n I C F f or t he st u d y.  
2.  A ge 1 8 years or ol der  at t he ti me of si g ni n g t he I C F.  
3.  E C O G perf or ma nce stat us of t he f oll o wi n g:  
a. 0 or 1 f or t he d ose -escalati o n sta ges.  
b.  0, 1, or 2 f or t he d ose -e x pa nsi o n sta ge.  
4.  Life e x pecta nc y > 6  m o nt hs.  
5.  A gree me nt t o a v oi d pre g na nc y or fat heri n g c hil dr e n base d o n t he criteria b el o w:  
a. Male partici pa nts wit h re pr o d ucti ve p ote ntial m ust a gree t o ta k e a p pr o priate 
preca uti o ns t o a v oi d f at heri n g c hil dre n fr o m scree ni n g t hr o u g h 9 0 da ys after t he last 
d ose  of st u d y dr u g a n d m ust refrai n fr o m d o nati n g s per m d uri n g t his peri o d.  
Per mitte d met h o ds i n pre ve nti n g pre g na nc y (see A p pe n di x  A ) s h o ul d be 
c o m m u n icate d t o t he partici pa nts a n d t heir u n derst a n di n g c o nfir me d. 
b.  Fe male p artici pa nts w h o are W O C B P  m ust ha ve a ne gati ve ser u m pre g na n c y test at 
scree ni n g b ef ore t he first d ose ( wit hi n 3 da ys of t h e first d ose of st u d y dr u g ), m ust 
a gree t o ta k e a p pr o priate pre ca uti o ns t o a v oi d pr e g na nc y fr o m scree ni n g t hr o u g h t he 
safet y f oll o w-u p visit , a n d m ust n ot d o nate o oc ytes d uri n g t his peri o d (see Ta ble  3  
a n d Secti o n  8. 9. 1 ).  Per mitte d met h o ds i n pre ve nti n g pre g na nc y (see A p pe n di x  A ) 
s h o ul d be c o m m u nicate d t o t he partici pa nts a n d t h eir u n dersta n di n g c o nfir me d . 
c. Fe male p artici pa nts n ot c o nsi dere d t o be of  c hil d beari n g p ote ntial as d efi ne d i n  
A p pe n di x  A  are eli gi ble.  
I ncl usi o n criteri a defi ni n g t he dise ase c h ar acteristics: 
6.  Partici pa nts w h o are  tra nsf usi o n-de pe n de nt or prese nt wit h s y m pt o matic a ne mia, defi ne d 
as f oll o ws:  
a. A ne mia:  a n H g b val u e  <  1 0  g/ d L rec or de d o n 3 se parate occasi o ns wit h at l east 
7  da ys bet wee n meas ur e me nts d uri n g t he 1 2 wee ks i m me diatel y pri or t o C 1 D 1.  T he 
m ost rece nt meas ure me nt m ust ha ve occ urre d d uri n g t he 2 8 da y scree ni n g peri o d 
i m me diatel y pri or t o C 1 D 1 (n o te:  R B C tra nsf usi o n m ust be at least 2 wee ks bef ore 
t he H g b meas ur e me nt d uri n g scree ni n g). 

I nc yte C orp orati o n  
Pa ge 3 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
b.  Tra nsf usi o n -de p e n de nt:  p artici pa nt has recei v e d at least 4 u nits of R B C tra nsf usi o ns 
d uri n g t he 2 8  da ys i m me diatel y prece di n g C 1 D 1  O R has recei ve d at least 4  u nits of 
R B C tra nsf usi o ns i n t he 8  wee ks i m me diatel y pr ece di n g C 1 D 1 , f or a n H g b le vel 
of  <  8. 5 g/ d L, i n t he a bse nce of ble e 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 de m ust ha ve occ urre d i n t he 2 8 d a ys bef ore C 1 D 1 .  
F or M D S partici p a nts : 
7.  I n eli gi ble t o recei v e or h a ve n ot res p o n d e d t o a vaila ble t hera pies f or a n e mia s uc h as 
E S As or le nali d o mi de.  
8.  N ot re q uiri n g c yt ore d u cti ve t hera p y ot her t ha n h y dr o x y urea.  
9.  B M a n d peri p heral bl o o d m yel o blast c o u nt < 1 0 %.  
1 0.  Hist ol o gicall y c o nfir me d dia g n osis of t he f oll o wi n g (acc or di n g t o t he 2 0 1 6 W H O criteria 
[S wer dl o w et al 2 0 1 7 ]): 
a. M D S.  
b.  C M M L.  
c. M D S/ M P N o verla p s y n dr o me s. 
N ote:   Partici pa nts prese nti n g wit h at y pical c hr o nic m yel oi d le u ke mia, or j u ve nile 
m yel o m o n oc ytic le u ke mia  will n ot be i ncl u de d . 
F or M M partici p a nts:  
1 1.  Hist ol o gicall y c o nfir me d dia g n osis of M M  (acc or di n g t o t he 2 0 1 6 W H O criteria 
[S wer dl o w et al 2 0 1 7 ]). 
1 2.  A fter fail ure of a vaila ble sta n dar d treat me nts; sta n dar d treat me nt o pti o ns i ncl u de t he 
f oll o wi n g:  al k ylati n g a ge nt s, gl uc oc ortic oi ds, i m m u n o m o d ulat or y dr u gs (le nali d o mi de, 
p o mali d o mi de , or t hali d o mi de), pr oteas o me i n hi bit ors ( b ortez o mi b or carfil z o mi b), a n d 
darat u m u ma b.  
5. 2.  
E xcl usi o n Criteri a  
Partici pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
1.  A n y pri or all o ge n ei c ste m cell tra ns pla ntati o n or a ca n di dat e f or s uc h tra ns pla ntati o n.  
2.  A n y maj or s ur ger y wit hi n 2 8 da ys bef ore t he first d ose of st u d y dr u g.  
3.  A n y pri or c he m ot hera p y, i m m u n o m o d ulat or y dr u g t hera p y, i m m u n os u p pressi ve t hera p y, 
bi ol o gical t hera p y, e n d o cri ne t hera p y, t ar gete d  t h era p y, or a nti b o d y or h y p o met h ylati n g 
a ge nt t o treat t he p artici p a nt 's disease wit hi n 5 half-li ves or 2 8 da ys ( w hic h e ver is s h orter) 
bef ore t h e first d ose of st u d y dr u g.  
a. E xce pt i o ns i ncl u de gl uc o c ortic oi ds ( c ortic oster oi ds ma y be c o nti n ue d d uri n g t he 
st ud y if t he partici pa nt ha d a sta ble d ose f or t he 4 wee ks i m me diatel y bef ore C 1 D 1  
a n d d oes n ot pres e nt a n y Gra de  2 or hi g her t o xicit y d ue t o t he treat me nt) a n d 
h y dr o x y urea ( ma y be us e d  t o treat h y per pr oliferati ve disease fr o m C ycle 2 i n 
d ose -escalati o n c o h or ts a n d fr o m C ycle 1 i n d ose e x pa nsi o n).  

I nc yte C orp orati o n  
Pa ge 3 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
4.  U n der g oi n g treat me nt wit h a n ot her i n vesti gati o nal me dicati o n or ha vi n g bee n treate d 
wit h a n i n vesti gati o nal me dicati o n wit hi n 2 8 da ys bef ore t h e first d ose of st u d y dr u g.  
N ote:   T h e sp o ns or 's me dical m o nit or s h o ul d be c o ntacte d i n t he e v e nt a partici pa nt 
recei v ed  a n y tr eat me nt f or si g ns or s y m pt o ms of C O VI D -1 9 . 
5.  U n der g oi n g treat me nt wit h E S As, gra n ul oc yte c ol o n y -sti m ulati n g fact or or 
gra n ul oc yte/ macr o p ha g e c ol o n y -sti m ulati n g fact or, r o mi pl osti n, or eltr o m b o pa g at a n y 
ti me wit hi n 2 8 da ys or 5 half -li ves ( w hic he ver is s h orter) bef ore t h e first d ose of st u d y 
dr u g.  
6.  U n der g oi n g treat me nt wit h a str o n g or p ote nt  i n hi bit or or i n d ucer of C Y P 3 A 4/ 5 wit hi n 
2 8  da ys or 5 half -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 or 
e x pecte d t o recei ve s uc h treat me nt d uri n g t he st u d y  (see t he U ni v ersit y of Was hi n gt o n 
Sc h o ol of P har mac y  Dr u g I nteracti o n Data bas e Pr o gra m  [2 0 0 2 ] f or pr o hi bite d 
me dicati o ns) . 
7.  A n y pri or ra di ati o n t hera p y wit hi n 2 8 da ys bef ore t he first d ose of st u d y dr u g.  Palliati ve 
ra diati o n t hera p y t o si n gl e sites or s mall fiel ds is all o we d wit h at least a 1-wee k was h o ut 
bef ore t h e f irst d ose of st u d y dr u g. 
8.  Prese nce of a n y h e mat ol o gic mali g na nc y ot her t h a n M D S or M M, as a p pli ca ble.  
9.  Acti ve i n vasi ve mali g na n c y o ver t he pre vi o us 2  years.  E xce pti o ns i ncl u de partici pa nts 
wit h earl y -sta ge b asal c ell or s q ua m o us cell s ki n ca ncer, c o m pletel y res ecte d 
i ntrae pit helial carci n o ma of t he cer vi x, or c o m plet el y resecte d pa pillar y t h yr oi d a n d 
f ollic ular t h yr oi d ca n cers, w h o ma y be eli gi ble t o partici pate at t he i n v esti gat or's 
discreti o n.  Partici pa nts wit h mali g na ncies 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 he y ha ve a reas o na ble 
e x pectati o n t o ha v e bee n c ure d wit h t he tr eat me nt m o dalit y recei ve d.  
1 0.  K n o w n acti ve dise ase i n v ol vi n g t he C N S.  
1 1.  Hist or y of cli nicall y si g nifica nt or u nc o ntr oll e d car diac diseas e , i ncl u di n g r ece nt ( wit hi n 
t he past 1 2  m o nt hs) u nsta ble a n gi na or ac ute m y ocar dial i nfarcti 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, or cli nicall y si g nifica nt arr h yt h mias 
n ot c o ntr olle d b y me dicati o n.  Parti ci pa nts wit h a pace ma ker a n d well -c o ntr olle d r h yt h m 
f or at least 1 m o nt h bef ore t he first d ose of st u d y me dicati o n will be all o we d. 
1 2.  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.  Scree ni n g Q Tc > 4 5 0  m illisec o n ds is e xcl u de d u nless a p pr o ve d b y t he 
s p o ns or's me dical m o nit or.  F or partici pa nts wit h a n i ntra ve ntric ular c o n d ucti o n dela y 
( Q R S i nter val > 1 2 0 millisec o n ds), t he J Tc ma y be use d i n place of t he Q Tc wit h s p o ns or 
a p pr o val.  Partici pa nts wit h left b u n dle bra nc h bl o c k deter mi ne d t o be cli nicall y 
si g nifica nt b y t he i n vesti gat or will be e xcl u de d.  P artici pa nts wit h Q Tc pr ol o n gati o n d ue 
t o a pace m a ker ma y e nr oll wit h pri or a p pr o val fr o m t he s p o ns or's me dical m o nit or. 
1 3.  Prese nce of c hr o ni c or c urre nt acti ve i nfecti o us dis ease re q uiri n g s yste mic a nti bi otic, 
a ntif u n gal, or a nti viral treat me nt.  Partici pa nts wit h ac ute i nfecti o n re q uiri n g a nti bi otic, 
a ntif u n gal, or a nti viral treat me nt use s h o ul d dela y scree ni n g/e nr oll me nt u ntil t he c o urse 
of a nti b i otic, a ntif u n gal, or a nti viral treat me nt h as bee n c o m plete d a n d t he i nfecti o n is n o 
l o n ger acti ve.  

I nc yte C orp orati o n  
Pa ge 4 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 4.  D ia g n osis of c hr o nic li ver disease (e g, c hr o nic alc o h olic li ver disease, a ut oi m m u ne 
he patitis, scler osi n g c h ol a n gitis, pri mar y biliar y cirr h osis, here ditar y  he m oc hr o mat osis, 
n o nalc o h olic steat o he p atitis).  
1 5.  K n o w n acti ve h e patitis A, H B V, or H C V i nfecti o n , or at ris k of H B V reacti vati o n, or 
k n o w n HI V  i nfecti o n. 
Acti ve H B V or at ris k of reacti vati o n are defi ne d as f oll o ws: p ositi ve H Bs A g res ult 
(la b orat or y tests r e q uire d at scree ni n g), a n d/ or p ositi ve t otal a nti-H Bc a nti b o d y res ult 
(la b orat or y tests r e q uire d at scree ni n g), a n d/ or q u a ntitati ve H B V D N A test res ult greater 
t ha n t he l o wer li mits of detecti o n of t he ass a y (if k n o w n, la b orat or y tests not re q uire d f or 
eli gi bilit y p ur p ose, b ut ca n be d o ne as p art of scree ni n g if l ocall y a vaila ble).  
N ote:   Partici pa nts wit h n o pri or hist or y of H B V i nfecti o n, w h o ha v e bee n v acci nat e d 
a gai nst H B V a n d w h o ha ve a p ositi ve a nti -H Bs res ult as t he o nl y e vi de nce o f pri or 
e x p os ure, ma y p artici pat e i n t he st u d y.  
Acti ve H C V is defi ne d as f oll o ws: p ositi ve a nti -H C V a nti b o d y (la b orat or y test re q uire d 
at scree ni n g) a n d q ua ntit ati ve H C V -R N A test res ult greater t ha n t h e l o wer li mits of 
detecti o n of t he ass a y (la b orat or y te st re q uir e d if a nti-H C V a nti b o d y p ositi ve o nl y; t his 
ca n be d o n e as part of scree ni n g if a vaila bl e l ocall y).  
N ote:  A nti -H C V a nti b o d y p ositi ve partici pa nts w h o recei v e d a n d c o m plet e d treat me nt f or 
he patitis C t hat was i nte n de d t o era dicate t he vir us ma y par tici pate if H C V-R N A le vels 
are u n det ecta ble at least 1 2 wee ks after last d ose of t hera p y .  A nti -H C V a nti b o d y p ositi ve 
partici pa nts wit h n o a vail a ble c o nfir m at or y ne gati ve H C V -R N A test res ults will be 
e xcl u de d. 
1 6.  U n willi n g ness t o be u n der g o tra nsf usi o n wit h b l o o d c o m p o ne nts, i ncl u di n g R B C pac ks 
a n d platelet tra nsf usi o ns.  
1 7.  A n y c o n diti o n i n t he i n vesti gat or 's j u d g me nt t hat w o ul d i nterfere wit h f ull partici pati o n i n 
t he st u d y (e g, u na ble, u nli kel y, or u n willi n g t o c o m pl y wit h t he d ose sc he d ule a n d st u d y 
e val uati o ns), 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 uir e d st u d y visits; 
p ose a si g nifica nt ris k t o t he partici pa nt; or i nterfere wit h i nter pret ati o n of st u d y data.  
1 8.  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 he  partici p a nt 's a bilit y t o 
c o m pl y wit h t he st u d y re q uire me nts.  
1 9.  Gastr oes o p ha g eal r efl u x disease n ot c o ntr olle d b y me dicati o n (ie, c urre ntl y s y m pt o matic 
or e n d osc o pic e vi de nce of es o p ha gitis) wit hi n 2 8 da ys bef ore t he first d ose of st u d y dr u g.  
2 0.  Prese nce of  a n y u nres ol v e d t o xicit y ≥ Gra de 2 fr o m pre vi o us t hera p y e x ce pt f or sta ble 
c hr o nic t o xicities ( ≤ Gra de 2) n ot e x pecte d t o res ol ve, s uc h as sta ble Gra d e 2 peri p heral 
ne ur o pat h y.  
2 1.  K n o w n h y perse nsiti vit y, se vere reacti o n, or a n y k n o w n c o ntrai n dicati o ns t o t he use of 
a n y of t h e acti ve s u bsta n ces or e x ci pie nts i n I N C B 0 0 0 9 2 8.  
2 2.  W o me n w h o are pre g na nt or breastf ee di n g.  
2 3.  U na ble t o s wall o w a n d retai n oral me dicati o n.  
2 4.  C urre nt use of pr o hi bite d me dicati o n  (see Secti o n  6. 7. 3 ). 

I nc yte C orp orati o n  
Pa ge 4 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
2 5.  Partici pa nts wit h la b orat or y val ues at scree ni n g as defi ne d i n Ta ble  1 0 . 
T a ble  1 0 : 
E xcl usi o n ar y L a b or at or y V al ues  
L a b or at or y P ar a meter  
E xcl usi o n Criteri o n  
He m at ol o g y  
a Platelets  
< 2 5 × 1 0 9/ L wit h o ut t he assista nce of gr o wt h fact ors, t hr o m b o p oietic 
fact ors, or platelet tra nsf usi o ns 
b  A N C  
< 0. 5 0  × 1 0 9/ L 
He p atic  
c A L T  
≥ 2. 5 × U L N  
d  A S T  
≥ 2. 5 × U L N  
e T otal bilir u bi n  
≥ 2. 0  U L N, u nless c o nj u gate d ( direct) bilir u bi n is ≤ 1. 5  U L N ( direct  
bilir u bi n o nl y nee ds t o be teste d if t otal bilir u bi n e xcee ds t he U L N ; e xce pt 
k n o w n Gil bert 's s y n dr o me, i n w hic h case direct bilir u bi n has t o be 
teste d).  If t here is n o i nstit uti o nal U L N, t he n direct bilir u bi n m ust be  <  4 0 % 
of t otal bilir u bi n.  
Re n al  
f 
Creati ni ne cleara nce  
< 3 0 m L/ mi n acc or di n g t o C oc kcr oft -Ga ult f or m ula  
Ot her  
g  Ir o n meta b olis m 
Ser u m ferriti n le vel  of  ≥ 1 0 0 0 n g/ m L a n d d oc u me nte d cli nicall y si g nifica nt 
ir o n o verl oa d as per i n vesti gat or o pi ni o n (e g,  lea di n g t o li ver cirr h osis) o n 
li ver M RI or bi o ps y ( C T sca n ma y be acce pte d) . 
2 6.  Ir o n c hel ati o n treat me nt is all o we d bef ore t he first d ose of st u d y dr u g pr o vi d e d t he d ose 
is sta ble d uri n g t he 2 wee ks pri or t o t he first d ose of I N C B 0 0 0 9 2 8. 
5. 3.  
Lifest yle C o nsi der ati o ns  
5. 3. 1.  
Me als a n d Diet ar y Restricti o ns  
Partici pa nts s h o ul d r efrai n fr o m c o ns u m pti o n of Se ville ora n ges, gra pefr uit or gra pefr uit j uice, 
a n d p o me gra n ates or p o me gra nate j uice  fr o m t he ti me of si g nat ure of t he I C F u ntil after t he last 
d ose of st u d y dr u g . 
5. 4.  
Scree n F ail ures  
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y e nter e d in t he st u d y.  
I n di vi d ual tests wit h res ults t hat fail eli gi bilit y re q uire me nts ma y be re peat e d d uri n g scree ni n g if 
t he i n vesti gat or believes t he res ult t o be i n err or.  
A d diti o nall y, a partici pa nt w h o d oes n ot meet t he criteria f or partici p ati o n i n t his st u d y 
(ie, scree n fail ure) a n d t h us fails scree ni n g ma y re peat t he scree ni n g pr o cess 1  ti me if t he 

I nc yte C orp orati o n  
Pa ge 4 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
i n vesti gat or belie ves t hat t here has b ee n a c ha n g e i n eli gi bilit y stat us.  Partici pa nts w h o are 
rescree ne d m ust rec o nse nt a n d be assi g ne d a n e w partici pa nt n u m be r. 
5. 5.  
Re pl ace me nt of P artici p a nts  
Partici pa nts ma y be  re pl ace d for a n y of t he f oll o wi n g reas o ns:  
•  I n t he d os e -es calati o n sta ges: 
− E ac h partici pa nt will be o bser ve d f or at least t he first st u d y dr u g treat me nt c ycle 
(ie, 2 8  da ys) t o be e val ua ble t o assess safety of t he d ose  f or t he p ur p os es of D L T 
assess me nt.  Partici pa nts w h o recei ve at least 7 5 % of d oses of st u d y dr u g at t he 
le vel assi g ne d t o t hat c o h ort (ie, 2 1 da ys of treat m e nt) or ha v e a D L T d uri n g t he 
first st u d y dr u g treat me nt c ycle will be c o nsi dered e val ua ble f or deter mi ni n g 
safet y of t he d os e a n d f or D L T assess me nt p ur p os es.  Partici pa nts prese nti n g d ose 
re d ucti o ns, d ose i nterr u pti o ns ( b ut n ot meeti n g D L T criteria), or dr u g 
disc o nti n uati o n  beca use of a n e ve nt t hat d o es n ot meet t he criteri a f or a D L T , 
w hic h res ults i n <  7 5 % of t he prescri be d d ose of st u d y dr u g bei n g a d mi nistere d  
d uri n g t he first st u d y dr u g treat me nt c ycl e , will be c o nsi dere d n o n e val ua ble f or 
t he p ur p oses of det er mi ni n g t he M T D a n d will be re place d. 
− A partici pa nt w h o ha d t o recei v e a n y str o n g or p ot e nt C Y P 3 A 4/ 5 i n hi bit or or 
i n d ucer d uri n g  t he first st u d y dr u g treat me nt c ycle ( D L T assess me nt p eri o d) will 
be re pla ce d.  
− Partici pa nts w h o d o n ot meet all of t he eli gi bilit y re q uire me nts of t h e st u d y ma y 
be re pla ce d.  
•  I n t he ex pa nsi o n sta ges, a n e val ua bl e partici pa nt is defi ne d as a partici pa nt w h o has 
recei v e d at least 1  d ose of st u d y dr u g a n d ha d at least 1  p ost baseli ne o n -st u d y 
assess me nt.  
− T he n o ne val ua bl e partici pa nts i n a n y of t he e x p a nsi o n sta ges will be re place d.  
− Partici pa nts w h o d o n ot meet all t he eli gi bilit y re q uire me nts of t he st u d y ma y be 
re place d. 
5. 6.  
D at a M o nit ori n g C o m mittee  
T his st u d y will use a D M C  t o m o nit or safet y a n d efficac y at t he pla n ne d a n al yses. 
T he D M C will re vie w t h e st u d y i nf or mati o n pr o vi de d bef ore  eac h meeti n g a n d m a ke 
rec o m me n dati o ns r e gar di n g ste ps t o e ns ure b ot h p artici pa nt safet y a n d t he c o nti n ue d et hical 
i nte grit y of t he st u d y.  Als o, t he D M C will c o nsi der t he o verall ris k a n d be nefit t o st u d y 
partici pa nts a n d pr o vi de rec o m me n dati o ns s uc h as st u d y c o nti n uati o n i n acc or da nce wit h t he 
Pr ot oc o l or s u g gest st u d y pr ot oc ol a me n d me nts , st u d y i nterr u pti o n, or st u d y ter mi nati o n, as 
a p plica ble. 
S pecific details re g ar di n g c o m p ositi o n, res p o nsi bilities, a n d g o ver na n ce, i ncl u di n g t he r oles a n d 
res p o nsi bilities of t he vari o us me m bers , t he st u d y tea m, a n d re q uire me nts f or a n d pr o per 
d oc u me ntati o n of D M C r e p orts, mi n utes, a n d rec o m me n dati o ns , will be descri be d i n t he D M C 
c harter t hat is re vie we d a n d a p pr o ve d b y all D M C me m bers.  

I nc yte C orp orati o n  
Pa ge 4 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
6.  
S T U D Y T R E A T M E N T  
6. 1.  
St u d y Tre at me nt  A d mi nistere d  
Ta ble  1 1  pres e nts t he st u d y treat me nt i nf or mati o n. 
T he treat me nt peri o d be gi ns o n t he da y t he partici pa nt recei ves t he first d os e of st u d y  dr u g  
(C 1 D 1 ) a n d e n ds w h e n  t he i n vesti gat or deter mi nes t he partici pa nt will be p er ma ne ntl y 
disc o nti n ue d fr o m st u d y dr u g .  T he first d ose o n C 1 D 1  m ust be n o m ore t ha n 2 8 da ys aft er t he 
partici pa nt has si g ne d t he I C F a n d n o m or e t ha n  7  da ys after t h e date of  e nr oll me nt 
(ie, e nr oll me nt  a p pr o ve d b y me dical m o nit or).  
I N C B 0 0 0 9 2 8 will be a d mi nistere d dail y  b y oral r o ute  i n c o nsec uti ve, c o nti n u o us , 2 8 -da y 
treat me nt c ycl es.  T he d oses of I N C B 0 0 0 9 2 8 ca n be a d mi nistere d b y h os pital pers o n nel i n a n 
i n patie nt setti n g or self-a d mi nistere d b y t he partici pa nt i n a n o ut patie nt setti n g.  
I N C B 0 0 0 9 2 8 will be a d mi nistere d t o t he st u d y partici pa nts as l o n g as t he y be nefit fr o m t he st u d y 
dr u g  a n d t he y d o n ot pres e nt a n y st u d y dr u g  disc o nti n uati o n criteri o n as per i n vesti gat or 's 
assess me nt (see Secti o n  7. 1 ) f or u p t o 6  m o nt hs  of treat me nt .  T he p artici p a nts w h o are still 
recei vi n g I N C B 0 0 0 9 2 8 a n d are deri vi n g cli nical b e nefit at t his ti me ma y re mai n o n st u d y dr u g 
treat me nt if t he st u d y is still o pe n wit h t he s p o ns or's a p pr o val (see Secti o n 4. 2  f or o pti o ns at ti me 
of st u d y cl os ure). 
T a ble  1 1 : 
St u d y Tre at me nt  I nf or m ati o n 
 
I N C B 0 0 0 9 2 8 ( St u d y Dr u g) 
Mec h a nis m of acti o n:  
I n hi biti o n of A L K 2, a n u pstrea m re g ulat or of he pci di n 
D os a ge f or m ul ati o n:  
Ta blets  
U nit d ose stre n gt h(s)/  
d os a ge le vel(s):  
St a rti n g d oses  
D ose esc al ati o n:  5 0 m g Q D  
Alter nati ve a d mi nistrati o n sc he d ules ma y be e x pl ore d as descri be d i n 
Secti o n  4. 1. 2 .  
E x p a nsi o n:  T he R D E (s) as defi ne d i n t he d ose -escalati o n sta ge .  
O n -st u d y d oses  
See  Secti o n  4. 1 , Secti o n 6. 5 , a n d Secti o n 6. 6 . 
A d mi nistr ati o n 
i nstr ucti o ns: 
•  I N C B 0 0 0 9 2 8 ca n be ta ke n wit h o ut re gar d t o f o o d.  Partici pa nts will be 
i nstr ucte d n ot t o ma ke u p f or a n y misse d d oses. 
•  If v o miti n g occ urs d uri n g t he c o urse of treat me nt, partici pa nts will be 
i nstr ucte d n ot t o ta ke t he st u d y dr u g a gai n bef ore t he ne xt sc he d ule d d ose. 
•  O n da ys of pre d ose P K sa m pli n g, partici pa nts s h o ul d refrai n fr o m ta ki n g t he 
st u d y dr u g u ntil P K sa m ples are c ollecte d.  
P ac k a gi n g a n d l a beli n g:  
I N C B 0 0 0 9 2 8 will be pr o vi de d i n b ottles.  Eac h b ottle will be la bele d as re q uire d 
per c o u ntr y re q uire me nt.  
St o r a ge:  
Bet wee n 1 5° C a n d 3 0° C ( 5 9° F a n d 8 6° F)  
St at us of tre at m e nt i n 
p artici p ati n g c o u ntries:  
I n vesti gati o nal  

I nc yte C orp orati o n  
Pa ge 4 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
6. 2.  
Pre p ar ati o n , H a n dli n g , a n d Acc o u nt a bilit y  
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or st u d y dr u g  recei ve d a n d a n y discre pa nci es are re p ort e d a n d 
res ol ve d bef ore us e of t h e st u d y dr u g . 
O nl y partici pa nts e nr olle d i n t he st u d y m a y recei v e st u d y dr u g , a n d o nl y a ut h orize d staff m a y 
s u p pl y or a d mi nister st u d y dr u g .  All st u d y dr u g  m ust be st ore d i n a sec ure, e n vir o n me ntall y 
c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mat e d) area i n acc or da n ce wit h t he la bele d st ora ge 
c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d st aff.  
T he i n vesti gat or ( or desi g nee) is res p o nsi ble f or st u d y treat me nt acc o u nta bilit y, rec o nciliati o n, 
a n d rec or d mai nte na n ce ( ie, recei pt, rec o n ciliati o n, a n d fi nal dis p ositi o n rec or ds).  I n ve nt or y a n d 
acco u nta 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 p e 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.  T he 
i n vesti gat or or desi g nee m ust mai ntai n rec or ds t h at d oc u me nt t he f oll o wi ng : 
•  Deli ver y of st u d y dr u g t o t he st u d y site. 
•  I n v e nt or y of st u d y dr u g  at t he site.  
•  Partici pa nt use of t he st u d y dr u g , i ncl u di n g ta blet a n d b ottle c o u nts fr o m eac h s u p pl y 
dis pe nse d.  
•  Ret ur n of st u d y dr u g  t o t he i n vesti gat or or desi g n ee b y partici p a nts. 
T he i n vesti gati o nal pr o d uct m ust be use d o nl y i n acc or da 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 partici pa nts were pr o vi de d t he 
s pecifie d st u d y dr u g .  T h ese rec or ds s h o ul d i ncl u d e dates, q ua ntities, a n d a n y a vaila ble batc h or 
serial n u m bers or u ni q ue c o de n u m bers assi g ne d t o t he i n vesti gati o nal pr o d uct a n d st u d y 
partici pa nts.  
C o m plete d acc o u nta bilit y rec or ds will be arc hi v e d b y t he site.  T he i n vesti gat or or desi g ne e 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 nt ai ners of st u d y dr u g 
u ntil verifie d b y t he st u d y m o nit or ( u nless ot her wise a gree d t o b y t he s p o ns or).  At t he 
c o ncl usi 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  bac k t o t he s p o ns or or its desi g nee f or destr ucti o n acc or di n g t o i nstit uti o nal S O P s.  If 
l ocal pr oce d ures ma n d ate o n-site destr ucti o n of t he i n vesti gati o nal s u p pl y, t he site s h o ul d ( w here 
l ocal pr oce d ures all o w) mai ntai n t he i n vesti gati o nal s u p pl y u ntil t he st u d y m o nit or i ns pects t he 
acc o u nta bilit y rec or ds i n or der t o e v al uate c o m plia nce a n d acc urac y of acc o u nta bilit y b y t he 
i n vesti gati ve site.  At sites w here t he st u d y dr u g  is destr o ye d bef ore m o nit or i ns pecti o n, t he 
m o nit ors rel y o n d oc u me ntati o n of destr ucti o n per t he site S O P.  
F urt her g ui d a nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y dr u g  are pr o vi de d i n 
t he P har mac y Ma n u al. 
See A p pe n di x  B  f or i nstr ucti o ns t o partici pa nt s f or t he ha n dli n g of I N C B 0 0 0 9 2 8. 

I nc yte C orp orati o n  
Pa ge 4 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
6. 3.  
Me as ures t o Mi ni mize Bi as:  R a n d o miz ati o n a n d Bli n di n g  
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 p articipa nts or a gai nst 
hist orical c o ntr ols.  Meas ure me nts of safet y a n d efficac y are o bj ecti 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.  
St u d y dr u g  will be dis pe nse d at t he st u d y visits s u m marize d i n t he S o A ( see Ta ble  3 ) a n d refer t o 
Secti o n  4. 1. 3  re gar di n g ra n d o mizati o n i n d ose e x pa nsi o n . 
Ret ur ne d st u d y dr u g  s h o ul d n ot be re dis pe nse d t o t he partici pa nts. 
6. 4.  
St u d y Tre at me nt  C o m pli a nce  
C o m plia nce wit h st u d y dr u g  s h o ul d be e m p hasize d t o t he partici pa nt b y t he site pers o n nel, a n d 
a p pr o priate 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 will be 
calc ulate d b y t he s p o ns or / desi g nee base d o n t h e st u d y dr u g acc o u nta bilit y (e g, ta blet c o u nts), 
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.  Partici pa nts will be 
i nstr ucte d t o bri n g all st u d y dr u g  wit h t he m t o t he st u d y visits i n or der f or site pers 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 nt a bilit y.  
6. 5.  
D ose -Li miti n g T o xicit y a n d Deter mi n ati o n of M a xi m u m T oler ate d 
D ose  a n d/ or P h ar m ac ol o gic all y Acti ve D ose  
6. 5. 1.  
Defi niti o n of a D ose -Li miti n g T o xicit y  
D ose -li miti n g t o xicit y will be defi ne d as t he o cc urre nce of a n y of t h e t o xicities i n Ta ble  1 2  
occ urri n g d uri n g t he first st u d y dr u g treat me nt c ycle, fr o m C 1 D 1  u p t o a n d i ncl u di n g C ycle 1 
Da y  2 8 ( per re gi me n c ycl e sc he d ule), e xce pt t h ose wit h a clear alter nati ve e x pla nati o n 
(e g, disease pr o g ressi o n) or tra nsie nt ( ≤ 7 2  h o urs) a b n or mal la b orat or y val u es wit h o ut ass ociate d 
cli nicall y si g nifica nt si g ns or s y m pt o ms base d o n i n vesti gat or deter mi nati o n.  
All D L Ts will be assesse d f or se verit y b y t he i n vesti gat or usi n g C T C A E  v 5 . 0.  Partici pa nts w h o 
recei v e at least 7 5 % of d oses of st u d y dr u g at t he le vel assi g ne d or ha v e a D L T will be 
c o nsi dere d e val ua ble f or deter mi ni n g t olera bilit y of t he d ose  (see Secti o n 5. 5 ). 
I n di vi d ual partici pa nt d ose re d ucti o ns ma y be m a de base d o n e ve nts o bser ve d at a n y ti me d uri n g 
st u d y dr u g treat me nt; h o we ver, f or t he p ur p os es of d ose c o h ort escalati o n/ de-escalati o n, 
e x pa n di n g a d ose c o h ort, a n d dete r mi ni n g t he M T D of I N C B 0 0 0 9 2 8, decisi o ns will be ma de 
base d o n e ve nts t hat are o bser ve d fr o m C 1 D 1  t hr o u g h a n d i ncl u di n g t he fi nal da y of C ycle 1 
(ie, Da y 2 8).  

I nc yte C orp orati o n  
Pa ge 4 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 2 : 
Defi niti o n of D ose -Li miti n g T o xicit y  
T o xicit y  
De fi niti o n 
N o n he mat ol o gic  
•  A n y ≥ Gra de 3 n o n he mat ol o gic t o xicit y of a n y d urati o n E X C E P T:  
− Tra nsie nt ( ≤ 7 2 h o urs) a b n or mal la b orat or y val ues wit h o ut ass ociate d cli nicall y 
si g nifica nt si g ns or s y m pt o ms.  N O T E:  All Gr a de 4 electr ol yte a b n or m alities will be 
c o nsi dere d a D L T re g ar dless of d ur ati o n . 
− Gra d e 3 na usea, v o miti n g, a n d diarr hea a de q uatel y c o ntr olle d wit h me dical t hera p y 
wit hi n 4 8 h o urs.  N O T E:  All Gr a de 4 v o miti n g a n d di arr he a will be c o nsi dere d a 
D L T re g ar dless of pr o p hyl actic tre at me nt, res p o nse t o m a n a ge me nt, or d ur ati o n.  
− Gra d e 3 ras h i n  t he a bse nce of des q ua mati o n, wit h n o m uc osal i n v ol ve me nt, t hat d oes 
n ot re q uire s yste mic c ortic o ster oi ds a n d t hat res ol ves t o Gra de 1 i n ≤ 1 4 da ys. 
− C ha n ges i n c h olester ol a n d tri gl yceri des.  
− A n e v e nt clearl y ass ociate d wit h t he u n derl yi n g disease, disease pr o gressi o n, a 
c o nc o mita nt me dicati o n, or c o m or bi dit y.  
•  Si n g ular or n o nfasti n g ele v ati o ns i n bl o o d gl uc ose (ie, bl o o d gl uc ose e xc ursi o ns will be 
c o nsi dere d t o xicities if fasti n g bl o o d gl uc ose is ele v ate d o n 2 se parate occasi o ns).  
C he mistr y  
•  A S T or A L T ele v ati o n  
− A S T a n d/ or A L T ele v ati o n is > 5. 0 a n d ≤ 2 0 × U L N ( Gra de 3) f or > 3 da ys ( 7 2 h o urs) 
or rec urs o n rec halle n ge.  
− A S T a n d/ or A L T is > 2 0 × U L N ( Gra de 4) of a n y d urati o n . 
•  A n y a b n or malities t hat meet t he defi niti o n of H y 's la w, defi ne d as 1) A L T or 
A S T  >  3  ×  U L N c o nc urre nt wit h 2) ser u m t otal bilir u bi n ele v ati o n t o > 2 × U L N wit h o ut 
fi n di n gs of c h olestasis (ser u m A L P <  2  ×  U L N) a n d 3) n o ot her reas o n or a p pare nt 
p ossi ble ca uses of a mi n otra nsferase ele v ati o n a n d h y per bilir u bi n e mia, i ncl u di n g b ut n ot 
li mite d t o viral he patitis, pre-e xisti n g c hr o nic or ac ute li ver disease, or t he a d mi nistrati o n 
of ot her dr u g(s) k n o w n t o be he pat ot o xic ca n be f o u n d t o e x plai n t he c o m bi nati o n of 
i ncrease d A L T a n d t otal bilir u bi n.  
He m at ol o gic  
•  A n y Gra d e 5 t o xicit y.  
•  Gra d e 3 t hr o m b oc yt o pe nia wit h blee di n g.  
•  Gra d e 4 t hr o m b oc yt o pe nia.  
•  Fe brile ne utr o pe nia ( A N C < 1. 0 × 1 0 9/ L wit h a si n gle te m perat ure > 3 8. 3° C [1 0 1° F ] or a 
s ustai ne d te m perat ure ≥ 3 8° C [1 0 0. 4° F ] f or m ore t ha n 1 h o ur). 
•  Gra d e 4 ne utr o pe nia > 7  da ys.  
•  A ne mia will n ot b e c o nsi dere d i n t he defi niti o n of a D L T.  
Ir o n st u dies 
•  Ir o n a b n or malities t hat are s y m pt o matic or affect a n or ga n f u ncti o n will be c o nsi dere d a 
D L T.  
Ot her t o xicities n ot 
meeti n g D L T 
criteria  
•  Alt h o u g h t he r ules f or a dj u dicati n g D L Ts i n t he c o nte xt of d ose escalati o n are s pecifie d 
i n t his ta ble, a n A E n ot liste d i n t his ta ble ma y be c o nsi dere d a D L T after a c o ns ultati o n 
wit h t he s p o ns or a n d i n vesti gat ors base d o n t he e mer gi n g safet y pr ofile.  
A d diti o nal bl o o d sa m ples ma y be dra w n ( per i n v esti gat or discreti o n) t o c o nfir m a p ote ntial D L T 
e ve nt or t o better defi ne its d urati o n.  

I nc yte C orp orati o n  
Pa ge 4 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
6. 5. 2.  
Pr oce d ures f or C o h ort Re vie w a n d D ose Esc al ati o n  
6. 5. 2. 1.  
Assess m e nt of S afet y a n d P h ar m ac o ki netic Res ults  
Safet y tele p h o ne c o nfere nces wit h st u d y i n vesti gat ors will be sc he d ule d b y t he s p o ns or t o re vie w 
c o h ort-s pecific data a n d o verall safet y a n d a v aila ble P K  data c ollect e d d uri n g at least t he first 
treat me nt c ycl e f or eac h c o h ort i n or der t o a gree o n d ose escal ati o n/ d ose de -escal ati o n/c o h ort 
e x pa nsi o n, a dj u dicate i n di vi d ual hi g h -gra de A Es as p ote ntiall y d ose -li miti n g, a n d g ui de ot her 
maj or st u d y decisi o ns.  
T he s p o ns or, i n c o ns ultati o n wit h partici pati n g i n vesti gat ors, ma y elect t o e x pa n d d ose c o h orts 
dee me d t o lera ble, be y o n d w hat is descri be d i n t he prece di n g te xt, i n or d er t o o btai n s u p pleme ntal 
P K, P D, a n d safet y data.  
6. 5. 2. 2.  
I nterc o h ort D ose I ncre ase Al g orit h m 
T he d ose le vel of t h e ne xt s u bse q ue nt c o h ort will be base d o n t he t y pe a n d se verit y of t he 
t o xicit y a n d o n t he a vaila ble P K  data o btai ne d  d uri n g at least t he first st u d y dr u g treat me nt c y cle 
(ie, 2 8  da ys , fr o m C 1 D 1  t o Cycle 1  D a y 2 8 ) i n eac h c o h ort as per Secti o n  4. 1. 1 .  The d ose 
i ncreas e will ne ver e xcee d 1 0 0 % i ncrease ( 2-f ol d i ncreas e).  A d diti o nal p artici pa nt s ma y  be 
e nr olle d t o e ns ure t h e mi ni m u m of 3 e val ua ble partici pa nts per c o h ort is ac hie ve d.  
T he starti n g d ose le vel i n t he d ose-escalati o n sta ges will be 5 0 m g Q D . 
D ose i ncreases will be perf or me d u p t o 2 -f ol d u ntil a Gra de 2 or greater t o xicit y t hat has a 
reas o na bl e p ossi bilit y of bei n g relate d t o st u d y dr u g is o bser ve d ( n ot i ncl u di n g t o xicities wit h a 
clear alter nati ve e x pla nati o n or tra nsie nt a b n or mal la b orat or y val u es wit h o ut cli nicall y 
si g nifica nt si g ns or s y m pt o ms).  O nce t he t o xicit y is o bser ve d, s u bse q ue nt i ncreas es i n st u d y 
dr u g will be li mite d t o n o m ore t ha n 5 0 % i n s uccessi ve c o h orts.  D ose es calati o n will c o nti n ue 
u ntil t he M T D is reac he d a n d/ or t he R D E (s) are d eter mi ne d.  
If t he first d ose le v el is n ot t olera ble, t he re d uce d d ose le vel will be teste d ( 2 5 m g).  F urt her d ose 
de -escalati o ns ma y  be perf or me d as n ee d e d wit h at leas t 2 5 % re d ucti o ns of t he d ose a n d bas e d 
o n a vaila ble ta blet stre n gt hs.   
If m o derat e or se v ere A Es are c o nsiste ntl y o bser ve d acr oss p artici pa nts i n a c o h ort or if 
u nacce pta ble p har mac ol o gical effects, r eas o na bl y attri b uta ble t o I N C B 0 0 0 9 2 8 i n t he o pi ni o n of 
t he i n vesti gat or, are o bs er ve d i n m ore t ha n o ne -t hir d ( 3 3 %) of t he partici p a nts i n a c o h ort, t he n 
d ose escal ati o n will be te m p oraril y halte d a n d n o f urt her partici p a nts will be d ose d u ntil a f ull 
safet y re vi e w of t he st u d y has ta ke n place.  Rele va nt re p orti n g a n d disc ussi o n wit h t he me dical 
m o nit or, rele va nt pers o n nel i ncl u di n g i n vesti gat ors, a n d t he I R B/I E C as n ecessar y/a p plica ble 
will ta ke place bef ore res u m pti o n of a d mi nistrati o n .  
6. 5. 3.  
Defi niti o n of t he M a xi m u m T oler ate d D ose  
As per t he B OI N d esi g n, M T D is d efi ne d as t he d ose at w hic h t he o bser ve d D L T rate is cl osest  
t o t he tar get D L T rate of 2 8% usi n g  a n is ot o nical met h o d t hat ta kes t he ass u m pti o n of a 
m o n ot o nic d ose -t o xicit y relati o ns hi p i nt o acc o u nt.  
F or t he p ur p os es of d ose c o h ort escalati o n/ de -es calati o n / d ose fi n di n g a n d deter mi ni n g t he M T D 
of I N C B 0 0 0 9 2 8, decisi o ns will be ma de base d o n i nf or mati o n o bser ve d fr o m t he first da y of 

I nc yte C orp orati o n  
Pa ge 4 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
st u d y dr u g a d mi nistrati o n t hr o u g h a n d i ncl u di n g t he fi nal da y of C ycl e 1 ( Da y 2 8).  A l o wer 
M T D ma y s u bse q ue ntl y be deter mi ne d b ase d o n rele va nt t o xicities t h at bec o me e vi de nt after 
Da y 2 8.  
6. 5. 4.  
Defi niti o n of t he Rec o m me n de d D ose f or E x p a nsi o n   
T he R D E  d ose(s) as a p plica ble  will be deter mi ne d b y e val uati o n of all a v aila ble data (i e, safet y, 
P K , a n d P D data) fr o m t he d ose-es calati o n sta ge of t he st u d y f or f urt h er i n v esti gati o n i n t he 
e x pa nsi o n c o h orts, i ncl u di n g safet y (l o w -gra de b ut c hr o nic t o xicities, d ose re d ucti o n, d ose 
i nterr u pti o n, or misse d d oses of I N C B 0 0 0 9 2 8).  
T he  R D E (s) will ne ver e xcee d t he M T D.  
6. 6.  
D ose M o dific a ti o ns 
I n di vi d ual partici pa nt d ose re d ucti o ns, i nterr u pti o ns, or m o dificati o ns ma y be perf or me d bas e d 
o n e ve nts o bser ve d at a n y ti me d uri n g treat me nt wit h st u d y dr u g.  
T he occ urre n ce of D L Ts ( see Secti o n  6. 5. 1 ) a n d ot her t o xicities (relat e d or u nrelate d t o st u d y 
dr u g ) will g ui de decisi o ns f or treat me nt i nterr u pti o ns a n d disc o nti n uati o n f or i n di vi d ual 
partici pa nts . 
I n di vi d ual de cisi o ns re gar di n g d ose m o dificati ons of I N C B 0 0 0 9 2 8 s h o ul d be ma de usi n g cli nical 
j u d g me nt i n c o ns ultati o n wit h t he s p o ns or's me dical m o nit or ( w he ne v er p ossi ble), ta ki n g i nt o 
acc o u nt r elate d ness of t he A E t o t he st u d y dr u g a n d t he partici pa nt 's u n derl yi n g c o n diti o n.  
6. 6. 1.  
M a n a ge me nt of D ose -Li miti n g T o xicities or Ot her Ur ge nt Sit u ati o ns  
In v esti gat ors ma y e m pl o y a n y meas ur es or c o n c o mit a nt me dicati o ns necessar y t o o pti mall y treat 
t he partici pa nt aft er disc ussi o n wit h t he s p o ns or's me dical m o nit or  ( w he n e ver p ossi ble). 
6. 6. 2.  
F oll o w -U p of D ose -Li miti n g T o xicities  
A n y D L T s h o ul d be m o nit ore d u ntil it res ol ves t o baseli ne or a p p ears t o h a ve sta bili ze d f or a 
mi ni m u m of 4  wee ks .  D uri n g f oll o w -u p, partici p a nts s h o ul d be see n as ofte n as me dicall y 
i n dicate d t o ass ure s afet y. 
6. 6. 3.  
Criteri a a n d Pr oce d ures f or D ose I nterr u pti o ns a n d A dj ust me nts of St u d y Dr u g  
Safet y c o ncer ns s h o ul d b e disc usse d wit h t he s p o ns or i m me diatel y u p o n occ urre n ce or a ware n ess 
t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y treat me nt. 
Beca use p artici pa nts ma y e nter t he st u d y wit h e xte nsi ve pretreat me nt a n d/ or se vere  B M  
i nfiltrati o n/s u p pressi o n d ue t o t he pri mar y diseas e, t he d ose re d u cti o n/i nterr u pti o n r ules are 
pr o vi de d as g ui deli nes  (s ee Ta ble  1 3 ).  I n di vi d ual decisi o ns re gar di n g d ose 
re d ucti o ns/i nterr u pti o ns s h o ul d be ma de usi n g cli nical j u d g me nt a n d i n c o ns ultati o n wit h t he 
s p o ns or's me dical m o nit or ( w he n e ver p ossi ble), t a ki n g i nt o acc o u nt relate d ness of t he A E t o t he 
st u d y dr u g a n d t he partici pa nt 's u n derl yi n g c o n diti o n.  A d verse e ve nts t hat ha ve a clear 
alter nati ve e x pl a nati o n or tra nsie nt ( ≤ 7 2 h o urs) a b n or mal la b orat or y v al ues wit h o ut ass ociate d 
cli nicall y si g nifica nt si g ns or s y m pt o ms ma y be e xe m pt fr o m d ose -re d ucti o n/i nterr u pti o n r ules. 

I nc yte C orp orati o n  
Pa ge 4 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Treat me nt wit h I N C B 0 0 0 9 2 8 ma y be dela ye d u p t o 2 1 da ys t o all o w f or a n a de q uate rec o v er y 
fr o m t o xicit y.  Partici pa nts ma y res u me treat me nt if n o me dical c o n diti o n or ot her cir c u msta nce 
e xists t hat, i n t he o pi ni o n of t he i n vesti gat or, w o ul d ma ke t he partici p a nt u n s uita ble f or f urt her 
partici pati o n i n t he st u d y.  T he treati n g i n vesti gat or s h o ul d c o ntact t he s p o ns or 's me dical m o nit or 
t o disc uss t he case of a n y partici pa nt w h ose tr eat m e nt has bee n d ela ye d f or m ore t ha n 2 1 da ys 
bef ore restarti n g tr eat me nt wit h I N C B 0 0 0 92 8 . 
Cli nical, h e mat ol o gic, a n d bi oc he mistr y e ve nts ( e g, t hr o m b oc yt o pe nia, a ne mia, ne utr o pe nia, 
L F T a b n or malities) occ urri n g a n d preci pitati n g d ose re d ucti o ns or i nterr u pti o ns d uri n g C ycle 1 
of st u d y dr u g treat me nt will be e val uate d as p ote ntial D L Ts a n d mana ge d as per t he g ui deli nes i n 
Ta ble  1 3 .  Cli nical, h e mat ol o gic , a n d bi oc he mistr y A Es t hat preci pitate d os e i nterr u pti o ns s h o ul d 
be m o nit ore d f or rec o v er y  at least o n a wee kl y basis, if feasi ble.  
T a ble  1 3 : 
G ui deli nes f or I nterr u pti o n a n d Rest arti n g of St u d y Dr u g  
A d verse E ve nt  
Acti o n  T a k e n  
T o xicit y  
N CI C T C A E Gr a de  
He m at ol o g y  
Ne utr o pe nia  
( A N C) 
Gra d e 3  
C o nti n ue st u d y dr u g, a n d m o nit or A N C as cli nicall y 
i n dicate d. 
Gra d e 4  
( A N C < 0. 5  × 1 0 9/ L) 
H ol d st u d y dr u g u p t o 2 1 da ys, a n d m o nit or A N C at least 
wee kl y u ntil t o xicit y res ol ves t o ≤ Gra de 1 or baseli ne le vel.  
•  If t o xicit y lasts ≤ 2 1 da ys, t he partici pa nt ma y res u me 
I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose or at least 
at a 2 5 % re d ucti o n, a n d A N C s h o ul d be m o nit ore d as 
cli nicall y i n dicate d.  
•  If t o xicit y lasts > 2 1 da ys, per ma ne ntl y disc o nti n ue 
I N C B 0 0 0 9 2 8. 
Fe bri le ne utr o pe nia A N C < 1. 0 × 1 0 9/ L + a si n gle 
te m perat ure > 3 8. 3° C 
( 1 0 1° F) or a s ustai ne d 
te m perat ure of ≥ 3 8° C 
( 1 0 0. 4° F) f or > 1  h o ur  
H ol d st u d y dr u g u p t o 2 1 da ys, a n d m o nit or A N C at least 
wee kl y a n d te m perat ure at least dail y u ntil t o xicit y res ol ves 
( disa p peara nce of fe brile ne utr o pe nia). 
•  If fe brile ne utr o pe nia lasts ≤ 2 1 da ys, t he partici pa nt 
ma y res u me I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble 
d ose or at least at a 2 5 % re d ucti o n, a n d A N C s h o ul d be 
m o nit ore d as cli nicall y i n dicate d.  
•  If fe brile ne utr o pe nia lasts > 2 1 da ys, per ma ne ntl y 
disc o nti n ue I N C B 0 0 0 9 2 8.  
T hr o m b oc yt o pe nia  
( platelet c o u nt) 
Gra d e 3  
C o nti n ue st u d y dr u g, a n d m o nit or platelet c o u nts as 
cli nicall y i n dicate d.  
Gra d e 3  
( platelet c o u nt ≥ 2 5  ×  1 0 9/ L 
a n d <  5 0  ×  1 0 9/ L) ass ociate d 
wit h a n y blee di n g  
H ol d st u d y dr u g u p t o 2 1 da ys, a n d m o nit or platelet c o u nts 
at least wee kl y a n d blee di n g at least dail y u ntil t o xicit y 
res ol ves t o ≤ Gra de 1 or baseli ne le vel. 
•  If t o xicit y lasts ≤ 2 1 da ys, t he partici pa nt ma y res u me 
I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose or at least 
at a 2 5 % re d ucti o n, a n d platelet c o u nts s h o ul d be 
m o nit ore d as cli nicall y i n dicate d.  
•  If t o xicit y lasts > 2 1 da ys, per ma ne ntl y disc o nti n ue 
I N C B 0 0 0 9 2 8. 

I nc yte C orp orati o n  
Pa ge 5 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 3 : 
G ui deli nes f or I nterr u pti o n a n d Rest arti n g of St u d y Dr u g ( C o nti n ue d) 
A d verse E ve nt  
Acti o n T a k e n  
T o xicit y  
N CI C T C A E Gr a de  
He m at ol o g y (c o nti n ue d)  
T hr o m b oc yt o pe nia  
( platelet c o u nt) 
(c o nti n ue d) 
Gra d e 4  
( platelet c o u nt < 2 5  ×  1 0 9/ L) 
H ol d st u d y dr u g u p t o 2 1 da ys, a n d m o nit or platelet c o u nts 
at least wee kl y u ntil t he t o xicit y res ol ves t o ≤ Gra de 1 or 
baseli ne le vel.  
•  If t o xicit y lasts ≤ 2 1 da ys, t he partici pa nt ma y res u me 
I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose or at least 
at a 2 5 % re d ucti o n, a n d platelet c o u nts  s h o ul d be 
m o nit ore d  as cli nicall y i n dicate d.  
•  If t o xicit y lasts > 2 1 da ys, per ma ne ntl y disc o nti n ue 
I N C B 0 0 0 9 2 8. 
Ser u m c he mistr y  
A L T/ A S T 
ele v ati o n 
Gra d e 2  
C o nti n ue st u d y dr u g, a n d m o nit or L F Ts at least e ver y 
2  wee ks u ntil t o xicit y res ol ves t o ≤ Gra de 1 or baseli ne 
le vel. 
A L T/ A S T ele v ati o n > 5 a n d 
<  1 0 × U L N  
I nterr u pt st u d y dr u g u p t o 2 1 da ys, a n d m o nit or L F Ts at 
least wee kl y u ntil t he t o xicit y res ol ves t o ≤ Gra de 1 or 
baseli ne le vel.  
•  If L F Ts res ol ve t o ≤ Gra de 1 or baseli ne le vel wit hi n 
7  da ys after i nterr u pti o n, t he partici pa nt ma y res u me 
I N C B 0 0 0 9 2 8 at t he sa me d ose, a n d L F Ts s h o ul d be 
m o nit ore d as cli nicall y i n dicate d.  
•  If L F Ts d o n ot res ol ve t o ≤ Gra de 1 or baseli ne le vel 
wit hi n 7  da ys after i nterr u pti o n, disc uss wit h t he 
s p o ns or's me dical m o nit or. 
A L T/ A S T ele v ati o n ≥ 1 0 a n d 
≤ 2 0 × U L N  
I nterr u pt st u d y dr u g u p t o 2 1 da ys, a n d m o nit or L F Ts at 
least wee kl y u ntil t he t o xicit y res ol ves t o ≤ Gra de 1 or 
baseli ne le vel.  
•  If L F Ts res ol ve t o ≤ Gra de 1 or baseli ne le vel wit hi n 
2 1  da ys after i nterr u pti o n, t he partici pa nt ma y res u me 
I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose or at least 
at a 2 5 % re d ucti o n, a n d L F Ts s h o ul d be m o nit ore d as 
cli nicall y i n dicate d.  
•  If L F Ts d o n ot res ol ve t o ≤ Gra de 1 or baseli ne le vel 
wit hi n 2 1  da ys after i nterr u pti o n, disc uss wit h t he 
s p o ns or's me dical m o nit or. 
Rec urre n ce of Gra d e 3 o n 
rec halle n ge ( A L T/ A S T 
ele v ati o n  > 5 a n d 
≤ 2 0  ×  U L N)  
If A S T a n d/ or A L T > 5 × U L N rec urs u p o n restart of st u d y 
dr u g, i nterr u pt st u d y dr u g u p t o 2 1  da ys, a n d m o nit or L F Ts 
at least wee kl y u ntil t he t o xicit y res ol ves t o ≤ Gra de  1 or 
baseli ne le vel.  
•  If L F Ts res ol ve t o ≤ Gra de 1 or baseli ne le vel wit hi n 
2 1  da ys after i nterr u pti o n, t he partici pa nt ma y res u me 
I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose or at least 
at a 2 5 % re d ucti o n, a n d L F Ts s h o ul d be m o nit ore d as 
cli nicall y i n dicate d.  
•  If L F Ts d o n ot res ol ve t o ≤ Gra de 1 or baseli ne le vel 
wit hi n 2 1 da ys after i nterr u pti o n, per ma ne ntl y 
disc o nti n ue I N C B 0 0 0 9 2 8.  

I nc yte C orp orati o n  
Pa ge 5 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 3 : 
G ui deli nes f or I nterr u pti o n a n d Rest arti n g of St u d y Dr u g ( C o nti n ue d)  
A d verse E ve nt  
Acti o n T a k e n  
T o xicit y  
N CI C T C A E Gr a de  
Ser u m c he mistr y (c o nti n ue d)  
A L T/ A S T 
ele v ati o n 
(c o nti n ue d) 
Gra d e 4 or H y's la w  
Per ma ne ntl y disc o nti n ue I N C B 0 0 0 9 2 8 a n d rec o m me n d 
li ver bi o ps y, ultras o u n d, or ot her i ma gi n g as well as 
he patitis ser ol o g y (e ve n if ne gati ve at baseli ne).  
Ot her t o xicities  
F or partici pa nts wit h a scree ni n g ferriti n le vel of 
<  1 0 0 0 n g/ m L:  w he n t he ferriti n le vel d uri n g t he 
st u d y bec o mes > 1. 5 × t he scree ni n g ferriti n le vel 
A N D t he ferriti n le vel is ≥ 1 0 0 0 n g/ m L  
I nterr u pt st u d y dr u g a n d perf or m n o n– c o ntrast -e n ha nce d 
M RI i n c o nj u ncti o n wit h s oft ware use d f or t he esti mati o n of 
he patic ir o n c o nc e ntrati o n (ie, T 2 -wei g hte d M RI) t o 
n o ni n vasi vel y meas ure li ver ir o n c o nce ntrati o ns.  If t here is 
a c o nc o mita nt nee d t o sta ge he patic fi br osis or e val uate f or 
alter nate li ver diseases, t he n li ver bi o ps y ma y be perf or me d.  
If M RI or li ver bi o ps y d oc u me nts a ne wl y i de ntifie d 
cli nicall y si g nifica nt ir o n o verl oa d, or i n dicati o n t o i nitiate 
ir o n c helati o n, or if t he i ncrease d ferriti n/ir o n o verl oa d ma y 
be d ue t o t he st u d y treat me nt as per i n vesti gat or o pi ni o n (e g, 
li ver cirr h osis), per ma ne ntl y disc o nti n ue I N C B 0 0 0 92 8.  
Ot her wise, if t he ferriti n le vel ret ur ns t o scree ni n g le vel or 
l o wer wit hi n 2 1 da ys after i nterr u pti o n, t he partici pa nt ma y 
res u me I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose or at 
least at a 2 5 % re d ucti o n, a n d ferriti n s h o ul d be m o nit ore d as 
cli nical l y i n dicate d. 
F or partici pa nts wit h a scree ni n g ferriti n le vel of 
≥ 1 0 0 0 n g/ m L WI T H O U T  d oc u me nte d cli nicall y 
si g nifica nt ir o n o verl oa d o n li ver M RI or bi o ps y:  
w he n t he ferriti n le vel d uri n g t he st u d y bec o mes 
>  1. 5 × t he scree ni n g ferriti n le v el.  
Perf or m n o n – c o ntrast-e n ha nce d M RI i n c o nj u ncti o n wit h 
s oft ware use d f or t he esti mati o n of he patic ir o n 
c o nce ntrati o n (ie, M RI T 2) t o n o ni n vasi vel y meas ure li ver 
ir o n c o nce ntrati o ns.  If t here is a c o nc o mita nt nee d t o sta ge 
he patic fi br osis or e val uate f or alter nat e li ver diseases, t he n 
li ver bi o ps y ma y be perf or me d. 
If M RI or li ver bi o ps y d oc u me nts a ne wl y i de ntifie d 
cli nicall y si g nifica nt ir o n o verl oa d or i n dicati o n t o i nitiate 
ir o n c helati o n, or if t he i ncrease d ferriti n/ir o n o verl oa d ma y 
be d ue t o t he st u d y trea t me nt as per i n vesti gat or o pi ni o n (e g, 
li ver cirr h osis), disc o nti n ue per ma ne ntl y. 
Ot her wise, if ele v ate d ferriti n is dee me d t o be res ult of 
tra nsf usi o n a n d n o cli nicall y si g nifica nt c ha n ge i n li ver ir o n 
c o nte nt or e vi de nce of cli nicall y si g nifica nt ir o n o v erl oa d, 
t he n d ose ca n be mai ntai ne d a n d M RI m o nit ori n g will be 
i ncrease d t o e ver y 3 m o nt hs. 
A n y Gra d e 1 or Gra d e 2 t o xicit y  
C o nti n ue st u d y dr u g treat me nt a n d treat t he t o xicit y; m o nit or 
as cli nicall y i n dicate d.  

I nc yte C orp orati o n  
Pa ge 5 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 3 : 
G ui deli nes f or I nterr u pti o n a n d Rest arti n g of St u d y Dr u g ( C o nti n ue d)  
A d verse E ve nt  
Acti o n T a k e n  
T o xicit y  
N CI C T C A E Gr a de  
Ot her t o xicities (c o nti n ue d)  
A n y Gra d e 3 t o xicit y, if cli nicall y si g nifica nt a n d 
n ot ma n a gea ble b y s u p p orti ve care (i ncl u di n g 
Gra d e  3 Q Tc pr ol o n gati o n [ Q Tc F  >  5 0 0  ms] 
wit h o ut life -t hreate ni n g arr h yt h mias) 
I nterr u pt st u d y dr u g u p t o 2 1 da ys u ntil t o xicit y res ol ves 
t o ≤ Gra de 1 or t o baseli ne.  
•  If t o xicit y res ol ves t o ≤ Gra de 1 or baseli ne le vel 
wit hi n 2 1  da ys after i nterr u pti o n, t he partici pa nt ma y 
res u me I N C B 0 0 0 9 2 8 at t he ne xt l o wer t olera ble d ose 
or at least at a 2 5 % re d ucti o n, a n d t o xicit y s h o ul d be 
m o nit ore d as cli nicall y i n dicate d.  
•  If t o xicit y d oes n ot res ol ve t o ≤ Gra de 1 or baseli ne 
le vel wit hi n 2 1 da ys after i nterr u pti o n, per ma ne ntl y 
disc o nti n ue I N C B 0 0 0 9 2 8.  
•  If assesse d as N O T relate d t o st u d y dr u g, I N C B 0 0 0 9 2 8 
ma y be res u me d at t he sa me d ose.  
A n y rec urre nt Gra d e ≥ 3 t o xicit y after 2 d ose  
re d ucti o ns 
Per ma ne ntl y disc o nti n ue I N C B 0 0 0 9 2 8, a n d f oll o w -u p per 
Pr ot oc ol (e xce pti o ns re q uire a p pr o val of s p o ns or's me dical 
m o nit or).  
A n y ot her Gra d e 4 t o xicit y e xce pt Gra d e 4 
ne utr o pe nia a n d Gra d e 4 t hr o m b oc yt o pe nia  
Per ma ne ntl y disc o nti n ue I N C B 0 0 0 9 2 8, a n d f oll o w-u p per 
Pr ot oc ol u nless c o nsi dere d n ot relate d t o st u d y dr u g.  
Ot her  
I n t he e ve nt t hat a partici pa nt's H g b le vel bec o mes 
> 1 4 g/ d L  
M o me ntaril y halt a d mi nistrati o n of I N C B 0 0 0 9 2 8 w he n t he 
partici pa nt's H g b le vel is > 1 4 g/ d L.  A d mi nistrati o n of 
I N C B 0 0 0 9 2 8 ma y be res u me d w he n t he partici pa nt's H g b 
le vel is < 1 2 g/ d L. 
T he d ose re d ucti o ns f or I N C B 0 0 0 9 2 8 will be at least 2 5 % a n d de pe n d o n t he st u d y dr u g stre n gt hs a vaila ble at t he 
site. 
6. 6. 3. 1.  
D ose Re d ucti o ns of St u d y Dr u g f or C o nc o mit a nt  Use of I n d ucer s or I n hi bit ors of 
C Y P 3 A 4/ 5  
T he precli nical st u dies ha ve s h o w n t he f oll o wi n g:  
•  I N C B 0 0 0 9 2 8 is pri maril y meta b olize d b y C Y P 3 A 4/ 5 ( 7 7 %-8 7 %) a n d C Y P 2 D 6 
( 1 3 %-2 3 %), a n d t heref ore P K of I N C B 0 0 0 9 2 8 ma y be affecte d b y c o a d mi nistrati o n 
of p ote nt i n hi bit ors or i n d ucers of C Y P 3 A 4/ 5. 
•  I N C B 0 0 0 9 2 8 is a s u bstrate of t he effl u x tra ns p orter P-g p wit h mi ni mal i n v ol ve me nt 
of B C R P a n d M R P 2.  It is a wea k i n hi bit or of B C R P a n d a ver y wea k i n hi bit or of 
P -g p  ( M D R 1). 
6. 6. 3. 1. 1.  D ose Re d ucti o ns f or C o nc o mit a nt Use of Str o n g  t o P ote nt I n d ucer s or I n hi bit ors 
of C Y P 3 A 4/ 5  
T he use of str o n g  or p ot e nt i n hi bit ors or i n d ucers of C Y P 3 A 4/ 5 is pr o hi bite d i n t he prese nt st u d y 
(see Secti o n 6. 7. 2  a n d refer t o t he U ni versit y of Was hi n gt o n Sc h o ol of P har mac y Dr u g 
I nteracti o n Data bas e Pr o gra m [2 0 0 2 ]) a n d i n parti c ular d uri n g D L T assess me nt i n t he first st u d y 
dr u g  treat me nt c y cle, a n d all eff orts s h o ul d be use d t o a v oi d t he utilizati o n of str o n g or p ote nt 

I nc yte C orp orati o n  
Pa ge 5 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
i n hi bit ors or i n d ucers of C Y P 3 A 4/ 5.  If a partici p a nt m ust  recei ve o ne of t hese c o m p o u n ds, t he 
d ose of I N C B 0 0 0 9 2 8 has  t o be decrease d b y at least 5 0 % c o m pare d t o t he t he oretical d os e.  T he 
precise d ose will be deter mi ne d acc or di n g t o t he stre n gt h of I N C B 0 0 0 9 2 8 t a blets a vaila ble.  If 
feasi ble, bl o o d sa m ples will be dra w n f or P K p ur p oses as defi ne d f or C 1 D 1  ( pre d ose a n d 
2  h o urs, 4  h o urs , a n d bet wee n 6 a n d 8 h o urs p ost d ose) d uri n g t he first c y cle w he n t he partici p a nt 
is a d mi nistere d t he str o n g or p ote nt i n hi bit or or i n d ucer of C Y P 3 A 4/ 5.  
If a partici pa nt m ust  recei ve o ne of t hese c o m p o u n ds d uri n g t he first st u d y dr u g  treat me nt c y cle, 
t his partici pa nt will be declare d n o n e val ua ble f or D L T assess me nt a n d will ha ve t o be re place d.  
6. 6. 3. 1. 2.  D ose Re d ucti o ns f or C o nc o mit a nt Use of We a k  t o M o der ate I n d ucer s o r 
I n hi bit ors of C Y P 3 A 4/ 5, I n hi bit ors or I n d ucers of C Y P 2 D 6 , a n d C o m p o u n ds 
Affecti n g P -G l yc o pr otei n or B C R P  
N o d ose a dj ust me nt s or restricti o ns are rec o m me n de d f or t he us e of wea k t o m o derate i n hi bit ors 
or i n d ucers  of C Y P 3 A 4/ 5 , f or i n hi bit ors or i n d ucers of C Y P 2 D 6 , a n d f or c o m p o u n ds affecti n g 
P -g p or B C R P.  
Please n ote t hat wea k t o m o derate i n d ucers or i n hi bit ors of C Y P 3 A 4/ 5, i n hi bit ors or i n d ucers of 
C Y P 2 D 6 , a n d c o m p o u n ds affecti n g t he effl u x tra ns p orter P-g p a n d B C R P are restri cte d or 
pr o hi bite d, b ut a d diti o nal care s h o ul d b e ta ke n t o i nstr uct t he partici pa nt n ot t o ta k e t he m at t he 
sa me ti me as t he st u d y dr u g, a n d a d diti o nal m o nit ori n g s h o ul d be perf or me d if cli nicall y 
i n dicate d.   
6. 6. 4.  
Criteri a f or Per m a ne nt Disc o nti n u ati o n of St u d y Dr u g  
See Secti o n  7  f or disc o nti n uati o n pr oce d ures.  
6. 6. 5.  
Criteri a a n d Pr oce d ures f or D ose I ncre ases of St u d y Dr u g  
Partici pa nts will ha ve t he o pti o n of escalati n g I N C B 0 0 0 9 2 8 t o a d ose f o u n d t o be t olerate d , as 
defi ne d  i n t he f oll o wi n g t e xt. 
I ntr a partici p a nt st u d y dr u g i ncreas e will be perf or me d at t he i n vesti gat or 's discreti o n wit h 
s p o ns or pre a p pr ov al i n t he f oll o wi n g circ u msta nces: 
•  T he Pr ot oc ol eli gi bilit y criteria are met at t he ti me of escal ati o n.  
•  T he partici pa nt ha s recei ve d ≥ 2 c ycles ( ≥ 6 c ycles f or partici pa nts i n t he 
d ose -e x pa nsi o n sta g es) of st u d y dr u g wit h o ut dr u g -relate d t o xicit y ≥ Gra de 3 a n d 
d oes n ot prese nt dr u g -rel ate d t o xicit y ≥ Gra de 2 at ti me of d ose escal ati o n. 
•  T he partici pa nt is still recei vi n g R B C t ra nsf usi o ns or t here is a n H g b i ncrease of 
<  1. 5  g/ d L i n a n y of t heir assess me nts.  
•  T he ne xt hi g her d ose l e v el has bee n d eter mi ne d t o be safe b ase d o n t he M T D criteria 
(ie, d oes n ot e xcee d t he M T D le vel as deter mi ne d d uri n g t he d ose-es calati o n sta ge s).  
•  D uri n g t he first c ycl e wit h i ncreas e d d ose, partici pa nts m ust be willi n g t o s u b mit t o P K 
sa m pli n g o n Da y 1 5 (as i n C 1 D 1 ) a n d E C G sc he d ule as i n C ycle 1 (see Ta ble  3 , 
Ta ble  4 , Secti o n 8. 3. 5 , a n d Secti o n 8. 5. 1 ).  I n a d diti o n, t he C ycle 1 safet y pr oce d ures 
will be re peat e d f or t he ti me p oi nts of t he first c ycl e wit h i ncreas e d d ose.  

I nc yte C orp orati o n  
Pa ge 5 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  I n t he o pi ni o n of t h e i n vesti gat or, t he partici pa nt d oes n ot ha ve a n y c o nc urre nt 
c o n diti o n or circ u msta nce t hat w o ul d c o m plicate t he d os e escalati o n or P K sa m pli n g 
or p ose i ncrease d ris k t o t he partici pa nt.  
D oses of I N C B 0 0 0 9 2 8 will ne ver e xcee d t he M T D as i de ntifie d i n t he d os e -escalati o n sta ges as 
a p plica ble. 
6. 6. 6.  
Tre at me nt After I niti al R a di ol o gic E vi de nce of Dise ase Pr o g ressi o n  
See  Secti o n  7. 1  a n d Secti o n  8. 9 . 
6. 7.  
C o nc o mit a nt Me dic ati o ns  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 partici pa nt 
eli gi bilit y. 
All c o nc o mita nt me dicati o ns a n d treat me nts (i nc l u di n g o ver-t he-c o u nter or prescri pti o n 
me dici nes, vita mi ns, vacci nes, a n d/ or her bal s u p ple 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 fr o m 3 0 da ys bef ore  C 1 D 1  a n d u p t o 3 0 da ys after t he last d ose of 
st u d y dr u g or u ntil t he partici pa nt be gi ns a ne w a ntica ncer t h era p y, w hic he ver occ urs first, will 
be rec or de d i n t he e C R F.  A n y a d diti o n, deleti o n, or c ha n ge i n t he d os e of t hese me dicati o ns will 
als o be rec or de d.  C o nc o mita nt me dicati o ns a d mi nistere d after 3 0 da ys aft er t he last d ose o f 
st u d y dr u g s h o ul d be rec or de d f or S A Es as defi ne d i n Secti o n  9. 2 .  C o nc o mita nt 
treat me nts/ pr oce d ures t h at are re q uire d t o ma n a ge a partici pa nt'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 de d i n t he e C R F.  T he s p o ns or's me dical m o nit or s h o ul d be c o ntacte d if 
t here are a n y q u esti o ns re gar di n g c o nc o mita nt or pri or t hera p y. 
6. 7. 1.  
Per mitte d Me dic ati o ns  a n d Pr oce d ures  
Wit h t he e xce pti o n of t h ose m e nti o ne d i n Secti o n  6. 7. 2  a n d Secti o n  6. 7. 3 , all me dicati o ns a n d 
treat me nts (i ncl u di n g o ver-t he-c o u nt er or prescri pti o n me dici nes, vita mi ns, vacci nes, a n d/ or 
her bal s u p ple me nts) n ecessar y f or t he st u d y partici pa nts ' o pti mal cli nical care a n d ma na ge me nt 
ca n be a d mi nistere d t o st u d y partici pa nts . 
6. 7. 2.  
Rest ricte d Me dic ati o ns  a n d Pr oce d ures  
T he f oll o wi n g me dicati o ns ha ve restri cti o ns o n use or d oses or re q uire c ha n ges t o t he wa y i n 
w hic h I N C B 0 0 0 9 2 8 is a d mi nistere d d uri n g t he st u d y. 
•  L o w -d ose as piri n ( ≤ 1 5 0 m g/ da y) a n d n o nster oi dal a nti -i nfla m mat or y a ge nts 
(i b u pr ofe n) m a y be use d; h o we ver, ca uti o n s h o ul d be use d w he n a d mi nisteri n g 
i b u pr ofe n or ot her n o nster oi dal a nti-i nfla m mat or y dr u gs wit h l o n g eli mi nati o n 
half -li ves.  P artici pa nts s h o ul d be m o nit ore d c l osel y f or t o xicit y, es peciall y f or 
m yel os u p pressi o n a n d re nal a n d GI t o xicit y  
•  If a partici pa nt is t o recei ve a C O VI D-1 9 vacci nati o n d uri n g t he prese nt st u d y, t he 
s p o ns or d oes n ot rec o m me n d perf or mi n g t his va cci nati o n d uri n g t he D L T assess me nt 
peri o d (ie, d uri n g t he first st u d y treat me nt c ycle ). 

I nc yte C orp orati o n  
Pa ge 5 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  I n d u cers or i n hi bit ors of t he meta b olizi n g e nz y me C Y P 3 A 4/ 5  (refer t o t he U ni versit y 
of Was hi n gt o n Sc h o ol of P har mac y Dr u g I nteracti o n Data base Pr o gra m  [2 0 0 2 ]): 
− W he n co n c o mita nt  a d mi nistrati o n of a str o n g  or p ote nt i n hi bit or of C Y P 3 A 4/ 5 is 
re q uire d f or partici p a nt ma na ge me nt, t he d ose of I N C B 0 0 0 9 2 8 m ust be a dj uste d 
as prese nte d i n Secti o n 6. 6. 3. 1 . 
− T he  use of wea k  t o m o derate i n hi bit ors or i n d ucers of C Y P 3 A 4/ 5 is disc o ura ge d; 
alter nati ve t hera pies s h o ul d be c o nsi dere d w here ver p ossi ble.  S h o ul d o ne of t hese 
me dicati o ns be me dicall y nece ssar y, its use s h o ul d be d oc u me nte d; h o w e ver, d ose 
a dj ust me nt of I N C B 0 0 0 9 2 8 is n ot re q uire d.  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 mes ma y res ult i n t he 
nee d f or a re d u ce d d os e of I N C B 0 0 0 9 2 8 d uri n g  a peri o d of c o n c o mita nt 
me dicati o n use.  If re q uir e d f or safet y, t he n t he d ose of I N C B 0 0 0 9 2 8 ma y be 
re d uce d t o at least 5 0 %  c o m pare d t o t he t he oretical d ose .  I n t h ese cir c u msta nces, 
t his s h o ul d be clearl y d oc u me nte d i n t he partici pa nts' me dical s o urce.  T h e 
s p o ns or's me dical 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 g e nts . 
6. 7. 3.  
Pr o hi bite d Me dic ati o ns  a n d Pr oce d ures  
T he f oll o wi n g me dicati o ns are pr o hi bite d d uri n g t he st u d y:  
•  A n y i n vesti gati o nal me dicati o n ot her t ha n I N C B 0 0 0 9 2 8.  Use of s uc h me di cati o ns 
wit hi n 2 8 da ys 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 . 
•  Use of i nterfer o n, t hali d o mi de, b us ulfa n, le nali d o mi de, or a na greli de 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 . 
•  As piri n at d oses e xcee di n g 1 5 0 m g /da y is pr o hi bite d . 
•  Str o n g or p ote nt  i n d ucers a n d i n hi bit ors of C Y P 3 A 4/ 5 are n ot per mitte d  wit h t he 
e xce pti o n of t o pical k et oc o naz ole , b ase d o n its l o w o verall bi oa vaila bilit y . 
•  E S As.  
T he sp o ns or 's me dical m o nit or s h o ul d be c o ntacte d i n t he e ve nt a partici pa nt recei ved  a n y 
treat me nt f or si g ns or s y m pt o ms of C O VI D -1 9 . 
6. 8.  
Tre at me nt After t he E n d of t he St u d y  
After t he e n d of t he st u d y, t he partici pa nts will recei ve t hera p y/treat me nt as per t he l ocal 
i nstit uti o n's sta n dar d of care a p plica ble t o t heir dis ease (see Secti o n 4. 2  f or t he defi niti o n of t he 
e n d of t he st u d y). 

I nc yte C orp orati o n  
Pa ge 5 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
7.  
DI S C O N TI N U A TI O N O F S T U D Y T R E A T M E N T  A N D 
P A R TI CI P A N T WI T H D R A W A L  
7. 1.  
Disc o nti n u ati o n of St u d y Tre at me nt  
7. 1. 1.  
Re as o ns f or Disc o nti n u ati o n  
Partici pa nts m ust  be disc o nti n ue d fr o m st u d y treat me nt f or t he f oll o wi n g reas o ns:  
•  Occ urre nce of u nacce pta ble t o xicit y, defi ne d as t h e occ urre n ce of a n A E t h at is 
relate d t o st u d y dr u g t hat, i n t he j u d g me nt of t he i n vesti gat or or t he s p o ns or's me dical 
m o nit or, c o m pr o mises t he partici pa nt 's a bilit y t o c o nti n ue st u d y-s pecific pr oce d ures 
or is c o nsi dere d t o n ot be i n t he partici pa nt 's best interest.  T he occ urre nce of 
u nacce pta ble t o xicit y n ot ca use d b y t he u n derl yi n g mali g na nc y will be pres u me d t o 
be relate d t o st u d y dr u g a n d will re q uire t hat t he st u d y dr u g be per m a ne ntl y 
disc o nti n ue d.  
•  T he partici pa nt bec o mes pre g na nt.  
•  T he partici pa nt re q ui res a d diti o nal a nti ne o plastic s yste mic t hera p y, w hic h will q ualif y 
as disease pr o gressi o n.  
•  F urt her partici pati o n w o ul d be i nj uri o us t o t he partici pa nt 's healt h or well-b ei n g, i n 
t he i n vesti gat or's me dical j u d g me nt. 
•  T he partici pa nt wit h dr a ws t heir c o nse nt t o partici p ate i n t he st u d y.  N O T E:  C o nse nt 
wit h dra w n mea ns t hat t h e partici pa nt has e x plicitl y i n dicate d t hat t he y d o n ot wa nt t o 
be f oll o we d a n y l o n ger; i n t his case, n o f urt her dat a, e xce pt data i n t he p u blic d o mai n, 
ma y be s olicite d fr o m or c ollecte d o n t he partici pa nt.  Partici pa nts ma y c h o ose t o 
disc o nti n ue st u d y dr u g treat me nt a n d re mai n i n t he st u d y t o be f oll o we d f or 
pr o gressi o n a n d p ost -tr eat me nt assess me nts (see T a ble  3 ). 
•  T he st u d y is ter mi nate d b y t he s p o ns or.  
•  T he st u d y is ter mi nate d b y t he l ocal healt h a ut h orit y , I R B, or I E C. 
•  T he partici pa nt prese nts a st u d y dr u g treat me nt f ail ure, defi ne d as eit her  of t he 
f oll o wi n g: 
− Decrease of H g b d uri n g t he st u d y dr u g treat me nt p eri o d of at least 1. 5 g/ d L 
relati ve t o baseli ne s ustai ne d f or at least 4 wee ks O R  
− A bse nce of a n y H g b i ncrease of at least 1. 5 g/ d L relati ve t o baseli ne or 
persiste nce of tra nsf usi o n re q uire me nt d uri n g at le ast 6 m o nt hs ( 2 4 wee ks) of t he 
st u d y dr u g treat me nt peri o d. 
•  A persiste nt A E re q uiri n g a n i nterr u pti o n of I N C B 0 0 0 9 2 8 a d mi nistrati o n f or m ore 
t ha n 2 1 da ys, u nless a l o n ger i nterr u pti o n has b ee n a p pr o ve d b y t he s p o ns or 's me dical 
m o nit or.  
•  Treat me nt -e mer ge nt ir o n o verl oa d wit h s y m pt o ms or da ma ge i n or g a n f u ncti o n.  

I nc yte C orp orati o n  
Pa ge 5 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  T he partici pa nt is u na ble t o t olerate I N C B 0 0 0 9 2 8 at a re d u ce d d ose s p ecifi e d f or t he 
c o h ort d ue t o o ne of t h e f oll o wi n g reas o ns:  
− Rec urre n ce of a Gra de 3 t o xicit y after 2 d ose re d u cti o ns (see  Secti o n  6. 6. 3 ). 
− A n y Gra d e 4 t o xicit y ot her t ha n Gra de 4 n e utr o pe nia a n d Gra d e 4 
t hr o m b oc yt o pe nia (see Secti o n  6. 6. 3 ).  
A partici pa nt  m a y be per ma ne ntl y disc o nti n ue d fr o m st u d y dr u g treat me nt as f oll o ws:  
•  If, d uri n g t he c o urse of t h e st u d y, a partici pa nt is f o u n d n ot t o ha ve met all 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 he p artici pa nt s h o ul d be per ma ne ntl y dis c o nti n ue d fr o m st u d y dr u g 
treat me nt. 
•  If a partici pa nt is n o nc o m plia nt wit h st u d y pr oce d ures or st u d y dr u g a d mi nistrati o n i n 
t he i n vesti gat or's o pi ni o n, t he 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 he partici pa nt. 
•  If a Gra de 4 cli nical e ve nt has N O T bee n c o nfir me d u p o n rec halle n g e wit h t he st u d y 
dr u g, at t he o pti o n of t he i n vesti gat or.  
I n a d diti o n t o t he criteria descri be d i n t he prece di n g te xt, partici pa nts wit h M D S will o nl y 
per ma ne ntl y disc o nti n ue st u d y dr u g i n t he e ve nt of a blast perce nta ge of ≥ 2 0 % i n t he B M  or t he 
peri p heral bl o o d at a n y ti me d uri n g t he st u d y.  
F urt her m ore, t he i n vesti g at or is all o we d t o disc o nti n ue I N C B 0 0 0 9 2 8 a d mi nistrati o n if i n his/ her 
o pi ni o n, t he partici pa nt is n o l o n ger be nefitti n g fr o m treat me nt wit h I N C B 0 0 0 9 2 8.  I n s u c h a 
sit uati o n, t he i n vesti gat or will d oc u me nt his/ her assess me nt a n d decisi o n i n t he partic i pa nt's 
e C R F a n d s o urce d oc u m e nts.  
I n t he e ve nt t hat a p artici pa nt per ma ne ntl y disc o nti n ues st u d y dr u g, re gar dless of reas o n(s), 
reas o na bl e eff orts s h o ul d be ma de t o ha ve t he partici pa nt ret ur n f or a n earl y E O T visit as well as 
t he safet y f oll o w-u p visit a n d ha ve e val uati o ns c o m plete d as descri b e d i n  Ta ble  3 . 
7. 1. 2.  
Disc o nti n u ati o n Pr oce d ures  
T he decisi o n t o disc o nti n ue st u d y dr u g  will n ot c o nstit ute st u d y wit h dra wal or st u d y c o m pleti o n.  
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 st u d y dr u g , t he E O T visit 
s h o ul d be c o n d ucte d, t he st u d y dr u g treat me nt peri o d  will be c o nsi dere d c o m plete , a n d t he 
f oll o w-u p peri o d  will be gi n.  Reas o na ble eff orts s h o ul d be ma de t o ha ve t h e partici pa nt ret ur n f or 
t he safet y f oll o w-u p visit.  T hese visits are des cri b e d i n  Ta ble  3  a n d T a ble  4 .  T he date of t h e last 
d ose of st u d y dr u g  a n d t h e reas o n f or disc o nti n uati o n of st u d y dr u g  will be rec or de d i n t he e C R F.  
If a p artici p a nt is disc o nti n ue d fr o m st u d y dr u g tre at me nt: 
•  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 wa l m ust be d oc u me nte d i n t he partici pa nt's me dical rec or d 
a n d t he pri mar y reas o n f or wit h dra wal m ust be i n cl u de d i n t he e C R F.  
•  T he E O T visit s h o ul d be perf or me d a n d date rec or de d.  
•  T he stat us of t he partici p a nt s h o ul d be u p date d t o E O T i n t he I R T.  

I nc yte C orp orati o n  
Pa ge 5 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  Partici pa nt s m ust be f oll o we d f or s afet y u ntil t he ti me of t he safet y f oll o w-u p visit or 
u ntil st u d y dr u g – relate d t o xicities res ol ve, ret ur n t o baseli ne, or are dee me d 
irre versi ble, w hic he v er is l o n gest.  
If t he partici p a nt disc o nti n ues st u d y dr u g a n d acti vel y wit h dr a ws c o ns e nt f or c ollecti o n of 
f oll o w-u p data (s afet y f oll o w -u p or disease assess me nt), t he n n o a d diti o nal data c ollecti o n 
s h o ul d occ ur; h o we v er, partici pa nts will ha ve t he o pti o n of wit h dra wi n g c o nse nt f or st u d y dr u g 
b ut c o nti n ui n g i n t he f oll o w -u p peri o d of t h e st u d y f or safet y/efficac y assess me nts.  
7. 2.  
P artici p a nt Wit h dr a w al F r o m t he St u d y 
A partici pa nt ma y wit h dra w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or f or safet y, be ha vi oral, c o m plia nce, or 
a d mi nistrati ve reas o ns.  
If t he partici p a nt wit h dra ws c o nse nt f or discl os ur e of f ut ure i nf or mati o n, t he s p o ns or ma y ret ai n 
a n d c o nti n ue t o use a n y d ata c ollecte d bef ore s uc h a wit h dra wal of c o nse nt.  
If a partici pa nt wit h dra ws fr o m t he st u d y, he/s he ma y re q uest destr u cti o n of a n y sa m ples ta ke n 
a n d n ot teste d, a n d t he i n vesti gat or m ust d oc u me nt t his i n t he site st u d y rec or ds.  
See  Ta ble  3  a n d Ta ble  4  f or data t o be c ollecte d at t he ti me of st u d y wit h dra w al a n d f oll o w -u p 
a n d f or a n y f urt her e val u ati o ns t hat nee d t o be c o m plete d.  
7. 3.  
L ost t o F oll o w -U p  
A partici pa nt  will be c o nsi dere d l ost t o f oll o w -u p if he /s he re p eate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site. 
T he f oll o wi n g acti o ns m ust be ta ke n if a p artici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit: 
•  T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ul e t he misse d visit as 
s o o n as p ossi ble a n d c o u nsel t he partici pa nt o n t h e i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascert ai n w het her or n ot t he partici pa nt wis hes t o a n d/ or 
s h o ul d c o nti n ue i n t he st u d y. 
•  Bef ore a p artici pa nt is dee me d l ost t o f oll o w -u p, t he i n vesti gat or or desi g n ee m ust 
ma ke e ver y eff ort t o re g ai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he parti ci pa nt 's last k n o w n maili n g a d dress 
or l ocal e q ui vale nt met h o ds).  T hese c o nt act atte m pts s h o ul d be d oc u me nte d i n t he 
partici pa nt 's me dical r ec or d. 
•  S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o  ha ve 
wit h dra w n fr o m t he st u d y.  

I nc yte C orp orati o n  
Pa ge 5 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  
All st u d y assess me nts will be perf or me d as i n dicat e d i n t he S o A ( see T a ble  3 ), a n d all la b orat or y 
assess me nts will be perf or me d as i n dicate d i n  T a ble  4 .  F urt h er deta ils 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 i n vesti gat or site file.  
8. 1.  
A d mi nistr ati ve a n d Ge ner al Pr oce d ures  
8. 1. 1.  
I nf or me d C o nse nt Pr ocess  
•  T he i n vesti gat or or his/ he r re prese nt ati ve will e x plai n t he nat ure of t h e st u d y t o t he 
partici pa nt or his/ her le g all y a ut h orize d re pres e nt ati ve a n d a ns w er all q uesti o ns 
re gar di n g t he st u d y. 
− 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 he I R B /I E C-a p pr o ve d versi o n i n a 
la n g ua ge t hat is nati ve a n d u n dersta n da ble t o t he partici pa nt.  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 nee 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 ne e a n d re g ul at or y a ut h oriti es ha ve 
direct access t o partici pa nt rec or ds.  
− T he I C F m ust c o ntai n all re q uire d ele me nts a n d d escri be t he nat ure, s c o pe, a n d 
p ossi ble c o nse q ue n ces of t he st u d y i n a f or m u n dersta n da ble t o t he st u d y 
partici pa nt.  
•  Partici pa nts m ust be i nf or me d t hat t heir partici p ati o n is v ol u ntar y.  Partici pa nts or 
t heir le gall y a ut h orize d re prese nt ati ve will be re q uire d t o si g n a state me nt of i nf or me d 
c o nse nt t hat meets t he a p plica ble re q uir e me nts a n d re g ulati o ns f or t he c o u ntr ies i n 
w hic h t he st u d y is bei n g c o n d ucte d as well as t he I R B /I EC  or st u d y ce nt er.  
•  T he partici pa nt m ust be i nf or me d t hat his/ her pers o nal st u d y -relate d d ata will be use d 
b y t he s p o ns or i n acc or da nce wit h l ocal dat a pr otecti o n la ws.  T he le vel of discl os ure 
m ust als o be e x plai ne d t o t he partici pa nt.  
•  T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y be e xa mi ne d b y 
Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he 
s p o ns or, b y a p pr o priat e I R B/I EC  me m bers, a n d b y i ns pect ors fr o m re g ulat or y 
a ut h orities.  
•  T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was 
o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y a n d t he date t he writte n 
c o nse nt was o btai ne d.  T he a ut h orize d p ers o n o bt ai ni n g t he i nf or me d c o ns e nt m ust 
als o si g n t he I C F.  
•  Partici pa nts m ust pr o vi de c o nse nt t o t he m ost c urre nt versi o n of t he I C F d uri n g t heir 
partici pati o n i n t he st u d y.  
•  A c o p y of t he I C F(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt 's le gall y 
a ut h orize d re pres e ntati ve.  

I nc yte C orp orati o n  
Pa ge 6 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Partici pa nts w h o are rescree ne d are re q uir e d t o si g n a ne w I C F.  
8. 1. 2.  
Scree ni n g Pr oce d ures  
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 da y t he partici pa nt recei ves t h e f irst 
d ose of st u d y dr u g .  Scree ni n g ma y n ot e xcee d 2 8 da ys.  Assess me nts t hat are re q uire d t o 
de m o nstrate eli gi bilit y ma y be perf or me d o ver t he c o urse of 1  or m ore d a ys d uri n g t he scree ni n g 
pr ocess.  
Pr oce d ures c o n d ucte d as part of t he partici pa nt 's r o uti ne cli nical ma na ge m e nt ( e g, bl o o d c o u nt, 
i ma gi n g st u d y) a n d o btai ne d bef ore si g ni n g of i nf or me d c o nse nt ma y b e use d f or scree ni n g or 
baseli ne p ur p oses pr o vi de d t he pr oce d ure m eets t he Pr ot oc ol -defi ne d criteria a n d has b ee n 
perf or me d i n t he ti mefra me of t he s t u d y (ie, wit hi n 2 8 da ys of C 1 D 1 ).  F or partici pa nts w h o are 
e nr olle d i n t he st u d y, i nf or mati o n ass ociate d wit h eli gi bilit y re q uire me nts m ust be e ntere d i nt o 
t he a p pr o priat e e C R F pa ges. 
Res ults fr o m t he scree ni n g visit e val uati o ns will be re vie we d t o c o nfi r m eli gi bilit y bef ore t he 
first a d mi nistrati o n of st u d y dr u g .  I n di vi d ual tests wit h res ults t hat fail eli gi bilit y re q uire me nts 
ma y be re p eate d d uri n g scree ni n g if t h e i n vesti gat or belie ves t he res ults t o be i n err or.  F or 
scree ni n g assess me nts t hat are repeate d, t he m ost rece nt a vaila ble res ult bef ore recei vi n g t he first 
d ose of st u d y dr u g will be use d t o deter mi ne eli gi bilit y.  Treat me nt wit h st u d y dr u g s h o ul d start 
as s o o n as p ossi ble b ut wit hi n 2 da ys after c o nfir mati o n of t he partici pa nt 's eli gi bilit y. 
See Secti o ns  5. 4  a n d 5. 5  f or i nf or mati o n re g ar di n g scree n fail ures a n d re pl ace me nt of 
partici pa nts, res p ecti vel y . 
8. 1. 3.  
I nter acti ve Res p o nse Tec h n ol o g y Pr oce d ure 
Eac h partici pa nt will be i de ntifie d i n t he st u d y b y a partici pa nt I D n u m ber, w hic h is a 
c o m bi nati o n of t he site I D a n d partici pa nt n u m ber.  Site staff s h o ul d c o ntact t he I R T t o o btai n t he 
partici pa nt I D n u m ber at scree ni n g.  U p o n d eter mi ni n g t hat t he partici pa nt is eli gi ble f or st u d y 
e ntr y, t he I R T will be c o ntacte d t o o btai n t he st u d y dr u g .  A d diti o nall y, t he I R T will be c o nt acte d 
as a p pr o priat e t o u p date t he st u d y dr u g s u p pl y a n d t he partici pa nt 's stat us i n t he st u d y.  
A d diti o nal details are pr o vi de d i n t he I R T M a n ual.  
8. 1. 4.  
De m o gr a p h y a n d Me dic al Hist or y  
8. 1. 4. 1.  
De m o gr a p hics a n d Ge ner al Me dic al Hist or y  
De m o gra p hic d ata a n d g e neral me di cal hist or y will be c ollecte d at scree ni n g  b y t he i n vesti gat or 
or q ualifie d desi g ne e a n d will i ncl u de year of birt h/ a ge, race, et h nicit y, me dical a n d s ur gical 
hist or y, a n d c urre nt ill nesses.  Me dical hist or y will i ncl u de rele va nt me dical or s ur gical treat me nt 
wit hi n t he last 1 0 years t hat are c o nsi dere d t o b e cli nicall y si g nifica nt b y t he i n vesti gat or.  
8. 1. 4. 2.  
Dise ase C h ar acteristi cs a n d Tre at me nt  Hist or y  
A disease -tar gete d m e dic al a n d treat me nt hist or y will be c ollecte d at scree ni n g .  Details 
re gar di n g t he p artici pa nt 's mali g na nc y u n der st u d y, i ncl u di n g date of dia g n osis, i nitial a n d 
c urre nt sta g e, t u m or hist ol o g y, rele va nt diseas e c h aract eristics, a n d pri or treat me nts, i ncl u di n g 
s yste mic treat me nts, ra di ati o n, a n d s ur gical pr o ce d ures, will be rec or de d.  

I nc yte C orp orati o n  
Pa ge 6 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8. 2.  
Effic ac y Assess me nts  
8. 2. 1.  
Effic ac y Assess m e nts f o r All Dise ase  G r o u ps  
T he f oll o wi n g pieces of i nf or mati o n will be c ollecte d f or eac h tra n sf usi o n: 
•  T he bl o o d pr o d uct(s) tra nsf use d a n d its q ua ntit y ( u nits) . 
•  T he date of t h e tra nsf usi o n(s) . 
•  T he H g b/ platelet val ue(s) t hat tri g gere d t he tra nsf usi o n(s) as a p plica ble.  
T he c ollecti o n of R B C tra nsf usi o ns a n d H g b val u es will be perf or me d as f oll o ws:  
•  B ef ore st u d y e ntr y:  
− R B C tra nsf usi o ns a n d H g b val ues ha ve t o be rec or de d f or u p t o 1 2  wee ks b ef ore 
t he first st u d y dr u g d ose, if a vaila ble.  T he c ollecti o n of H g b val ues a n d R B C 
tra nsf usi o ns are m a n dat or y o nl y d uri n g t he 8 wee ks i m me diatel y prece di n g t he 
first d ose of st u d y dr u g , res pecti vel y.  
•  D uri n g t he st u d y dr u g treat me nt peri o d:  
− T he R B C tra nsf usi o ns will be c ollecte d fr o m t he first d ose of st u d y dr u g , 
t hr o u g h o ut t he w h ole st u d y dr u g treat me nt peri o d, a n d u ntil 3 0 da ys after t h e last 
d ose of st u d y dr u g .  
− T he H g b val ues will be c ollecte d at least w ee kl y f or t he first c ycl e, e ver y 2 wee ks 
f or eac h c y cle t hereafter, a n d at t he E O T a n d safet y f oll o w-u p visits.  
T he B M  as pirate/ bi o ps y assess me nts will be per f or me d a n d a n al yze d l ocall y b y t he i n vesti gat or 
as per t he l oc al sta n dar ds  d uri n g scree ni n g .  F or partici pa nts wit h M M, B M as pirate/ bi o ps y 
perf or me d wit hi n 3 m o nt hs pri or t o scree ni n g  is all o we d as l o n g as arc hi val tiss ue is  a vaila ble. 
F or partici pa nts wit h  M D S, a B M as pirate/ bi o ps y s h o ul d be o btai ne d wit hi n 3 m o nt hs pri or t o 
scree ni n g.  T h e B M  as pir ate/ bi o ps y assess me nts (bl o o d s mears all o we d f or dr y ta ps ) will be 
re peat e d t o c o nfir m a res p o nse ( C R or P R f or M D S a n d C R f or M M) i n cas e of s us pecte d disease 
pr o gressi o n a n d as cli nicall y i n dicate d per i nstit uti o nal sta n dar ds.  T he dise ase res p o ns e 
assess me nt will be perf or me d o n -site b y t he i n vesti gat or as per T a ble  3 .  
I n a d diti o n, f or M M parti ci pa nts o nl y, ser u m a n d uri ne pr otei n electr o p h oresis, ser u m free li g ht 
c hai ns, q ua ntitati ve i m m u n o gl o b uli ns , a n d beta 2-macr o gl o b uli n  assess me nts will be c o n d ucte d 
d uri n g scree ni n g, e ver y 6  c ycles, at t he E O T visit , a n d i n case of s us pecte d pr o gressi o n.  S keletal 
s ur ve y s h o ul d be c o n d u cte d at scree ni n g ( u nless p erf or me d  wit hi n 8 wee ks pri or t o C 1 D 1 ) a n d 
s u bse q ue ntl y as cli nicall y i n dicate d at t he discreti o n of t he i n v esti gat or.  T hese assess me nts will 
be perf or me d a n d a nal yz e d l ocall y b y t he i n vesti gat or.  
Pretreat me nt bas eli ne me as ures of c yt o pe nias are a vera g es of at least 2  meas ure me nts ( n ot 
i nfl ue nce d b y tr a nsf usi o ns [ie, n o R B C tra nsf usi o ns f or at least 2  wee ks a n d n o platelet 
tra nsf usi o ns f or at least 1  wee k ]) o ver at least 1  wee k pri or t o t hera p y.  D uri n g  t he st u d y dr u g 
treat me nt peri o d, all R B C tra nsf usi o ns recei ve d b y t he partici pa nts will acco u nt f or t he defi niti o n 
of tra nsf usi o n i n de pe n d e nce, re g ar dless of t h e reas o n f or t he tra nsf usi o n a n d irres pecti ve of t he 
H g b val ue t hat  tri g gere d t he tra nsf usi o n.  H o we v er, tra nsf usi o ns s h o ul d be a v oi de d u nless t he 
H g b val ue is  <  8. 5  g/ d L, a ne mia is s y m pt o matic, or acti ve blee di n g is detect e d.  

I nc yte C orp orati o n  
Pa ge 6 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8. 2. 2.  
Me dic al Res o urce Utiliz ati o n a n d He alt h Ec o n o mics  
N ot a p plica ble.  
8. 3.  
S afet y Assess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A  (see Ta ble  3 ) a n d T a ble  4 . 
See Secti o n  6. 6  f or g ui deli nes re gar di n g t he ma n a ge me nt of rel e va nt la b orat or y or ot her safet y 
assess me nt a b n or malities.  
T he safet y assess me nts  d escri be d i n t he f oll o wi n g secti o ns a p pl y t o b ot h disease gr o u ps.  
8. 3. 1.  
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 partici pa nt si g ns t he I C F  u ntil at least 
3 0  da ys after t h e last d ose of st u d y dr u g or u ntil t he start of ne w a ntica n cer t hera p y, w hic h e ver 
occ urs first .  T h e S A Es s us pecte d t o be relate d t o st u d y dr u g as per t he i n v esti gat or 's assess me nt 
will be rec or de d a n yti me.  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 v erse E ve nts F or m i n t he e C R F re gar dl ess of t he ass u m pti o n of a ca usal 
relati o ns hi p wit h t he st u d y dr u g .  C o n diti o ns t hat were alrea d y pres e nt at t he ti me of i nf or me d 
c o nse nt s h o ul d be rec or de d o n t he Me dical Hist or y F or m i n t he e C R F .  A d verse e v e 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 ne ver p ossi ble rat her t ha 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.  
A d verse e ve nts will be re p orte d b y t he  partici p a nt ( or, w he n a p pr o priat e, b y a care gi ver, 
s urr o gate, or t h e partici p a nt's le gall y a ut h orize d re prese nt ati ve).  T he i n v esti gat or a n d a n y 
q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d rec or di n g e ve nts t hat meet 
t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or f oll o wi n g  u p o n A Es t hat are s eri o us, 
c o nsi dere d relate d t o t he st u d y dr u g /pr oce d ures, or t hat ca use d t h e partici p a nt t o disc o nti n ue t he 
st u d y dr u g treat me nt or wit h dra w fr o m t he st u d y.  Care will be ta ke n n ot t o i ntr o d uce bias w he n 
detecti n g A Es a n d/ or S A Es .  O pe n -e n d e d a n d n o nlea di n g ver bal q u esti o ni n g of t he partici pa nt 
s uc h as "H o w are y o u feeli n g? " is t he preferre d met h o d t o i n q uire a b o ut A E occ urre nces .  
A d verse e ve nts ma y als o be detect e d w he n t he y are v ol u nteere d b y t h e parti ci pa nt  d uri n g t he 
scree ni n g pr o cess or b et wee n visits or t hr o u g h p h ysical e xa mi nati o ns, la b orat or y tests, or ot her 
assess me nts .  T he defi 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 des cri be d i n 
Secti o n  9 . 
All S A Es will be rec or de d a n d re p ort e d t o t he s p o ns or or desi g nee wit hi n 2 4 h o urs .  T he 
i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs of it bei n g 
a vaila ble.  
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr o acti vel y f oll o w eac h partici pa nt 
at s u bse q ue nt visits/c o ntacts .  All S A Es w ill be f oll o we d u ntil res ol uti o n, stabilizati o n, t he e ve nt 
is ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w-u p (as defi ne d i n Secti o n  7. 3 ). 
8. 3. 2.  
P h ysic al E x a mi n ati o ns  
P h ysical e xa mi nati o ns m ust be perf or m e d b y a me dicall y q ualifie d i n di vi d ual  as per T a ble  3 , 
s uc h as a lice ns e d p h ysicia n, a p h ysicia n assista nt, or a n a d va n ce d re gistere d n urse pract iti o ner, 
as l ocal la w per mits.   A b n or malities i de ntifie d aft er si g nat ure of t he I C F b y t he partici pa nt a n d 
u p u ntil 3 0 da ys after t he last d ose of st u d y dr u g c o nstit ute a n A E if t he y w orse n fr o m bas eli ne, 

I nc yte C orp orati o n  
Pa ge 6 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
are c o nsi d ere d cli nicall y mea ni n gf ul i n t he me dical a n d scie ntific j u d ge me nt of t he i n vesti gat or, 
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 .  T he y will be gra d e d as per t he N CI C T C A E v 5. 0 w here a p plica ble.  I n vesti gat ors s h o ul d 
pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us ill nesses.  
8. 3. 3.  
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 at scree ni n g a n d ot her st u d y visits per  Ta ble  3 .  
Perf or ma nce stat us m ust be assesse d b y a me dicall y q ualifie d i n di vi d ual, sc ore d as per Ta ble  1 4 , 
a n d rec or de d i n t he p artici pa nt 's e C R F. 
T a ble  1 4 : 
E aster n C o o per ati ve O nc ol o g y Gr o u p P erf or m a nce St at us  
Sc ore  
E C O G Perf or m a nce St at us  
0  
F ull y acti ve, a ble t o carr y o n all pre disease perf or ma nce wit h o ut restricti o n.  
1  
Restricte d i n p h 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 hair m ore t ha n 5 0 % of wa ki n g h o urs.  
4  
C o m pletel y disa ble d.  Ca n n ot carr y o n a n y self -care.  T otall y c o nfi ne d t o be d or c hair.  
5  
Dea d.  
S o urce:  O ke n et al 1 9 8 2 . 
8. 3. 4.  
Vit al Si g ns  
See Ta ble  3  f or t he ti mi n g a nd fre q u e nc y of assess me nts.  
Vital si g n meas ure me nts (t o be ta ke n be f ore bl o o d c ollecti o n f or la b orat or y tests, e xce pt d uri n g 
scree ni n g) i n cl 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 partici pa nt i n t he rec u m be nt, se mirec u m be nt, or sitti n g p ositi o n 
after at least 5 mi n utes of rest.  If vital si g ns ca n n ot be ta ke n bef ore bl o o d c ollecti o n f or 
la b orat or y tests, t here m ust be a mi ni m u m of 3 0 mi n utes fr o m t he c o m pleti o n of t he bl o o d 
c ollecti o n pr oce d ures t o t he be gi n ni n g of t he vital si g ns c ollecti o n.  
A b n o r mal vital si g n res ults i de ntifie d after si g nat ure of t he I C F b y t he partici pa nt a n d u p u ntil 
3 0  da ys after t h e last d ose of st u d y dr u g c o nstit ute a n A E if t he y w orse n fr o m baseli ne, are 
c o nsi dere d cli nicall y mea ni n gf ul i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or, 
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 . 

I nc yte C orp orati o n  
Pa ge 6 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8. 3. 5.  
C ar di ac F u ncti o n A ssess me nts 
8. 3. 5. 1.  
1 2 -Le a d E lectr oc a r di o gr a ms a n d C ar di ac E c h o gr a p h y or M ulti g ate d 
Ac q uisiti o n  
Car diac f u ncti o n will be assesse d b y t he f oll o wi n g e xa mi nati o ns, w hic h will be perf or me d as 
i n dicate d i n Ta ble  1 5 : 
•  1 2 -lea d E C Gs:  at mi ni m u m, t he heart rate a n d meas ure me nt of P R, Q R S, a n d Q T  
i nter vals a n d Q Tc will be c ollecte d.  
•  Ec h ocar di o gra p h y  or M U G A  sca n:  at mi ni m u m, t he ejecti o n fracti o n will be 
rec or de d. 
T he 1 2 -lea d E C G will be o btai ne d as o utli ne d i n t he S o A (see T a ble  3 ) usi n g a n E C G mac hi ne 
t hat a ut o maticall y calc ul ates t he heart rate a n d meas ures P R, Q R S, a n d Q T  i nter vals a n d Q Tc.  
All 1 2 -lea d E C Gs will be perf or me d wit h t he parti ci pa nt 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 rest.  
T he 1 2 -lea d E C Gs a n d ec h ocar di o gra p h y  or M U G A sca ns will be i n ter prete d b y t he i n vesti gat or 
at t he site t o be use d f or i m me diate partici pa nt ma na ge me nt.  A d diti o nal 1 2 -lea d E C Gs or 
ec h ocar di o gra p h y e xa mi nati o ns ma y be perf or me d as cli nicall y i n dicate d t o ma na ge partici pa nt  
safet y.  T he d ecisi o n t o i ncl u de or e x cl u de a p arti ci pa nt or disc o nti n ue  st u d y dr u g treat me nt 
base d o n a n E C G fl a 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 medical m o nit or, as a p pr o priate.  
I n t he e ve nt t hat a p artici pa nt 's Q Tc is  >  4 5 0  millisec o n ds at scree ni n g, t he partici pa nt  ma y e nr oll 
wit h pri or a p pr o val fr o m t he s p o ns or's me dical m o nit or.  F or partici pa nt s wit h a n i ntra ve ntric ular 
c o n d ucti o n dela y ( Q R S i nter val >  1 2 0  millisec o n ds) at scree ni n g, t he J Tc ma y be use d i n place 
of t he Q Tc wit h me dic al m o nit or a p pr o val.  I n a d diti o n, t he J Tc s h o ul d be use d f or all 
s u bse q ue nt assess ments.  
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 he 
i n vesti gat or a n d t hat occ ur fr o m si g nat ure of t he I C F u p u ntil 3 0  da ys  after t he last d ose of st u d y 
dr u g as a p plica bl e are t o be re p ort e d as A Es  a n d grade d as p er t he N CI C T C A E v 5. 0 (2 0 1 7 ) 
w here a p plica ble . 
8. 3. 5. 2.  
Tri plic ate 1 2 -le a d E C Gs 
Tri plicate 1 2 -le a d E C Gs will be o btai ne d o n t he da ys a n d ti mes n ote d i n t he sc he d ule of 
assess me nts ( see T a ble  3 ) a n d Ta ble  1 5  b el o w.  O n C ycle 1 o n Da ys 1 a n d 1 5, t he  ti me d 1 2-lea d 
tri plicate E C Gs will be c o n d ucte d pr e d os e a n d at 2, 4, a n d bet wee n 6 -8 h o urs p ost d ose, 
a p pr o xi matel y wit hi n 5  mi n utes bef ore t he P K bl o o d dra w at t he c orres p o n di n g ti me p oi nts.  T he 
s pecifie d p ost d ose ti me p oi nt(s) ma y be a dj uste d b ase d o n e mer gi n g P K data.  A d diti o nal  E C Gs 
ma y be perf or me d if cli nicall y i n dicate d.   Electr ocar di o gra ms fr o m C ycle  2 a n d be y o n d o nl y 
nee d t o be perf or me d i n tri plicate if t here has bee n a Q T pr ol o n gati o n o n st u d y or t he E C G 
s h o ws a cli nicall y si g nifica nt a b n or malit y n ot pres e nt at baseli ne. 
All 1 2 -lea d E C Gs will be perf or me d wit h t he parti ci pa nt i n a rec u m be nt or se mirec u m be nt 
p ositi o n after a p pr o xi mat el y 5 t o 1 0 mi n utes of rest.   Baseli ne E C G i nter vals will be e q ual t o t he 
a vera g e of all E C G i nter vals o btai ne d bef ore t he first st u d y dr u g d os e a d mi nistrati o n.  All 

I nc yte C orp orati o n  
Pa ge 6 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 2 -lea d E C Gs o btai ne d at s u bse q ue nt ti me p oi nts d uri n g t he st u d y will be c o m pare d wit h t hese 
baseli ne 1 2 -le a d E C G i nter vals.  F or E C G m or p h ol o g y, t he E C G perf or me d cl osest t o t he ti me of 
a d mi nistrati o n o n C ycle 1 Da y 1 will be use d as t he baseli ne.  
T he st u d y ma n ual f or pr oce d ures t h at m ust be f oll o we d f or t he rec or di n g a n d tra ns missi o n of 
E C Gs t o a ce ntral v e n d or a n d t he o perat or's ma n ual wit h i nstr ucti o ns f or o perati n g t he di gital 
ca pt ure m o d ule will be s hi p pe d t o t he site al o ng wit h t he de vice.  
I n a d diti o n, t he 1 2-lea d E C Gs will be i nter prete d b y t he i n vesti gat or at t he site a n d will be use d 
f or i m me diate partici p a nt ma na ge me nt.  T he d ecisi o n t o i ncl u de or e xcl u de a partici pa nt or 
disc o nti n ue a partici pa n t fr o m t he st u d y base 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. T wel ve -l ea d E C Gs t hat are i de ntifie d b y t h e 
i n vesti gat or as " A b n or m al, Cli nicall y Si g nifica nt" ma y nee d e v al uati o n b y a c o ns ulta nt 
car di ol o gist as per t he i n stit uti o n sta n dar d of care. 
T a ble  1 5 : 
Sc he d ule of C ar di ac F u ncti o n Assess m e nts  
Visit/ E x a mi n ati o n  
A n y ti m e 
Pre d ose a 
P ost d ose b 
1 2 -le a d E C Gs 
Scree ni n g  
X  
 
 
C 1 D 1  
 
X  
X  
C 2 D 1  
 
X  
 
Da y 1 of e v er y t hir d c ycle 
( C ycles 3, 6, 9, a n d 1 2) 
 
X  
 
E O T  
X  
 
 
Safet y f oll o w -u p  
X  
 
 
Ec h oc a r di o gr a p h y /M U G A s c a n  
Scree ni n g  
X  
 
 
Da y 1 of e v er y si xt h c y cle 
( C ycles 6 a n d 1 2) 
X c 
 
 
E O T  
X  
 
 
Tri plic ate 1 2 -le a d E C Gsd 
 
 
 
Scree ni n g  
X  
 
 
Wit hi n 7 da ys pri or t o C 1 D 1   
X  
 
 
C 1 D 1  a n d C 1 D 1 5   
 
X  
X ( 2, 4 , a n d bet wee n 
6 -8  h o urs ) 
a Pre d ose is b ef ore t h e m or ni n g d ose of I N C B 0 0 0 9 2 8, wit hi n 9 0 mi n utes bef ore recei vi n g t h e st u d y dr u g.  
b P ost d ose is 4 h o urs ( ± 5 mi n u tes) after t he m or ni n g d ose of I N C B 0 0 0 9 2 8. 
c Wit hi n 3 da ys of t he visit.  
d T hree  rec or ds ali g ne d wit h t he P K or P D bl o o d dra w as a p pli ca ble: wit hi n a p pr o xi matel y 5 mi n utes bef ore t h e res pecti ve P K or 
P D bl o o d dra w.  
8. 3. 6.  
Ir o n O verl o a d Assess m e nt  
Ir o n h o me ostasis assess me nt will be perf or me d at scree ni n g; o n Da ys 1, 8, a n d 1 5 of C ycle 1; o n 
Da y 1 of C ycle 2; o n D a y 1 of eac h c ycle after C ycle 2; at t he E O T; a n d at t he safet y f oll o w -u p 
visits.  

I nc yte C orp orati o n  
Pa ge 6 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A  n o n – c o ntrast -e n ha nce d M RI will be perf or me d i n c o nj u ncti o n wit h s oft ware us e d f or t he 
esti mati o n of he patic ir o n c o nce ntr ati o n (ie, T 2 -wei g hte d M RI) t o n o ni n vasi vel y meas ure li ver 
ir o n c o nce ntr ati o ns i n t he f oll o wi n g sit uati o ns.  N ote: If t here is a c o nc o mita nt nee d t o sta ge 
he patic fi br osis or e v al uate f or alter nate li ver dise ases, t he n a li ver bi o ps y m a y be perf or me d.  
N ote t hat t he scree ni n g M RI ma y n ot be re peate d if alrea d y p erf or me d wit hi n 3 m o nt hs p ri or t o 
scree ni n g. 
•  F or partici pa nts wit h a scree ni n g f erriti n le vel of < 1 0 0 0 n g/ m L:  
− W he n t he ferriti n le vel d uri n g t he st u d y bec o mes > 1. 5 × t he scree ni n g ferriti n 
le vel A N D t he ferriti n le vel is ≥ 1 0 0 0 n g/ m L, M RI s h o ul d be p erf or me d e v er y 
3  c ycles t hereaft er, pr o vi di n g t he c o n diti o ns are m ai ntai ne d.  
− E O T.  
•  F or partici pa nts wit h a scree ni n g f erriti n le vel of ≥ 1 0 0 0 n g/ m L:  
− E ver y 6 c y cles (ie, at c ycles 6, 1 2, 1 8, 2 4, 3 6, a n d 4 2 as a p plica ble) a n d  
o  W he n t he ferriti n le vel d uri n g t he st u d y bec o mes > 1. 5 × t he scree ni n g 
ferriti n le vel, M RI s h o ul d be perf or me d  e v er y 3 c ycles t hereafter, 
pr o vi di n g t he c o n diti o ns are mai ntai ne d.  
o  E O T.  
At sites w here a M RI is n ot a vaila ble, a C T sca n ma y be use d t o i de ntif y a n y li ver lesi o n(s) or 
disease, wit h pri or sp o ns or 's me dical m o nit or a p pr o val . 
8. 4.  
L a b or at or y Assess me nts  
See Ta ble  1 6  f or t he list of cli nical la b orat or y tests t o be perf or m e d a n d Ta ble  4  f or t he ti mi n g 
a n d fre q u e nc y.  T h ese a n al ytes will be meas ure d f or safet y, efficac y a n d/ or P D p ur p oses (see 
Secti o n  8. 6 ).  All para meters fr o m Ta ble  4  will be meas ure d l ocall y ; o nl y he pci di n a n d E R F E  
para meters will be meas ure d ce ntrall y.  A certifie d la b orat or y l ocal t o t he i n vesti gati ve site will 
perf or m all cli nic al la b orat or y ass ess me nts f or s afet y ( ie, bl o o d c he mistries, he mat ol o g y 
assess me nts, c oa g ulati o n tests, ser ol o g y, li pi d pa nel, a n d uri nal ysis).  A d diti o nal tests ma y als o 
be perf or me d if cli nicall y i n dicate d.  
See Secti o n  6. 6  f or g ui deli nes re gar di n g t he ma n a ge me nt of rel e va nt la b orat or y a n d ot her s afet y 
assess me nt a b n or malities.  
Scree ni n g la b orat or y ass ess me nts m ust be perf or me d wit hi n 2 8 da ys of C 1 D 1 .  If perf or me d 
m ore t ha n 2 8 da ys bef ore C 1 D 1 , t he n t he tests m ust be re peate d a n d eli gi bilit y c o nfir me d bef ore 
st u d y dr u g a d mi nistrati o n o n C 1 D 1 .  La b orat or y s a m ples c ollecte d o n C 1 D 1  m ust be perf or me d 
bef ore st u d y dr u g a d mi nistrati o n.  After C ycle  1, pre d ose la b ora t or y pr o ce d ures ca n b e 
c o n d ucte d u p t o 7 2 h o urs bef ore st u d y dr u g a d mi nistrati o n ( wit hi n t he 3 -da y st u d y wi n d o w), a n d 
res ults s h o ul d be re vie we d b y t he i n vesti gat or or q ualifie d desi g nee a n d f o u n d t o be acce pta ble 
bef ore a ne w c ycle of st u d y dr u g is i nitiate d. 
Pr oce d ures c o n d ucte d as part of t he partici pa nt 's r o uti ne cli nical ma na ge m e nt bef ore si g ni n g t he 
I C F ma y be us e d f or scree ni n g or baseli ne p ur p os es pr o vi de d t hat t he pr o ce d ure meets t he 
Pr ot oc ol -defi ne d criteria a n d has bee n perf o r me d i n t he scree ni n g i nter val. 

I nc yte C orp orati o n  
Pa ge 6 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T he cli nical fi n di n gs fr o m bl o o d c he mistr y, he mat ol o g y  assess me nts , li pi d pa nel, c oa g ul ati o n 
tests, a n d uri nal ysis will be rec or de d as A Es if t he y are c o nsi d ere 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 n c o mita nt t hera p y, or re q uir e c ha n g es i n st u d y dr u g 
treat me nt a n d will be gra de d as per t h e N C I C T C A E v 5. 0 w here a p plica bl e. 
Cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hi c h are n ot ass ociate d wit h t he 
u n derl yi n g disease, u nless j u d ge d b y t he i n vesti gat or t o be m ore se v ere t h a n e x pecte d f or t he 
partici pa nt 's c o n diti o n (s ee als o t he defi niti o n i n Secti o n  9. 1 ).  All la b orat or y tests wit h val ue s 
c o nsi dere d cli nicall y si g nifica ntl y a b n or mal d uri n g partici pati o n i n t he st u d y (fr o m si g nat ure  of 
t he I C F a n d u p t o 3 0 da ys after t he last d ose of st u d y dr u g ) s h o ul d be re p eat e d u ntil t he val ues 
ret ur n t o n or mal or b aseli ne, sta bilize, or are n o l o n ger c o nsi dere d cli nicall y si g nifica nt b y t he 
i n vesti gat or or me dical m o nit or. 
Uri nal ysis meas ure me nts will be perf or me d usi n g a di pstic k , a n d a b n or mal/ d o u btf ul res ults ma y 
be c o nfir me d b y q u a ntitati ve meas ure me nt.  W he n e ver p ossi ble, a dia g n osis s h o ul d be rec or de d 
i n t he e C R F rat her t ha n t he a b n or mal la b orat or y res ult.  
W he ne v er p ossi ble, t he bl o o d sa m ples f or all la b orat or y tests will be c ollect e d at eac h visit as 
a p plica ble bef ore d osi n g,  i n t he m or ni n g, bef ore a n y R B C tra nsf usi o ns .  E ver y eff ort s h o ul d be 
ma de t o mi ni mize t he v ol u me of bl o o d dra w n f or eac h partici p a nt.  

I nc yte C orp orati o n  
Pa ge 6 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 6 : 
Re q uire d L a b or at or y A n al ytes  
Bl o o d C he mistries  
He m at ol o g y  
Uri n al ysis ( Di pstic k)  
Scree ni n g Ser ol o g y  
C o a g ul ati o n  
I o ns:  
Bicar b o nate or C O 2, calci u m , c hl ori de , 
ma g nesi u m, p h os p hate, p otassi u m, 
s o di u m 
 
Ir o n h o me ostasis  a n d  er yt hr o p oiesis:  
T S I, ferriti n, tra nsferri n, T S A T, TI B C , 
UI B C  
 
Pa ncreatic mar kers:  
A m ylase, li pase, gl uc ose  
 
He p atic mar kers:  
Al b u mi n, t otal bilir u bi n, direct bilir u bi n, 
A L P, A L T, A S T, t otal pr otei n  
 
Re n al mar kers:  
Bl o o d urea nitr o ge n or urea , creati ni ne , 
uric aci d 
 
Ot hers:  
L actate de h y dr o ge nase , fi bri n o ge n, C R P, 
H b A 1c, vita mi n B 1 2, M M A  
C o m plete bl o o d cell c o u nt , 
i ncl u di n g: 
•  H g b  
•  Hct  
•  Platelet c o u nt  
•  R B C  c o u nt 
•  W hite bl o o d cell  c o u nt 
 
Differe ntial c o u nt (a bs ol ute val ues) , 
i ncl u di n g: 
•  Bas o p hils  
•  E osi n o p hils  
•  L y m p h oc ytes  
•  M o n oc ytes  
•  Ne utr o p hils  
 
A d diti o nal para meters  f or 
er yt hr o p oiesis : 
•  R C  
•  N R B C  
•  M C V  
•  M C H  
•  M C H C  
•  R D W  
•  Retic ul oc yte he m o gl o bi n c o nte nt a 
•  M y el o blasts i n peri p heral bl o o d  
•  E P O  
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  
He p atitis B s urface 
a ntige n  
He p atitis B s urface 
a nti b o d y 
He p atitis B c ore 
a nti b o d y 
H C V a nti b o d y  
 
H B V  D N A b 
H C V  R N A b 
Pr ot hr o m bi n ti me  
Partial t hr o m b o plasti n 
ti me or acti vate d 
partial t hr o m b o plasti n 
ti me 
I nter nati o nal 
n or malize d rati o  
Li pi d P a nel  
Pre g n a nc y Testi n g  
T otal c h olester ol  
Tri gl yceri des  
L o w -de nsit y li p o pr otei n   
Hi g h -de nsit y li p o pr otei n  
Fe male partici pa nts of c hil d beari n g p ote ntial 
o nl y.  
Ser u m test s at scree ni n g a n d E O T a n d safet y 
f oll o w-u p visits; uri ne pre g na nc y test bef ore 
t he first st u d y dr u g d ose  at eac h c y cle  after 
C ycle 1 .  
Pre g na n c y tests (ser u m or uri ne) s h o ul d be 
re p eate d if re q uire d b y l ocal re g ulati o ns. 
N ote:  A d diti o nal tests ma y be re q uire d, as a gree d u p o n b y t h e i n vesti g at or a n d s p o ns or, base d o n e mer gi n g safet y data. 
a Retic ul o c yte he m o gl o bi n c o nte nt meas ure m e nt is n ot re q uire d at i n vesti g ati o nal sites w here t his p ara mete r ca n n ot be meas ure d b y t h e l o cal la b orat or y. 
b D N A a n d R N A o nl y if ser ol o g y is p ositi ve.

I nc yte C orp orati o n  
Pa ge 6 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8. 4. 1.  
Pre g n a nc y Testi n g  
A l ocall y  perf or me d ser u m pre g na nc y test will be re q uire d f or all w o me n of c hil d beari n g 
p ote ntial d uri n g scree ni n g (wit hi n 3 da ys of  C 1 D 1 ) bef ore t he first d ose of st u d y dr u g  (i n all 
cases, t he i n vesti gat or s h o ul d c o nfir m t he test res ult is ne gati ve bef ore st arti n g st u d y dr u g  
a d mi nistrati o n ) a n d at t he E O T a n d safet y f oll o w -u p visits.  
I n a d diti o n, a uri ne pre g n a nc y test will be perf or m e d l ocall y bef ore t he start of eac h c ycle  after 
C ycle 1  a n d as me dicall y i n dicate d ( e g, i n case of l oss of me nstr ual c ycle, w he n pre g n a nc y is 
s us pecte d) or per c o u ntr y-s pecific re q uire m e nt.  If a uri ne pre g na nc y t est is p ositi ve or d o u btf ul , 
t he res ults s h o ul d be c o nfir med wit h a ser u m pre g na nc y test.  
If t he ser u m pre g na n c y test is ne gati ve after a uri n e test was p ositi ve, t he i n vesti gat or will assess 
t he p ote ntial be nefit/ris k t o t he partici pa nt a n d det er mi ne w het her it is i n t he partici pa nt's best 
i nterest t o res u me st u d y dr u g treat me nt a n d c o nti n ue partici pati o n i n t he st u d y. 
If a pre g na nc y is c o nfir m e d b y a ser u m pre g na n c y test, see Secti o n  9. 6  f or re p orti n g 
re q uire me nts. 
8. 4. 2.  
Ser ol o g y  
He patitis scree ni n g assess me nts will be perf or me d at  t he scree ni n g visit t o r ule o ut he patitis 
i nfecti o n; re q uire d a nal yt es are s h o w n i n Ta ble  1 6 .  Ge nerall y, he patitis tests s h o ul d be 
perf or me d earl y i n t he scree ni n g pr o cess d ue t o t h e le n gt h of ti me nee d e d t o o btai n t he res ults .  
A d diti o nal tests ma y be perf or me d if cli nicall y i n dicate d.  
8. 5.  
P h ar m ac o ki netic Assess me nts  
Bl o o d sa m ples will be c ollecte d f or meas ure me nt of c o nce ntrati o ns of I N C B 0 0 0 9 2 8 as s pecifie d 
i n Ta ble  4 .  A ma xi m u m of 4  sa m ples ma y be c oll ecte d at a d diti o nal ti me p oi nts d uri n g t he st u d y 
if warra nte d a n d a gree d u p o n bet wee n t he i n v esti gat or a n d t he s p o ns or.  Sa m ples c ollecte d f or 
a nal yses of I N C B 0 0 0 9 2 8 c o nce ntr ati o n ma y als o be use d t o e val uat e safet y or efficac y as pects 
relate d t o c o n cer ns arisi n g d uri n g or after t he st u d y.  T he act ual d ate a n d ti me ( 2 4-h o ur cl o c k 
ti me) of eac h sa m pl e will be rec or de d  i n t he e C R F. 
8. 5. 1.  
Bl o o d S a m ple C ollecti o n  
Ti mi n g of bl o o d P K assess me nts is o utli ne d i n  Ta ble  1 7 .  Details a n d met h o ds f or o btai ni n g, 
pr ocessi n g, ha n dli n g , a n d s hi p pi n g sa m ples will be pr o vi de d i n t he La b orat or y Ma n ual f or t his 
st u d y.  After t he pre d ose P K sa m ple is dra w n, partici pa nts wi ll recei ve t he st u d y dr u g .  Pre d ose 
is defi ne d as wit hi n 9 0 mi n utes bef ore a d mi nistrati o n of st u d y dr u g .  A dj ust me nts t o t he ti mi n g 
of bl o o d sa m pli n g ma y be ma de bas e d o n e mer gi n g P K data.  
I n t he e ve nt a BI D a d mi nistrati o n sc he d ule is e x pl ore d, t he refere nce f or P K bl o o d sa m pli n g will 
be t he m or ni n g d ose.  

I nc yte C orp orati o n  
Pa ge 7 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T a ble  1 7 : 
P h ar m ac o ki netic Bl o o d S a m ple Ti mi n g  
St u d y Visit  
Ti mi n g of S a m ples  
C ycle 1 a Da y 1  
C ycle 1 Da y 1 5  
•  Pre d ose ( wit hi n 9 0 mi n utes  pri or t o recei vi n g t he st u d y dr u g)  
•  2 h o urs p ost d ose ( ± 1 5 mi n utes)  
•  4 h o urs p ost d ose ( ± 1 5 mi n utes)  
•  1 sa m ple bet wee n 6 a n d 8 h o urs p ost d ose  
First c y cle of I N C B 0 0 0 9 2 8 wit h 
i ntr a p artici p a nt d ose esc al ati o n 
Ti mi n g of S a m ples  
O n Da y 1 5 of t he first c ycle wit h 
i ntra p artici pa nt d ose escalati o n 
•  Pre d ose ( wit hi n 9 0 mi n utes  pri or t o recei vi n g t he st u d y dr u g)  
•  2 h o urs p ost d ose ( ± 1 5 mi n utes)  
•  4 h o urs p ost d ose ( ± 1 5 mi n utes)  
•  1 sa m ple bet wee n 6 a n d 8 h o urs p ost d ose  
a C ycle 1 of b ot h t h e d ose -escalati o n a n d d ose -e x pa nsi o n  p hases . 
8. 6.  
P h ar m ac o d y n a mic a n d Tr a nsl ati o n al Assess me nts  
8. 6. 1.  
Bl o o d a n d B o ne M arr o w S a m ple C ollecti o n  
As of Pr ot oc ol A me n d m e nt 5, n o f urt her P D /tra nslati o nal assess me nt sa m ples will be c ollecte d. 
8. 6. 2.  
P h ar m ac o d y n a mic a n d Tr a nsl ati o n al Rese arc h P ar a meters  
•  Assess me nt of ir o n h o me ostasis a n d er yt hr o p oiesis  c o m prises t he f oll o wi n g ( part of 
t he he mat ol o g y a n d bl o o d c he mistr y sa mpli n g):  
− Ir o n h o me ostasis:  T SI, ferriti n, t ra nsferri n, T S A T, TI B C, a n d UI B C . 
− Er yt hr o p oiesis:  R C, N R B C, M C V , M C H, H g b, Hct , R B C c o u nt , M C H C, R D W , 
a n d retic ul oc yte h e m o gl o bi n c o nte nt . 
− E P O . 
•  T he plas ma P D sa m ple will ai m at e val uati n g, b ut n ot restricte d t o, t he le vel of 
plas ma he pci di n usi n g a vali da te d i m m u n oassa y.  He pci di n meas ure me nt will be 
perf or me d ce ntr all y.  
•  T he B M  as pirate or B M  as pirate s mears t o deter mi ne 
 
.  If a fres h B M  as pirat e is c o ntrai n dicate d or ca n n ot be 
c ollecte d d uri n g scree ni n g, arc hi v al B M  s mears (c ollecte d after t he c o m pleti o n of t he 
m ost rece nt a ntica ncer tre at me nt a n d wit hi n 3  m o nt hs bef ore C 1 D 1  of t h e st u d y) ma y 
be s u b mitte d.  T he p ur p oses of t he meas ure me nts perf or me d o n t h ese sa m ples are t o 
e val uate a n y c orrelati o n bet wee n 
 a n d a ne mia res p o ns e t o 
I N C B 0 0 0 9 2 8 i n M D S a n d M M partici pa nts. 
•  
T he res ults of t he a n al yses of t hese p ara meters will be c orrelate d wit h t he safet y a n d efficac y 
data o btai ne d fr o m t he st u d y partici pa nts.  

I nc yte C orp orati o n  
Pa ge 7 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
8. 7.  
U nsc he d ule d Visits  
Cli nic visits or dia g n ostic la b orat or y visits n ot prescri be d i n t he Pr ot oc ol ma y be perf or me d at 
a n y ti me cli nicall y i n dicate d at t he i n vesti gat or 's discreti o n.  Res ults of assess me nts perf or me d at 
t hese visits s h o ul d be e ntere d as u ns c he d ule d visits i n t he e C R F.  T he s p o ns or ma y als o re q u est 
a d diti o nal visits t o be perf or me d, if nee de d, bas e d o n e mer gi n g safet y data.  
8. 8.  
E n d of Tre at me nt  a n d/ or E arl y Ter mi n ati o n  
W he n t he partici pa nt per ma ne ntl y disc o nti n ues st u d y dr u g treat me nt, w h et her t he partici pa nt is 
ter mi nati n g t he st u d y earl y or t he partici pa nt has c o m plete d t he st u d y, t he E O T visit s h o ul d be 
c o n d ucte d.  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 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 partici pa nt s h o ul d be e nc o ura ge d t o r et ur n f or t he s afet y f oll o w -u p visit.  
8. 9.  
F oll o w -U p  
8. 9. 1.  
S afet 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 safet y 
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 l ast d ose of st u d y dr u g .  A d verse 
e ve nts a n d S A Es m ust be re p orte d u p u ntil 1) at least 3 0  da ys after t h e last d ose of st u d y dr u g or 
t he start of a ne w a ntica n cer t hera p y or 2) u ntil t o xicities res ol ve, ret ur n t o baseli ne, or are 
dee me d irre versi ble, w hic he ver is l o n ger .  Reas o n a ble eff orts s h o ul d be ma de t o ha ve t he 
partici pa nt ret ur n f or t he safet y f oll o w -u p visit a n d re p ort a n y A Es t hat ma y occ ur d uri n g t his 
peri o d.  If t he p artici pa nt 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 wa y), t he p artici pa nt s h o ul d be c o ntacte d b y t ele p h o ne f or ass ess me nt of A Es a n d S A Es , a n d 
t he i n vesti gat or or desi g n ee s h o ul d d oc u me nt t his c o ntact i n t he s o urce. 
If a partici pa nt is sc he d ul e d t o be gi n a ne w a ntica n cer t hera p y bef ore t h e e n d of t he 3 0-da y s afet y 
f oll o w-u p peri o d, t he safet y f oll o w -u p visit s h o ul d be perf or me d bef ore a ne w a ntica n cer t h e ra p y 
is starte d.  O nce a ne w a ntica ncer t h era p y h as bee n i nitiate d, t he partici pa nt will m o ve i nt o t he 
p ost -treat me nt f oll o w-u p peri o d . 
8. 9. 2.  
P ost -T re at me nt F oll o w -U p  
Partici pa nts w h o disc o nti n ue st u d y dr u g treat me nt will m o ve i nt o t he p ost -treat me nt f oll o w-u p 
peri o d a n d s h o ul d be ass esse d as per i nstit uti o n 's sta n dar d of care (i deall y e ver y 6  m o nt hs 
[1 8 0  ±  1 4 da ys ]) t o c olle ct i nf or mati o n o n disease/life stat us.  E ver y eff ort s h o ul d be ma de t o 
c ollect i nf or m ati o n re g ar di n g disease /life stat us u ntil o ne of t he f ollo w i n g c o n diti o ns occ urs: 
•  Wit h dra wal of c o nse nt.  
•  L ost t o f oll o w -u p.  
•  Deat h.  
•  T he e n d of t he st u d y.  
F or partici pa nts ha vi n g e ntere d t he p ost -tr eat me nt f oll o w-u p peri o d of t he st u d y, t he site will use 
c o nti n ui n g partici pa nt rec or ds t o s u p pl y data o n s u bse q ue nt treat me nt r e gi me ns, t u m or 

I nc yte C orp orati o n  
Pa ge 7 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
assess me nts (if disc o nti n ue d treat me nt f or a reas o n ot her t ha n pr o gressi o n), a n d life stat us if 
a p plica ble i n t he e C R F.  F or partici pa nts w h o d o n ot i nte n d t o ret ur n t o t he st u d y i n vesti gat or f or 
t heir o n g oi n g care, f oll o w-u p s h o ul d be mai ntai n e d b y p h o ne c o ntact, partici pa nt rec or ds, a n d 
p u blic rec or ds/ dat a bases at i nter v als of n o l o n ger t ha n 6 m o nt hs.  

I nc yte C orp orati o n  
Pa ge 7 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
9.  
A D V E R S E E V E N T S:  D E FI NI TI O N S A N D P R O C E D U R E S F O R 
R E C O R DI N G, E V A L U A TI N G, F O L L O W -U P, A N D R E P O R TI N G  
9. 1.  
Defi niti o n of A d verse E ve nt  
A d verse E ve nt  Defi niti o n  
•  A n A E is a n y u nt o war d me dical occ urre nce ass ociate 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 -relate d. 
•  A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he use of st u d y dr u g . 
A d diti o n al G ui d a nce f or E ve nts Meeti n g t he A d verse E ve nt  Defi niti o n  
•  A n y safet y assess me nts (e g, E C G, vital si g ns meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m 
baseli ne, c o nsi dere d cli nicall y si g nifica nt i n t he me dical a n d scie ntific j u d g me nt of t he i n vesti gat or 
(ie, n ot relate d t o pr o gressi o n of u n derl yi n g disease) , are t o be re p orte d as a n A E . 
•  A b n or mal  la b orat or y test res ults are t o be re p orte d as a n A E if t he y are 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 .  W he ne ver p ossi ble, a dia g n osis ( e g, a ne mia, t hr o m b oc yt o pe nia) s h o ul d be rec or de d i n 
t he e C R F rat her t ha n t he a b n or mal la borat or y  test res ult (e g, l o w he m o gl o bi n , platelet c o u nt 
decrease d).  
•  E xacer bati o n of a c hr o nic or i nter mitte nt pre -e xisti n g c o n diti o n/ disease, i ncl u di n g eit her a n i ncrease 
i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n, is t o be re p orte d as a n A E. 
•  Ne w c o n diti o ns detecte d or dia g n ose d after t he start of st u d y dr u g a d mi nistrati o n are t o  be re p orte d 
as a n A E. 
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n are t o be re p orte d as 
a n A E. 
•  Si g ns  a n d/ or  s y m pt o ms fr o m d osi n g err ors of a st u d y dr u g/treat me nt (e g, o ver d ose) or a c o nc o mita nt 
me dicati o n are t o be re p orte d as a n A E . 
•  "Lac k of efficac y ," "disease pr o gressi o n ," or "fail ure of e x pecte d p har mac ol o gical acti o n" will n ot be 
re p orte d as a n A E or S A E.  S uc h i nsta nces will be ca pt ure d i n t he efficac y assess me nts .  H o we ver, 
t he si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y will be re p orte d as a n 
A E or S A E if t he y f ulfill t he defi niti o n of a n A E or S A E.  
•  A  c o n diti o n t hat lea ds t o  a me dical or s ur gical  pr oce d ure  (e g e n d osc o p y, a p pe n dect o m y) will be 
re p orte d as a n A E if it occ urs after o btai ni n g i nf or me d c o nse nt.  If t he c o n diti o n is prese nt bef ore 
e nteri n g t he st u d y, t he n it  s h o ul d be ca pt ure d as me dical hist or y. 
•  P re-e xisti n g diseases or c o n diti o ns wit h e x pecte d fl uct uati o ns i n si g ns or s y m pt o ms s h o ul d be 
re p orte d as a n A E o nl y if t he i n vesti gat or j u d ges t he fl uct uati o n t o ha ve w orse ne d m ore t ha n 
e x pecte d d uri n g st u d y partici pati o n . 

I nc yte C orp orati o n  
Pa ge 7 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
9. 2.  
Defi niti o n of S eri o us A d verse E ve nt  
If a n e v e nt is n ot a n A E per defi niti o n a b o ve, t h e n it ca n n ot be a n S A E e v e n if seri o us c o n diti o ns 
are met ( e g, h os pitalizati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y, deat h d ue t o 
pr o gressi o n of diseas e).  
A seri o us a d verse e ve nt is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose: 
a.  Res ults i n de at h  
b.  Is life-t hre ate ni n g 
T he ter m 'life-t hreate ni n g' i n t he defi niti o n of 'seri o us' refers t o a n a d verse dr u g e x perie nce t hat places 
t he partici pa nt , i n t he o pi ni o n of t he i nitial re p orter, at i m me diate ris k of deat h fr o m t he a d verse 
e x perie nce as it occ urre d.  T his d oes n ot i ncl u de a n a d verse dr u g e x perie nce t hat, ha d it occ urre d i n a 
m ore se vere f or m, mi g ht ha ve ca use d deat h . 
c. Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n  
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n detai ne d ( us uall y i n v ol vi n g at least a n 
o ver ni g ht sta y) at t he h os pital  or e mer ge nc y war d f or o bser vati o n a n d/ or treat me nt t hat w o ul d n ot ha ve 
bee n a p pr o priate i n t he p h ysicia n 's office or o ut patie nt setti n g .  C o m plicati o ns t hat occ ur d uri n g 
h os pitalizati o n are A Es .  If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, 
t he e ve nt is seri o us.  W he n i n d o u bt as t o w het her h os pitalizati o n occ urre d or was necessar y,  t he A E 
s h o ul d be c o nsi dere d seri o us. 
H os pitalizati o n f or electi ve treat me nt or pla n ne d s ur ger y (e g, ste nt re place me nt, hi p s ur ger y) is n ot 
c o nsi dere d a n S A E.  
H os pitalizati o n f or me dical i nter ve nti o ns i n w hic h n o u nfa v ora ble me dical occ urre nce occ urre d 
(ie, electi ve pr oce d ures or r o uti ne me dical visits) are n ot c o nsi dere d S A Es . 
d.  Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y  
•  T he ter m "disa bilit y " mea ns a s u bsta ntial disr u pti o n of a pers o n 's a bilit y t o c o n d uct n or mal life 
f u ncti o ns.  T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, i nfl ue nza, a n d acci de ntal 
tra u ma (e g, s prai ne d a n kle), t hat ma y i nterfere wit h or pre ve nt e ver y da y life f u ncti o ns b ut d o n ot 
c o nstit ute a s u bsta ntial disr u pti o n.  
e. Is a c o n ge nit al a n o m al y/ birt h defect 
f. Is a n i m p ort a nt me dic al eve nt  
A n i m p orta nt me dical e ve nt is a n e ve nt t hat ma y n ot res ult i n deat h, be i m me diatel y life -t hreate ni n g, or 
re q uire h os pitalizati o n b ut ma y be c o nsi dere 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 par dize t he partici pa nt a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t he o utc o mes liste d i n t he a b o ve defi niti o n.   E xa m ples of  s uc h e ve nts i ncl u de ne w i n vasi ve or 
mali g na nt ca ncers, i nte nsi ve treat me nt i n a n e mer ge nc y de part me nt or at h o me f or aller gic 
br o nc h os pas m, bl o o d d yscrasias, or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of 
dr u g de pe n de nc y or dr u g a b use, or s us pecte d tra ns missi o n of a n i nfecti o us a ge nt via a me dici nal 
pr o d uct.  Sec o n dar y mali g na ncies s h o ul d al wa ys be c o nsi dere d S A Es . 

I nc yte C orp orati o n  
Pa ge 7 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
9. 3.  
Rec or di n g a n d F oll o w -U p of A d verse E ve nt s a n d/ or S eri o us A d verse 
E ve nt s 
A d verse E ve nt  a n d S eri o us A d verse E ve nt  Rec or di n g  
•  A n A E/ S A E t hat be gi ns or w orse ns after i nf or me d c o nse nt is si g ne d s h o ul d be rec or de d o n t he 
A d verse E ve nt  F or m i n t he e C R F.  A Es/ S A Es s h o ul d be re p orte d f or e nr olle d partici pa nts, b ut o nl y 
S A Es nee d t o be re p orte d f or scree n fail ure partici pa nts.  F or e nr olle d partici pa nts, c o n diti o ns t hat 
were prese nt at t he ti me i nf or me d c o nse nt was gi ve n s h o ul d be rec or de d o n t he Me dical Hist or y 
e C R F.  F or detaile d i nf or mati o n refer t o t he e C R F g ui deli nes . 
•  W he n a n A E/ S A E occ urs, it is t he res p o nsi b ilit y of t he i n vesti gat or t o re vie w all d oc u me ntati o n 
(e g, h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostics re p orts) relate d t o t he e ve nt.  
•  T he i n vesti gat or ( or dele gate) will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t he eC R F.  
•  It is n ot  acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt 's me dical rec or ds i n 
lie u of c o m pleti n g  t he A d verse E ve nt F or m i n t he e C R F . 
•  T here ma y be  rare i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d.  I n t his 
case, all partici pa nt i de ntifiers, wit h t he e xce pti o n of t he partici pa nt n u m ber, will be re dacte d b y t he 
site staff o n t he c o pies of t he me dical rec or ds bef ore s u b missi o n.   T hese rec or ds ca n be s u b mitte d t o 
I nc yte P har mac o vi gila nce b y e mail/fa x per t he c o ntact i nf or mati o n liste d i n t he i n vesti gat or site file 
or as per S A E c o m pleti n g g ui deli nes .  
•  T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, a n d/ or 
ot her cli nical i nf or mati o n .  W he ne ver p ossi ble, t he dia g n osis ( n ot t he i n di vi d ual si g ns/s y m pt o ms) 
will be d oc u me nte d as t he A E/ S A E .  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 orte d as a se parate A E/ S A E. 
T o t he e xte nt p ossi ble, eac h A E / S A E s h o ul d be e val uate d t o deter mi ne t he f oll o wi n g: 
•  T he  se verit y gra de ( C T C A E v 5 . 0 Gra de 1 t o 5 ).  See bel o w f or f urt her i nstr ucti o ns o n t he assess me nt 
of i nte nsit y.  
•  W het her t here is at least a reas o na ble p ossi bilit y t hat t he A E is relate d t o t he st u d y dr u g  
(I N C B 0 0 0 9 2 8):  s us pecte d ( yes) or n ot s us pecte d ( n o).  See bel o w f or f urt her i nstr ucti o ns o n t he 
assess me nt of ca usalit y . 
•  T he start a n d e n d dates, u nless u nres ol ve d at fi nal safet y f oll o w-u p  visit . 
•  T he acti o n ta ke n wit h re gar d t o st u d y dr u g  as a res ult of t he A E/ S A E (s). 
•  T he e ve nt o utc o me ( e g, n ot rec o vere d/ not 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 per t he S A E defi niti o n pr o vi de d i n Secti o n  9. 2 . 
•  T he acti o n ta ke n wit h re gar d t o t he e ve nt .  N ote:  If a n A E is treate d wit h a c o nc o mita nt me dicati o n 
or n o n dr u g t hera p y, t his acti o n s h o ul d be rec or de d o n  t he A d verse E ve nt F or m a n d t he trea t me nt 
s h o ul d be s pecifie d o n t he a p pr o priate e C R F ( e g, Pri or/ C o nc o mita nt Me dicati o ns , Pr oce d ures a n d 
N o n -Dr u g T hera p y ). 

I nc yte C orp orati o n  
Pa ge 7 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Assess me nt of I nte nsit y  
T he se verit y of A Es will be assesse d usi n g C T C A E v 5. 0  Gra des 1 t hr o u g h 5 .  If a n e ve 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 bel o w t o esti mate t he 
gra de of se verit y . 
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d d uri n g t he st u d y 
a n d assi g n it t o o ne of t he f oll o wi n g cate g ories: 
•  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; treat me nt 
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 treat me nt 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 treat me nt i n dicate d. 
•  Gr a de 5:   Fatal.  
Assess me nt of C a us alit y  
•  T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y dr u g a n d eac h occ urre nce of 
eac h A E/ S A E .  If refere nce t hera p y is use d i n c o m bi nati o n wit h a n I nc yte st u d y dr u g or m ulti ple 
I nc yte st u d y dr u gs are use d, t he n t he relati o ns hi p t o t he st u d y dr u g/refere nce t hera p y m ust be 
assesse d ( ie, f or t he I nc yte pr o d uct(s) a n d f or t he ot her pr o d uct(s) t hat is use d i n c o m bi nati o n wit h 
t he I nc yte pr o d uct).  If a p pr o priate, t he relati o ns hi p t o t he c o m bi nati o n ma y be assesse d as well. 
•  A "reas o na ble p ossi bilit y" of a relati o ns hi p c o n ve ys t hat t here are  me dical  facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n t hat a relati o ns hi p ca n n ot be r ule d o ut.  
•  T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he p ossi bilit y of a relati o ns hi p. 
•  T he i n vesti gat or will als o c o ns ult t he R SI  i n t he I B or Pr o d uct I nf or mati o n f or st u d y dr u g or 
mar kete d pr o d ucts, res pecti vel y, f or ma ki n g his/ her assess me nt.  
•  Alter nati ve ca uses, s uc h as u n derl yi n g or c o nc urre nt disease(s), c o nc o mita nt t hera p y, a n d ot her ris k 
fact ors, as well as t he te m p oral relatio ns hi p of t he e ve nt t o st u d y dr u g a d mi nistrati o n , will be 
c o nsi dere d a n d i n vesti gate d.  
•  F or eac h A E/ S A E, t he i n vesti gat or m ust  d oc u me nt i n t he me dical n otes t hat he/s he has re vie we d t he 
A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y.  
•  Wit h re gar d t o asse ssi n g ca usalit y of S A Es: 
− T here ma y be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort.  H o we ver,  t he ca usalit y assess me nt is o ne of t he criteria 
use d w he n deter mi ni n g re g ulat or y re p orti n g re q uire me nts.  T heref ore,  it is ver y i m p ort a nt t h at 
t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y b ase d o n t he a v ail a ble i nf or m ati o n 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E. 
− T he i n vesti gat or ma y c ha n ge his/ her o pi ni o n of ca us alit y i n li g ht of f oll o w -u p i nf or mati o n a n d 
s u b mit t he u p date d ca usalit y assess me nt. 

I nc yte C orp orati o n  
Pa ge 7 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
F oll o w -U p of A d verse E ve nt s a n d Seri o us A d verse E ve nt s 
•  T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal meas ure me nts 
a n d/ or e val uati o ns as me dicall y i n dicate d or as re q ueste d b y t he s p o ns or t o el uci date t he nat ure 
a n d/ or ca usalit y of t he A E or S A E as f ull y as p ossi ble .  T his ma y i ncl u de a d diti o nal la b orat or y tests 
or i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her healt h care 
pr ofessi o nals.  
•  O nce a n A E is detecte d, it s h o ul d be f oll o we d i n t he A E e C R Fs 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 verit y, t he s us pecte d relati o ns hi p t o t he st u d y dr u g, t he i nter ve nti o ns re q uire d t o 
treat t he e ve 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 ver ti me f or a re p orti n g peri o d (e g, bet wee n visits), eac h 
c ha n ge i n se verit y will be re p orte d as a se parate A E.  
•  If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d f oll o w-u p peri o d, t he 
i n vesti gat or will pr o vi de t he s p ons or wit h a c o p y of a n y p ost m orte m fi n di n gs i ncl u di n g 
hist o pat h ol o g y . 
•  U p date d S A E i nf or mati o n will be rec or de d i n t he ori gi nall y c o m plete d e C R F a n d re p orte d t o I nc yte 
P har mac o vi gila nce (i n t he S A E E D C C R F or via e mail/fa x if pa per S A E f or m is use d d ue t o 
u na vaila bilit y of e C R F) u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, or t he 
partici pa nt is l ost t o f oll o w -u p.  
•  A n y u p date d S A E data (i ncl u di n g S A Es bei n g d o w n gra de d t o n o nseri o us) will be s u b mitte d t o t he 
s p o ns or ( or desi g nee) wit hi n 2 4  h o urs of recei pt of t he i nf or mati o n.  
See  A p pe n di x  C  f or t he ma na ge me nt of P H L  cas es. 
9. 4.  
Re p orti n g of S eri o us A d verse E ve nt s 
Re gar dless of s us pe cte d ca usalit y (e g, relati o ns hi p t o st u d y dr u g, refere nce t hera p y or st u d y 
pr oce d ure[s]), all S A Es occ urri n g after t h e partici p a nt has si g ne d t he I C F t hr o u g h 3 0 da ys aft er 
t he last d ose of st u d y dr u g or  u ntil t he partici pa nt  starts a ne w a ntica ncer t hera p y, w hic h e ver 
occ urs earlier , m ust be re p orte d t o t he s p o ns or ( or desi g nee) i m me diatel y, wit h o ut u n d ue dela y 
b ut n ot later t ha n wit hi n 2 4 h o urs  of o btai ni n g k n o wle d ge of its occ urre n ce, u nless ot her wise 
s pecifie d b y t he Pr ot oc ol.  T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or ( or 
desi g nee) i m me diatel y, wit h o ut u n d ue dela y b ut n ot later t ha n wit hi n 2 4 h o urs of it bei n g 
a vaila ble.  
I n v esti gat ors are n ot o bli gate d t o acti vel y se e k A E or S A E i nf or mati o n after c o ncl usi o n of st u d y 
partici pati o n .  If t he i n vesti gat or lear ns of a n y S A E, i ncl u di n g a deat h, at a n y ti me after a 
partici pa nt has bee n disc har ge d fr o m t he st u d y, a n d he/s he c o nsi ders t he e ve nt t o be reas o n a bl y 
relate d t o t he st u d y dr u g or st u d y partici pati o n, t he n t he i n vesti gat or m ust n otif y 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 ware of t he e ve nt . 
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o pr o acti vel y f oll o w eac h partici pa nt 
at s u bse q ue nt visits/c o ntacts .  All S A Es will be f oll o we d u ntil res ol uti o n , sta bilizati o n, t he e ve nt 
is ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w-u p (as defi ne d i n Secti o n  7. 3 ). 
Pr o m pt n otificati o n b y t he i n vesti gat or t o t he s p o ns or of a n  S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts a n d t he safet y of a s t u d y 
dr u g u n der cli nic al i n vesti gati o n are met . 

I nc yte C orp orati o n  
Pa ge 7 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
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 occ 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 he s p o ns or or its desi g nee ma y ur ge ntl y re q uire f urt her 
i nf or mati o n fr o m the 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 nee 
ma y nee d t o iss ue a n I n v esti gat or N otificati o n t o i nf or m all i n vesti 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 ad verse 
reacti o ns will be c ollecte d a n d re p ort e 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 r e g ulat or y re q uire m e nts 
i n partici pati n g c o u ntries. 
T he s p o ns or has a l e gal r es p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a g e ncies a b o ut t he safet y of a st u d y dr u g u n der cli nical i n vesti gati o n .  T he s p o ns or 
will c o m pl y wit h c o u ntr y -s pecific re g ulat or y re q uire me nts relati ng t o safet y re p orti n g t o t he 
re g ulat or y a ut h orit y, I R B/I E C, a n d i n vesti gat ors. 
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x p ecte d s eri o us a d verse reacti o ns 
acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as 
necessar y.  
A n i n vesti gat or w h o recei ves a n i n vesti gat or safet y re p ort descri bi n g a n  S A E or ot her s pecific 
safet y i nf or mati o n (e g, s u m mar y or listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t h e n file it 
al o n g wit h t he I B a n d will n otif y t he  I R B/I E C, if a p pr o priate acc or di n g t o l ocal re q uir e me nts. 
S eri o us A d verse E ve nt  Re p orti n g  
•  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 i n t he e C R F. 
•  T he i n vesti gat or m ust re p ort wit hi n 2 4 h o urs of lear ni n g of its occ urre nc e a n y S A Es via t he E D C 
s yste m ( pri mar y met h o d) or b y c o m pleti n g t he Seri o us A d verse E ve nt Re p ort F or m i n E n glis h ( o nl y 
if t he E D C s yste m is n ot a vaila ble .  T he c o ntact i nf or mati o n f or I nc yte P har mac o vi gila nce b y 
e mail/fa x is liste d i n t he i n vesti gat or site file or as per t he I nc yte Refere nce G ui de f or C o m pleti n g t he 
Seri o us A d verse E ve nt Re p ort F or m ). 
•  I n circ u msta nces w here t he E D C s yste m is n ot accessi ble f or re p orti n g S A E i nf or mati o n (i nitial 
a n d/ or f oll o w-u p S A E i nf or mati o n) t o t he s p o ns or wit hi n 2 4 h o urs, refer t o t he I nc yte Refere nce 
G ui de f or C o m pleti n g t he Seri o us A d verse Re p ort F or m.  O nce t he E D C s yste m is f u ncti o nal, t he 
S A E re p ort s h o ul d be retr os pecti vel y a d de d t o t he E D C s yste m a n d f oll o w -u p s h o ul d be c o m plete d 
t hr o u g h t he E D C.  T he ori gi nal c o p y of t he Seri o us A d verse E ve nt Re p ort F or m a n d t he e mail or 
facsi mile c o nfir mati o n s heet m ust be ke pt at t he st u d y site (refer t o t he I nc yte Refere nce G ui de f or 
C o m pleti n g t he Seri o us A d verse Re p ort F or m f or details a n d f or t he e mail a d dre ss or fa x n u m ber). 
•  F oll o w -u p i nf or mati o n is als o rec or de d i n t he e C R F a n d tra ns mitte d t o I nc yte P har mac o vi gila nce via 
t he E D C s yste m.  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 pre vi o usl y, 
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 t he 
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 partici pa nt 
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 ve 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.  
9. 5.  
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.  

I nc yte C orp orati o n  
Pa ge 7 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
9. 6.  
Pre g n a nc y  
Pre g na nc y, i n a n d of itself, is n ot re gar de 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 ma y 
ha ve i nterfere 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 partici p a nt d uri n g mater nal or p at er nal e x p os ure t o st u d y 
dr u g , t he f oll o wi n g pr oce d ures s h o ul d be f oll o we d i n or der t o e ns ure 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 p artici pa nts o nl y). 
•  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 yte 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.  
Data o n fet al o utc o me are c ollecte d f or re g ulat or y re p orti n g a n d dr u g s afet 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 n ta 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 n ce or a bse n ce of a n y birt h defects, 
c o n ge nital a b n or malities, or mater nal 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 n c y s h o ul d be rec or de d o n a C li nical Trial Pre g na n c y F or m a n d re p orte 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 nc 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 he sa me f or m a n d s h o ul d i ncl u de a n assess 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 pecifie d i n l ocal re g ul ati o ns, w hic he ver is lat er .  Refer t o t he I n c yte 
Refere n ce G ui d e f or C o m pleti n g t he Cli nical Trial Pre g na nc y F or m.  
A n y S A E occ u rri n g d uri n g pre g n a nc y of a st u d y p artici p a nt m ust be rec or de d o n t he 
Seri o us A d verse E ve nt F or m i n t he e C R F  a n d s u b mitte d t o t he s p o ns or or desi g nee  (see 
Secti o n  9. 4 ). 
A b n or mal pre g n a nc y o ut c o mes ( e g, s p o nta n e o us a b orti o n, fetal deat h, still birt h, c o n ge nital 
a n o malies, or ect o pic pre g na nc y) are c o nsi dere d S A Es  (if occ urri n g i n t he st u d y partici pa nt) a n d 
m ust be re p orte d as d escri be d i n Secti o n  9. 4 .  If a n a b n or mal pre g n a nc y o ut c o me is re p orte d i n a 
st u d y partici pa nt's part ner, t he e ve nt s h o ul d be re p orte d t o t he s p o ns or o n t he Cli nical Trial  
Pre g na nc y F or m.  
9. 7.  
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 ollecte d b y 
t he s p o ns or or its desi g nee, are prese nt e d i n t he I B.  A d diti o nal safet y i nf or mati o n c ollecte 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 vesti gat or N otificati o 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 partici pa nt d uri n g t he st u d y, as 
necessar y.  If ne w si g nifi ca nt ris ks are i de ntifie d, t he y will  be a d de d t o t he I C F . 
9. 8.  
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 g s 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 g e 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 material will be re p orte d directl y t o t he res pective ma n ufact urer.  

I nc yte C orp orati o n  
Pa ge 8 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
T he i n vesti gat or or his/ her desi g ne e 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 mat i 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 rec or de d as des cri be d i n Secti o n  9. 3 . 
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.  
9. 9.  
Tre at me nt of O ver d ose  
T here h as bee n n o cli nical e x perie nce wit h o ver d ose of I N C B 0 0 0 9 2 8.  Treat me nt of o ver d ose 
s h o ul d c o nsist of ge neral s u p p orti ve meas ures. 
F or t he p ur p os es of t his st u d y, a n o ver d ose will be defi ne d as t he us e of st u d y dr u g  i n d oses i n 
e xcess of t h ose s p ecifie d i n t he Pr ot oc ol .  Partici pa nts o ver d ose d s h o ul d be treate d wit h 
a p pr o priate s u p p orti ve care u ntil rec o v er y.  Use of st u d y dr u g i n d oses i n e xcess of t h ose 
s pecifie d i n t he Pr ot oc ol s h o ul d n ot be rec or de d i n t he eC R Fs as a n A E of O ver d ose.  A n 
o ver d ose wit h ass oci ate d S A Es s h o ul d be rec or de d as t he S A E dia g n osis/s y m pt o ms o n t he 
rele va nt A E a n d S A E f or ms i n t he eC R Fs.  A n o ver d ose wit h ass oci ate d n o nseri o us A Es s h o ul d 
be rec or de d as t he A E di a g n osis/s y m pt o ms o n t he rele va nt A E f or ms i n t he eC R Fs.  A n o ver d os e  
wit h o ut ass ociate d s y m pt o ms s h o ul d n ot be rec or de d as a n A E i n t he e C R Fs.  
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d: 
•  C o ntact t he me dical m o nit or i m me diatel y.  
•  Cl osel y m o nit or t he partici pa nt f or a n y A E/ S A E a n d la b orat or y a b n or malities u ntil 
a p pr o priate rec o v er y/sta bilizati o n (at least 1 4 da ys).  
•  O btai n plas ma sa m ples (sa me sc he d ule as f or C 1 D 1 ) f or P K a n al ysis wit hi n 1 da y 
fr o m t he date of t h e last d ose of st u d y dr u g if re q ueste d b y t he me dical m o nit or 
( deter mi ne d o n a cas e-b y -case b asis).  
•  D oc u me nt t he q ua ntit y of t he e xcess d ose as w ell as t he d urati o n of t he o ver d ose i n 
t he e C R F. 
Decisi o ns re g ar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t he i n vesti gat or i n 
c o ns ultati o n wit h t he s p o ns or's me dical m o nit or base d o n t he cli nical e val u ati o n of t he 
partici pa nt.  

I nc yte C orp orati o n  
Pa ge 8 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 0.  
S T A TI S TI C S  
1 0. 1.  
S a m ple Size Deter mi n ati o n  
1 0. 1. 1.  
D ose E sc al ati o n 
I n t he d os e-es calati o n sta ge, a B OI N desi g n (Li u a n d Y ua n 2 0 1 5 ) will be us e d t o deter mi ne t he 
M T D.  T he c o h ort siz e will be 3 . A p p r o xi matel y 2 4  e val ua ble p artici pa nts ma y be treat e d i n t he 
d ose -escalati o n sta ge, a n d t he d ose -escalati o n pr o ce d ure m a y be st o p pe d if  > 9  e val ua bl e 
partici pa nts are treat e d at a n y d ose le vel.  T h e e xact n u m ber of partici pa nts treate d will de pe n d 
o n t he n u m ber of partici pa nts re q uire d p er d ose le vel a n d t he n u m ber of d ose le vels st u die d.  
1 0. 1. 2.  
D ose E x p a nsi o n  
A n a d diti o nal 1 5 e val ua ble partici pa nts  at eac h i de ntifie d R D E i n eac h dise ase gr o u p will be 
e nr olle d i n t he e x pa nsi o n sta ge . 
Fiftee n  p artici pa nts per c o h ort will pr o vi de a > 7 5 % c ha nce of i de ntif yi n g a t o xicit y wit h a tr ue 
e ve nt rate of 9 %.  
I n t otal, a p pr o xi matel y 1 2 0 partici pa nts will be i ncl u de d i n t he st u d y .  
1 0. 2.  
P o p ul ati o ns f or A n al ys es 
T he p o p ulati o ns f or a n al ys es are pr o vi de d i n Ta bl e  1 8 . 
T a ble  1 8 : 
P o p ul ati o ns f or A n al ys es 
P o p ul ati o n  
Descri pti o n  
F A S  
T he F A S  i ncl u des all partici pa nts w h o recei ve d at least 1 d ose of I N C B 0 0 0 9 2 8.  
T he F A S  will be use d f or t he s u m mar y of de m o gra p hics, baseli ne c haracteristics, 
partici pa nt dis p ositi o n, a n d a nal yses of all safet y a n d efficac y data.  
P K/ P D e val ua ble  
T he P K e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o recei ve d at least 
1  d ose of I N C B 0 0 0 9 2 8 a n d pr o vi de d at least 1  p ost d ose plas ma sa m ple ( 1  P K 
meas ure me nt).  
T he P D e val ua ble p o p ulati o n will i ncl u de all partici pa nts w h o recei ve d at least 
1  d ose of I N C B 0 0 0 9 2 8 a n d pr o vi de d at least 1  plas ma /ser u m sa m ple (1 P D 
meas ure me nt).  
1 0. 3.  
Le vel of Si g nific a nce  
All statistical a nal yses are e x pl orat or y i n n at ure.  All CIs pr o vi de d will be at t he 9 5 % c o nfi d e nce 
le vel.  

I nc yte C orp orati o n  
Pa ge 8 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 0. 4.  
St atistic al A n al yses  
1 0. 4. 1.  
Pri m ar y A n al ysis :  S afet y  
T he safe t y of I N C B 0 0 0 9 2 8 a d mi nistere d al o ne i n M D S a n d M M partici pa nts will be a nal yze d 
usi n g t he f oll o wi n g para meters descri pti vel y b y disease t y pe , o verall, a n d b y d ose le vel i n t he 
F A S p o p ulati o n:  
•  Fre q u e nc y a n d se verit y of A Es, S A Es, a n d D L Ts.  
•  C ha n ges i n vital si g ns a n d cli nical e val uati o ns i ncl u di n g E C Gs.  
•  C ha n ges i n cli nical bl o o d a n d uri ne la b orat or y para meters.  
•  Partici pa nts wit h D L Ts will be ta b ulate d f or eac h c o h ort of t he d ose-escalati o n sta ges.  
1 0. 4. 2.  
Sec o n d ar y A n al ys es 
1 0. 4. 2. 1.  Effic ac y  
T he effi cac y of I N C B 0 0 0 9 2 8 a d mi nistere d al o ne i n M D S a n d M M partici pa nts will be a nal yze d 
usi n g t he f oll o wi n g para meters b y disease t y p e a n d d ose le vel i n t he F A S p o p ulati o n.  
T he pr o p orti o n of partici pa nts ac hie vi n g a n a ne mi a res p o nse, defi ne d as a n H g b 
i ncreas e ≥ 1. 5  g/ d L relati ve t o baseli ne f or  a n y ≥ 8 -wee k p eri o d d uri n g t he first 2 4 wee ks of 
treat me nt if tra nsf usi o n-i n de pe n de nt at b aseli ne, will be esti mate d wit h its 9 5 % CI. 
T he pr o p orti o n of partici pa nts ac hie vi n g R B C tra nsf usi o n i n de pe n de nce f or ≥ 8  c o nsec uti ve 
wee ks if tra nsf us i o n-de p e n de nt at baseli ne d uri n g t he first 2 4 wee ks of treat me nt will be 
esti mate d wit h its 9 5 % CI.  
F or tra nsf usi o n-i n de pe n d e nt partici pa nts at bas eli ne, d urati o n of a n e mia res p o nse, defi ne d as t he 
i nter val fr o m t he first o ns et of a ne mia res p o nse t o t he earliest date of l oss of a ne mia res p o nse 
t hat persists f or at least 4 wee ks or d eat h fr o m a n y ca use , will be esti mate d usi n g t he 
Ka pla n -Mei er met h o d.  T he Ka pla n -M eier  esti mate of me dia n d urati o n of a ne mia res p o nse will 
be prese nt e d wit h 9 5 % CI.  
F or tra nsf usi o n-de pe n d e nt partici pa nts  at baseli ne ac hie vi n g R B C -TI , defi n e d as t he a bs e nce of 
a n y R B C tra nsf usi o n  f or at least 8 c o nsec uti ve wee ks d uri n g t he first 2 4 wee ks of treat me nt, 
d urati o n of R B C -TI p eri o d will be esti mate d usi n g t he Ka pla n -M eier met h o d.  T he  Ka pla n -Meier 
esti mate of me dia n d urati o n of R B C -TI p eri o d will be prese nt e d wit h 9 5 % CI.  
T he r ate of R B C tra nsf usi o n t hr o u g h Wee ks 1 2 a n d 2 4, defi ne d as t he a vera ge n u m ber of R B C 
u nits per partici pa nt -m o nt h d uri n g t he treat me nt p eri o d, will be esti mate d.  
T he lar gest i ncreas e fr o m baseli ne i n t he mea n H g b val ues o ver a n y r olli n g 8 -wee k tr eat me nt 
peri o d d uri n g t he first 2 4 wee ks of treat me nt  will be s u m marize d d escri pti vel y .  

I nc yte C orp orati o n  
Pa ge 8 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
F or M D S partici p a nts:  
•  O verall res p o nse rate, defi ne d as t he pr o p orti o n of partici pa nts wit h C R or P R as per 
C hes o n et al ( 2 0 0 6 ) defi niti o ns f or M D S  a n d as per Sa v o na et al ( 2 0 1 5 ) defi niti o ns 
f or M D S/ M P N overla p s y n dr o mes, as a p plica bl e, will be esti mate d wit h its 9 5 % CI.  
•  P F S a n d L F S will be esti mate d usi n g t he Ka pla n -Meier met h o d.  
F or partici pa nts  wit h M M :  
•  O verall res p o nse rate, defi ne d as t he pr o p orti o n of partici pa nts wit h stri n ge nt C R , C R , 
ver y g o o d P R , a n d P R  as per K u mar et al  (2 0 1 6 ), will be esti mate d wit h its 9 5 % CI.  
•  P F S  will be esti mate d usi n g t he Ka pla n -M eier met h o d . 
1 0. 4. 2. 2.  P h ar m ac o ki netics  
1 0. 4. 2. 3.  P h ar m ac o d y n a mics  
1 0. 4. 3.  
S afet y A n al yses  
Safet y a nal yses will be c o n d ucte d f or t he F A S  p o p ulati o n.  A d verse e v e nts will be c o de d b y t he 
Me d D R A dicti o nar y, a n d treat me nt-e mer ge nt a d verse e ve nts  (i e, A Es re p ort e d f or t he first ti me 

I nc yte C orp orati o n  
Pa ge 8 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
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 ) will be t a b ulate d b y preferre d 
ter m a n d s yste m or ga n class f or all e v e nts, relate d e ve nts, a n d e v e nts of Gra de 3 or hi g her.  
Q ua ntitati ve safet y v aria bles a n d t heir c h a n ges fr o m baseli ne ( e g, la b orat or y para m eters , vital 
si g ns) will be s u m marize d wit h descri pti ve statistics.  Cli nicall y n ota ble a b n or mal val ues will be 
fla g ge d a n d ta b ul ate d bas e d o n pre defi ne d criteria. 
T he cli nical la b orat or y d ata will be a nal yze d usi n g s u m mar y statistics; n o f or mal disease  gr o u p 
c o m paris o ns are pla n ne d.  I n a d diti o n, dis tri b uti o ns of ke y la b orat or y para meters ma y be pl otte d 
o ver ti me; t hese val ues will als o be classifie d i nt o C T C A E v 5. 0 t o xicit y gra des a n d ta b ulate d.  
Descri pti ve statistics a n d mea n c ha n g e fr o m b aseli ne will be deter mi ne d f or vital si g ns at eac h 
assess me nt ti me.  Vital si g n res ults will be re vie we d f or cli nicall y n ota ble a b n or malities (see 
Ta ble  1 9 ). 
Descri pti ve statistics a n d mea n c ha n g e fr o m b aseli ne wil l be deter mi ne d f or eac h E C G para meter 
at eac h assess me nt ti me.  Electr ocar di o gra m r es ults will be re vie we d f or cli nicall y n ota ble 
a b n or malities acc or di n g t o pre defi n e d criteria (see  Ta ble  2 0 ).  Partici pa nts e x hi biti n g cli nicall y 
n ota ble E C G a b n or malities will be liste d.  
T a ble  1 9 : 
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 5 b p m  
Te m perat ure  
> 3 8° C  
< 3 5. 5° C  
Res pirat or y rate  
> 2 4 breat hs/ mi n  
< 8 breat hs/ mi n  
T a ble  2 0 : 
Criteri a f or Cli nic all y N ot a ble Electr o c ar di o gr a m 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  
Q Tc  
> 4 5 0 ms  
< 2 9 5 ms  
P R  
> 2 2 0 ms  
< 7 5 ms  
Q R S  
> 1 2 0 ms  
< 5 0 ms  
Q T  
> 5 0 0 ms  
< 3 0 0 ms  
R R  
> 1 3 3 0 ms  
< 6 0 0 ms  
Meas ures of e x p os ur e ( e g, da ys of e x p os ure, d ose i nte nsit y) of st u d y dr u g will be s u m marize d b y 
mea ns of s u m mar y statistics.  
1 0. 4. 4.  
E x pl or at or y A n al ys es 

I nc yte C orp orati o n  
Pa ge 8 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 0. 5.  
I nteri m A n al ysis 
Safet y data will be m o nit ore d c o nti n u o usl y i n or der t o deter mi ne d osi n g i n s u bse q ue nt c o h orts, 
per t he al g orit h m i n t his Pr ot oc ol . 

I nc yte C orp orati o n  
Pa ge 8 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 1.  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S  
1 1. 1.  
I n vesti g at or Res p o nsi bilities 
•  T he Pr ot oc ol, Pr ot oc ol A me n d me nts, I C F, I B, a n d ot her rele va nt d oc u me nts 
(e g, a d vertise me nts) m ust be s u b mitte d t o a n I R B /I E C b y t he i n vesti gat or a n d 
re vie we d a n d a p pr o ve d b y t he I R B/I E C a n d h ealt h a ut h orities bef ore t he st u d y is 
i nitiate d. 
•  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 r e p orts pr o vi de d b y t he 
s p o ns or are re vie we d a n d pr ocesse d i n acc or da nce wit h re g ulat or y re q uire m e nts, 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 n d i nstit uti o nal re q uire me nts. 
•  A n y a me n d me nts t o t he Pr ot oc ol will re q uire  a p pr o val fr o m  b ot h h ealt h aut h orities 
a n d I R B/I E C bef ore i m pl e me ntati o n of c ha n g es m a de t o t he st u d y  desi g n, e xce pt f or 
c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o st u d y partici pa nts.  
•  T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:  
− Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y t o t he I R B/I E C a n n uall y or 
m ore fre q u e ntl y i n acc or da nce wit h t he re q uire m e nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/I E C.  
− N otif yi n g t he I R B/I E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y 
I R B/I E C pr oce d ures. 
− Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nc e t o G C P, 
I R B/I E C re q uir e me nts, i nstit uti o nal re q uire me nts, a n d a p plica ble la ws a n d 
c o u ntr y-s pecific re g ul ati o ns. 
•  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 greei n g t hat c ha n ges t o 
t he Pr ot oc ol pr oce d ures, wit h t he e xce 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, 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/I E C.  Eac h i n v esti gat or is res p o nsi ble f or e nr olli n g partici pa nts w h o ha ve met 
t he s pecifie d eli gi bilit y criteria. 
•  Retai ni n g rec 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 here 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 he a vaila bilit y of st u d y d oc u me 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  d uri n g t he 
rete nti o n peri o d 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 g at 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 
destr ucti o n of a n y st u d y rec or ds.  If t he i n vesti gat or lea 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 or its desi g nee 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.  

I nc yte C orp orati o n  
Pa ge 8 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
− 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 ware a n d s oft ware (f or accessi n g t he data), wi ll 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 r e g ulati o ns.  
T he s p o ns or will retai n t he ori gi nal e C R F data a n d a u dit trail.  
1 1. 1. 1.  
I de ntific ati o n of t he C o or di n ati n g Pri nci p al I n vesti g at or  
A c o or di nati n g pri nci pal i n vesti gat or will be a p p oi nte d b y t he s p o ns or's m e dical m o nit or bef ore  
t he e n d of t he st u d y.  As part of his or her res p o nsi bilities, t he c o or di nati n g pri nci pal i n vesti gat or 
will re vie w t he fi nal C S R.  A gree me nt wit h t he fi nal C S R will be d oc u me nte d b y t he date d 
si g nat ure of t he c o or di nati n g pri nci pal i n vesti gat or . 
1 1. 2.  
D at a M a n a ge me nt  
Data ma na g e me nt will be perf or me d i n a vali dat e d E D C s yste m.  T he i n vesti gat or will be 
pr o vi de d wit h access t o a n E D C s yste m s o t hat a n e C R F ca n b e c o m plete d f or eac h p artici pa nt.  
T he site will be pr o vi de d wit h e C R F c o m pleti o n g ui deli nes f or i nstr ucti o ns o n data e ntr y i n t he 
e C R F.  T he st u d y m o nit or will refere nce t he M o nit ori n g Pla n i n or der t o e ns ure t hat eac h iss ue 
i de ntifie d 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 da nce 
wit h t he pla n 's re q uire me nts.  Ot her data o utsi de t he E D C s yste m re q uire d i n t he st u d y c o n d uct 
of t he Pr ot oc ol , s uc h as d oc u me nts or res ults tra ns mitte d t o t he s p o ns or via a ce ntr al la b orat or y 
or s pecializ e d tec h nic al ve n d ors  a n d as d esi g nate d b y t he s p o ns or, will ha ve t heir o w n data fl o w 
ma na ge me nt pla ns, st u d y c harters, or bi o mar ker pl a ns, as a p plica bl e.  
T he s p o ns or ( or desi g nee) will be res p o nsi ble f or  t he f oll o wi n g: 
•  Ma na gi n g t he i nte grit y of t he data a n d t h e q ualit y of t he  c o n d uct of t h e st u d y, s uc h as 
e ns uri n g t hat st u d y m o nit ors perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat 
data e ntere d i nt o t he e C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d 
verifia ble fr o m s o urce d o c u me nts; t hat t he safet y a n d r i g hts of partici pa nts are bei n g 
pr otecte d; a n d t hat t he st u d y is bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y 
a p pr o ve d Pr ot oc ol a n d a n y ot her st u d y a gree me nts, I C H G C P, a n d all a p plica ble 
re g ulat or y re q uire me nts. 
•  Ma na gi n g a n d rec o ncili n g t he data ge n erate d a n d/ or c ollecte d , i ncl u di n g d o c u me nts 
a n d res ults s uc h as la b orat or y or i ma gi n g data a n al yze d ce ntrall y b y a desi g nate d 
ve n d or of t he s p o ns or.  
T he i n vesti gat or will be res p o nsi ble f or  t he f oll o wi n g: 
•  Rec or di n g, or e ns uri n g t he rec or di n g of, all rele va nt data relati n g t o t he st u d y i n t he 
e C R F. 
•  Deli veri n g, or e ns uri n g t he deli ver y of, all ot her res ults, d oc u me nts, data, k n o w -h o w, 
or f or m ulas rel ati n g t o t he st u d y t o t he s p o ns or or desi g nee electr o nicall y a n d/ or 
ce ntrall y ( e g, la b orat or y data, i ma gin g data, bi o mar ker data, p h ot o gra p hs, diar y data) 
or as ot her wise s p eci fie d i n t he Pr ot oc ol. 

I nc yte C orp orati o n  
Pa ge 8 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  Mai ntai ni n g a de q uate a n d acc urate s o urce d oc u m e nts a n d trial rec or ds t hat i ncl u de all 
perti ne nt o bser vati o ns o n eac h of t h e site's trial partici pa nts.  S o urce data  s h o ul d be 
attri b uta ble, le gi ble, c o nt e m p ora ne o us, ori gi nal, acc urat e, a n d c o m plet e.  C ha n ges t o 
s o urce dat a s h o ul d be tracea ble, s h o ul d n ot o bsc ure t he ori gi nal e ntr y, a n d s h o ul d be 
e x plai ne d if necessar y (e g, via a n a u dit trail).  S o urce dat a are, i n ge n eral, all 
i nf or mati o n i n ori gi nal rec or ds a n d certifie d c o pies of ori gi nal rec or ds of cli nical 
fi n di n gs, o bser vati o ns, or ot her acti vities i n a cli nical trial necessar y f or t he 
rec o nstr ucti o n a n d e val u ati o n of t he trial.  S o urce data are c o ntai ne d i n s o urc e 
d oc u me nts ( ori gi nal rec or ds or certifie d c o pies).  
•  Verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or electr o nicall y 
si g ni n g t he e C R F. 
•  Mai ntai ni n g acc urate d oc u me ntati o n (s o urce d ata) t hat s u p p orts t he i nf or mati o n 
e ntere d i n t he e C R F, s e nt t o a ce ntral v e n d or desi g nate d b y t he s p o ns or, or as 
descri be d i n ot her st u d y a n d data fl o w ma n uals.  
− S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste n ce of t he p artici pa nt a n d 
s u bsta ntiate t he i nte grit y of t he data c ollecte d.  S o urce d oc u m e nts are filed a n d 
a vaila ble at t he i n vesti gat or 's site.  E xa m ples of s o urce d oc u m e nts are ori gi nal 
d oc u me nts, data, a n d rec or ds (e g, h os pital rec or ds; electr o nic h os pital rec or ds; 
cli nical a n d office c h arts; la b orat or y n otes; me m ora n da; partici pa nts' diaries or 
e val uati o n c hec klists; p har mac y dis pe nsi n g rec or ds; rec or de d d ata fr o m 
a ut o mate d i nstr u me nts; c o pies or tra nscri pti o ns certifie d after verificati o n as 
bei n g acc urate c o pies; micr ofic h es; p h ot o gra p hic ne gati ves; micr ofil m or 
ma g netic me dia; x -ra ys; partici pa nts' files; a n d e-rec or ds/rec or ds ke pt at t he 
p har mac y, at t he la b orat ories, a n d at me dic o -tec h nical de part me nts i n v ol ve d i n 
t he cli nical trial). 
− Data e ntere d i n t he e C R F t hat are tr a nscri be d fr o m s o urce d oc u m e nts m ust be 
c o nsiste nt wit h t he s o urce d oc u me nts or  t he discre pa ncies m ust be e x plai n e d.  T he 
i n vesti gat or ma y nee d t o re q uest pre vi o us me di cal rec or ds or tra nsfer rec or ds, 
de pe n di n g o n t he st u d y.  C urre nt a p plica ble m e dical rec or ds m ust be a vaila ble.  
•  S e n di n g partici pa nts ' dat a, eit her as u ni q u e sa m ples, c o pies, or p h ot o gr a p hs, t o be 
e val uate d ce ntrall y or a n al yze d ce ntrall y, or b ot h, b y a q ualifie d ve n d or desi g nate d b y 
t he s p o ns or. 
− As re q uire d b y pri vac y a n d data pr otecti o n re g ulati o ns a n d I n c yte's pri vac y 
p olicies, if a n y p h ot o gra p hs of partici pa nts are t o b e ta ke n, t he p h ot o gra p hs m ust 
be li mite d t o t he area of t he face or t he b o d y t h at is strictl y necessar y a n d t he 
p h ot o gra p hs s h o ul d be mas ke d (ie, i de ntif yi n g feat ures s uc h as e yes, m o ut h, scars, 
tatt o os, or u ni q ue mar ki n gs or feat ur es s h o ul d be eit her obsc ure d wit h a blac k bar 
or di gitall y pi xelate d s o as t o n ot per mit t he rei de ntificati o n of t he partici pa nts a n d 
preser ve t heir c o nfi de ntialit y) b y a s peciall y desi g nate d p h ot o gra p h y ve n d or pri or 
t o se n di n g t he p h ot o gra p hs t o I nc yt e or a n y ot her t hir d-part y ve n d ors f or a nal ysis 
or f urt her pr ocessi n g.  

I nc yte C orp orati o n  
Pa ge 8 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  Per mitti n g st u d y -relate d 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 ulat 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 re pr ese ntati ves of t h e s p o ns or or its desi g nee, 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 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 vie w a n y st u d y materi als a n d 
partici pa nt rec or ds at e ac h m o nit ori n g visit.  
− A u diti n g:  Q ualifie d re prese ntati ves of t he s p o ns or or its desi g nee ma y a u dit t he 
cli nical st u d y site a n d st u d y data 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 ulati o ns, a n d o verall st u d y c o n d uct.  T he 
i n vesti gat or m ust all o w t he a udit 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 partici pa nts.  
− 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 de 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 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-relate 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 nta cte d b y a n y re g ulat or y a u t 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. 
1 1. 3.  
D at a Q u alit y Ass ur a nce  
T he s p o ns or ass u mes acc o u nta bilit y f or acti o ns dele gate d t o ot her i n di vi d uals (e g, c o ntr act 
researc h or ga nizati o ns).  T he s p o ns or or desi g ne e is res p o nsi ble f or t he dat a ma na ge m e n t of t his 
st u d y, i ncl u di n g q ualit y c hec ki n g of t he dat a.  F urt her, m o nit ori n g details descri bi n g strate g y, 
i ncl u di n g defi niti o n of st u d y-critical data ite ms a n d pr ocesses (e g, ris k -b ase d i nitiati ves i n 
o perati o ns a n d q ualit y s u c h as ris k ma na g e me nt a n d mit i gati o n strate gies a n d a nal ytical 
ris k-base d m o nit ori n g), met h o ds, res p o nsi bilities, a n d re q uir e me nts, i ncl u di n g ha n dli n g of 
n o nc o m plia nce iss ues, Pr ot oc ol de viati o ns, a n d m o nit ori n g tec h ni q ues (e g, ce ntral, r e m ote, or 
o n -site m o nit ori n g) are pr o vi de d i n the ( m o nit ori n g pla n or e q ui vale nt).  
1 1. 4.  
D at a Pri v ac y a n d C o nfi 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 data pr otecti o n la ws 
a n d re g ulati o ns .  T he i n v esti 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 hat pers o nal i nf or mati o n is ha n dle d i n acc or da nce wit h l ocal data pr otecti o n la ws (i ncl u di n g b ut 
n ot li mite d t o  HI P A A  a n d G D P R ) as a p plica ble , a n d t he s p o ns or o perat es c o m pre he nsi ve dat a 
pri vac y a n d d ata sec urit y pr o gra ms t hat are a p plica ble t o t his st u d y.  A p pr o priate n otice, or 
n otice a n d c o nse nt (as m a y be re q uire d b y eac h a p plica ble j uris dicti o n), f or c ollecti o n, use, 
discl os ure, a n d/ or tra nsfer (if a p plica bl e) of p ers o nal i nf or mati o n m ust be o btai ne d i n acc or da nce 
wit h l ocal data pr otecti o n la ws.  A p pr o priat e data pr otecti o n ter ms t hat c o m pl y wit h a p plica ble 
la ws will be i ncl u de d i n r ele va nt st u d y a gree me nts. 
T o e ns ure c o nfi de ntialit y of re c or ds a n d pr ot ect pers o nal data, p artici pa nt n a mes will n ot be 
s u p plie d t o t he s p o ns or or its desi g nee.  O nl y t he partici pa nt n u m ber will b e rec or de d i n t he 
e C R F; if t he partici pa nt 's na me a p pears o n a n y ot h er d oc u me nt (e g, la b orat or y re p ort), it m ust be 

I nc yte C orp orati o n  
Pa ge 9 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
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 da nce wit h a p pr o priat e tec h nical a n d 
or ga nizati o nal meas ures as re q uire d b y l ocal data pr otecti o n la ws. 
I n t he e ve nt of a data breac h i n v ol vi n g partici pa nt data, t he s p o ns or or its d esi g nee will f oll o w 
t he s p o ns or's i nci de nt res p o nse pr oce d ures.  T h e precise d efi niti o n of a data breac h v aries i n 
acc or da nce wit h a p plica ble la w b ut ma y ge nerall y be u n derst o o d as a b reac h of sec urit y lea di n g 
t o t he acci de ntal or u nla wf ul destr ucti o n, l oss, alterati o n, u na ut h orize d discl os ure of, or access t o, 
pers o nal data.   I n acc or da nce wit h its i nci de nt res p o nse pr oce d ures, t he s p o ns or will assess t he 
breac h t o c o nsi der its n otific ati o n a n d re me diati o n o bli gati o ns u n der a p plica ble la w.  
1 1. 5.  
Fi n a nci al Discl os ure  
Bef ore st u d y i nitiati o n, 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 F R Part 5 4 –  Fi na ncial Dis cl os ure b y Cli nical I n vesti gat o rs (ie, "c o vere d 
st u dies") are re q uire d t o s u b mit a c o m plete d Cli nical I n vesti gat or Fi na nci al Discl os ure F or m t hat 
s ufficie ntl y details 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 partici pa nts, i ncl u di n g t he s p o use a n d eac h 
de pe n de nt c hil d of t he cli nical i n vesti gat or or s u bi n vesti gat or .  T hese re q uir e me nts a p pl y t o b ot h 
U S a n d f orei 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 ne w cli nical 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 nci al Discl os ure F or m.  D uri n g a c o vere d cli nical 
st u d y, a n y c ha n ges t o t he fi na ncial i nf or mati o n pr e vi o usl y re p orte d b y a cli nical i n vesti gat or 
m ust be re p orte d t o t he s p o ns or or its desi g nee .  At t he c o ncl 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 ns.  I n t he e v e nt t hat t he cli nical 
i n vesti gat or is n ot re mi n de d, t he y ne vert heless will re mai n o bli gate d t o re p ort t o t he s p o ns or or 
its desi g nee a n y c h a n ges t o t he fi na ncial i nf or mati o n pre vi o usl y re p orte d, as well as a n y c h a n ges 
i n t heir fi na ncial i nf or mati o n f or a peri o d of 1 y ear after c o m pleti o n of t he c o vere d cli nical st u d y. 
1 1. 6.  
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 /her i nstit uti o n a gree t hat t he res ults of t he 
st u d y ma y be use d b y t he s p o ns or, I n c yte C or p orati o n (I n c yte), f or t he p ur p oses of nati o nal a n d 
i nter nati o nal re 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 res ults will be p u blis he d i n acc or da nce wit h a p plica ble l ocal a n d nati o nal 
re g ulati ons.  If necessar y, t he a ut h orities will be n otifie d of t he i n vesti gat or 's na me, 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 ne d 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 nee .  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 nee.  
T he res ults of t his st u d y ma y be p u blis he d or pres e nte d at scie ntific meeti n gs .  If t his is f oresee n, 
t he i n vesti gat or a grees t o s u b mit all ma n uscri pts or a bstracts t o t he s p o ns or bef ore s u b missi o n .  
T his all o ws t he s p o ns or t o pr otect pr o priet ar y i nf or mati o n a n d t o pr o vi de c o m me nts . 
T he s p o ns or will c o m pl y wit h t he re q uire me nts f or p u blicati o n of st u d y res ults .  I n acc or da nce 
wit h sta n dar d e dit orial a n d et hical practice, t he s p o ns or will  ge nerall y s u p p ort p u blicati o n of 

I nc yte C orp orati o n  
Pa ge 9 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as i n di vi d ual site data .  I n t his case, a 
c o or di nati n g i n vesti gat or will be desi g nate d b y m ut ual a gree m e nt.  
A ut h ors hi p will be deter mi ne d i n li ne wit h I nter n ati o nal C o m mit tee of Me dical J o ur nal E dit ors 
a ut h ors hi p re q uire m e nts.  
1 1. 7.  
St u d y a n d Site Cl os ure  
T he s p o ns or or desi g ne e reser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y 
ti me f or a n y reas o n at t he s ole discreti o n of t he s p o ns or.  St u d y sites will be cl ose d u p o n st u d y 
c o m pleti o n .  A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d o c u me nts a n d st u d y s u p plies 
ha ve bee n c ollecte d a n d a st u d y -site cl os ure visit has bee n perf or m e d. 
T he i n vesti gat or ma y i nitiate st u d y -site cl os ure at a n y ti me, pr o vi de d t here is reas o na ble ca use 
a n d s ufficie nt n otice is gi ve n i n a d va nce of t he i nt e n de d ter mi nati o n.  
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or or i n vesti gat or ma y i ncl u de b ut are 
n ot li mite d t o:  
•  Fail ure of t he i n vesti gat or t o c o m pl y wit h t he P r ot oc ol, t he re q uir e me nts of t he 
I R B/I E C or l ocal h ealt h a ut h orities, t he s p o ns or 's pr oce d ures, or G C P g ui deli nes. 
•  I n a de q uat e recr uit me nt of partici pa nts b y t he i n vesti gat or. 
•  Disc o nti n uati o n of f urt her st u d y treat me nt de vel o p me nt . 

I nc yte C orp orati o n  
Pa ge 9 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 2.  
R E F E R E N C E S  
A n dl T, A h n K, Kair o A, et al. E pit helial B m pr 1a re g ulates differe ntiati o n a n d pr oliferati o n i n 
p ost natal hair f ollicles a n d is esse ntial f or t o ot h de vel o p me nt. De vel o p me nt 
2 0 0 4; 1 3 1: 2 2 5 7 -2 2 6 8.  
A n dri o p o ul os B Jr, C orra di ni E, Xia Y, et al. B M P 6 is a ke y e n d o ge n o us re g ulat or of he pci di n 
e x pressi o n a n d ir o n met a b olis m. Nat Ge net  2 0 0 9; 4 1: 4 8 2 -4 8 7.  
Ar ma n d P, Ki m H T, C utler C S, et al. Pr o g n ostic i m pact of ele vate d pretra ns pla ntati o n ser u m 
ferriti n i n patie nts u n der g oi n g m yel oa blati ve ste m cell tra ns pla ntati o n. Bl o o d  
2 0 0 7; 1 0 9: 4 5 8 6 -4 5 8 8.  
Bir ge g år d G, G asc ó n P, L u d wi g H. E val uati o n of a nae mia i n patie nts wit h m ulti ple m yel o ma 
a n d l y m p h o ma: fi n di n gs of t he E ur o pea n C A N C E R A N A E MI A S U R V E Y. E ur J Hae mat ol  
2 0 0 6; 7 7: 3 7 8‐ 3 8 6.  
Bl o be G C, Sc hie ma n n W P, L o dis h H F. R ole of tra nsf or mi n g gr o wt h fact or beta i n h u ma n 
disease. N E n gl J Me d  2 0 0 0; 3 4 2: 1 3 5 0 -1 3 5 8.  
B o n d u S, Alar y A S, Lefè vre C, et al. A varia nt er yt hr oferr o n e disr u pts ir o n h o me ostasis i n 
S F 3 B 1 -m utate d m yel o d ys plastic s y n dr o me. Sci Tra ns l Me d 2 0 1 9; 1 1:eaa v 5 4 6 7.  
B o we n D T , Hellstr o m -Li n d ber g E. Best s u p p orti ve care f or t h e a nae mia of m yel o d ys plasia: 
i ncl usi o n of rec o m bi na nt er yt hr o p oieti n t hera p y ?. Le u k Res  2 0 0 1; 2 5: 1 9‐ 2 1.  
Casa de vall N. U p d ate o n t he r ole of e p o eti n alfa i n he mat ol o gic mali g na ncies a n d 
m yel o d ys plastic s y n dr o mes. Se mi n O nc ol  1 9 9 8; 2 5(s u p pl 7): 1 2‐ 1 8.  
Cella D, Kallic h J, Mc Der m ott A, X u X. T he l o n git u di nal relati o ns hi p of he m o gl o bi n, fati g ue 
a n d q ualit y of life i n a ne mic ca ncer patie nts: res ults fr o m fi ve ra n d o mize d cli nical tria ls. A n n 
O nc ol 2 0 0 4; 1 5: 9 7 9‐ 9 8 6.  
C hes o n B D, Gree n b er g P L, Be n nett J M, et al. Cli nical a p plicati o n a n d pr o p osal f or m o dificati o n 
of t he I nter n ati o nal W or ki n g Gr o u p (I W G) res p o nse criteria i n m yel o d ys pl asia. Bl o o d 
2 0 0 6; 1 0 8: 4 1 9 -4 2 5.  
C hi hara D, It o H, K ata n o da K, et al. I n ci de nce of m yel o d ys plastic s y n dr o me i n Ja pa n. J 
E pi de mi ol  2 0 1 4; 2 4: 4 6 9‐ 4 7 3.  
Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p. Rec o m me n dati o ns relate d t o c o ntrace pti o n 
a n d pre g na n c y testi n g i n cli nical trials. 2 0 2 0 . 
C o gle C R. I nci de n ce a n d b ur de n of t he m yel o d ys plastic s y n dr o mes. C urr He mat ol Mali g Re p 
2 0 1 5; 1 0: 2 7 2‐ 2 8 1.    
C ortelezzi A, Catta n e o C, Cristia ni S, et al. N o n -tra nsferri n-b o u n d ir o n i n m yel o d ys plastic 
s y n dr o mes: a mar ker of i neffecti ve er yt hr o p oiesis? He mat ol J 2 0 0 0; 1: 1 5 3 -1 5 8.  
Da m macc o F, Sil vestris F, Cast ol di G L, et al. T he effecti ve ness a n d t olera bilit y of e p oeti n alfa i n 
patie nts wit h m ulti ple m yel o ma refract or y t o c he m ot hera p y. I nt J Cli n La b Res 1 9 9 8; 2 8: 1 2 7‐ 1 3 4 . 
Di n m o ha me d A G, Visser O, va n N or d e n Y, et al. Tre n ds i n i nci de nce, i nitial treat me nt a n d 
s ur vi val of m yel o d ys plastic s y n dr o mes: a p o p ulati o n-base d st u d y of 5 1 4 4 p atie nts dia g n ose d i n 
t he Net herla n ds fr o m 2 0 01 t o 2 0 1 0. E ur J Ca ncer  2 0 1 4; 5 0: 1 0 0 4‐ 1 0 1 2.  

I nc yte C orp orati o n  
Pa ge 9 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Fe na u x P , A d ès L. H o w we treat l o w er -ris k m yel o d ys plastic s y n dr o mes. Bl o o d 
2 0 1 3; 1 2 1: 4 2 8 0 -4 2 8 6.   
Ferla y J, Steliar o v a -F o uc her E, L ortet -Tie ule nt J, et al. Ca ncer i nci de nce a n d m ortalit y patter ns 
i n E ur o pe: esti mates f or 4 0 c o u ntries i n 2 0 1 2. E ur J Ca ncer  2 0 1 3; 4 9: 1 3 7 4‐ 1 4 0 3.  
F o o d a n d Dr u g A d mi nistrati o n. G ui da nce f or I n d ustr y: S 9 N o ncli nical E val uati o n f or A ntica n cer 
P har mace uticals. 2 0 1 0.  
F o o d a n d Dr u g A d mi ni strati o n. G ui da nce f or I n d ustr y: Se verel y De bilitati n g or Life -T hreat e ni n g 
He mat ol o gic Dis or ders: N o ncli nical De v el o p me nt of P har mace uticals. 2 0 1 9.  
Gallitz I, L ofr ut he N, Trae ger L, et al. Defi cie nc y of t he B M P T y pe I rece pt or A L K 3 partl y 
pr otects mice fr o m a ne mia of i nfla m mati o n. B M C P h ysi ol  2 0 1 8; 1 8: 3 .  
Ga n gat N, Pat nai k M M, Be g na K, et al. S ur vi val tre n ds i n pri mar y m yel o d ys plastic s y n dr o mes: a 
c o m parati ve a nal ysis of 1 0 0 0 patie nts b y year of dia g n osis a n d treat me nt. Bl o o d Ca ncer J  
2 0 1 6; 6:e 4 1 4.  
Ga nz T. A n e mia of i nfla m mati o n. N E n gl J Me d  2 0 1 9; 3 8 1: 1 1 4 8‐ 1 1 5 7.  
Ga nz T, Ne met h E. He p ci di n a n d dis or ders of ir o n meta b olis m. A n n u Re v Me d  
2 0 1 1; 6 2: 3 4 7 -3 6 0.  
G ol d ber g S L, C he n E, C orral M, et al. I n ci de nce a n d cli nical c o m plicati o ns of m yel o d ys plastic 
s y n dr o mes a m o n g U nite d States Me dicare b e neficiaries. J Cli n O nc ol 2 0 1 0; 2 8: 2 8 4 7‐ 2 8 5 2.  
G o o d n o u g h L T . Er yt hr o p oieti n a n d ir o n -restrict e d er yt hr o p oiesis. E x p He mat ol  2 0 0 7; 3 5(s u p pl 
1): 1 6 7‐ 1 7 2.  
I brice vic-Balic L, Ici n dic-Na kas E, Hasic S, Kiselj a k o vic E, S of o -Hafiz o vic A, Balic S. 
Dile m ma: c orrelati o n bet wee n ser u m le vel of he p ci di n a n d I L -6 i n a ne mic m yel o ma patie nts. 
Me d Arc h  2 0 1 6; 7 0: 4 2 9‐ 4 3 2.  
I N C B 0 0 0 9 2 8 I n v esti gat or's Br oc h ure. Wil mi n gt o n, D E: I n c yte C or p orati o n. 
J o nes H B, Bj ör k ma n J A, Sc h ofiel d J. C or o nar y a n d s yste mic arterial p h ysi ol o g y a n d 
i m m u n o hist oc he mical mar kers relate d t o earl y c or o nar y art erial lesi o ns i n bea gle d o gs gi ve n t he 
p otassi u m c ha n nel o pe ner, Z D 6 1 6 9, or t he e n d ot heli n rece pt or a nta g o nist, Z D 1 6 1 1. T o xic ol  
Pat h ol 2 0 1 3; 4 1: 7 2 2 -7 3 5.  
Kat o drit o u E, Verr o u E, Ha djia g geli d o u C, et al. Er yt hr o p oiesis -sti m ulati n g a ge nts are ass ociat e d 
wit h re d uce d s ur vi val i n patie nts wit h m ulti ple m yel o ma. A m J He mat ol  2 0 0 8; 8 3: 6 9 7‐ 7 0 1.  
Kelai di C, Sta mat o ullas A, Be y ne -Ra u z y O, et a l. Dail y practice ma na g e me nt of m yel o d ys plastic 
s y n dr o mes i n Fra n ce: dat a fr o m 9 0 7 patie nts i n a o ne-wee k cr oss -secti o nal st u d y b y t he Gr o u pe 
Fra n c o p h o ne d es M yel o d ys plasies. Hae mat ol o gica  2 0 1 0; 9 5: 8 9 2‐ 8 9 9.   
K ö ni g C, Kle ber M, I h orst G, et al. Pre vale nce of  ir o n o verl oa d vs ir o n deficie nc y i n m ulti ple 
m yel o ma: rese m bli n g or differe nt fr o m M D S --a n d ste m cell tra ns pla nt ( S C T) --patie nts?. Cli n 
L y m p h o ma M yel o ma Le u k  2 0 1 3; 1 3: 6 7 1‐ 6 8 0.e 3.  
K uij pers M H, va n de K o oij AJ, Sl o ot we g PJ. T he rat i ncis or i n t o xic ol o gic pat h ol o g y. T o xic ol 
Pat h ol  1 9 9 6; 2 4: 3 4 6 -3 6 0 . 

I nc yte C orp orati o n  
Pa ge 9 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
K u mar S, Pai va B, A n ders o n K C, et al. I nter nati o n al M yel o ma W or ki n g Gr o u p c o nse ns us 
criteria f or res p o ns e a n d mi ni mal resi d ual disease assess me nt i n m ulti ple m yel o ma. La ncet 
O nc ol 2 0 1 6; 1 7:e 3 2 8‐e 3 4 6.  
K yle R A, Gertz M A , Wit zi g T E, et al. Re vie w of 1 0 2 7 patie nts wit h ne wl y dia g n ose d m ulti ple 
m yel o ma. Ma y o Cli n Pr oc  2 0 0 3; 7 8: 2 1‐ 3 3.  
K yle R A, Raj k u mar S V. M ulti ple m yel o ma [ p u blis he d c orrecti o n a p pears i n N E n gl J Me d 
2 0 0 5; 3 5 2: 1 1 6 3]. N E n gl J Me d  2 0 0 4; 3 5 1: 1 8 6 0‐ 1 8 7 3.  
K yle R A, Raj k u mar S V. M ulti ple m yel o ma. Bl o o d 2 0 0 8; 1 1 1: 2 9 6 2 -2 9 7 2.  
Le yla n d -J o nes B, B o n dare n k o I, Ne msa d ze G, et al. A ra n d o mize d, o pe n -la bel, m ultice nter, 
p hase III st u d y of e p oeti n alfa vers us best sta n dar d of care i n a ne mic p atie nts wit h metastatic 
breast c a ncer recei vi n g sta n dar d c h e m ot hera p y. J Cli n O nc ol 2 0 1 6; 3 4: 1 1 9 7‐ 1 2 0 7.  
Le yla n d -J o nes B, Se mi glaz o v V, Pa wlic ki M, et al. Mai ntai ni n g n or mal h e m o gl o bi n le vels wit h 
e p oeti n alfa i n mai nl y n o na ne mic patie nts wit h metastatic breast ca n cer recei vi n g first -li ne 
c he m ot hera p y: a s ur vi val st u d y. J Cli n O nc ol 2 0 0 5; 2 3: 5 9 6 0‐ 5 9 7 2.  
Li u S, Y ua n Y. Ba yesia n o pti mal i nter val desi g ns f or p hase I cli nical trials.  J R Stat S oc C 
2 0 1 5; 6 4: 5 0 7 -5 2 3.  
Ma X. E pi de mi ol o g y of m yel o d ys plastic s y n dr o mes. A m J Me d  2 0 1 2; 1 2 5(s u p pl): S 2‐ S 5.  
Ma X, D oes M, Raza A, Ma y ne S T. M yel o d ys plastic s y n dr o mes: i nci de nce a n d s ur vi val i n t he 
U nite d States. Ca ncer  2 0 0 7; 1 0 9: 1 5 3 6‐ 1 5 4 2.  
Maes K, Ne m et h E, R o o d ma n G D, et al. I n a ne mi a of m ulti ple m yel o ma, he pci di n is i n d uce d b y 
i ncreas e d b o ne m or p h o g e netic pr otei n 2. Bl o o d 2 0 1 0; 1 1 6: 3 6 3 5‐ 3 6 4 4.   
Malc o vati L, Della P orta M G, Laara k kers C M, et al. Er yt hr oi d acti vit y, tra nsf usi o n ir o n 
o verl oa d, a n d h e pci di n le vels i n patie nt wit h m yel o d ys plastic s y n dr o me. Bl o o d 2 0 0 8; 1 1 2: 2 6 7 6 
[a bstr]. 
Malc o vati L, Della P orta M G, Pasc utt o C, et al. Pr o g n ostic fact ors a n d life e x pecta nc y i n 
m yel o d ys plastic s y n dr o mes classifie d acc or di n g t o W H O criteria: a basis f or cli nical decisi o n 
ma ki n g. J Cli n O nc ol 2 0 0 5; 2 3: 7 5 9 4 -7 6 0 3 . 
Massa g ué J, W ott o n D. Tra nscri pti o nal c o ntr ol b y t he T G F -b eta/ S ma d si g nali n g s yste m. E M B O 
J 2 0 0 0; 1 9: 1 7 4 5 -1 7 5 4.  
Mc Q uilte n Z K, P olizz ott o M N, W o o d E M, S u n dararaj a n V. M yel o d ys plastic s y n dr o me 
i nci de nce, tr a nsf usi o n de pe n de nce, healt h care us e, a n d c o m plicati o ns: a n A ustralia n 
p o p ulati o n -base d st u d y 1 9 9 8 t o 2 0 0 8. Tra nsf usi o n  2 0 1 3; 5 3: 1 7 1 4‐ 1 7 2 1.  
Mei S, Wa n g H, F u R, et al. He pci di n a n d G D F 1 5 i n a ne mia of m ulti ple m yel o ma. I nt J He mat ol 
2 0 1 4; 1 0 0: 2 6 6‐ 2 7 3.  
Me y nar d D, K a utz L, D ar na u d V, Ca n o n ne -Her ga u x F, C o p pi n H, R ot h M P. Lac k of t he b o ne 
m or p h o ge netic pr otei n B M P 6 i n d uces massi ve ir o n o verl oa d. Nat Ge net  2 0 0 9; 4 1: 4 7 8 -4 8 1.  
Mi n g K wa n K, Li A G, Wa n g XJ, W urst W, Be hri n ger R R. E sse ntial r oles of B M P R-I A 
si g nali n g i n differe ntiati o n a n d gr o wt h of hair f ollicles a n d i n s ki n t u m ori ge nesis. Ge nesis  
2 0 0 4; 3 9: 1 0 -2 5.  

I nc yte C orp orati o n  
Pa ge 9 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Nati o nal  Ca ncer I nstit ute. C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts ( C T C A E) Versi o n 
5. 0. 2 0 1 7.  
Ne met h E, T uttle M S, P o wels o n J, et al. He p ci di n re g ulates cell ular ir o n effl u x b y bi n di n g t o 
ferr o p orti n a n d i n d uci n g its i nter nalizati o n. Scie nce  2 0 0 4; 3 0 6: 2 0 9 0 -2 0 9 3.   
O ke n M M, Creec h R H, T or me y D C, et al. T o xicit y a n d res p o nse criteria of t he Easter n 
C o o perati ve O nc ol o g y Gr o u p. A m J Cli n O nc ol 1 9 8 2; 5: 6 4 9 -6 5 5.  
Oster b or g A, B o o gaerts M A, Ci mi n o R, et al. Rec o m bi na nt h u ma n er yt hr o p oieti n i n tra nsf usi o n -
de pe n de nt a n e m ic patie nts wit h m ulti ple m yel o ma a n d n o n-H o d g ki n 's l y m p h o ma--a ra n d o mize d 
m ultice nter st u d y. T he E ur o pea n St u d y Gr o u p of Er yt hr o p oieti n ( E p oeti n Beta) Treat me nt i n 
M ulti ple M yel o ma a n d N o n -H o d g ki n 's L y m p h o ma. Bl o o d  1 9 9 6; 8 7: 2 6 7 5‐ 2 6 8 2.   
Oz k urt Z N, Y e gi n Z A,  S u ya ni E, et al. Fact ors affecti n g ste m cell m o bilizati o n f or a ut ol o g o us 
he mat o p oietic ste m cell tra ns pla ntati o n. J Cli n A p her 2 0 1 0; 2 5: 2 8 0‐ 2 8 6 . 
Pal u m b o A, A n ders o n K. M ulti ple m yel o ma. N E n gl J Me d  2 0 1 1; 3 6 4: 1 0 4 6‐ 1 0 6 0.  
Par k S, Gra bar S, Kelai di C, et al. Pre dicti ve fact ors of res p o nse a n d s ur vi v al i n m yel o d ys plastic 
s y n dr o me treate d wit h er yt hr o p oieti n a n d G-C S F: t he G F M e x p erie n ce. Bl o o d  
2 0 0 8; 1 1 1: 5 7 4 -5 8 2.  
P ullar kat V. O bjecti ves of ir o n c helati o n t hera p y i n m yel o d ys plastic s y n d r o mes: m ore t ha n meets 
t he e ye? Bl o o d  2 0 0 9; 1 1 4: 5 2 5 1 -5 2 5 5.  
R ollis o n D E, H o wla der N, S mit h M T, et al. E pi de mi ol o g y of m yel o d ys plastic s y n dr o mes a n d 
c hr o nic m yel o pr oliferati ve dis or ders i n t he U nite d States, 2 0 0 1 -2 0 0 4: utilizi n g data fr o m t he 
N A A C C R a n d S E E R pr o gra ms. Bl o o d  2 0 0 8; 1 1 2: 4 5 -5 2.  
R oss S L, Tra n L, Wi nters A, et al. M olec ular m ec ha nis m of he pci di n -me di ate d ferr o p orti n 
i nter nalizati o n re q uir es f err o p orti n l ysi nes, n ot t yr osi nes or J A K-S T A T. Cell Meta b 
2 0 1 2; 1 5: 9 0 5 -9 1 7 . 
Sa nt M, Mi nic ozzi P, M o u nier M, et al. S ur vi val f or hae mat ol o gical mali g n a nc ies i n E ur o pe 
bet wee n 1 9 9 7 a n d 2 0 0 8 b y re gi o n a n d a g e: res ults of E U R O C A R E -5, a p o p ulati o n -base d st u d y 
[ p u blis he d c orrecti o n a p p ears i n La n cet O nc ol 2 0 1 4; 1 5: 4 1 7]. La ncet O n c ol  2 0 1 4; 1 5: 9 3 1‐ 9 4 2.  
Sa nti ni V. Cli nical use of er yt hr o p oietic sti m ulati n g a ge nts i n  m yel o d ys plastic s y n dr o mes. 
O nc ol o gist 2 0 1 1a; 1 6(s u p pl 3): 3 5 ‐ 4 2.  
Sa nti ni V, Girelli D, Sa n na A, et al. H e pci di n le vels a n d t heir deter mi na nts i n differe nt t y pes of 
m yel o d ys plastic s y n dr o mes. P L o S O ne  2 0 1 1 b; 6:e 2 3 1 0 9.  
Sa v o na M R, Malc o vati L, K o mr o kji R, et al. A n i nter nati o nal c o ns orti u m pr o p osal of u nif or m 
res p o nse criteria f or m yel o d ys plastic/ m yel o pr oliferati ve ne o plas ms ( M D S/ M P N) i n a d ults. 
Bl o o d  2 0 1 5; 1 2 5: 1 8 5 7 -1 8 6 5.   
S har ma S, Ne met h E, C he n Y H, et al. I n v ol ve me nt of he pci di n i n t he a ne mia of m ulti ple 
m yel o ma. Cli n Ca ncer Res  2 0 0 8; 1 4: 3 2 6 2‐ 3 2 6 7.   
Sie gel R L, Miller K D, Je mal A. Ca ncer statistics, 2 0 1 7. C A Ca ncer J Cli n 2 0 1 7; 6 7: 7 -3 0.  
Stei n bic ker A U, Bart ni kas T B, L o h me yer L K, et al. Pert ur bati o n of he pci di n e x pressi o n b y B M P 
t y pe I rece pt or del eti o n i n d uces ir o n o verl oa d i n mice. Bl o o d 2 0 1 1a; 1 1 8: 4 2 2 4 -4 2 3 0.   

I nc yte C orp orati o n  
Pa ge 9 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
Stei n bic ker A U, Sac hi da na n da n C, V o n ner AJ, et al. I n hi biti o n of b o ne m or p h o ge netic pr ot ei n 
si g nali n g atte n uates a ne mia ass ociate d wit h i nfla m mati o n. Bl o o d  2 0 1 1 b; 1 1 7: 4 9 1 5 -4 9 2 3 .  
S wer dl o w S H, Ca m p o E, Harris N L, et al, e ds. W H O Classificati o n of T u m o urs of 
Hae mat o p oietic a n d L y m p h oi d Tiss ues. 4t h re v e d. L y o n, Fra n ce: I A R C Press, 2 0 1 7.  
Ta yl or K R, Vi nci M, B ull oc k A N, J o nes C. A C V R 1 m utati o ns i n DI P G: less o ns lear ne d fr o m 
F O P. Ca ncer Res 2 0 1 4; 7 4: 4 5 6 5 -4 5 7 0.  
Ter p os E, Kle b er M, E n g el har dt M, et al. E ur o p ea n M yel o ma Net w or k g ui deli nes f or t he 
ma na ge me nt of m ulti ple m yel o ma -relate d c o m plicati o ns. Hae mat ol o gica  2 0 1 5; 1 0 0: 1 2 5 4‐ 1 2 6 6 .  
T he url I, Sc hr oll A, Nair z M, et al. Pat h wa ys f or t he re g ulati o n of h e pci di n e x pressi o n i n a ne mia 
of c hr o nic dise ase a n d ir o n deficie nc y a ne mia i n vi v o. Hae mat ol o gica  2 0 1 1; 9 6: 1 7 6 1 -1 7 6 9.  
T h o mas G, Ali S, H oe bers FJ, et al. P hase  III trial t o e val uate t he efficac y of mai ntai ni n g 
he m o gl o bi n le vels a b o ve 1 2. 0 g/ d L wit h er yt hr o p oieti n vs a b o ve 1 0. 0 g/ d L wit h o ut 
er yt hr o p oieti n i n a ne mic patie nts recei vi n g c o nc urre nt ra diati o n a n d cis plati n f or cer vical ca ncer. 
G y nec ol O nc ol  2 0 0 8; 1 0 8: 3 1 7‐ 3 2 5.  
T o nia T, Mettler A, R o bert N, et al. Er yt hr o p oieti n or dar be p o eti n f or patie nts wit h ca ncer. 
C oc hra ne D ata bas e S yst Re v  2 0 1 2; 1 2: C D 0 0 3 4 0 7.  
U ni versit y of Was hi n gt o n Sc h o ol of P har mac y. Dr u g I nteracti o n Data base Pr o gra m. 2 0 0 2. 
htt p :// w w w. dr u gi nteracti o ni nf o. or g. 
U ntc h M, v o n Mi nc k witz G, K o nec n y G E, et al. P R E P A R E trial: a ra n d o mize d p hase III trial 
c o m pari n g pre o p erati ve, d ose -de nse, d os e -i nte nsifie d c he m ot hera p y wit h e pir u bici n, paclita xel, 
a n d C M F vers us a sta n dar d -d ose d e pir u bi c i n-c ycl o p h os p ha mi de f oll o we d b y paclita xel wit h or 
wit h o ut dar be p oeti n alf a i n pri mar y breast ca ncer --o utc o me o n pr o g n osis. A n n O nc ol  
2 0 1 1; 2 2: 1 9 9 9‐ 2 0 0 6.   
Va n der ker ke n K, As osi n g h K, Cr o uc her P, V a n Ca m p B. M ulti ple m yel o ma bi ol o g y: less o ns 
fr o m t he 5 T M M m odels. I m m u n ol Re v 2 0 0 3; 1 9 4: 1 9 6‐ 2 0 6.  
Va n der Wall K, D a niels -Wells T R, Pe nic het M, Lic hte nstei n A. Ir o n i n m ulti ple m yel o ma. Crit 
Re v O nc o g  2 0 1 3; 1 8: 4 4 9‐ 4 6 1.  
Va n u ytsel  T, Se n ger S, Fasa n o A, S hea -D o n o h ue T. Maj or si g nali n g pat h wa ys i n i ntesti nal ste m 
cells. Bi oc hi m Bi o p h ys Acta  2 0 1 3; 1 8 3 0: 2 4 1 0 -2 4 2 6.  
Vict or M, E v ge ni y H, G er ga na T, et al. Ser u m he p ci di n le vels i n m ulti ple m yel o ma. Cli n La b 
2 0 1 7; 6 3: 1 2 7 3‐ 1 2 7 7.   
Wa n g Y, Li L, Z he n g Y, et al. B M P acti vit y is re q uire d f or t o ot h de vel o p m e nt fr o m t he la mi na t o 
b u d sta ge. J De nt Res 2 0 1 2; 9 1: 6 9 0 -6 9 5.  
Weiss G , G o o d n o u g h L T. A ne mia of c hr o nic dise ase. N E n gl J Me d  2 0 0 5; 3 5 2: 1 0 1 1 -1 0 2 3.  
Z ha o N, Z ha n g A S, E n ns C A. Ir o n re g ulati o n b y h e pci di n. J Cli n I n vest 2 0 1 3; 1 2 3: 2 3 3 7 -2 3 4 3.  

I nc yte C orp orati o n  
Pa ge 9 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A P P E N DI X  A.  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  A N D D E FI NI TI O N S  
Defi niti o ns  
W O C B P:  A w o ma n w h o is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma n e ntl y sterile (see bel o w)  
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:  
•  Pre me n arc h al  
•  Pre me n o pa usal wit h 1 of t he f oll o wi n g: a 
− D oc u me nte d h ysterect o m y  
− D oc u me nte d bilateral sal pi n gect o m y  
− D oc u me nte d bilateral o o p h orect o m y  
•  P ost me n o pa usal  
− A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n alter nati ve me dical ca use.  
o  A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge ma y be use d t o c o nfir m a p ost me n o pa usal state i n 
w o me n n ot usi n g h or m o nal c o ntrace pti o n or H R T.  H o we v er, i n t he a bse nce of 1 2 m o nt hs of 
a me n orr hea, c o nfir mati o n wit h 2 F S H meas ure me nts i n t he p o st me n o pa usal ra n ge is re q uire d. 
− Fe males o n H R T a n d w h ose me n o pa usal stat us i s i n d o u bt will be re q uire d t o use 1 of t he n o n h or m o nal, 
hi g hl y effecti ve c o ntrace pti o n met h o ds if t he y wis h t o c o nti n ue t heir H R T d uri n g t he st u d y.  Ot her wise, 
t he y m ust disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y e nr oll me nt. 
F or m ale p artici p a nts of re pr o d ucti ve p ote nti al b  
T he f oll o wi n g met h o ds d uri n g t he Pr ot oc ol -defi ne d ti mefra me i n Secti o n  5. 1  are hi g hl y effecti ve:  
•  Use of a male c o n d o m pl us part ner use of a n a d diti o nal c o ntrace pti ve met h o d w he n ha vi n g pe nile -va gi nal 
i nterc o urse wit h a w o ma n of c hil d beari n g p ote ntial w h o is n ot c urre ntl y pre g na nt.  
•  Vasect o m y wit h me dical assess me nt of t he s ur gical s uccess ( verifie d b y site pers o n nel 's re vie w of t he 
partici pa nt 's me dical rec or ds) 
•  Se x ual a bsti ne n ce c. 
− A bsti ne n ce fr o m pe nile -va gi nal i nte rc o urse 

I nc yte C orp orati o n  
Pa ge 9 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
F or fe m ale p artici p a nts w h o are W O C B P  
T he f oll o wi n g met h o ds d uri n g t he Pr ot oc ol -defi ne d ti mefra me i n Secti o n  5. 1  t hat ca n ac hie ve a fail ure rate of less 
t ha n 1 % per year w he n use d c o nsiste ntl y a n d c orrectl y are c o nsi dere d as hi g hl y effecti ve birt h c o ntr ol met h o ds: 
•  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. d 
− oral  
− i ntra v a 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 n d 
− oral  
− i njecta ble 
− i m pla nta blee 
•  I ntra uteri ne de vicee 
•  I ntra uteri ne h or m o ne-releasi n g s yste me 
•  Bilateral t u bal occl usi o n e 
•  Vasect o mize d part ner e,f 
•  Se x ual a bsti ne n ce c 
a D oc u me ntati o n ca n c o me fr o m t he site p ers o n nel 's re vie w of t he partici p a nt's me dical rec or ds, me dical e xa mi n ati o n, or me dical 
hist or y i nter vie w.  
b If t h e male partici p a nt has a part ner wit h c hil d-beari n g p ote ntial t he part n er s h o ul d als o use c o ntrace pti ves.  
c I n t h e c o nte xt of t his g ui d a nce, se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y if defi ne d as refrai ni n g fr o m 
heter ose x ual i nterc o urse d uri n g t he e ntire peri o d of ris k ass ociate d wit h t he st u d y treat me nts.  T h e relia bilit y of se x ual 
a bsti ne nce nee ds t o be e val u ate d i n relati o n t o t h e d urati o n of t h e cli nic al st u d y a n d t he preferre d a n d us ual lifest yle of t h e 
partici p a nt.  
d 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 h e i n vesti g ati o nal me dici nal pr o d uct, w hic h ma y re d uce t h e 
efficac y of t h e c o ntrace pti o n met h o d.  
e C o ntrace pti o n met h o ds t h at i n t he c o nte xt of t his g ui d a nce are c o nsi d ere d t o ha ve l o w user de pe n de nc y.  
f Vasect o mize d part n er is a hi g hl y effecti ve met h o d of a v oi di n g pre g na nc y pr o vi d e d t h at part n er is t he s ole se x ual part n er of t he 
W O C B P st u d y partici p a nt a n d t hat t h e vasect o mize d part ner has recei v e d me dical assess m e nt of t he s ur gical s uccess.  
S o urce :  Cli nical Trials Facilitati o n a n d C o or di nati o n Gr o u p 2 0 2 0 . 

I nc yte C orp orati o n  
Pa ge 9 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A P P E N DI X  B.  I N S T R U C TI O N T O P A R TI CI P A N T S F O R H A N D LI N G 
S T U D Y D R U G (I N C B 0 0 0 9 2 8) 
T he partici pa nt m ust be i nstr ucte d i n t he ha n dli n g of st u d y dr u g as f oll o ws:  
•  St ore t he st u d y dr u g at r o o m te m perat ure, i n a safe place , a n d o ut of reac h of c hil dre n.  
•  O nl y re m o ve t he n u m ber of ta blets nee d e d at t he ti me of a d mi nistrati o n.  
•  D o n ot re m o ve ta blets i n a d va nce of t he ne xt s c he d ule d a d mi nistrati o n. 
•  Ma ke e ver y eff ort t o ta ke d oses o n sc he d ule  in t he m or ni n g ar o u n d t he sa me ti me 
e ver y da y . 
•  I N C B 0 0 0 9 2 8 ca n be ta k e n wit h a  f ull glass of wat er  (a b o ut 1 5 0 m L). 
•  If v o miti n g occ urs  aft er t a ki n g st u d y dr u g, d o  n ot ta ke a n ot her d os e.  
•  B ri n g all use d a n d u n use d st u d y dr u g b ottles t o t he site at eac h visit. 
•  R efrai n fr o m ta ki n g st u d y dr u g o n t he da y of t he cli nic visits u ntil aft er bl o o d sa m ples 
are c ollecte d.  
•  If a d ose of I N C B 0 0 0 9 2 8 is misse d b y m ore t ha n 4  h o urs, 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 ul e d d ose s h o ul d be a d mi nis tere d at t he us ual ti me. 

I nc yte C orp orati o n  
Pa ge 1 0 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A P P E N DI X  C.  M A N A G E M E N T O F P O T E N TI A L H Y 'S L A W C A S E S  
I N T R O D U C TI O N 
D uri n g t he c o urs e of t he st u d y , t he i n vesti gat or will re mai n vi gila nt f or i ncreases i n li ver 
bi oc he mistr y.  T he i n vesti gat or is res p o nsi ble f or deter mi ni n g w het her a partici pa nt  meets P H L 
criteria at a n y p oi nt d uri n g t he st u d y.  
T he i n vesti gat or partici p ates, i n c o nj u ncti o n wit h I n c yte c li nical pr oj ect a n d P h V  re pres e ntati ves, 
i n t he re vie w a n d assess me nt of cases f ulfilli n g P H L criteria t o ascertai n w het her t here is a n 
alter nati ve e x pl a nati o n f or t he ele vati o ns i n li ver bi oc he mistr y ot her t ha n dr u g -i n d uce d li ver 
i nj ur y ca use d b y t he st u dy dr u g . 
T he i n vesti gat or f ulfil ls r e q uire me nts f or t h e rec or di n g of data pert ai ni n g t o P H L or H y's la w 
cases a n d A E/ S A E re p orti n g acc or di n g t o t he o utc o me of t he re vi e w a n d assess me nt i n li ne wit h 
sta n dar d safet y re p orti n g pr ocesses. 
D E FI NI TI O N S  
F or t he p u r p os e of t his pr ocess, defi niti o ns are as f oll o ws : 
P ote ntial H y 's La w 
A n i ncreas e i n A S T or  A L T > 3 × U L N a n d t otal bilir u bi n > 2 × U L N at a n y p oi nt d uri n g t he 
st u d y.  T he ele vati o ns d o n ot ha ve t o be at t he sa m e ti me or wit hi n a s pecifi e d ti mefra me.  
H y 's La w  
A n i ncreas e i n A S T or A L T ≥ 3 × U L N a n d t otal bilir u bi n > 2 × U L N, w h ere n o ot her reas o n ca n 
be f o u n d t o e x plai n t he c o m bi nati o n of i ncreases (e g, ele vat e d ser u m A L P i n dicati n g c h olestasis, 
viral he patitis, a n ot her dr u g ). 
A C TI O N S R E Q UI R E D I N C A S E S O F A S T O R A L T  > 3 × U L N O R T O T A L 
BI LI R U BI N  ≥ 2 × U L N  
I de ntific ati o n a n d Deter mi n ati o n of P ote nti al H y's L a w 
T o i de ntif y cases of A S T or A L T > 3 × U L N or t otal bilir u bi n > 2  ×  U L N a n d c o nse q ue ntl y 
deter mi ne w het h er t he p artici pa nt  meets P H L criteria, please f ol l o w t he i nstr ucti o ns bel o w: 
•  Re vie w t he la b orat or y re p ort a n d if a partici pa nt  h as A S T or A L T > 3 × U L N O R 
t otal bilir u bi n > 2 × U L N at a n y visit: 
− Deter mi ne wit h o ut dela y w het her t he p artici pa nt  meets P H L criteria b y re vie wi n g 
la b orat or y re p orts fr o m all pre vi o us visits. 
− E nter t he la b orat or y data i nt o t he la b orat or y eC R F as s o o n as p ossi ble.  

I nc yte C orp orati o n  
Pa ge 1 0 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
P ote nti al H y 's L a w Criteri a N ot Met 
If t he partici p a nt  has N O T ha d A S T or A L T ≥ 3 × U L N A N D t otal bilir u bi n > 2 × U L N at a n y 
p oi nt i n t he st u d y (t he ele vati o ns d o n ot ha ve t o be at t he sa me ti me or wit hi n a s pecifie d 
ti mefra me), irres pecti ve of A L P, please f oll o w t h e i nstr ucti o n bel o w: 
•  Perf or m f oll o w -u p o n s u bse q ue nt la b orat or y res ul ts acc or di n g t o t he g ui da nce 
pr o vi de d i n  Secti o n  6. 6. 3 . 
P ote nti al H y 's L a w Criteri a Met 
If t he partici p a nt  has ha d A S T or A L T ≥ 3 × U L N A N D t otal bilir u bi n > 2 × U L N at a n y p oi nt i n 
t he st u d y (t he ele vati o ns d o n ot ha ve t o be at t he s a me ti me or wit hi n a s pecifie d ti mefra m e), 
irres pecti ve of A L P, please f oll o w t he i nstr ucti o n bel o w: 
•  Ha ve t he p artici pa nt  i nterr u pt st u d y dr u g. 
•  N otif y I n c yte st u d y tea m wit h o ut dela y.  
− T he i n vesti gat or, or desi g nee, s h o ul d c o ntact t he m e dical m o nit or t o disc uss a n d 
a gree u p o n a n a p pr oac h f or t he st u d y partici pa nt 's f oll o w-u p a n d t he c o nti n u o us 
re vie w of data. 
•  M o nit or t he partici pa nt  u ntil li ver bi oc he mistr y para meters a n d a p pr o priate cli nical 
s y m pt o ms a n d si g ns ret ur n t o n or mal or baseli ne l e vels, or as me dicall y i n dicate d.  
•  I n v esti gate t he eti ol o g y of t he e ve nt a n d perf or m a n y rele va nt dia g n ostic 
i n vesti gati o ns as disc usse d wit h t he me dical m o nit or. 
•  E nter t he la b orat or y data i n t o t he la b orat or y C R F as s o o n as p ossi ble. 
•  If at a n y ti me (i n c o ns ult ati o n wit h t he me dical m o nit or) t he P H L case m eets seri o us 
criteria, re p ort it as a n S A E usi n g sta n dar d re p orti n g pr oce d ures.  
R E VI E W A N D A S S E S S M E N T  
N o later t ha n 3 wee ks after t he bi oc he m istr y a b n or malit y was  i nitiall y detecte d a n d t he criteria 
f or P H L were  met, t he m e dical m o nit or, I nc yte P h V  p h ysicia n, a n d i n vesti g at or will disc uss a n d 
re vie w a v aila ble dat a a n d a gree o n w het her t here is a n alter nati ve e x pla nati o n f or t he ele vati o ns 
i n li ver bi oc he mistr y ot her t ha n dr u g-i n d u ce d li ver i nj ur y ca use d b y t he st u d y dr u g.  P artici pa nt 
matter e x perts  will be i ncl u de d i n t he re vie w as a p pr o priate.  

I nc yte C orp orati o n  
Pa ge 1 0 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
E v al u ati o n of Alter n ati ve C a uses  
I n or der t o gat h er a d diti o nal cli nical i nf or mati o n t o see k ot her p ossi ble ca uses of t he o bser ve d 
li ver test a b n or malities, t he f oll o wi n g alter nati ve eti ol o gies s h o ul d be c o nsidere d, i ncl u di n g b ut 
n ot li mite d t o : 
•  Acti ve viral he p atitis  
•  Alc o h olic a n d a ut oi m m u ne he patitis  
•  He pat o biliar y dis or ders  
− Biliar y tract disease, s u c h as mi grati o n of gallst o nes or i ntra he p atic lesi o ns, m ore 
ofte n ca us es c h olestatic i nj ur y i nitiall y a n d s h o ul d  be i n vesti gate d wit h 
gall bla d der a n d d u ctal i ma gi n g st u dies, es peciall y if A L P  is i ncrease d.  M ali g na nt 
i nterr u pti o n of t he biliar y tract als o s h o ul d be c o nsi dere d. 
•  C o nc o mita nt treat me nt  
•  Ot her ca us es s uc h as s yst e mic i nfecti o ns ( e g, b act erial, f u n gal, viral), n o nal c o h olic 
steat o he patitis, a n d car di o vasc ular dise ases 
Acti o ns A fter Re vi e w a n d Assess m e nt 
Acc or di n g t o o utc o me of t he re vie w a n d assess me nt, please f oll o w t he i nstr ucti o ns bel o w:  
If t here is a n a gree d alter nati ve e x pla nati o n f or t he A S T  or A L T a n d  t otal bilir u bi n ele vati o ns, a 
deter mi nati o n of w het h er t he alter nati ve e x pla nati o n is a n A E will be ma de a n d s u bse q ue ntl y 
w het her t he A E meets t h e criteri a f or a n  S A E.  
•  If t he alter nati ve e x pla n ati o n is n ot a n A E, rec or d t he alter nati ve e x pla nati o n o n t he 
a p pr o priate C R F if p ossi ble.  
•  If t he alter nati ve e x pla n ati o n is a n A E/ S A E, rec or d t he A E/ S A E i n t he eC R F 
acc or di n gl y a n d f oll o w t he sta n dar d st u d y pr o cesses.  
•  Ha ve t he p artici pa nt  res u me st u d y dr u g  as per Pr ot oc ol g ui deli nes.  
If it is a gree d t h at t here is n o e x pla nati o n t hat w o ul d e x plai n t he A S T or A L T a n d t otal bilir u bi n 
ele vati o ns:  
•  Ha ve t he p artici pa nt  per ma ne ntl y disc o nti n ue st u d y dr u g a n d perf or m E O T  
pr oce d ures.  
•  Re p ort a n S A E (re p ort ter m "H y 's La w"). 
− T he 'me dicall y i m p orta nt ' seri o us criteri o n s h o ul d be use d if n o ot her s eri o us 
criteria a p pl y.  
− As t here is n o alter nati ve e x pla nati o n f or t he H y 's la w case, a ca usalit y assess me nt 
of relate d s h o ul d be assi g ne d.  

I nc yte C orp orati o n  
Pa ge 1 0 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
•  If t here is a n u na v oi da ble dela y of o ver 3 wee ks i n o btai ni n g t he i nf or mati o n 
necessar y t o assess w h et her or n ot t he case meets t he criteria f or a H y 's la w case, t he n 
it is ass u me d t hat t here is n o alter nati ve e x pl a nati o n u ntil s uc h ti me as a n i nf or me d 
decisi o n ca n be m a de.  R e p ort a n S A E (re p ort ter m "P ote ntial H y 's La w") ap pl yi n g 
seri o us criteria a n d ca usalit y assess me nt as per a b o ve. 
A C TI O N S R E Q UI R E D F O R R E P E A T E PI S O D E S O F A S T O R A L T > 3 × U L N A N D/ O R 
T O T A L BI LI R U BI N > 2 × U L N  
T he re q uir e me nt t o c o n d uct f oll o w -u p, re vie w, a n d assess me nt of a re peat occ urre nce(s) of P H L 
is base d o n t he nat ure of t he alter nati ve ca use i de ntifie d f or t he pre vi o us occ urre n ce.  
If t he alter nati ve ca use f or t he pre vi o us occ urre nce of P H L was n ot c hr o nic or pr o gressi n g 
mali g na nt disease, pleas e f oll o w t he pr ocess f or P H L re vie w a n d assess me nt as des cri be d i n t his 
a p pe n di x.  
If t he alter nati ve ca use f or t he pre vi o us occ urre nce of P H L was c hr o ni c or pr o gressi n g mali g na nt 
disease , pleas e f oll o w t he i nstr ucti o ns bel o w:  
•  Deter mi ne  w h et her t here has bee n a si g nifica nt c ha n ge * i n t he partici p a nt 's c o n diti o n. 
− If t here is n o si g nifica nt c ha n ge, n o acti o n is re q uire d. 
− If t here is a si g nifica nt c ha n ge, f oll o w t he pr ocess descri be d f or P H L re vi e w a n d 
assess me nt as descri be d i n t his a p pe n di x.  
* A 'si g nifica nt' c h a n ge i n t he partici pa nt 's c o n diti o n refers t o a cli nicall y rele v a nt c ha n ge i n A L T, A S T, or t otal 
bilir u bi n, or ass ociate d s y m pt o ms.  T he deter mi nati o n of w het her t here has bee n a si g nifica nt c ha n ge will be at t he 
discreti o n of t he i n vesti gat or; t his ma y be i n c o ns ultati o n wit h t he me dical m o nit or if t here is a n y u ncertai nt y.  

I nc yte C orp orati o n  
Pa ge 1 0 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A P P E N DI X  D.  C O VI D -1 9 P A N D E MI C MI TI G A TI O N S T R A T E GI E S A N D 
I N S T R U C TI O N S 
T he C O VI D -1 9 gl o b al pa n de mic pres e nts c halle n ges t o t he o n g oi n g c o n d uct of cli nical trials.  I n 
li ne wit h re g ulat or y g ui d a nce re gar di n g cli nical trial e xec uti o n d uri n g t he p a n de mic, t he s p o ns or 
has iss ue d t he f oll o wi n g Pr ot oc ol c o nsi derati o ns t o e ns ure partici pa nt safet y is mai ntai ne d a n d 
a de q uate b e nefit/ris k a n al yses are a p plie d relati ve t o t he c o m pleti o n of st u d y pr oce d ures a n d 
mai ntai ni n g t he i n vesti gati o nal pr o d uct s u p p l y c hai n. 
Rec o g nizi n g t he d y na mic nat ure a n d fle xi bilit y re q uire d t o ma na ge t he i m pact of t he pa n de mic 
o n t his cli nical trial, a d diti o nal details will b e i nc or p orate d i nt o res p ecti ve  site-s pecific 
m o nit ori n g pla ns as a p plica ble, wit h i nstit uti o nal re q uire m e nts as warra nte d, a n d c o m m u nicate d 
t o t he i n vesti gati ve sites as nee de d.  R ele va nt test res ults will be d oc u me nte d i n t he e C R F, a n d 
a p plica ble c h a n ges t o t he I C F will be ma de a n d m o nit ore d.  
St u d y Site Visits  
If l ocal tra v el restricti o ns, is olati o n re q uire me nts, or t he i n vesti gat or 's be nefit/ris k assess me nt 
deter mi nes it t o be u nsafe f or partici pa nts t o atte n d st u d y visits at t he i n vesti gati o nal site, t he site 
staff ma y ele ct t o p urs ue t he f oll o wi n g: 
•  I n or der t o mi ni mize partici pa nt ris k, st u d y visits ma y be c o n d uct e d via tel e me dici ne 
m o dalities ( p h o ne or vi de o) or as p er site i nstit uti o nal g ui deli nes.  At a mi ni m u m, a 
re vie w of A Es a n d c o n c o mita nt me dicati o ns m ust be c o m plete d.  O n-site visits 
s h o ul d be c o n d ucte d w h e ne ver feasi ble a n d are re q uire d f or a d mi nistrati o n of st u d y 
treat me nt.  T he partici pa nt ma y als o be as ke d t o u n der g o a d diti o nal safet y la b orat or y 
assess me nts.  
•  I n or der t o s u p p ort i n vesti gat or o versi g ht of partici pa nt safet y a n d disease 
ma na ge me nt, t he p artici p a nt ma y be as ke d t o u n d er g o s o me la b orat or y t ests or st u d y 
pr oce d ures at a l ocal la b orat or y or facilit y cl oser t o t he partici pa nt 's resi d e nce rat her 
t ha n at t he i n vesti gati o nal site.  I n t his cas e, t he st u d y p h ysicia n will pr o vi de t he 
partici pa nt wit h t he list of para m eters t o be c hec k e d.  T hese tests s h o ul d be perf or me d 
i n certifie d la b orat ories. 
•  S o me tests, s uc h as E C G or C T sca n assess me nts, ma y re q uire l o n g er wi n d o ws of 
ti me t o perf or m d ue t o t h e C O VI D-1 9 p a n de mic a n d ma y be perf or me d o utsi de t he 
re g ularl y sc h e d ule d visit wi n d o w or ma y be c o n d u cte d at t he ne xt sc h e d ule d visit.  It 
is t he i n vesti gat or's res p o nsi bilit y t o c hec k wit h t he facilit y (if perf or me d at a 
differe nt facilit y) t hat t he data will be o btai ne d a n d a vaila ble f or e val uati o n.  Ge neral 
pr oce d ures perf or me d o utsi de of pr ot oc o l para met ers will be ca pt ur e d as pr ot oc ol 
de viati o ns d ue t o C O VI D -1 9 i n t he e C R F.    
P artici p a nt S A R S -C o V -2 I nfecti o n a n d St u d y Tre at me nt  
A n e ve nt of acti ve S A R S -C o V -2 i nfecti o n i n a partici pa nt i n t he st u d y s h o ul d be re p orte d as a n 
A E or S A E a n d a p pr o pri a te me dical i nter v e nti o n pr o vi de d.  F or partici pa nts wit h acti ve 
S A R S -C o V -2 i nfecti o n, st u d y treat me nt ma y be d ela ye d u ntil t he res ol uti o n of s y m pt o ms a n d 
u ntil it is all o wa ble f or t he partici pa nt t o ret ur n t o t he cli nic per i nstit uti o nal g ui deli nes.  Pri or  t o 
restarti n g treat me nt, t he treati n g p h ysicia n s h o ul d deter mi ne t hat t he partici pa nt's c o n diti o n is 

I nc yte C orp orati o n  
Pa ge 1 0 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
sta ble e n o u g h t o res u me st u d y treat me nt.  T he st u d y p h ysicia n s h o ul d als o c o nsi der if t he 
partici pa nt is S A R S -C o V -2 ne gati ve ( b y t est) bef ore restarti n g s t u d y treat m e nt if C O VI D-1 9 was 
dia g n ose d d uri n g t he trial.  T he st u d y tea m s h o ul d be n otifie d w he n t he st u d y treat me nt is 
restarte d.  Safet y m o nit ori n g f oll o wi n g C O VI D-1 9 s h o ul d be i m ple me nte d as per i nstit uti o nal 
g ui da nce or cli nical j u d g me nt (e g, c oa g ul a ti o n fact ors).   
C O VI D -1 9 V acci n ati o n  
Partici pa nts ma y recei ve t he C O VI D -1 9 v acci n e (see Secti o n 6. 7. 2 ).  C O VI D-1 9 vacci nati o n will 
be ca pt ur e d i n t he e C R F as a c o nc o mita nt me dicati o n.  A d mi nistrati o n of st u d y treat me nt ma y be 
dela ye d t o e ns ure vacci n ati o n is c o m plete d.   
Cli nic al Tri al M o nit ori n g  
St u d y m o nit ori n g visits c o ul d be p ost p o ne d; h o we ver, t he site m o nit or a n d s p o ns or will c o nti n ue 
t o e m pl o y off -site m o nit ori n g practices s uc h as r o uti ne c o m m u nicati o n met h o ds (e g, p h o ne calls, 
e mails, vi de o visits) wit h t he sites t o get i nf or mati o n o n trial pr o gress, partici pa nt stat us, a n d 
i nf or mati o n o n iss ue res ol uti o n.  T he st u d y m o nit or ma y re m otel y r e view data e ntere d i nt o t he 
E D C f or acc urac y a n d c o m plete ness if all o we d b y t he nati o nal re g ulat or y b o d y, i n vesti gati o nal 
site, a n d/ or i n c o m plia nce wit h l ocal a ut h orities.   
Rei m b urse me nt of A d diti o n al E x pe nses  
T he s p o ns or will rei m b urse f or a n y e xtra or di nar y  e x pe nses, kee pi n g a p pr o priate d oc u me ntati o n 
as e vi de nce (e g, tr a vel e x pe nses f or l ocal la b orat or y visit[s], c ost of l ocal [ pr o xi mate] la b orat or y 
tests). 

I nc yte C orp orati o n  
Pa ge 1 0 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A P P E N DI X  E.  P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S  
D oc u me nt  
D ate  
A me n d me nt 1  
1 7 N O V 2 0 2 0  
A me n d me nt 2  
0 8  A P R 2 0 2 1  
A me n d me nt 3  
2 2  D E C  2 0 2 1  
A me n d me nt 4  
2 0  D E C  2 0 2 2  
A me n d me nt 5  
0 6  D E C 2 0 2 3  
A me n d me nt 5 ( 0 6  D E C 2 0 2 3)  
O ver all R ati o n ale f or t he A me n d me nt:  
T he pri mar y p ur p os e of t he a me n d me nt is t o re d u ce t he i n vesti gati o nal sa m pli n g f or partici pa nts 
o n t he st u d y f oll o wi n g t he S p o ns or 's strate gic decisi o n t o st o p f urt her recr uit me nt.  Partici pa nts  
will be f oll o we d f or effic ac y a n d safet y w hile  o n st u d y b ut n o f urt her P K  or P D/ tra nslati o nal 
sa m pli n g will occ ur. U n n ecessar y assess me nts or s a m ples ha ve als o b ee n re m o ve d. C ha n ges are 
s u m marize d bel o w. 
1.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 3:  Sc he d ule of Acti vities, T a ble 4: Sc he d ule of 
L a b or at or y Ass ess m e nts)  
Descri pti o n of c h a n ge:   U p date d t he Da y 1 5 he m o gl o bi n assess me nts t o be ma n dat or y 
o nl y at C ycles 2  t o 6. 
R ati o n ale f or c h a n ge:   Re m o val of u n necessar y assess me nts.  
2.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 3:  Sc he d ule of Acti vities); Secti o n 8. 3. 5. 2, 
T ri plic ate 1 2 -Le a d E C G s ( T a ble 1 5:  Sc he d ule of C ar di ac F u ncti o n Assess m e nts) 
Descri pti o n of c h a n ge:   Re m o ve d 1 2 -lea d E C G p ost d ose assessme nt at C ycle 3  D a y 1 
a n d C ycle 6  D a y 1.  
R ati o n ale f or c h a n ge:   Re m o val of u n necessar y assess me nts.  
3.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 4: Sc he d ule of L a b or at or y Ass ess m e nts); 
Secti o n 8. 5. 1, Bl o o d S a m ple C ollecti o n ( T a ble 1 7: P h ar m ac o ki netic Bl o o d S a m ple 
Ti mi n g); Secti o n 8. 6, P h ar m ac o d y n a mic a n d Tr a nsl ati o n al Assess me nts ; 
Secti o n  8. 6. 1, Bl o o d a n d B o ne M arr o w S a m ple C ollecti o n ( T a ble 1 8 :  Bi o m ar ker/ 
Tr a nsl ati o n al S a m ple Ti mi n g) ; Secti o n 8. 6. 2, P h ar m ac o d y n a mic a n d Tr a nsl ati o n al 
Rese arc h P ar a meters  
Descri pti o n of c h a n ge:   Re m o ve d t he P K a n d P D/ tra nslati o nal sa m ples  fr o m C ycles 3 
t o 6 . 
R ati o n ale f or c h a n ge:   Re m o val of u n necessar y assess me nts.  
4.  Secti o n 4. 3, St u d y Ter mi n ati o n  
Descri pti o n of c h a n ge:   A d de d ti mi n g t o i n dicate w he n t he st u d y will be c o nsi dere d 
cl ose d f or dat a c ollecti o n f or t he pri mar y a nal ysis. 
R ati o n ale f or c h a n ge:   Clarificati o n.  

I nc yte C orp orati o n  
Pa ge 1 0 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
5.  I nc or p or ati o n of a d mi nistr ati ve c h a n ges. Ot her re g ulat or y g ui da nce a n d a d mi nistrati ve 
c ha n ges ha v e bee n i nc or p orate d t hr o u g h o ut t he Pr ot oc ol a n d are n ote d i n t he re dli ne 
versi o n of t he a me n d m e nt.  

I nc yte C orp orati o n  
Pa ge 1 0 8  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A me n d me nt 4  (2 0  D E C  2 0 2 2)  
O ver all R ati o n ale f or t he A me n d me nt:  
T he rati o nale f or t his a m e n d me nt is t o i m ple me nt c ha n ges t o clarif y t he d os e -e x pa nsi o n s c he me 
a n d t o all o w a m ore c o m plete e x pl orati o n of t he s afet y a n d efficac y of 1 or m ore R D E(s).   
A d diti o nal c ha n ges are s u m marize d bel o w.  
1.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 2 :  Ke y St u d y Desi g n Ele me nts; 
Fi g ure  1 :  St u d y Desi g n Sc he m a ); Secti o n 4. 1 .1, D ose  Esc al ati o n a n d De -Esc al ati o n 
Al g orit h m; Secti o n 4. 1. 3 , E x p a nsi o n St a ge s; Secti o n 6. 5. 4, Defi niti o n of t he 
Rec o m me n de d D o se f or E x p a nsi o n; Secti o n 1 0. 1. 2, D ose E x p a nsi o n  
Descri pti o n of c h a n ge:   T he i de ntificati o n of 1 or m ore R D E (s) i n eac h dis ease gr o u p 
a n d t he e x pa nsi o n of eac h R D E i nt o t he d ose -e x p a nsi o n sta ges h a ve b ee n a d de d.   As a 
res ult, t he sa m ple size i n creas e d fr o m 8 0 t o 1 2 0 p artici pa nts. 
R ati o n ale f or c h a n ge:   T he safet y a n d efficac y of I N C B 0 0 0 9 2 8 i n M D S or M M 
partici pa nts will be f urt h er e x pl or e d b y e x pa n di n g 1 or m ore R D E d ose(s).  
2.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 3:  Sc he d ule of Acti vities); Secti o n 8. 3. 5, 
C ar di ac F u ncti o n Assess m e nts ( T a ble 1 5:  Sc he d ule of C ar di ac F u ncti o n 
Assess m e nts)  
Descri pti o n of c h a n ge:   A d de d t ri plicate E C Gs t o scree ni n g a n d o n C ycle 1 Da ys 1 a n d 
1 5, a n d o n C ycles 3 a n d 6 Da y 1, t o ali g n wit h t he P K or P D sa m pli n g sc he d ule.  
A d diti o nal 1 2 -lea d E C Gs w ere a d de d t o  be p erf or me d pre d ose  o n C ycle 2 Da y  1  a n d 
p ost d ose o n C ycles 3 a n d 6 Da y 1 . 
R ati o n ale f or c h a n ge:   T o i n cl u de car diac para m eter meas ure me nts via tri plicate E C G t o 
e val uate t he effects of t h e st u d y dr u g o n t he car diac para meters . 
3.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 3:   Sc he d ule of Acti vities); Secti o n 8. 2. 1, 
Effic ac y Assess m e nts f o r All Dise ase Gr o u ps  
Descri pti o n of c h a n ge:  Clarifi e d t hat t he rec or di n g of H g b a n d R B C tra nsf usi o ns are 
ma n dat or y wit hi n 8 wee ks pri or t o C ycle 1  D a y 1.  
R ati o n ale f or c h a n ge:   Clarificati o n  t o i nsist u p o n rec or di n g all H g b a n d R B C 
tra nsf usi o n wit hi n 8 wee ks pri or t o C ycle 1 Da y 1 . 

I nc yte C orp orati o n  
Pa ge 1 0 9  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
4.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 4 :  Sc he d ule of L a b or at or y Assess me nts); 
Secti o n 8. 5. 1, Bl o o d S a m ple C ollecti o n ( T a ble 1 7: P h ar m ac o ki netic Bl o o d S a m ple 
Ti mi n g); Secti o n 8. 6. 1, Bl o o d a n d B o ne M arr o w S a m ple C ollecti o n 
( T a ble 1 8:   Bi o m ar ker/ Tr a nsl a ti o n al S a mple Ti mi n g)  
Descri pti o n of c h a n ge:   A d diti o nal bl o o d sa m ples t hat will be c ollecte d f or P D a n d P K 
p ur p oses ha ve b ee n a d de d o n  t o C ycle 3 a n d C ycle 6 Da y 1 bet w ee n 4 a n d 8 h o urs 
p ost d ose .  F or plas ma P D sa m ples o nl y , clarificati o n  was  a d de d t o state t h at sa m ples are 
t o be c ollecte d u ntil Cycle  2 4  D a y 1 . 
R ati o n ale f or c h a n ge:   T o b etter assess t he P D a n d P K pr ofile s of t he st u d y dr u g.  
5.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 4:  Sc he d ule of L a b or at or y Assess me nts); 
Secti o n 8. 6. 1, Bl o o d a n d B o ne M arr o w S a m ple C ollecti o n 
( T a ble 1 8:   Bi o m ar ker/ Tr a nsl ati o n al S a m ple Ti mi n g)  
Descri pti o n of c h a n ge:   U p date d t o i ncl u de a n a d diti o nal c ollecti o n ti me p oi nt ( C ycle 7 
Da y 1) f or ser u m bi o mar kers.  
R ati o n ale f or c h a n ge:   T o better assess t he P D pr ofile of t h e st u d y dr u g.  
6.  Secti o n 2. 3. 2, R ole of H e pci di n i n M yel o d ys pl astic S y n dr o me –  a n d M ulti ple 
M yel o m a – Rel ate d A ne mi a; Secti o n  5. 1, I ncl usi o n Criteri a  
Descri pti o n of c h a n ge:  F or i ncl usi o n criteri o n 6a, t he eli gi bilit y criteria re gar di n g 
defi niti o n of a ne mia w as clarifie d.  F or i ncl usi o n criteri o n 1 0, patie nts wit h M D S -R S a n d 
M D S/ M P N o verla p s y n dr o mes wit h ri n g si der o blasts a n d t hr o m b oc yt osis are n o w 
all o we d i n t he st u d y  a n d as a res ult t he te xt r e gar di n g e xcl usi o n fr o m st u d y of 
partici pa nts wit h M D S -R S a n d M D S/ M P N o verla p s y n dr o mes wit h ri n g si der o blasts a n d 
t hr o m b oc yt osis has bee n re m o ve d. 
R ati o n ale f or c h a n ge:  T o all o w m ore fle xi bilit y t o t he i n vesti gat ors t o e nr oll st u d y 
partici pa nts.  
7.  Secti o n 4. 1. 1, D ose Esc al ati o n a n d De -Esc al ati o n  ( T a ble 9:  Decisi o n B o u n d aries) 
Descri pti o n of c h a n ge:  A ta ble detaili n g t he  decisi o n b o u n daries i n t he D ose escal ati o n 
sta ges a n d t he defi niti o n of t he R D E ha ve b ee n a d de d.  
R ati o n ale f or c h a n ge:  Clarificati o n of t he decisi o n b o u n daries i n t he D os e escal ati o n 
sta ges a n d t he defi niti o n of t he R D E. 
8.  Secti o n  4. 1. 3, E x p a nsi o n St a ges  
Descri pti o n of c h a n ge:   A d de d t he perce nta ge of tra nsf usi o n -de p e n de nt partici pa nts t o 
b e e nr olle d i n  eac h e x p a nsi o n c o h ort .  
R ati o n ale f or c h a n ge:   T o clarif y t he perce nta ge of tra nsf usi o n-de p e n de nt partici pa nts t o 
be e nr olle d i n eac h e x p a nsi o n c o h ort  t o o btai n rele va nt res ults. 

I nc yte C orp orati o n  
Pa ge 1 1 0  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
9.  Secti o n 5. 2, E xcl usi o n Criteri a  ( E xcl usi o n Criteri a 5 a n d 9) 
Descri pti o n of c h a n ge:  F or e x cl usi o n criteri o n 5, t he ti me bef ore first d ose of st u d y 
dr u g was u p date d .  F or e xcl usi o n criteri o n 9 , t he n u m ber of pre vi o us years of acti ve 
i n vasi ve mali g na nc y were u p date d.  
R ati o n ale f or c h a n ge :  T o all o w m ore fle xi bilit y t o t he i n vesti gat ors t o e nr oll st u d y 
partici pa nts.  
1 0.  Secti o n 5. 2, E xcl usi o n Criteri a ( E xcl usi o n Criteri o n 1 2)  
Descri pti o n of c h a n ge:  Clarifie d t hat o nl y partici pa nts wit h left b u n dle bra nc h bl oc k 
will be e xcl u de d if det er mi ne d t o be cli nicall y si g nifica nt b y i n vesti gat or.  
R ati o n ale f or c h a n ge:  T o clarif y t he eli gi bilit y criteri o n re g ar di n g prese nce of left 
b u n dle bra nc h bl oc k . 
1 1.  Secti o n 5. 2, E xcl usi o n Criteri a ( E xcl usi o n Criteri o n 1 4)  
Descri pti o n of c h a n ge:  Clarifie d t hat he m oc hr o mat osis is t o be here ditar y.  
R ati o n ale f or c h a n ge:  Clarificati o n.  
1 2.  Secti o n 5. 2, E xcl usi o n Criteri a ( E xcl usi o n Criteri o n 1 5)  
Descri pti o n of c h a n ge:  Re vise d defi niti o ns of he patitis A, B, a n d C.  
R ati o n ale f or c h a n ge:  Clarificati o n  of t he defi niti o n a n d har m o nizati o n acr oss st u dies.  
1 3.  Secti o n 5. 2, E xcl usi o n Criteri a ( E xcl usi o n Criteri o n 2 5)  
Descri pti o n of c h a n ge:  Re m o ve d t he eli gi bilit y criteri o n f or A L P (e xcl usi o n criteri o n 
2 5f).  L o were d t he t hres h ol ds f or platelet a n d A N C val ues ( e xcl usi o n criteria 2 5a a n d 
2 5 b, res pecti vel y) t o all o w e nr oll me nt i n t he st u d y.  
R ati o n ale f or c h a n ge:  T o all o w m ore fle xi bilit y t o t he i n vesti gat ors t o e nr oll st u d y 
partici pa nts.  
1 4.  Secti o n 5. 2 E xcl usi o n Criteri a ( E xcl usi o n Criteri o n 2 5 g); Secti o n  8. 3. 6, Ir o n 
O verl o a d Assess m e nt  
Descri pti o n of c h a n ge:  Clarificati o n t hat t he use of C T sca n i nstea d of M RIs t o meas ure 
a p ote ntial ir o n o verl oa d i n t he li ver is all o we d at sites w here M RI is n o a v aila ble  has 
bee n a d d e d.  
R ati o n ale f or c h a n ge:  Clarifie d base d o n re q uest fr o m ke y i n vesti gat ors.  
1 5.  Secti o n 5. 2, E xcl usi o n Criteri a ( E xcl usi o n Criteri o n 2 6 ) 
Descri pti o n of c h a n ge:  A d de d t o all o w f or ir o n c helati o n treat me nt.  
R ati o n ale f or c h a n ge:  T o all o w m ore fle xi bilit y t o t he i n vesti gat ors t o e nr oll st u d y 
partici pa nts.  

I nc yte C orp orati o n  
Pa ge 1 1 1  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 6.  Secti o n 6. 5. 1, Defi nit i o n of a D ose-Li miti n g -T o xicit y  
Descri pti o n of c h a n ge:   Clarifi e d t hat a d diti o nal bl o o d sa m ples ma y be dra w n t o m ore 
precisel y c h aracteriz e a p ote ntial D L T e ve nt . 
R ati o n ale f or c h a n ge:   T o all o w a better assess me nt of a n y p ote ntial D L T . 
1 7.  Secti o n  6. 6. 3, Criteri a a n d Pr oce d ures f or D os e I nterr u pti o ns a n d A dj ust me nts of 
St u d y Dr u g ( T a ble 1 3:  G ui deli nes f or I nterr u pti o n a n d Rest arti n g of St u d y Dr u g)  
Descri pti o n of c h a n ge:  T he g ui deli nes f or i nterr u pti o n a n d restarti n g of t he st u d y dr u g 
i n t he e ve nt of i ncrease d ferriti n d uri n g t he st u d y ha ve bee n clarifie d. 
R ati o n ale f or c h a n ge:  Clarificati o n.  
1 8.  Secti o n  6. 6. 5, Criteri a a n d Pr oce d ures f or D os e I ncre ase s of St u d y Dr u g 
Descri pti o n of c h a n ge:  Clarif ie d t he c o n diti o ns f or i ntra partici pa nt d os e i ncreas e has 
bee n a d d e d.  
R ati o n ale f or c h a n ge:  Clarificati o n.  
1 9.  Secti o n  8. 5. 1, Bl o o d S a m ple C ollecti o n ( T a ble 1 7:   P h ar m ac o ki netic Bl o o d S a m ple 
Ti mi n g); Secti o n 8. 6. 1 , Bl o o d a n d B o ne M arr o w S a m ple C ollecti o n 
( T a ble 1 8:   Bi o m ar ker/ Tr a nsl ati o n al S a m ple Ti mi n g)  
Descri pti o n of c h a n ge:  T he 2 - a n d 4-h o ur p ost d ose P K a n d tra nsiti o nal bl o o d sa m ples 
t o be dra w n o n Cycle 1  D a y 1 a n d C ycle 1  D a y 1 5 ca n be p erf or m e d wit h a ti me-wi n d o w 
of ±  1 5  mi n utes.  
R ati o n ale f or c h a n ge:  T o a d d fle xi bilit y t o dra w P K a n d tra nslati o nal bl o o d sa m ples as 
re q ueste d b y k e y i n vesti gat ors. 
2 0.  Secti o n 1 0. 4. 2. 2; P h ar m ac o ki netics; Secti o n 1 0. 4. 2. 3, P h ar m ac o d y n a mics; 
Secti o n  1 0. 4. 4; E x pl or at or y A n al ys es 
Descri pti o n of c h a n ge:  
 
 
R ati o n ale f or c h a n ge:  Clarificati o n.  
2 1.  I nc or p or ati o n of a d mi nistr ati ve c h a n ges. Ot her re g ulat or y g ui da nce a n d a d mi nistrati ve 
c ha n ges ha v e bee n i nc or p orate d t hr o u g h o ut t he Pr ot oc ol a n d are n ote d i n t he re dli ne 
versi o n of t he a me n d m e nt.  
 

I nc yte C orp orati o n  
Pa ge 1 1 2  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A me n d me nt 3  (2 2  D E C  2 0 2 1)  
O ver all R ati o n ale f or t he A me n d me nt:  
T he rati o nale f or t his a m e n d me nt is t o i m ple me nt c ha n ges t o clarif y t he d os e -escalati o n sc he me.  
1.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 2:  Ke y St u d y Desi g n Ele me nts; Fi g ure 1:  
St u d y Desi g n Sc he m a);  Secti o n 2. 3. 3, Scie ntific R ati o n ale f or St u d y Desi g n;  
Secti o n  4. 1. 1, D ose Esc al ati o n a n d De -Esc al ati o n Al g orit h m ; Secti o n 4. 1.3 , 
E x p a nsi o n St a ges; Secti o n 6. 1, St u d y Tre at me nt A d mi nistere d  ( T a ble 1 2:  St u d y 
Tre at me nt I nf or m ati o n) ; Secti o n 6. 5. 2. 2, I nterc o h ort D ose I ncre ase Al g orit h m; 
Secti o n 6. 5. 4, Defi niti o n of t he Rec o m me n de d D ose f or E x p a nsi o n ; Secti o n 6. 6. 5, 
Criteri a a n d Pr oce d ures f or D ose I ncre ases of St u d y Dr u g; Secti o n 1 0. 1. 1, D ose 
Esc al ati o n; Secti o n 1 0. 4. 1, Pri m ar y A n al ysis:  S afet y  
Descri pti o n of c h a n ge:   D ata fr o m p artici pa nts i n  b ot h disease gr o u ps  will be e val uat e d 
t o get her i n t he d ose -escal ati o n sta ge of t he st u d y.   
R ati o n ale f or c h a n ge:   T o e na ble t he d os e -es cal ati o n c o h orts t o be c o m p ose d of 
partici pa nts fr o m b ot h disease gr o u p s.   
2.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 3:  Sc he d ule of Acti vities); Secti o n 8. 2 . 1, 
Effic ac y Assess m e nts  f or All Dise ase Gr o u ps; Secti o n 8. 3. 6, Ir o n O verl o a d 
Assess m e nt ; Secti o n 8. 6. 1, Bl o o d a n d B o ne M arr o w S a m ple C ollecti o n ( T a ble 1 9:  
Bi o m ar ker/ Tr a nsl ati o n al S a m ple Ti mi n g)  
Descri pti o n of c h a n ge:   A d de d fle xi bilit y t o perf or m t he b o ne marr o w bi o ps y a n d M RI 
assess me nt wit hi n 3 m o nt hs pri or t o scree ni n g.  
R ati o n ale f or c h a n ge:   T o a d d fle xi bilit y f or t he sites t o dra w s o me scree ni n g sa m ples.  
3.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 3:  Sc he d ule of Acti vities ; T a ble 4:  Sc he d ule of 
L a b or at or y Assess m e nts ); Secti o n 5. 2, E xcl usi o n Criteri a ( T a ble 11 :  E xcl usi o n ar y 
L a b or at or y V al ues) ; Secti o n 6. 6. 3, Criteri a a n d Pr oce d ures f or D ose I nterr u pti o ns 
a n d A dj ust me nts of St u d y Dr u g ( T a ble 1 4 :  G ui deli nes f or I nterr u pti o n a n d 
Rest arti n g of St u d y Dr u g); Secti o n  8. 3. 6, Ir o n O verl o a d Assess m e nt  
Descri pti o n of c h a n ge:   A d de d li ver M RI assess me nts f or partici pa nts wit h a scree ni n g 
ferriti n val ue of < 1 0 0 0 n g/ m L or ≥ 1 0 0 0 n g/ m L t o i de ntif y p ote ntial ir o n o verl oa d.  
Ta ble 1 1  a n d T a ble 1 4  w ere u p dat e d t o s pecif y t h e r ules f or p artici pa nt eli gi bilit y a n d t he 
r ules f or st u d y dr u g i nterr u pti o n/restarti n g base d o n t he partici pa nt's ser u m ferriti n le vels. 
R ati o n ale f or c h a n ge:   T o assess p ote ntial ir o n o verl oa d a n d t o cl arif y t he r ules f or st u d y 
dr u g i nterr u pti o n/restarti n g a n d f or partici pa nt eli gi bilit y.  
4.  Secti o n 2. 3. 4, J ustific ati o n f or St arti n g D ose ; Secti o n 2. 3. 5, U p d ate d D at a Fr o m 
O n g oi n g Cli nic al Tri als   
Descri pti o n of c h a n ge:   U p date d Secti o n 2. 3. 4 a n d a d de d Secti o n 2. 3. 5 t o reflect latest 
cli nical data o n I N C B 0 0 0 9 2 8 . 
R ati o n ale f or c h a n ge:   T o ali g n wit h latest cli nical data.  

I nc yte C orp orati o n  
Pa ge 1 1 3  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
5.  Secti o n 4. 1. 2,  E x pl or ati o n of Alter n ati ve A d mi nistr ati o n Sc he d ules; Secti o n 6. 1, 
St u d y Tre at me nt A d mi nist ere d ( T a ble 1 2:  St u d y Tre at me nt I nf or m ati o n); 
Secti o n  8. 5. 1, Bl o o d S a m ple C ollecti o n  
Descri pti o n of c h a n ge:   A d de d t he p ossi bilit y t o e x pl ore alter nati ve a d mi nistra ti o n 
sc he d ules a n d t o e x p a n d c o h orts.  
R ati o n ale f or c h a n ge:   Alter nati ve a d mi nistrati o n sc he d ules ma y be e x pl ore d i n or der t o 
o btai n s u p ple me ntal P K, p har mac o d y n a mic, a n d s afet y data, a n d c o h orts ca n be 
e x pa n de d as necessar y .  
6.  Secti o n 6. 6. 5, Criteri a a n d Pr oce d ures f or D os e I ncre ases of St u d y Dr u g  
Descri pti o n of c h a n ge:   Re vise d t o all o w d ose es calati o n after a partici pa nt has recei ve d 
o nl y 2 c ycles of st u d y dr u g treat me nt, i nstea d of 6  c ycles, a n d ad de d t hat d ose escal ati o n  
ca n occ ur if a p artici pa nt is still recei vi n g R B C tra nsf usi o ns or t here is a n H g b i ncreas e of 
<  1. 5  g/ d L i n a n y of t heir assess me nts.  
R ati o n ale f or c h a n ge:   T o clarif y t he r ules all o wi n g i ntra partici pa nt d ose escalati o n.  
7.  I nc or p or ati o n of a d mi nistr ati ve c h a n ges.  Ot her mi n or, a d mi nistrati ve c ha n ges ha ve 
bee n i nc or p orate d t hr o u g h o u t t he Pr ot oc ol a n d are n ote d i n t he re dli ne versi o n of t he 
a me n d me nt.  

I nc yte C orp orati o n  
Pa ge 1 1 4  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A me n d me nt 2  (0 8  A P R 2 0 2 1)  
O ver all R ati o n ale f or t he A me n d me nt:  
T he o verall rati o nale f or t his a me n d me nt is t o i m ple me nt c ha n ges a n d clarificati o ns t o t he 
pr ot oc ol.  
1.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 4:  Sc he d ule of L a b or at or y Assess me nts); 
Secti o n 3, O bjecti ves a n d E n d p oi nts ( T a ble 1 0 :  O bjecti ves a n d E n d p oi nts); 
Secti o n  8. 6. 1, Bl o o d S a m ple C ollecti o n  ( T a ble 2 0 :  Bi o m ar ker/ Tr a nsl ati o n al S a m ple 
Ti mi n g) ; Secti o n 8. 6. 2, P h ar m ac o d y n a mic a n d Tr a nsl ati o n al Rese arc h P ar a meter s; 
Secti o n 1 0. 2, P o p ul ati o ns f or A n al ysis ( T a ble 2 1:  P o p ul ati o ns f or A n al ysis); 
Secti o n  1 0. 4. 4, E x pl or at or y A n al yses  
Descri pti o n of c h a n ge:   
 
 
 
 
R ati o n ale f o r c h a n ge:   Clarificati o n  a n d i nc or p orati o n of cli nicall y rel e va nt P D 
bi o mar kers.  
2.  Secti o n 1, Pr ot oc ol S u m m ar y ( T a ble 4:  Sc he d ule of L a b or at or y Assess me nts); 
Secti o n 3, O bjecti ves a n d E n d p oi nts ( T a ble 1 0:  O bjecti ves a n d E n d p oi nts); 
Secti o n  8. 6. 1, Bl o o d S a m ple C ollecti o n ( T a ble 2 0:  Bi o m ar ker/ Tr a nsl ati o n al S a m ple 
Ti mi n g); Secti o n  8. 6. 2, P h ar m ac o d y n a mic a n d Tr a nsl ati o n al Rese arc h P ar a meters; 
Secti o n  1 0. 4. 4, E x pl or at or y A n al yses  
Descri pti o n of c h a n ge:   
 
 
R ati o n ale f or c h a n ge:   
 
 
3.  Secti o n 1, Pr ot oc ol S u m m ar y; Secti o n 8, St u d y Assess m e nts a n d Pr oce d ures; 
Secti o n  9. 3, Rec o r di n g a n d F oll o w -U p of A d verse E ve nts a n d/ or Seri o us A d verse 
E ve nts; Secti o n 9. 4, Re p orti n g of Seri o us A d verse E ve nts  
Descri pti o n of c h a n ge:   Refere n ces t o t he s t u d y r efere nce ma n ual a n d st u d y pr oce d ure 
ma n ual ha ve b ee n re place d wit h t he i n vesti gat or site file. 
R ati o n ale f or c h a n ge:   Clarificati o n.  
4.  Secti o n 2. 3. 4, J ustific ati o n f or St arti n g D ose  
Descri pti o n of c h a n ge:   S ecti o n u p date d  wit h  preli mi nar y res ults fr o m I N C B  0 0 9 2 8 -1 0 1 
a n d I N C B  0 0 9 2 8 -1 0 2 st u dies. 
R ati o n ale f or c h a n ge:   T o ali g n wit h latest data. 

I nc yte C orp orati o n  
Pa ge 1 1 5  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
5.  Secti o n 5. 1 , I ncl usi o n Criteri a ( Criterio n  5 ); Secti o n 5. 2, E xcl usi o n Criteri a 
( Criteri o n 1 5); Secti o n 9. 1, Defi niti o n of A d verse E ve nt; Secti o n 9. 2, Defi niti o n of 
Seri o us A d verse E ve nt; Secti o n 9. 3, Rec o r di n g a n d F oll o w -U p of A d verse E ve nts 
a n d/ or Seri o us A d verse E ve nts; Secti o n 9. 4, Re p orti n g of Seri o us A d verse E ve nts; 
A p pe n di x A, I nf or m ati o n Re g ar di n g Effecti ve ness of C o ntr ace pti v e Met h o ds a n d 
Defi niti o ns  
Descri pti o n of c h a n ge:   S ecti o ns ha ve bee n u p d at e d t o reflect t he c urre nt t e m plate.  
R ati o n ale f or c h a n ge:   Te m plate u p date d.  
6.  Secti o n 5. 2, E xcl usi o n Criteri a ( T a ble 1 2 :  E xcl usi o n ar y L a b or at or y V al ues) 
Descri pti o n of  c h a n ge:   Clarificati o n of t he eli gi bilit y t hres h ol ds f or bilir u bi n a n d direct 
bilir u bi n val ues  has bee n a d de d . 
R ati o n ale f or c h a n ge:   Clarificati o n.  
7.  Secti o n 6. 6. 3, Criteri a a n d Pr oce d ures f or D os e I nterr u pti o ns a n d A dj ust me nts of 
St u d y Dr u g ( T a ble 1 5 :  G ui deli nes f or I nterr u pti o n a n d Rest arti n g of St u d y Dr u g) 
Descri pti o n of c h a n ge:   I n c or p orate d g ui da nce f or st u d y tre at me nt i nterr u pti o n/ restart if 
a partici pa nt e nt ers t he st u d y wit h a hi g h ser u m ferriti n le vel.  
R ati o n ale f or c h a n ge:   Clarificati o n.  
8.  Secti o n  6. 7. 2, Restri cte d Me dic ati o ns a n d Pr oce d ures  
Descri pti o n of c h a n ge:   Restricti o ns re gar di n g C O VI D-1 9 v acci n ati o n d uri n g t he first 
st u d y treat me nt c ycle h a ve  bee n a d de d.  
R ati o n ale f or c h a n ge:   Clarificati o n.  
9.  Secti o n 8. 1. 1, I nf or me d C o nse nt Pr ocess  
Descri pti o n of c h a n ge:   T he se nte nce re g ar di n g t he o pti o nal e x pl orat or y researc h has 
bee n re m o v e d. 
R ati o n ale f or c h a n ge:   N o l o n ger a p plica bl e.  
1 0.  Secti o n 8. 4, L a b or at or y Assess m e nts ( T a ble 1 8 :  Re q uire d L a b or at or y A n al ytes)  
Descri pti o n of c h a n ge:   Re vise d t o  i n dicate b ot h bilir u bi n a n d direct bilir u bi n are part of 
t he bl o o d c he mistries  pa nel.  
R ati o n ale f or c h a n ge:   Clarificati o n of la b orat or y assess me nts.  
1 1.  Secti o n 8. 4, L a b or at or y Assess m e nts ( T a ble 1 8 :  Re q uire d L a b or at or y A n al ytes); 
Secti o n 8. 6. 2, P h ar m ac o d y n a mic a n d Tr a nsl ati o n al Rese arc h P ar a mete rs; 
Secti o n  1 0. 4. 2. 3, P h ar m ac o d y n a mics  
Descri pti o n of c h a n ge:   A d de d  retic ul oc yt e he m o gl o bi n c o nte nt (as part of t he 
he mat ol o gical pa nel) a n d clarifie d t hat t his a nal yte assess me nt is n ot re q uire d at sites 
w here t his para meter ca n n ot be meas ure d b y t h e l ocal la b orat or y.  I n a d diti o n, t he a nal yte 
 
. 
R ati o n ale f or c h a n ge:   Clarificati o n of la b orat or y assess me nts.  

I nc yte C orp orati o n  
Pa ge 1 1 6  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
1 2.  A p pe n di x D , C O VI D-1 9 P a n de mic Miti g at i o n Str ate gies a n d I nstr ucti o ns 
Descri pti o n of c h a n ge:   G ui da nce t o ma n a ge st u d y partici pa nts d uri n g t he C O VI D -1 9 
pa n de mic  has bee n a d d e d . 
R ati o n ale f or c h a n ge:   T o ali g n wit h re g ulat or y g ui da nce re gar di n g cli nical trial  
e xec uti o n d uri n g t he pa n de mic . 
1 3.  I nc or p or ati o n of a d mi nistr ati ve c h a n ges.  Ot her mi n or, a d mi nistrati ve c ha n ges ha ve 
bee n i nc or p orate d t hr o u g h o ut t he Pr ot oc ol a n d are n ote d i n t he re dli ne versi o n of t he 
a me n d me nt .  

I nc yte C orp orati o n  
Pa ge 1 1 7  of 1 1 7  
Pr ot oc ol I N C B  0 0 9 2 8 -1 0 5 A m 5  
Versi o n 6  
0 6  D E C 2 0 2 3  
V V -C LI N -0 1 0 4 6 6  
C O N FI D E N TI A L  
A me n d me nt 1 ( 1 7 N O V 2 0 2 0)  
O ver all R ati o n ale f or t he A me n d me nt:  
T he o verall rati o nale f or t his a me n d me nt is t o i m ple me nt c ha n ges b ase d o n Fre n c h A N S M 
c o m me nts a n d re q u ests.  
1.  Secti o n 4. 3, St u d y T er mi n ati o n 
Descri pti o n of c h a n ge:   E nr ol lme nt h ol d a n d st o p pi n g r ules  were a d de d t h at f urt her 
e nr oll me nt of partici pa nts will be s us pe n de d if 1) m ore t ha n 1  partici p a nt i n t he first 
5  partici pa nts e nr olle d i n  a s pecific dise ase gr o u p ha ve a n A E ≥ Gra d e 3 t hat is 
attri b uta ble t o t he i n vesti gati o nal a ge nt, or 2) at least 4 0 % of 5 or m or e partici pa nts 
e nrolle d i n a s pecific dise ase gr o u p ha v e a n A E ≥ Gra de 3 t hat is attri b uta bl e t o t he 
i n vesti gati o nal a ge nt. 
R ati o n ale f or c h a n ge:   D osi n g st o p pi n g r ules at a p o p ulati o n le vel i n d ose e x pa nsi o n 
c o h orts were a d de d  t o t he P r ot oc ol. 

Si g nat ure Pa ge f or V V- C LI N- 0 1 0 4 6 6 v 6. 0
Si g nat ure Pa ge f or V V- C LI N- 0 1 0 4 6 6 v 6. 0
A p pr o val Tas k
A p pr o ver
, Bi ostatistics
0 6- Dec- 2 0 2 3 1 5: 1 9: 5 2 G M T + 0 0 0 0
A p pr o val Tas k
A p pr o ver
of Earl y De vel o p me nt
0 6- Dec- 2 0 2 3 1 5: 3 1: 2 5 G M T + 0 0 0 0
A p pr o val Tas k
D oc u me nt Pre parer
 Cli nical Researc h Scie ntist
0 6- Dec- 2 0 2 3 1 5: 4 8: 1 1 G M T + 0 0 0 0
A p pr o val Tas k
A p pr o ver
 Earl y Cli nical De vel o p me nt
0 6- Dec- 2 0 2 3 1 7: 5 9: 0 0 G M T + 0 0 0 0
A p pr o val Tas k
A p pr o ver
P S R, 
 Cli nical Trial Hea d
0 7- Dec- 2 0 2 3 1 5: 0 9: 1 2 G M T + 0 0 0 0