Clinical trial NCT04827576
Conditions: Solid Tumor
Sponsor: Gilead Sciences
Start date: 2021-10-01; Completion date: 2024-10-01
Enrollment: 106 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of magrolimab in combination with docetaxel in participants with solid tumors.

Detailed description:
This study will consist of a Safety Run-in Cohort 1 (magrolimab + docetaxel combination). After completion of the Safety Run-in Cohort 1, Phase 2 Cohort 1 will occur as follows:

* Phase 2 Cohort 1: a cohort of participants with solid tumors (metastatic non-small cell lung cancer (mNSCLC) (Phase 2 Cohort 1a), metastatic urothelial cancer (mUC) (Phase 2 Cohort 1b), and metastatic small cell lung cancer (mSCLC) (Phase 2 Cohort 1c).

Arms: arm 1: Participants with solid tumors (including metastatic non small cell lung cancer (mNSCLC), metastatic urothelial cancer (mUC), and metastatic small cell lung cancer (mSCLC)) will receive 1 mg/kg magrolimab intravenously (IV) on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 113 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 113 weeks; each cycle length = 21 days. arm 2: Participants with mNSCLC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 90 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 69 weeks; each cycle length = 21 days. arm 3: Participants with mUC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 68 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 68 weeks; each cycle length = 21 days. arm 4: Participants with mSCLC will receive 1 mg/kg magrolimab IV on Day 1, 30 mg/kg IV on Days 8 and 15 of cycle 1; 30 mg/kg IV on Days 1, 8 and 15 of Cycle 2; 60 mg/kg IV on Day 1 of Cycle 3 and onwards for up to 72 weeks; and 75 mg/m\^2 docetaxel IV on Day 1 of each cycle for up to 72 weeks; each cycle length = 21 days.
Interventions: intervention 1: Magrolimab intervention 2: Docetaxel
Intervention descriptions: intervention 1: Administered intravenously intervention 2: Administered intravenously

Protocol documents:
Prot_000.pdf: 
C LI NI C A L S T U D Y P R O T O C O L
St u d y Title:
A P hase 2, M ulti- Ar m St u d y of Ma gr oli ma b i n Patie nts Wit h S oli d 
T u m ors
Pl ai n L a n g u a ge S h ort 
Title:
St u d y of Ma gr oli ma b i n Patie nts Wit h S oli d T u m ors
S p o ns or:
Gilea d Scie nces, I nc.
3 3 3 La kesi de Dri ve
F oster Cit y, C A 9 4 4 0 4
I N D N u m ber:
E u dr a C T N u m ber:
Cli nic al Tri als. g o v 
I de ntifier:
1 1 7 6 8 7
2 0 2 0- 0 0 5 2 6 5- 1 4
N C T 0 4 8 2 7 5 7 6
I n dic ati o n:
S oli d T u m ors
Pr ot oc ol I D:
G S- U S- 5 4 8- 5 9 1 8
C o nt act I nf or m ati o n: 
T he me dical m o nit or na me a n d c o ntact i nf or mati o n will be 
pr o vi de d o n t he Ke y St u d y Tea m C o ntact List.
Pr ot oc ol Versi o n/ D ate 
A me n d me nt 5:
2 4 Oct o ber 2 0 2 3
A me n d me nt Hist or y: 
Ori gi nal:
1 5 Dece m ber 2 0 2 0
A me n d me nt 1:
0 3 Marc h 2 0 2 1
A me n d me nt 2:
1 5 Marc h 2 0 2 1
A me n d me nt 3:
1 4 Dece m ber 2 0 2 1
A me n d me nt 4:
2 7 Ja n uar y 2 0 2 2
Hi g h-le vel s u m mar y of t he hist or y of a me n d me nts is pr o vi de d i n 
A p pe n di x 1 0 .
C o u ntr y-s pecific 
Re q uire me nts:
C o u ntr y-s pecific re q uire me nts, as a p plica ble, are liste d i n 
A p pe n di x 9 .
T his st u d y will be c o n d ucte d u n der U nite d States F o o d a n d Dr u g A d mi nistrati o n i n vesti gati o nal 
ne w dr u g (I N D) re g ulati o ns ( 2 1 C o de of Fe deral Re g ulati o ns Part 3 1 2); h o we ver, sites l ocate d i n 
t he E ur o pea n Ec o n o mic Area, U nite d Ki n g d o m, a n d S witzerla n d are n ot i ncl u de d u n der t he I N D 
a n d are n ot c o nsi dere d t o be I N D sites.
T his st u d y will be c o n d ucte d i n c o m plia nce wit h t his pr ot oc ol a n d i n acc or da nce wit h t he et hical 
pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n of Helsi n ki, a n d t hat are c o nsiste nt wit h 
I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) G o o d Cli nical Practice ( G C P) a n d a p plica ble 
re g ulat or y re q uire me nts.
GI L E A U 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2
2 4 Oct o ber 2 0 2 3
C O N FI D E N TI A LI T Y S T A T E M E N T
T he i nf or mati o n c o ntai ne d i n t his d oc u me nt, partic ularl y u n p u blis he d data, is t he pr o pert y or 
u n der c o ntr ol of Gilea d Scie nces, I nc., a n d is pr o vi de d t o y o u i n c o nfi de nce as a n i n vesti gat or, 
p ote ntial i n vesti gat or, or c o ns ulta nt, f or re vie w b y y o u, y o ur staff, a n d a n a p plica ble 
i nstit uti o nal re vie w b oar d or i n de pe n de nt et hics c o m mittee. T he i nf or mati o n is o nl y t o be use d 
b y y o u i n c o n necti o n wit h a ut h orize d cli nical st u dies of t he i n vesti gati o nal dr u g descri be d i n 
t he pr ot oc ol. Y o u will n ot discl ose a n y of t he i nf or mati o n t o ot hers wit h o ut writte n 
a ut h orizati o n fr o m Gilea d Scie nces, I nc., e xce pt t o t he e xte nt necessar y t o o btai n i nf or me d 
c o nse nt fr o m t h ose pers o ns t o w h o m t he dr u g ma y be a d mi nistere d.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3
2 4 Oct o ber 2 0 2 3
T A B L E O F C O N T E N T S
T A B L E O F C O N T E N T S................................................................................................................................................ 3
LI S T O F I N- T E X T T A B L E S......................................................................................................................................... 6
LI S T O F I N- T E X T FI G U R E S........................................................................................................................................ 6
P R O T O C O L S Y N O P SI S................................................................................................................................................ 7
G L O S S A R Y O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S .................................................................... 1 7
1.  
I N T R O D U C TI O N................................................................................................................................................ 2 0
1. 1.  
Bac k gr o u n d.............................................................................................................................................. 2 0
1. 1. 1.  
Bac k gr o u n d o n Rela pse d/ Refract or y S oli d T u m ors I ncl u di n g Metastatic 
N o n- S mall Cell L u n g Ca ncer, Metastatic Ur ot helial Ca ncer, a n d 
Metastatic S mall Cell L u n g Ca ncer....................................................................................... 2 0
1. 2.   
Ma gr oli ma b ............................................................................................................................................. 2 2
1. 2. 1.   
Ge neral I nf or mati o n .............................................................................................................. 2 2
1. 2. 2.   
N o ncli nical P har mac ol o g y a n d T o xic ol o g y.......................................................................... 2 3
1. 2. 3.  
Cli nical Bac k gr o u n d f or Ma gr oli ma b ................................................................................... 2 5
1. 3.  
I nf or mati o n A b o ut D oceta xel.................................................................................................................. 2 8
1. 3. 1.   
Descri pti o n of D oceta xel....................................................................................................... 2 8
1. 3. 2.  
Cli nical Data f or D oceta xel................................................................................................... 2 8
1. 4.  
I nf or mati o n A b o ut A u xiliar y Me dici nal Pr o d ucts .................................................................................. 2 9
1. 5.  
Rati o nale f or T his St u d y.......................................................................................................................... 2 9
1. 5. 1.  
Safet y R u n-i n C o h ort 1 a n d P hase 2 C o h ort 1 ...................................................................... 3 0
1. 6.  
Rati o nale f or D ose Selecti o n of Ma gr oli ma b.......................................................................................... 3 0
1. 6. 1.  
Safet y R u n-i n C o h ort 1 a n d P hase 2 C o h ort 1 ...................................................................... 3 1
1. 7.  
Ris k/ Be nefit Assess me nt f or t he St u d y................................................................................................... 3 1
1. 8.  
C o m plia nce.............................................................................................................................................. 3 2
2.   
O BJ E C TI V E S A N D E N D P OI N T S...................................................................................................................... 3 3
3.  
S T U D Y D E SI G N................................................................................................................................................. 3 4
3. 1.  
St u d y Desi g n ........................................................................................................................................... 3 4
3. 1. 1.  
Safet y R u n-i n C o h ort 1.......................................................................................................... 3 5
3. 1. 2.  
P hase 2 C o h ort 1.................................................................................................................... 3 7
3. 2.  
St u d y Treat me nts..................................................................................................................................... 3 7
3. 2. 1.  
Safet y R u n-i n C o h ort 1 a n d P hase 2 C o h ort 1 ...................................................................... 3 7
3. 3.   
D urati o n of Treat me nt............................................................................................................................. 3 9
3. 4.   
Disc o nti n uati o n Criteria .......................................................................................................................... 3 9
3. 5.   
Disc o nti n uati o n Fr o m St u d y Criteria/ E n d of St u d y................................................................................ 4 0
3. 6.  
P ostst u d y Care......................................................................................................................................... 4 0
3. 7.  
S o urce Data ............................................................................................................................................. 4 0
3. 8.  
Bi o mar ker Sa m ples t o A d dress t he St u d y O bjecti ves............................................................................. 4 0
3. 8. 1.  
P har mac o ki netics/ Bi o mar ker Sa m ples f or   
 
.................................. 4 2
4.  
P A TI E N T P O P U L A TI O N................................................................................................................................... 4 3
4. 1.   
N u m ber of Patie nts a n d Patie nt Selecti o n............................................................................................... 4 3
4. 1. 1.  
Patie nt Re place me nt.............................................................................................................. 4 3
4. 2.  
I ncl usi o n Criteria..................................................................................................................................... 4 3
4. 3.  
E xcl usi o n Criteria.................................................................................................................................... 4 5
5.  
I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T S............................................................................................. 4 7
5. 1.  
Ra n d o mizati o n, Bli n di n g, a n d Treat me nt C o des Access........................................................................ 4 7
5. 1. 1.  
Ra n d o mizati o n....................................................................................................................... 4 7
C CI 
C CI-


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4
2 4 Oct o ber 2 0 2 3
5. 1. 2.  
Bli n di n g................................................................................................................................. 4 7
5. 2.   
Descri pti o n a n d Ha n dli n g of Ma gr oli ma b............................................................................................... 4 7
5. 2. 1.  
F or m ulati o n ........................................................................................................................... 4 7
5. 2. 2.  
Pac ka gi n g a n d La beli n g ........................................................................................................ 4 7
5. 2. 3.  
St ora ge a n d Ha n dli n g............................................................................................................ 4 7
5. 3.   
Descri pti o n a n d Ha n dli n g of D oceta xel.................................................................................................. 4 8
5. 3. 1.  
F or m ulati o n ........................................................................................................................... 4 8
5. 3. 2.  
Pac ka gi n g a n d La beli n g ........................................................................................................ 4 8
5. 3. 3.  
St ora ge a n d Ha n dli n g............................................................................................................ 4 8
5. 4.   
D osa ge a n d A d mi nistrati o n of Ma gr oli ma b............................................................................................ 4 8
5. 5.   
D ose M o dificati o ns a n d Dela ys f or Ma gr oli ma b.................................................................................... 4 9
5. 6.   
Ma gr oli ma b Pre me dicati o n a n d Pr o p h yla xis .......................................................................................... 5 1
5. 7.  
Pri or a n d C o nc o mita nt Me dicati o ns........................................................................................................ 5 1
5. 7. 1.  
Pri or a n d C o nc o mita nt Me dicati o ns Wit h Ma gr oli ma b........................................................ 5 1
5. 7. 2.  
Pri or a n d C o nc o mita nt Me dicati o ns Wit h D oceta xel............................................................ 5 2
5. 8.   
D osa ge a n d A d mi nistrati o n of D oceta xel................................................................................................ 5 2
5. 9.   
D oceta xel Pre me dicati o n a n d Pr o p h yla xis.............................................................................................. 5 2
5. 1 0.   
D ose M o dificati o ns f or D oceta xel........................................................................................................... 5 2
5. 1 0. 1.   
Ne utr o pe nia ........................................................................................................................... 5 2
5. 1 0. 2.   
He patic T o xicit y.................................................................................................................... 5 3
5. 1 0. 3.  
Peri p heral Ne ur o pat h y........................................................................................................... 5 4
5. 1 0. 4.   
Ot her T o xicities..................................................................................................................... 5 4
5. 1 1.   
Acc o u nta bilit y f or I n vesti gati o nal Me dici nal Pr o d uct............................................................................ 5 5
5. 1 1. 1.  
I n vesti gati o nal Me dici nal Pr o d uct Ret ur n or Dis p osal ......................................................... 5 5
6.  
S T U D Y P R O C E D U R E S...................................................................................................................................... 5 6
6. 1.  
Patie nt E nr oll me nt a n d Treat me nt Assi g n me nt....................................................................................... 5 6
6. 2.  
Pretreat me nt Assess me nts....................................................................................................................... 5 6
6. 2. 1.  
Scree ni n g Visit ...................................................................................................................... 5 6
6. 3.  
Ra n d o mizati o n......................................................................................................................................... 5 7
6. 4.  
Treat me nt Assess me nts........................................................................................................................... 5 7
6. 4. 1.  
Pre g na nc y Test ...................................................................................................................... 5 7
6. 4. 2.  
T y pe a n d Scree n a n d Direct A nti gl o b uli n Test..................................................................... 5 7
6. 4. 3.   
Vital Si g ns............................................................................................................................. 5 7
6. 4. 4.  
P h ysical E xa mi nati o n............................................................................................................ 5 8
6. 4. 5.  
Perf or ma nce Stat us................................................................................................................ 5 8
6. 4. 6.  
Electr ocar di o gra ms................................................................................................................ 5 8
6. 4. 7.   
A d verse E ve nts...................................................................................................................... 5 8
6. 4. 8.  
C o nc o mita nt Me dicati o ns...................................................................................................... 5 8
6. 5.  
Safet y Assess me nts ................................................................................................................................. 5 8
6. 6.  
Efficac y Assess me nts.............................................................................................................................. 6 0
6. 7.  
P har mac o ki netic Assess me nts................................................................................................................. 6 1
6. 8.  
I m m u n o ge nicit y ( A nti dr u g A nti b o dies).................................................................................................. 6 1
6. 9.  
Bi o mar ker Assess me nts........................................................................................................................... 6 1
6. 1 0.  
P osttreat me nt Assess me nts...................................................................................................................... 6 2
6. 1 1.   
Assess me nts f or Earl y Disc o nti n uati o n Fr o m St u d y............................................................................... 6 2
6. 1 1. 1.  
Criteria f or Disc o nti n uati o n of St u d y Treat me nt................................................................... 6 3
6. 1 2.  
Criteria f or Disc o nti n uati o n Fr o m St u d y/ E n d of St u d y .......................................................................... 6 3
6. 1 3.  
P ostst u d y Care......................................................................................................................................... 6 3
6. 1 4.  
Sa m ple St ora ge........................................................................................................................................ 6 3
7.   
A D V E R S E E V E N T S A N D T O XI CI T Y M A N A G E M E N T................................................................................ 6 4
7. 1.   
Defi niti o ns of A d verse E ve nts a n d Seri o us A d verse E ve nts................................................................... 6 4
7. 1. 1.   
A d verse E ve nts...................................................................................................................... 6 4
7. 1. 2.  
Seri o us A d verse E ve nts......................................................................................................... 6 4


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5
2 4 Oct o ber 2 0 2 3
7. 1. 3.  
St u d y Dr u gs a n d Gilea d C o nc o mita nt T hera p y S pecial Sit uati o ns Re p orts ......................... 6 5
7. 2.   
Assess me nt of A d verse E ve nts a n d Seri o us A d verse E ve nts.................................................................. 6 6
7. 2. 1.   
Assess me nt of Ca usalit y f or St u d y Dr u gs, A ut h orize d A x M Ps, a n d 
Pr oce d ures............................................................................................................................. 6 6
7. 2. 2.   
Assess me nt of Se verit y.......................................................................................................... 6 7
7. 3.  
I n vesti gat or Re p orti n g Re q uire me nts a n d I nstr ucti o ns........................................................................... 6 7
7. 3. 1.  
Re q uire me nts f or C ollecti o n Pri or t o St u d y Dr u g I nitiati o n................................................. 6 7
7. 3. 2.   
A d verse E ve nts...................................................................................................................... 6 7
7. 3. 3.  
Seri o us A d verse E ve nts......................................................................................................... 6 7
7. 3. 4.  
St u d y Dr u g S pecial Sit uati o ns Re p orts ................................................................................. 6 8
7. 3. 5.  
C o nc o mita nt T hera p y Re p orts............................................................................................... 6 8
7. 4.  
Re p orti n g Pr ocess f or Seri o us A d verse E ve nts a n d S pecial Sit uati o n Re p orts....................................... 6 8
7. 4. 1.  
Seri o us A d verse E ve nt Re p orti n g Pr ocess............................................................................ 6 8
7. 4. 2.  
S pecial Sit uati o ns Re p orti n g Pr ocess.................................................................................... 6 9
7. 5.   
Gilea d Re p orti n g Re q uire me nts.............................................................................................................. 7 1
7. 6.  
Cli nical La b orat or y A b n or malities a n d Ot her A b n or mal Assess me nts as A d verse E ve nts or 
Seri o us A d verse E ve nts........................................................................................................................... 7 1
7. 7.   
A b n or mal Li ver F u ncti o n Tests............................................................................................................... 7 2
7. 8.  
T o xicit y Ma na ge me nt.............................................................................................................................. 7 2
7. 8. 1.   
Ma gr oli ma b ........................................................................................................................... 7 2
7. 8. 2.   
D oceta xel............................................................................................................................... 7 7
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S................................................................................................................. 7 8
8. 1.   
A nal ysis O bjecti ves a n d E n d p oi nts......................................................................................................... 7 8
8. 2.  
Pla n ne d A nal yses..................................................................................................................................... 7 8
8. 2. 1.   
D ose Deter mi nati o n A nal ysis................................................................................................ 7 8
8. 2. 2.  
Pri mar y A nal ysis................................................................................................................... 7 8
8. 2. 3.  
Fi nal A nal ysis........................................................................................................................ 7 8
8. 3.   
A nal ysis C o n ve nti o ns.............................................................................................................................. 7 8
8. 3. 1.   
A nal ysis Sets ......................................................................................................................... 7 8
8. 3. 2.   
Data Ha n dli n g C o n ve nti o ns .................................................................................................. 7 9
8. 4.   
De m o gra p hic a n d Baseli ne C haracteristics A nal ysis.............................................................................. 8 0
8. 5.  
Efficac y A nal ysis..................................................................................................................................... 8 0
8. 5. 1.  
Pri mar y Efficac y E n d p oi nt A nal ysis..................................................................................... 8 0
8. 5. 2.  
Sec o n dar y Efficac y E n d p oi nt A nal yses ................................................................................ 8 0
8. 6.  
Safet y A nal ysis........................................................................................................................................ 8 0
8. 6. 1.  
Pri mar y Safet y E n d p oi nt A nal ysis ........................................................................................ 8 0
8. 6. 2.   
Ot her Safet y A nal ysis............................................................................................................ 8 0
8. 6. 3.  
E xte nt of E x p os ure................................................................................................................ 8 0
8. 6. 4.   
A d verse E ve nts...................................................................................................................... 8 1
8. 6. 5.  
La b orat or y E val uati o ns ......................................................................................................... 8 1
8. 6. 6.   
Ot her Safet y E val uati o ns....................................................................................................... 8 1
8. 7.  
P har mac o ki netic A nal ysis....................................................................................................................... 8 1
8. 8.  
I m m u n o ge nicit y A nal ysis........................................................................................................................ 8 2
8. 9.  
Bi o mar ker A nal ysis................................................................................................................................. 8 2
8. 1 0.  
Sa m ple Size............................................................................................................................................. 8 2
9.  
R E S P O N SI BI LI TI E S........................................................................................................................................... 8 3
9. 1.  
I n vesti gat or Res p o nsi bilities ................................................................................................................... 8 3
9. 1. 1.   
G o o d Cli nical Practice........................................................................................................... 8 3
9. 1. 2.  
Fi na ncial Discl os ure.............................................................................................................. 8 3
9. 1. 3.  
I nstit uti o nal Re vie w B oar d/I n de pe n de nt Et hics C o m mittee Re vie w a n d 
A p pr o val................................................................................................................................ 8 3
9. 1. 4.  
I nf or me d C o nse nt.................................................................................................................. 8 3
9. 1. 5.  
C o nfi de ntialit y....................................................................................................................... 8 4


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6
2 4 Oct o ber 2 0 2 3
9. 1. 6.  
St u d y Files a n d Rete nti o n of Rec or ds................................................................................... 8 4
9. 1. 7.  
Case Re p ort F or ms................................................................................................................ 8 5
9. 1. 8.  
I n vesti gat or I ns pecti o ns......................................................................................................... 8 6
9. 1. 9.  
Pr ot oc ol C o m plia nce............................................................................................................. 8 6
9. 2.  
S p o ns or Res p o nsi bilities ......................................................................................................................... 8 6
9. 2. 1.  
Pr ot oc ol M o dificati o ns.......................................................................................................... 8 6
9. 2. 2.  
St u d y Re p ort a n d P u blicati o ns .............................................................................................. 8 6
9. 3.  
J oi nt I n vesti gat or/ S p o ns or Res p o nsi bilities ............................................................................................ 8 7
9. 3. 1.  
Pa y me nt Re p orti n g................................................................................................................ 8 7
9. 3. 2.   
Access t o I nf or mati o n f or M o nit ori n g................................................................................... 8 7
9. 3. 3.   
Access t o I nf or mati o n f or A u diti n g or I ns pecti o ns............................................................... 8 7
9. 3. 4.  
St u d y Disc o nti n uati o n........................................................................................................... 8 7
1 0. 
R E F E R E N C E S..................................................................................................................................................... 8 8
1 1. 
A P P E N DI C E S...................................................................................................................................................... 9 2
A p pe n di x 1.  
I n vesti gat or Si g nat ure Pa ge..................................................................................................... 9 3
A p pe n di x 2.   
Mar keti n g A ut h orizati o n Stat us of St u d y I nter ve nti o ns.......................................................... 9 4
A p pe n di x 3.  
Sc he d ules of Assess me nt......................................................................................................... 9 5
A p pe n di x 4.  
Pa n de mic Ris k Assess me nt a n d Miti gati o n Pla n .................................................................. 1 0 2
A p pe n di x 5.  
T o xicit y Gra di n g Scale f or Se verit y of A d verse E ve nts a n d La b orat or y 
A b n or malities ........................................................................................................................ 1 0 6
A p pe n di x 6.  
Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P ote ntial, a n d 
C o ntrace pti ve Re q uire me nts.................................................................................................. 1 0 7
A p pe n di x 7.  
Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) Perf or ma nce Stat us.................................... 1 1 0
A p pe n di x 8.  
Res p o nse E val uati o n Criteria i n S oli d T u m ors ( R E CI S T, Versi o n 1. 1)............................... 1 1 1
A p pe n di x 9.  
C o u ntr y- S pecific Re q uire me nts ............................................................................................ 1 1 2
A p pe n di x 1 0.   
A me n d me nt Hist or y .............................................................................................................. 1 1 3
LI S T O F I N- T E X T T A B L E S
Ta ble 1.   
G S- U S- 5 4 8- 5 9 1 8: St u d y O bjecti ves a n d E n d p oi nts ............................................................... 3 3
Ta ble 2.  
Safet y R u n-i n C o h ort 1: D ose Le vel, Sc he d ule, a n d De-escalati o n........................................ 3 8
Ta ble 3.  
P hase 2 C o h ort 1: D ose Le vel a n d Sc he d ule........................................................................... 3 8
Ta ble 4.  
Re pri mi n g G ui deli nes f or Ma gr oli ma b ................................................................................... 5 0
Ta ble 5.   
Ma gr oli ma b D osi n g G ui da nce f or Pla n ne d S ur gical Pr oce d ures o n St u d y............................. 5 1
Ta ble 6.   
D oceta xel D ose M o dificati o ns f or Ne utr o pe nia...................................................................... 5 3
Ta ble 7.   
D oceta xel D ose Re d ucti o ns f or He patic T o xicit y................................................................... 5 4
Ta ble 8.   
D oceta xel D ose M o dificati o ns f or Ot her Gra de 3/ 4 T o xicities............................................... 5 5
Ta ble 9.  
Scree ni n g La b orat or y A nal ytes............................................................................................... 5 9
Ta ble 1 0.  
St u d y La b orat or y A nal ytes...................................................................................................... 6 0
Ta ble 1 1.   
Ma na ge me nt of I nf usi o n-relate d Reacti o ns............................................................................. 7 4
Ta ble 1 2.  
P ne u m o nitis Ma na ge me nt Al g orit h m...................................................................................... 7 6
Ta ble 1 3.  
Sa m ple Size Calc ulati o ns ........................................................................................................ 8 2
LI S T O F I N- T E X T FI G U R E S
Fi g ure 1.  
Effect of Ma gr oli ma b o n A ne mia a n d Miti gati o n wit h a Pri mi n g/ Mai nte na nce 
D osi n g Re gi me n...................................................................................................................... 2 7
Fi g ure 2.  
St u d y Sc he ma.......................................................................................................................... 3 4


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7
2 4 Oct o ber 2 0 2 3
P R O T O C O L S Y N O P SI S
Gile a d Scie nces, I nc.
3 3 3 L a kesi de Dri ve
F oster Cit y, C A 9 4 4 0 4
St u d y Title:  
A P hase 2, M ulti- Ar m St u d y of Ma gr oli ma b i n Patie nts wit h S oli d T u m ors
Pl ai n L a n g u a ge 
S h ort Title:
St u d y of Ma gr oli ma b i n Patie nts Wit h S oli d T u m ors
I N D N u m ber:
E u dr a C T 
N u m ber:
Cli nic al 
Tri als. g o v 
I de ntifier:
1 1 7 6 8 7
2 0 2 0- 0 0 5 2 6 5- 1 4
N C T 0 4 8 2 7 5 7 6
St u d y Ce nters 
Pl a n ne d:
A p pr o xi matel y 5 0 ce nters gl o ball y
O bjecti ves a n d 
E n d p oi nts:
Pri m ar y O bjecti ves
Pri m ar y E n d p oi nts
• 
T o e val uate t he safet y, t olera bilit y, 
a n d rec o m me n de d P hase 2 d ose of 
ma gr oli ma b + d oceta xel 
c o m bi nati o n t hera p y i n s oli d 
t u m ors ( Safet y R u n-i n C o h ort 1, 
P hase 2 C o h orts 1a, 1 b, a n d 1c)
• 
T o e val uate t he efficac y of 
ma gr oli ma b + d oceta xel 
c o m bi nati o n t hera p y i n s oli d 
t u m ors as deter mi ne d b y 
i n vesti gat or-assesse d o bjecti ve 
res p o nse rate ( O R R) ( P hase 2 
C o h orts 1a, 1 b, a n d 1c)
• 
I nci de nce of a d verse e ve nts ( A Es) a n d 
la b orat or y a b n or malities acc or di n g t o t he 
Nati o nal Ca ncer I nstit ute ( N CI) C o m m o n 
Ter mi n ol o g y Criteria f or A d verse E ve nts 
( C T C A E), Versi o n 5. 0 (A p pe n di x 5 ; 
Safet y R u n-i n C o h ort 1, P hase 2 
C o h orts 1a, 1 b, a n d 1c)
• 
O R R, defi ne d as t he pr o p orti o n of patie nts 
w h o ac hie ve a c o m plete res p o nse or 
partial res p o nse, as meas ure d b y Res p o nse 
E val uati o n Criteria i n S oli d T u m ors 
( R E CI S T), Versi o n 1. 1, as deter mi ne d b y 
i n vesti gat or assess me nt ( P hase 2 
C o h orts 1a, 1 b, a n d 1c)
Sec o n d ar y O bjecti ve s
Sec o n d ar y E n d p oi nts
• 
T o e val uate pr o gressi o n-free 
s ur vi val ( P F S) b y i n vesti gat or 
assess me nt ( P hase 2 C o h orts 1a, 
1 b, a n d 1c)
• 
T o e val uate a d diti o nal meas ures of 
efficac y of ma gr oli ma b + 
d oceta xel c o m bi nati o n t hera p y, 
i ncl u di n g d urati o n of res p o nse 
( D O R) a n d o verall s ur vi val ( O S) 
( P hase 2 C o h orts 1a, 1 b, a n d 1c)
• 
P F S fr o m date of d ose i nitiati o n as 
deter m i ne d b y i n vesti gat or assess me nt 
per R E CI S T, Versi o n 1. 1 ( P hase 2 
C o h orts 1a, 1 b, a n d 1c)
• 
D O R, defi ne d as ti me fr o m first 
d oc u me ntati o n of c o m plete res p o nse or 
partial res p o nse t o t he earliest date of 
d oc u me nte d disease pr o gressi o n, per 
R E CI S T, Versi o n 1. 1, or deat h fr o m a n y 
ca use, w hic he ver occ urs first, as 


M a gr oli m a b 
Gil e a d  S ci e n c e s , I n c. 
St u d y D e si g n: 
C O N FI D E N TI A L 
• 
T o  e v al u at e  th e  p h a 1 m a c o ki n eti cs 
( P K) a n d  illllll u n o g e ni cit y of 
m a gr oli m a b  w h e n  gi v e n  wit h 
d o c et a x el  as  a  c o m bi n ati o n  t h er a p y 
( S af et y R u n -i n C o h ort  1,  P h a s e  2 
C o h orts l a, l b, a n d l e) 
• 
• 
Pr o to c ol  G S -U S - 5 4 8- 5 9 1 8 
A m e n d m e nt s 
d et e 1 mi n e d  b y  i n v esti g ator  ass ess m e nt 
( P h as e 2 C o h o 1is l a, l b, a n d l e) 
O S , d efi n e d  a s d a t e of d o s e  i niti ati o n 
( P h as e 2  C o h o 1is l a, l b, a n d l e) t o d e a t h 
fr o m a n y  c a us e . 
M a gr oli m a b  c o n c e ntr ati o n v ers us  ti m e 
a n d a nti dt u g  a nti b o di es  t o m a gr oli m a b 
(S af et y  R u n -i n C o h o 1t  1;  P h a s e  2 
C o h o 1ts l a, l b, a n d l e) 
T hi s  P h a s e  2,  o p e n -l a b el, m ulti c e nt er , m ulti- a n n  st u d y i s e v al u ati n g 
m a gr oli m a b  +  d o c et a x el  c o m bi n ati o n  t h er a p y f or p ati e nts  wit h  s o li d t u m ors. 
T hi s  stu d y  will  c o nsi st of t h e f oll o wi n g S af et y  R u n-i n  C o h o 1t: 
•  S af et y  R u n-i n  C o h o rt 1: m a gr oli m a b  +  d o c et a x el  c o m b i nati o n  i n 
p ati e nts  wit h  s oli d t u m or s ( m et ast ati c n o n- sm all  c e ll l u n g c a n c e r 
[ m N S C L C] , m et ast ati c  ur ot h eli al  c a n c e r  [ m U C] , a n d m et ast ati c  sm all 
c e ll l u n g c a n c e r  [ m S C L C]) 
Aft e r c o m pl eti o n of S af et y  R u n-i n  C o h o rt 1,  P h as e  2  C o h o 1i  1  w ill o c c ur  as 
f oll o ws: 
•  P h a s e  2  C o h o rt 1: a  c o h o 1i of p ati e nts  wit h  s o li d t u m ors  (m N S C L C 
[P h as e  2  C o h o 1i  l a] , m U C  [ P h as e 2  C o h o 1i  l b], a n d m S C L C  [ P h as e 2 
C o h o 1i  l e]) 
T h e  st u d y s c h e m ati c i s pr o v i de d b el o w. 
S af et y R u n- i n C o h ort 1 
m N S C L C, m u c ,    mS C L C 
M a gr o lim a b + 
D o c et a x e l 
N  =  1 8 
S af et y E v al u ati o n a n d R P 2 D 
P h a s e 2 C o h ort  1 
( M a gr olim a b + D o c et a x e l ) 
P h a s e  2 C o h ort l a 
( m N S C LC) 
N  = 3 0 
P h a s e  2  C o h ort l b 
( m U C) 
N  =  2 6 
P h a s e  2 C o h ort l e 
( m S C L C) 
N  = 4 0 
m N S C L C = m et ast ati c  n o n- s m all  c ell  l u n g c a n c er ; m S C L C = m et ast ati c  s m a ll c ell  l u n g c a n c er ; 
m U C = m et a s t ati c ur ot h eli al  c a n c er ; R P 2 D = r e c o m m e n d e d P h a s e  2  d o s e 
P a g e 8 
2 4  O c to b er  2 0 2 3 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9
2 4 Oct o ber 2 0 2 3
S afet y R u n-i n C o h ort 1 : 
A d ose ‑li miti n g t o xicit y ( D L T) e val uati o n peri o d of 1 c ycle ( 2 1 da ys) will 
occ ur. After 6 patie nts ha ve c o m plete d t he D L T e val uati o n peri o d, a 
decisi o n will be ma de o n f urt her e x pa nsi o n or d ose de-escalati o n. 
E ve n t h o u g h n o d ose- de pe n de nt t o xicities ha ve bee n o bser ve d wit h 
ma gr oli ma b, i n or der t o preser ve t he efficaci o us d oses of t he c o m bi nati o n 
part ner dr u gs, d ose de-escalati o n will ta ke place f or ma gr oli ma b.
D ose de-escalati o n decisi o ns will be ma de as f oll o ws:
•
If 2 or fe wer of 6 D L T-e val ua ble patie nts e x perie nce a D L T i n C ycle 1, 
e nr oll me nt i nt o P hase 2 C o h ort 1 will be gi n at t his d ose le vel as t he 
rec o m me n de d P hase 2 d ose.
•
If m ore t ha n 2 patie nts e x perie nce at least 1 D L T d uri n g C ycle 1, 
e nr oll me nt at t he c urre nt d ose le vel will i m me diatel y st o p a n d d ose 
de-escalati o n will occ ur. U p t o a n ot her 6 patie nts will t he n be e nr olle d 
a n d e val uate d at a l o wer d ose le vel i n t he sa me ma n ner.
U p t o a p pr o xi matel y 1 8 patie nts c o ul d be p ote ntiall y e nr olle d a n d e val uate d 
d uri n g t he Safet y R u n-i n C o h ort.
D L T Assess me nt Peri o d:  T he D L T assess me nt peri o d will be t he first 
c ycle ( 2 1 da ys) a n d a p plies t o Safet y R u n-i n C o h ort 1. Patie nts are 
c o nsi dere d e val ua ble f or assess me nt of a D L T if eit her of t he f oll o wi n g 
criteria are met i n t he D L T assess me nt peri o d:
•
T he patie nt e x perie nce d a D L T at a n y ti me after i nitiati o n of t he first 
i nf usi o n of ma gr oli ma b.
•
T he patie nt di d n ot e x perie nce a D L T a n d c o m plete d at least 2 i nf usi o ns 
of ma gr oli ma b ( 2 1- da y c ycle) a n d at least 1 d ose of d oceta xel i n Safet y 
R u n-i n C o h ort 1.
If a patie nt e x perie nces a D L T d uri n g t he D L T assess me nt peri o d, t he 
patie nt will disc o nti n ue treat me nt.
Patie nts w h o are n ot e val ua ble f or D L T assess me nt i n t he Safet y R u n-i n 
C o h ort 1 will be re place d.
T he D L T defi niti o n is pr o vi de d i n t he mai n pr ot oc ol ( Secti o n 3. 1. 1. 2 ).
P h ase 2 C o h ort 1:  O nce Safet y R u n-i n C o h ort 1 is c o m plete d a n d t he 
rec o m me n de d d ose f or P hase 2 C o h ort 1 is deter mi ne d, t he s p o ns or will 
o pe n P hase 2 C o h ort 1. P hase 2 C o h ort 1 will treat u p t o 3 0 patie nts wit h 
m N S C L C ( P hase 2 C o h ort 1a), u p t o 2 6 patie nts wit h m U C ( P hase 2 
C o h ort 1 b), a n d u p t o 4 0 patie nts wit h m S C L C ( P hase 2 C o h ort 1c) t o 
e val uate efficac y.
N u m ber of 
P atie nts 
Pl a n ne d:
U p t o a p pr o xi matel y 1 1 4 patie nts i n t otal
•
Safet y R u n-i n C o h ort 1: u p t o a p pr o xi matel y 1 8 patie nts
•
P hase 2 C o h ort 1: u p t o a p pr o xi matel y 9 6 patie nts


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0
2 4 Oct o ber 2 0 2 3
T ar get 
P o p ul ati o n:
P h ase 2 C o h ort 1:  Patie nts wit h m N S C L C, m U C, a n d m S C L C 
D ur ati o n of 
Tre at me nt:
C ycle le n gt hs are 2 1 da ys f or t he Safet y R u n-i n C o h ort 1 a n d P hase 2 
C o h ort 1. All patie nts will c o nti n ue st u d y treat me nt u nless t he y meet st u d y 
treat me nt disc o nti n uati o n criteria.
Di a g n osis a n d 
M ai n Eli gi bilit y 
Criteri a:
I ncl usi o n Criteri a:
All patie nts m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble 
f or partici pati o n i n t his st u d y:
1)
Patie nt has pr o vi de d i nf or me d c o nse nt.
2)
Patie nt is willi n g a n d a ble t o c o m pl y wit h cli nic visits a n d pr oce d ures 
o utli ne d i n t he st u d y pr ot oc ol.
3)
Male or fe male, ≥ 1 8 years of a ge
4)
Patie nts m ust ha ve a n Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) 
perf or ma nce stat us of ≤ 2.
5)
La b orat or y meas ure me nts, bl o o d c o u nts:
a)
He m o gl o bi n m ust be ≥ 9 g/ d L pri or t o i nitial d ose of st u d y dr u g. 
N O T E: Tra nsf usi o ns are all o we d t o meet eli gi bilit y (see 
Secti o n 7. 8. 1. 1. 1  i n t he cli nical pr ot oc ol a n d e xcl usi o n criteri o n 4)
b)
A bs ol ute ne utr o p hil c o u nt ≥ 1. 5  1 09/ L
c)
Platelets ≥ 1 0 0  1 09/ L
6)
La b orat or y meas ure me nts, re nal f u ncti o n:
a)
Patie nts m ust ha ve a de q uate re nal f u ncti o n as de m o nstrate d b y a 
creati ni ne cleara nce of at least 3 0 m L/ mi n; calc ulate d b y t he 
C oc kcr oft Ga ult f or m ula
7)
A de q uate li ver f u ncti o n, as de m o nstrate d b y:
a)
A S T less t ha n or e q ual t o 2. 5  u p per li mit of n or mal ( U L N) or less 
t ha n or e q ual t o 5  U L N i n patie nts wit h li ver metastases 
b)
A L T less t ha n or e q ual t o 2. 5  U L N or less t ha n or e q ual t o 
5  U L N i n patie nts wit h li ver metastases
c)
Bilir u bi n less t ha n or e q ual t o 1. 5  U L N, or less t ha n or e q ual 
t o 3. 0  U L N a n d pri maril y u nc o nj u gate d if patie nt has a 
d oc u me nte d hist or y of Gil bert’s s y n dr o me or ge netic e q ui vale nt
8)
Pretreat me nt bl o o d cr oss- matc h c o m plete d ( See Secti o n 7. 8. 1. 1. 1  i n t he 
cli nical pr ot oc ol)


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 1
2 4 Oct o ber 2 0 2 3
9) 
Male a n d fe male patie nts of c hil d beari n g p ote ntial w h o e n ga ge i n 
heter ose x ual i nterc o urse m ust a gree t o use pr ot oc ol-s pecifie d met h o d(s) 
of c o ntrace pti o n as descri be d i n A p pe n di x 6 .
1 0) Meas ura ble disease acc or di n g t o R E CI S T, Versi o n 1. 1. Pre vi o usl y 
irra diate d lesi o ns ca n be c o nsi dere d as meas ura ble disease o nl y if 
disease pr o gressi o n has bee n u ne q ui v ocall y d oc u me nte d at t hat site 
si nce ra diati o n.
1 1) Criteri o n re m o ve d.
C o h ort- S pecific I ncl usi o n Criteri a
Patie nts nee d t o f ulfill t he f oll o wi n g c o h ort-s pecific criteria, i n a d diti o n t o 
satisf yi n g t he i ncl usi o n criteria f or all patie nts:
1 2) Criteri o n re m o ve d.
1 3) Criteri o n re m o ve d.
1 4) Safet y R u n-i n C o h ort 1: Patie nts wit h metastatic a d va nce d s oli d t u m ors 
w h o ha ve ha d at least 1 pri or li ne of s yste mic a ntica ncer t hera p y 
( m N S C L C a n d m S C L C) i n a l ocall y a d va nce d/ metastatic setti n g, or 
2 pri or li nes of s yste mic a ntica ncer t hera p y ( m U C) i n a l ocall y 
a d va nce d/ metastatic setti n g, a n d n ot m ore t ha n 3 pri or li nes of s yste mic 
a ntica ncer t hera p y i n a l ocall y a d va nce d/ metastatic setti n g.
1 5) P hase 2 C o h ort 1a ( m N S C L C): Patie nts wit h N S C L C w h o ha ve ha d 
treat me nt wit h plati n u m- base d c he m ot hera p y a n d i m m u ne c hec k p oi nt 
i n hi bit or t hera p y i n a l ocall y a d va nce d/ metastatic setti n g, eit her i n 
c o m bi nati o n or se q ue ntiall y ( u nless n ot eli gi ble f or o ne of t hese 
t hera pies) are eli gi ble. At least 1 pri or li ne of s yste mic a ntica ncer 
t hera p y i n a l ocall y a d va nce d/ metastatic setti n g is re q uire d a n d n ot 
m ore t ha n 2 pri or li nes of s yste mic a ntica ncer t hera p y i n a l ocall y 
a d va nce d/ metastatic setti n g are all o we d. Patie nts treate d wit h a ta xa ne 
wit hi n 1 2 m o nt hs or patie nts refract or y t o pri or ta xa ne treat me nt are 
e xcl u de d. Patie nts w h ose t u m ors ha ve ge n o mic alterati o ns f or w hic h 
t here are a p pr o ve d t hera pies (e g, E G F R, R O S 1, A L K, N T R K, M E T 
e x o n 1 4) are e xcl u de d.
1 6) P hase 2 C o h ort 1 b ( m U C): Patie nts wit h U C w h o ha ve ha d pri or 
treat me nt wit h s yste mic c he m ot hera p y a n d i m m u ne c hec k p oi nt 
i n hi bit or t hera p y i n a l ocall y a d va nce d/ metastatic setti n g ( u nless n ot 
eli gi ble f or o ne of t hese t hera pies) are eli gi ble. At least 2 pri or li nes of 
s yste mic a ntica ncer t hera p y i n a l ocall y a d va nce d/ metastatic setti n g are 
re q uire d a n d n ot m ore t ha n 3 pri or li nes of s yste mic a ntica ncer t hera p y 
i n a l ocall y a d va nce d/ metastatic setti n g are all o we d. Patie nts treate d 
wit h a ta xa ne wit hi n 1 2 m o nt hs or patie nts refract or y t o pri or ta xa ne 
treat me nt are e xcl u de d.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 2
2 4 Oct o ber 2 0 2 3
1 7) P hase 2 C o h ort 1c ( m S C L C): Patie nts wit h S C L C w h o ha ve ha d pri or 
treat me nt wit h plati n u m- base d c he m ot hera p y wit h or wit h o ut 
i m m u n ot hera p y are eli gi ble. At least 1 pri or li ne of s yste mic a ntica ncer 
t hera p y i n a l ocall y a d va nce d/ metastatic setti n g is re q uire d a n d n ot 
m ore t ha n 2 pri or li nes of s yste mic a ntica ncer t hera p y i n a l ocall y 
a d va nce d/ metastatic setti n g are all o we d. Patie nts treate d wit h a ta xa ne 
wit hi n 1 2 m o nt hs or patie nts refract or y t o pri or ta xa ne treat me nt are 
e xcl u de d.
N ote: Mai nte na nce t hera pies are n ot c o u nte d as se parate li nes of t hera p y.
E xcl usi o n Criteri a:
Patie nts w h o meet a ny  of t he f oll o wi n g e xcl usi o n criteria are n ot t o be 
e nr olle d i n t his st u d y:
1)
P ositi ve ser u m pre g na nc y test
2)
Breastfee di n g fe male
3)
Acti ve ce ntral ner v o us s yste m ( C N S) disease. Patie nts wit h 
as y m pt o matic a n d sta ble, treate d C N S lesi o ns (ra diati o n a n d/ or s ur ger y 
a n d/ or ot her C N S- directe d t hera p y w h o ha ve n ot recei ve d 
c ortic oster oi ds f or at least 4 wee ks) are all o we d.
4)
Re d bl o o d cell ( R B C) tra nsf usi o n de pe n de nce, defi ne d as re q uiri n g 
m ore t ha n 2 u nits of pac ke d re d bl o o d cell tra nsf usi o ns d uri n g t he 
4- wee k peri o d pri or t o scree ni n g. R B C tra nsf usi o ns are per mitte d 
d uri n g t he scree ni n g peri o d a n d pri or t o e nr oll me nt t o meet t he 
he m o gl o bi n i ncl usi o n criteria.
5)
Hist or y of he m ol ytic a ne mia, a ut oi m m u ne t hr o m b oc yt o pe nia, or E va ns 
s y n dr o me i n t he last 3 m o nt hs
6)
K n o w n h y perse nsiti vit y t o a n y of t he st u d y dr u gs, t he meta b olites, or 
f or m ulati o n e xci pie nt
7)
Pri or treat me nt wit h C D 4 7- or si g nal re g ulat or y pr otei n al p ha-tar geti n g 
a ge nts
8)
C urre nt partici pati o n i n a n ot her i nter ve nti o nal cli nical trial
9)
K n o w n i n herite d or ac q uire d blee di n g dis or ders
1 0) Si g nifica nt disease or me dical c o n diti o ns, as assesse d b y t he i n vesti gat or 
a n d s p o ns or, t hat w o ul d s u bsta ntiall y i ncrease t he ris k- be nefit rati o of 
partici pati n g i n t he st u d y. T his i ncl u des, b ut is n ot li mite d t o, ac ute 
m y ocar dial i nfarcti o n wit hi n t he last 6 m o nt hs, u nsta ble a n gi na, 
u nc o ntr olle d dia betes mellit us, si g nifica nt acti ve i nfecti o ns, a n d c o n gesti ve 
heart fail ure Ne w Y or k Heart Ass ociati o n Class III-I V.
1 1) Sec o n d mali g na nc y, e xce pt treate d basal cell or l ocalize d  s q ua m o us 
s ki n carci n o mas, l ocalize d pr ostate ca ncer, or ot her mali g na ncies f or 
w hic h patie nts are n ot o n acti ve a ntica ncer t hera pies a n d w h o are i n 
c o m plete re missi o n f or o ver 3 years.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 3
2 4 Oct o ber 2 0 2 3
1 2) K n o w n acti ve or c hr o nic he patitis B or C i nfecti o n or h u ma n 
i m m u n o deficie nc y vir us i nfecti o n i n me dical hist or y.
1 3) Pri or a ntica ncer t hera p y i ncl u di n g b ut n ot li mite d t o c he m ot hera p y, 
i m m u n ot hera p y, or i n vesti gati o nal a ge nts wit hi n 4 wee ks pri or t o 
ma gr oli ma b is n ot per mitte d.
N O T E: Palliati ve, l ocalize d, n o n- C N S ra di ot hera p y t o areas of 
n o n-tar get disease, pre vi o us h or m o nal t hera p y wit h l utei nizi n g h or m o ne 
releasi n g h or m o ne a g o nists f or pr ostate or breast ca ncer, a n d treat me nt 
wit h bis p h os p h o nates a n d rece pt or acti vat or of n uclear fact or ka p pa B 
li ga n d ( R A N K L) i n hi bit ors are n ot criteria f or e xcl usi o n. T here is n o 
re q uire d mi ni m u m was h o ut peri o d f or t hese t hera pies. Patie nts s h o ul d 
be rec o vere d fr o m t he effects of ra diati o n.
St u d y 
Pr oce d ures/
Fre q ue nc y:
I n Safet y R u n-i n C o h ort 1, eli gi ble patie nts will recei ve ma gr oli ma b + 
d oceta xel. T he st u d y treat me nts are s h o w n bel o w.
S afet y R u n-i n C o h ort 1: D ose Le vel, Sc he d ule, a n d De-esc al ati o n 
D osi n g ( C ycles Are 2 1 D a ys)
Dr u g
D ose Le vel 
C ycle 1
C ycle 2
C ycle 3 + 
( m ai nte n a nce 
d osi n g)
Starti n g 
d ose
3 0 m g/ k g
1 m g/ k g I V ( 3 h 
± 3 0 mi n) o n 
Da y 1 ( pri mi n g 
d ose), 3 0 m g/ k g 
I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da ys 1, 8, 
a n d 1 5
6 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da y 1
De-escalati o
n
Le vel −1
2 0 m g/ k g
1 m g/ k g I V ( 3 h 
± 3 0 mi n) o n 
Da y 1 ( pri mi n g 
d ose); 2 0 m g/ k g 
I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
2 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da ys 1, 8, 
a n d 1 5
4 5 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da y 1
Ma gr oli ma b
De-escalati o
n
Le vel −2
1 5 m g/ k g
1 m g/ k g I V ( 3 h 
± 3 0 mi n) o n 
Da y 1 ( pri mi n g 
d ose); 1 5 m g/ k g 
I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
1 5 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da ys 1, 8, 
a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da y 1
D oceta xel 
7 5 m g/ m 2
7 5 m g/ m 2 I V ( 1 h 
± 5 mi n) o n Da y 
1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) 
o n Da y 1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) 
o n Da y 1
I V = i ntra ve n o us


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 4
2 4 Oct o ber 2 0 2 3
P h ase 2 C o h ort 1: D ose Le vel a n d Sc he d ule 
D ose Sc he d ule ( C ycles Are 2 1 D a ys)
Dr u g
R P 2 D a
St arti n g 
D ose
C ycle 1
C ycle 2
C ycle 3 + 
( m ai nte n a nce 
d osi n g)
3 0 m g/ k g 
1 m g/ k g I V 
( 3 h ± 3 0 mi n) o n 
Da y 1 ( pri mi n g 
d ose); 3 0 m g/ k g 
I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da ys 1, 8, 
a n d 1 5
6 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da y 1
O R
2 0 m g/ k g
1 m g/ k g I V 
( 3 h ± 3 0 mi n) o n 
Da y 1 ( pri mi n g 
d ose); 2 0 m g/ k g 
I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
2 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da ys 1, 8, 
a n d 1 5
4 5 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da y 1
Ma gr oli ma b
O R
1 5 m g/ k g
1 m g/ k g I V 
( 3 h ± 3 0 mi n) o n 
Da y 1 ( pri mi n g 
d ose); 1 5 m g/ k g 
I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
1 5 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da ys 1, 8, 
a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) 
o n Da y 1
D oceta xel 
7 5 m g/ m 2 
I V
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) o n 
Da y 1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) o n 
Da y 1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) o n 
Da y 1
I V = i ntra ve n o us; R P 2 D = rec o m me n de d P hase 2 d ose
a  
R P 2 D as deter mi ne d i n Safet y R u n-i n C o h ort 1.
C ycle le n gt hs are 2 1 da ys f or Safet y R u n-i n C o h ort 1 a n d P hase 2 C o h ort 1. 
Patie nts ma y c o nti n ue treat me nt u nless t he y de vel o p u nacce pta ble t o xicit y 
t hat ca n n ot be cli nicall y ma na ge d b y d ose or sc he d ule m o dificati o ns or if 
t he y ha ve c o nfir me d pr o gressi ve disease acc or di n g t o R E CI S T, Versi o n 1. 1.
Test Pr o d uct, 
D ose, a n d M o de 
of 
A d mi nistr ati o n:
Safet y R u n-i n C o h ort 1 D oses:
•
Ma gr oli ma b 1 m g/ k g I V ( pri mi n g)
•
Ma gr oli ma b 3 0 m g/ k g I V
•
Ma gr oli ma b 6 0 m g/ k g I V
I n c o m bi nati o n wit h d oceta xel 7 5 m g/ m2 I V
P hase 2 C o h ort 1:
Ma gr oli ma b d ose will be deter mi ne d i n Safet y R u n-i n C o h ort 1.
Refere nce 
T her a p y, D ose, 
a n d M o de of 
A d mi nistr ati o n:
N ot a p plica ble


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 5
2 4 Oct o ber 2 0 2 3
Criteri a f or 
E v al u ati o n:
Safet y: 
Safet y will be e val uate d b y data i ncl u di n g t he i nci de nce of a d verse e ve nts 
( A Es) f or t he d urati o n of t he st u d y, assess me nt of cli nical la b orat or y test 
fi n di n gs, p h ysical e xa mi nati o n, 1 2-lea d electr ocar di o gra m, E C O G 
perf or ma nce stat us, a n d vital si g ns meas ure me nts. A d verse e ve nts will be 
gra de d usi n g N CI C T C A E, Versi o n 5. 0.
Efficac y: 
Efficac y will be e val uate d b y P F S, O R R, D O R, a n d O S. Assess me nt of 
res p o nse will be meas ure d b y R E CI S T, Versi o n 1. 1 as deter mi ne d b y 
i n vesti gat or assess me nt.
P har mac o ki netics:
Ma gr oli ma b ser u m dr u g c o nce ntrati o ns will be assesse d at pre d ose at 
m ulti ple ti me p oi nts u ntil st u d y disc o nti n uati o n. Peri p heral bl o o d f or 
i m m u n o ge nicit y assess me nts f or a nti dr u g a nti b o dies a gai nst ma gr oli ma b 
will als o be c ollecte d at pre d ose a n d m ulti ple ti me p oi nts d uri n g t he st u d y.
St atistic al 
Met h o ds:
A nal ysis Data Sets
T he D L T E val ua ble A nal ysis Set f or Safet y R u n-i n C o h ort 1 will i ncl u de all 
patie nts w h o meet 1 of t he f oll o wi n g criteria i n t he D L T e val ua ble peri o d:
•
T he patie nt e x perie nce d a D L T at a n y ti me after i nitiati o n of t he first 
i nf usi o n of ma gr oli ma b
•
T he patie nt di d n ot e x perie nce a D L T a n d c o m plete d at least 2 i nf usi o ns 
of ma gr oli ma b ( 2 1- da y c ycle) a n d at least 1 d ose of d oceta xel i n Safet y 
R u n-i n C o h ort 1
F or Safet y R u n-i n C o h ort 1, t he m o difie d I nte nt-t o- Treat (I T T) a n d Safet y 
A nal ysis Sets will i ncl u de all patie nts w h o recei ve d at least 1 d ose of a n y 
st u d y dr u g.
F or P hase 2 C o h ort 1, t he m o difie d I T T A nal ysis Set a n d t he Safet y 
A nal ysis Set will i ncl u de all patie nts w h o recei ve d at least 1 d ose of a n y 
st u d y dr u g.
T he P K A nal ysis Set will i ncl u de all patie nts w h o recei ve d a n y a m o u nt of 
ma gr oli ma b a n d ha ve at least 1 meas ura ble p osttreat me nt ser u m 
c o nce ntrati o n of ma gr oli ma b.
T he I m m u n o ge nicit y A nal ysis Set will i ncl u de all patie nts w h o recei ve d a n y 
a m o u nt of ma gr oli ma b a n d ha d at least 1 e val ua ble a nti- ma gr oli ma b 
a nti b o d y test res ult.
T he Bi o mar ker A nal ysis Set i ncl u des all patie nts w h o recei ve d a n y st u d y 
dr u g a n d ha ve at least 1 e val ua ble bi o mar ker meas ure me nt a vaila ble. T his 
will be t he pri mar y a nal ysis set f or all bi o mar ker data a nal yses.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 6
2 4 Oct o ber 2 0 2 3
D ose Deter mi nati o n A nal ysis
F or t he p ur p oses of ma ki n g t he d ose de-escalati o n decisi o ns f or Safet y 
R u n-i n C o h ort 1, d ose deter mi nati o n a nal yses of rele va nt safet y data 
f oc usi n g o n D L Ts a n d o verall safet y pr ofile will be c o n d ucte d b y t he 
s p o ns or after all patie nts ha ve c o m plete d re q uire d d osi n g c ycles ( 2 1 da ys) 
a n d t he f oll o w- u p peri o d as s pecifie d i n Secti o n 3. 1. 1 . Safet y assess me nts 
(e g, A Es, electr ocar di o gra m, la b orat or y res ults) will be dis pla ye d b y c o h ort 
t o facilitate t he d ose de-escalati o n decisi o ns.
Efficac y A nal ysis
F or P hase 2 C o h ort 1, O R R al o n g wit h t he 9 5 % CI base d o n t he 
Cl o p per- Pears o n met h o d will be esti mate d f or eac h c o h ort ( P hase 2 
C o h orts 1a, 1 b, a n d 1c). Patie nts w h o d o n ot ha ve s ufficie nt baseli ne or 
o n-st u d y t u m or assess me nt t o c haracterize res p o nse will be c o u nte d as 
n o nres p o n ders.
Safet y A nal ysis
Safet y will be assesse d via A Es, cli nical la b orat or y tests, a n d c o nc o mita nt 
me dicati o ns i n t he Safet y A nal ysis Set. I nf or mati o n re gar di n g st u d y dr u g 
a d mi nistrati o n, st u d y dr u g c o m plia nce, a n d ot her safet y varia bles will als o 
be s u m marize d.
Sa m ple Size Calc ulati o n
F or P hase 2 C o h ort 1, a sa m ple size of 3 0 patie nts i n t he m N S C L C c o h ort 
a n d 4 0 patie nts f or m S C L C c o h ort were calc ulate d usi n g o ne sa m ple 
pr o p orti o n test. T he sa m ple size of 2 6 patie nts f or t he m U C c o h ort was 
calc ulate d usi n g e xact met h o d i nstea d of o ne sa m ple test d ue t o s maller 
sa m ple size.
T u m or 
T y pe
S a m ple 
Size 
N ull O R R
Alter n ati ve 
O R R
1-si de d 
al p h a 
P o wer
m N S C L C 
3 0 
1 3 % 
2 5 % 
0. 2 
8 1 %
m U C
2 6 
1 2. 4 % 
2 8 % 
0. 1 
7 8 %
m S C L C
4 0
9 %
2 0 % 
0. 1 5 
8 4 %
T he n ull O R R f or eac h of t he res pecti ve t u m or c o h orts are base d o n 
hist orical ta xa ne efficac y data i n t he sec o n d li ne setti n g. P o wer calc ulati o ns 
were perf or me d usi n g E A S T 6. 5 a n d n Q uer y 8. 0.
T his st u d y will be c o n d ucte d i n acc or da nce wit h t he g ui deli nes of G o o d Cli nical Practice, 
i ncl u di n g arc hi vi n g of esse ntial d oc u me nts.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 7
2 4 Oct o ber 2 0 2 3
G L O S S A R Y O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S
A B O
a n y of t he 4 bl o o d gr o u ps A, B, A B, a n d O c o m prisi n g t he A B O s yste m
A D A
a nti dr u g a nti b o d y
A D C
a nti b o d y- dr u g c o nj u gate
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A M L
ac ute m yel oi d le u ke mia
A N C
a bs ol ute ne utr o p hil c o u nt
A S C O
A merica n S ociet y of Cli nical O nc ol o g y
A S T
as partate a mi n otra nsferase
C D 4 7
cl uster of differe ntiati o n 4 7
CI
c o nfi de nce i nter val
C M V
c yt o me gal o vir us
C N S
ce ntral ner v o us s yste m
C O VI D- 1 9
c or o na vir us disease 2 0 1 9
C R
c o m plete res p o nse
C R C
c ol orectal ca ncer
C R F
case re p ort f or m
C R O
c o ntract/cli nical researc h or ga nizati o n
C S R
cli nical st u d y re p ort
C T
c o m p ute d t o m o gra p h y
C T C 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 P 4 5 0 e nz y me
D A T
direct a nti gl o b uli n test
D L B C L
diff use lar ge B-cell l y m p h o ma
D L T
d ose-li miti n g t o xicit y
D N A
de o x yri b o n ucleic aci d
D O R
d urati o n of res p o nse
E C
et hic c o m mittee
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 LI S A
e nz y me-li n ke d i m m u n os or be nt assa y
E O T
e n d of treat me nt
E U
E ur o pea n U ni o n
Fc
fra g me nt cr ystalliza ble
F D A
F o o d a n d Dr u g A d mi nistrati o n
G C P
G o o d Cli nical Practice
Gilea d
Gilea d Scie nces


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 8
2 4 Oct o ber 2 0 2 3
H R
hazar d rati o
H U
h y dr o x y urea
I B
i n vesti gat or’s br oc h ure
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 g G 4
i m m u n o gl o b uli n G 4
I N D
i n vesti gati o nal ne w dr u g
I R B
i nstit uti o nal re vie w b oar d
I R R
i nf usi o n-relate d reacti o n
I R T
I nteracti ve Res p o nse Tec h n ol o g y
I T T
i nte nt-t o-treat
I U D
i ntra uteri ne de vice
I V
i ntra ve n o us
K D
diss ociati o n c o nsta nt
K M
Ka pla n- Meier
L H R H
l utei nizi n g h or m o ne releasi n g h or m o ne
m A b
m o n ocl o nal a nti b o d y
M D S
m yel o d ys plastic s y n dr o me
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Acti vities
m N S C L C
metastatic n o n-s mall cell l u n g ca ncer
M O A
mec ha nis m of acti o n
m S C L C
metastatic s mall cell l u n g ca ncer
M T D
ma xi m u m t olerate d d ose
m U C
metastatic ur ot helial ca ncer
na b
na n o particle al b u mi n- b o u n d
N CI
Nati o nal Ca ncer I nstit ute
N H L
n o n- H o d g ki n l y m p h o ma
N S C L C
n o n-s mall cell l u n g ca ncer
O R R
o bjecti ve res p o nse rate
O S
o verall s ur vi val
P B M C
peri p heral bl o o d m o n o n uclear cell
P D
p har mac o d y na mic(s)
P D- 1
pr o gra m me d cell deat h pr otei n 1
P D- L 1
pr o gra m me d cell deat h li ga n d 1
P F S
pr o gressi o n-free s ur vi val
P K
p har mac o ki netic(s)
P S
Patie nt Safet y
R A N K L
rece pt or acti vat or of n uclear fact or ka p pa B li ga n d
R B C
re d bl o o d cell


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 9
2 4 Oct o ber 2 0 2 3
R E CI S T
Res p o nse E val uati o n Criteria i n S oli d T u m ors
R h
r hes us
R N A
ri b o n ucleic aci d
R O
rece pt or occ u pa nc y
R P 2 D
rec o m me n de d P hase 2 d ose
S A E
seri o us a d verse e ve nt
S C L C
s mall cell l u n g ca ncer
SI R P α
si g nal re g ulat or y pr otei n al p ha
S m P C
s u m mar y of pr o d uct c haracteristics
S O P
sta n dar d o perati n g pr oce d ure
S R T
safet y re vie w tea m
S S Rs
s pecial sit uati o n re p orts
S U S A R
s us pecte d u ne x pecte d seri o us a d verse reacti o n
T C R
T cell rece pt or
U C
ur ot helial ca ncer
U L N
u p per li mit of n or mal
U S
U nite d States
U S PI
U nite d States prescri bi n g i nf or mati o n
w/ v
wei g ht-t o- v ol u me rati o
W E S
w h ole e x o me se q ue nci n g


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 0
2 4 Oct o ber 2 0 2 3
1.  
I N T R O D U C TI O N
1. 1.  
B ac k gr o u n d
1. 1. 1.  
B ac k gr o u n d o n Rel a pse d/ Refr act or y S oli d T u m ors I ncl u di n g Met ast atic 
N o n- S m all Cell L u n g C a ncer, Met ast atic Ur ot heli al C a ncer, a n d Met ast atic 
S m all Cell L u n g C a ncer
F or ma n y s oli d t u m ors, i m m u ne c hec k p oi nt i n hi bit ors, s pecificall y a nti – pr o gra m me d cell deat h 
pr otei n 1 ( P D- 1) a n d a nti – pr o gra m me d cell deat h li ga n d- 1 ( P D- L 1) a nti b o dies, ha ve dra maticall y 
i m pr o ve d t he treat me nt o utc o mes f or patie nts. Se veral T-cell c hec k p oi nt i n hi bit ors are 
U nite d States ( U S) F o o d a n d Dr u g A d mi nistrati o n ( F D A) a p pr o ve d f or m ulti ple s oli d t u m ors 
i ncl u di n g pe m br oliz u ma b, ni v ol u ma b, atez oliz u ma b, d ur val u ma b, a vel u ma b, a n d ce mi pli ma b. 
F or m ost t u m or t y pes, sta n dar d of care f or fr o ntli ne treat me nt c o nsists of c o m bi nati o n 
c he m ot hera p y, i m m u ne c hec k p oi nt i n hi bit ors, or t he c o m bi nati o n. H o we ver, o nce patie nts fail 
sta n dar d c he m ot hera p y a n d/ or i m m u ne c hec k p oi nt i n hi bit ors, treat me nt o pti o ns are ge nerall y 
m ore li mite d. Ofte n, si n gle-a ge nt c he m ot hera p y is sta n dar d of care i n t his setti n g. Efficac y is 
li mite d i n t his setti n g wit h o bser ve d o bjecti ve res p o nse rates ( O R Rs) ar o u n d 1 0 % f or m ost 
si n gle-a ge nt c he m ot hera pe utic re gi me ns. T h us, n o vel a ge nts t hat ca n safel y c o m bi ne a n d 
e n ha nce efficac y of t hese c he m ot hera pies are nee de d t o i m pr o ve treat me nt o utc o mes i n t his 
setti n g. T his st u d y will i nitiall y e val uate ma gr oli ma b c o m bi nati o n wit h c he m ot hera p y i n m ulti ple 
s oli d t u m ors i ncl u di n g metastatic n o n –s mall cell l u n g ca ncer ( m N S C L C), metastatic ur ot helial 
ca ncer ( m U C), a n d metastatic s mall cell l u n g ca ncer ( m S C L C).
1. 1. 1. 1.   
N S C L C Bac k gr o u n d
L u n g ca ncer is t he lea di n g ca use of ca ncer-relate d m ortalit y. A p pr o xi matel y 8 0 % t o 8 5 % of all 
l u n g ca ncers are N S C L C. Rece nt a d va nces wit h i m m u ne c hec k p oi nt i n hi bit or t hera p y ha ve 
dra maticall y i m pr o ve d t he pr o g n osis of l u n g ca ncer a n d t hese i m m u ne c hec k p oi nt i n hi bit or 
t hera pies, as m o n ot hera p y or i n c o m bi nati o n, are mai nl y use d i n t he fr o ntli ne metastatic setti n g. 
H o we ver, after fail ure of i m m u ne c hec k p oi nt i n hi bit or t hera p y a n d/ or fr o ntli ne c he m ot hera p y, 
t here are li mite d treat me nt o pti o ns f or t he maj orit y of patie nts. Acc or di n g t o Nati o nal 
C o m pre he nsi ve Ca ncer Net w or k ( N C C N) g ui deli nes, t he use of si n gle-a ge nt c he m ot hera p y 
(i ncl u di n g ta xa nes) is t he sta n dar d of care f or patie nts wit h rec urre nt or metastatic N S C L C after 
fail ure of plati n u m- base d t hera p y a n d/ or i m m u ne c hec k p oi nt t hera p y {Etti n ger 2 0 1 9 }. T he mai n 
o pti o ns f or si n gle-a ge nt c he m ot hera p y i n t his setti n g ge nerall y i ncl u de d oceta xel ( wit h or 
wit h o ut ra m ucir u ma b), erl oti ni b, a n d pe metre xe d. Hist orical me dia n pr o gressi o n-free s ur vi val 
( P F S) rates i n sec o n d-li ne N S C L C treate d wit h si n gle-a ge nt c he m ot hera p y is a p pr o xi matel y 
3 m o nt hs wit h a me dia n s ur vi val of a p pr o xi matel y 6 t o 8 m o nt hs { S he p her d 2 0 0 0 }. T h us, n o vel 
a ge nts t hat ca n safel y c o m bi ne wit h si n gle-a ge nt c he m ot hera p y a n d i m pr o ve cli nical efficac y are 
nee de d.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 1
2 4 Oct o ber 2 0 2 3
1. 1. 1. 2.  
S C L C Bac k gr o u n d
S mall cell l u n g ca ncer is a ne ur oe n d ocri ne t u m or t hat re prese nts a p pr o xi matel y 1 5 % of all l u n g 
ca ncers. S mall cell l u n g ca ncer pre d o mi na ntl y occ urs i n s m o kers a n d is disti n g uis he d fr o m ot her 
N S C L C t y pes b y its ra pi d pr oliferati o n rate, earl y de vel o p me nt of metastases, a n d i nitial 
prese ntati o n wit h disse mi nate d disease. W hile patie nts wit h S C L C te n d t o i nitiall y prese nt wit h 
metastatic disease, S C L C is hi g hl y res p o nsi ve t o c he m ot hera pe utic a ge nts ( wit h a n d wit h o ut 
ra diati o n), w hic h are t he mai nsta y of fr o ntli ne treat me nt. Fr o ntli ne c he m ot hera p y ge nerall y 
c o nsists of plati n u m- base d c o m bi nati o ns (ie, plati n u m + et o p osi de). Me dia n o verall s ur vi val ( O S) 
wit h plati n u m- base d c he m ot hera pies i n t he fr o ntli ne metastatic setti n g is a p pr o xi matel y 9 t o 
1 0 m o nt hs { R ossi 2 0 1 2 }. Rece ntl y, t he a d diti o n of i m m u ne c hec k p oi nt i n hi bit ors t o fr o ntli ne 
plati n u m- base d c he m ot hera p y c o m bi nati o ns ha ve de m o nstrate d i m pr o ve me nt i n cli nical o utc o mes 
lea di n g t o F D A a p pr o val of c hec k p oi nt i n hi bit ors (atez oliz u ma b a n d d ur val u ma b) i n t he fr o ntli ne 
metastatic disease p o p ulati o n. I n a ra n d o mize d P hase 3 st u d y, atez oliz u ma b i n c o m bi nati o n wit h 
car b o plati n a n d et o p osi de de m o nstrate d a statisticall y si g nifica nt i m pr o ve me nt i n P F S c o m pare d t o 
car b o plati n + et o p osi de ( 1 2. 3 vs 1 0. 3 m o nt hs, hazar d rati o [ H R] = 0. 7 0) wit h a si milar t o xicit y 
pr ofile acr oss b ot h gr o u ps { H or n 2 0 1 8 }. I n a n ot her P hase 3 st u d y, d ur val u ma b i n c o m bi nati o n 
wit h plati n u m-et o p osi de le d t o a n i m pr o ve me nt i n O S c o m pare d t o c he m ot hera p y c o ntr ol ( 1 2. 9 vs 
1 0. 5 m o nt hs, H R = 0. 7 5) { Paz ‑Ares 2 0 1 9 }. T h us, t he a d diti o n of i m m u ne c hec k p oi nt i n hi bit ors t o 
c he m ot hera p y has le d t o m o derate i m pr o ve me nts t o patie nt o utc o mes i n t he fr o ntli ne metastatic 
setti n g. F or patie nts w h o fail fr o ntli ne c he m ot hera p y wit h or wit h o ut a n i m m u ne c hec k p oi nt 
i n hi bit or, t here are li mite d treat me nt o pti o ns, wit h si n gle-a ge nt c he m ot hera p y as t he mai n sta n dar d 
of care. T he me dia n O S i n t his a d va nce d later li ne setti n g is a p pr o xi matel y 6 m o nt hs { S mit 1 9 9 8 , 
Ya ma m ot o 2 0 0 6 }. N o vel treat me nt o pti o ns or c o m bi nati o ns i n t he a d va nce d later li ne setti n g are 
nee de d t o i m pr o ve o utc o mes.
1. 1. 1. 3.   
U C Bac k gr o u n d
Bla d der ca ncer is t he m ost c o m m o n mali g na nc y i n v ol vi n g t he uri nar y s yste m. Ur ot helial 
carci n o ma is t he pre d o mi na nt hist ol o gic t y pe i n t he U S a n d E ur o pe, acc o u nti n g f or o ver 9 0 % of all 
bla d der ca ncers. S yste mic c he m ot hera p y is t he sta n dar d a p pr oac h f or t he i nitial treat me nt of 
patie nts wit h i n o pera ble l ocall y a d va nce d or metastatic ur ot helial ca ncer ( U C). Alt h o u g h i nitial 
res p o nse rates are hi g h, t he me dia n O S wit h c o m bi nati o n c he m ot hera p y ( pri maril y cis plati n- base d) 
is a p pr o xi matel y 1 5 m o nt hs {v o n der Maase 2 0 0 0 }. Rece ntl y, i m m u ne c hec k p oi nt i n hi bit or 
t hera pies ( n ota bl y pe m br oliz u ma b a n d atez oliz u ma b) ha ve m o ve d i nt o t he fr o ntli ne setti n g, 
partic ularl y f or t h ose w h o are i neli gi ble f or cis plati n t hera p y. T his usa ge is pri maril y base d o n 
P hase 2 st u dies de m o nstrati n g a 2 9 % O R R, me dia n d urati o n of res p o nse ( D O R) of 3 0 m o nt hs, a n d 
me dia n O S of 1 1. 3 m o nt hs f or pe m br oliz u ma b { V u k y 2 0 2 0 }. Si milar efficac y data ha ve bee n 
o bser ve d wit h atez oliz u ma b { Balar 2 0 1 7 }. I m m u ne c hec k p oi nt t hera p y i n c o m bi nati o n wit h 
c he m ot hera p y is bei n g e val uate d i n t he fr o ntli ne metastatic setti n g. I n a d diti o n t o fr o ntli ne patie nts 
w h o are i neli gi ble f or cis plati n- base d c he m ot hera p y, i m m u ne c hec k p oi nt t hera p y is pri maril y use d 
i n patie nts w h o fail fr o ntli ne c he m ot hera p y. M ulti ple i m m u ne c hec k p oi nt i n hi bit ors are a p pr o ve d 
i n t his setti n g base d o n eit her P hase 2 or ra n d o mize d P hase 3 data base d o n eit her e nc o ura gi n g 
d ura ble res p o nse rates or i m pr o ve me nt i n P F S c o m pare d t o c he m ot hera p y sta n dar d of care. Lastl y, 
a n o vel m o dalit y of a nti b o d y- dr u g c o nj u gates ( A D Cs) ha ve als o rece ntl y de m o nstrate d be nefit i n 
U C. E nf ort u ma b ve d oti n, a necti n- 4 A D C, was a p pr o ve d i n 2 0 1 9 f or t he treat me nt of l ocall y 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 2
2 4 Oct o ber 2 0 2 3
a d va nce d or metastatic U C i n patie nts w h o pre vi o usl y recei ve d a n a nti- P D- 1/ L 1 i n hi bit or a n d a 
plati n u m-c o ntai ni n g c he m ot hera p y re gi me n. T his a p pr o val was base d o n a P hase 2 st u d y 
de m o nstrati n g a n O R R of 4 4 % wit h a me dia n P F S of 6 m o nt hs. I n s u m mar y, rece nt treat me nt 
a d va nces i ncl u di n g i m m u ne c hec k p oi nt i n hi bit ors a n d A D Cs ha ve i m pr o ve d t he treat me nt 
o utc o mes i n patie nts wit h m U C. H o we ver, patie nts i n t he a d va nce d later li ne setti n g, es peciall y 
after 2 li nes of t hera p y, ha ve li mite d treat me nt o pti o ns a n d re q uire m ore effecti ve t hera pies. 
C urre ntl y, atez oliz u ma b is bei n g i n vesti gate d i n c o m bi nati o n wit h ma gr oli ma b i n m U C 
( N C T I D # 0 3 8 6 9 1 9 0).
1. 2.   
M a gr oli m a b
1. 2. 1.   
Ge ner al I nf or m ati o n
Cl uster of differe ntiati o n 4 7 ( C D 4 7) is a ke y m olec ule me diati n g ca ncer cell e vasi o n of i n nate 
i m m u ne s ur veilla nce. C D 4 7 e x pressi o n is a well-c haracterize d mec ha nis m b y w hic h ca ncer cells, 
i ncl u di n g ca ncer ste m cells, o verc o me p ha g oc yt osis d ue t o i ntri nsic e x pressi o n of pr o p ha g oc ytic 
“eat me” si g nals { Jais wal 2 0 0 9, Majeti 2 0 0 9 }. T he pr o gressi o n fr o m n or mal cell t o ca ncer cell 
i n v ol ves c ha n ges i n ge nes a n d ge ne e x pressi o n t hat tri g ger pr o gra m me d cell deat h a n d 
pr o gra m me d cell re m o val { C ha o 2 0 1 2 }. Ma n y of t he ste ps i n ca ncer pr o gressi o n s u b vert t he 
m ulti ple mec ha nis ms of pr o gra m me d cell deat h, a n d t he e x pressi o n of t he d o mi na nt 
a nti p ha g oc ytic si g nal, C D 4 7, ma y re prese nt a n i m p orta nt c hec k p oi nt { C ha o 2 0 1 2 }. I ncrease d 
C D 4 7 e x pressi o n was i de ntifi e d first o n le u ke mic ste m cells i n h u ma n ac ute m yel oi d le u ke mia 
( A M L) {Majeti 2 0 0 9 }, a n d si nce t he n it has bee n f o u n d t hat C D 4 7 e x pressi o n is i ncrease d o n t he 
s urface of ca ncer cells i n a di verse set of h u ma n t u m or t y pes.
I n m o use xe n o graft m o dels, C D 4 7- bl oc ki n g m o n ocl o nal a nti b o dies ( m A bs) i n hi bit h u ma n 
xe n o graft t u m or gr o wt h a n d metastasis b y e na bli n g t he p ha g oc yt osis a n d eli mi nati o n of ca ncer 
cells fr o m vari o us he mat ol o gic mali g na ncies a n d s oli d t u m ors { C ha o 2 0 1 1a , C ha o 2 0 1 0a , C ha o 
2 0 1 1 b , E dris 2 0 1 2 , Ki m 2 0 1 2 , Majeti 2 0 0 9 , Willi n g ha m 2 0 1 2 }. Bi n di n g of C D 4 7 e x presse d b y 
ca ncer cells t o its li ga n d, si g nal re g ulat or y pr otei n al p ha ( SI R Pα ), e x presse d o n p ha g oc ytes lea ds 
t o i n hi biti o n of t u m or cell p ha g oc yt osis. T h us, bl oc ka de of t he C D 4 7 SI R Pα -si g nali n g pat h wa y 
b y a n a nti- C D 4 7 a nti b o d y lea ds t o p ha g oc yt osis a n d eli mi nati o n of t u m or cells. Selecti ve 
tar geti n g of t u m or cells b y a n a nti- C D 4 7 a nti b o d y is d ue t o t he prese nce of pr o p ha g oc ytic si g nals 
e x presse d mai nl y o n t u m or cells a n d n ot o n n or mal cell c o u nter parts { C ha o 2 0 1 0 b }. I n a d diti o n, 
t he a nti- C D 4 7 a nti b o d y ca n i n d uce a n a ntica ncer T-cell res p o nse t hr o u g h cr oss- prese ntati o n of 
t u m or a nti ge ns b y macr o p ha ge a n d a nti ge n- prese nti n g cells after t u m or cell p ha g oc yt osis {Li u 
2 0 1 5 b , Tse n g 2 0 1 3 }.
Ma gr oli ma b is a h u ma nize d a nti- C D 4 7 m A b t hat bl oc ks t he i nteracti o n of C D 4 7 wit h its rece pt or 
a n d e na bles p ha g oc yt osis of h u ma n ca ncer cells { Li u 2 0 1 5a }. T he acti vit y of ma gr oli ma b is 
pri maril y de pe n de nt o n bl oc ki n g C D 4 7 bi n di n g t o SI R P α a n d n ot o n t he recr uit me nt of fra g me nt 
cr ystalliza ble ( Fc)- de pe n de nt effect or f u ncti o ns, alt h o u g h t he prese nce of t he i m m u n o gl o b uli n 
G 4 (I g G 4) Fc d o mai n is re q uire d f or its f ull acti vit y. F or t his reas o n, ma gr oli ma b was 
e n gi neere d wit h a h u ma n I g G 4 is ot y pe t hat is relati vel y i nefficie nt at recr uiti n g Fc- de pe n de nt 
effect or f u ncti o ns t hat mi g ht e n ha nce t o xic effects o n n or mal C D 4 7-e x pressi n g cells { Li u 
2 0 1 5a }. N o ncli nical st u dies usi n g xe n o graft ca ncer m o dels pr o vi de c o m pelli n g e vi de nce t hat 
ma gr oli ma b tri g gers p ha g oc yt osis a n d eli mi nati o n of ca ncer cells fr o m h u ma n s oli d t u m ors a n d 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 3
2 4 Oct o ber 2 0 2 3
he mat ol o gic mali g na ncies. Base d o n t his mec ha nis m of acti o n ( M O A) a n d its p ote nt n o ncli nical 
acti vit y, ma gr oli ma b is bei n g de vel o pe d as a n o vel t hera pe utic ca n di date f or s oli d t u m ors a n d 
he mat ol o gic mali g na ncies.
T he ma gr oli ma b cli nical de vel o p me nt pr o gra m re prese nts a n o vel strate g y f or t he treat me nt of 
ca ncer a n d is t he first t hera pe utic a ge nt t o tar get t he C D 4 7- SI R P α a xis. E xte nsi ve n o ncli nical 
st u dies ha ve de m o nstrate d acti vit y a gai nst b ot h h u ma n s oli d t u m ors ( breast, o varia n, pa ncreas, 
c ol o n, lei o m y osarc o ma, bla d der, pr ostate, a n d ot hers) a n d he mat ol o gic mali g na ncies 
( A M L, ac ute l y m p h o blastic le u ke mia, n o n- H o d g ki n l y m p h o ma [ N H L], m yel o ma, 
m yel o d ys plastic s y n dr o me [ M D S], a n d ot hers).
As per t he 2 0 2 0 i n vesti gat or’s br oc h ure (I B), ma gr oli ma b is bei n g i n vesti gate d as a n a ntica ncer 
t hera pe utic i n 6 o n g oi n g cli nical st u dies i n t he U S a n d U nite d Ki n g d o m, as m o n ot hera p y or i n 
c o m bi nati o n wit h ot her t hera pe utics, f or t he treat me nt of N H L, c ol orectal ca ncer ( C R C), A M L, 
M D S, a n d o varia n ca ncer. A t otal of 5 6 8 patie nts ha ve bee n treate d as per t he data c ut- off dates 
i n t he 2 0 2 0 I B.
W hile ma gr oli ma b has si n gle-a ge nt n o ncli nical a n d cli nical acti vit y, efficac y is best e n ha nce d i n 
c o m bi nati o n wit h ot her a ntica ncer a ge nts. N o ncli nical a n d cli nical st u dies ha ve s h o w n t hat 
ma gr oli ma b c o m bi nati o ns wit h c yt ot o xic a ge nts ca n e n ha nce pr o p ha g oc ytic si g nals o n t u m or 
cells t hr o u g h c yt ot o xicit y, w hic h ca n lea d t o s y ner gistic p ha g oc yt osis of t u m or cells a n d 
e n ha nce d acti vit y. As s uc h, ma gr oli ma b is bei n g e val uate d cli nicall y i n se veral c o m bi nati o ns 
wit h c yt ot o xic a ge nts i ncl u di n g c he m ot hera p y.
F or f urt her i nf or mati o n o n ma gr oli ma b, refer t o t he c urre nt I B.
1. 2. 2.   
N o ncli nic al P h ar m ac ol o g y a n d T o xic ol o g y
1. 2. 2. 1.  
P har mac ol o g y
I n vitr o st u dies of ma gr oli ma b acti vit y i ncl u de d pr otei n a n d cell- base d assa ys usi n g ca ncer cell 
li nes. Ma gr oli ma b s h o we d hi g h bi n di n g affi nit y t o m o n o meric a n d bi vale nt h u ma n C D 4 7 a nti ge n 
wit h a K
D  of 8 × 1 0- 9 a n d 8 × 1 0- 1 2 M, res pecti vel y. Ma gr oli ma b b o u n d t o c y n o m ol g us m o n ke y 
a n d h u ma n C D 4 7 wit h hi g h affi nit y of K D  = 1 0 a n d 8. 0 p M, res pecti vel y, b ut di d n ot bi n d t o 
m o use C D 4 7. N o c o m ple me nt- de pe n de nt c yt ot o xicit y acti vit y of ma gr oli ma b was o bser ve d i n 
A M L cells, a n d n o a nti b o d y- de pe n de nt cell- me diate d c yt ot o xicit y acti vit y of ma gr oli ma b was 
o bser ve d i n Raji a n d H L 6 0 cells. Ma gr oli ma b-i n d uce d macr o p ha ge- me diate d p ha g oc yt osis i n rat 
m yel o ma a n d H L 6 0 cells a n d di d n ot i n d uce a p o pt osis i n A M L cells. E x pressi o n of C D 4 7 was 
o bser ve d o n h u ma n peri p heral bl o o d cells, a n d ma gr oli ma b di d n ot tri g ger p ha g oc yt osis b y 
h u ma n macr o p ha ges of n or mal re d bl o o d cells ( R B Cs) or n or mal h u ma n b o ne marr o w cells i n 
vitr o b ut was a p ote nt i n d ucer of p ha g oc yt osis of C D 4 7-e x pressi n g A M L cells i n vitr o. 
Treat me nt of A M L cells wit h h y dr o x y urea ( H U) ha d n o effect o n ma gr oli ma b-i n d uce d 
p ha g oc yt osis, n or di d H U treat me nt tri g ger ma gr oli ma b-i n d uce d p ha g oc yt osis of n or mal b o ne 
marr o w cells. I n c o ntrast, t he c o m bi nati o n of ma gr oli ma b a n d a vel u ma b effecti vel y e n ha nce d 
p ha g oc yt osis of o varia n ca ncer cells b y h u ma n macr o p ha ges c o m pare d t o ma gr oli ma b or 
a vel u ma b al o ne. M ore o ver, t he c o m bi nati o n of ma gr oli ma b wit h c yt ot o xic a ge nt azaciti di ne at a 
cli nicall y rele va nt c o nce ntrati o n e n ha nce d p ha g oc yt osis of H L 6 0 cells i n vitr o w he n c o m pare d t o 
ma gr oli ma b or azaciti di ne al o ne.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 4
2 4 Oct o ber 2 0 2 3
N o ncli nical i n vi v o p har mac ol o g y st u dies usi n g xe n o graft ca ncer m o dels pr o vi de c o m pelli n g 
e vi de nce t hat ma gr oli ma b tri g gers p ha g oc yt osis a n d eli mi nati o n of ca ncer cells fr o m m ulti ple 
h u ma n s oli d t u m ors a n d he mat ol o gic mali g na ncies. O verall, ma gr oli ma b i n c o m bi nati o n wit h 
azaciti di ne, trast uz u ma b, rit u xi ma b, cet u xi ma b, a n d pa nit u m u ma b de m o nstrate d a d diti ve effect 
o n eli mi nati n g ca ncer cells, res ulti n g i n a l o n g-ter m re missi o n a n d i ncrease d s ur vi val of a ni mals.
Rece pt or occ u pa nc y ( R O) assa ys s h o we d t hat o pti mal a ntit u m or acti vit y ( p ha g oc yt osis) i n 
H L 6 0 cells a n d pri mar y h u ma n A M L cells c o ul d be ac hie ve d wit h o ut f ull C D 4 7 R O.
T he safet y p har mac ol o g y e val uati o ns as part of a G o o d La b orat or y Practice 8- wee k t o xic ol o g y 
st u d y de m o nstrate d n o ma gr oli ma b-relate d effects o n ce ntral ner v o us s yste m ( C N S), 
car di o vasc ular, or res pirat or y f u ncti o n i n c y n o m ol g us m o n ke y.
1. 2. 2. 2.  
T o xic ol o g y
I n i n vitr o st u dies, ma gr oli ma b was n ot he m ol ytic a n d t here was n o e vi de nce of a d verse 
ele vati o ns of pr oi nfla m mat or y c yt o ki nes.
I n t he pi v otal 8- wee k re peat- d ose t o xic ol o g y st u d y, ma gr oli ma b was a d mi nistere d t o 
c y n o m ol g us m o n ke ys via a 1- h o ur i ntra ve n o us (I V) i nf usi o n as a pri mi n g d ose of 5 m g/ k g i n 
Wee k 1 ( Da y 1), f oll o we d b y t wice- wee kl y mai nte na nce d oses f or 7 c o nsec uti ve wee ks at d oses 
ra n gi n g fr o m 5 t o 1 0 0 m g/ k g.
Treat me nt-relate d fi n di n gs were li mite d t o c ha n ges i n he mat ol o g y a n d cli nical c he mistr y 
para meters a n d er yt hr oi d cell m or p h ol o g y.
He mat ol o g y c ha n ges i ncl u de d decreases i n R B C mass ass ociate d wit h decreases i n mea n 
c or p usc ular v ol u me a n d ha pt o gl o bi n; i ncreases i n mea n c or p usc ular he m o gl o bi n c o nce ntrati o n, 
retic ul oc ytes, a n d R B C distri b uti o n wi dt h; R B C m or p h ol o g y c ha n ges i ncl u di n g s p her oc ytes 
( micr oc ytes), ecce ntr oc ytes, at y pical er yt hr oc yte fra g me nts c o nsiste nt wit h er yt hr oc yte i nj ur y, 
er yt hr oc yte cl u m pi n g, a n d lar ge platelets; a n d c ha n ges ass ociate d wit h i ncrease d er yt hr o p oiesis 
c o nsisti n g of a nis oc yt osis, p ol yc hr o mat o p hilic macr oc ytes, a n d i ncrease d t otal bilir u bi n.
C ha n ges i n bl o o d cell m or p h ol o g y were c o nsiste nt wit h pre vi o us st u dies a n d c o nsi dere d t o be 
ass ociate d wit h accelerate d R B C destr ucti o n/cleara nce a n d i ncrease d er yt hr o p oiesis.
A d diti o nal cli nical c he mistr y c ha n ges were o bser ve d at t he hi g hest d ose o nl y ( 1 0 0 m g/ k g), 
w hic h i ncl u de d a sli g ht decrease i n al b u mi n, a sli g ht i ncrease i n gl o b uli n, a n d a c orres p o n di n g 
decrease i n al b u mi n: gl o b uli n rati o. T here was partial t o c o m plete rec o ver y f or all 
treat me nt-relate d c ha n ges e xce pt f or i ncrease d s plee n wei g hts i n males a n d fe males at 5 0 a n d 
1 0 0 m g/ k g at rec o ver y necr o ps y, w hic h ha d n o macr osc o pic or micr osc o pic c orrelate. Base d o n 
t hese res ults, t he hi g hest n o n –se verel y t o xic d ose f or t his st u d y was c o nsi dere d t o be 1 0 0 m g/ k g, 
t he hi g hest d ose e val uate d.
Re pr o d ucti ve a n d de vel o p me ntal t o xic ol o g y st u dies ha ve n ot bee n c o n d ucte d i n h o use, b ut all 
t he a vaila ble data (literat ure, data fr o m k n oc k o ut mice, a n d li mite d cli nical data) s u g gest n o r ole 
f or C D 4 7 o n e m br y o-fetal de vel o p me nt.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 5
2 4 Oct o ber 2 0 2 3
1. 2. 3.   
Cli nic al B ac k gr o u n d f or M a gr oli m a b
1. 2. 3. 1.  
S u m mar y of Cli nical P har mac ol o g y
Cli nical p har mac o ki netic ( P K) data ha ve bee n c ollecte d i n all o n g oi n g st u dies of ma gr oli ma b 
c o n d ucte d t o date. P har mac o ki netic data ha ve bee n a nal yze d i n a P hase 1 st u d y ( S CI -C D 4 7- 0 0 1) 
i n patie nts wit h s oli d t u m or. I n t his st u d y, patie nts were treate d wit h wee kl y ma gr oli ma b d oses 
ra n ge d fr o m 0. 1 t o 4 5 m g/ k g, wit h i ncreasi n g ser u m c o nce ntrati o ns ass ociate d wit h i ncreasi n g 
d ose. N o nli near P K c o nsiste nt wit h tar get- me diate d cleara nce was o bser ve d o ver t his d ose ra n ge. 
H o we ver, at mai nte na nce d oses of 1 0 m g/ k g a n d a b o ve, tar get- me diate d cleara nce was sat urate d 
wit hi n t he d osi n g re gi me n, a n d tr o u g h le vels ass ociate d wit h ma gr oli ma b efficac y i n n o ncli nical 
st u dies were ac hie ve d. Ni ne of 8 8 ( 1 0 %) e val ua ble patie nts teste d p ositi ve f or a nti dr u g a nti b o d y 
( A D A) a gai nst ma gr oli ma b at a n y ti me p oi nt i ncl u di n g baseli ne; A D A p ositi vit y ha d n o i m pact 
o n P K or cli nical safet y i n t hese patie nts.
I n a P hase 1 A M L st u d y ( S CI- C D 4 7- 0 0 2), si milar t o t he s oli d t u m or P hase 1 st u d y, n o nli near P K 
c o nsiste nt wit h tar get- me diate d cleara nce was o bser ve d. T hree of 2 0 ( 1 5 %) e val ua ble patie nts 
teste d p ositi ve f or A D A a gai nst ma gr oli ma b at a n y ti me p oi nt i ncl u di n g baseli ne; A D A 
p ositi vit y ha d n o i m pact o n P K. A nti dr u g a nti b o d y p ositi vit y i n eit her st u d y was n ot ass ociate d 
wit h i ncrease d a d verse e ve nts ( A Es).
Preli mi nar y P K data of ma gr oli ma b fr o m ot her o n g oi n g st u dies ( 5 F 9 0 0 3, 5 F 9 0 0 4, a n d 5 F 9 0 0 5) 
of ma gr oli ma b i n dicate si milar P K pr o perties acr oss all t u m or p o p ulati o ns a n d i n t he prese nce of 
c oa d mi nistere d dr u gs. Acr oss all st u dies, 4 6 of 4 3 0 ( 1 1 %) patie nts teste d p ositi ve f or A D A 
a gai nst ma gr oli ma b at a n y ti me p oi nt i ncl u di n g baseli ne. A nti dr u g a nti b o d y p ositi vit y was n ot 
ass ociate d wit h c ha n ges i n P K or A E pr ofile.
A preli mi nar y p o p ulati o n P K a nal ysis of c o m bi ne d ma gr oli ma b P K data i n dicate d t hat res ults f or 
ma gr oli ma b p o p ulati o n P K were t y pical of ot her n o nli near a nti b o dies. N o cli nicall y si g nifica nt 
c o variates of P K varia bilit y were i de ntifie d.
1. 2. 3. 2.  
S u m mar y of Cli nical Safet y
Ma gr oli ma b is a d mi nistere d as a n I V i nf usi o n a n d it is c urre ntl y bei n g st u die d i n 6 cli nical 
st u dies. T w o c o m plete d si n gle-a ge nt P hase 1 st u dies i ncl u de St u d y S CI-C D 4 7 -0 0 1 i n patie nts 
wit h a d va nce d s oli d t u m ors a n d l y m p h o mas, a n d St u d y S CI -C D 4 7 -0 0 2 i n patie nts wit h a d va nce d 
later li ne A M L, al o n g wit h 2 P hase 1 b part nere d st u dies i n A M L as well as U C. F o ur 
c o m bi nati o n st u dies i ncl u de t he f oll o wi n g: St u d y 5 F 9 0 0 3, a P hase 1 b/ 2 st u d y of ma gr oli ma b 
wit h rit u xi ma b i n patie nts wit h a d va nce d later li ne N H L; St u d y 5 F 9 0 0 4, a P hase 1 b/ 2 st u d y of 
ma gr oli ma b wit h cet u xi ma b i n patie nts wit h s oli d t u m or a n d C R C; St u d y 5 F 9 0 0 5, a P hase 1 b 
st u d y of ma gr oli ma b wit h azaciti di ne i n patie nts wit h A M L a n d M D S; a n d St u d y 5 F 9 0 0 6, a 
P hase 1 b st u d y of ma gr oli ma b wit h a vel u ma b i n patie nts wit h s oli d t u m or a n d o varia n ca ncer. As 
of J ul y 2 0 2 0, o ver 5 0 0 patie nts ha ve bee n treate d wit h ma gr oli ma b. O verall, t he safet y pr ofile 
has bee n acce pta ble wit h ma gr oli ma b as m o n ot hera p y or i n c o m bi nati o n, wit h n o ma xi m u m 
t olerate d d ose ( M T D) reac he d i n a n y st u d y wit h d osi n g u p t o 4 5 m g/ k g. T w o a ntici pate d a d verse 
reacti o ns i ncl u de d o n-tar get a ne mia a n d i nf usi o n-relate d reacti o ns (I R Rs), w hic h are e x pecte d 
wit h m A bs. I m p orta ntl y, o n-tar get a ne mia d ue t o C D 4 7 bl oc ka de- me diate d R B C cleara nce was 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 6
2 4 Oct o ber 2 0 2 3
miti gate d wit h a pri mi n g/ mai nte na nce d ose strate g y. T he a vera ge he m o gl o bi n decli ne wit h t he 
first ( pri mi n g) d ose was bet wee n a p pr o xi matel y 0. 4 t o 1. 5 g/ d L acr oss i n dicati o ns, wit h ma n y 
patie nts i m pr o vi n g t heir he m o gl o bi n o n t hera p y bac k t o baseli ne wit h a decrease i n R B C 
tra nsf usi o n re q uire me nts f or t h ose patie nts w h o were tra nsf usi o n- de pe n de nt at baseli ne.
Ma gr oli ma b has bee n e val uate d as a m o n ot hera p y or i n c o m bi nati o n i n m ulti ple s oli d t u m or 
t y pes. I n t he P hase 1 St u d y S CI- C D 4 7- 0 0 1 of ma gr oli ma b m o n ot hera p y, 8 8 patie nts wit h 
a d va nce d s oli d t u m ors were treate d wit h ma gr oli ma b d oses u p t o 4 5 m g/ k g. N o M T D was 
reac he d. As per t he 2 0 2 0 I B, acr oss 5 4 8 patie nts treate d wit h ma gr oli ma b, w hic h i ncl u des b ot h 
s oli d t u m ors a n d he mat ol o gic mali g na ncies, fati g ue, a ne mia, a n d hea dac he were t he 3 m ost 
fre q ue ntl y re p orte d A Es ( 4 3. 0 %, 4 0. 8 %, a n d 3 6. 4 % of patie nts, res pecti vel y). Patie nts 
e x perie nce d m ostl y Gra de 1 a n d 2 fati g ue ( 2. 8 % of patie nts re p orte d se vere fati g ue).
A ne mia is t he m ost c o m m o n treat me nt-relate d A E, re p orte d i n 3 5. 4 % of patie nts. A p pr o xi matel y 
1 3 % of all patie nts e x perie nce d a ne mia Gra de 1 or 2, a n d 2 2 % se vere a ne mia. N ota bl y ma n y of 
t h ose patie nts wit h se vere a ne mia occ urre d i n patie nts wit h A M L a n d M D S, w h o ha ve se vere 
a ne mia at baseli ne. A ne mia was t y picall y ma nifeste d as a decli ne i n he m o gl o bi n o bser ve d wit hi n 
t he first 2 wee ks of treat me nt. T he i nitial decrease i n he m o gl o bi n after t he first d ose is o n 
a vera ge 0. 5 t o 2 g/ d L. I n patie nts wit h s oli d t u m ors, t he fall i n he m o gl o bi n was f oll o we d b y a 
c o m pe nsat or y retic ul oc yt osis, wit h ma n y patie nts e x perie nci n g a gra d ual ret ur n t o baseli ne 
des pite c o nti n ue d d osi n g. T he c ha n ges i n he m o gl o bi n a n d retic ul oc ytes descri be d wit h 
ma gr oli ma b treat me nt are fairl y c o nsiste nt acr oss t u m or t y pes a n d are s h o w n i n Fi g ure 1 . 
H y per bilir u bi ne mia ( pre d o mi natel y u nc o nj u gate d) is i n dicati ve of e xtra vasc ular he m ol ysis 
c o nsiste nt wit h p ha g oc ytic re m o val of R B Cs arisi n g fr o m t he bl oc ka de of C D 4 7 si g nali n g. 
A d mi nistrati o n of a l o w pri mi n g d ose of ma gr oli ma b miti gate d o n-tar get a ne mia, a n effect t hat is 
m ostl y o bser ve d after t he first d ose.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 7
2 4 Oct o ber 2 0 2 3
Fi g ure 1.
Effect of M a gr oli m a b o n A ne mi a a n d Miti g ati o n wit h a 
Pri mi n g/ M ai nte n a nce D osi n g Re gi me n
T he re d bl o o d cell pr ofile of a s oli d t u m or patie nt treate d wit h ma gr oli ma b m o n ot hera p y is s h o w n { Si kic 2 0 1 9 }.
I nf usi o n-relate d reacti o ns are als o a c o m m o nl y o bser ve d A E wit h ma gr oli ma b. I n t otal, 2 9 % of 
patie nts re p orte d at least 1 I R R. M ost c o m m o n si g ns/s y m pt o ms of I R Rs relate d t o ma gr oli ma b 
i ncl u de d c hills, p yre xia, bac k pai n, hea dac he, na usea, v o miti n g, d ys p nea, a ne mia, a n d bl o o d 
bilir u bi n i ncrease. T hese I R Rs were ge nerall y o bser ve d d uri n g t he i nitial 2 d oses of ma gr oli ma b. 
C urre nt rec o m me n dati o ns f or pre me dicati o n a n d I R R ma na ge me nt are descri be d i n Secti o ns 5. 6  
a n d 7. 8. 1. 2 . Lastl y, he ma g gl uti nati o n ( R B C a g gl uti nati o n) as o bser ve d o n t he peri p heral s mear is 
a c o m m o n treat me nt effect a n d was re p orte d as a treat me nt-relate d A E i n 1 1. 8 % of all patie nts.
Tra nsie nt he ma g gl uti nati o n is o bser ve d after t he i nitial pri mi n g or first mai nte na nce d ose of 
dr u g, h o we ver, it is less c o m m o n t hereafter, a n d it has n ot bee n c o nsiste ntl y c orrelate d wit h a n y 
cli nical se q uelae.
I n s u m mar y, as of J ul y 2 0 2 0, 5 6 8 patie nts ( 3 4 6 s oli d t u m or/l y m p h o ma patie nts a n d 
2 2 2 A M L/ M D S patie nts) ha ve bee n treate d wit h ma gr oli ma b as m o n ot hera p y or i n c o m bi nati o n. 
Base d o n t his a g gre gate safet y data, ma gr oli ma b has a n acce pta ble safet y pr ofile b ot h as 
m o n ot hera p y a n d i n c o m bi nati o n wit h ot her a ge nts (rit u xi ma b, ge mcita bi ne, o xali plati n, 
cet u xi ma b, a vel u ma b, or azaciti di ne) acr oss m ulti ple a d va nce d s oli d t u m or a n d he mat ol o gic 
mali g na ncies. Refer t o t he ma gr oli ma b I B f or f urt her details.
1 6 
1 4 
::::i" 
"' C 1 2 -
0) 
1 0 
C 
Gr a d e  2  a n e mi a 
.. 0 
8 
0 
0) 
0 
6 
E 
Q.) 
4 
::: c 
D o s e  ( m g/k g) 
3 0 
3 0   
3 0   
3 0   
3 0 
3 0 
W e e k  
1 
2 
3 
4 
5 
6 
7 
5 F 9 
f pri mi n g 
1  m g /k g + 5 F 9 m ai nt e n a n c e 3 0 m g /k g  w e e kl y 
H e m o gl o bi n l o w er li mit of n or m al > 1 1 . 7-1 3 . 5  g/d L 
R eti c ul o c yt e s  u p p er li mit of n or m al  <  2. 2 8 % 
1 0 
8 
:: 0 
ct > 
d". 
6 
C ") 
C 
0 
C ") 
4 - s. 
ct > 
(/) -
2 
:::: R 
0 
3 0 
8 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 8
2 4 Oct o ber 2 0 2 3
1. 2. 3. 3.  
S u m mar y of Cli nical Efficac y
Cli nical efficac y wit h ma gr oli ma b has bee n o bser ve d i n m ulti ple he mat ol o gic a n d s oli d t u m or 
mali g na ncies. I n t he P hase 1 St u d y S CI- C D 4 7- 0 0 1 of ma gr oli ma b m o n ot hera p y i n a d va nce d 
s oli d t u m ors, 2 patie nts wit h clear cell o varia n a n d fall o pia n t u be carci n o mas ac hie ve d a partial 
res p o nse per Res p o nse E val uati o n Criteria i n S oli d T u m ors ( R E CI S T, Versi o n 1. 1) wit h ti me t o 
pr o gressi o n of 5. 2 a n d 9. 2 m o nt hs, res pecti vel y { Si kic 2 0 1 9 }. I n a P hase 1 b/ 2 st u d y of 
ma gr oli ma b i n c o m bi nati o n wit h cet u xi ma b i n a d va nce d later li ne C R C patie nts ( St u d y 5 F 9 0 0 4), 
2 o bjecti ve res p o nses o ut of 3 2 patie nts ( 6 %) were o bser ve d i n a d va nce d later li ne metastatic 
K R A S wil dt y pe C R C patie nts w h o were refract or y t o cet u xi ma b wit h a disease c o ntr ol rate of 
5 0 % { Fis her 2 0 2 0 }. T he O S i n K R A S wil dt y pe a n d K R A S m uta nt C R C patie nts treate d wit h 
ma gr oli ma b a n d cet u xi ma b was 9. 5 a n d 7. 6 m o nt hs, res pecti vel y. T hese data ma y c o m pare 
fa v ora bl y t o hist orical data i n K R A S wil dt y pe a n d m uta nt patie nts treate d wit h sta n dar d of care 
wit h a me dia n O S of 8. 0 a n d 6. 5 m o nt hs, res pecti vel y { Va n C utse m 2 0 1 8 }.
I n he mat ol o gic mali g na ncies, efficac y has bee n o bser ve d i n N H L, M D S, a n d A M L. I n st u d y 
5 F 9 0 0 3, patie nts wit h a d va nce d later li ne N H L were treate d wit h ma gr oli ma b i n c o m bi nati o n 
wit h rit u xi ma b. I n 9 7 N H L patie nts e val ua ble f or efficac y t hat i ncl u de d diff use lar ge B-cell 
l y m p h o ma ( D L B C L) a n d i n d ole nt l y m p h o ma, t he O R R was 4 5 % wit h a c o m plete res p o nse ( C R) 
rate of 1 9 %. T he O R R i n D L B C L was 3 6 % i n 5 9 patie nts a n d 6 1 % f or 3 8 i n d ole nt l y m p h o ma 
patie nts treate d. I n St u d y 5 F 9 0 0 5, patie nts wit h u ntreate d A M L i neli gi ble f or i n d ucti o n 
c he m ot hera p y a n d u ntreate d hi g her-ris k M D S patie nts were treate d wit h ma gr oli ma b i n 
c o m bi nati o n wit h azaciti di ne. I n 2 5 A M L patie nts, t he O R R was 6 4 % a n d C R rate was 4 0 %. I n 
3 3 M D S patie nts, t he O R R was 9 1 % a n d C R rate was 4 2 %. N o me dia n D O R was reac he d f or 
eit her c o h ort wit h me dia n f oll o w- u p peri o d of 9. 4 m o nt hs f or A M L a n d 5. 8 m o nt hs f or M D S.
I n s u m mar y, ma gr oli ma b has de m o nstrate d c o m bi nati o n efficac y acr oss b ot h s oli d t u m ors a n d 
he mat ol o gic mali g na ncies. Refer t o t he ma gr oli ma b I B f or f urt her details.
1. 3.  
I nf or m ati o n A b o ut D ocet a xel
1. 3. 1.   
Descri pti o n of D ocet a xel
D oceta xel ( Ta x otere) is a n a ntica ncer c he m ot hera p y dr u g classifie d as a n a nti- micr ot u b ule 
i n hi bit or a n d ta xa ne. D oceta xel is i n dicate d f or m ulti ple s oli d t u m ors as a si n gle a ge nt 
{ Ta x otere ® 1 9 9 5 , Ta x otere ® 1 9 9 6 }.
1. 3. 2. 
Cli nic al D at a f or D ocet a xel
D oceta xel is a p pr o ve d f or use as m o n ot hera p y i n m ulti ple s oli d t u m ors i ncl u di n g N S C L C, hea d 
a n d nec k s q ua m o us cell carci n o ma, breast ca ncer, h or m o ne refract or y pr ostate ca ncer, a n d 
gastric a de n ocarci n o ma. D oceta xel is als o wi del y use d as sta n dar d of care i n m ulti ple s oli d 
t u m ors, i ncl u di n g m U C a n d m S C L C, w h o fail fr o ntli ne c he m ot hera p y a n d/ or i m m u ne 
c hec k p oi nt t hera p y { Ta x otere ® 1 9 9 5 , Ta x otere ® 1 9 9 6 }.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 2 9
2 4 Oct o ber 2 0 2 3
T he m ost c o m m o n A Es acr oss all d oceta xel i n dicati o ns are i nfecti o ns, ne utr o pe nia, a ne mia, 
fe brile ne utr o pe nia, h y perse nsiti vit y, t hr o m b oc yt o pe nia, ne ur o pat h y, d ys ge usia, d ys p nea, 
c o nsti pati o n, a n ore xia, nail dis or ders, fl ui d rete nti o n, ast he nia, pai n, na usea, diarr hea, v o miti n g, 
m uc ositis, al o pecia, s ki n reacti o ns, a n d m yal gia { Ta x otere ® 1 9 9 5 , Ta x otere ® 1 9 9 6 }. D oceta xel 
is c o ntrai n dicate d i n patie nts wit h ne utr o p hil c o u nts less t ha n 1 5 0 0 cells/ m m3 a n d i n patie nts 
wit h h y perse nsiti vit y t o d oceta xel or p ol ys or bate 8 0. D oceta xel carries a blac k b o x war ni n g f or 
t o xic deat hs, he pat ot o xicit y, ne utr o pe nia, h y perse nsiti vit y reacti o ns, a n d fl ui d rete nti o n. I n 
a d diti o n, c uta ne o us reacti o ns, se vere s ki n t o xicit y, ne ur ol o gic reacti o ns (i ncl u di n g parest hesia, 
d ysest hesia, a n d pai n), ast he nia, a n d p ote ntial fetal har m ha ve bee n o bser ve d wit h d oceta xel.
D oceta xel is sta n dar d of care as m o n ot hera p y f or a d va nce d later li ne patie nts i n m ulti ple s oli d 
t u m or t y pes i ncl u di n g m N S C L C, m U C, a n d m S C L C, i n dicati o ns st u die d i n t his pr ot oc ol. I n 
ge neral t he efficac y o bser ve d wit h d oceta xel m o n ot hera p y i n t hese t u m or t y pes i n patie nts w h o 
fail sta n dar d c he m ot hera p y, i m m u ne c hec k p oi nt i n hi bit or, or t he c o m bi nati o n res ults i n a n O R R 
of a p pr o xi matel y 1 0 % (ra n gi n g fr o m 9 % t o 1 3 % i n S C L C, U C, a n d N S C L C) { Bell m u nt 2 0 1 7 , 
Ritt me yer 2 0 1 7 , S mit 1 9 9 8 }. Me dia n P F S ra n ges fr o m a p pr o xi matel y 3 t o 5 m o nt hs i n t hese 
i n dicati o ns.
I n s u m mar y, d oceta xel is use d as a sta n dar d- of-care o pti o n f or sec o n d a n d later li nes of t hera p y 
f or m ulti ple s oli d t u m or t y pes after fr o ntli ne c he m ot hera p y a n d/ or i m m u ne c hec k p oi nt t hera p y.
1. 4.  
I nf or m ati o n A b o ut A u xili ar y Me dici n al Pr o d ucts 
Aceta mi n o p he n (als o k n o w n as paraceta m ol), di p he n h y dra mi ne, a n d de xa met has o ne are 
c o nsi dere d a u xiliar y me dici nal pr o d ucts ( A x M Ps) f or t his cli nical st u d y ( A p pe n di x 2 ). 
Aceta mi n o p he n is a p pr o ve d f or pai n relief a n d fe ver re d ucti o n. Di p he n h y dra mi ne is a n 
a nti hista mi ne a n d is a p pr o ve d f or a meli orati o n of aller gic reacti o ns. De xa met has o ne is a n 
a nti-i nfla m mat or y me dicati o n a n d is use d f or t he a meli orati o n of aller gic reacti o ns. T he use of 
t hese me dicati o ns i n t his st u d y is descri be d i n Secti o ns 5. 6  a n d 7. 8. 1. 2 . 
A d diti o nal details o n aceta mi n o p he n, di p he n h y dra mi ne, a n d de xa met has o ne ca n be f o u n d i n t he 
prescri bi n g i nf or mati o n.
1. 5.   
R ati o n ale f or T his St u d y
Str o n g n o ncli nical a n d cli nical rati o nale e xists f or c o m bi ni n g ma gr oli ma b wit h c he m ot hera p y 
a ge nts, i ncl u di n g ta xa nes. First, c he m ot hera pe utic a ge nts ha ve bee n de m o nstrate d t o e n ha nce 
pr o p ha g oc ytic si g nals o n t u m or cells t hat lea ds t o s y ner gistic a ntit u m or acti vit y w he n c o m bi ne d 
wit h ma gr oli ma b, a C D 4 7-tar geti n g a nti b o d y t hat bl oc ks t he a nti p ha g oc ytic si g nal. Si m ulta ne o us 
bl oc ka de of t he a nti p ha g oc ytic si g nal C D 4 7 b y ma gr oli ma b wit h u pre g ulati o n of pr o p ha g oc ytic 
si g nals via c he m ot hera pies ca n lea d t o s y ner gistic p ha g oc yt osis of t u m or cells b y macr o p ha ges. 
I n dee d, ma gr oli ma b c o m bi nati o n wit h ta xa nes ( paclita xel) le d t o e n ha nce d p ha g oc yt osis of s oli d 
t u m or cells i n vitr o a n d a statisticall y si g nifica nt re d ucti o n a n d eli mi nati o n of o varia n ca ncers i n 
vi v o, w he n c o m pare d t o si n gle-a ge nt t hera p y { Si kic 2 0 1 6 }. Cli nicall y, ma gr oli ma b has bee n 
c o m bi ne d wit h c yt ot o xic a ge nts a n d c he m ot hera p y (i ncl u di n g azaciti di ne, ge mcita bi ne, a n d 
o xali plati n) i n he mat ol o gic mali g na ncies i ncl u di n g A M L, M D S, a n d N H L. T hese a ge nts als o 
u pre g ulate pr o p ha g oc ytic si g nals a n d ha ve le d t o e n ha nce d c o m bi nati o n acti vit y wit h 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 0
2 4 Oct o ber 2 0 2 3
ma gr oli ma b i n n o ncli nical m o dels. I n t he cli nical setti n g, ma gr oli ma b a n d azaciti di ne ha ve le d t o 
a 9 1 % O R R i n patie nts wit h u ntreate d hi g her ris k M D S a n d a 6 4 % O R R i n u ntreate d A M L 
patie nts { Sall ma n 2 0 2 0 }. C o m bi nati o n efficac y als o has bee n o bser ve d wit h ma gr oli ma b i n 
c o m bi nati o n wit h c he m ot hera pe utic a ge nts ( ge mcita bi ne, o xali plati n, a n d rit u xi ma b) i n patie nts 
wit h a d va nce d later li ne D L B C L. I m p orta ntl y, t he a d diti o n of ma gr oli ma b t o t hese 
c yt ot o xic/c he m ot hera pe utic a ge nts di d n ot ge nerall y e xacer bate t o xicities a n d t he c o m bi nati o n 
ha d a n acce pta ble safet y pr ofile wit h n o M T D reac he d ( Secti o n 1. 2. 3. 2 ).
1. 5. 1.  
S afet y R u n-i n C o h ort 1 a n d P h ase 2 C o h ort 1
Sta n dar d- of-care t hera p y f or ma n y ne wl y dia g n ose d metastatic s oli d t u m or ca ncers i ncl u de a 
plati n u m- base d c he m ot hera pe utic a ge nt a n d i m m u ne c hec k p oi nt i n hi bit or (ie, a nti- P D- 1/ P D- L 1 
a nti b o dies) w here a p plica ble. E nc o ura gi n g cli nical acti vit y has bee n see n s pecificall y wit h 
i m m u ne c hec k p oi nt i n hi bit ors as m o n ot hera p y or i n c o m bi nati o n wit h c he m ot hera p y i n t he 
fr o ntli ne setti n g a n d has dra maticall y i m pr o ve d res p o nse rates, P F S, a n d O S. H o we ver, patie nts 
wit h s oli d t u m ors w h o fail fr o ntli ne c he m ot hera pe utic re gi me ns a n d/ or i m m u ne c hec k p oi nt 
i n hi bit ors ha ve a p o or pr o g n osis wit h ge nerall y li mite d treat me nt o pti o ns. F or t he m ost part, 
si n gle-a ge nt or c o m bi nati o n c he m ot hera p y re prese nts t he maj or sta n dar d care o pti o n i n t he 
a d va nce d later li ne metastatic setti n g. F or ma n y s oli d t u m ors (i ncl u di n g t he s oli d t u m or t y pes 
e val uate d i n t his st u d y), ta xa nes re prese nt t he pre d o mi na nt sta n dar d- of-care c he m ot hera p y 
o pti o n p ost- plati n u m/i m m u ne c hec k p oi nt i n hi bit or t hera p y. W hile ta xa nes are mai nl y use d i n 
t hese i n dicati o ns p ost plati n u m- base d c he m ot hera p y a n d/ or i m m u ne c hec k p oi nt i n hi bit or t hera p y, 
t he cli nical acti vit y is m o dest. S pecificall y, t he O R Rs i n S C L C, U C, a n d N S C L C ra n ge fr o m 9 %, 
1 2. 4 %, a n d 1 3 %, res pecti vel y { Bell m u nt 2 0 1 7 , Ritt me yer 2 0 1 7 , S mit 1 9 9 8 }. Me dia n P F S i n 
t hese t u m or t y pes i n t his li ne of t hera p y is a p pr o xi matel y 3 t o 5 m o nt hs. T hese p o p ulati o ns 
t heref ore re prese nt a hi g h u n met me dical nee d. N o vel re gi me ns, es peciall y t h ose t hat ca n safel y 
a n d effecti vel y c o m bi ne wit h c he m ot hera p y, are nee de d t o i ncrease cli nical be nefit.
T he str o n g n o ncli nical a n d cli nical data s u p p ort t he e val uati o n of ma gr oli ma b i n c o m bi nati o n 
wit h c he m ot hera p y, i ncl u di n g ta xa nes, i n patie nts wit h a d va nce d later li ne s oli d t u m ors.
O ne of t he o bjecti ves of t his P hase 2 st u d y c o h ort is t o e val uate t he safet y, t olera bilit y, a n d 
rec o m me n de d P hase 2 d ose of ma gr oli ma b i n c o m bi nati o n wit h d oceta xel i n s oli d t u m ors. I n 
P hase 2 C o h ort 1, N S C L C, S C L C, a n d U C will be s pecificall y e val uate d f or efficac y gi ve n t hat 
ta xa nes re prese nt t he pre d o mi na nt sta n dar d- of-care c he m ot hera p y o pti o n i n t hese t u m or t y pes. 
D oceta xel was s pecificall y c h ose n gi ve n its hi g h usa ge patter n wit hi n ta xa nes i n t he U S a n d 
E ur o pe as well as t he lac k of a ntici pate d o verla p pi n g t o xicities.
I n s u m mar y, str o n g n o ncli nical a n d cli nical rati o nale e xists f or e val uati n g a c o m bi nati o n of 
ma gr oli ma b a n d d oceta xel i n s oli d t u m or mali g na ncies.
1. 6.   
R ati o n ale f or D ose Selecti o n of M a gr oli m a b
T he rati o nale f or t he ma gr oli ma b d ose pr o p ose d i n t his st u d y ori gi nates fr o m safet y, efficac y, 
a n d P K/ p har mac o d y na mic ( P D) data, a n d m o delli n g a n d si m ulati o n a nal yses base d o n data 
o btai ne d fr o m all o n g oi n g a n d c o m plete d cli nical st u dies wit h ma gr oli ma b i n patie nts wit h s oli d 
t u m ors, N H L, a n d A M L/ M D S.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 1
2 4 Oct o ber 2 0 2 3
I n t he first-i n- h u ma n st u d y of ma gr oli ma b ( S CI- C D 4 7- 0 0 1) i n patie nts wit h s oli d t u m ors a n d 
l y m p h o mas, after a n i nitial pri mi n g d ose of 1 m g/ k g o n t he first da y, ma gr oli ma b was teste d as a 
m o n ot hera p y at wee kl y d oses of u p t o 4 5 m g/ k g. T he use of a n i nitial 1 m g/ k g pri mi n g d ose was 
i nte grate d i nt o t he d osi n g re gi me n t o miti gate t he o n-tar get a ne mia i n d uce d b y C D 4 7 bl oc ka de. 
A n i nitial pri mi n g d ose lea ds t o eli mi nati o n of a ge d R B Cs t hat are se nsiti ve t o C D 4 7 bl oc ka de 
a n d tri g gers retic ul oc yt osis of y o u n g R B Cs t hat are n ot affecte d b y C D 4 7 bl oc ka de { C he n 
2 0 1 8 }. Utilizi n g a pri mi n g d ose lea ds t o a n i nitial, tra nsie nt, a n d mil d a ne mia t hat ge nerall y 
n or malizes bac k t o baseli ne o ver se veral wee ks, e ve n i n t he prese nce of re peate d t hera pe utic 
d oses of ma gr oli ma b { A d va ni 2 0 1 8 , Li u 2 0 1 5a , Si kic 2 0 1 9 }. 
I n a d diti o n, i n s oli d t u m ors w here t he c o m bi nati o n t hera p y (c he m ot hera p y or pe m br oliz u ma b) is 
gi ve n acc or di n g t o 3- wee k c ycles, d osi n g of ma gr oli ma b e ver y 3 wee ks o pti mizes patie nt a n d 
care gi ver c o n ve nie nce. Ma gr oli ma b 6 0 m g/ k g e ver y 3 wee ks is pre dicte d t o pr o vi de a si milar 
tr o u g h c o nce ntrati o n a n d R O as t he 3 0 m g/ k g e ver y 2 wee ks d ose, t he d ose bei n g use d i n 
P hase 3 st u dies i n A M L a n d M D S. Mai ntai ni n g a de q uate tr o u g h c o nce ntrati o n ma y be necessar y 
f or o pti mal efficac y c o nsi deri n g t hat s o me patie nts ma y e x perie nce d ose dela ys d ue t o t o xicit y. 
F urt her m ore, t he P K/ P D m o delli n g als o i n dicates t hat at t hese e xte n de d i nter val d osi n g 
re gi me ns, t he R O will be mai ntai ne d at ma xi mal le vels ( > 9 0 %) i n peri p heral bl o o d a n d t u m or 
tiss ues. T he pr o p ose d d osi n g re gi me n of ma gr oli ma b i n t his st u d y is e x pecte d t o ha ve a n 
acce pta ble safet y pr ofile base d o n t he e ntiret y of safet y data i n m ulti ple o nc ol o g y p o p ulati o ns, 
b ot h as a m o n ot hera p y a n d i n c o m bi nati o n wit h ot her t u m or-tar gete d a nti b o dies a n d 
c he m ot hera pe utics.
1. 6. 1.  
S afet y R u n-i n C o h ort 1 a n d P h ase 2 C o h ort 1
T he f oll o wi n g ma gr oli ma b d osi n g re gi me n is pr o p ose d f or Safet y R u n-i n C o h ort 1 a n d P hase 2 
C o h ort 1 o ver a 2 1- da y c ycle:
•
C ycle 1: pri mi n g ( 1 m g/ k g) o n Da y 1 a n d 3 0 m g/ k g o n Da ys 8 a n d 1 5
•
C ycle 2: wee kl y d oses of 3 0 m g/ k g o n Da ys 1, 8, a n d 1 5
•
C ycle 3 a n d o n war d: 6 0 m g/ k g e ver y c ycle o n Da y 1
1. 7.   
Ris k/ Be nefit Assess me nt f or t he St u d y
Patie nts wit h metastatic s oli d t u m ors w h o fail fr o ntli ne c o m bi nati o n c he m ot hera p y a n d/ or 
i m m u ne c hec k p oi nt i n hi bit or t hera p y ha ve li mite d treat me nt o pti o ns wit h a p o or pr o g n osis. I n 
ge neral, si n gle-a ge nt c he m ot hera p y (ie, ta xa nes) are utilize d i n t his setti n g acr oss se veral s oli d 
t u m or t y pes. H o we ver, res p o nse rates are a p pr o xi matel y 1 0 % wit h a li mite d me dia n O S. T h us, 
n o vel t hera pies t hat ca n safel y c o m bi ne wit h c he m ot hera p y t o e n ha nce efficac y are nee de d i n 
t his hi g h u n met nee d patie nt setti n g. 
Ma gr oli ma b ca n eli mi nate t u m or cells t hr o u g h macr o p ha ge- me diate d p ha g oc yt osis. Ma gr oli ma b 
acti vit y ca n be e n ha nce d wit h c he m ot hera pe utic a ge nts t hat ca n i ncrease pr o p ha g oc ytic si g nals 
o n t u m ors cells, lea di n g t o s y ner gistic p ha g oc yt osis. N o ncli nical data ha ve s h o w n t hat 
ma gr oli ma b i n c o m bi nati o n wit h ta xa nes lea d t o e n ha nce d p ha g oc yt osis of s oli d t u m or cells i n 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 2
2 4 Oct o ber 2 0 2 3
vitr o a n d pr ol o n ge d re missi o ns i n xe n o graft m o dels c o m pare d t o si n gle-a ge nt t hera p y. 
F urt her m ore, cli nical st u d y data has s h o w n t hat ma gr oli ma b ca n e n ha nce efficac y of c yt ot o xic 
a ge nts i ncl u di n g a n o ver 9 0 % O R R i n patie nts wit h ne wl y dia g n ose d hi g her-ris k M D S wit h 
ma gr oli ma b i n c o m bi nati o n wit h azaciti di ne { Sall ma n 2 0 2 0 }. A c o m bi nati o n st u d y wit h 
ma gr oli ma b a n d tra diti o nal c he m ot hera p y ( ge mcita bi ne, o xali plati n, a n d rit u xi ma b) is o n g oi n g i n 
patie nts wit h N H L t hat has als o s h o w n i nitial si g ns of acti vit y a n d a n acce pta ble safet y pr ofile. 
T h us, t he scie ntific rati o nale, n o ncli nical, a n d cli nical data s u p p ort a c o m bi nati o n of ma gr oli ma b 
wit h ta xa ne c he m ot hera p y, i ncl u di n g d oceta xel.
Treat me nt wit h t he pr o p ose d c o m bi nati o n of ma gr oli ma b a n d d oceta xel f or s oli d t u m ors is n ot 
a ntici pate d t o p ose a si g nifica ntl y i ncrease d ris k t o patie nts e nr olle d i n t his trial c o m pare d t o t he 
ris k of treat me nt wit h eit her a ge nt al o ne. Base d o n t he cli nical pr ofiles of ma gr oli ma b a n d 
d oceta xel, o verla p pi n g t o xicities (e xce pt f or p ote ntial a ne mia) are n ot a ntici pate d wit h t he 
c o m bi nati o n. W hile ma gr oli ma b d oes ca use a tra nsie nt, ge nerall y mil d t o m o derate a ne mia, 
d oceta xel ge nerall y i n d uces Gra de 1 or 2 a ne mia i n patie nts. P ote ntial a ne mia o bser ve d is 
ma na ge d b y a pri mi n g/ mai nte na nce d ose re gi me n f or ma gr oli ma b, fre q ue nt la b orat or y 
m o nit ori n g of bl o o d c o u nts, a n d R B C tra nsf usi o n g ui da nce. I n a d diti o n t o a ne mia, ne utr o pe nia, 
t hr o m b oc yt o pe nia, a n d i nfecti o ns ha ve bee n re p orte d i n patie nts treate d wit h ma gr oli ma b. 
S pecific cli nical a n d la b orat or y m o nit ori n g of ma gr oli ma b- a n d d oceta xel-relate d t o xicities will 
be i m ple me nte d i n t his st u d y. F urt her m ore, ma gr oli ma b has bee n c o m bi ne d wit h c yt ot o xic 
c he m ot hera p y ( ge mcita bi ne, o xali plati n, a n d rit u xi ma b i n N H L patie nts) wit h o ut o bser vati o n of 
e xacer bati o n of c he m ot hera p y t o xicities, wit h a n acce pta ble safet y pr ofile, a n d wit h n o M T D 
reac he d. T h us, t he a ntici pate d safet y pr ofile of ma gr oli ma b wit h ta xa ne c o m bi nati o ns re prese nt 
a n acce pta ble ris k- be nefit rati o t o patie nts.
D uri n g a pa n de mic, a d diti o nal p ote ntial ris ks t o patie nts ma y i ncl u de a de q uate st u d y dr u g 
a vaila bilit y, i nterr u pti o ns t o t he st u d y visit sc he d ule, a n d a d here nce t o pr ot oc ol-s pecifie d safet y 
m o nit ori n g or la b orat or y assess me nts. Refer t o A p pe n di x 4  f or f urt her details o n t he ris ks a n d 
ris k miti gati o n strate g y.
I n s u m mar y, base d o n str o n g scie ntific rati o nale, n o ncli nical a n d e mer gi n g cli nical data, li mite d 
o verla p pi n g t o xicities, a n d t he ris k miti gati o n meas ures bei n g i m ple me nte d f or t he pa n de mic, t he 
e val uati o n of ma gr oli ma b i n c o m bi nati o n wit h d oceta xel i n patie nts wit h s oli d t u m ors is 
a ntici pate d t o ha ve a n acce pta ble ris k- be nefit rati o t o t he patie nts e nr olle d i n t his st u d y.
1. 8.   
C o m pli a nce
T his st u d y will be c o n d ucte d i n c o m plia nce wit h t his pr ot oc ol, G o o d Cli nical Practice ( G C P), 
a n d all a p plica ble re g ulat or y re q uire me nts.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 3
2 4 Oct o ber 2 0 2 3
2.   
O B J E C TI V E S A N D E N D P OI N T S
Ta ble 1  prese nts t he st u d y o bjecti ves a n d e n d p oi nts. T he a nal ysis of t he e n d p oi nts is descri be d i n 
Secti o n 8 .
T a ble 1.
G S- U S- 5 4 8- 5 9 1 8: St u d y O bjecti ves a n d E n d p oi nts
Pri m ar y O bjecti ves
Pri m ar y E n d p oi nts
• 
T o e val uate t he safet y, t olera bilit y, a n d 
rec o m me n de d P hase 2 d ose of ma gr oli ma b + 
d oceta xel c o m bi nati o n t hera p y i n s oli d t u m ors 
( Safet y R u n-i n C o h ort 1, P hase 2 C o h orts 1a, 
1 b, a n d 1c)
•
T o e val uate t he efficac y of ma gr oli ma b + 
d oceta xel c o m bi nati o n t hera p y i n s oli d t u m ors 
as deter mi ne d b y i n vesti gat or-assesse d 
o bjecti ve res p o nse rate ( O R R) ( P hase 2 
C o h orts 1a, 1 b, a n d 1c)
• 
I nci de nce of a d verse e ve nts ( A Es) a n d la b orat or y 
a b n or malities acc or di n g t o t he Nati o nal Ca ncer 
I nstit ute ( N CI) C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E ve nts ( C T C A E), Versi o n 5. 0 ( A p pe n di x 5 ; 
Safet y R u n-i n C o h ort 1, P hase 2 C o h orts 1a, 1 b, a n d 
1c)
• 
O R R, defi ne d as t he pr o p orti o n of patie nts w h o 
ac hie ve a c o m plete res p o nse or partial res p o nse, as 
meas ure d b y Res p o nse E val uati o n Criteria i n S oli d 
T u m ors ( R E CI S T), Versi o n 1. 1, as deter mi ne d b y 
i n vesti gat or assess me nt ( P hase 2 C o h orts 1a, 1 b, a n d 
1c)
Sec o n d ar y O bjecti ves
Sec o n d ar y E n d p oi nts
• 
T o e val uate pr o gressi o n-free s ur vi val ( P F S) b y 
i n vesti gat or assess me nt ( P hase 2 C o h orts 1a, 
1 b, a n d 1c)
• 
T o e val uate a d diti o nal meas ures of efficac y of 
ma gr oli ma b + d oceta xel c o m bi nati o n t hera p y, 
i ncl u di n g d urati o n of res p o nse ( D O R) a n d 
o verall s ur vi val ( O S) ( P hase 2 C o h orts 1a, 1 b, 
a n d 1c)
•
T o e val uate t he P K a n d i m m u n o ge nicit y of 
ma gr oli ma b w he n gi ve n wit h d oceta xel as a 
c o m bi nati o n t hera p y ( Safet y R u n-i n C o h ort 1, 
P hase 2 C o h orts 1a, 1 b, a n d 1c)
• 
P F S fr o m date of d ose i nitiati o n as deter mi ne d b y 
i n vesti gat or assess me nt per R E CI S T, Versi o n 1. 1 
( P hase 2 C o h orts 1a, 1 b, a n d 1c)
• 
D O R, defi ne d as ti me fr o m first d oc u me ntati o n of 
c o m plete res p o nse or partial res p o nse t o t he earliest 
date of d oc u me nte d disease pr o gressi o n, per R E CI S T, 
Versi o n 1. 1, or deat h fr o m a n y ca use, w hic he ver 
occ urs first, as deter mi ne d b y i n vesti gat or assess me nt 
( P hase 2 C o h orts 1a, 1 b, a n d 1c)
• 
O S, defi ne d as date of d ose i nitiati o n ( P hase 2 
C o h orts 1a, 1 b, a n d 1c) t o deat h fr o m a n y ca use.
• 
Ma gr oli ma b c o nce ntrati o n vers us ti me a n d a nti dr u g 
a nti b o dies t o ma gr oli ma b ( Safet y R u n-i n C o h ort 1; 
P hase 2 C o h orts 1a, 1 b, a n d 1c)
C CI


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 4
2 4 Oct o ber 2 0 2 3
3.  
S T U D Y D E SI G N
3. 1.  
St u d y Desi g n
T his P hase 2, o pe n-la bel, m ultice nter, m ultiar m st u d y is e val uati n g ma gr oli ma b + d oceta xel 
c o m bi nati o n t hera p y f or patie nts wit h s oli d t u m ors. T his st u d y will c o nsist of t he f oll o wi n g 
Safet y R u n-i n C o h ort:
•
S afet y R u n-i n C o h ort 1:  ma gr oli ma b + d oceta xel c o m bi nati o n i n patie nts wit h s oli d t u m ors 
( m N S C L C, m U C, a n d m S C L C)
After c o m pleti o n of Safet y R u n-i n C o h ort 1, P hase 2 C o h ort 1 will occ ur as descri be d i n 
Secti o n 3. 1. 2 .
Patie nt partici pati o n will i ncl u de scree ni n g, treat me nt, a n d f oll o w- u p. Scree ni n g will last u p t o 
3 0 da ys bef ore first d ose of st u d y treat me nt, d uri n g w hic h ti me t he patie nt’s eli gi bilit y a n d 
baseli ne c haracteristics will be deter mi ne d. Patie nts will recei ve st u d y treat me nt per t he d ose 
sc he d ule i n A p pe n di x Ta ble 1 .
T he st u d y sc he matic is prese nte d i n Fi g ure 2 .
Fi g ure 2.
St u d y Sc he m a
m N S C L C = metastatic n o n –s mall cell l u n g ca ncer; m S C L C = metastatic s mall cell l u n g ca ncer; m U C = metastatic ur ot helial 
ca ncer; R P 2 D = rec o m me n de d P hase 2 d ose
S af et y  R u n-i n  C o h ort  1 
m N S C L C , m U C , m S C L C 
M a gr ol im a b  + 
D o c et a x el 
N = 1 8 
S a f et y E v a lu at i o n a n d R P 2 D 
P h a s e  2  C o h o rt  1 
( M a gr olim a b + D o c et a x e l ) 
P h a s e 2  C o h ort l a 
( m N S C L C) 
N = 3 0 
P h a s e 2  C o h ort l b 
( m U C) 
N =  2 6 
P h a s e 2  C o h ort l e 
( m S CLC) 
N = 4 0 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 5
2 4 Oct o ber 2 0 2 3
3. 1. 1.  
S afet y R u n-i n C o h ort 1
A d ose ‑li miti n g t o xicit y ( D L T) e val uati o n peri o d of 1 c ycle ( 2 1 da ys) will occ ur. After 6 patie nts 
ha ve c o m plete d t he D L T e val uati o n peri o d, decisi o n will be ma de o n f urt her e x pa nsi o n or d ose 
de-escalati o n.
E ve n t h o u g h n o d ose- de pe n de nt t o xicities ha ve bee n o bser ve d wit h ma gr oli ma b, i n or der t o 
preser ve t he efficaci o us d oses of t he c o m bi nati o n part ner dr u gs, d ose de-escalati o n will ta ke 
place f or ma gr oli ma b as s pecifie d bel o w.
D ose de-escalati o n decisi o ns will be ma de as f oll o ws:
•
If 2 or fe wer of 6 D L T-e val ua ble patie nts e x perie nce a D L T i n C ycle 1, e nr oll me nt i nt o 
P hase 2 C o h ort 1 will be gi n at t his d ose le vel as t he rec o m me n de d P hase 2 d ose.
•
If m ore t ha n 2 patie nts e x perie nce at least 1 D L T d uri n g C ycle 1, e nr oll me nt at t he c urre nt 
d ose le vel will i m me diatel y st o p a n d d ose de-escalati o n will occ ur. U p t o a n ot her 6 patie nts 
will t he n be e nr olle d a n d e val uate d at a l o wer d ose le vel i n t he sa me ma n ner.
U p t o a p pr o xi matel y 1 8 patie nts c o ul d be p ote ntiall y e nr olle d a n d e val uate d d uri n g Safet y 
R u n-i n C o h ort 1.
D ose de-escalati o n f or Safet y R u n-i n C o h ort 1 is prese nte d i n Ta ble 2 . Base d o n t he t otalit y of 
t he data, alter nati ve d oses of ma gr oli ma b n ot descri be d i n Ta ble 2  ma y be c o nsi dere d f or d ose 
de-escalati o n b y t he Safet y Re vie w Tea m ( S R T) a n d s p o ns or.
3. 1. 1. 1.   
D L T Assess me nt Peri o d
T he D L T assess me nt peri o d will be t he first c ycle ( 2 1 da ys) a n d a p plies t o Safet y R u n-i n 
C o h ort 1. Patie nts are c o nsi dere d e val ua ble f or assess me nt of a D L T if eit her of t he f oll o wi n g 
criteria are met i n t he D L T assess me nt peri o d:
•
T he patie nt e x perie nce d a D L T at a n y ti me after i nitiati o n of t he first i nf usi o n of ma gr oli ma b.
•
T he patie nt di d n ot e x perie nce a D L T a n d c o m plete d at least 2 i nf usi o ns of ma gr oli ma b 
( 2 1- da y c ycle) a n d at least 1 d ose of d oceta xel i n Safet y R u n-i n C o h ort 1.
If a patie nt e x perie nces a D L T d uri n g t he D L T assess me nt peri o d, t he patie nt will disc o nti n ue 
treat me nt. T h o u g h t he d osi n g d uri n g mai nte na nce c ycles is hi g her, t he t otal d ose gi ve n d uri n g 
t he pri mi n g c ycle is hi g her t ha n t he mai nte na nce d ose. H o we ver, t he t otalit y of t he data o n safet y 
d uri n g a l o n ger f oll o w- u p will be ta ke n i nt o c o nsi derati o n w he n R P 2 D is deter mi ne d.
Patie nts w h o are n ot e val ua ble f or D L T assess me nt i n Safet y R u n-i n C o h ort 1 will be re place d.
3. 1. 1. 2.   
D L T Defi niti o n
All t o xicities will be gra de d acc or di n g t o t he Nati o nal Ca ncer I nstit ute ( N CI) C o m m o n 
Ter mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E), Versi o n 5. 0 ( A p pe n di x 5 ). 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 6
2 4 Oct o ber 2 0 2 3
A D L T is defi ne d as a n y:
•
Gra de 3 or hi g her he mat ol o gic t o xicit y.
•
E ve nt meeti n g H y’s La w criteria ( Secti o n 7. 7 ).
•
Gra de 3 or hi g her n o n he mat ol o gic t o xicit y t hat has w orse ne d i n se verit y fr o m pretreat me nt 
baseli ne d uri n g t he D L T assess me nt peri o d.
I n t he o pi ni o n of t he i n vesti gat or, t he A E is at least p ossi bl y relate d t o ma gr oli ma b.
T he f oll o wi n g are e xce pti o ns t o t he D L T defi niti o n a n d are N O T c o nsi dere d a D L T:
•
Gra de 3 a ne mia; h o we ver, Gra de 3 he m ol ytic a ne mia t hat is me dicall y si g nifica nt, re q uiri n g 
h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n, disa bli n g, or li miti n g self-care 
acti vities of dail y li vi n g is c o nsi dere d a D L T.
•
Gra de 3 fe brile ne utr o pe nia t hat has res p o n de d cli nicall y wit hi n 7 2 h o urs of ma xi mal 
s u p p orti ve care.
•
Gra de 3 ne utr o pe nia t hat res ol ves t o Gra de 2 or pretreat me nt baseli ne wit h s u p p orti ve care 
(i ncl u di n g gr o wt h fact ors) wit hi n 1 4 da ys.
•
Gra de 3 i n direct/ u nc o nj u gate d h y per bilir u bi ne mia t hat res ol ves t o ≤ Gra de 2 wit h s u p p orti ve 
care wit hi n 1 wee k a n d is n ot ass ociate d wit h ot her cli nicall y si g nifica nt c o nse q ue nces.
•
Gra de 3 electr ol yte a b n or malities t hat i m pr o ve t o ≤ Gra de 2 or baseli ne wit hi n < 7 2 h o urs, 
are n ot cli nicall y c o m plicate d, a n d res ol ve s p o nta ne o usl y or res p o n d t o c o n ve nti o nal me dical 
i nter ve nti o ns.
•
Gra de 3 ele vati o n i n ala ni ne a mi n otra nsferase ( A L T), as partate a mi n otra nsferase ( A S T), or 
al kali ne p h os p hatase t hat res ol ves t o ≤ Gra de 2 wit h s u p p orti ve care wit hi n 1 wee k a n d is n ot 
ass ociate d wit h ot her cli nicall y si g nifica nt c o nse q ue nces.
•
Gra de 3 na usea/ v o miti n g or diarr hea t hat res ol ves t o ≤ Gra de 2 wit hi n 7 2 h o urs wit h 
a de q uate a ntie metic a n d ot her s u p p orti ve care.
•
Gra de 3 fati g ue t hat res ol ves t o ≤ Gra de 2 wit hi n 1 wee k o n st u d y.
•
Gra de 3 ma gr oli ma b a n d d oceta xel i nf usi o n reacti o ns i n t he a bse nce of a n o pti mal 
pretreat me nt re gi me n, w hic h is defi ne d as aceta mi n o p he n or a c o m para ble n o nster oi dal 
a nti-i nfla m mat or y a ge nt, pl us a n a nti hista mi ne a n d c ortic oster oi ds.
•
Gra de 3 t u m or l ysis s y n dr o me or electr ol yte dist ur ba nces ( h y per kale mia, h y p o p h os p hate mia, 
h y per urice mia) t hat res ol ve t o ≤ Gra de 2 or baseli ne wit hi n 7 2 h o urs.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 7
2 4 Oct o ber 2 0 2 3
•
Gra de 3 or 4 l y m p h o pe nia or le u k o pe nia n ot ass ociate d wit h ot her cli nicall y si g nifica nt 
c o nse q ue nces.
•
Tra nsie nt ( ≤ 4 8 h o urs) Gra de 3 l ocal reacti o ns, fl u-li ke s y m pt o ms, m yal gias, fe ver, hea dac he, 
ac ute pai n, or s ki n t o xicit y t hat res ol ves t o ≤ Gra de 2 wit hi n 7 2 h o urs after me dical 
ma na ge me nt (e g, s u p p orti ve care, i ncl u di n g i m m u n os u p pressa nt treat me nt) has bee n 
i nitiate d.
T he rec o m me n de d d ose f or P hase 2 C o h ort 1 will be deter mi ne d b y t he s p o ns or base d o n all 
rele va nt cli nical a n d P K data (a d diti o nal data s uc h as bi o mar kers ma y als o be c o nsi dere d) fr o m 
all patie nts treate d i n t he Safet y R u n-i n P hase.
3. 1. 1. 3.  
Safet y Re vie w Tea m
A n S R T will be esta blis he d t o assess safet y of t he patie nts i n vari o us c o h orts.
T he S R T will i ncl u de at least 1 i n vesti gat or, a Gilea d Safet y P h ysicia n, a n d t he Gilea d me dical 
m o nit or. Ot hers ma y be i n vite d t o partici pate as me m bers of t he S R T if a d diti o nal e x pertise is 
desire d. T he me dical m o nit or ser ves as t he c hair of t he S R T. A n S R T c harter ( or si milar 
d oc u me nt) will be a gree d o n b y all S R T me m bers pri or t o t he first S R T meeti n g. T he data 
re vie we d at t he S R T meeti n g t o ma ke decisi o ns will be defi ne d i n t he S R T c harter ( or si milar 
d oc u me nt). T he q ualit y c o ntr ol c hec ks perf or me d o n t he data re vie we d a n d use d f or ma ki n g 
decisi o ns will be descri be d i n t he S R T c harter ( or si milar d oc u me nt).
3. 1. 2.  
P h ase 2 C o h ort 1
After c o m pleti o n of t he Safet y R u n-i n C o h ort, P hase 2 C o h ort 1 will occ ur as f oll o ws:
•
P h ase 2 C o h ort 1:  a c o h ort of patie nts wit h s oli d t u m ors ( m N S C L C [ P hase 2 C o h ort 1a], 
m U C [ P hase 2 C o h ort 1 b], a n d m S C L C [ P hase 2 C o h ort 1c]).
O nce Safet y R u n-i n C o h ort 1 is c o m plete d a n d t he rec o m me n de d d ose f or P hase 2 C o h ort 1 is 
deter mi ne d, t he s p o ns or will o pe n P hase 2 C o h ort 1. P hase 2 C o h ort 1 will treat u p t o 3 0 patie nts 
wit h m N S C L C ( P hase 2 C o h ort 1a), u p t o 2 6 patie nts wit h m U C ( P hase 2 C o h ort 1 b), a n d u p t o 
4 0 patie nts wit h m S C L C ( P hase 2 C o h ort 1c) t o e val uate efficac y.
3. 2.  
St u d y Tre at me nts
3. 2. 1.  
S afet y R u n-i n C o h ort 1 a n d P h ase 2 C o h ort 1
Ta ble 2  s h o ws t he st u d y treat me nts f or Safet y R u n-i n C o h ort 1 a n d Ta ble 3  s h o ws t he st u d y 
treat me nts f or P hase 2 C o h ort 1. T he sc he d ules of assess me nt are pr o vi de d i n A p pe n di x 3 .


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 8
2 4 Oct o ber 2 0 2 3
T a ble 2.
S afet y R u n-i n C o h ort 1: D ose Le vel, Sc he d ule, a n d De-esc al ati o n
D osi n g ( C ycles Are 2 1 D a ys)
Dr u g
D ose Le vel
C ycle 1
C ycle 2
C ycle 3 + 
( m ai nte n a nce 
d osi n g)
Starti n g d ose
3 0 m g/ k g
1 m g/ k g I V ( 3 h ± 3 0 mi n) 
o n Da y 1 ( pri mi n g d ose), 
3 0 m g/ k g I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
3 0 m g/ k g I V ( 2 h ± 
3 0 mi n) o n Da ys 1, 
8, a n d 1 5
6 0 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da y 1
De-escalati o n
Le vel −1
2 0 m g/ k g
1 m g/ k g I V ( 3 h ± 3 0 mi n) 
o n Da y 1 ( pri mi n g d ose); 
2 0 m g/ k g I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
2 0 m g/ k g I V ( 2 h ± 
3 0 mi n) o n Da ys 1, 
8, a n d 1 5
4 5 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da y 1
Ma gr oli ma b
De-escalati o n
Le vel −2
1 5 m g/ k g
1 m g/ k g I V ( 3 h ± 3 0 mi n) 
o n Da y 1 ( pri mi n g d ose); 
1 5 m g/ k g I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
1 5 m g/ k g I V ( 2 h ± 
3 0 mi n) o n Da ys 1, 
8, a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da y 1
D oceta xel
7 5 m g/ m 2
7 5 m g/ m 2 I V ( 1 h ± 5 mi n) 
o n Da y 1
7 5 m g/ m 2 I V ( 1 h ± 
5 mi n) o n Da y 1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) o n 
Da y 1
I V = i ntra ve n o us
T a ble 3.
P h ase 2 C o h ort 1: D ose Le vel a n d Sc he d ule
D osi n g ( C ycles Are 2 1 D a ys)
Dr u g
R P 2 D a
St arti n g D ose
C ycle 1
C ycle 2
C ycle 3 + 
( m ai nte n a nce 
d osi n g)
3 0 m g/ k g
1 m g/ k g I V ( 3 h ± 3 0 mi n) 
o n Da y 1 ( pri mi n g d ose); 
3 0 m g/ k g I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da ys 1, 8, a n d 1 5
6 0 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da y 1
O R
2 0 m g/ k g
1 m g/ k g I V ( 3 h ± 3 0 mi n) 
o n Da y 1 ( pri mi n g d ose); 
2 0 m g/ k g I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
2 0 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da ys 1, 8, a n d 1 5 
4 5 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da y 1
Ma gr oli ma b
O R
1 5 m g/ k g
1 m g/ k g I V ( 3 h ± 3 0 mi n) 
o n Da y 1 ( pri mi n g d ose); 
1 5 m g/ k g I V ( 2 h ± 3 0 mi n) 
o n Da ys 8 a n d 1 5
1 5 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da ys 1, 8, a n d 1 5
3 0 m g/ k g I V 
( 2 h ± 3 0 mi n) o n 
Da y 1
D oceta xel
7 5 m g/ m 2 I V 
7 5 m g/ m 2 I V ( 1 h ± 5 mi n) 
o n Da y 1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) o n 
Da y 1
7 5 m g/ m 2 I V 
( 1 h ± 5 mi n) o n 
Da y 1
I V = i ntra ve n o us; R P 2 D = rec o m me n de d P hase 2 d ose
a  
R P 2 D as deter mi ne d i n Safet y R u n-i n C o h ort 1.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 3 9
2 4 Oct o ber 2 0 2 3
3. 3.   
D ur ati o n of Tre at me nt
C ycle le n gt hs are 2 1 da ys f or Safet y R u n-i n C o h ort 1 a n d P hase 2 C o h ort 1. Patie nts ma y 
c o nti n ue treat me nt u nless t he y de vel o p u nacce pta ble t o xicit y t hat ca n n ot be cli nicall y ma na ge d 
b y d ose or sc he d ule m o dificati o ns or if t he y ha ve c o nfir me d pr o gressi ve disease acc or di n g t o 
R E CI S T, Versi o n 1. 1. Patie nts are n ot re q uire d t o disc o nti n ue st u d y dr u gs f or disease 
pr o gressi o n per R E CI S T criteria, gi ve n t he o bser vati o n t hat dela ye d cli nical be nefit ca n occ ur 
wit h i m m u ne t hera pies be y o n d i nitial disease pr o gressi o n. Ma gr oli ma b ca n be c o nti n ue d if t he 
c o m bi nati o n part ner dr u g (ie, d oceta xel) is disc o nti n ue d f or u nacce pta ble t o xicit y. C o m bi nati o n 
part ner dr u g ca n be c o nti n ue d if ma gr oli ma b is disc o nti n ue d f or u nacce pta ble t o xicit y. St u d y 
dr u g treat me nt ma y c o nti n ue past t he i nitial deter mi nati o n of disease pr o gressi o n acc or di n g t o 
R E CI S T, Versi o n 1. 1 if t he f oll o wi n g criteria are met:
•
N o ne w s y m pt o ms or w orse ni n g of pre vi o us s y m pt o ms
•
T olera nce of ma gr oli ma b a n d d oceta xel
•
Sta ble Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) perf or ma nce stat us
•
Treat me nt be y o n d pr o gressi o n will n ot dela y a n i m mi ne nt i nter ve nti o n t o pre ve nt seri o us 
c o m plicati o ns of disease pr o gressi o n (f or e xa m ple, ce ntral ner v o us metastases).
T he decisi o n t o c o nti n ue treat me nt s h o ul d be a p pr o ve d b y t he s p o ns or. Patie nts w h o c o nti n ue 
st u d y dr u g treat me nt past t he i nitial deter mi nati o n of disease pr o gressi o n will be re q uire d t o 
re-c o nse nt t o t he c o nti n ue d treat me nt.
3. 4.   
Disc o nti n u ati o n Criteri a
Reas o ns f or disc o nti n uati o n of st u d y treat me nt ma y i ncl u de, b ut are n ot li mite d t o, t he f oll o wi n g:
•
Disease pr o gressi o n b y R E CI S T, Versi o n 1. 1 (treat me nt be y o n d disease pr o gressi o n b y 
R E CI S T, Versi o n 1. 1 is all o we d per criteria i n Secti o n 3. 3 )
•
U nacce pta ble t o xicit y
•
L oss of cli nical be nefit
•
Cli nicall y si g nifica nt c ha n ge i n t he patie nt’s stat us t hat precl u des f urt her treat me nt 
(e g, pre g na nc y or ot her A Es)
•
Patie nt re q uest, wit h or wit h o ut a state d reas o n
•
Patie nt n o nc o m plia nce
•
Disc o nti n uati o n of t he st u d y at t he re q uest of Gilea d, a re g ulat or y a ge nc y or a n i nstit uti o nal 
re vie w b oar d (I R B) or i n de pe n de nt et hics c o m mittee (I E C)
•
I n vesti gat or or treati n g p h ysicia n decisi o n i n t he a bse nce of a n y of t he a b o ve


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 0
2 4 Oct o ber 2 0 2 3
Alt h o u g h disease pr o gressi o n is c o nsi dere d a s ufficie nt reas o n f or disc o nti n ui n g a patie nt fr o m 
st u d y treat me nt, gi ve n t he dela ye d treat me nt be nefit c o m m o nl y see n i n i m m u ne t hera pies, t he 
i n vesti gat or is a d vise d t o c o nti n ue t o treat t he patie nt u ntil t he c o nfir mati o n of disease 
pr o gressi o n t hr o u g h a s u bse q ue nt res p o nse assess me nt at least 4 wee ks a part (ie, disease 
w orse ni n g c o m pare d t o t he pre vi o us assess me nt), or u ntil t he i n vesti gat or c o nsi ders t he st u d y 
treat me nt t o be n o l o n ger cli nicall y be neficial t o t he patie nt, or t he c ha n ge of disease state 
re n ders t he patie nt u nacce pta ble f or f urt her treat me nt i n t he j u d g me nt of t he i n vesti gat or. Patie nts 
ma y c o nti n ue st u d y dr u g treat me nt be y o n d R E CI S T, Versi o n 1. 1 disease pr o gressi o n as per 
criteria i n Secti o n 3. 3 . All patie nts m ust be f oll o we d t hr o u g h c o m pleti o n of all st u d y treat me nt.
3. 5.   
Disc o nti n u ati o n Fr o m St u d y Criteri a/ E n d of St u d y
All P atie nts : T he e n d of t he e ntire st u d y f or all patie nts is defi ne d as t he date o n w hic h t he last 
patie nt re mai ni n g o n st u d y c o m pletes t he last st u d y visit/call or w he n t he s p o ns or deci des t o e n d 
t he st u d y. T he s p o ns or reser ves t he ri g ht t o ter mi nate t he st u d y at a n y ti me f or a n y reas o n 
(i ncl u di n g safet y).
I n di vi d u al P atie nts: Patie nts are c o nsi dere d t o ha ve c o m plete d st u d y partici pati o n alt o get her 
w he n t he y are n o l o n ger f oll o we d f or s ur vi val.
All patie nts will be f oll o we d f or s ur vi val u ntil deat h, wit h dra w fr o m c o nse nt, l ost t o f oll o w- u p, 
a n d t he e n d of st u d y, w hic he ver occ urs first.
F or a n y patie nt w h o dies d uri n g t his f oll o w- u p peri o d, t he i m me diate ca use of deat h m ust be 
re p orte d t o t he s p o ns or.
3. 6.  
P ostst u d y C are
U p o n wit h dra wal fr o m st u d y treat me nt, patie nts will recei ve t he care u p o n w hic h t he y a n d t heir 
p h ysicia ns a gree. Patie nts will be f oll o we d f or disease pr o gressi o n if a p plica ble, s ur vi val, a n d 
A Es as s pecifie d i n A p pe n di x Ta ble 2 .
3. 7.  
S o urce D at a
T he s o urce data f or t his st u d y will be o btai ne d fr o m ori gi nal rec or ds (e g, cli nic n otes, h os pital 
rec or ds, patie nt c harts), ce ntral la b orat or y, l ocal la b orat or y, a n d/ or s pecialt y la b orat or y (f or P K, 
A D A, a n d/ or P D data) a n d/ or a d diti o nal bi o mar ker testi n g, a n d I nteracti ve Res p o nse Tec h n ol o g y 
(I R T).
3. 8.  
Bi o m ar ker S a m ples t o A d dress t he St u d y O bjecti ves
Peri p heral bl o o d a n d t u m or bi o ps y  sa m ples will be c ollecte d fr o m all patie nts w h o ha ve pr o vi de d 
c o nse nt t o partici pate i n t his st u d y. T he y ma y be use d t o e val uate t he ass ociati o n of s yste mic 
a n d/ or tiss ue- base d bi o mar kers wit h st u d y dr u g res p o nse, i ncl u di n g efficac y a n d/ or A Es, d osa ge 
selecti o n, a n d t o better u n dersta n d t he bi ol o g y of t he ca ncer i n dicati o ns st u die d, as well as t he 
efficac y a n d M O A f or ma gr oli ma b c o m bi nati o ns. Beca use bi o mar ker scie nce is a ra pi dl y 
e v ol vi n g area of i n vesti gati o n, a n d A Es, i n partic ular, are diffic ult t o pre dict, it ma y n ot be 
p ossi ble t o s pecif y pr os pecti vel y all tests t hat ma y be d o ne o n t he s peci me ns pr o vi de d. T he 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 1
2 4 Oct o ber 2 0 2 3
s pecific a nal yses will i ncl u de, b ut ma y n ot be li mite d t o, t he bi o mar kers a n d assa ys descri be d 
bel o w. T he testi n g o utli ne d bel o w is base d u p o n t he c urre nt state of scie ntific k n o wle d ge. It ma y 
be m o difie d d uri n g or after t he e n d of t he st u d y t o re m o ve tests n o l o n ger i n dicate d a n d/ or t o a d d 
ne w tests base d u p o n ne w state- of-t he-art k n o wle d ge.
Bi o mar ker assess me nts will i ncl u de:
•
Bl o o d sa m ple f or R O at select sites
•
Peri p heral bl o o d m o n o n uclear cell ( P B M C) t o assess i m m u ne cell p he n ot y pes (at selecte d 
sites)
•
Ser u m a n d plas ma bi o mar ker sa m ples f or t he a nal ysis of circ ulati n g fact ors s uc h as 
c yt o ki nes, s ol u ble i m m u ne rece pt ors, a n d a nti b o dies
•
W h ole bl o o d R N A sa m ples f or le u k oc yte ge ne e x pressi o n a nal ysis
•
I m m u n o p he n ot y pi n g assa y
•
T-cell rece pt or se q ue nci n g sa m ple t o assess i m m u ne re pert oire c ha n ges
•
Circ ulati n g t u m or D N A sa m ple t o m o nit or treat me nt res p o nse
•
St o ol sa m ples t o assess micr o bi o me
•
Ma n dat or y baseli ne t u m or tiss ue a n d o n treat me nt bi o psies t o assess i m m u ne cells, t u m or cell 
s urface pr otei ns, a n d/ or ge n o mic bi o mar kers
Bl o o d a n d t u m or bi o ps y sa m ples will be c ollecte d t o meas ure bi o mar kers, w hic h ma y i ncl u de 
b ut will n ot be li mite d t o t he prese nce of or c ha n ges t o i m m u ne cell p o p ulati o ns, secrete d pr otei n 
fact ors, t he e x pressi o n of cell s urface mar kers o n eit her t u m or cells or cells of t he t u m or 
micr oe n vir o n me nt, a n d ge netic m utati o ns i n t u m or cells or s u bcl o nes of t u m or cells at t he ti me 
p oi nts liste d i n t he sc he d ules of assess me nts ( A p pe n di x Ta ble 3 ). 
Bl o o d a n d t u m or sa m ples will als o be use d f or ge n o mic researc h. I n a d diti o n, a w h ole bl o o d 
sa m ple will be c ollecte d at C ycle 1 Da y 1 b ut ma y be c ollecte d at a n y ti me d uri n g t he st u d y, if 
necessar y. T hese sa m ples will be use d t o i de ntif y or vali date ge netic mar kers t hat ma y i ncrease 
o ur k n o wle d ge a n d u n dersta n di n g of t he bi ol o g y of t he st u d y disease a n d relate d diseases a n d t o 
st u d y t he ass ociati o n of ge netic mar kers wit h disease pat h o ge nesis, pr o gressi o n, a n d/ or treat me nt 
o utc o mes, i ncl u di n g efficac y, A Es, a n d t he pr ocesses of dr u g a bs or pti o n a n d dis p ositi o n. T hese 
s peci me ns ma y als o be use d t o de vel o p bi o mar ker or dia g n ostic assa ys a n d esta blis h t he 
perf or ma nce c haracteristics of t hese assa ys. Ge n o mics researc h ma y i ncl u de se q ue nci n g of 
ge netic material deri ve d fr o m b ot h ca ncer cells a n d n or mal cells. Se q ue nci n g of ge netic material 
deri ve d fr o m ca ncer cells will be use d t o better u n dersta n d t he M O A of ma gr oli ma b 
c o m bi nati o ns i n t his patie nt p o p ulati o n a n d t o p ote ntiall y t o i de ntif y s u bsets of patie nts w h o are 
li kel y t o be nefit. Se q ue nci n g of ge netic material deri ve d fr o m n or mal cells will be use d t o defi ne 
differe nces i n se q ue nce t hat are ca ncer s pecific.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 2
2 4 Oct o ber 2 0 2 3
Sa m ples c ollecte d f or bi o mar ker assess me nts will be destr o ye d n o later t ha n 1 5 years after t he 
e n d of st u d y or per c o u ntr y re q uire me nts.
3. 8. 1.  
P h ar m ac o ki netics/ Bi o m ar ker S a m ples f or 
I n a d diti o n t o t he st u d y-s pecific i nf or me d c o nse nt t o be si g ne d b y eac h patie nt partici pati n g i n 
t he st u d y, patie nts will be re q uire d t o d oc u me nt a gree me nt t o all o w t he use of t he re mai n der of 
t heir alrea d y c ollecte d bi o mar ker a n d P K s peci me ns f or 
, i n acc or da nce 
wit h a p plica ble re g ulati o ns.
T he re mai n der of t heir alrea d y c ollecte d s peci me ns f or
 ma y be use d t o 
a d va nce de vel o p me nt of t he dr u g a n d/ or i ncrease o ur k n o wle d ge a n d u n dersta n di n g of t he 
bi ol o g y of t he disease u n der i n vesti gati o n a n d relate d diseases. T hese s peci me ns ma y als o be 
use d t o st u d y t he ass ociati o n of bi o mar kers wit h bi ol o gical pat h wa ys, disease pat h o ge nesis, 
pr o gressi o n a n d/ or treat me nt o utc o mes, i ncl u di n g efficac y, A Es, a n d t he pr ocesses of dr u g 
a bs or pti o n a n d dis p ositi o n. I n a d diti o n, t hese s peci me ns ma y be use d t o de vel o p bi o mar ker 
a n d/ or dia g n ostic assa ys a n d esta blis h t he perf or ma nce c haracteristics of t hese assa ys. T he 
a nal ysis of 
 s peci me ns ma y facilitate t he desi g n of ne w p har mace utical 
a ge nts a n d t he de vel o p me nt of dia g n ostic tests, w hic h ma y all o w f or i n di vi d ualize d dr u g t hera p y 
f or patie nts 
Bl o o d sa m ples will be c ollecte d t o meas ure bi o mar kers w hic h ma y i ncl u de b ut n ot be li mite d t o 
t he ti mes p oi nts s pecifie d i n t he sc he d ules of assess me nts (A p pe n di x Ta ble 3 ). 
T he alrea d y c ollecte d s peci me ns f or 
 will be destr o ye d n o later t ha n 
1 5 years after t he e n d of st u d y or per c o u ntr y re q uire me nts.
C CI
C CI
C CI
C CI
C CI
C CI


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 3
2 4 Oct o ber 2 0 2 3
4.  
P A TI E N T P O P U L A TI O N
4. 1.   
N u m ber of P atie nts a n d P atie nt Selecti o n
U p t o a p pr o xi matel y 1 1 4 patie nts ma y be e nr olle d i n t he st u d y, wit h u p t o a p pr o xi matel y 
1 8 patie nts i n Safet y R u n-i n C o h ort 1 a n d  u p t o a p pr o xi matel y 9 6 patie nts i n P hase 2 C o h ort 1.
4. 1. 1.  
P atie nt Re pl ace me nt
Patie nts ma y be re place d d uri n g t he Safet y R u n-i n C o h ort if n ot e val ua ble f or D L T assess me nt 
as descri be d i n Secti o n 3. 1. 1 .
4. 2.  
I ncl usi o n Criteri a
All patie nts m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or partici pati o n i n t his 
st u d y:
1)
Patie nt has pr o vi de d i nf or me d c o nse nt.
2)
Patie nt is willi n g a n d a ble t o c o m pl y wit h cli nic visits a n d pr oce d ures o utli ne d i n t he st u d y 
pr ot oc ol.
3)
Male or fe male, ≥ 1 8 years of a ge
4)
Patie nts m ust ha ve a n E C O G perf or ma nce stat us of ≤ 2.
5)
La b orat or y meas ure me nts, bl o o d c o u nts:
a)
He m o gl o bi n m ust be ≥ 9 g/ d L pri or t o i nitial d ose of st u d y dr u g. N O T E: Tra nsf usi o ns are 
all o we d t o meet eli gi bilit y (see Secti o n 7. 8. 1. 1. 1  a n d e xcl usi o n criteri o n 4).
b)
A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1. 5  1 09/ L
c)
Platelets ≥ 1 0 0  1 09/ L
6)
La b orat or y meas ure me nts, re nal f u ncti o n:
a)
Patie nts m ust ha ve a de q uate re nal f u ncti o n as de m o nstrate d b y a creati ni ne cleara nce of 
at least 3 0 m L/ mi n; calc ulate d b y t he C oc kcr oft Ga ult f or m ula.
7)
A de q uate li ver f u ncti o n, as de m o nstrate d b y:
a)
A S T less t ha n or e q ual t o 2. 5  u p per li mit of n or mal ( U L N) or less t ha n or e q ual t o 
5  U L N i n patie nts wit h li ver metastases
b)
A L T less t ha n or e q ual t o 2. 5  U L N or less t ha n or e q ual t o 5  U L N i n patie nts wit h 
li ver metastases


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 4
2 4 Oct o ber 2 0 2 3
c)
Bilir u bi n less t ha n or e q ual t o 1. 5  U L N, or less t ha n or e q ual t o 3. 0  U L N a n d 
pri maril y u nc o nj u gate d if patie nt has a d oc u me nte d hist or y of Gil bert’s s y n dr o me or 
ge netic e q ui vale nt
8)
Pretreat me nt bl o o d cr oss- matc h c o m plete d (see Secti o n 7. 8. 1. 1. 1 )
9) 
Male a n d fe male patie nts of c hil d beari n g p ote ntial w h o e n ga ge i n heter ose x ual i nterc o urse 
m ust a gree t o use pr ot oc ol-s pecifie d met h o d(s) of c o ntrace pti o n as descri be d i n A p pe n di x 6 .
1 0) Meas ura ble disease acc or di n g t o R E CI S T, Versi o n 1. 1. Pre vi o usl y irra diate d lesi o ns ca n be 
c o nsi dere d as meas ura ble disease o nl y if disease pr o gressi o n has bee n u ne q ui v ocall y 
d oc u me nte d at t hat site si nce ra diati o n.
1 1) Criteri o n re m o ve d.
C o h ort- S pecific I ncl usi o n Criteri a
Patie nts nee d t o f ulfill t he f oll o wi n g c o h ort-s pecific criteria, i n a d diti o n t o satisf yi n g t he 
i ncl usi o n criteria f or all patie nts:
1 2) Criteri o n re m o ve d.
1 3) Criteri o n re m o ve d.
1 4) Safet y R u n-i n C o h ort 1: Patie nts wit h metastatic a d va nce d s oli d t u m ors w h o ha ve ha d at least 
1 pri or li ne of s yste mic a ntica ncer t hera p y ( m N S C L C a n d m S C L C) i n a l ocall y 
a d va nce d/ metastatic setti n g, or 2 pri or li nes of s yste mic a ntica ncer t hera p y ( m U C) i n a 
l ocall y a d va nce d/ metastatic setti n g, a n d n ot m ore t ha n 3 pri or li nes of s yste mic a ntica ncer 
t hera p y i n a l ocall y a d va nce d/ metastatic setti n g.
1 5) P hase 2 C o h ort 1a ( m N S C L C): Patie nts wit h N S C L C w h o ha ve ha d treat me nt wit h plati n u m 
- base d c he m ot hera p y a n d i m m u ne c hec k p oi nt i n hi bit or t hera p y i n a l ocall y 
a d va nce d/ metastatic setti n g, eit her i n c o m bi nati o n or se q ue ntiall y ( u nless n ot eli gi ble f or o ne 
of t hese t hera pies) are eli gi ble. At least 1 pri or li ne of s yste mic a ntica ncer t hera p y i n a l ocall y 
a d va nce d/ metastatic setti n g is re q uire d a n d n ot m ore t ha n 2 pri or li nes of s yste mic a ntica ncer 
t hera p y i n a l ocall y a d va nce d/ metastatic setti n g are all o we d. Patie nts treate d wit h a ta xa ne 
wit hi n 1 2 m o nt hs or patie nts refract or y t o pri or ta xa ne treat me nt are e xcl u de d. Patie nts 
w h ose t u m ors ha ve ge n o mic alterati o ns f or w hic h t here are a p pr o ve d t hera pies (e g, E G F R, 
R O S 1, A L K, N T R K, M E T e x o n 1 4) are e xcl u de d. 
1 6) P hase 2 C o h ort 1 b ( m U C): Patie nts wit h U C w h o ha ve ha d pri or treat me nt wit h s yste mic 
c he m ot hera p y a n d i m m u ne c hec k p oi nt i n hi bit or t hera p y i n a l ocall y a d va nce d/ metastatic 
setti n g ( u nless n ot eli gi ble f or o ne of t hese t hera pies) are eli gi ble. At least 2 pri or li nes of 
s yste mic a ntica ncer t hera p y i n a l ocall y a d va nce d/ metastatic setti n g are re q uire d a n d n ot 
m ore t ha n 3 pri or li nes of s yste mic a ntica ncer t hera p y i n a l ocall y a d va nce d/ metastatic 
setti n g are all o we d. Patie nts treate d wit h a ta xa ne wit hi n 1 2 m o nt hs or patie nts refract or y t o 
pri or ta xa ne treat me nt are e xcl u de d.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 5
2 4 Oct o ber 2 0 2 3
1 7) P hase 2 C o h ort 1c ( m S C L C): Patie nts wit h S C L C w h o ha ve ha d pri or treat me nt wit h 
plati n u m- base d c he m ot hera p y wit h or wit h o ut i m m u n ot hera p y are eli gi ble. At least 1 pri or 
li ne of s yste mic a ntica ncer t hera p y i n a l ocall y a d va nce d/ metastatic setti n g is re q uire d a n d 
n ot m ore t ha n 2 pri or li nes of s yste mic a ntica ncer t hera p y i n a l ocall y a d va nce d/ metastatic 
setti n g are all o we d. Patie nts treate d wit h a ta xa ne wit hi n 1 2 m o nt hs or patie nts refract or y t o 
pri or ta xa ne treat me nt are e xcl u de d.
N ote: Mai nte na nce t hera pies are n ot c o u nte d as se parate li nes of t hera p y.
4. 3.  
E xcl usi o n Criteri a
Patie nts w h o meet a ny  of t he f oll o wi n g e xcl usi o n criteria are n ot t o be e nr olle d i n t his st u d y:
1)
P ositi ve ser u m pre g na nc y test
2)
Breastfee di n g fe male
3)
Acti ve C N S disease. Patie nts wit h as y m pt o matic a n d sta ble, treate d C N S lesi o ns (ra diati o n 
a n d/ or s ur ger y a n d/ or ot her C N S- directe d t hera p y w h o are off c ortic oster oi ds f or at least 
4 wee ks) are all o we d.
4)
Re d bl o o d cell tra nsf usi o n de pe n de nce, defi ne d as re q uiri n g m ore t ha n 2 u nits of pac ke d 
R B C tra nsf usi o ns d uri n g t he 4- wee k peri o d pri or t o scree ni n g. Re d bl o o d cell tra nsf usi o ns 
are per mitte d d uri n g t he scree ni n g peri o d a n d pri or t o e nr oll me nt t o meet t he he m o gl o bi n 
i ncl usi o n criteria.
5)
Hist or y of he m ol ytic a ne mia, a ut oi m m u ne t hr o m b oc yt o pe nia or E va ns s y n dr o me i n t he last 
3 m o nt hs
6)
K n o w n h y perse nsiti vit y t o a n y of t he st u d y dr u gs, t he meta b olites, or f or m ulati o n e xci pie nt
7)
Pri or treat me nt wit h C D 4 7- or SI R P α-tar geti n g a ge nts
8)
C urre nt partici pati o n i n a n ot her i nter ve nti o nal cli nical st u d y 
9)
K n o w n i n herite d or ac q uire d blee di n g dis or ders
1 0) Si g nifica nt disease or me dical c o n diti o ns, as assesse d b y t he i n vesti gat or a n d s p o ns or, t hat 
w o ul d s u bsta ntiall y i ncrease t he ris k- be nefit rati o of partici pati n g i n t he st u d y. T his i ncl u des, 
b ut is n ot li mite d t o, ac ute m y ocar dial i nfarcti o n wit hi n t he last 6 m o nt hs, u nsta ble a n gi na, 
u nc o ntr olle d dia betes mellit us, si g nifica nt acti ve i nfecti o ns, a n d c o n gesti ve heart fail ure 
Ne w Y or k Heart Ass ociati o n Class III-I V.
1 1) Sec o n d mali g na nc y, e xce pt treate d basal cell or l ocalize d s q ua m o us s ki n carci n o mas, 
l ocalize d pr ostate ca ncer, or ot her mali g na ncies f or w hic h patie nts are n ot o n acti ve 
a ntica ncer t hera pies a n d w h o are i n c o m plete re missi o n f or o ver 3 years


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 6
2 4 Oct o ber 2 0 2 3
1 2) K n o w n acti ve or c hr o nic he patitis B or C i nfecti o n or h u ma n i m m u n o deficie nc y vir us 
i nfecti o n i n me dical hist or y
1 3) Pri or a ntica ncer t hera p y i ncl u di n g b ut n ot li mite d t o c he m ot hera p y, i m m u n ot hera p y, or 
i n vesti gati o nal a ge nts wit hi n 4 wee ks pri or t o ma gr oli ma b is n ot per mitte d.
N O T E: Palliati ve, l ocalize d, n o n- C N S ra di ot hera p y t o areas of n o ntar get disease, pre vi o us 
h or m o nal t hera p y wit h l utei nizi n g h or m o ne releasi n g h or m o ne ( L H R H) a g o nists f or pr ostate 
or breast ca ncer, a n d treat me nt wit h bis p h os p h o nates a n d rece pt or acti vat or of n uclear fact or 
ka p pa B li ga n d ( R A N K L) i n hi bit ors are n ot criteria f or e xcl usi o n. T here is n o re q uire d 
mi ni m u m was h o ut peri o d f or t hese t hera pies. Patie nts s h o ul d be rec o vere d fr o m t he effects of 
ra diati o n.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 7
2 4 Oct o ber 2 0 2 3
5.  
I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T S
5. 1.   
R a n d o miz ati o n, Bli n di n g, a n d Tre at me nt C o des Access
5. 1. 1.   
R a n d o miz ati o n
Ra n d o mizati o n will n ot be perf or me d i n t his st u d y.
5. 1. 2.  
Bli n di n g
Bli n di n g of treat me nt assi g n me nts or data will n ot be perf or me d i n t his st u d y.
5. 2.   
Descri pti o n a n d H a n dli n g of M a gr oli m a b
5. 2. 1.  
F or m ul ati o n
Ma gr oli ma b is f or m ulate d as a sterile, clear, preser vati ve-free li q ui d i nte n de d f or I V 
a d mi nistrati o n c o ntai ni n g 1 0 m M s o di u m acetate, 5 % ( wei g ht-t o- v ol u me rati o [ w/ v]) s or bit ol, 
0. 0 1 % ( w/ v) p ol ys or bate 2 0 at p H of 5. 0. Eac h vial is ma n ufact ure d t o e ns ure a deli vera ble 
v ol u me of 1 0 m L c o ntai ni n g 2 0 0 m g of ma gr oli ma b at a c o nce ntrati o n of 2 0 m g/ m L.
5. 2. 2.  
P ac k a gi n g a n d L a beli n g
Ma gr oli ma b is s u p plie d i n si n gle- use, 1 0- m L glass vials wit h c oate d elast o meric st o p pers a n d 
al u mi n u m cri m p o verseals wit h a fli p- off ca p.
St u d y dr u g(s) t o be distri b ute d t o ce nters i n t he U S a n d ot her partici pati n g c o u ntries s hall be 
la bele d t o meet a p plica ble re q uire me nts of t he U S F D A, E ur o pea n U ni o n ( E U) G ui deli ne t o 
G o o d Ma n ufact uri n g Practice - A n ne x 1 3 (I n vesti gati o nal Me dici nal Pr o d ucts), a n d/ or ot her 
l ocal re g ulati o ns.
5. 2. 3.  
St or a ge a n d H a n dli n g
Ma gr oli ma b s h o ul d be st ore d at 2 ° C t o 8 ° C ( 3 6 ° F t o 4 6 ° F). Ma gr oli ma b s h o ul d n ot be fr oze n. 
Pr otect fr o m li g ht d uri n g st ora ge. D o n ot s ha ke. St ora ge c o n diti o ns are s pecifie d o n t he la bel. 
U ntil dis pe nse d t o t he patie nts, st u d y dr u gs s h o ul d be st ore d i n a sec urel y l oc ke d area, accessi ble 
o nl y t o a ut h orize d site pers o n nel.
T o e ns ure t he sta bilit y a n d pr o per i de ntificati o n, st u d y dr u g(s) s h o ul d n ot be st ore d i n a c o ntai ner 
ot her t ha n t he c o ntai ner i n w hic h t he y were s u p plie d.
C o nsi derati o n s h o ul d be gi ve n t o ha n dli n g, pre parati o n, a n d dis p osal t hr o u g h meas ures t hat 
mi ni mize dr u g c o ntact wit h t he b o d y. A p pr o priate preca uti o ns s h o ul d be f oll o we d t o a v oi d direct 
e ye c o ntact or e x p os ure w he n ha n dli n g.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 8
2 4 Oct o ber 2 0 2 3
5. 3.   
Descri pti o n a n d H a n dli n g of D ocet a xel
5. 3. 1.  
F or m ul ati o n
D oceta xel is c o m merciall y s o urce d. I nf or mati o n re gar di n g t he f or m ulati o n ca n be f o u n d i n t he 
c urre nt prescri bi n g i nf or mati o n.
5. 3. 2.  
P ac k a gi n g a n d L a beli n g
C o m mercial pr o d uct of d oceta xel will be use d f or t his st u d y. St u d y dr u g(s) t o be distri b ute d t o 
ce nters i n t he U S a n d ot her partici pati n g c o u ntries s hall be la bele d t o meet a p plica ble 
re q uire me nts of t he U S F D A, E U G ui deli ne t o G o o d Ma n ufact uri n g Practice – A n ne x 1 3 
(I n vesti gati o nal Me dici nal Pr o d ucts), a n d/ or ot her l ocal re g ulati o ns. Alter nati vel y, i n ali g n me nt 
wit h l ocal re g ulati o ns, c o m mercial pr o d uct ma y be s o urce d l ocall y b y t he sites.
5. 3. 3.  
St or a ge a n d H a n dli n g
D oceta xel is c o m merciall y s o urce d. I nf or mati o n re gar di n g t he st ora ge a n d ha n dli n g ca n be f o u n d 
i n t he c urre nt prescri bi n g i nf or mati o n.
5. 4.   
D os a ge a n d A d mi nistr ati o n of M a gr oli m a b
Vital si g ns will be assesse d pri or t o a n y I V st u d y dr u g a d mi nistrati o n.
Ma gr oli ma b s h o ul d be a d mi nistere d as o utli ne d i n t he P har mac y Ma n ual f or t he st u d y. T he d ose 
of ma gr oli ma b will be calc ulate d base d o n act ual wei g ht e nr oll me nt ( usi n g wei g ht o btai ne d 
eit her at scree ni n g or o n Da y 1) a n d will re mai n c o nsta nt t hr o u g h o ut t he st u d y, u nless t here is a 
> 1 0 % c ha n ge i n wei g ht fr o m baseli ne. M o dificati o ns t o t he st u d y dr u g d oses a d mi nistere d 
s h o ul d be ma de f or a > 1 0 % c ha n ge i n b o d y wei g ht a n d/ or acc or di n g t o l ocal a n d re gi o nal 
prescri bi n g sta n dar ds. D ose m o dificati o ns f or c ha n ges i n b o d y wei g ht < 1 0 % ma y be ma de 
acc or di n g t o l ocal i nstit uti o nal g ui deli nes.
T he d urati o n f or t he first ma gr oli ma b ( pri mi n g) i nf usi o n will be 3 h o urs ( ± 3 0 mi n utes). F or 
s u bse q ue nt d oses, t he ma gr oli ma b ( mai nte na nce) i nf usi o n will be 2 h o urs ( ± 3 0 mi n utes). T he 
re d uce d i nf usi o n ti me t o 2 h o urs is utilize d base d o n pri or data de m o nstrati n g maj orit y C D 4 7 R O 
o n peri p heral bl o o d cells, t h us miti gati n g a ntici pate d R B C t o xicities fr o m ma gr oli ma b. All 
patie nts s h o ul d be m o nit ore d h o url y d uri n g i nf usi o n. Patie nts s h o ul d be m o nit ore d (i ncl u di n g 
meas ure me nt of vital si g ns, as cli nicall y a p pr o priate) f or si g ns a n d s y m pt o ms of I R Rs, w hic h 
ha ve bee n o bser ve d i n pre vi o us ma gr oli ma b st u dies.
Ma gr oli ma b d oses will be gi ve n wee kl y d uri n g C ycles 1 a n d 2. Ma gr oli ma b is t he n a d mi nistere d 
e ver y 3 wee ks d uri n g C ycle 3 a n d be y o n d f or a 2 1- da y c ycle. M a gr oli m a b d oses are n ot t o be 
gi ve n o n c o nsec uti ve d a ys .
W he n ma gr oli ma b is gi ve n i n c o m bi nati o n wit h d oceta xel ( Safet y R u n-i n C o h ort 1 a n d P hase 2 
C o h ort 1), ma gr oli ma b will be i nf use d first. All patie nts will be m o nit ore d f or 1 h o ur 
p osti nf usi o n f or pri mi n g, re pri mi n g, a n d mai nte na nce d oses d uri n g C ycle 1. P osti nf usi o n 
m o nit ori n g s h o ul d be gi n after t he i nf usi o n is c o m plete b ut pri or t o a d mi nisteri n g d oceta xel. 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 4 9
2 4 Oct o ber 2 0 2 3
P osti nf usi o n m o nit ori n g is n ot re q uire d f or d oses after C ycle 1. Patie nts w h o e x perie nce a n y 
treat me nt-e mer ge nt A Es d uri n g t he o bser vati o n peri o d s h o ul d be f urt her m o nit ore d, as cli nicall y 
a p pr o priate. Refer t o Secti o n 7. 8. 1. 1. 2  f or p osti nf usi o n he m o gl o bi n re p orti n g re q uire me nts.
Patie nts ma y c o nti n ue st u d y treat me nt u ntil t he y s h o w e vi de nce of disease pr o gressi o n, rela pse, 
l oss of cli nical be nefit, or u nacce pta ble t o xicit y (f urt her details a b o ut treat me nt disc o nti n uati o n 
are i n Secti o n 3. 4 ).
Tre at me nt Del a y a n d Re pri mi n g f or M a gr oli m a b
Gi ve n t he lar ge C D 4 7 a nti ge n si n k o n n or mal cells, patie nts w h o ha ve a l o n g d ose dela y of 
ma gr oli ma b are re q uire d t o be re pri me d wit h ma gr oli ma b d osi n g t o resat urate t he C D 4 7 a nti ge n 
si n k. G ui deli nes f or re pri mi n g/re-escalati o n f or ma gr oli ma b after a d ose dela y is pr o vi de d i n 
Secti o n 5. 5 .
T he ma gr oli ma b d osi n g re gi me ns f or eac h c o h ort are descri be d i n Ta ble 2  a n d Ta ble 3 .
5. 5.   
D ose M o dific ati o ns a n d Del a ys f or M a gr oli m a b
T he d ose of ma gr oli ma b s h o ul d n ot be re d uce d e xce pt i n Safet y R u n-i n C o h ort 1 i n t he case of 
d ose de-escalati o n base d o n D L Ts. 
Cli nical safet y a n d P K data fr o m d ose-fi n di n g st u dies i n b ot h s oli d t u m or a n d he mat ol o gic 
mali g na ncies ha ve n ot de m o nstrate d a n y d ose- de pe n de nt t o xicities ass ociate d wit h ma gr oli ma b. 
D ose re d ucti o n/ m o dificati o n ma y be all o we d i n certai n A Es/circ u msta nces t hat m ust be 
a p pr o ve d b y t he s p o ns or. If a d ose re d ucti o n is c o nsi dere d, a n i nitial a p pr o xi matel y 3 3 % d ose 
re d ucti o n fr o m t he rec o m me n de d P hase 2 d ose s h o ul d be d o ne (e g, fr o m 3 0 m g/ k g t o 2 0 m g/ k g 
a n d fr o m 2 0 m g/ k g t o 1 5 m g/ k g).
W he n d oceta xel is dela ye d d ue t o t o xicities, ma gr oli ma b s h o ul d c o nti n ue i n de pe n de ntl y as per 
t he ma gr oli ma b a d mi nistrati o n sc he d ule. C o nti n u o us d osi n g of ma gr oli ma b is nee de d t o 
mai ntai n efficaci o us e x p os ures a n d o pti mal efficac y. D uri n g t he mai nte na nce p hase 
( C ycle 3 o n war ds), if t he last d ose of ma gr oli ma b was a d mi nistere d wit hi n t he pre vi o us 1 0 t o 
2 0 da ys, t he s u bse q ue nt ma gr oli ma b d ose ma y be a d mi nistere d earlier t ha n sc he d ule d i n or der t o 
s y nc hr o nize wit h t he bac k b o ne c he m ot hera p y a d mi nistrati o n. 
Ma gr oli ma b ma y be wit h hel d if treat me nt-e mer ge nt a n d/ or relate d A Es occ ur, a n d will re q uire 
c o ns ultati o n wit h t he s p o ns or if t he dela y is l o n ger t ha n 3 da ys. I n t he e ve nt of ma gr oli ma b 
dela y, d osi n g s h o ul d res u me as s o o n as it is cli nicall y a p pr o priate a n d l o gisticall y p ossi ble, 
wit h o ut waiti n g t o ali g n wit h t he patie nt’s ori gi nal e ver y- 3- wee ks sc he d ule. 
T he re pri mi n g g ui deli nes s h o w n i n Ta ble 4  s h o ul d be f oll o we d f or patie nts wit h ma gr oli ma b 
d ose dela ys. D uri n g re pri mi n g, c ycle n u m beri n g a n d efficac y, bi o mar ker, P K, a n d 
i m m u n o ge nicit y assess me nts s h o ul d c o nti n ue as per assi g ne d c ycle n u m ber. T he safet y 
assess me nt s h o ul d f oll o w t he C ycle 1 safet y assess me nts a n d s witc h bac k t o assi g ne d c ycle 
sc he d ule s u bse q ue ntl y. If re pri mi n g is necessar y bef ore t he patie nt c o m pletes C ycle 1 or C ycle 2, 
t he re pri mi n g c ycle is a d mi nistere d b y re peati n g C ycle 1 d osi n g, f oll o we d b y C ycle 2 bef ore 
pr ocee di n g t o us ual sc he d uli n g.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 0
2 4 Oct o ber 2 0 2 3
Criteria f or per ma ne nt disc o nti n uati o n of ma gr oli ma b i ncl u de t he f oll o wi n g:
•
Gra de 4 I R R, as descri be d i n Secti o n 7. 8. 1
•
Gra de 4 n o n he mat ol o gic A E relate d t o ma gr oli ma b t hat d oes n ot i m pr o ve t o Gra de 2 or 
baseli ne wit hi n 3 0 da ys
If ma gr oli ma b is disc o nti n ue d f or reas o ns ot her t ha n disease pr o gressi o n, t he re mai ni n g dr u g(s) 
i n t he c o m bi nati o n re gi me n ma y be c o nti n ue d. Ma gr oli ma b ma y be wit h hel d if 
treat me nt-e mer ge nt a n d/ or ma gr oli ma b-relate d A Es occ ur, u ntil cli nical res ol uti o n or 
i m pr o ve me nt per t he treati n g p h ysicia n.
Treat me nt dela ys ( n ot d ue t o A Es) of m ore t ha n 4 wee ks (s uc h as a n u nrelate d me dical c o n diti o n 
wit h e x pecte d rec o ver y) m ust be a p pr o ve d b y t he s p o ns or.
T a ble 4.
Re pri mi n g G ui deli nes f or M a gr oli m a b
D ose
D osi n g fre q ue nc y
Mi ni m u m d ur ati o n of tre at me nt 
g a p t h at will le a d t o re pri mi n g
1 m g/ k g
N A – use d at i nitial pri mi n g
2 wee ks
1 5 m g/ k g
Wee kl y ( d uri n g C ycles 1 a n d/ or 2)
2 wee ks
Wee kl y ( d uri n g C ycles 1 a n d/ or 2)
2 wee ks
2 0 m g/ k g
E ver y 3 wee ks
4 wee ks
Wee kl y ( d uri n g C ycles 1 a n d/ or 2)
4 wee ks
3 0 m g/ k g
E ver y 3 wee ks
4 wee ks
4 5 m g/ k g
E ver y 3 wee ks
4 wee ks
6 0 m g/ k g
E ver y 3 wee ks
4 wee ks
N A = n ot a p plica ble
If pla n ne d s ur gical pr oce d ures are nee de d f or patie nts o n st u d y treat me nt, ma gr oli ma b will be 
dela ye d a n d restarte d i n acc or da nce wit h Ta ble 5 .


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 1
2 4 Oct o ber 2 0 2 3
T a ble 5.
M a gr oli m a b D osi n g G ui d a nce f or Pl a n ne d S ur gic al Pr oce d ures o n 
St u d y
Pl a n ne d S ur gic al Pr oce d ure
M a gr oli m a b D ose G ui d a nce
Mi ni mall y i n vasi ve pr oce d ure
( E xa m ples: bi o psies [e xcl u di n g l u n g/li ver], s ki n/s u bc uta ne o us 
lesi o n re m o val, cataract/ gla uc o ma/e ye s ur ger y/c yst osc o p y)
H ol d ma gr oli ma b d ose 3 da ys pri or t o pr oce d ure a n d 
restart after 3 da ys
M o deratel y i n vasi ve pr oce d ure
( E xa m ples: l u n g/li ver bi o ps y, h ysterect o m y, c h olec ystect o m y, 
hi p/ k nee re place me nt, mi n or la par osc o pic pr oce d ures, 
ste nt/a n gi o pat h y)
H ol d ma gr oli ma b d ose 3 da ys pri or t o pr oce d ure a n d 
restart after 5 da ys
Hi g hl y i n vasi ve pr oce d ure
( E xa m ples: ce ntral ner v o us s yste m/s pi ne s ur ger y, maj or vasc ular 
s ur ger y, car di ot h oracic s ur ger y, maj or la par osc o pic s ur ger y)
H ol d ma gr oli ma b d ose 3 da ys pri or t o pr oce d ure a n d 
restart after 7 da ys
5. 6.   
M a gr oli m a b Pre me dic ati o n a n d Pr o p h yl a xis
Pre me dicati o n is re q uire d pri or t o t he a d mi nistrati o n of t he first 2 d oses of ma gr oli ma b a n d i n 
case of rei ntr o d ucti o n wit h re pri mi n g. Pre me dicati o n d uri n g s u bse q ue nt i nf usi o ns ma y be 
c o nti n ue d base d o n t he treati n g p h ysicia n’s cli nical j u d g me nt a n d t he prese nce/se verit y of pri or 
I R Rs. G ui da nce is pr o vi de d i n Secti o n 7. 8. 1. 2 .
Pre me dicati o ns s h o ul d i ncl u de oral aceta mi n o p he n 6 5 0 t o 1 0 0 0 m g, oral or I V di p he n h y dra mi ne 
2 5 t o 5 0 m g, a n d I V de xa met has o ne 4 t o 2 0 m g, or c o m para ble re gi me n. If less t ha n 4 h o urs has 
ela pse d si nce a pri or d ose of aceta mi n o p he n has bee n gi ve n, t he d ose of aceta mi n o p he n 
pre me dicati o n ma y be o mitte d.
5. 7.  
Pri or a n d C o nc o mit a nt Me dic ati o ns
5. 7. 1.  
Pri or a n d C o nc o mit a nt Me dic ati o ns Wit h M a gr oli m a b
5. 7. 1. 1.  
Per mitte d C o nc o mita nt Me dicati o ns
Pre me dicati o n a n d pr o p h yla xis f or A Es is per mitte d w hile o n st u d y treat me nt. Palliati ve, 
l ocalize d n o n- C N S ra di ot hera p y t o areas of n o ntar get disease, er yt hr oi d a n d/ or m yel oi d gr o wt h 
fact ors, h or m o nal t hera p y, L H R H a g o nists f or pr ostate ca ncer, h or m o nal mai nte na nce t hera p y 
f or breast ca ncers, a n d treat me nt wit h bis p h os p h o nates/ R A N K L i n hi bit ors are per mitte d. 
C ortic oster oi d use is per mitte d f or s y m pt o matic treat me nt, pre me dicati o n, pse u d o pr o gressi o n, 
a n d/ or s pecific patie nt c o n diti o ns. C hr o nic hi g h- d ose ster oi d use is n ot rec o m me n de d u nless 
cli nicall y i n dicate d. Re d bl o o d cell a n d platelet tra nsf usi o n are per mitte d d uri n g t he st u d y as 
cli nicall y i n dicate d a n d rec or de d i n t he electr o nic case re p ort f or m (e C R F) de dicate d t o o n-st u d y 
tra nsf usi o ns. All c o nc o mita nt me dicati o ns, i ncl u di n g all prescri pti o n, o ver-t he-c o u nter, her bal 
s u p ple me nts, a n d I V me dicati o ns a n d fl ui ds recei ve d wit hi n 3 0 da ys bef ore t he first d ose of 
st u d y treat me nt t hr o u g h t he 3 0- da y safet y f oll o w- u p visit are t o be rec or de d i n t he e C R F. O nl y 
t he dr u g na me, i n dicati o n, r o ute, a n d dates of c o nc o mita nt me dicati o ns will be ca pt ure d i n t he 
e C R F.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 2
2 4 Oct o ber 2 0 2 3
T here are n o s u bsta ntial safet y data re gar di n g t he c o nc o mita nt a d mi nistrati o n of t he C O VI D ‑1 9 
vacci nes a n d ma gr oli ma b. Patie nts are all o we d t o recei ve t he C O VI D ‑1 9 vacci ne, a n d st u d y 
visits s h o ul d c o nti n ue as pla n ne d if vacci nati o n occ urs w hile t he patie nt is o n t he st u d y. 
I n vesti gat ors s h o ul d f oll o w l ocal g ui deli nes f or c o nc o mita nt a d mi nistrati o n of t he C O VI D- 1 9 
vacci nes wit h t he st u d y dr u gs.
5. 7. 1. 2.  
Pr o hi bite d C o nc o mita nt Me dicati o ns
A ntica ncer t hera pies i ncl u di n g c he m ot hera p y, tar gete d t hera pies, a n d i m m u n ot hera p y (a part 
fr o m st u d y dr u gs) are n ot per mitte d w hile patie nts are o n st u d y.
5. 7. 2.  
Pri or a n d C o nc o mit a nt Me dic ati o ns Wit h D ocet a xel
T he c urre nt prescri bi n g i nf or mati o n s h o ul d be f oll o we d f or per mitte d a n d pr o hi bite d 
c o nc o mita nt me dicati o ns.
5. 8.   
D os a ge a n d A d mi nistr ati o n of D ocet a xel
T he d oceta xel d osi n g re gi me ns f or Safet y R u n-i n C o h ort 1 a n d P hase 2 C o h ort 1 are descri be d i n 
Ta ble 2  a n d Ta ble 3 , res pecti vel y.
5. 9.   
D ocet a xel Pre me dic ati o n a n d Pr o p h yl a xis
F or d oceta xel treat me nt, all patie nts s h o ul d be pre me dicate d t o re d uce t he i nci de nce a n d se verit y 
of h y perse nsiti vit y reacti o ns a n d fl ui d rete nti o n per t heir i nstit uti o nal sta n dar d of care or as 
f oll o ws. S uc h pre me dicati o n ma y c o nsist of oral c ortic oster oi ds s uc h as de xa met has o ne 1 6 m g 
per da y (e g, 8 m g t wice dail y) f or 3 da ys starti n g 1 da y pri or t o d oceta xel. F or i nsta nces w he n a 
patie nt d oes n ot start oral c ortic oster oi ds pri or t o d oceta xel a d mi nistrati o n, I V de xa met has o ne 
per i nstit uti o nal sta n dar d of care ca n be gi ve n pri or t o d oceta xel a d mi nistrati o n.
5. 1 0.   
D ose M o dific ati o ns f or D ocet a xel
D oceta xel is k n o w n t o ca use ne utr o pe nia, he pat ot o xicit y, peri p heral ne ur o pat h y, fl ui d rete nti o n, 
a n d h y perse nsiti vit y reacti o ns. D ose re d ucti o ns per ke y t o xicities are descri be d bel o w as 
rec o m me n dati o ns a n d are i n acc or da nce wit h t he d oceta xel prescri bi n g i nf or mati o n. A d diti o nal 
t o xicit y ma na ge me nt g ui deli nes are pr o vi de d i n d oceta xel prescri bi n g i nf or mati o n.
5. 1 0. 1.   
Ne utr o pe ni a
D oceta xel ca uses ne utr o pe nia; g ui da nce o n d ose re d ucti o ns are s h o w n i n Ta ble 6 . Patie nts s h o ul d 
ha ve a n A N C of at least 1 5 0 0 cells/ µ L bef ore i nitiati n g t he ne xt c ycle of d oceta xel t hera p y. 
M yel oi d gr o wt h fact or s u p p ort is all o we d per i nstit uti o nal g ui deli nes.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 3
2 4 Oct o ber 2 0 2 3
T a ble 6.
D ocet a xel D ose M o dific ati o ns f or Ne utr o pe ni a
He m at ol o gic T o xicit y
Occ urre nce
D ocet a xel D ose per 
C ycle ( m g/ m 2)a
First
5 5
Sec o n d
3 7. 5
Ne utr o pe nic fe ver ( na dir A N C < 5 0 0 cells/ µ L wit h fe ver > 3 8 ° C) 
f or > 7 da ys des pite gr o wt h fact or s u p p ort
Dela y of ne xt c ycle b y > 1 4 da ys f or na dir A N C < 1 5 0 0 cells/ µ L
or
Na dir A N C < 5 0 0 cells/ µl f or > 7 da ys
T hir d 
Disc o nti n ue treat me nt
A N C = a bs ol ute ne utr o p hil c o u nt
a  
If d oceta xel is d ose de-escalate d i n Safet y R u n-i n C o h ort 1 a n d t his d ose is utilize d i n P hase 2, t he n d ose re d ucti o ns s h o ul d 
f oll o w t he ne xt l o west d ose. F or e xa m ple, if a 5 5 m g/ m2 d oceta xel d ose is selecte d wit h ma gr oli ma b (as part of d ose 
de-escalati o n), t he n i n t he first i nsta nce of t o xicit y, d oceta xel s h o ul d be d ose re d uce d t o 3 7. 5 m g/ m 2. If a 3 7. 5 m g/ m2 
d oceta xel d ose is selecte d wit h ma gr oli ma b (as part of d ose de-escalati o n), t he n i n t he first i nsta nce of t o xicit y, d oceta xel 
w o ul d be disc o nti n ue d.
5. 1 0. 2.   
He p atic T o xicit y
D oceta xel s h o ul d be wit h hel d f or Gra de 3 or 4 he patic t o xicit y dee me d relate d t o d oceta xel as 
s pecifie d i n Ta ble 7 . Gi ve n t hat ma gr oli ma b ca n ca use tra nsie nt i ncrease i n i n direct bilir u bi n d ue 
t o o n-tar get a ne mia, d ose m o dificati o ns f or d oceta xel i n t he case of bilir u bi n m ust n ot be 
attri b ute d t o ma gr oli ma b. I n a d diti o n, t he i n vesti gat or s h o ul d ma ke all eff orts t o e xcl u de 
mali g na nt disease pr o gressi o n as a ca use of li ver e nz y me dera n ge me nt, w hic h w o ul d n ot be 
c o nsi dere d a t o xicit y f or d oceta xel.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 4
2 4 Oct o ber 2 0 2 3
T a ble 7.
D ocet a xel D ose Re d ucti o ns f or He p atic T o xicit y
He p atic T o xicit y
Occ urre nce 
D ocet a xel D ose M o dific ati o n a
First 
I nterr u pt treat me nt u ntil A S T/ A L T le vel is 
≤ 1. 5  U L N a n d  al kali ne p h os p hatase le vel is 
≤ 2. 5  U L N, t he n re d uce t o 5 5 m g/ m2.
I nterr u pt treat me nt u ntil bilir u bi n ≤ 1. 2 5  U L N, t he n 
re d uce t o 5 5 m g/ m2.
If t o xicit y d oes n ot res ol ve t o a b o ve criteria wit hi n 
3 wee ks, disc o nti n ue treat me nt.
Sec o n d 
I nterr u pt treat me nt u ntil A S T/ A L T le vel is 
< 1. 5  U L N a n d  al kali ne p h os p hatase le vel is 
≤ 2. 5  U L N, t he n re d uce t o 3 7. 5 m g/ m2.
I nterr u pt treat me nt u ntil bilir u bi n ≤ 1. 2 5  U L N, t he n 
re d uce t o 3 7. 5 m g/ m2.
If t o xicit y d oes n ot res ol ve t o a b o ve criteria wit hi n 
3 wee ks, disc o nti n ue treat me nt.
A S T or A L T le vel > 1. 5  U L N ( or 
baseli ne if hi g her) a n d al kali ne 
p h os p hatase > 2. 5  U L N
or
Bilir u bi n le vel > 1. 2 5  U L N ( n ot 
attri b ute d t o ma gr oli ma b a n d is m ostl y 
direct)
T hir d 
Disc o nti n ue treat me nt
A S T or A L T > 3  U L N ( or baseli ne if 
hi g her) a n d  bilir u bi n > 2  U L N ( n ot 
attri b ute d t o ma gr oli ma b a n d is m ostl y 
direct)
A n y 
Disc o nti n ue treat me nt
Bilir u bi n > 5  U L N ( n ot attri b ute d t o 
ma gr oli ma b a n d is m ostl y direct)
A n y 
Disc o nti n ue treat me nt
A S T or A L T > 5 t o 1 0  U L N f or 
> 2 wee ks
or
A S T or A L T > 1 0  U L N or baseli ne
A n y 
Disc o nti n ue treat me nt
A L T = ala ni ne a mi n otra nsferase; A S T = as partate a mi n otra nsferase; U L N = u p per li mit of n or mal
a  
If d oceta xel is d ose de-escalate d i n Safet y R u n-i n C o h ort 1 a n d t his d ose is utilize d i n P hase 2, t he n d ose re d ucti o ns s h o ul d 
f oll o w t he ne xt l o west d ose. F or e xa m ple, if a 5 5 m g/ m2 d oceta xel d ose is selecte d wit h ma gr oli ma b (as part of d ose 
de-escalati o n), t he n i n t he first i nsta nce of t o xicit y, d oceta xel s h o ul d be d ose re d uce d t o 3 7. 5 m g/ m 2. If a 3 7. 5 m g/ m² 
d oceta xel d ose is selecte d wit h ma gr oli ma b (as part of d ose de-escalati o n), t he n i n t he first i nsta nce of t o xicit y, d oceta xel 
w o ul d be disc o nti n ue d.
5. 1 0. 3.  
Peri p her al Ne ur o p at h y
Patie nts w h o de vel o p ≥ Gra de 3 peri p heral ne ur o pat h y relate d t o d oceta xel s h o ul d ha ve 
d oceta xel disc o nti n ue d per ma ne ntl y.
5. 1 0. 4.   
Ot her T o xicities
Ta ble 8  s h o ws t he d oceta xel d ose m o dificati o ns f or ot her Gra de 3 or 4 he mat ol o gic or 
n o n he mat ol o gic t o xicities dee me d relate d t o d oceta xel. D oceta xel s h o ul d be dela ye d u ntil 
i m pr o ve me nt of Gra de 3 or 4 t o xicit y t o at least Gra de 2 or better or baseli ne.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 5
2 4 Oct o ber 2 0 2 3
T a ble 8.
D ocet a xel D ose M o dific ati o ns f or Ot her Gr a de 3/ 4 T o xicities 
Ot her T o xicit y
Occ urre nce
D ocet a xel D ose per C ycle 
( m g/ m2)a
First
5 5
Sec o n d
3 7. 5
Gra de 3 or 4 n o n he mat ol o gic or 
he mat ol o gic t o xicit y b t hat d oes n ot 
res ol ve t o ≤ Gra de 2 wit hi n 1 4 da ys 
T hir d
Disc o nti n ue treat me nt
a  
If d oceta xel is d ose de-escalate d i n Safet y R u n-i n C o h ort 1 a n d t his d ose is utilize d i n P hase 2, t he n d ose re d ucti o ns s h o ul d 
f oll o w t he ne xt l o west d ose. F or e xa m ple, if a 5 5 m g/ m2 d oceta xel d ose is selecte d wit h ma gr oli ma b (as part of d ose 
de-escalati o n), t he n i n t he first i nsta nce of t o xicit y, d oceta xel s h o ul d be d ose re d uce d t o 3 7. 5 m g/ m 2. If a 3 7. 5 m g/ m² 
d oceta xel d ose is selecte d wit h ma gr oli ma b (as part of d ose de-escalati o n), t he n i n t he first i nsta nce of t o xicit y, d oceta xel 
w o ul d be disc o nti n ue d.
b   
Gra de 3 or 4 n o n he mat ol o gic or he mat ol o gic t o xicities a p pl y t o t h ose n ot descri be d i n t he a b o ve d ose m o dificati o n secti o ns.
5. 1 1.   
Acc o u nt a bilit y f or I n vesti g ati o n al Me dici n al Pr o d uct
T he i n vesti gat or is res p o nsi ble f or e ns uri n g a de q uate acc o u nta bilit y of all use d a n d u n use d st u d y 
dr u g ( kits, vials, etc). T his i ncl u des ac k n o wle d g me nt of recei pt of eac h s hi p me nt of st u d y dr u g 
( q ua ntit y a n d c o n diti o n).
Eac h st u d y site m ust kee p acc o u nta bilit y rec or ds t hat ca pt ure:
•
T he date recei ve d a n d q ua ntit y of st u d y dr u g ( kits, vials, etc)
•
T he date, patie nt n u m ber, a n d t he st u d y l ot n u m ber dis pe nse d
•
T he date, q ua ntit y of use d a n d u n use d st u d y dr u g ret ur ne d, al o n g wit h t he i nitials of t he 
pers o n rec or di n g t he i nf or mati o n
5. 1 1. 1.  
I n vesti g ati o n al Me dici n al Pr o d uct Ret ur n or Dis p os al
Gilea d rec o m me n ds t hat use d a n d u n use d st u d y dr u g s u p plies be destr o ye d at t he site. If t he site 
has a n a p pr o priate sta n dar d o perati n g pr oce d ure ( S O P) f or dr u g destr ucti o n as deter mi ne d b y 
Gilea d, t he site ma y destr o y use d (e m pt y or partiall y e m pt y) a n d u n use d st u d y dr u g s u p plies i n 
acc or da nce wit h t hat site’s a p pr o ve d S O P. A c o p y of t he site’s a p pr o ve d S O P will be o btai ne d 
f or t he electr o nic trial master file. If st u d y dr u g is destr o ye d at t he site, t he i n vesti gat or m ust 
mai ntai n acc urate rec or ds f or all st u d y dr u gs destr o ye d. Rec or ds m ust s h o w t he i de ntificati o n 
a n d q ua ntit y of eac h u nit destr o ye d, t he met h o d of destr ucti o n, a n d t he pers o n w h o dis p ose d of 
t he st u d y dr u g. U p o n st u d y c o m pleti o n, c o pies of t he st u d y dr u g acc o u nta bilit y rec or ds m ust be 
file d at t he site. A n ot her c o p y will be ret ur ne d t o Gilea d.
If t he site d oes n ot ha ve a n a p pr o priate S O P f or st u d y dr u g destr ucti o n, use d a n d u n use d st u d y 
dr u g s u p plies are t o be se nt t o t he desi g nate d dis p osal facilit y f or destr ucti o n. T he st u d y m o nit or 
will pr o vi de i nstr ucti o ns f or ret ur n.
T he st u d y m o nit or will re vie w st u d y dr u g s u p plies a n d ass ociate d rec or ds at peri o dic i nter vals.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 6
2 4 Oct o ber 2 0 2 3
6.  
S T U D Y P R O C E D U R E S
T he st u d y pr oce d ures t o be c o n d ucte d f or eac h patie nt e nr olle d i n t he st u d y are prese nte d i n 
ta b ular f or m i n A p pe n di x Ta ble 1  a n d A p pe n di x Ta ble 2 , a n d descri be d i n t he f oll o wi n g 
secti o ns.
T he i n ve sti gat or m ust d oc u me nt a n y de viati o n fr o m t he pr ot oc ol pr oce d ures a n d n otif y Gilea d or 
t he c o ntract researc h or ga nizati o n ( C R O).
6. 1.  
P atie nt E nr oll me nt a n d Tre at me nt Assi g n me nt
E ntr y i nt o scree ni n g d oes n ot g uara ntee e nr oll me nt o nt o t he st u d y. T o ma na ge t he t otal st u d y 
e nr oll me nt, Gilea d, at its s ole discreti o n, ma y s us pe n d scree ni n g a n d/ or e nr oll me nt at a n y site or 
st u d y- wi de at a n y ti me.
All patie nts will recei ve ma gr oli ma b + d oceta xel.
6. 2.  
Pretre at me nt Assess me nts
6. 2. 1.  
Scree ni n g Visit
Patie nts will be scree ne d wit hi n 3 0 da ys bef ore d osi n g o n C ycle 1 Da y 1 t o deter mi ne eli gi bilit y 
f or partici pati o n i n t he st u d y. Data fr o m assess me nts perf or me d as part of sta n dar d of care pri or 
t o o btai ni n g i nf or me d c o nse nt si g nat ure ma y be use d if t he y are wit hi n t he re q uire d scree ni n g 
peri o d. T he f oll o wi n g will be perf or me d a n d d oc u me nte d at scree ni n g per A p pe n di x 3 :
•
O btai n writte n i nf or me d c o nse nt
•
O btai n me dical hist or y i ncl u di n g c o nc o mita nt me dicati o ns
•
O btai n de m o gra p hic i nf or mati o n
•
C o m plete p h ysical e xa mi nati o n, i ncl u di n g vital si g ns, b o d y wei g ht, a n d hei g ht
•
O btai n bl o o d a n d uri ne sa m ples f or t he f oll o wi n g tests: c he mistr y, he mat ol o g y, c oa g ulati o n, 
uri nal ysis, ser u m pre g na nc y, e xte n de d R B C p he n ot y pi n g or ge n ot y pi n g, t y pe, a n d scree n, 
a n d direct a nti gl o b uli n test. Bl o o d f or bi o mar ker sa m ples will als o be c ollecte d (ie, P B M C [at 
selecte d sites], ser u m a n d plas ma, a n d w h ole bl o o d R N A).
•
T u m or bi o ps y
•
E C O G
•
Perf or m 1 2-lea d electr ocar di o gra m ( E C G; si n gle)
•
Rec or d all seri o us A Es ( S A Es) a n d A Es relate d t o pr ot oc ol- ma n date d pr oce d ures occ urri n g 
after si g ni n g of t he i nf or me d c o nse nt f or m (I C F)


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 7
2 4 Oct o ber 2 0 2 3
Fr o m t he ti me of o btai ni n g i nf or me d c o nse nt t hr o u g h t he first a d mi nistrati o n of st u d y dr u g, 
rec or d all S A Es, as well as a n y A Es relate d t o pr ot oc ol- ma n date d pr oce d ures o n t he A d verse 
E ve nts electr o nic case re p ort f or m (e C R F). All ot her u nt o war d me dical occ urre nces o bser ve d 
d uri n g t he scree ni n g peri o d, i ncl u di n g e xacer bati o n or c ha n ges i n me dical hist or y, are t o be 
c o nsi dere d me dical hist or y. See Secti o n 7 , A d verse E ve nts a n d T o xicit y Ma na ge me nt, f or 
a d diti o nal details.
6. 3.   
R a n d o miz ati o n
Ra n d o mizati o n will n ot be perf or me d i n t his st u d y.
6. 4.  
Tre at me nt Assess me nts
6. 4. 1.  
Pre g n a nc y Test
Pre g na nc y tests are re q uire d o nl y f or fe male patie nts of c hil d beari n g p ote ntial. N ote t hat a 
w o ma n is c o nsi dere d t o be of c hil d beari n g p ote ntial f oll o wi n g t he i nitiati o n of p u bert y ( Ta n ner 
Sta ge 2) u ntil bec o mi n g p ost me n o pa usal, u nless per ma ne ntl y sterile or wit h me dicall y 
d oc u me nte d o varia n fail ure. Per ma ne nt sterilizati o n i ncl u des h ysterect o m y, bilateral 
o o p h orect o m y, or bilateral sal pi n gect o m y i n a fe male patie nt of a n y a ge. W o me n are c o nsi dere d 
t o be i n a p ost me n o pa usal state w he n t he y are ≥ 5 4 years of a ge wit h cessati o n of pre vi o usl y 
occ urri n g me nses f or ≥ 1 2 m o nt hs wit h o ut a n alter nati ve ca use. I n a d diti o n, w o me n of < 5 4 years 
of a ge wit h a me n orr hea of ≥ 1 2 m o nt hs ma y als o be c o nsi dere d p ost me n o pa usal if t heir 
f ollicle-sti m ulati n g h or m o ne le vel is i n t he p ost me n o pa usal ra n ge a n d t he y are n ot usi n g 
h or m o nal c o ntrace pti o n or h or m o nal re place me nt t hera p y. A ne gati ve ser u m pre g na nc y test is 
re q uire d at scree ni n g, a n d a ne gati ve pre g na nc y test is re q uire d pri or t o st u d y treat me nt 
a d mi nistrati o n o n C ycle 1 Da y 1. T he C ycle 1 Da y 1 pre g na nc y test d oes n ot nee d t o be re peate d 
if t he scree ni n g pre g na nc y test was perf or me d wit hi n t he 7 2 h o urs bef ore st u d y treat me nt 
a d mi nistrati o n. Pre g na nc y tests will als o be re q uire d at Da y 1 of eac h s u bse q ue nt c ycle, a n d 
c o nti n ue m o nt hl y u p t o 6 m o nt hs after t he e n d of treat me nt per t he d urati o n of re q uire d 
c o ntrace pti o n as disc usse d i n A p pe n di x 6 . Testi n g d uri n g s ur vi val f oll o w- u p ma y be d o ne at 
h o me a n d t he res ult self-re p orte d b y t he patie nt. F or f urt her details, refer t o A p pe n di x 6 .
6. 4. 2.  
T y pe a n d Scree n a n d Direct A nti gl o b uli n Test
Please refer t o Secti o n 7. 8. 1. 1  f or detaile d g ui da nce o n t y pe a n d scree n a n d direct a nti gl o b uli n 
test. 
6. 4. 3.   
Vit al Si g ns
Vital si g ns are t o i ncl u de heart rate, res pirat or y rate, o x y ge n sat urati o n, bl o o d press ure, 
te m perat ure, a n d wei g ht. Hei g ht will be rec or de d d uri n g scree ni n g o nl y. Wei g ht will be rec or de d 
d uri n g scree ni n g a n d o n Da y 1 of eac h c ycle. Vital si g ns are t o be rec or de d pri or t o 
i nf usi o n/i njecti o n of ma gr oli ma b a n d d oceta xel at t he visits s pecifie d i n t he sc he d ules of 
assess me nts i n A p pe n di x 3 .


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 8
2 4 Oct o ber 2 0 2 3
6. 4. 4.  
P h ysic al E x a mi n ati o n
C o m plete p h ysical e xa mi nati o n is t o be perf or me d at scree ni n g. T hereafter, s y m pt o m- directe d 
p h ysical e xa mi nati o ns are acce pta ble a n d ma y als o i ncl u de r o uti ne e xa mi nati o n of t he s ki n 
(i ncl u di n g fi n gers, t oes, a n d ears) a n d ne ur ol o gic s yste m.
6. 4. 5.  
Perf or m a nce St at us
Perf or ma nce stat us will be sc ore d usi n g t he E C O G perf or ma nce stat us scale i n de x (refer t o 
A p pe n di x 7 ).
6. 4. 6.  
Electr oc ar di o gr a ms
A si n gle E C G will be perf or me d at scree ni n g.
6. 4. 7.   
A d verse E ve nts
At eac h visit, all A Es o bser ve d b y t he i n vesti gat or or re p orte d b y t he patie nt t hat occ ur after t he 
first d ose of st u d y treat me nt t hr o u g h 3 0 da ys after t he last d ose of st u d y treat me nt are t o be 
re p orte d usi n g t he a p plica ble e C R F ( Secti o n 7. 1. 1 ). F ull details o n t he defi niti o ns, assess me nt 
a n d re p orti n g i nstr ucti o ns f or A Es are pr o vi de d i n Secti o n 7 .
6. 4. 8.   
C o nc o mit a nt Me dic ati o ns
All c o nc o mita nt me dicati o ns ta ke n b y t he patie nt w hile o n st u d y are t o be d oc u me nte d. C ha n ges 
i n baseli ne c o nc o mita nt me dicati o n i nf or mati o n is t o be c ollecte d after i nf or me d c o nse nt t hr o u g h 
t he st u d y treat me nt peri o d, a n d u p u ntil 3 0 da ys after treat me nt disc o nti n uati o n. C o nc o mita nt 
me dicati o n ass ociate d wit h pr oce d ure-relate d A Es will be ca pt ure d fr o m t he ti me of i nf or me d 
c o nse nt a n d o n war d. I nf or mati o n t o be c ollecte d i ncl u des t hera p y na me, i n dicati o n, r o ute, start 
date, a n d st o p date a n d m ust be re p orte d usi n g t he a p plica ble e C R F. N ote t hat a n y a ntica ncer 
t hera pies after t he st u d y treat me nt peri o d s h o ul d als o be c ollecte d per t he sc he d ules of 
assess me nts ( A p pe n di x 3 ).
6. 5. 
S afet y Assess me nts
Ta ble 9  prese nts a nal ytes t o be assesse d b y t he l ocal a n d/ or ce ntral la b orat or y or s pecialt y 
la b orat ories at scree ni n g. Refer t o Secti o n 7. 8. 1. 1  f or he m o gl o bi n testi n g re q uire me nts f or t he 
first 2 ma gr oli ma b d oses pre d ose a n d p ost d ose m o nit ori n g.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 5 9
2 4 Oct o ber 2 0 2 3
T a ble 9.
Scree ni n g L a b or at or y A n al ytes
C he mistr y
( Ser u m or Pl as m a) 
He m at ol o g y
Uri n al ysis a
Ot her L a b or at or y 
Me as ure me nts
S o di u m
P otassi u m
C hl ori de
Bicar b o nate
T otal pr otei n
Al b u mi n
Calci u m
Ma g nesi u m
P h os p h or us
Gl uc ose
B U N or urea
Creati ni ne
Uric aci d
T otal bilir u bi n
Direct bilir u bi n
I n direct bilir u bi n
A S T ( S G O T)
A L T ( S G P T)
Al kali ne p h os p hatase
R B C
He m o gl o bi n
He mat ocrit
Platelets
W B C t otal
W B C differe ntial
A bs ol ute a n d perce nt 
ne utr o p hil c o u nt
A bs ol ute a n d perce nt 
e osi n o p hils
A bs ol ute a n d perce nt 
bas o p hils
A bs ol ute a n d perce nt 
l y m p h oc ytes
A bs ol ute a n d perce nt 
m o n oc ytes
Retic ul oc ytes
C o a g ul ati o n
P T
I N R
a P T T or P T T
Gl uc ose
Pr otei n
Uri ne p H
Ket o nes
Bilir u bi n
Uri ne s pecific gra vit y
Pre g na nc y (ser u m)
Bl o o d t y pe a n d scree n 
( A B O/ R h), D A T, a n d 
E xte n de d R B C p he n ot y pi n g 
or ge n ot y pi n g 
A B O = a n y of t he 4 bl o o d gr o u ps A, B, A B, a n d O c o m prisi n g t he A B O s yste m; A L T = ala ni ne a mi n otra nsferase; 
a P T T = acti vate d partial t hr o m b o plasti n ti me; A S T = as partate a mi n otra nsferase; B U N = bl o o d urea nitr o ge n; D A T = direct 
a nti gl o b uli n test; I N R = i nter nati o nal n or malize d rati o; P T = pr ot hr o m bi n ti me; P T T = partial t hr o m b o plasti n ti me; R B C = re d 
bl o o d cell; R h = r hes us; S G O T = ser u m gl uta mic o xal oacetic tra nsa mi nase; S G P T = ser u m gl uta mic p yr u vic tra nsa mi nase; 
W B C = w hite bl o o d cell
N ote: A nal ytes are re q uire d t o be c ollecte d at scree ni n g. Refer t o A p pe n di x Ta ble 1  f or c ollecti o n ti me p oi nts.
a  
Refle x micr osc o pic testi n g base d o n ot her a b n or malities.
Ta ble 1 0  prese nts a nal ytes t o be assesse d b y t he l ocal a n d/ or ce ntral la b orat or y or s pecialt y 
la b orat ories d uri n g t he st u d y.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 0
2 4 Oct o ber 2 0 2 3
T a ble 1 0.
St u d y L a b or at or y A n al ytes 
C he mistr y 
( Ser u m or Pl as m a)
He m at ol o g y
Ot her L a b or at or y Me as ure me nts
S o di u m
P otassi u m
C hl ori de
Bicar b o nate
T otal pr otei n
Al b u mi n
Calci u m
Ma g nesi u m
P h os p h or us
Gl uc ose
B U N or urea
Creati ni ne
Uric aci d
T otal bilir u bi n
Direct bilir u bi n
I n direct bilir u bi n
A S T ( S G O T)
A L T ( S G P T)
Al kali ne p h os p hatase
Ha pt o gl o bi n
L D H
R B C
He m o gl o bi n
He mat ocrit
Platelets
W B C t otal
W B C differe ntial
A bs ol ute a n d perce nt ne utr o p hil 
c o u nt
A bs ol ute a n d perce nt e osi n o p hils
A bs ol ute a n d perce nt bas o p hils
A bs ol ute a n d perce nt l y m p h oc ytes
A bs ol ute a n d perce nt m o n oc ytes
Retic ul oc ytes
Pre g na nc y ( uri ne or ser u m)
Bl o o d sa m ples c orrelati ve st u dies  a
P har mac o ki netics
A nti dr u g a nti b o dies  a
A B O = a n y of t he 4 bl o o d gr o u ps A, B, A B, a n d O c o m prisi n g t he A B O s yste m; A L T = ala ni ne a mi n otra nsferase; 
A S T = as partate a mi n otra nsferase; B U N = bl o o d urea nitr o ge n; L D H = lactate de h y dr o ge nase; R B C = re d bl o o d cell; 
R h = r hes us; S G O T = ser u m gl uta mic o xal oacetic tra nsa mi nase; S G P T = ser u m gl uta mic p yr u vic tra nsa mi nase; W B C = w hite 
bl o o d cell
N ote: A nal ytes are re q uire d t o be c ollecte d at visits d uri n g st u d y. Refer t o A p pe n di x Ta ble 1  f or c ollecti o n ti me p oi nts.
a  
T hese assa ys will be perf or me d at a ce ntral la b orat or y.
6. 6.  
Effic ac y Assess me nts
Eit her c o ntrast-e n ha nce d c o m p ute d t o m o gra p h y ( C T), ga d oli ni u m-e n ha nce d ma g netic res o na nce 
i ma gi n g, or p ositr o n e missi o n t o m o gra p h y- C T (t hat i ncl u des a c o ntrast-e n ha nce d C T 
c o m p o ne nt) of t he c hest, a b d o me n, a n d pel vis will be perf or me d at scree ni n g, e ver y 9 wee ks 
( 2 1- da y d osi n g c ycle) d uri n g t he st u d y (starti n g fr o m C ycle 1 Da y 1) a n d at t he e n d- of-treat me nt 
( E O T) visit if o ne has n ot bee n perf or me d wit hi n t he last 3 0 da ys or pr o gressi ve disease has bee n 
d oc u me nte d. T he o n-treat me nt i ma gi n g wi n d o w is ± 7 da ys. T u m or b ur de n will be e val uate d 
s olel y base d o n ra di o gra p hic i ma gi n g per R E CI S T, Versi o n 1. 1. C hest x-ra y, ultras o u n d, 
e n d osc o p y, la par osc o p y, p ositr o n-e missi o n t o m o gra p h y, ra di o n ucli de sca ns, or t u m or mar kers 
will n ot be c o nsi dere d f or res p o nse assess me nt.
F or ra di o gra p hic e val uati o ns, t he sa me met h o d of assess me nt a n d t he sa me tec h ni q ue 
(e g, sca n t y pe, sca n ner, patie nt p ositi o n, d ose of c o ntrast, i njecti o n/sca n i nter val) s h o ul d be use d 
t o c haracterize eac h i de ntifie d a n d re p orte d lesi o n at baseli ne a n d d uri n g st u d y treat me nt a n d 
f oll o w- u p.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 1
2 4 Oct o ber 2 0 2 3
Sca ns ta ke n as part of sta n dar d me dical practice u p t o 3 0 da ys pri or t o e nr oll me nt ca n be use d f or 
scree ni n g as l o n g as t he y meet all st u d y re q uire me nts. D uri n g t he treat me nt p hase, sca ns ma y be 
perf or me d at ti me p oi nts ot her t ha n e ver y 9 wee ks ( 2 1- da y d osi n g c ycle) as cli nicall y i n dicate d 
t o assess t u m or pr o gressi o n.
F or patie nts w h o st o p st u d y treat me nt n ot relate d t o ra di o gra p hic disease pr o gressi o n (e g, 
e x perie nce d u ne x pecte d t o xicit y), sca ns s h o ul d c o nti n ue t o be c ollecte d a p pr o xi matel y e ver y 
9 wee ks ( 2 1- da y d osi n g c ycle) u ntil ra di o gra p hic disease pr o gressi o n (ie, pre pr o gressi o n visit 
[A p pe n di x Ta ble 2 ]) or i nitiati o n of s yste mic a ntit u m or t hera p y ot her t ha n t he st u d y treat me nt, 
w hic he ver i s earlier. Pre- pr o gressi o n visits will be c o m plete d first bef ore pr ocee di n g t o s ur vi val 
f oll o w- u p.
All rele va nt cli nical a n d ra di o gra p hic i nf or mati o n re q uire d t o ma ke eac h assess me nt m ust be 
ma de a vaila ble f or s o urce verificati o n. Disease pr o gressi o n will be deter mi ne d b y t he 
i n vesti gat or or q ualifie d desi g nee.
Patie nts will be assesse d f or res p o nse usi n g R E CI S T, Versi o n 1. 1 { Eise n ha uer 2 0 0 9 } f or t he 
pri mar y e fficac y e n d p oi nt a n d f or t he sec o n dar y efficac y e n d p oi nt (A p pe n di x 8 ).
6. 7.  
P h ar m ac o ki netic Assess me nts
Ma gr oli ma b ser u m c o nce ntrati o n will be meas ure d b y a vali date d e nz y me-li n ke d i m m u n os or be nt 
assa y ( E LI S A) i m m u n oassa y met h o d.
Bl o o d sa m ples f or P K assess me nt will be c ollecte d pre d ose at m ulti ple ti me p oi nts acc or di n g t o 
t he sc he d ules of assess me nts i n A p pe n di x Ta ble 3  ( n ote t he a d diti o nal sa m ple c ollecte d p ost d ose 
o n C ycle 3 Da y 1 at 1 h ± 1 5 mi n after t he e n d of ma gr oli ma b i nf usi o n). Resi d ual sa m ples use d 
f or P K a n d A D A a nal ysis ma y als o be use d f or   
 P K or P D a nal yses relate d t o 
ma gr oli ma b treat me nt al o ne as well as c o m bi nati o n t hera p y wit h a ntica ncer c he m ot hera pies. 
T his c o ul d i ncl u de usi n g left o ver ser u m f or   
 alter nati ve P K assa y de vel o p me nt a n d 
a nal ysis.
6. 8.  
I m m u n o ge nicit y ( A nti dr u g A nti b o dies)
Peri p heral bl o o d f or i m m u n o ge nicit y assess me nts f or A D A a gai nst ma gr oli ma b will be c ollecte d 
as descri be d i n t he sc he d ules of assess me nts f or all patie nts ( A p pe n di x Ta ble 3 ). W he n c ollecte d 
o n t he da y of st u d y dr u g d osi n g, t he A D A bl o o d sa m ple m ust be c ollecte d at t he sa me ti me as t he 
pre d ose P K sa m ple. T he prese nce of a nti- ma gr oli ma b a nti b o dies will be deter mi ne d b y a 
vali date d electr oc he mil u mi nesce nce i m m u n oassa y met h o d.
6. 9.  
Bi o m ar ker Assess me nts
Bi o mar ker sa m ples will be c ollecte d t o assess t he P D, M O A, a n d treat me nt res p o nse bi o mar kers, 
a n d t o defi ne c orrelates of cli nical efficac y a n d/ or safet y, as o utli ne d i n Secti o n 3. 8 . T he 
bi o mar ker sa m ple c ollecti o n sc he d ule is o utli ne d i n A p pe n di x Ta ble 3 .
C CI
C CI--


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 2
2 4 Oct o ber 2 0 2 3
Patie nts are re q uire d t o s u b mit a ma n dat or y pretreat me nt c ore nee dle or e xcisi o nal t u m or bi o ps y 
(fi ne nee dle as pirate is n ot a de q uate) fr o m a site n ot pre vi o usl y irra diate d, u nless n ot feasi ble as 
deter mi ne d b y t he i n vesti gat or a n d disc usse d wit h t he s p o ns or. A ne wl y o btai ne d bi o ps y, 
c ollecte d wit hi n 9 0 da ys pri or t o st u d y treat me nt start, is str o n gl y preferre d, b ut a n arc hi val 
sa m ple is acce pta ble. F or arc hi val sa m ples s u b mitte d i n lie u of ne wl y o btai ne d bi o psies, tiss ue 
c ollecte d wit hi n 6 m o nt hs pri or t o st u d y treat me nt start is str o n gl y preferre d w he ne ver p ossi ble.
Patie nts will als o s u b mit a ma n dat or y o n-treat me nt c ore nee dle or e xcisi o nal t u m or bi o ps y u nless 
n ot feasi ble as deter mi ne d b y t he i n vesti gat or a n d disc usse d wit h t he s p o ns or.
F or a d diti o nal details a n d i nstr ucti o ns re gar di n g tiss ue re q uire me nts a n d pr oce d ures f or sa m ple 
c ollecti o n, st ora ge, a n d s hi p me nt, refer t o t he St u d y La b orat or y Ma n ual.
6. 1 0.  
P osttre at me nt Assess me nts
P osttreat me nt assess me nts are pr o vi de d i n A p pe n di x Ta ble 2 . T here are 2 t y pes of f oll o w- u p 
visit: safet y f oll o w- u p ( 3 0 da ys [ ± 7 da ys] after t he last d ose of st u d y dr u g) a n d s ur vi val 
f oll o w- u p (e ver y 2 m o nt hs after safet y f oll o w- u p [ ± 7 da ys]). Patie nts w h o disc o nti n ue st u d y 
treat me nt are t o ret ur n f or a n E O T visit f or e val uati o n of safet y wit hi n 7 da ys of t heir last d ose or 
t he decisi o n t o e n d st u d y treat me nt. I n a d diti o n, patie nts are t o ha ve a safet y f oll o w- u p tele p h o ne 
call 3 0 da ys ( ± 7 da ys) after t heir last d ose of st u d y treat me nt. W he n a seri o us a d verse e ve nt 
( S A E) or treat me nt-relate d A E is re p orte d d uri n g t he tele p h o ne call, t he patie nt s h o ul d c o me t o 
t he cli nic f or p h ysical e xa mi nati o n a n d bl o o d tests, if cli nicall y nee de d. F oll o w- u p f or o n g oi n g 
S A Es or treat me nt-relate d A Es after t he safet y f oll o w- u p visit/call will st o p if a patie nt be gi ns 
a n ot her a ntica ncer t hera p y. Pre g na nc y testi n g will c o nti n ue m o nt hl y u p t o 6 m o nt hs after t he e n d 
of treat me nt per t he d urati o n of re q uire d c o ntrace pti o n as disc usse d i n A p pe n di x 6 . Testi n g 
d uri n g s ur vi val f oll o w- u p ma y be d o ne at h o me a n d t he res ult self-re p orte d b y t he patie nt. 
S ur vi val f oll o w- u p will be c o n d ucte d via a p h o ne call e ver y 2 m o nt hs u ntil deat h or e n d of st u d y. 
D urati o n of s ur vi val f oll o w- u p will be li mite d t o 3 years.
6. 1 1.   
Assess me nts f or E arl y Disc o nti n u ati o n Fr o m St u d y
If a patie nt disc o nti n ues st u d y d osi n g (f or e xa m ple, as a res ult of a n A E), e ver y atte m pt s h o ul d 
be ma de t o kee p t he patie nt i n t he st u d y a n d c o nti n ue t o perf or m t he re q uire d st u d y-relate d 
f oll o w- u p a n d pr oce d ures ( Secti o n 6. 1 1. 1 , Criteria f or Disc o nti n uati o n of St u d y Treat me nt). I n 
t he a bse nce of disease pr o gressi o n, sca ns s h o ul d c o nti n ue t o be c ollecte d per Secti o n 6. 6  
Efficac y Assess me nt, u ntil disease pr o gressi o n or i nitiati o n of s yste mic a ntit u m or t hera p y ot her 
t ha n t he st u d y treat me nt, w hic he ver is earlier. If t his is n ot p ossi ble or acce pta ble t o t he patie nt or 
i n vesti gat or, t he patie nt ma y be wit h dra w n fr o m t he st u d y. F or patie nts w h o disc o nti n ue fr o m t he 
st u d y pri or t o c o m pleti o n of all pr ot oc ol-re q uire d visits f or st u d y assess me nts or s ur vi val 
f oll o w- u p as descri be d i n t he sc he d ule of assess me nts (A p pe n di x Ta ble 2 ), t he i n vesti gat or ma y 
searc h p u blicl y a vaila ble rec or ds ( w here per mitte d b y l ocal la ws a n d re g ulati o ns) t o ascertai n 
s ur vi val stat us u nless t he patie nt wit h dra ws c o nse nt f or s uc h f oll o w- u p. T his e ns ures re d uce d 
ris k of missi n g critical efficac y data.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 3
2 4 Oct o ber 2 0 2 3
6. 1 1. 1.   
Criteri a f or Disc o nti n u ati o n of St u d y Tre at me nt
Criteria f or disc o nti n uati o n of st u d y treat me nt is pr o vi de d i n i n Secti o n 3. 4 .
6. 1 2.   
Criteri a f or Disc o nti n u ati o n Fr o m St u d y/ E n d of St u d y
Criteria f or disc o nti n uati o n fr o m st u d y is pr o vi de d i n Secti o n 3. 5 .
6. 1 3. 
P ostst u d y C are
U p o n wit h dra wal fr o m st u d y treat me nt, patie nts will recei ve t he care u p o n w hic h t he y a n d t heir 
p h ysicia ns a gree. Patie nts will be f oll o we d f or disease pr o gressi o n if a p plica ble, s ur vi val, a n d 
A Es as s pecifie d i n A p pe n di x Ta ble 1 . P ostst u d y treat me nt assess me nts are descri be d i n 
A p pe n di x Ta ble 2 .
6. 1 4.  
S a m ple St or a ge
T he st ore d bi ol o gical sa m ples ma y be use d b y Gilea d or its researc h part ner f or  
 testi n g t o 
pr o vi de a d diti o nal data t o a ns wer q uesti o ns t hat relate t o t he mai n st u d y. At t he e n d of t his st u d y, 
t hese sa m ples ma y be retai ne d i n st ora ge b y Gilea d f or a peri o d u p t o 1 5 years. If patie nts 
pr o vi de a d diti o nal s pecific c o nse nt, resi d ual P K sa m ples ma y be destr o ye d n o later t ha n 1 5 years 
after t he e n d of st u d y or per c o u ntr y re q uire me nts.
C CI-


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 4
2 4 Oct o ber 2 0 2 3
7.   
A D V E R S E E V E N T S A N D T O XI CI T Y M A N A G E M E N T
7. 1.   
Defi niti o ns of A d verse E ve nts a n d Seri o us A d verse E ve nts
7. 1. 1.   
A d verse E ve nts
A n A E is a n y u nt o war d me dical occ urre nce i n a cli nical st u d y patie nt a d mi nistere d a st u d y dr u g 
t hat d oes n ot necessaril y ha ve a ca usal relati o ns hi p wit h t he treat me nt. A n A E ca n t heref ore be 
a n y u nfa v ora ble a n d/ or u ni nte n de d si g n, s y m pt o m, or disease te m p orall y ass ociate d wit h t he use 
of a st u d y dr u g, w het her or n ot t he A E is c o nsi dere d relate d t o t he st u d y dr u g. A d verse e ve nts 
ma y als o i ncl u de pretreat me nt or p osttreat me nt c o m plicati o ns t hat occ ur as a res ult of 
pr ot oc ol-s pecifie d pr oce d ures or s pecial sit uati o ns ( Secti o n 7. 1. 3 ). A n A E d oes n ot i ncl u de t he 
f oll o wi n g:
•
Me dical or s ur gical pr oce d ures s uc h as s ur ger y, e n d osc o p y, t o ot h e xtracti o n, a n d tra nsf usi o n. 
T he c o n diti o n t hat le d t o t he pr oce d ure ma y be a n A E a n d m ust be re p orte d.
•
Pree xisti n g diseases, c o n diti o ns, or la b orat or y a b n or malities prese nt or detecte d bef ore t he 
scree ni n g visit t hat d o n ot w orse n
•
Sit uati o ns w here a n u nt o war d me dical occ urre nce has n ot occ urre d (e g, h os pitalizati o n f or 
electi ve s ur ger y, s ocial a n d/ or c o n ve nie nce a d missi o ns)
•
O ver d ose wit h o ut cli nical se q uelae ( Secti o n 7. 1. 3 )
•
A n y me dical c o n diti o n or cli nicall y si g nifica nt la b orat or y a b n or malit y wit h a n o nset date 
bef ore t he I C F is si g ne d a n d n ot relate d t o a pr ot oc ol-ass ociate d pr oce d ure is n ot a n A E b ut 
rat her c o nsi dere d t o be pree xisti n g a n d s h o ul d be d oc u me nte d as me dical hist or y.
Pree xisti n g e ve nts t hat i ncrease i n se verit y or c ha n ge i n nat ure after st u d y dr u g i nitiati o n or as a 
c o nse q ue nce of partici pati o n i n t he cli nical st u d y will als o be c o nsi dere d A Es.
7. 1. 2.  
Seri o us A d verse E ve nts
A n S A E is defi ne d as a n e ve nt t hat, at a n y d ose, res ults i n t he f oll o wi n g:
•
Deat h
•
A life-t hreate ni n g sit uati o n ( N ote: T he ter m “life-t hreate ni n g” i n t he defi niti o n of “seri o us” 
refers t o a n e ve nt i n w hic h t he patie nt was at ris k of deat h at t he ti me of t he e ve nt; it d oes n ot 
refer t o a n e ve nt t hat h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere.)
•
I n- patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n
•
Persiste nt or si g nifica nt disa bilit y/i nca pacit y


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 5
2 4 Oct o ber 2 0 2 3
•
A c o n ge nital a n o mal y/ birt h defect
•
A me dicall y i m p orta nt e ve nt or reacti o n: S uc h e ve nts ma y n ot be i m me diatel y 
life-t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut ma y je o par dize t he patie nt or ma y 
re q uire i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes c o nstit uti n g S A Es. Me dical a n d 
scie ntific j u d g me nt m ust be e xercise d t o deter mi ne w het her s uc h a n e ve nt is re p orta ble u n der 
e x pe dite d re p orti n g r ules. E xa m ples of me dicall y i m p orta nt e ve nts i ncl u de i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m; bl o o d d yscrasias or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n; a n d de vel o p me nt of dr u g de pe n de nc y or 
dr u g a b use.
7. 1. 2. 1.  
Pr ot oc ol- S pecific A d verse E ve nt/ Seri o us A d verse E ve nt Clarificati o ns
Gi ve n pr o gressi o n of disease is o ne of t he e n d p oi nts of t he st u d y, i n or der t o mai ntai n st u d y 
i nte grit y, t he f oll o wi n g e ve nts t hat are assesse d as u nrelate d t o st u d y dr u g will n ot be c o nsi dere d 
A Es/ S A Es:
•
Pr o gressi o n of disease
•
Deat hs relate d t o pr o gressi o n of disease
E ve nts t hat are c o nsi dere d t o re prese nt pr o gressi o n of disease s h o ul d n ot be rec or de d as 
A Es/ S A Es u nless it is assesse d t hat st u d y dr u gs c o ntri b ute d t o disease pr o gressi o n. T hese data 
will be ca pt ure d as efficac y assess me nt data o nl y. If t here is a n y u ncertai nt y as t o w het her a n 
e ve nt is d ue t o disease pr o gressi o n, it s h o ul d be re p orte d as a n A E/ S A E.
Deat h t hat is attri b ute d b y t he i n vesti gat or as s olel y d ue t o disease pr o gressi o n a n d t hat occ urs 
d uri n g t he pr ot oc ol-s pecifie d A E re p orti n g peri o d s h o ul d be rec or de d o nl y o n t he deat h e C R F 
(ie, n ot c ollecte d as a n S A E o n t he A E e C R F).
7. 1. 2. 1. 1.   
Deat hs N ot Relate d t o Disease Pr o gressi o n
All ot her deat hs (ie, deat hs t hat are n ot d ue t o disease pr o gressi o n) occ urri n g d uri n g t he 
pr ot oc ol-s pecifie d A E re p orti n g peri o d, re gar dless of attri b uti o n, will be rec or de d o n t he A E 
e C R F a n d re p orte d wit hi n 2 4 h o urs of a ware ness a n d n o later t ha n t he ne xt b usi ness da y.
W he n rec or di n g a deat h o n t he e C R F, t he e ve nt or c o n diti o n t hat is c o nsi dere d t he pri mar y ca use 
of deat h s h o ul d be t he A E ter m, a n d t he o utc o me s h o ul d be deat h. A patie nt ca n o nl y ha ve 1 A E 
( S A E) wit h o utc o me of deat h a n d se verit y of C T C A E Gra de 5.
7. 1. 3.  
St u d y Dr u gs a n d Gile a d C o nc o mit a nt T her a p y S peci al Sit u ati o ns Re p orts
S pecial sit uati o n re p orts ( S S Rs) i ncl u de all re p orts of me dicati o n err or, a b use, mis use, o ver d ose, 
occ u pati o nal e x p os ure, dr u g i nteracti o ns, e x p os ure via breastfee di n g, u ne x pecte d be nefit, 
tra ns missi o n of i nfecti o us a ge nts via t he pr o d uct, c o u nterfeit or falsifie d me dici ne, a n d 
pre g na nc y re gar dless of a n ass ociate d A E.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 6
2 4 Oct o ber 2 0 2 3
Me dicati o n err or is a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, pre parati o n f or 
a d mi nistrati o n, or a d mi nistrati o n of a st u d y dr u g w hile t he me dicati o n is i n t he c o ntr ol of a 
healt h care pr ofessi o nal, patie nt, or c o ns u mer. Me dicati o n err ors ma y be classifie d as a 
me dicati o n err or wit h o ut a n A E, w hic h i ncl u des sit uati o ns of misse d d ose, me dicati o n err or wit h 
a n A E, i nterce pte d me dicati o n err or, or p ote ntial me dicati o n err or.
A b use is defi ne d as persiste nt or s p ora dic i nte nti o nal e xcessi ve use of a st u d y dr u g b y a patie nt.
Mis use is defi ne d as a n y i nte nti o nal a n d i na p pr o priate use of a st u d y dr u g t hat is n ot i n 
acc or da nce wit h t he pr ot oc ol i nstr ucti o ns or t he l ocal prescri bi n g i nf or mati o n.
A n o ver d ose is defi ne d as a n acci de ntal or i nte nti o nal a d mi nistrati o n of a q ua ntit y of a st u d y 
dr u g gi ve n per a d mi nistrati o n or c u m ulati vel y t hat is a b o ve t he ma xi m u m rec o m me n de d d ose as 
per pr ot oc ol or i n t he pr o d uct la beli n g (as it a p plies t o t he dail y d ose of t he patie nt i n q uesti o n). 
I n cases of a discre pa nc y i n dr u g acc o u nta bilit y, o ver d ose will be esta blis he d o nl y w he n it is 
clear t hat t he patie nt has ta ke n t he e xcess d ose(s). O ver d ose ca n n ot be esta blis he d w he n t he 
patie nt ca n n ot acc o u nt f or t he discre pa nc y, e xce pt i n cases i n w hic h t he i n vesti gat or has reas o n 
t o s us pect t hat t he patie nt has ta ke n t he a d diti o nal d ose(s).
Occ u pati o nal e x p os ure is defi ne d as e x p os ure t o a st u d y dr u g as a res ult of o ne’s pr ofessi o nal or 
n o n pr ofessi o nal occ u pati o n.
Dr u g i nteracti o n is defi ne d as a n y dr u g/ dr u g, dr u g/f o o d, or dr u g/ de vice i nteracti o n.
U ne x pecte d be nefit is defi ne d as a n u ni nte n de d t hera pe utic effect w here t he res ults are j u d ge d t o 
be desira ble a n d be neficial.
Tra ns missi o n of i nfecti o us a ge nts is defi ne d as a n y s us pecte d tra ns missi o n of a n i nfecte d a ge nt 
t hr o u g h a Gilea d st u d y dr u g.
C o u nterfeit or falsifie d me dici ne is defi ne d as a n y st u d y dr u g wit h a false re prese ntati o n of (a) its 
i de ntit y, ( b) its s o urce, or (c) its hist or y.
7. 2.   
Assess me nt of A d verse E ve nts a n d Seri o us A d verse E ve nts
T he i n vesti gat or or q ualifie d s u bi n vesti gat or is res p o nsi ble f or assessi n g A Es a n d S A Es f or 
ca usalit y a n d se verit y, a n d f or fi nal re vie w a n d c o nfir mati o n of acc urac y of e ve nt i nf or mati o n 
a n d assess me nts.
7. 2. 1.   
Assess me nt of C a us alit y f or St u d y Dr u gs, A ut h orize d A x M Ps, a n d 
Pr oce d ures
T he i n vesti gat or or q ualifie d s u bi n vesti gat or is res p o nsi ble f or assessi n g t he relati o ns hi p t o st u d y 
dr u g a n d A x M P usi n g cli nical j u d g me nt a n d t he f oll o wi n g c o nsi derati o ns:
•
N o : E vi de nce e xists t hat t he A E has a n eti ol o g y ot her t ha n t he st u d y dr u g. F or S A Es, a n 
alter nati ve ca usalit y m ust be pr o vi de d (e g, pree xisti n g c o n diti o n, u n derl yi n g disease, 
i nterc urre nt ill ness, or c o nc o mita nt me dicati o n).
•
Yes : T here is reas o na ble p ossi bilit y t hat t he e ve nt ma y ha ve bee n ca use d b y t he st u d y dr u g.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 7
2 4 Oct o ber 2 0 2 3
It s h o ul d be e m p hasize d t hat i neffecti ve treat me nt s h o ul d n ot be c o nsi dere d as ca usall y relate d i n 
t he c o nte xt of A E re p orti n g.
T he relati o ns hi p t o st u d y pr oce d ures (e g, i n vasi ve pr oce d ures s uc h as ve ni p u nct ure or bi o ps y) 
s h o ul d be assesse d usi n g t he f oll o wi n g c o nsi derati o ns:
•
N o: E vi de nce  e xists t hat t he A E has a n eti ol o g y ot her t ha n t he st u d y pr oce d ure.
•
Yes:  T he A E occ urre d as a res ult of pr ot oc ol pr oce d ures (e g, ve ni p u nct ure).
W he n t here is a reas o na ble p ossi bilit y t hat t he ca usalit y of t he A E/ S A E ca n be assi g ne d t o t he 
a ut h orize d A x M P, t he i n vesti gat or or q ualifie d s u bi n vesti gat or will nee d t o re p ort t he ca usalit y 
assess me nt f or t he a ut h orize d A x M Ps i n acc or da nce wit h t he e C R F.
7. 2. 2.   
Assess me nt of Se verit y
T he se verit y of A Es will be gra de d usi n g t he N CI C T C A E, Versi o n 5. 0. F or eac h e pis o de, t he 
hi g hest gra de attai ne d s h o ul d be re p orte d as defi ne d i n t he T o xicit y Gra di n g Scale ( A p pe n di x 5 ).
7. 3.  
I n vesti g at or Re p orti n g Re q uire me nts a n d I nstr ucti o ns
7. 3. 1.   
Re q uire me nts f or C ollecti o n Pri or t o St u d y Dr u g I niti ati o n
After i nf or me d c o nse nt, b ut pri or t o i nitiati o n of st u d y me dicati o n, t he f oll o wi n g t y pes of e ve nts 
m ust be re p orte d o n t he a p plica ble e C R Fs: all S A Es a n d A Es relate d t o pr ot oc ol- ma n date d 
pr oce d ures.
7. 3. 2.   
A d verse E ve nts
F oll o wi n g i nitiati o n of st u d y me dicati o n, all A Es, re gar dless of ca use or relati o ns hi p, will be 
c ollecte d u ntil 3 0 da ys after last a d mi nistrati o n of st u d y dr u g a n d re p orte d o n t he e C R Fs as 
i nstr ucte d.
All A Es will be f oll o we d u p u ntil res ol uti o n or u ntil t he A E is sta ble, if p ossi ble. Gilea d ma y 
re q uest t hat certai n A Es be f oll o we d be y o n d t he pr ot oc ol- defi ne d f oll o w- u p peri o d.
7. 3. 3.  
Seri o us A d verse E ve nts
All S A Es, re gar dless of ca use or relati o ns hi p, t hat occ ur after t he patie nt first c o nse nts t o 
partici pate i n t he st u d y (ie, si g ni n g t he I C F) a n d t hr o u g h o ut t he d urati o n of t he st u d y, i ncl u di n g 
t he p osttreat me nt f oll o w- u p visit, m ust be re p orte d o n t he a p plica ble e C R Fs a n d t o Gilea d 
Patie nt Safet y ( P S) as i nstr ucte d bel o w i n t his secti o n. T his als o i ncl u des a n y S A Es res ulti n g 
fr o m pr ot oc ol-ass ociate d pr oce d ures perf or me d after t he I C F is si g ne d.
A n y S A Es a n d deat hs t hat occ ur after t he p osttreat me nt f oll o w- u p visit b ut wit hi n 3 0 da ys of t he 
last d ose of st u d y dr u g, re gar dless of ca usalit y, s h o ul d als o be re p orte d.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 6 8
2 4 Oct o ber 2 0 2 3
I n vesti gat ors are n ot o bli gate d t o acti vel y see k S A Es after t he pr ot oc ol- defi ne d f oll o w- u p peri o d; 
h o we ver, if t he i n vesti gat or lear ns of a n y S A Es t hat occ ur after t he pr ot oc ol- defi ne d f oll o w- u p 
peri o d has c o ncl u de d a n d t he e ve nt is dee me d rele va nt t o t he use of st u d y dr u g, t he i n vesti gat or 
s h o ul d pr o m ptl y d oc u me nt a n d re p ort t he e ve nt t o Gilea d P S.
I nstr ucti o ns f or re p orti n g S A Es are descri be d i n Secti o n 7. 4. 1 .
7. 3. 4.  
St u d y Dr u g S peci al Sit u ati o ns Re p orts
All st u d y dr u g S S Rs t hat occ ur fr o m st u d y dr u g i nitiati o n a n d t hr o u g h o ut t he d urati o n of t he 
st u d y, i ncl u di n g t he p osttreat me nt f oll o w- u p visit, m ust be re p orte d t o Gilea d P S ( Secti o n 7. 4. 2 ). 
A d verse e ve nts a n d S A Es res ulti n g fr o m S S Rs m ust be re p orte d i n acc or da nce wit h t he A E a n d 
S A E re p orti n g g ui da nce ( Secti o n 7. 4 ).
7. 3. 5.   
C o nc o mit a nt T her a p y Re p orts
7. 3. 5. 1.   
Gilea d C o nc o mita nt T hera p y S pecial Sit uati o ns Re p ort
S pecial sit uati o ns i n v ol vi n g a Gilea d c o nc o mita nt t hera p y ( n ot c o nsi dere d st u d y dr u g) t hat occ ur 
after t he patie nt first c o nse nts t o partici pate i n t he st u d y (ie, si g ni n g t he i nf or me d c o nse nt) a n d 
t hr o u g h o ut t he d urati o n of t he st u d y, i ncl u di n g t he p osttreat me nt f oll o w- u p visit, m ust be 
re p orte d t o Gilea d P S utilizi n g t he pa per S S R f or m ( Secti o n 7. 4. 2. 2 ).
7. 3. 5. 2.   
N o n- Gilea d C o nc o mita nt T hera p y Re p ort
S pecial sit uati o ns i n v ol vi n g n o n- Gilea d c o nc o mita nt me dicati o ns d o n ot nee d t o be re p orte d o n 
t he S S R f or m; h o we ver, f or s pecial sit uati o ns t hat res ult i n A Es d ue t o a n o n- Gilea d c o nc o mita nt 
me dicati o n, t he A E s h o ul d be re p orte d o n t he A E f or m.
A n y i na p pr o priate use of c o nc o mita nt me dicati o ns pr o hi bite d b y t his pr ot oc ol s h o ul d n ot be 
re p orte d as “ mis use,” b ut ma y be m ore a p pr o priatel y d oc u me nte d as a pr ot oc ol de viati o n.
All cli nical se q uelae i n relati o n t o t hese S S Rs will be re p orte d as A Es or S A Es at t he sa me ti me 
usi n g t he A E e C R F a n d/ or t he S A E re p ort f or m. Details of t he s y m pt o ms a n d si g ns, cli nical 
ma na ge me nt, a n d o utc o me will be re p orte d, w he n a vaila ble.
7. 4.   
Re p orti n g Pr ocess f or Seri o us A d verse E ve nts a n d S peci al Sit u ati o n Re p orts
7. 4. 1.  
Seri o us A d verse E ve nt Re p orti n g Pr ocess
F or fatal or life-t hreate ni n g e ve nts, c o pies of h os pital case re p orts, a ut o ps y re p orts, a n d ot her 
d oc u me nts are als o t o be tra ns mitte d b y e mail or fa x w he n re q ueste d a n d a p plica ble. 
Tra ns missi o n of s uc h d oc u me nts s h o ul d occ ur wit h o ut pers o nal patie nt i de ntificati o n, 
mai ntai ni n g t he tracea bilit y of a d oc u me nt t o t he patie nt i de ntifiers.
A d diti o nal i nf or mati o n ma y be re q ueste d t o e ns ure t he ti mel y c o m pleti o n of acc urate safet y 
re p orts.


M a gr oli m a b 
Gil e a d  S ci e n c e s , I n c. 
Pr o to c ol  G S -U S- 5 4 8 -5 9 1 8 
A m e n d m e nt s 
A n y  m e di c ati o ns  n e c e s s ai y  f or tr e atm e nt of th e  S A E  m u st b e r e c or d ed  o n t o t h e c o n c o mi t a nt 
m e di c at i o n s e ctio n of t h e p ati e n t' s e C R F  a n d t h e  S A E  n a n at iv e s e cti o n of t h e S af et y  R e p o 1t 
F o n n e C R F . 
7. 4. 1. 1.  
El e ctr o n i c S e ri ous  A d v er s e  E v e nt  R e p o rti ng  P r o c ess 
Sit e  p er s o n n el  wi ll r e c or d  all S A E  d at a  o n t h e  a p p li c a bl e e C R F s  a n d fro m t h er e  tr an s mit t he  S A E 
i nf on n ati o n t o Gi le a d  P S  wit h i n 2 4 h o ur s of th e  i nv e s tig at or' s  k n o wl e d g e of t h e e v e nt  fr o m IC F 
si g n atur e t h r ou g h o ut t h e  d ur at i o n of t h e st u d y , i ncl u di ng t h e  pr ot o c ol -r e quir e d p o stt re at m e nt 
f ollo w - u p p er i o d. 
If it is n ot  p o s si bl e  t o re c o r d  a n d tr a n s mit t h e S A E  i nf on n ati o n  el e ctr o n i c ally, r e c o r d t he  S A E  o n 
t h e p a p e r S A E  r ep o 1ti n g f o 1 m a n d t r a n s mit wit hi n 2 4 h o ur s: 
Gi l e a d: 
P P D 
If a n  S A E  h as  b e e n r e p o 1t e d  vi a  a  p a p er  f on n  b e c a u s e  t h e e C R F  d at a b as e  h as  b e e n  l o ck e d,  n o 
fi nth er  a cti o n i s  n e c ess a 1y. If th e  d at a b as e  i s  not l o c k e d,  a n y S A E  re p o 1t e d  vi a p a p er  m u st  b e 
tr an s cri b e d as  s o o n as  p o s si bl e  o n t h e  a p p li c a bl e e C R F s  a n d  tr a n smi tte d t o Gil e a d  P S. 
7 . 4. 2. 
7. 4. 2. 1. 
S p e ci al  S it u ati o ns R e p o rti n g  P r o c e s s 
P a p e r S p e ci al  Sit u ati o ns  R e p o 1t i ng  P r o c e s s f or St u d y  D r n g 
A ll s p e ci al sit u ati o ns  wi ll b e re c o rd e d  o n t h e S S R f on n  a n d  tr a n smi tte d b y e m ai li ng  or  f a xi ng t h e 
r ep o 1t  f on n  wit hi n 2 4 h o ur s of t h e i nv e sti g at o r' s k n o w le d g e of t h e e v e nt  t o t h e att e n ti on of 
Gi le a d  P S  fr om  stu d y  d r ng  i niti ati on t h r ou g h o ut t h e  d ur at i o n of t h e st u d y , i ncl u di ng t h e  pr ot o c ol -
r e quir e d p o stt re at m e nt  f oll o w- u p p er io d. 
P P D 
S e e  S e c tio n  7 . 4.2. 2  f or i nstr ncti o ns  o n r e p o rti ng  s p e ci al sit u ati o ns  wi t h Gi le a d  c o n c o mi t a nt 
m e di c at i o ns. 
C O N FI D E N TI A L 
P a g e  6 9 
2 4  O c to b er  2 0 2 3 


M a gr oli m a b 
Gil e a d  S ci e n c e s , I n c. 
7. 4. 2. 2. 
R e p o 1ii n g  P r o c e s s f or  Gil e a d  C o n c o mit ant  M e di c ati o n s 
Pr o to c ol  G S -U S - 5 4 8- 5 9 1 8 
A m e n d m e nt s 
S p e ci a l  sit uati o ns t h at  i nv ol v e  c o n c o mit ant  m e di c ati o n s  m a n uf a ct ur e d  b y  Gil e a d  th at  ar e  n ot 
c o n s i de r e d st u d y di u g s  m u st  b e  re p o1ie d wit hi n 2 4 h o ur s of t h e i nv e st ig at or' s  k n o wl e d g e  of  t h e 
e v e nt  t o Gil e a d  P S  utili z i ng  t h e p a p er  S S R  f o1 m  t o: 
Gil e a d: 
P P D 
A n y  i n a p pr o pri at e u s e of c o n c o mit ant m e di c ati o n s pr o hi bit e d b y  t hi s pr ot o c ol  s h oul d  n ot  b e 
r e p o 1i e d as  " mi s u s e, "  b ut  m a y  b e  m or e  a p pr o p riat e l y d o c u m e nt e d  as  a  pr ot o c ol  d e vi ati o n. 
S p e ci a l  sit uati o ns  i nv ol v i ng  n o n- Gil e a d c o n c o mit ant  m e di c ati o n s  d o  n ot  n e e d  t o b e  r ep o 1i e d  o n 
t h e S S R  f o 1 m;  ho w e v er , s p e ci al  sit uati o ns t h at res ult i n A E s  d u e  t o a  n o n- Gil e a d  c o n c o mit a nt 
m e di c ati o n m u st b e  r e p o 1i e d as a n A E. 
7. 4. 2. 3. 
Pr e g n a n c y  R e p o 1ii n g  Pr o c e s s 
T h e  i n v esti g at or w ill r e p o 1i pr e g n a n ci e s i n f em al e  st u d y p at i ent s  w h o  ar e i de ntifi e d  aft er 
i niti atio n of st u d y di u g  a n d t hr o u g h o ut th e  st u d y , i ncl u di ng t h e  pr ot o c ol -re quir e d  p o stt re at m e nt 
f oll o w- u p p eri o d  or  6  m o nt h s  aft er th e  last  d os e of l at e st a di ni n ist er e d st u d y tr e at m en t, 
w h i ch e v er  i s l o ng e r, t o Gil e a d  P S  wit hi n 2 4 h o ur s of b e c o mi n g  a w a r e of t h e pr e g n a n c y  us i ng  t h e 
pr e g n a n c y  r e p o 1i f on n.  C a nt a .ct d et ail s  f or tr a ns mitti n g  t h e pr e g n a n c y  r e p o 1i f o1 m  ar e  as  f oll o ws: 
Gil e a d 
P P D 
T h e  pr e g n a n c y  its elf is n ot  c o n s i de r e d a n A E ,  n or is a n  i n d u c e d el e cti v e  a b o 1ii o n  t o t e 1 mi n at e a 
pr e g n a n c y  wit h o ut  m e di c al  r eas o ns. 
A ll ot h er  pr e m at ur e  t e 1 mi n ati o ns of pr e g n a n c y  ( e g ,  a s p o nt a n e ou s  a b o 1ii on,  a n  i nd u c e d 
t her a p e u ti c a b orti o n  d u e  t o c o m p lic ati o ns  or  ot h er  m e di c al  re a s o n s) m u st b e  r e p o 1i e d wit hi n 
2 4 h o ur s  as  a n  S A E,  as  d e s cr i be d i n S e cti o n 7. 4 . 1. T h e  u n d e rly i ng  m e di c al  re a s o n  f or t hi s 
pr o c e d ur e  s h oul d  b e  re c or d e d  as  th e A E t e 1 m. 
A s p o nt a n e o u s a b o 1ii o n i s al w a y s  c o ns i d er e d t o b e  a n  S A E  an d w ill b e  re p o1ie d as  d e s cr i be d i n 
S e cti o n  7. 4. 1.  F mi h e 1 m o r e ,  a n y S A E  o c c u ni n g  as  a n  a d v ers e  pr e g n a n c y  o u t c o m e aft er  t h e st u d y 
m u st b e r ep o 1i e d  t o t h e Gil e a d  P S. 
C O N FI D E N TI A L 
P a g e  7 0 
2 4  O c to b er  2 0 2 3 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 1
2 4 Oct o ber 2 0 2 3
T he patie nt will recei ve a p pr o priate m o nit ori n g a n d care u ntil t he c o ncl usi o n of t he pre g na nc y. 
T he o utc o me of t he pre g na nc y s h o ul d be re p orte d t o Gilea d P S usi n g t he pre g na nc y o utc o me 
re p ort f or m. If t he e n d of t he pre g na nc y occ urs after t he st u d y has bee n c o m plete d, t he o utc o me 
s h o ul d be re p orte d directl y t o Gilea d P S. Gilea d P S c o ntact i nf or mati o n is as f oll o ws: e mail: 
Refer t o A p pe n di x 6  f or Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P ote ntial, 
a n d C o ntrace pti ve Re q uire me nts.
7. 5.   
Gile a d Re p orti n g Re q uire me nts
De pe n di n g o n rele va nt l ocal le gislati o n or re g ulati o ns, i ncl u di n g t he a p plica ble U S F D A C o de of 
Fe deral Re g ulati o ns, t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C) a n d rele va nt u p dates, a n d 
ot her c o u ntr y-s pecific le gislati o n or re g ulati o ns, Gilea d ma y be re q uire d t o e x pe dite t o 
w orl d wi de re g ulat or y a ge ncies re p orts of S A Es t hat ma y be i n t he f or m of li ne listi n gs, seri o us 
a d verse dr u g reacti o ns, or s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs). I n 
acc or da nce wit h t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C), Gilea d or a s pecifie d desi g nee 
will n otif y w orl d wi de re g ulat or y a ge ncies a n d t he rele va nt I E C i n c o ncer ne d Me m ber States of 
a p plica ble S U S A Rs as o utli ne d i n c urre nt re g ulati o ns.
Assess me nt of e x pecte d ness f or S A Es will be deter mi ne d b y Gilea d usi n g refere nce safet y 
i nf or mati o n s pecifie d i n t he I B or rele va nt l ocal la bel as a p plica ble.
All i n vesti gat ors will recei ve a safet y letter n otif yi n g t he m of rele va nt S U S A R re p orts ass ociate d 
wit h a n y st u d y dr u g. T he i n vesti gat or s h o ul d n otif y t he I R B or I E C of S U S A R re p orts as s o o n as 
is practical, w here t his is re q uire d b y l ocal re g ulat or y a ge ncies, a n d i n acc or da nce wit h t he l ocal 
i nstit uti o nal p olic y.
7. 6.   
Cli nic al L a b or at or y A b n or m alities a n d Ot her A b n or m al Assess me nts as 
A d verse E ve nts or Seri o us A d verse E ve nts
La b orat or y a b n or malities wit h o ut cli nical si g nifica nce are n ot t o be rec or de d as A Es or S A Es. 
H o we ver, la b orat or y a b n or malities (e g, cli nical c he mistr y, he mat ol o g y, uri nal ysis) t hat re q uire 
me dical or s ur gical i nter ve nti o n or lea d t o st u d y dr u g i nterr u pti o n, m o dificati o n, or 
disc o nti n uati o n m ust be rec or de d as a n A E, as well as a n S A E, if a p plica ble. I n a d diti o n, 
la b orat or y or ot her a b n or mal assess me nts (e g, E C G, x-ra ys, vital si g ns) t hat are ass ociate d wit h 
si g ns a n d/ or s y m pt o ms m ust be rec or de d as a n A E or S A E if t he y meet t he defi niti o n of a n A E 
or S A E as descri be d i n Secti o ns 7. 1. 1  a n d 7. 1. 2 . If t he la b orat or y a b n or malit y is part of a 
s y n dr o me, rec or d t he s y n dr o me or dia g n osis (e g, a ne mia), n ot t he la b orat or y res ult (e g, 
decrease d he m o gl o bi n).
Se verit y s h o ul d be rec or de d a n d gra de d acc or di n g t o t he N CI C T C A E, Versi o n 5. 0. F or A Es 
ass ociate d wit h la b orat or y a b n or malities, t he e ve nt s h o ul d be gra de d o n t he basis of t he cli nical 
se verit y i n t he c o nte xt of t he u n derl yi n g c o n diti o ns; t his ma y or ma y n ot be i n a gree me nt wit h 
t he gra di n g of t he la b orat or y a b n or malit y.
P P D


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 2
2 4 Oct o ber 2 0 2 3
7. 7.   
A b n or m al Li ver F u ncti o n Tests
Li ver t o xicit y will be e val uate d f or all patie nts.
I n t he a bse nce of a n e x pla nati o n f or i ncrease d li ver f u ncti o n tests, s uc h as viral he patitis, 
pre-e xisti n g or ac ute li ver disease, or e x p os ure t o ot her a ge nts ass ociate d wit h li ver i nj ur y, t he 
patie nt ma y be disc o nti n ue d fr o m t he st u d y treat me nt if t he i n vesti gat or deter mi nes t hat it is n ot 
i n t he patie nt’s best i nterest t o c o nti n ue. Disc o nti n uati o n of treat me nt s h o ul d be c o nsi dere d if 
t here is a n i n dicati o n of se vere li ver i nj ur y acc or di n g t o H y’s La w, defi ne d b y F D A G ui da nce f or 
I n d ustr y, Dr u g-I n d uce d Li ver I nj ur y: Pre mar keti n g Cli nical E val uati o n {U. S. De part me nt of 
Healt h a n d H u ma n Ser vices 2 0 0 9 }, as:
•
Treat me nt-e mer ge nt A L T or A S T ele vati o n ( ≥ 3  U L N), A N D
•
Treat me nt-e mer ge nt t otal bilir u bi n ele vati o n ( > 2  U L N), a n d a bse nce of c h olestasis 
( defi ne d as al kali ne p h os p hatase < 2  U L N), A N D
•
N o ot her g o o d e x pla nati o n f or t he i nj ur y ( he patitis A, B, C, or ot her viral he patic i nj ur y, 
alc o h ol i n gesti o n, c o n gesti ve heart fail ure, w orse ni n g li ver metastases).
7. 8.  
T o xicit y M a n a ge me nt
7. 8. 1.   
M a gr oli m a b
7. 8. 1. 1.  
T y pe a n d Scree n a n d Direct A nti gl o b uli n Test
Ma gr oli ma b ma y i nterfere wit h R B C p he n ot y pi n g d ue t o e x pecte d c oati n g of t he R B C 
me m bra ne. D ue t o t he ris k of de vel o pi n g a ne mia, a n d beca use ma gr oli ma b ma y ma ke 
p he n ot y pi n g diffic ult, A B O/ R h t y pe, a nti b o d y scree n, e xte n de d R B C p he n ot y pi n g or ge n ot y pi n g, 
a n d direct a nti gl o b uli n test ( D A T) nee d t o be perf or me d at scree ni n g bef ore e x p os ure t o 
ma gr oli ma b, as descri be d i n Secti o n 7. 8. 1. 1. 1 . 
Re d bl o o d cell p he n ot y pi n g/ ge n ot y pi n g, A B O t y pe, a n d D A T nee d n ot be re peate d if res ults 
date d bef ore scree ni n g are a vaila ble. A nti b o d y scree n nee d n ot be re peate d if res ults date d bef ore 
scree ni n g are a vaila ble, u nless t he patie nt was tra nsf use d si nce t hat ti me. 
7. 8. 1. 1. 1.   
A ne mia, Bl o o d Cr oss- matc hi n g, a n d Pac ke d Re d Bl o o d Cell Tra nsf usi o n 
Pr oce d ures
Ma gr oli ma b bi n ds t o R B Cs a n d lea ds t o er yt hr o p ha g oc yt osis. C D 4 7 is a me m ber of t he R h 
c o m ple x i n t he R B C’s me m bra ne. T heref ore, w he n ma gr oli ma b bi n ds t o C D 4 7, it is li kel y t o 
i nterfere wit h r o uti ne bl o o d ba n k tests nee de d i n case of tra nsf usi o n. N otif y bl o o d tra nsf usi o n 
ce nters/ bl o o d ba n ks of t his i nterfere nce wit h bl o o d ba n k testi n g a n d i nf or m t he m t hat a patie nt 
will recei ve ma gr oli ma b.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 3
2 4 Oct o ber 2 0 2 3
I n cli nical st u dies, a ne mia is t he m ost c o m m o n treat me nt-relate d A E a n d is t y picall y ma nifeste d 
as a decli ne i n he m o gl o bi n of a b o ut 0. 5 g/ d L t o 1. 5 g/ d L o bser ve d i n t he first 1 t o 2 wee ks of 
treat me nt. T his decrease i n he m o gl o bi n le vel has bee n acce pta ble i n patie nts wit h n o ot her 
si g nifica nt diseases or me dical c o n diti o ns. H o we ver, f or patie nts wit h si g nifica nt diseases or 
me dical c o n diti o ns, s uc h as u nsta ble a n gi na, isc he mic heart disease, or u nc o ntr olle d dia betes 
mellit us, treat me nt ‑relate d a ne mia c o ul d be life‑t hreate ni n g or fatal. Si g nifica nt dr o ps i n 
he m o gl o bi n le vel ( 2 g/ d L or hi g her) ha ve als o bee n o bser ve d i n earl y d oses.
Patie nts wit h a l o w baseli ne he m o gl o bi n le vel, es peciall y t h ose wit h car diac hist or y or ris k 
fact ors, m ust be m o nit ore d cl osel y after i nitial a d mi nistrati o ns of ma gr oli ma b as pree xisti n g 
a ne mia c o ul d be e xacer bate d. Re d bl o o d cell tra nsf usi o ns are per mitte d pri or t o st u d y treat me nt 
t o e ns ure a de q uate he m o gl o bi n le vel as per i n vesti gat or cli nical j u d g me nt. 
Wit hi n 2 4 h o urs pri or t o eac h of t he first 2 d oses of ma gr oli ma b i nf usi o n d uri n g i nitial treat me nt, 
all patie nts m ust ha ve a d oc u me nte d he m o gl o bi n ≥ 9 g/ d L. Patie nts w h o d o n ot meet t hese 
criteria m ust be tra nsf use d a n d ha ve t heir he m o gl o bi n rec hec ke d t o meet 9 g/ d L pri or t o eac h of 
t he first 2 d oses of ma gr oli ma b. He m o gl o bi n s h o ul d be m o nit ore d fre q ue ntl y f or res p o nse a n d/ or 
t o xicit y pri or t o eac h d ose a n d 3 t o 6 h o urs after t he i nitiati o n of t he first a n d sec o n d d oses of 
ma gr oli ma b. Bl o o d tra nsf usi o ns s h o ul d be c o nsi dere d as cli nicall y a p pr o priate. C o nsi der 
a d diti o nal he m o gl o bi n m o nit ori n g d uri n g t he first wee k of ma gr oli ma b treat me nt i n patie nts wit h 
s y m pt o ms of a ne mia or at i ncrease d ris k f or c o m plicati o ns of a ne mia.
Pri or t o i nitiati o n of ma gr oli ma b, A B O/ R h t y pe a n d scree n, D A T, a n d e xte n de d R B C 
p he n ot y pi n g (i ncl u di n g mi n or a nti ge ns s uc h as R h, Cc Ee, C w, M N Ss, K k, F ya, F y b, J ka, a n d 
J k b) are t o be perf or me d f or eac h patie nt. Re d bl o o d cell ge n ot y pi n g i nstea d of e xte n de d R B C 
p he n ot y pi n g is acce pta ble f or a n y patie nt. Re d bl o o d cell ge n ot y pi n g (i nstea d of a n e xte n de d 
R B C p he n ot y pe) m ust be perf or me d if a patie nt recei ve d a n y R B C or w h ole bl o o d tra nsf usi o n 
wit hi n t he pre vi o us 3 m o nt hs ( u nless la b orat or y has a vaila bilit y f or s pecial tec h ni q ues f or 
perf or mi n g p he n ot y pi n g f or patie nts wit h rece nt tra nsf usi o n). Res ults m ust be a vaila ble bef ore 
t he first d ose of ma gr oli ma b. 
7. 8. 1. 1. 2.  
F or Patie nts After E x p os ure t o Ma gr oli ma b
A n a d diti o nal he m o gl o bi n m ust be c hec ke d 3 t o 6 h o urs after t he i nitiati o n of t he first a n d sec o n d 
d oses of ma gr oli ma b d uri n g i nitial treat me nt. T he patie nt s h o ul d be tra nsf use d as cli nicall y 
a p pr o priate. I n vesti gat ors s h o ul d c o nsi der a d diti o nal he m o gl o bi n m o nit ori n g d uri n g t he first 
wee k of treat me nt i n patie nts wit h s y m pt o ms of a ne mia or at i ncrease d ris k f or c o m plicati o ns of 
a ne mia.
F or all electi ve R B C a n d platelet tra nsf usi o ns, use le u k oc yte-re d uce d a n d ga m ma-irra diate d u nits 
per i nstit uti o nal g ui deli nes. F or R B C tra nsf usi o ns, p he n ot y pe/ ge n ot y pe- matc he d u nits are 
preferre d. H o we ver, C M V-ser o ne gati ve u nits f or C M V-ser o ne gati ve patie nts will n ot be re q uire d 
f or t his st u d y.
I n case A B O/ R h t y pe ca n n ot be res ol ve d, use pretreat me nt p he n ot y pe/ ge n ot y pe- matc he d u nits 
f or mi n or R B C a nti ge ns ( Cc Ee a n d K k, t o t he feasi ble e xte nt). Re gar di n g t he A B O t y pe, t he 
i nstit uti o n ca n use hist orical bl o o d gr o u p or O t y pe as per t he i nstit uti o nal g ui deli nes. 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 4
2 4 Oct o ber 2 0 2 3
F or e mer ge nc y tra nsf usi o ns, t he tra nsf usi o n ce nters ma y c o nsi der usi n g e mer ge nc y Gr o u p O re d 
cells if p he n ot y pe/ ge n ot y pe- matc he d u nits are n ot a vaila ble.
W he ne ver p ossi ble, bl o o d plas ma t hera p y s h o ul d be bl o o d t y pe s pecific. Platelets s h o ul d be 
bl o o d t y pe c o m pati ble w he ne ver p ossi ble a n d, if n ot, s h o ul d ha ve bee n teste d a n d f o u n d n ot t o 
ha ve hi g h titer a nti- A or a nti- B. Ot her wise, plas ma a n d platelet pr o d ucts ca n be pr o vi de d as per 
t he i nstit uti o nal p olic y.
A rece nt re p ort has s u g geste d t hat cr oss- matc h i nterfere nce b y R B Cs d ue t o treat me nt wit h 
ma gr oli ma b ma y be res ol ve d b y use of ga m ma-cl o ne a nti-I g G a n d m ulti ple all oa ds or pti o ns wit h 
pa pai n-treate d R B C sa m ples, p o ole d si n gle d o n or a p heresis platelets, or c o m mercial h u ma n 
platelet c o nce ntrate pr o d uct if re q uire d { Tr o u g ht o n 2 0 1 8 , Velli q uette 2 0 1 9 }.
7. 8. 1. 2.   
Ma na ge me nt of I nf usi o n-relate d Reacti o ns
I nf usi o n-relate d reacti o ns are defi ne d b y t he N CI C T C A E, Versi o n 5. 0 as “a dis or der 
c haracterize d b y a d verse reacti o n t o t he i nf usi o n of p har mac ol o gical or bi ol o gical s u bsta nces” 
(A p pe n di x 5 ). F or t he p ur p oses of t his st u d y, t he ti me fra me f or I R R assess me nt is t he 2 4- h o ur 
peri o d be gi n ni n g fr o m t he start of t he i nf usi o n. Pre me dicati o n use descri be d i n Secti o n 5. 6  will 
be use d t o ma na ge I R Rs pree m pti vel y.
Rec o m me n dati o ns f or t he ma na ge me nt of I R Rs relate d t o ma gr oli ma b are pr o vi de d i n Ta ble 1 1 .
T a ble 1 1.
M a n a ge me nt of I nf usi o n-rel ate d Re acti o ns
I nf usi o n- Rel ate d Re acti o ns
C T C A E Gr a de 
M a n a ge me nt
Gr a de 1
Mil d tra nsie nt reacti o n.
Re mai n at be dsi de a n d m o nit or patie nt u ntil rec o ver y fr o m s y m pt o ms.
Patie nts w h o e x perie nce I R Rs wit h t he first 2 d oses of ma gr oli ma b s h o ul d 
c o nti n ue pre me dicati o n wit h c ortic oster oi ds pri or t o s u bse q ue nt d oses at t he 
i n vesti gat or’s discreti o n.
Gr a de 2
Re q uiri n g s y m pt o matic treat me nt 
a n d pr o p h ylactic me dicati o ns f or 
≤ 2 4 h o urs.
I nterr u pt ma gr oli ma b t hera p y per pr ot oc ol a n d be gi n a n I V i nf usi o n of 
n or mal sali ne a n d c o nsi der treati n g t he patie nt wit h di p he n h y dra mi ne 5 0 m g 
I V ( or e q ui vale nt) a n d/ or 5 0 0 t o 7 5 0 m g of oral aceta mi n o p he n.
Re mai n at be dsi de a n d m o nit or patie nt u ntil res ol uti o n of s y m pt o ms.
C ortic oster oi d t hera p y ma y als o be gi ve n at t he discreti o n of t he i n vesti gat or.
If t he i nf usi o n is i nterr u pte d, wait u ntil s y m pt o ms res ol ve, t he n restart t he 
i nf usi o n at 5 0 % of t he ori gi nal i nf usi o n rate.
If n o f urt her c o m plicati o ns occ ur after 1 h o ur ( ± 1 0 mi n utes), t he rate ma y be 
i ncrease d t o 1 0 0 % of t he ori gi nal i nf usi o n rate. M o nit or t he patie nt cl osel y.
If s y m pt o ms rec ur, st o p i nf usi o n a n d disc o n nect patie nt fr o m t he i nf usi o n 
a p parat us. N o f urt her ma gr oli ma b will be a d mi nistere d at t hat visit.
Patie nts w h o e x perie nce I R Rs wit h t he first 2 d oses of ma gr oli ma b s h o ul d 
c o nti n ue pre me dicati o n wit h c ortic oster oi ds pri or t o s u bse q ue nt d oses at t he 
i n vesti gat or’s discreti o n.
T he a m o u nt of ma gr oli ma b i nf use d m ust be rec or de d o n t he e C R F.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 5
2 4 Oct o ber 2 0 2 3
I nf usi o n- Rel ate d Re acti o ns
C T C A E Gr a de 
M a n a ge me nt
Patie nts w h o e x perie nce a Gra de 2 i nf usi o n-relate d reacti o n d uri n g t he 
p osti nf usi o n o bser vati o n peri o d t hat d oes n ot res ol ve t o ≤ Gra de 1 d uri n g t hat 
ti me s h o ul d be o bser ve d u ntil t he A E res ol ves or sta bilizes, wit h vital si g n 
meas ure me nts as me dicall y i n dicate d f or t he ma na ge me nt of t he A E.
Gr a de 3- 4
Gra de 3: Pr ol o n ge d reacti o ns or 
rec urre nce of s y m pt o ms 
f oll o wi n g i nitial i m pr o ve me nt, or 
w here h os pitalizati o n is i n dicate d 
f or ot her cli nical se q uelae.
Gra de 4: Life-t hreate ni n g 
c o nse q ue nces, w here ur ge nt 
i nter ve nti o n is i n dicate d.
I m me diatel y disc o nti n ue i nf usi o n of ma gr oli ma b.
Be gi n a n I V i nf usi o n of n or mal sali ne a n d c o nsi der treati n g t he patie nt as 
f oll o ws: A d mi nister br o nc h o dilat ors, e pi ne p hri ne 0. 2 t o 1 m g of a 
1: 1 0 0 0 s ol uti o n f or S C a d mi nistrati o n or 0. 1 t o 0. 2 5 m g of a 
1: 1 0, 0 0 0 s ol uti o n i njecte d sl o wl y f or I V a d mi nistrati o n a n d/ or 
di p he n h y dra mi ne 5 0 m g I V wit h met h yl pre d nis ol o ne 1 0 0 m g I V ( or 
e q ui vale nt), as nee de d.
T he patie nt s h o ul d be m o nit ore d u ntil t he i n vesti gat or is c o mf orta ble t hat t he 
s y m pt o ms will n ot rec ur.
Patie nts w h o e x perie nce Gra de 3 I R Rs m ust be gi ve n pre me dicati o n pri or t o 
s u bse q ue nt d oses. I n t his setti n g, pre me dicati o n wit h oral aceta mi n o p he n 
( 6 5 0 t o 1 0 0 0 m g), oral or I V di p he n h y dra mi ne ( 2 5 t o 5 0 m g), a n d I V 
de xa met has o ne ( 4 t o 2 0 m g), or a c o m para ble re gi me n, is rec o m me n de d f or 
t he s u bse q ue nt 2 d oses. C o nti n ue d pre me dicati o n wit h c ortic oster oi ds 
be y o n d t hese 2 d oses ma y be a d mi nistere d at t he discreti o n of t he treati n g 
p h ysicia n. 
Patie nts w h o recei ve pre me dicati o n a n d still e x perie nce a rec urre nt Gra de 3 
I R R or patie nts w h o e x perie nce a Gra de 4 I R R at a n y ti me s h o ul d be 
per ma ne ntl y disc o nti n ue d fr o m t he st u d y treat me nt.
F or a na p h yla xis, i n vesti gat ors s h o ul d f oll o w t heir i nstit uti o nal g ui deli nes f or 
treat me nt.
All patie nts wit h ≥ Gra de 3 I R Rs will be o bser ve d u ntil t he A E res ol ves or 
sta bilizes, wit h vital si g n meas ure me nts a n d a d diti o nal e val uati o ns as 
me dicall y i n dicate d f or t he ma na ge me nt of t he A Es.
A E = a d verse e ve nt; 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; e C R F = electr o nic case re p ort f or m; 
I R R = i nf usi o n-relate d reacti o n; I V = i ntra ve n o us; S C = s u bc uta ne o us
7. 8. 1. 3.   
Ma na ge me nt of P ne u m o nitis
P ne u m o nitis has bee n i nfre q ue ntl y o bser ve d i n patie nts recei vi n g ma gr oli ma b. Ge nerall y, 
i m m u ne-relate d A Es ha ve n ot bee n o bser ve d i n cli nical use wit h ma gr oli ma b. I n c o ntrast t o 
T-cell c hec k p oi nt i n hi bit ors, ma gr oli ma b pri maril y e xerts its a ntit u m or efficac y t hr o u g h 
macr o p ha ge- me diate d p ha g oc yt osis of t u m or cells. N o ns pecific T-cell or ot her h ost i m m u ne 
res p o nses t hat are see n wit h T-cell c hec k p oi nt i n hi bit ors ha ve n ot bee n o bser ve d wit h 
ma gr oli ma b i n n o ncli nical st u dies. A d diti o nall y, n o e ve nts of macr o p ha ge acti vati o n s y n dr o me 
or he m o p ha g oc ytic l y m p h o histi oc yt osis ha ve bee n re p orte d i n cli nical st u dies.
I n i nsta nces of s us pecte d p ne u m o nitis, first r ule o ut n o ni nfla m mat or y ca uses (e g, i nfecti o ns). If a 
n o ni nfla m mat or y ca use is i de ntifie d, treat acc or di n gl y a n d c o nti n ue t hera p y per pr ot oc ol. 
E val uate wit h i ma gi n g (e g, c hest x-ra y or C T) a n d p ul m o nar y c o ns ultati o n.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 6
2 4 Oct o ber 2 0 2 3
Ma na ge me nt of p ote ntial p ne u m o nitis is detaile d i n Ta ble 1 2  a n d f oll o ws A merica n S ociet y of 
Cli nical O nc ol o g y ( A S C O) g ui deli nes f or i m m u ne-relate d A Es { Bra h mer 2 0 1 8 }. Patie nts w h o 
e x perie nce Gra de 3 or 4 p ne u m o nitis will be per ma ne ntl y disc o nti n ue d fr o m st u d y treat me nt.
T a ble 1 2.
P ne u m o nitis M a n a ge me nt Al g orit h m
C T C A E Gr a de of 
P ne u m o nitis
M a n a ge me nt
F oll o w- U p
Gr a de 1
Ra di o gra p hic c ha n ges 
( C X R or C T) o nl y.
M o nit or f or si g ns a n d s y m pt o ms wee kl y a n d 
c o nsi der m o nit ori n g wit h C X R.
C o nsi der p ul m o nar y a n d i nfecti o us disease 
c o ns ults.
C o nsi der re-i ma gi n g wit h C T i n 
3- 4 wee ks as cli nicall y i n dicate d.
Ma y res u me ma gr oli ma b wit h 
ra di o gra p hic e vi de nce of 
i m pr o ve me nt or res ol uti o n.
If n o cli nical i m pr o ve me nt or 
w orse ni n g, treat as Gra de 2.
Gr a de 2
Mil d t o m o derate ne w 
s y m pt o ms.
I nterr u pt ma gr oli ma b t hera p y per pr ot oc ol.
P ul m o nar y a n d i nfecti o us disease c o ns ults.
C o nsi der e m pirical a nti bi otics.
M o nit or si g ns a n d s y m pt o ms e ver y 2- 3 da ys; 
c o nsi der h os pitalizati o n.
1 m g/ k g/ da y oral pre d nis o ne or I V e q ui vale nt.
C o nsi der br o nc h osc o p y, l u n g bi o ps y.
Re-i ma ge e ver y 1- 3 da ys.
If i m pr o vi n g t o baseli ne, ta per 
c ortic oster oi ds o ver 4- 6 wee ks 
a n d res u me ma gr oli ma b t hera p y 
per pr ot oc ol.
If n o cli nical i m pr o ve me nt after 
4 8- 7 2 h o urs or w orse ni n g, treat 
as Gra de 3- 4.
Gr a de 3- 4
Se vere ne w s y m pt o ms; 
ne w/ w orse ni n g h y p o xia; 
life-t hreate ni n g.
Disc o nti n ue ma gr oli ma b t hera p y.
H os pitalize.
P ul m o nar y a n d i nfecti o us disease c o ns ults.
1- 2 m g/ k g/ da y met h yl pre d nis ol o ne I V or I V 
e q ui vale nt.
A d d e m pirical a nti bi otics a n d c o nsi der 
pr o p h ylactic a nti bi otics f or o p p ort u nistic 
i nfecti o ns.
C o nsi der br o nc h osc o p y, l u n g bi o ps y.
If i m pr o vi n g t o baseli ne, ta per 
c ortic oster oi ds o ver 4- 6 wee ks.
If n o cli nical i m pr o ve me nt after 
4 8 h o urs or w orse ni n g, c o nsi der 
a d diti o nal i m m u n os u p pressi o n 
(e g, i nfli xi ma b, 
c ycl o p h os p ha mi de, I V 
i m m u n o gl o b uli n, m yc o p he n olate 
m ofetil).
C T = c o m p ute d t o m o gra p h y; C T C A E = C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts; C X R = c hest x-ra y; 
I V = i ntra ve n o us
7. 8. 1. 4.  
T hr o m b oe m b olic E ve nts
T hr o m b oe m b olic e ve nts, i ncl u di n g dee p vei n t hr o m b oses a n d p ul m o nar y e m b olis ms, ha ve bee n 
re p orte d i n s o me patie nts recei vi n g ma gr oli ma b, s o meti mes earl y i n t hera p y. A vaila ble data f or 
ma gr oli ma b d o n ot s u p p ort a clear or c o nsiste nt relati o ns hi p bet wee n cli nical t hr o m b oe m b olic 
e ve nts a n d ma gr oli ma b use. Patie nts s h o ul d be cl osel y m o nit ore d f or t he s y m pt o ms of 
t hr o m b oe m b olic e ve nts a n d treate d acc or di n gl y.
7. 8. 1. 5.  
Se vere Ne utr o pe nia
Se vere ne utr o pe nia a n d fe brile ne utr o pe nia ha ve bee n re p orte d i n patie nts treate d wit h 
ma gr oli ma b. Cl ose m o nit ori n g of he mat ol o gic para meters ( A p pe n di x Ta ble 1  a n d 
A p pe n di x Ta ble 2 ) i ncl u di n g ne utr o p hils is re q uire d f or all patie nts treate d wit h ma gr oli ma b. 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 7
2 4 Oct o ber 2 0 2 3
Pr o p h ylactic a nti bi otics a n d/ or a nti m yc otics s h o ul d be c o nsi dere d. A d mi nister 
gra n ul oc yte-c ol o n y sti m ulati n g fact or if cli nicall y i n dicate d.
Rec o m me n dati o ns f or ma gr oli ma b d ose dela y i n case of se vere ne utr o pe nia: 
•
F or Gra de 3 ne utr o pe nia wit h o ut fe ver or i nfecti o n, dela y of ma gr oli ma b d osi n g is n ot 
rec o m me n de d.
•
F or Gra de 4 ne utr o pe nia ( A N C < 5 0 0/ μ L) wit h o ut fe ver or i nfecti o n, or Gra de 3 or hi g her 
ne utr o pe nia wit h fe ver or i nfecti o n, ma gr oli ma b d ose dela y s h o ul d be c o nsi dere d. U p o n 
res ol uti o n t o Gra de ≤ 2, res u mi n g ma gr oli ma b at t he sa me d ose s h o ul d be c o nsi dere d.
•
F or persiste nt se vere ne utr o pe nia or fe brile ne utr o pe nia ( > 2 occ urre nces), disc o nti n uati o n of 
ma gr oli ma b ca n be c o nsi dere d.
7. 8. 1. 6.  
Seri o us I nfecti o ns
Patie nts ( wit h or wit h o ut ne utr o pe nia) s h o ul d be re g ularl y m o nit ore d f or si g ns a n d s y m pt o ms of 
i nfecti o n. F or patie nts wit h pr ol o n ge d ne utr o pe nia or patie nts at ris k, c o nsi der i nfecti o n 
pr o p h yla xis i ncl u di n g a nti bi otics (e g, fl u or o q ui n ol o ne) or a ntif u n gal a ge nts (e g, oral triaz oles or 
pare nteral ec hi n oca n di n) i n acc or da nce wit h c urre nt g ui deli nes.
F or seri o us i nfecti o ns, h ol d ma gr oli ma b u ntil t he i nfecti o n has res ol ve d cli nicall y. F or seri o us 
i nfecti o ns t hat re mai n acti ve f or ≥ 1 4 da ys, c o nsi der disc o nti n uati o n of ma gr oli ma b.
7. 8. 2.   
D ocet a xel
Safet y ma na ge me nt g ui deli nes f or d oceta xel are descri be d i n Secti o n 5. 3. 3 . A d diti o nal safet y 
g ui deli nes are pr o vi de d i n t he d oceta xel prescri bi n g i nf or mati o n. D oceta xel prescri bi n g 
i nf or mati o n pr o vi des g ui da nce o n a d mi nistrati o n, c o ntrai n dicati o ns, s pecial war ni n gs a n d 
preca uti o ns, as well as i nteracti o n wit h ot her me dici nal pr o d ucts.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 8
2 4 Oct o ber 2 0 2 3
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S
T his secti o n pr o vi des a hi g h-le vel descri pti o n of t he pla n ne d a nal yses a n d assesse d sa m ple sizes 
wit h ass u m pti o ns. A d diti o nal details of t he statistical met h o ds will be pr o vi de d i n t he statistical 
a nal ysis pla n, i ncl u di n g a n y de viati o ns fr o m t he ori gi nal statistical a nal yses pla n ne d. 
8. 1.   
A n al ysis O bjecti ves a n d E n d p oi nts
T he o bjecti ves a n d e n d p oi nts are pr o vi de d i n Secti o n 2 .
8. 2.  
Pl a n ne d A n al yses
8. 2. 1.   
D ose Deter mi n ati o n A n al ysis
F or t he p ur p oses of ma ki n g t he d ose de-escalati o n decisi o ns f or Safet y R u n-i n C o h ort 1, d ose 
deter mi nati o n a nal yses of rele va nt safet y data f oc usi n g o n D L Ts a n d o verall safet y pr ofile will 
be c o n d ucte d b y t he s p o ns or after all patie nts ha ve c o m plete d re q uire d d osi n g c ycles ( 2 1 da ys) 
a n d t he f oll o w- u p peri o d as defi ne d i n Secti o n 3. 1. 1 . Safet y assess me nts (e g, A Es, E C G, 
la b orat or y res ults) will be dis pla ye d b y c o h ort t o facilitate d ose de-escalati o n decisi o ns.
8. 2. 2.  
Pri m ar y A n al ysis
F or eac h of t he s u bc o h orts i n P hase 2 C o h ort 1, t he pri mar y a nal ysis of O R R will be c o n d ucte d 
at least a p pr o xi matel y 6 m o nt hs after t he last patie nt is e nr olle d, o utsta n di n g data q ueries ha ve 
bee n res ol ve d or a dj u dicate d as u nres ol va ble, a n d t he data ha ve bee n clea ne d a n d fi nalize d f or 
t he a nal ysis.
8. 2. 3.  
Fi n al A n al ysis
A fi nal a nal ysis ma y be perf or me d after all patie nts ha ve c o m plete d t he st u d y or disc o nti n ue d 
earl y, o utsta n di n g data q ueries ha ve bee n res ol ve d or a dj u dicate d as u nres ol va ble, a n d t he data 
ha ve bee n clea ne d a n d fi nalize d.
8. 3.   
A n al ysis C o n ve nti o ns
8. 3. 1.   
A n al ysis Sets
8. 3. 1. 1.   
M o difie d I T T A nal ysis Set
T he m o difie d I T T A nal ysis Set i ncl u des all e nr olle d patie nts w h o t o o k at least 1 d ose of a n y 
st u d y dr u g. T his is t he pri mar y a nal ysis set f or efficac y a nal yses of P hase 2 C o h orts 1a, 1 b, 
a n d 1c.
8. 3. 1. 2.  
Safet y A nal ysis Set
T he Safet y A nal ysis Set i ncl u des all patie nts w h o t o o k at least 1 d ose of a n y st u d y dr u g. T his is 
t he pri mar y a nal ysis set f or safet y a nal yses (e xce pt f or D L Ts) of b ot h Safet y R u n-i n C o h ort 1 
a n d P hase 2 C o h orts 1a, 1 b, a n d 1c.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 7 9
2 4 Oct o ber 2 0 2 3
8. 3. 1. 3.   
D ose- Li miti n g T o xicit y E val ua ble A nal ysis Set
F or Safet y R u n-i n C o h ort 1, t he pri mar y a nal ysis set f or t he pri mar y D L T a nal ysis is t he D L T 
E val ua ble A nal ysis Set, defi ne d as all patie nts w h o meet 1 of t he f oll o wi n g criteria i n t he D L T 
e val ua ble peri o d ( defi ne d as wit hi n 2 1 da ys of t he first d osi n g c ycle):
•
T he patie nt e x perie nce d a D L T at a n y ti me after i nitiati o n of t he first i nf usi o n of ma gr oli ma b.
•
T he patie nt di d n ot e x perie nce a D L T a n d c o m plete d at least 2 i nf usi o ns of ma gr oli ma b 
( 2 1- da y c ycle) a n d at least 1 d ose of d oceta xel i n Safet y R u n-i n C o h ort 1.
8. 3. 1. 4.  
P har mac o ki netics
T he P K a nal ysis will be c o n d ucte d o n t he P K A nal ysis Set, defi ne d as all patie nts w h o recei ve d 
a n y a m o u nt of ma gr oli ma b a n d ha ve at least 1 meas ura ble p osttreat me nt ser u m c o nce ntrati o n of 
ma gr oli ma b.
8. 3. 1. 5.  
I m m u n o ge nicit y
T he i m m u n o ge nicit y a nal ysis will be c o n d ucte d o n t he I m m u n o ge nicit y A nal ysis Set, defi ne d as 
all patie nts w h o recei ve d a n y a m o u nt of ma gr oli ma b a n d ha ve at least 1 e val ua ble 
a nti- ma gr oli ma b a nti b o d y test res ult.
8. 3. 1. 6.  
Bi o mar ker
T he bi o mar ker a nal ysis will be c o n d ucte d o n t he Bi o mar ker A nal ysis Set, defi ne d as all patie nts 
w h o recei ve d a n y st u d y dr u g a n d ha ve at least 1 e val ua ble bi o mar ker meas ure me nt a vaila ble.
8. 3. 2.   
D at a H a n dli n g C o n ve nti o ns
B y- patie nt listi n gs will be create d f or i m p orta nt varia bles fr o m eac h e C R F m o d ule. S u m mar y 
ta bles f or c o nti n u o us varia bles will c o ntai n t he f oll o wi n g statistics: N ( n u m ber i n a nal ysis set), 
n ( n u m ber wit h data), mea n, S D, 9 5 % CIs o n t he mea n, me dia n, mi ni m u m, a n d ma xi m u m. 
S u m mar y ta bles f or cate g orical varia bles will i ncl u de: N, n, perce nta ge, a n d 9 5 % CIs o n t he 
perce nta ge. U nless ot her wise i n dicate d, 9 5 % CIs f or bi nar y varia bles will be calc ulate d usi n g t he 
bi n o mial distri b uti o n (e xact met h o d) a n d will be 2-si de d. Data will be descri be d a n d s u m marize d 
b y treat me nt gr o u p a n d c o h ort.
T he baseli ne val ue use d i n eac h a nal ysis will be t he last ( m ost rece nt) pretreat me nt val ue bef ore 
or o n t he first d osi n g date of st u d y treat me nt. As a p pr o priate, c ha n ges fr o m baseli ne t o eac h 
s u bse q ue nt ti me p oi nt will be descri be d a n d s u m marize d. Gra p hical tec h ni q ues (ie, waterfall 
pl ots, Ka pla n- Meier [ K M] c ur ves, li ne pl ots) ma y be use d w he n s uc h met h o ds are a p pr o priate 
a n d i nf or mati ve. A nal yses will be base d u p o n t he o bser ve d data u nless met h o ds f or ha n dli n g 
missi n g data are s pecifie d. If t here is a si g nifica nt de gree of n o n n or malit y, a nal yses ma y be 
perf or me d o n l o g-tra nsf or me d data or n o n para metric tests ma y be a p plie d, as a p pr o priate.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 0
2 4 Oct o ber 2 0 2 3
8. 4.   
De m o gr a p hic a n d B aseli ne C h ar acteristics A n al ysis
De m o gra p hic a n d baseli ne meas ure me nts will be s u m marize d usi n g sta n dar d descri pti ve 
met h o ds. De m o gra p hic s u m maries will i ncl u de se x, race/et h nicit y, a n d a ge. Baseli ne data will 
i ncl u de a s u m mar y of b o d y wei g ht, hei g ht, b o d y mass i n de x, selecte d la b orat or y data, me dical 
a n d ca ncer hist or y, pri or treat me nt a n d n u m ber of pri or treat me nt(s), t u m or i ma gi n g f or baseli ne 
res p o nse assess me nt, a n d E C O G perf or ma nce stat us.
8. 5.  
Effic ac y A n al ysis
8. 5. 1.  
Pri m ar y Effic ac y E n d p oi nt A n al ysis
F or P hase 2 C o h ort 1, O R R al o n g wit h t he 9 5 % CI base d o n t he Cl o p per- Pears o n met h o d will be 
esti mate d f or eac h c o h ort ( P hase 2 C o h orts 1a, 1 b, a n d 1c). Patie nts w h o d o n ot ha ve s ufficie nt 
baseli ne or o n-st u d y t u m or assess me nt t o c haracterize res p o nse will be c o u nte d as 
n o nres p o n ders.
8. 5. 2.  
Sec o n d ar y Effic ac y E n d p oi nt A n al yses
F or a nal yses of P F S, O S, a n d D O R, t he K M esti mate of t he s ur vi val f u ncti o n will be c o m p ute d, 
a n d t he res ults will be prese nte d usi n g a K M c ur ve. T he me dia n d urati o n will be pr o vi de d al o n g 
wit h c orres p o n di n g 9 5 % CIs.
8. 6.  
S afet y A n al ysis
8. 6. 1.  
Pri m ar y S afet y E n d p oi nt A n al ysis
F or Safet y R u n-i n C o h ort 1, t he i nci de nce of D L Ts d uri n g t he D L T assess me nt peri o d b y c o u nt 
a n d perce nta ge will be re p orte d f or Safet y R u n-i n C o h ort 1 usi n g t he D L T E val ua ble A nal ysis 
Set. T he D L T assess me nt peri o d is defi ne d as t he first c ycle ( 2 1 da ys).
8. 6. 2.   
Ot her S afet y A n al ysis
All safet y data c ollecte d o n or after t he date t hat st u d y dr u g was first dis pe nse d u p t o t he date of 
last d ose of st u d y dr u g + 3 0 da ys will be s u m marize d b y c o h ort ( Safet y R u n-i n C o h ort 1, P hase 2 
C o h orts 1a, 1 b, a n d 1c, res pecti vel y). Data f or t he pretreat me nt a n d treat me nt-free safet y 
f oll o w- u p peri o ds will be i ncl u de d i n data listi n gs. F or cate g orical safet y data, i ncl u di n g 
i nci de nce of A Es a n d cate g orizati o ns of la b orat or y data, c o u nts a n d perce nta ges of patie nts will 
be s u m marize d. F or c o nti n u o us safet y data, i ncl u di n g la b orat or y data, n u m ber of patie nts, mea n, 
S D, mi ni m u m, q uartiles, me dia n, a n d ma xi m u m will be s u m marize d.
8. 6. 3.  
E xte nt of E x p os ure
A patie nt’s e xte nt of e x p os ure t o st u d y dr u gs data will be ge nerate d fr o m t he st u d y dr u g 
a d mi nistrati o n data. E x p os ure data will be s u m marize d b y c o h ort ( Safet y R u n-i n C o h ort 1, 
P hase 2 C o h orts 1a, 1 b, a n d 1c, res pecti vel y).


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 1
2 4 Oct o ber 2 0 2 3
8. 6. 4.   
A d verse E ve nts
Cli nical a n d la b orat or y A Es will be c o de d usi n g t he Me d D R A. S yste m or ga n class, hi g h-le vel 
gr o u p ter m, hi g h-le vel ter m, preferre d ter m, a n d l o wer-le vel ter m will be attac he d t o t he cli nical 
data base.
E ve nts will be s u m marize d o n t he basis of t he date of o nset f or t he e ve nt. A treat me nt-e mer ge nt 
A E will be defi ne d as a n y A E t hat be gi ns o n or after t he date of t he first d ose of a n y st u d y dr u g 
u p t o 3 0 da ys after t he date of t he last d ose of a n y st u d y dr u g or t he da y bef ore i nitiati o n of 
s u bse q ue nt a ntica ncer t hera p y, w hic he ver occ urs first.
S u m maries ( n u m ber a n d perce nta ge of patie nts) of treat me nt-e mer ge nt A Es ( b y s yste m or ga n 
class a n d preferre d ter m) will be pr o vi de d b y c o h ort ( Safet y R u n-i n C o h ort 1, P hase 2 
C o h orts 1a, 1 b, a n d 1c, res pecti vel y).
8. 6. 5.  
L a b or at or y E v al u ati o ns
Selecte d la b orat or y data ( usi n g c o n ve nti o nal u nits) will be s u m marize d usi n g o nl y o bser ve d data. 
Data a n d c ha n ge fr o m baseli ne at all sc he d ule d ti me p oi nts will be s u m marize d.
Gra de d la b orat or y a b n or malities will be defi ne d usi n g t he gra di n g sc he me i n A p pe n di x 5 .
I nci de nce of treat me nt-e mer ge nt la b orat or y a b n or malities, defi ne d as val ues t hat i ncrease at least 
1 t o xicit y gra de fr o m baseli ne at a n y ti me p oi nt p ost baseli ne, u p t o a n d i ncl u di n g t he date of t he 
last d ose of st u d y dr u g pl us 3 0 da ys or t he da y bef ore i nitiati o n of ne w a ntica ncer t hera p y, 
w hic he ver is earlier, will be s u m marize d b y c o h ort ( Safet y R u n-i n C o h ort 1, P hase 2 C o h orts 1a, 
1 b, a n d 1c, res pecti vel y). If baseli ne data are missi n g, t he n a n y gra de d a b n or malit y (ie, at least a 
Gra de 1) will be c o nsi dere d treat me nt-e mer ge nt.
La b orat or y a b n or malities t hat occ ur bef ore t he first d ose of st u d y dr u g or after t he patie nt has 
bee n disc o nti n ue d fr o m treat me nt f or at least 3 0 da ys will be i ncl u de d i n a data listi n g.
8. 6. 6.   
Ot her S afet y E v al u ati o ns
Vital si g ns a n d p h ysical e xa mi nati o n fi n di n gs will be s u m marize d b y c o h ort ( Safet y R u n-i n 
C o h ort 1, P hase 2 C o h orts 1a, 1 b, a n d 1c, res pecti vel y). Details will be pr o vi de d i n t he statistical 
a nal ysis pla n.
8. 7.  
P h ar m ac o ki netic A n al ysis
T he P K A nal ysis Set will be use d f or s u m maries of P K c o nce ntrati o n of ma gr oli ma b vers us ti me. 
Ser u m c o nce ntrati o ns will be liste d a n d s u m marize d f or ma gr oli ma b usi n g descri pti ve statistics 
b y sa m pli n g ti me p oi nt a n d treat me nt. Gra p hical pl ots of i n di vi d ual ser u m c o nce ntrati o n vers us 
ti me a n d mea n c o nce ntrati o n vers us ti me b y treat me nt will be ge nerate d. All data fr o m t his st u d y 
ma y be c o m bi ne d wit h P K data fr o m ot her c o m pa n y s p o ns ore d cli nical st u dies a n d a nal yze d 
usi n g a p o p ulati o n P K m o del. S uc h a n a nal ysis w o ul d be re p orte d se paratel y.


M a gr oli m a b 
Gil e a d S c ie n c es , I n c. 
8. 8.  
I m m u n o g e ni cit y A n al ysis 
Pr ot o c ol  G S -U S - 5 48- 5 9 1 8 
A m e n d m e nt s 
I m m u no g e ni cit y w ill b e  ass ess e d  us i n g a  3- ti er-s cre e n , c o nf n m at o 1 y , a n d tit er-a p pr o a c h  o n 
st u d y s a m pl e s. T h e  r at e a n d m a g nit u d e of a nti- m a gr oli m a b  a nti b o d y  i n ci d e n c e, pr e v a l e n c e, 
p er s ist en c e , a n d tr a nsi e n c e  w ill b e  su m m a ri z e d f or t h e I m m u no  
A n al  sis  S et.  Ti t er 
su m m ari e s m a 
al s o  b e  e n er at e d  if rel e v a nt. 
8. 9.  
Bi o m a r k e r  A n al ysis 
T h e  b a s e li ne l e v e l, a bs ol ut e  l ev e l, a n d  c h a n g e  fro m  b a s e li ne l e v e l o v e r ti m e wi ll b e  su m m ari z e d 
u si n g d e s cri ptiv e  statisti cs  f or e a c h  bi o m a r k er at  s a m  l e c o lle cti o n  ti m e  o i nt  b  c o h ort , as 
8. 1 0.  
S a m pl e  S i z e 
T a bl e 1 3 pr e s ent s t h e s am pl e  si z e  c al c ul ati o n s.  F or  P h a s e  2  C o h o 1i  1,  a  s am pl e  si z e of  3 0  p ati e nts 
i n t h e m N S C L C  c o h o 1i  a n d  4 0  p ati e nts f or t h e  mS C L C  c o h o 1i w er e  c al c ul at e d u s i ng  o n e s am pl e 
pr o p o 1ii o n  t est.  T h e  s a mpl e  si z e of  2 6  p ati e nts  f or t h e m U C  c o h o 1i  w as  c al c ul at e d  us i n g e x a ct 
m et h o d  i nst ea d of o n e  s am pl e  t e st d u e  t o s m aller  s a mpl e  si z e . 
T a bl e  1 3. 
S a m pl e  S i z e C al c ul ati o n s 
1- s i d e d 
T u m o r  T y p e  
S a m pl e  Si z e  
N ull O R R 
Alt e m ati v e  O R R 
al p h a 
P o w e 1· 
m N S C L C 
3 0 
1 3 % 
2 5 % 
0. 2 
8 1 % 
m U C 
2 6 
1 2. 4 % 
2 8 % 
0. 1 
7 8 % 
m S C L C 
4 0 
9 % 
2 0 % 
0. 1 5 
8 4 % 
m N S C L C  =  m et a s t ati c n o ~ m a ll c ell  lu n g  c a n c er ; m S C L C  =  m et ast ati c  s m all  c e ll lu n g  c a n c er ;  mU C  =  m et ast ati c  ur ot h eli a l 
c a n c er ; O R R =  o bj e cti v e  r esp o n s e r at e 
T h e  n ull  O R R  f or e a c h of t h e res p e cti v e  t u m or c o h o rts  ar e  b a s e d o n  h i st oric a l t a x a n e effi c a c y 
d at a  i n t h e s e c on d li n e s etti n g { B ell m u nt  2 0 1 7 , Ritt m e y er  2 0 1 7 , S mit  1 9 9 8 }.  P o w e r c al c ul ati o ns 
w er e  p erf o n n e d  u s i ng  E A S T  6. 5  a n d  n Q u e 1 y 8. 0. 
C O N FI D E N TI A L 
P a g e  8 2 
2 4  O c to b er  2 0 2 3 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 3
2 4 Oct o ber 2 0 2 3
9.   
R E S P O N SI BI LI TI E S
9. 1.  
I n vesti g at or Res p o nsi bilities
9. 1. 1.   
G o o d Cli nic al Pr actice
T he i n vesti gat or will e ns ure t hat t his st u d y is c o n d ucte d i n acc or da nce wit h I nter nati o nal C o u ncil 
f or Har m o nisati o n (I C H) E 6( R 2) a d de n d u m t o its g ui deli ne f or G C P a n d a p plica ble la ws a n d 
re g ulati o ns.
9. 1. 2.  
Fi n a nci al Discl os ure
T he i n vesti gat or a n d s u bi n vesti gat ors will pr o vi de pr o m pt a n d acc urate d oc u me ntati o n of t heir 
fi na ncial i nterest or arra n ge me nts wit h Gilea d, or pr o prietar y i nterests i n t he st u d y dr u g d uri n g 
t he c o urse of a cli nical st u d y. T his d oc u me ntati o n m ust be pr o vi de d pri or t o t he i n vesti gat or’s 
(a n d a n y s u bi n vesti gat or’s) partici pati o n i n t he st u d y. T he i n vesti gat or a n d s u bi n vesti gat or a gree 
t o n otif y Gilea d of a n y c ha n ge i n re p orta ble i nterests d uri n g t he st u d y a n d f or 1 year f oll o wi n g 
c o m pleti o n of t he st u d y. St u d y c o m pleti o n is defi ne d as t he date w he n t he last patie nt c o m pletes 
t he pr ot oc ol- defi ne d acti vities.
9. 1. 3.  
I nstit uti o n al Re vie w B o ar d/I n de pe n de nt Et hics C o m mittee Re vie w a n d 
A p pr o v al
T he i n vesti gat or ( or Gilea d as a p pr o priate acc or di n g t o l ocal re g ulati o ns) will s u b mit t his 
pr ot oc ol, I C F, a n d a n y acc o m pa n yi n g material t o be pr o vi de d t o t he patie nt (s uc h as 
a d vertise me nts, patie nt i nf or mati o n s heets, or descri pti o ns of t he st u d y use d t o o btai n i nf or me d 
c o nse nt) t o a n I R B/I E C. T he i n vesti gat or will n ot be gi n a n y st u d y patie nt acti vities u ntil 
a p pr o val fr o m t he I R B/I E C has bee n d oc u me nte d a n d pr o vi de d as a letter t o t he i n vesti gat or.
Bef ore i m ple me ntati o n, t he i n vesti gat or will s u b mit t o a n d recei ve d oc u me nte d a p pr o val fr o m 
t he I R B/I E C a n y m o dificati o ns ma de t o t he pr ot oc ol or a n y acc o m pa n yi n g material t o be 
pr o vi de d t o t he patie nt after i nitial I R B/I E C a p pr o val, wit h t he e xce pti o n of t h ose necessar y t o 
re d uce i m me diate ris k t o st u d y patie nts.
9. 1. 4.  
I nf or me d C o nse nt
T he i n vesti gat or is res p o nsi ble f or o btai ni n g writte n i nf or me d c o nse nt fr o m eac h i n di vi d ual 
partici pati n g i n t his st u d y after a de q uate e x pla nati o n of t he ai ms, met h o ds, o bjecti ves, a n d 
p ote ntial hazar ds of t he st u d y bef ore u n derta ki n g a n y st u d y-relate d pr oce d ures. T he i n vesti gat or 
m ust use t he m ost c urre nt I R B-  or I E C-a p pr o ve d I C F f or d oc u me nti n g writte n i nf or me d c o nse nt. 
Eac h I C F ( or asse nt as a p plica ble) will be a p pr o priatel y si g ne d a n d date d b y t he patie nt or t he 
patie nt’s le gall y a ut h orize d re prese ntati ve, t he pers o n c o n d ucti n g t he c o nse nt disc ussi o n, a n d a n 
i m partial wit ness (if re q uire d b y I R B or I E C or l ocal re q uire me nts).


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 4
2 4 Oct o ber 2 0 2 3
T he I C F will i nf or m patie nts a b o ut ge n o mic testi n g a n d/ or pla n ne d sa m ple rete nti o n. I n a d diti o n 
t o t he st u d y-s pecific I C F t o be si g ne d b y eac h patie nt partici pati n g i n t he st u d y, patie nts will be 
re q uire d t o d oc u me nt a gree me nt t o pr o vi de a d diti o nal sa m ples or t o all o w t he use of t he 
re mai n der of t heir alrea d y c ollecte d s peci me ns f or 
, i n acc or da nce wit h 
a p plica ble re g ulati o ns. T he res ults of t he tests perf or me d o n t he sa m ples will n ot be gi ve n t o t he 
patie nt or t he i n vesti gat or.
9. 1. 5.   
C o nfi de nti alit y
T he i n vesti gat or m ust e ns ure t hat patie nts’ a n o n y mit y will be strictl y mai ntai ne d a n d t hat t heir 
i de ntities are pr otecte d fr o m u na ut h orize d parties. O nl y a n i de ntificati o n c o de a n d a n y ot her 
u ni q ue i de ntifier(s) as all o we d b y l ocal la w (s uc h as year of birt h) will be rec or de d o n a n y f or m 
or bi ol o gical sa m ple s u b mitte d t o Gilea d, I R B/I E C, or t he la b orat or y. La b orat or y s peci me ns 
m ust be la bele d i n s uc h a wa y as t o pr otect patie nt i de ntit y w hile all o wi n g t he res ults t o be 
rec or de d t o t he pr o per patie nt. Refer t o s pecific la b orat or y i nstr ucti o ns. N O T E: T he i n vesti gat or 
m ust kee p a scree ni n g l o g wit h details f or all patie nts scree ne d a n d e nr olle d i n t he st u d y, i n 
acc or da nce wit h t he site pr oce d ures a n d re g ulati o ns. Patie nt data will be pr ocesse d i n acc or da nce 
wit h all a p plica ble re g ulati o ns.
T he i n vesti gat or a grees t hat all i nf or mati o n recei ve d fr o m Gilea d, i ncl u di n g b ut n ot li mite d t o t he 
I B, t his pr ot oc ol, C R Fs/e C R Fs, st u d y dr u g i nf or mati o n, a n d a n y ot her st u d y i nf or mati o n, re mai n 
t he s ole a n d e xcl usi ve pr o pert y of Gilea d d uri n g t he c o n d uct of t he st u d y a n d t hereafter. T his 
i nf or mati o n is n ot t o be discl ose d t o a n y t hir d part y (e xce pt e m pl o yees or a ge nts directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y or as re q uire d b y la w) wit h o ut pri or writte n c o nse nt fr o m 
Gilea d. T he i n vesti gat or f urt her a grees t o ta ke all reas o na ble preca uti o ns t o pre ve nt t he 
discl os ure b y a n y e m pl o yee or a ge nt of t he st u d y site t o a n y t hir d part y or ot her wise i nt o t he 
p u blic d o mai n.
9. 1. 6.  
St u d y Files a n d Rete nti o n of Rec or ds
T he i n vesti gat or m ust mai ntai n a de q uate a n d acc urate rec or ds t o e na ble t he c o n d uct of t he st u d y 
t o be f ull y d oc u me nte d a n d t he st u d y data t o be s u bse q ue ntl y verifie d. T hese d oc u me nts s h o ul d 
be classifie d i nt o at least t he f oll o wi n g 2 cate g ories: ( 1) i n vesti gat or’s st u d y file, a n d ( 2) patie nt 
cli nical s o urce d oc u me nts.
T he i n vesti gat or’s st u d y file will c o ntai n t he pr ot oc ol/a me n d me nts, C R Fs/e C R Fs, I R B/I E C a n d 
g o ver n me ntal a p pr o val wit h c orres p o n de nce, t he I C F, dr u g rec or ds, staff c urric ul u m vitae a n d 
a ut h orizati o n f or ms, a n d ot her a p pr o priate d oc u me nts a n d c orres p o n de nce.
T he re q uire d s o urce data s h o ul d i ncl u de se q ue ntial n otes c o ntai ni n g at least t he f oll o wi n g 
i nf or mati o n f or eac h patie nt:
•
Patie nt i de ntificati o n
•
D oc u me ntati o n t hat patie nt meets eli gi bilit y criteria (ie, me dical hist or y, p h ysical 
e xa mi nati o n, a n d c o nfir mati o n of dia g n osis [t o s u p p ort i ncl usi o n a n d e xcl usi o n criteria])
C CI


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 5
2 4 Oct o ber 2 0 2 3
•
D oc u me ntati o n of t he reas o n(s) a c o nse nte d patie nt is n ot e nr olle d
•
Partici pati o n i n st u d y (i ncl u di n g st u d y n u m ber)
•
St u d y disc usse d a n d date of i nf or me d c o nse nt
•
Dates of all visits
•
D oc u me ntati o n t hat pr ot oc ol-s pecific pr oce d ures were perf or me d
•
Res ults of efficac y para meters, as re q uire d b y t he pr ot oc ol
•
Start a n d e n d date (i ncl u di n g d ose re gi me n) of st u d y dr u g, i ncl u di n g dates of dis pe nsi n g a n d 
ret ur n
•
Rec or d of all A Es a n d ot her safet y para meters (start a n d e n d date, a n d i ncl u di n g ca usalit y 
a n d se verit y) a n d d oc u me ntati o n t hat a de q uate me dical care has bee n pr o vi de d f or a n y A E
•
C o nc o mita nt me dicati o n (start a n d e n d date; d ose if rele va nt; d ose c ha n ges)
•
Date of st u d y c o m pleti o n a n d reas o n f or earl y disc o nti n uati o n, if it occ urs
All cli nical st u d y d oc u me nts m ust be retai ne d b y t he i n vesti gat or f or at least 2 years or acc or di n g 
t o l ocal la ws, w hic he ver is l o n ger, after t he last a p pr o val of a mar keti n g a p plicati o n i n a n I C H 
re gi o n (ie, U S, E ur o pe, or Ja pa n) a n d u ntil t here are n o pe n di n g or pla n ne d mar keti n g 
a p plicati o ns i n a n I C H re gi o n; or, if n o a p plicati o n is file d or if t he a p plicati o n is n ot a p pr o ve d 
f or s uc h i n dicati o n, f or 2 years after t he i n vesti gati o n is disc o nti n ue d a n d re g ulat or y a ut h orities 
ha ve bee n n otifie d. I n vesti gat ors ma y be re q uire d t o retai n d oc u me nts l o n ger if s pecifie d b y 
re g ulat or y re q uire me nts, b y l ocal re g ulati o ns, or b y a n a gree me nt wit h Gilea d. T he i n vesti gat or 
m ust n otif y Gilea d bef ore destr o yi n g a n y cli nical st u d y rec or ds.
S h o ul d t he i n vesti gat or wis h t o assi g n t he st u d y rec or ds t o a n ot her part y or m o ve t he m t o a n ot her 
l ocati o n, Gilea d m ust be n otifie d i n a d va nce.
If t he i n vesti gat or ca n n ot pr o vi de f or t his arc hi vi n g re q uire me nt at t he st u d y site f or a n y or all of 
t he d oc u me nts, s pecial arra n ge me nts m ust be ma de bet wee n t he i n vesti gat or a n d Gilea d t o st ore 
t hese rec or ds sec urel y a wa y fr o m t he site s o t hat t he y ca n be ret ur ne d seale d t o t he i n vesti gat or 
i n case of a n i ns pecti o n. W he n s o urce d oc u me nts are re q uire d f or t he c o nti n ue d care of t he 
patie nt, a p pr o priate c o pies s h o ul d be ma de f or st ora ge a wa y fr o m t he site.
9. 1. 7.   
C ase Re p ort F or ms
F or eac h patie nt c o nse nte d, a n e C R F case b o o k will be c o m plete d b y a n a ut h orize d st u d y staff 
me m ber w h ose trai ni n g f or t his f u ncti o n is c o m plete d i n t he electr o nic data ca pt ure ( E D C) 
s yste m. T he e C R F case b o o k will o nl y ca pt ure t he data re q uire d per t he pr ot oc ol sc he d ules of 
assess me nts. T he I ncl usi o n/ E xcl usi o n Criteria a n d E nr oll me nt e C R Fs s h o ul d be c o m plete d o nl y 
after all data relate d t o eli gi bilit y ha ve bee n recei ve d. Data e ntr y s h o ul d be perf or me d i n 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 6
2 4 Oct o ber 2 0 2 3
acc or da nce wit h t he C R F C o m pleti o n G ui deli nes pr o vi de d b y t he s p o ns or. S u bse q ue nt t o data 
e ntr y, a st u d y m o nit or will perf or m s o urce data verificati o n wit hi n t he E D C s yste m. S yste m-
ge nerate d or ma n ual q ueries will be iss ue d i n t he E D C s yste m as data discre pa ncies are 
i de ntifie d b y t he m o nit or or Gilea d staff w h o r o uti nel y re vie w t he data f or c o m plete ness, 
c orrect ness, a n d c o nsiste nc y. T he site i n vesti gat or, site c o or di nat or, or ot her desi g nee is 
res p o nsi ble f or res p o n di n g t o t he q ueries i n a ti mel y ma n ner, wit hi n t he s yste m, eit her b y 
c o nfir mi n g t he data as c orrect or u p dati n g t he ori gi nal e ntr y, a n d pr o vi di n g t he reas o n f or t he 
u p date (e g, data e ntr y err or). Ori gi nal e ntries as well as a n y c ha n ges t o data fiel ds will be st ore d 
i n t he a u dit trail of t he s yste m. At a mi ni m u m, pri or t o a n y i nteri m ti me p oi nts or data base l oc k 
(as i nstr ucte d b y Gilea d), t he i n vesti gat or will use his/ her l o gi n cre de ntials t o c o nfir m t hat t he 
f or ms ha ve bee n re vie we d, a n d t hat t he e ntries acc uratel y reflect t he i nf or mati o n i n t he s o urce 
d oc u me nts. At t he c o ncl usi o n of t he st u d y, Gilea d will pr o vi de t he site i n vesti gat or wit h a rea d-
o nl y arc hi ve c o p y of t he data e ntere d b y t hat site. T his arc hi ve m ust be st ore d i n acc or da nce wit h 
t he rec or ds rete nti o n re q uire me nts o utli ne d i n Secti o n 9. 1. 6 .
9. 1. 8.  
I n vesti g at or I ns pecti o ns
T he i n vesti gat or will ma ke a vaila ble all s o urce d oc u me nts a n d ot her rec or ds f or t his st u d y t o 
Gilea d’s a p p oi nte d st u d y m o nit ors, t o I R Bs/I E Cs, or t o re g ulat or y a ut h orit y or healt h a ut h orit y 
i ns pect ors.
9. 1. 9.  
Pr ot oc ol C o m pli a nce
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t he st u d y is c o n d ucte d i n acc or da nce wit h t he 
pr oce d ures a n d e val uati o ns descri be d i n t his pr ot oc ol.
9. 2.  
S p o ns or Res p o nsi bilities
9. 2. 1.  
Pr ot oc ol M o dific ati o ns
Pr ot oc ol m o dificati o ns ma y be ma de o nl y b y t he s p o ns or.
9. 2. 2.  
St u d y Re p ort a n d P u blic ati o ns
A cli nical st u d y re p ort ( C S R) will be pre pare d a n d pr o vi de d t o t he re g ulat or y a ge ncies w he n 
a p plica ble a n d i n acc or da nce wit h l ocal re g ulat or y re q uire me nts. Gilea d will e ns ure t hat t he 
re p ort meets t he sta n dar ds set o ut i n t he I C H G ui deli ne f or Str uct ure a n d C o nte nt of Cli nical 
St u d y Re p orts (I C H E 3). N ote t hat a n a b bre viate d re p ort ma y be pre pare d i n certai n cases. F or 
st u dies wit h sites i n c o u ntries f oll o wi n g t he E U Re g ulati o n N o. 5 3 6/ 2 0 1 4, a C S R will be 
s u b mitte d wit hi n 1 year ( 6 m o nt hs f or pe diatric st u dies, i n acc or da nce wit h Re g ulati o n [ E C] 
N o. 1 9 0 1/ 2 0 0 6) after t he gl o bal e n d of st u d y (as defi ne d i n Secti o n 3. 5 ).
I n vesti gat ors i n t his st u d y ma y c o m m u nicate, orall y prese nt, or p u blis h st u d y data i n scie ntific 
j o ur nals or ot her sc h olarl y me dia i n acc or da nce wit h t he Gilea d cli nical trial a gree me nt:


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 7
2 4 Oct o ber 2 0 2 3
9. 3.  
J oi nt I n vesti g at or/ S p o ns or Res p o nsi bilities
9. 3. 1.  
P a y me nt Re p orti n g
I n vesti gat ors a n d t heir st u d y staff ma y be as ke d t o pr o vi de ser vices perf or me d u n der t his 
pr ot oc ol (e g, atte n da nce at i n vesti gat or meeti n gs). If re q uire d u n der t he a p plica ble stat ut or y a n d 
re g ulat or y re q uire me nts, Gilea d will ca pt ure a n d discl ose t o fe deral a n d state a ge ncies a n y 
e x pe nses pai d or rei m b urse d f or s uc h ser vices, i ncl u di n g a n y cli nical st u d y pa y me nts, meal, 
tra vel e x pe nses or rei m b urse me nts, c o ns ulti n g fees, a n d a n y ot her tra nsfer of val ue.
9. 3. 2.   
Access t o I nf or m ati o n f or M o nit ori n g
T he m o nit or is res p o nsi ble f or r o uti ne re vie w of t he C R F/e C R F at re g ular i nter vals t hr o u g h o ut 
t he st u d y t o verif y a d here nce t o t he pr ot oc ol a n d t he c o m plete ness, c o nsiste nc y, a n d acc urac y of 
t he data bei n g e ntere d o n t he m. T he m o nit or s h o ul d ha ve access t o a n y patie nt rec or ds nee de d t o 
verif y t he e ntries i n t he C R F/e C R F. T he i n vesti gat or a grees t o c o o perate wit h t he m o nit or t o 
e ns ure t hat a n y pr o ble ms detecte d t hr o u g h a n y t y pe of m o nit ori n g (ce ntral, o n site) are res ol ve d.
9. 3. 3.   
Access t o I nf or m ati o n f or A u diti n g or I ns pecti o ns
Re prese ntati ves of re g ulat or y a ut h orities or Gilea d ma y c o n d uct i ns pecti o ns or a u dits of t he 
cli nical st u d y. If t he i n vesti gat or is n otifie d of a n i ns pecti o n b y a re g ulat or y a ut h orit y, t he 
i n vesti gat or a grees t o n otif y t he Gilea d me dical m o nit or i m me diatel y. T he i n vesti gat or a grees t o 
pr o vi de t o re prese ntati ves of a re g ulat or y a ge nc y or Gilea d access t o rec or ds, facilities, a n d 
pers o n nel f or t he effecti ve c o n d uct of a n y i ns pecti o n or a u dit.
9. 3. 4.  
St u d y Disc o nti n u ati o n
B ot h Gilea d a n d t he i n vesti gat or reser ve t he ri g ht t o ter mi nate t he st u d y at a n y ti me. S h o ul d t his 
be necessar y, b ot h parties will arra n ge disc o nti n uati o n pr oce d ures a n d n otif y t he patie nts, 
a p pr o priate re g ulat or y a ut h orit y, I R Bs, a n d I E Cs. I n ter mi nati n g t he st u d y, Gilea d a n d t he 
i n vesti gat or will e ns ure t hat a de q uate c o nsi derati o n is gi ve n t o t he pr otecti o n of t he patie nts’ 
i nterests.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 8
2 4 Oct o ber 2 0 2 3
1 0.   
R E F E R E N C E S
A d va ni R, Fli n n I, P o p ple well L, F orer o A, Bartlett N L, G h os h N, et al. C D 4 7 Bl oc ka de b y 
H u 5 F 9- G 4 a n d Rit u xi ma b i n N o n- H o d g ki n's L y m p h o ma. N E n gl J Me d 2 0 1 8; 3 7 9 
( 1 8): 1 7 1 1- 2 1.
Balar A V, Gals k y M D, R ose n ber g J E, P o wles T, Petr yla k D P, Bell m u nt J, et al. Atez oliz u ma b as 
first-li ne treat me nt i n cis plati n-i neli gi ble patie nts wit h l ocall y a d va nce d a n d 
metastatic ur ot helial carci n o ma: a si n gle-ar m, m ultice ntre, p hase 2 trial. La ncet 
2 0 1 7; 3 8 9 ( 1 0 0 6 4): 6 7- 7 6.
Bell m u nt J, de Wit R, Va u g h n DJ, Fra det Y, Lee J L, F o n g L, et al. Pe m br oliz u ma b as Sec o n d-
Li ne T hera p y f or A d va nce d Ur ot helial Carci n o ma. N E n gl J Me d 2 0 1 7; 3 7 6 
( 1 1): 1 0 1 5- 2 6.
Bra h mer J, Lacc hetti C, Sc h nei der B, At ki ns M, Brassil K, Cateri n o J, et al. Ma na ge me nt of 
I m m u ne- Relate d A d verse E ve nts i n Patie nts Treate d Wit h I m m u ne C hec k p oi nt 
I n hi bit or T hera p y: A merica n S ociet y of Cli nical O nc ol o g y Cli nical Practice 
G ui deli ne. J o ur nal of cli nical O nc ol o g y 2 0 1 8; 3 6 ( 1 7).
C ha o M P, Aliza de h A A, Ta n g C, Ja n M, Weiss ma n- Ts u ka m ot o R, Z ha o F, et al. T hera pe utic 
a nti b o d y tar geti n g of C D 4 7 eli mi nates h u ma n ac ute l y m p h o blastic le u ke mia. 
Ca ncer Res 2 0 1 1a; 7 1 ( 4): 1 3 7 4- 8 4.
C ha o M P, Aliza de h A A, Ta n g C, M y kle b ust J H, Var g hese B, Gill S, et al. A nti- C D 4 7 a nti b o d y 
s y ner gizes wit h rit u xi ma b t o pr o m ote p ha g oc yt osis a n d era dicate n o n- H o d g ki n 
l y m p h o ma. Cell 2 0 1 0a; 1 4 2: 6 9 9- 7 1 3.
C ha o M P, Jais wal S, Weiss ma n- Ts u ka m ot o R, Aliza de h A A, Ge ntles AJ, V ol k mer J, et al. 
Calretic uli n Is t he D o mi na nt Pr o- P ha g oc ytic Si g nal o n M ulti ple H u ma n Ca ncers 
a n d Is C o u nter bala nce d b y C D 4 7. Scie nce tra nslati o nal me dici ne 2 0 1 0 b; 2 
( 6 3): 6 3ra 9 4.
C ha o M P, Majeti R, Weiss ma n I L. Pr o gra m me d cell re m o val: a ne w o bstacle i n t he r oa d t o 
de vel o pi n g ca ncer. Nat Re v Ca ncer. 2 0 1 2; 1 2 ( 1): 5 8- 6 7.
C ha o M P, Ta n g C, Pac h y ns ki R K, C hi n R, Majeti R, Weiss ma n I L. E xtra n o dal disse mi nati o n of 
n o n- H o d g ki n l y m p h o ma re q uires C D 4 7 a n d is i n hi bite d b y a nti- C D 4 7 a nti b o d y 
t hera p y. Bl o o d 2 0 1 1 b; 1 1 8 ( 1 8): 4 8 9 0- 9 0 1.
C he n J Y, Mc Ke n na K M, C h oi T S, D ua n J, Br o w n L, Ste wart JJ, et al. R B C- S pecific C D 4 7 
Pr u ni n g C o nfers Pr otecti o n a n d U n derlies t he Tra nsie nt A ne mia i n Patie nts 
Treate d wit h A nti- C D 4 7 A nti b o d y 5 F 9 [ A bstract]. Bl o o d ( A S H A n n ual Meeti n g 
A bstracts) 2 0 1 8; 1 3 2 ( S u p pl 1): 2 3 2 7.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 8 9
2 4 Oct o ber 2 0 2 3
E dris B, Weis k o pf K, V ol k mer A K, V ol k mer J P, Willi n g ha m S B, C o ntreras- Tr ujill o H, et al. 
A nti b o d y t hera p y tar geti n g t he C D 4 7 pr otei n is effecti ve i n a m o del of a g gressi ve 
metastatic lei o m y osarc o ma. Pr oc Natl Aca d Sci U S A 2 0 1 2; 1 0 9 ( 1 7): 6 6 5 6- 6 1.
Eise n ha uer E A, T herasse P, B o gaerts J, Sc h wartz L H, Sar ge nt D, F or d R, et al. Ne w Res p o nse 
E val uati o n Criteria i n S oli d T u m o urs: Re vise d R E CI S T G ui deli ne ( Versi o n 1. 1). 
E ur J Ca ncer 2 0 0 9; 4 5 ( 2): 2 2 8- 4 7.
Etti n ger D S, W o o d D E, A g gar wal C, Ais ner D L, A kerle y W, Ba u ma n J R, et al. N C C N 
G ui deli nes I nsi g hts: N o n- S mall Cell L u n g Ca ncer, Versi o n 1. 2 0 2 0. J Natl C o m pr 
Ca nc Net w 2 0 1 9; 1 7 ( 1 2): 1 4 6 4- 7 2.
Fis her G A, La k ha ni NJ, E n g C, Hec ht J R, Be n dell J C, P hili p P A, et al. A p hase I b/II st u d y of t he 
a nti- C D 4 7 a nti b o d y ma gr oli ma b wit h cet u xi ma b i n s oli d t u m or a n d c ol orectal 
ca ncer patie nts [ A bstract 1 1 4]. Gastr oi ntesti nal Ca ncers S y m p osi u m; 2 0 2 0 2 3- 2 5 
Ja n uar y; Sa n Fra ncisc o, C A. 
H or n L, Ma nsfiel d A S, Szczes na A, Ha vel L, Krza k o ws ki M, H oc h mair MJ, et al. First- Li ne 
Atez oliz u ma b pl us C he m ot hera p y i n E xte nsi ve- Sta ge S mall- Cell L u n g Ca ncer. N 
E n gl J Me d 2 0 1 8; 3 7 9 ( 2 3): 2 2 2 0- 9.
Jais wal S, Ja mies o n C H, Pa n g W W, Par k C Y, C ha o M P, Majeti R, et al. C D 4 7 Is U p- Re g ulate d 
o n Circ ulati n g He mat o p oietic Ste m Cells a n d Le u ke mia Cells t o A v oi d 
P ha g oc yt osis. Cell 2 0 0 9; 1 3 8 ( 2): 2 7 1- 8 5.
Ki m D, Wa n g J, Willi n g ha m S B, Marti n R, Wer ni g G, Weiss ma n I L. A nti- C D 4 7 a nti b o dies 
pr o m ote p ha g oc yt osis a n d i n hi bit t he gr o wt h of h u ma n m yel o ma cells. Le u ke mia 
2 0 1 2; 2 6 ( 1 2): 2 5 3 8- 4 5.
Li u J, Wa n g L, Z ha o F, Tse n g S, Nara ya na n C, S h ura L, et al. Pre- Cli nical De vel o p me nt of a 
H u ma nize d A nti- C D 4 7 A nti b o d y wit h A nti- Ca ncer T hera pe utic P ote ntial. P L o S 
O ne. 2 0 1 5a; 1 0 ( 9):e 0 1 3 7 3 4 5.
Li u X, P u Y, Cr o n K, De n g L, Kli ne J, Frazier W A, et al. C D 4 7 bl oc ka de tri g gers T cell-
me diate d destr ucti o n of i m m u n o ge nic t u m ors. Nat Me d 2 0 1 5 b; 2 1 ( 1 0): 1 2 0 9- 1 5.
Majeti R, C ha o M P, Aliza de h A A, Pa n g W W, Jais wal S, Gi b bs K D, Jr., et al. C D 4 7 Is a n 
A d verse Pr o g n ostic Fact or a n d T hera pe utic A nti b o d y Tar get o n H u ma n Ac ute 
M yel oi d Le u ke mia Ste m Cells. Cell 2 0 0 9; 1 3 8 ( 2): 2 8 6- 9 9.
O ke n M M, Creec h R H, T or me y D C, H ort o n J, Da vis T E, Mc Fa d de n E T, 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): 6 4 9- 5 5.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 0
2 4 Oct o ber 2 0 2 3
Paz ‑Ares L, D v or ki n M, C he n Y, Rei n m ut h N, H otta K, Tr u k hi n D, et al. D ur val u ma b pl us 
plati n u m-et o p osi de vers us plati n u m-et o p osi de i n first-li ne treat me nt of e xte nsi ve-
sta ge s mall-cell l u n g ca ncer ( C A S PI A N): a ra n d o mise d, c o ntr olle d, o pe n-la bel, 
p hase 3 trial. La ncet 2 0 1 9; 3 9 4 ( 1 0 2 1 2): 1 9 2 9- 3 9.
Ritt me yer A, Barlesi F, Water ka m p D, Par k K, Ciar diell o F, v o n Pa wel J, et al. Atez oliz u ma b 
vers us d oceta xel i n patie nts wit h pre vi o usl y treate d n o n-s mall-cell l u n g ca ncer 
( O A K): a p hase 3, o pe n-la bel, m ultice ntre ra n d o mise d c o ntr olle d trial. La ncet 
2 0 1 7; 3 8 9 ( 1 0 0 6 6): 2 5 5- 6 5.
R ossi A, Di Mai o M, C hi o di ni P, R u d d R M, O ka m ot o H, S karl os D V, et al. Car b o plati n- or 
cis plati n- base d c he m ot hera p y i n first-li ne treat me nt of s mall-cell l u n g ca ncer: t he 
C O CI S meta-a nal ysis of i n di vi d ual patie nt data. J Cli n O nc ol 2 0 1 2; 3 0 ( 1 4): 1 6 9 2-
8.
Sall ma n D A, Asc h A, Al- Mal ki M, Lee D, Garcia- Ma ner o G, D o n nella n W, et al. T olera bilit y 
a n d Efficac y of t he First-i n- Class A nti- C D 4 7 A nti b o d y Ma gr oli ma b C o m bi ne d 
Wit h Azaciti di ne i n M D S a n d A M L Patie nts: P hase 1 b Res ults [ Prese ntati o n]. 
A merica n S ociet y of Cli nical O nc ol o g y ( A S C O) A n n ual Meeti n g Virt ual; 2 0 2 0. 
S he p her d F A, Da nce y J, Ra mla u R, Matts o n K, Gralla R, O' R o ur ke M, et al. Pr os pecti ve 
ra n d o mize d trial of d oceta xel vers us best s u p p orti ve care i n patie nts wit h n o n-
s mall-cell l u n g ca ncer pre vi o usl y treate d wit h plati n u m- base d c he m ot hera p y. J 
Cli n O nc ol 2 0 0 0; 1 8 ( 1 0): 2 0 9 5- 1 0 3.
Si kic BI, La k ha ni N, Pat nai k A, S ha h S A, C ha n da na S R, Rasc o D, et al. First-i n- H u ma n, First-
i n- Class P hase I Trial of t he A nti- C D 4 7 A nti b o d y H u 5 F 9- G 4 i n Patie nts Wit h 
A d va nce d Ca ncers. J Cli n O nc ol 2 0 1 9; 3 7 ( 1 2): 9 4 6- 5 3.
Si kic BI, Pa d da S K, S ha h S A, C ole vas A D, Nara ya na n S, Fis her G A, et al. A first-i n- h u ma n, 
first-i n-class p hase I trial of t he a nti- C D 4 7 a nti b o d y H u 5 F 9- G 4 i n patie nts wit h 
a d va nce d ca ncers.  2 0 1 6:
S mit E F, F o k ke ma E, Bies ma B, Gr oe n HJ, S n oe k W, P ost m us P E. A p hase II st u d y of paclita xel 
i n hea vil y pretreate d patie nts wit h s mall-cell l u n g ca ncer. Br J Ca ncer 1 9 9 8; 7 7 
( 2): 3 4 7- 5 1.
Ta x otere ®, Gilea d Scie nces I nc. Ta x otere ® ( d oceta xel) S u m mar y of Pr o d uct C haracteristics. 
F oster Cit y, C A. Re vise d 0 6/ 2 0 2 0.  1 9 9 5:
Ta x otere ®, Gilea d Scie nces I nc. Ta x otere ® ( d oceta xel) I njecti o n C o nce ntrate, I ntra ve n o us 
I nf usi o n. U. S. Prescri bi n g I nf or mati o n. F oster Cit y, C A. Re vise d 0 5/ 2 0 2 1.  1 9 9 6:
Tr o u g ht o n M C, Si m m o ns L W, La n gle y C, Y o ussef M, Mar q ues M B. A N o vel Use of H u ma n 
Platelet C o nce ntrate t o Res ol ve I nterfere nce of A nti- C D 4 7 i n Ser ol o gic Testi n g 
[I G T 4 6]. Tra nsf usi o n 2 0 1 8; 5 8 ( S 2): 1 7 9 A- 8 0 A.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 1
2 4 Oct o ber 2 0 2 3
Tse n g D, V ol k mer J P, Willi n g ha m S B, C o ntreras- Tr ujill o H, Fat h ma n J W, Fer n h off N B, et al. 
A nti- C D 4 7 a nti b o d y- me diate d p ha g oc yt osis of ca ncer b y macr o p ha ges pri mes a n 
effecti ve a ntit u m or T-cell res p o nse. Pr oc Natl Aca d Sci U S A 2 0 1 3; 1 1 0 
( 2 7): 1 1 1 0 3- 8.
U. S. De part me nt of Healt h a n d H u ma n Ser vices, F o o d a n d Dr u g A d mi nistrati o n, Ce nter f or 
Dr u g E val uati o n a n d Researc h ( C D E R), Ce nter f or Bi ol o gics E val uati o n a n d 
Researc h ( C B E R). G ui da nce f or I n d ustr y Dr u g-I n d uce d Li ver I nj ur y:  
Pre mar keti n g Cli nical E val uati o n.  J ul y, 2 0 0 9.
Va n C utse m E, Ma yer RJ, La ure nt S, Wi n kler R, Gra val os C, Be na vi des M, et al. T he s u b gr o u ps 
of t he p hase III R E C O U R S E trial of trifl uri di ne/ti piracil ( T A S- 1 0 2) vers us 
place b o wit h best s u p p orti ve care i n patie nts wit h metastatic c ol orectal ca ncer. 
E ur J Ca ncer 2 0 1 8; 9 0: 6 3- 7 2.
Velli q uette R W, Aesc hli ma n n J, Kir ke gaar d J, S ha karia n G, L o mas- Fra ncis C, West h off C M. 
M o n ocl o nal a nti- C D 4 7 i nterfere nce i n re d cell a n d platelet testi n g. Tra nsf usi o n 
2 0 1 9; 5 9 ( 2): 7 3 0- 7.
v o n der Maase H, Ha nse n S W, R o berts J T, D o gli otti L, Oli ver T, M o ore MJ, et al. Ge mcita bi ne 
a n d cis plati n vers us met h otre xate, vi n blasti ne, d o x or u bici n, a n d cis plati n i n 
a d va nce d or metastatic bla d der ca ncer: res ults of a lar ge, ra n d o mize d, 
m ulti nati o nal, m ultice nter, p hase III st u d y. J Cli n O nc ol 2 0 0 0; 1 8 ( 1 7): 3 0 6 8- 7 7.
V u k y J, Balar A V, Castella n o D, O' D o n nell P H, Gri vas P, Bell m u nt J, et al. L o n g- Ter m 
O utc o mes i n K E Y N O T E- 0 5 2: P hase II St u d y I n vesti gati n g First- Li ne 
Pe m br oliz u ma b i n Cis plati n-I neli gi ble Patie nts Wit h L ocall y A d va nce d or 
Metastatic Ur ot helial Ca ncer. J Cli n O nc ol 2 0 2 0; 3 8 ( 2 3): 2 6 5 8- 6 6.
Willi n g ha m S B, V ol k mer J P, Ge ntles AJ, Sa h o o D, Daler ba P, Mitra S S, et al. T he C D 4 7-si g nal 
re g ulat or y pr otei n al p ha ( SI R Pa) i nteracti o n is a t hera pe utic tar get f or h u ma n 
s oli d t u m ors. Pr oc Natl Aca d Sci U S A 2 0 1 2; 1 0 9 ( 1 7): 6 6 6 2- 7.
Ya ma m ot o N, Ts ur uta ni J, Y os hi m ura N, Asai G, M ori ya ma A, Na ka ga wa K, et al. P hase II 
st u d y of wee kl y paclita xel f or rela pse d a n d refract or y s mall cell l u n g ca ncer. 
A ntica ncer Res 2 0 0 6; 2 6 ( 1 B): 7 7 7- 8 1.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 2
2 4 Oct o ber 2 0 2 3
1 1.   
A P P E N DI C E S
A p pe n di x 1.  
I n vesti gat or Si g nat ure Pa ge
A p pe n di x 2.   
Mar keti n g A ut h orizati o n Stat us of St u d y I nter ve nti o ns
A p pe n di x 3.  
Sc he d ules of Assess me nt
A p pe n di x 4.  
Pa n de mic Ris k Assess me nt a n d Miti gati o n Pla n
A p pe n di x 5.  
T o xicit y Gra di n g Scale f or Se verit y of A d verse E ve nts a n d La b orat or y 
A b n or malities
A p pe n di x 6.  
Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P ote ntial, a n d 
C o ntrace pti ve Re q uire me nts
A p pe n di x 7.  
Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) Perf or ma nce Stat us
A p pe n di x 8.  
Res p o nse E val uati o n Criteria i n S oli d T u m ors ( R E CI S T, Versi o n 1. 1)
A p pe n di x 9.  
C o u ntr y- S pecific Re q uire me nts
A p pe n di x 1 0.   
A me n d me nt Hist or y


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 3
2 4 Oct o ber 2 0 2 3
A p pe n di x 1.  
I n vesti g at or Si g n at ure P a ge
GI L E A D S CI E N C E S, I N C.
3 3 3 L A K E SI D E D RI V E
F O S T E R CI T Y, C A 9 4 4 0 4
S T U D Y A C K N O W L E D G M E N T
A P hase 2, M ulti- Ar m St u d y of Ma gr oli ma b i n Patie nts wit h S oli d T u m ors
G S- U S- 5 4 8- 5 9 1 8 A me n d me nt 5; 2 4 Oct o ber 2 0 2 3
T his pr ot oc ol has bee n a p pr o ve d b y Gilea d Scie nces, I nc. T he f oll o wi n g si g nat ure d oc u me nts 
t his a p pr o val.
[ See a p pe n de d electr o nic si g n at ure]
Na me ( Pri nte d)
Me dical M o nit or
Si g nat ure
[ See a p pe n de d electr o nic si g n at ure]
Date
I N V E S TI G A T O R S T A T E M E N T
I ha ve rea d t he pr ot oc ol, i ncl u di n g all a p pe n dices, a n d I a gree t hat it c o ntai ns all necessar y 
details f or me a n d m y staff t o c o n d uct t his st u d y as descri be d. I will c o n d uct t his st u d y as 
o utli ne d herei n a n d will ma ke a reas o na ble eff ort t o c o m plete t he st u d y wit hi n t he ti me 
desi g nate d.
I will pr o vi de all st u d y pers o n nel u n der m y s u per visi o n c o pies of t he pr ot oc ol a n d access t o all 
i nf or mati o n pr o vi de d b y Gilea d Scie nces, I nc. I will disc uss t his material wit h t he m t o e ns ure 
t hat t he y are f ull y i nf or me d a b o ut t he dr u gs a n d t he st u d y.
Pri nci pal I n vesti gat or Na me ( Pri nte d)
Si g nat ure
Date
Site N u m ber
P P D-


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 4
2 4 Oct o ber 2 0 2 3
A p pe n di x 2.   
M ar keti n g A ut h oriz ati o n St at us of St u d y I nter ve nti o ns
St u d y 
I nter ve nti o n 
N a me
C ate g or y
A ut h orize d i n 
≥ 1 C o u ntr y 
F oll o wi n g E U 
Re g ul ati o n 
N o. 5 3 6/ 2 0 1 4
A ut h orize d 
i n ≥ 1 I C H 
C o u ntr y
A ut h orize d b y 
S wiss me dic
Ma gr oli ma b 
St u d y dr u g
N o a
N o a
N o a
D oceta xel
St u d y dr u g
Yes
Yes
Yes
Aceta mi n o p he n
A x M P
Yes
Yes
Yes
Di p he n h y dra mi ne
A x M P
Yes
Yes
Yes
De xa met has o ne
A x M P
Yes
Yes
Yes
A x M P = a u xiliar y me dici nal pr o d uct; E U = E ur o pea n U ni o n; 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) 
a  
Rati o nale descri be d i n Secti o n 1


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 5
2 4 Oct o ber 2 0 2 3
A p pe n di x 3.  
Sc he d ules of Assess me nt
A p pe n di x T a ble 1. 
S afet y R u n-i n C o h ort 1 a n d P h ase 2 C o h ort 1: Sc he d ule of Assess me nts – Scree ni n g a n d Tre at me nt 
Peri o d 
Visit Wi n d o w ( D a ys)
Scree ni n g
D a y - 3 0 t o - 1
C ycle ( 2 1- d a y c ycles)
1 a
2 a
3 a
4 + a
N o ne 
± 3 b
± 3 b
± 3 b
± 3 b
C ycle D a y
1 
2 
8 
1 5 
1 
8 
1 5 
1
1
I nf or me d c o nse nt
X
De m o gra p hics
X
Me dical a n d ca ncer hist or y
X
E C O G
X
X
X
X
X
Vital si g ns, hei g ht, a n d wei g ht c
X
X
X 
X 
X 
X 
X 
X
X
P h ysical e xa mi nati o n d
X
X
X 
X 
X 
X 
X
X
E C G (si n gle)
X
Pre g na nc y test e 
X
X
X
X
X
He mat ol o g y b, f
X
X f
X 
X f
X 
X 
X 
X 
X
X
Ha pt o gl o bi n a n d L D H b
X
X 
X
Ser u m or plas ma c he mistr y b
X
X
X 
X 
X 
X 
X 
X
X
C oa g ulati o n g
X
Bl o o d, t y pe a n d scree n ( A B O/ R h), D A T, a n d 
e xte n de d R B C p he n ot y pi n g a n d ge n ot y pi n g
X
Uri nal ysis b, h
X
T u m or i ma gi n g i 
X
X, Q 9 W
T u m or bi o ps y 
Refer t o A p pe n di x Ta ble 3


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 6
2 4 Oct o ber 2 0 2 3
Visit Wi n d o w ( D a ys)
Scree ni n g
D a y - 3 0 t o - 1
C ycle ( 2 1- d a y c ycles)
1 a
2 a
3 a
4 + a
N o ne 
± 3 b
± 3 b
± 3 b
± 3 b
C ycle D a y
1 
2 
8 
1 5 
1 
8 
1 5 
1
1
A d verse e ve nts j 
X
C o nc o mita nt me dicati o ns
X
Rece pt or occ u pa nc y
Circ ulati n g t u m or D N A
P B M C
Ser u m a n d plas ma bi o mar kers
W h ole bl o o d R N A
I m m u n o p he n ot y pi n g assa y
T C R se q ue nci n g
St o ol micr o bi o me
Ge n o mic bl o o d sa m ple
P K
A nti dr u g a nti b o dies
Refer t o A p pe n di x Ta ble 3
I R T re gistrati o nk
X
X
X 
X 
X 
X 
X 
X
X
Pre me dicati o n f or ma gr oli ma b l
X
X
Ma gr oli ma b
m
X
X 
X 
X 
X 
X 
X
X
D oceta xel
X
X
X
X
A B O = a n y of t he 4 bl o o d gr o u ps A, B, A B, a n d O c o m prisi n g t he A B O s yste m; a P T T = acti vate d partial t hr o m b o plasti n ti me; C T = c o m p ute d t o m o gra p h y; D A T = direct 
a nti gl o b uli n test; 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; I N R = i nter nati o nal n or malize d rati o; I R T = I nteracti ve Res p o nse Tec h n ol o g y; 
L D H = lactate de h y dr o ge nase; M RI = ma g netic res o na nce i ma gi n g; P B M C = peri p heral bl o o d m o n o n uclear cell; P K = p har mac o ki netics; P T = pr ot hr o m bi n ti me; P T T = partial 
t hr o m b o plasti n ti me; Q 9 W = e ver y 9 wee ks; R E CI S T = Res p o nse E val uati o n Criteria i n S oli d T u m ors; R h = r hes us; R P 2 D = rec o m me n de d P hase 2 d ose; T C R = T cell rece pt or
N ote: Refer t o Secti o n 6. 5  Safet y Assess me nts f or c o m plete list of a nal ytes t o be teste d.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 7
2 4 Oct o ber 2 0 2 3
a  
I n cases of ma gr oli ma b re pri mi n g f oll o wi n g a treat me nt dela y ( Secti o n 5. 5 ), efficac y, bi o mar ker, P K, a n d i m m u n o ge nicit y assess me nts will f oll o w t he sc he d ule of t he 
assi g ne d c ycle n u m ber. Ma gr oli ma b d osi n g a n d t he safet y assess me nt will f oll o w C ycle 1 (refer t o Ta ble 2  or Ta ble 3  as a p pr o priate), a n d t he n s u bse q ue ntl y s witc h bac k t o 
t he ne xt assi g ne d c ycle sc he d ule. Ma gr oli ma b s h o ul d n ot be gi ve n o n c o nsec uti ve da ys. Refer t o f o ot n ote (l) f or pre me dicati o n re q uire me nt.
b  
Pretreat me nt assess me nts are t o be c ollecte d wit hi n 3 da ys pri or t o a n y st u d y treat me nt a d mi nistrati o n. Wit hi n 2 4 h o urs pri or t o eac h of t he first 2 d oses of ma gr oli ma b 
i nf usi o n d uri n g i nitial treat me nt, all patie nts m ust ha ve a d oc u me nte d he m o gl o bi n ≥ 9 g/ d L. Patie nts w h o d o n ot meet t hese criteria m ust be tra nsf use d a n d ha ve t heir 
he m o gl o bi n rec hec ke d t o meet 9 g/ d L pri or t o eac h of t he first 2 d oses of ma gr oli ma b.
c   
Hei g ht will be c ollecte d at scree ni n g o nl y. Vital si g n meas ure me nts will be c ollecte d pre d ose o n t he sa me da y as i nf usi o n of a n y st u d y treat me nt. Wei g ht will be c ollecte d at 
scree ni n g a n d Da y 1 of eac h c ycle.
d  
C o m plete p h ysical e xa mi nati o n is t o be perf or me d at scree ni n g a n d s y m pt o m- directe d p h ysical e xa mi nati o n is t o be perf or me d fr o m C ycle 1 Da y 1.
e  
Ser u m pre g na nc y test will be c o n d ucte d at scree ni n g. T he C ycle 1 Da y 1 pre g na nc y test d oes n ot nee d t o be re peate d if t he scree ni n g pre g na nc y test was perf or me d wit hi n t he 
7 2 h o urs bef ore st u d y treat me nt a d mi nistrati o n. Uri ne or ser u m pre g na nc y tests will be c o n d ucte d fr o m C ycle 1 Da y 1.
f   
A c o m plete bl o o d c o u nt wit h differe ntial, platelets, a n d retic ul oc ytes will be c o n d ucte d. A n a d diti o nal he m o gl o bi n m ust be c hec ke d  3 t o 6 h o urs after t he i nitiati o n of t he first 
a n d sec o n d d oses of ma gr oli ma b d uri n g i nitial treat me nt (refer t o Secti o n 7. 8. 1. 1 ). Pretreat me nt assess me nts are t o be c ollecte d wit hi n 2 4 h o urs pri or t o t he first 2 ma gr oli ma b 
d oses per Secti o n 7. 8. 1. 1 .
g  
T he a nal ytes t o be teste d are P T, I N R, a n d a P T T ( or P T T).
h  
Refle x micr osc o pic testi n g base d o n ot her a b n or malities.
i  
C T/ M RI will be perf or me d per Secti o n 6. 6 . Per R E CI S T, Versi o n 1. 1, if a patie nt ac hie ves a n i nitial o bjecti ve res p o nse o n i ma gi n g, a n i ma gi n g assess me nt at least 4 wee ks 
later is re q uire d f or c o nfir me d res p o nse. C o nfir mati o n of disease pr o gressi o n t hr o u g h a s u bse q ue nt res p o nse assess me nt at least 4 wee ks a part ma y als o be c o nsi dere d per 
Secti o n 3. 4 . T he o n-treat me nt i ma gi n g wi n d o w is ± 7 da ys.
j   
D uri n g scree ni n g, c ollect a d verse e ve nts relate d t o pr ot oc ol- ma n date d pr oce d ures.
k  
I R T re gistrati o n will be re q uire d f or scree ni n g, e nr oll me nt, a n d w he n dis pe nsi n g a n y st u d y dr u g s u p plie d b y Gilea d.
l  
Pre me dicati o n wit h aceta mi n o p he n a n d di p he n h y dra mi ne is re q uire d pri or t o t he a d mi nistrati o n of t he first 2 d oses of st u d y treat me nt a n d i n case of rei ntr o d ucti o n wit h 
re pri mi n g.
m   
Ma gr oli ma b will be a d mi nistere d first bef ore d oceta xel. All patie nts s h o ul d be m o nit ore d h o url y d uri n g i nf usi o n. Patie nts t o be m o nit ore d (i ncl u di n g meas ure me nt of vital 
si g ns, as cli nicall y a p pr o priate) f or si g ns a n d s y m pt o ms of I R Rs, w hic h ha ve bee n o bser ve d i n pre vi o us ma gr oli ma b st u dies. P osti nf usi o n m o nit ori n g t o be gi n after t he 
i nf usi o n is c o m plete b ut pri or t o a d mi nisteri n g d oceta xel. P osti nf usi o n m o nit ori n g is n ot re q uire d f or d oses after C ycle 1. T he R P 2 D will be deter mi ne d i n Safet y R u n-i n 
C o h ort 1. T he ma gr oli ma b d osi n g re gi me n is descri be d i n Ta ble 2  f or Safet y R u n-i n C o h ort 1 a n d Ta ble 3  f or P hase 2 C o h ort 1.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 8
2 4 Oct o ber 2 0 2 3
A p pe n di x T a ble 2. 
Sc he d ule of Assess me nts – P osttre at me nt
E O T Visit
S afet y F oll o w- u p 
Visit/ C all ( Tele p h o ne) a
Pre- Pr o gressi o n Visit b
S ur vi v al F oll o w- u p
Wit hi n 7 D a ys after L ast 
D ose or E O T Decisi o n
3 0 D a ys
after L ast D ose
After S afet y F oll o w- U p 
U ntil Dise ase 
Pr o gressi o n
E ver y 2 M o nt hs 
After S afet y 
F oll o w- U p
Visit Wi n d o w
± 7 D a ys
± 7 D a ys
± 7 D a ys
Uri ne or ser u m pre g na nc y test c
X
X
X
X
He mat ol o g y d 
X
Ser u m or plas ma c he mistr y 
X
P har mac o ki netics
A nti dr u g a nti b o dies 
Rece pt or occ u pa nc y
Circ ulati n g t u m or D N A
W h ole bl o o d R N A
Ser u m a n d plas ma bi o mar kers
Refer t o A p pe n di x Ta ble 3
T u m or i ma gi n g f or res p o nse assess me nt e
X
X
E C O G
X
Vital si g ns 
X
S y m pt o m- directe d p h ysical e xa mi nati o n
X
A d verse e ve nts f
X
X
C o nc o mita nt me dicati o ns
X
X
Ne w a ntica ncer t hera p y g
X
X
X
S ur vi val f oll o w- u p
E ver y 2 m o nt hs h
C T = c o m p ute d t o m o gra p h y; E C O G = Easter n C o o perati ve O nc ol o g y Gr o u p; E O T = e n d of treat me nt; M RI = ma g netic res o na nce i ma gi n g; T C R = T cell rece pt or


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 9 9
2 4 Oct o ber 2 0 2 3
a  
If t he patie nt e x perie nces a treat me nt-relate d A E or a n S A E (re gar dless of attri b uti o n), t he patie nt m ust be as ke d t o c o me t o t he site.
b  
T his will o nl y a p pl y f or patie nts w h o st o p st u d y treat me nt n ot relate d t o ra di o gra p hic disease pr o gressi o n a n d will c o nti n ue t o ha ve t u m or i ma gi n g. See f o ot n ote (e) f or details 
o n t u m or i ma gi n g sc he d ule. Pre- pr o gressi o n visits will be c o m plete d first bef ore pr ocee di n g t o s ur vi val f oll o w- u p.
c  
Pre g na nc y testi n g will c o nti n ue m o nt hl y u p t o 6 m o nt hs after t he e n d of treat me nt per t he d urati o n of re q uire d c o ntrace pti o n as disc usse d i n A p pe n di x 6 . Testi n g d uri n g 
s ur vi val f oll o w- u p ma y be d o ne at h o me a n d t he res ult self-re p orte d b y t he patie nt.
d   
A c o m plete bl o o d c o u nt wit h differe ntial, platelets, a n d retic ul oc ytes will be c o n d ucte d.
e  
T u m or i ma gi n g at E O T visit n ot re q uire d if perf or me d wit hi n t he last 3 0 da ys or pr o gressi ve disease has bee n d oc u me nte d. C T/ M RI will be perf or me d per Secti o n 6. 6 . F or 
patie nts w h o st o p st u d y treat me nt n ot relate d t o ra di o gra p hic disease pr o gressi o n (e g, e x perie nce d u ne x pecte d t o xicit y), sca ns s h o ul d c o nti n ue t o be c ollecte d a p pr o xi matel y 
e ver y 9 wee ks ( 2 1- da y d osi n g c ycle) u ntil disease pr o gressi o n or i nitiati o n of s yste mic a ntit u m or t hera p y ot her t ha n t he st u d y treat me nt, w hic he ver is earlier.
f  
Re p ort all A Es t hr o u g h t he Safet y F oll o w- u p Visit/ Call, a n d a n y treat me nt-relate d S A Es t hereafter.
g  
C ollect ne w a ntica ncer t hera p y data f oll o wi n g t he last d ose of st u d y treat me nt u ntil t he e n d of s ur vi val f oll o w- u p.
h  
S ur vi val f oll o w- u p will be c o n d ucte d via a p h o ne call e ver y 2 m o nt hs u ntil deat h or e n d of st u d y. D urati o n of s ur vi val f oll o w- u p will be li mite d t o 3 years.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 0
2 4 Oct o ber 2 0 2 3
A p pe n di x T a ble 3. 
P h ar m ac o ki netic, A nti dr u g A nti b o dies, a n d Bi o m ar ker: Sc he d ule of Assess me nts
C ycle 1 
C ycle 2 
C ycle 3 
C ycle 4 
C ycle 5 
C ycle 7 
C ycle 1 0 
C ycle 1 3 
E O T
C ycle D a y
Scree ni n g
D a y −3 0 
t o −1
1 
8 
1 5 
1 
1 
1 
1 
1 
1 
1
P K a
X 
X
X 
X b
X 
X 
X 
X 
X
A nti dr u g a nti b o dies c
X
X 
X
X 
X 
X 
X 
X
Rece pt or occ u pa nc y d
X 
X 
X
X 
X 
X
X
X
Circ ulati n g t u m or D N A e
X 
X
X
X 
X
X
X
P B M C f
X 
X
X 
X
T C R se q ue nci n g f
X 
X
X 
X
I m m u n o p he n ot y pi n g assa yf
X 
X g
X 
X
Ser u m a n d plas ma bi o mar kers h
X 
X g
X 
X 
X
X
X
W h ole bl o o d R N A
h
X 
X g
X 
X 
X
X
X
St o ol micr o bi o me i
X
X
Ge n o mic bl o o d sa m ple j
X
T u m or bi o ps y
X
X k
A D A = a nti dr u g a nti b o dies; E O T = e n d of treat me nt; P B M C = peri p heral bl o o d m o n o n uclear cell; P K = p har mac o ki netic; R O = rece pt or occ u pa nc y; T C R = T-cell rece pt or
a  
P K sa m ples will be c ollecte d fr o m patie nts w h o are assi g ne d t o recei ve ma gr oli ma b. P K sa m ples are t o be c ollecte d pre d ose wit hi n 1 2 h o urs pri or t o t he first a d mi nistrati o n of 
ma gr oli ma b gi ve n i n C ycles 1, 2, 3, 5, 7, 1 0, 1 3, a n d o n C ycle 1 Da y 8 a n d at t he e n d of treat me nt.
b  
I n C ycle 3, P K sa m ples are t o be c ollecte d pre d ose ( wit hi n 1 2 h o urs) a n d p ost- d ose at 1 h o ur ( ± 1 5 mi n) after t he e n d of t he i nf usi o n of t he first a d mi nistrati o n of ma gr oli ma b 
gi ve n.
c   
A D A sa m ples will be c ollecte d fr o m patie nts w h o are assi g ne d t o recei ve ma gr oli ma b. A D A sa m ples are t o be c ollecte d pri or t o t he a d mi nistrati o n of ma gr oli ma b at t he sa me 
ti me as t he pre d ose P K sa m ples i n C ycles 1, 2, 3, 5, 7, 1 0, 1 3, a n d e n d of treat me nt.
d  
R O sa m ples will be c ollecte d fr o m patie nts w h o are assi g ne d t o recei ve ma gr oli ma b. R O sa m ples are t o be c ollecte d pre d ose wit hi n 1 2 h o urs pri or t o a d mi nistrati o n of 
ma gr oli ma b o n C ycle 1 Da y 1, C ycle 1 Da y 8, a n d C ycle 1 Da y 1 5, pre d ose wit hi n 1 2 h o urs pri or t o t he first a d mi nistrati o n of ma gr oli ma b gi ve n i n C ycles 3, 4, 5, a n d 1 0, 
a n d at e n d of treat me nt, if occ urri n g bef ore C ycle 1 0. R O sa m ples will be c ollecte d at select sites o nl y.
e  
Sa m ples will be c ollecte d at scree ni n g a n d pre d ose wit hi n 1 2 h o urs pri or t o t he a d mi nistrati o n of ma gr oli ma b o n C ycle 1 Da y 1 a n d C ycle 1 Da y 1 5, pre d ose wit hi n 1 2 h o urs 
pri or t o t he first a d mi nistrati o n of ma gr oli ma b gi ve n i n C ycles 3, 4, a n d 7, a n d at e n d of treat me nt (re gar dless of ti me of occ urre nce).
f  
Sa m ples will be c ollecte d pre d ose wit hi n 1 2 h o urs pri or t o a d mi nistrati o n of ma gr oli ma b o n C ycle 1 Da y 1 a n d C ycle 1 Da y 8, a n d pre d ose wit hi n 1 2 h o urs pri or t o t he first 
a d mi nistrati o n of ma gr oli ma b gi ve n i n C ycles 2 a n d 3. P M B C a n d i m m u n o p he n ot y pi n g will be c ollecte d at select sites o nl y.
g  
F or ser u m a n d plas ma bi o mar kers, w h ole bl o o d R N A, a n d i m m u n o p he n ot y pi n g assa y, a n a d diti o nal sa m ple will be c ollecte d 4 h o urs p ost d ose o n C ycle 1 Da y 8.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 1
2 4 Oct o ber 2 0 2 3
h  
Sa m ples will be c ollecte d pre d ose wit hi n 1 2 h o urs pri or t o a d mi nistrati o n of ma gr oli ma b o n C ycle 1 Da y 1 a n d C ycle 1 Da y 8, pre d ose wit hi n 1 2 h o urs pri or t o t he first 
a d mi nistrati o n of ma gr oli ma b gi ve n i n C ycles 2, 3, 4, a n d 7, a n d at e n d of treat me nt if occ urri n g bef ore C ycle 7.
i  
St o ol micr o bi o me t o be c ollecte d pre d ose o n or bef ore C ycle 1 Da y 1 a n d a n yti me wit hi n 7 da ys of C ycle 3 Da y 1.
j  
T he ge n o mic bl o o d sa m ple ca n be c ollecte d at C ycle 1 Da y 1 or at a n y ti me d uri n g t he st u d y.
k   
O n-treat me nt t u m or bi o ps y ca n be c ollecte d a n y ti me bet wee n C ycle 3 Da y 1 a n d C ycle 4 Da y 1.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 2
2 4 Oct o ber 2 0 2 3
A p pe n di x 4.  
P a n de mic Ris k Assess me nt a n d Miti g ati o n Pl a n
D uri n g a n o n g oi n g pa n de mic, p ote ntial ris ks ass ociate d wit h patie nts bei n g u na ble t o atte n d 
st u d y visits ha ve bee n i de ntifie d f or t his st u d y. S pecial pa n de mic meas ures ca n be a p plie d o nl y 
w he n i n acc or da nce wit h t he c urre nt sit uati o n a n d a p plica ble l ocal a ut h orit y re g ulati o ns, 
rec o m me n dati o ns, or si milar.
T hese p ote ntial ris ks a n d miti gati o n pla ns ca n be s u m marize d as f oll o ws:
1)
Sc he d ule of assess me nts:
a)
P h ysical e xa mi nati o n:
i)
I n or der t o li mit a patie nt’s ti me i n t he cli nic, a virt ual visit ma y be c o n d ucte d f or t he 
p h ysical e xa mi nati o n assess me nt. Vital si g ns ma y be o mitte d f or virt ual visits. 
H o we ver, d osi n g a n d bi ol o gical sa m ple c ollecti o n s h o ul d occ ur per pr ot oc ol i n t he 
cli nic.
b)
D osi n g:
i)
Patie nts ma y be u na ble t o ret ur n t o t he site f or a n u m ber of visits t o recei ve t he st u d y 
dr u g, or t he site ma y be u na ble t o acce pt a n y patie nt visits. Wit h o ut st u d y dr u gs, t he 
patie nt w o ul d n ot be a ble t o sta y o n t he st u d y dr u g as pla n ne d per pr ot oc ol.
Miti gati o n pla n: If per mitte d b y l ocal et hics c o m mittee/i nstit uti o nal re vie w b oar ds 
n o n-i n vesti gati o nal pr o d uct as deter mi ne d b y s p o ns or (ie, d oceta xel) ca n be a d mi nistere d 
at a cli nic cl oser t o t he patie nt, u n der t he s u per visi o n of a lice nse d p h ysicia n. If 
necessar y, a d osi n g dela y f or ma gr oli ma b m ust be disc usse d wit h t he s p o ns or i n t his 
i nsta nce. A virt ual st u d y visit, via p h o ne or vi de o c o nfere nci n g, m ust be perf or me d pri or 
t o re m ote d osi n g. At t he earliest o p p ort u nit y, t he site will sc he d ule i n- pers o n patie nt 
visits a n d ret ur n t o t he pr ot oc ol’s re g ular sc he d ule of assess me nts. A q ualifie d c o urier 
ma y be c o nsi dere d t o s hi p t he dr u g fr o m sites t o t he alter nate cli nic.
c)
Ge neral patie nt selecti o n g ui da nce:
i)
T o mi ni mize patie nts recei vi n g re d bl o o d cell tra nsf usi o ns, we rec o m me n d selecti n g 
patie nts wit h hi g her he m o gl o bi n t hres h ol ds at baseli ne a n d use i ntra ve n o us ir o n 
a n d/ or er yt hr o p oieti n w here cli nicall y i n dicate d.
2)
St u d y dr u g s u p plies t o patie nts a n d sites:
a)
S hi p me nts of st u d y dr u g fr o m t he s p o ns or t o t he i n vesti gati o nal site c o ul d be dela ye d 
beca use of tra ns p ortati o n iss ues. Wit h o ut st u d y dr u g, t he patie nt w o ul d n ot be a ble t o sta y 
o n t he st u d y dr u g as pla n ne d per pr ot oc ol.
Miti gati o n pla n: T he sites’ st u d y dr u g i n ve nt or y s h o ul d be cl osel y m o nit ore d. Site staff 
s h o ul d n otif y t he s p o ns or or dele gate if t he y f oresee s h orta ge i n st u d y dr u g i n ve nt or y or if 
t here is a n y i nterr u pti o n i n l ocal s hi p pi n g ser vice. T he s p o ns or will c o nti n ue t o m o nit or 
i n ve nt or y at t he st u d y dr u g de p ot a n d st u d y sites. Ma n ual s hi p me nts will be tri g gere d as 
necessar y.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 3
2 4 Oct o ber 2 0 2 3
3)
Patie nt safet y m o nit ori n g a n d f oll o w- u p:
a)
Patie nts ma y be u na ble or u n willi n g t o c o me t o t he st u d y site f or t heir sc he d ule d st u d y 
visits as re q uire d per pr ot oc ol.
Miti gati o n pla n: F or patie nts w h o ma y be u na ble or u n willi n g t o visit t he st u d y site f or 
t heir sc he d ule d st u d y visits as re q uire d per pr ot oc ol, t he pri nci pal i n vesti gat or or 
q ualifie d dele gate will c o n d uct a virt ual st u d y visit, via p h o ne or vi de o c o nfere nci n g, t o 
assess t he patie nt wit hi n t he tar get visit wi n d o w date w he ne ver p ossi ble. D uri n g t he 
virt ual st u d y visit, t he f oll o wi n g i nf or mati o n at mi ni m u m will be re vie we d:
i) 
C o nfir m if patie nt has e x perie nce d a n y a d verse e ve nts ( A Es)/seri o us a d verse e ve nts 
( S A Es)/s pecial sit uati o ns (i ncl u di n g pre g na nc y) a n d f oll o w- u p o n a n y u nres ol ve d 
A E/ S A Es
ii)
Re vie w c urre nt list of c o nc o mita nt me dicati o ns a n d d oc u me nt a n y ne w c o nc o mita nt 
me dicati o ns
iii) If a p plica ble, c o nfir m t hat patie nt-re p orte d o utc o mes ha ve bee n c o m plete d a n d 
tra ns mitte d w here p ossi ble
b)
Patie nts ma y be u na ble or u n willi n g t o tra vel t o t he site f or pla n ne d assess me nts (e g, 
safet y bl o o d dra ws); he nce, sa m ples ma y n ot be a nal yze d at t he site la b orat or y a n d/ or 
se nt f or ce ntral la b orat or y a nal yses.
Miti gati o n pla n: Accre dite d l ocal la b orat ories t hat are n ot affiliate d wit h t he site ma y be 
utilize d as a p pr o priate t o m o nit or patie nt safet y u ntil t he patie nt ca n ret ur n t o t he site f or 
t heir re g ular f oll o w- u p per pr ot oc ol. A n y la b orat or y assess me nts c o n d ucte d at a l ocal 
la b orat or y d ue t o t he pa n de mic will be d oc u me nte d acc or di n gl y. Pre g na nc y testi n g ma y 
be perf or me d usi n g a h o me uri ne pre g na nc y test if l ocal la b orat or y pre g na nc y testi n g is 
n ot feasi ble. Alter nati ve sa m ple ha n dli n g a n d st ora ge ma y be p ossi ble f or sa m ples 
r o uti nel y se nt t o t he ce ntral la b orat or y, sites s h o ul d refer t o t he st u d y la b orat or y ma n ual 
a n d disc uss wit h t he s p o ns or f or f urt her g ui da nce.
c)
Patie nts ma y be u na ble or u n willi n g t o atte n d t he st u d y visit t o si g n a n u p date d i nf or me d 
c o nse nt f or m versi o n if t here is a n u p date.
Miti gati o n pla n: T he site staff will f oll o w t heir a p pr o ve d c o nse nt pr ocess a n d re mai n i n 
c o m plia nce wit h l ocal E C/I R B a n d nati o nal la ws a n d re g ulati o ns. Re m ote c o nse nt will be 
all o we d if it has bee n a p pr o ve d b y t he l ocal E C/I R B. T he c o nse nt pr ocess will be 
d oc u me nte d a n d c o nfir me d b y n or mal c o nse nt pr oce d ure at t he earliest o p p ort u nit y.
d)
T he safet y of trial patie nts is i m p orta nt a n d testi n g of c or o na vir us disease 2 0 1 9 
( C O VI D- 1 9) i nfecti o n will be base d o n l ocal cli nical g ui deli nes f or testi n g base d o n 
si g ns/s y m pt o ms a n d or s us pecte d e x p os ure t o C O VI D- 1 9.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 4
2 4 Oct o ber 2 0 2 3
Miti gati o n pla n: If patie nt has a dia g n osis of C O VI D- 1 9 w hile o n t his cli nical st u d y, 
st u d y dr u gs ma y be hel d u ntil cli nical i m pr o ve me nt or res ol uti o n i n acc or da nce wit h t he 
treati n g p h ysicia n’s j u d g me nt a n d ge neral ma gr oli ma b d ose dela y g ui da nce i n t he 
pr ot oc ol. A d diti o nal s u p p orti ve care a n d treat me nt meas ures f or C O VI D- 1 9 i nfecti o n o n 
t he st u d y will be perf or me d i n acc or da nce wit h l ocal i nstit uti o nal g ui deli nes. Patie nts 
wit h a C O VI D- 1 9 i nfecti o n w hile partici pati n g i n t he cli nical trial will ha ve t his e ve nt 
d oc u me nte d as a n a d verse e ve nt i n t he cli nical data base.
4)
Pr ot oc ol a n d m o nit ori n g c o m plia nce:
a)
Pr ot oc ol de viati o ns ma y occ ur, i n case sc he d ule d visits ca n n ot occ ur as pla n ne d per 
pr ot oc ol.
Miti gati o n pla n: If it is n ot p ossi ble t o c o m plete a re q uire d pr oce d ure, a n u nsc he d ule d 
visit s h o ul d be c o n d ucte d as s o o n as p ossi ble w he n c o n diti o ns all o w. T he sit uati o n s h o ul d 
be rec or de d a n d e x plai ne d as a pr ot oc ol de viati o n. A n y misse d patie nt visits or de viati o n 
t o t he pr ot oc ol d ue t o t he pa n de mic m ust be re p orte d i n t he electr o nic case re p ort f or m 
a n d descri be d i n t he cli nical st u d y re p ort. A n y virt ual st u d y visits t hat are c o n d ucte d i n 
lie u of cli nic visits d ue t o t he pa n de mic will be d oc u me nte d as a pr ot oc ol de viati o n 
relate d t o t he pa n de mic.
b) 
M o nit ors ma y be u na ble t o carr y o ut s o urce data re vie w, s o urce data verificati o n, or st u d y 
dr u g acc o u nta bilit y or assess pr ot oc ol a n d G o o d Cli nical Practice c o m plia nce. T his ma y 
lea d t o dela ys i n s o urce data verificati o n, a n i ncrease i n pr ot oc ol de viati o ns, or u n der 
re p orti n g of A Es.
Miti gati o n pla n: T he st u d y m o nit or is t o re mai n i n cl ose c o m m u nicati o n wit h t he site t o 
e ns ure data e ntr y a n d q uer y res ol uti o n. T he st u d y m o nit or is t o refere nce t he St u d y 
M o nit ori n g Pla n f or g ui da nce o n h o w t o c o n d uct a re m ote m o nit ori n g visit. T he st u d y 
staff is t o sa ve a n d d oc u me nt all rele va nt c o m m u nicati o n i n t he st u d y files. T he stat us of 
sites t hat ca n n ot acce pt m o nit ori n g visits a n d/ or patie nts o n site m ust be trac ke d ce ntrall y 
a n d u p date d o n a re g ular basis.
5) 
Missi n g data a n d data i nte grit y:
a)
T here ma y be a n i ncrease d a m o u nt of missi n g data d ue t o patie nts missi n g 
visits/assess me nts. T his c o ul d ha ve a n i m pact o n t he a nal ysis a n d t he i nter pretati o n of 
cli nical st u d y data.
Miti gati o n pla n: I m plicati o ns of a pa n de mic o n met h o d ol o gical as pects f or t he st u d y will 
be t h or o u g hl y assesse d a n d d oc u me nte d, a n d rele va nt acti o ns will be ta ke n as a p pr o priate 
(ie, m o dificati o n of t he statistical a nal ysis pla n) a n d i n c o m plia nce wit h re g ulat or y 
a ut h orities’ g ui da nce. O verall, t he cli nical st u d y re p ort will descri be t he i m pact of t he 
pa n de mic o n t he i nter preta bilit y of st u d y data.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 5
2 4 Oct o ber 2 0 2 3
Ris ks will be assesse d c o nti n u o usl y, a n d te m p orar y meas ures will be i m ple me nte d t o miti gate 
t hese ris ks as part of a miti gati o n pla n, as descri be d a b o ve. T hese meas ures will be 
c o m m u nicate d t o t he rele va nt sta ke h ol ders as a p pr o priate a n d are i nte n de d t o pr o vi de alter nati ve 
met h o ds t hat will e ns ure t he e val uati o n a n d assess me nt of t he safet y of patie nts w h o are e nr olle d 
i n t his st u d y.
Si nce t hese p ote ntial ris ks are c o nsi dere d miti gate d wit h t he i m ple me ntati o n of t hese meas ures, 
t he e x pecte d be nefit-ris k assess me nt of ma gr oli ma b i n st u d y patie nts re mai ns u nc ha n ge d. I n case 
of a n i ncrease i n t hese p ote ntial ris ks, w hic h ca n n ot be miti gate d d ue t o t he escalati o n of a 
pa n de mic, e nr oll me nt of ne w patie nts will be place d o n h ol d u ntil t he pa n de mic o ut brea k is 
u n der c o ntr ol b y f oll o wi n g l ocal re g ulat or y g ui deli nes.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 6
2 4 Oct o ber 2 0 2 3
A p pe n di x 5.  
T o xicit y Gr a di n g Sc ale f or Se verit y of A d verse E ve nts a n d 
L a b or at or y A b n or m alities
htt ps://cte p.ca ncer. g o v/ pr ot oc ol De vel o p me nt/electr o nic _a p plicati o ns/ d ocs/ C T C A E _ v 5 _ Q uic k _ R 
efere nce _ 8. 5 x 1 1. p df


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 7
2 4 Oct o ber 2 0 2 3
A p pe n di x 6.  
Pre g n a nc y Prec a uti o ns, Defi niti o n f or Fe m ale of C hil d be ari n g 
P ote nti al, a n d C o ntr ace pti ve Re q uire me nts
1)   
Defi niti o ns
a.   
Defi niti o n of C hil d be ari n g P ote nti al
F or t he p ur p oses of t his st u d y, a fe male- b or n patie nt is c o nsi dere d of c hil d beari n g p ote ntial 
f oll o wi n g t he i nitiati o n of p u bert y ( Ta n ner sta ge 2) u ntil bec o mi n g p ost me n o pa usal, u nless t he 
patie nt is per ma ne ntl y sterile or has me dicall y d oc u me nte d o varia n fail ure.
W o me n are c o nsi dere d t o be i n a p ost me n o pa usal state w he n t he y are ≥ 5 4 years of a ge wit h 
cessati o n of pre vi o usl y occ urri n g me nses f or ≥ 1 2 m o nt hs wit h o ut a n alter nati ve ca use. I n 
a d diti o n, w o me n of < 5 4 years of a ge wit h a me n orr hea of ≥ 1 2 m o nt hs ma y als o be c o nsi dere d 
p ost me n o pa usal if t heir f ollicle-sti m ulati n g h or m o ne le vel is i n t he p ost me n o pa usal ra n ge a n d 
t he y are n ot usi n g h or m o nal c o ntrace pti o n or h or m o nal re place me nt t hera p y.
Per ma ne nt sterilizati o n i ncl u des h ysterect o m y, bilateral o o p h orect o m y, or bilateral 
sal pi n gect o m y i n a fe male patie nt of a n y a ge.
b.   
Defi niti o n of M ale Fertilit y
F or t he p ur p oses of t his st u d y, a male- b or n patie nt is c o nsi dere d fertile after t he i nitiati o n of 
p u bert y u nless t he patie nt is per ma ne ntl y sterile b y bilateral orc hi dect o m y or me dical d oc u me ntati o n.
2)   
C o ntr ace pti o n Re q uire me nts f or Fe m ale P atie nts
a.  
St u d y Dr u g Effects o n Pre g n a nc y a n d H or m o n al C o ntr ace pti o n
Ma gr oli ma b is c o ntrai n dicate d i n pre g na nc y as a hi g her i nci de nce of t otal pre g na nc y l oss has 
bee n o bser ve d i n a n e m br y ofetal de vel o p me nt t o xicit y st u d y i n c y n o m ol g us m o n ke ys a n d t here 
is a str o n g s us pici o n of h u ma n fet ot o xicit y i n earl y pre g na nc y base d o n t he n o ncli nical data. F or 
ma gr oli ma b, t here is n o a ntici pate d p har mac o ki netic i nteracti o n wit h pr o gesti n or ot her ster oi ds 
base d o n t he disti nct cleara nce pat h wa ys.
Base d o n t he mec ha nis m of acti o n ( M O A) a n d fi n di n gs i n a ni mals, d oceta xel ca n ca use fetal 
har m w he n a d mi nistere d t o a pre g na nt w o ma n. W o me n of c hil d beari n g p ote ntial s h o ul d be 
a d vise d t o use effecti ve c o ntrace pti o n a n d a v oi d bec o mi n g pre g na nt d uri n g t hera p y wit h 
d oceta xel. If t he patie nt bec o mes pre g na nt w hile recei vi n g d oceta xel, t he patie nt s h o ul d be 
a p prise d of t he p ote ntial hazar d t o t he fet us. T here is n o c o ntrai n dicati o n t o h or m o nal 
c o ntrace pti o n acc or di n g t o t he d oceta xel prescri bi n g i nf or mati o n.
b.   
C o ntr ace pti o n Re q uire me nts f or Fe m ale P atie nts of C hil d be ari n g P ote nti al
T he i ncl usi o n of fe male patie nts of c hil d beari n g p ote ntial re q uires t he use of hi g hl y effecti ve 
c o ntrace pti ve meas ures wit h a fail ure rate of < 1 % per year. T he y m ust ha ve a ne gati ve ser u m 
pre g na nc y test at scree ni n g a n d a ne gati ve pre g na nc y test is re q uire d pri or t o st u d y treat me nt 
a d mi nistrati o n o n C ycle 1 Da y 1. T he C ycle 1 Da y 1 pre g na nc y test d oes n ot nee d t o be re peate d 
if t he scree ni n g pre g na nc y test was perf or me d wit hi n t he 7 2 h o urs bef ore st u d y treat me nt 
a d mi nistrati o n. Pre g na nc y tests will be perf or me d at t he be gi n ni n g of eac h c ycle t hereafter 
( descri be d i n t he pr ot oc ol), a n d c o nti n ue m o nt hl y u p t o 6 m o nt hs after t he e n d of treat me nt per 
t he d urati o n of re q uire d c o ntrace pti o n.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 8
2 4 Oct o ber 2 0 2 3
D urati o n of re q uire d c o ntrace pti o n f or fe male patie nts i n t his cli nical trial s h o ul d start fr o m 
Scree ni n g visit u ntil 6 m o nt hs after last d ose of t he latest a d mi nistere d st u d y dr u g.
Fe male patie nts m ust a gree t o o ne of t he f oll o wi n g c o ntrace pti ve met h o ds:
C o m plete a bsti ne nce fr o m i nterc o urse of re pr o d ucti ve p ote ntial. A bsti ne nce is a n acce pta ble 
met h o d of c o ntrace pti o n o nl y w he n it is i n li ne wit h t he patie nt’s preferre d a n d us ual lifest yle.
Or
•
C o nsiste nt a n d c orrect use of 1 of t he f oll o wi n g met h o ds of birt h c o ntr ol liste d bel o w:

N o n- h or m o nal i ntra uteri ne de vice (I U D)

H or m o nal I U D ( m ust be use d i n c o nj u ncti o n wit h a barrier met h o d)

Bilateral t u bal occl usi o n ( u p o n me dical assess me nt of s ur gical s uccess)

Vasect o m y i n t he male part ner ( u p o n me dical assess me nt of s ur gical s uccess)
Or
Fe male patie nts w h o wis h t o use a h or m o nall y base d met h o d m ust use it i n c o nj u ncti o n wit h a 
barrier met h o d, prefera bl y a male c o n d o m. H or m o nal met h o ds are restricte d t o t h ose ass ociate d 
wit h t he i n hi biti o n of o v ulati o n. H or m o nall y base d c o ntrace pti ves a n d barrier met h o ds per mitte d 
f or use i n t his pr ot oc ol are as f oll o ws:
•
H or m o nal met h o ds (eac h met h o d m ust be use d wit h a barrier met h o d, prefera bl y male 
c o n d o m)

Oral c o ntrace pti ves (eit her c o m bi ne d or pr o gester o ne o nl y)

I njecta ble pr o gester o ne

Tra ns der mal c o ntrace pti ve patc h

C o ntrace pti ve va gi nal ri n g

S u b der mal c o ntrace pti ve i m pla nt
•
Barrier met h o ds (eac h met h o d m ust be use d wit h a h or m o nal met h o d)

Male c o n d o m ( wit h or wit h o ut s per mici de)

Fe male c o n d o m ( wit h or wit h o ut s per mici de)

Dia p hra g m wit h s per mici de

Cer vical ca p wit h s per mici de

S p o n ge wit h s per mici de


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 0 9
2 4 Oct o ber 2 0 2 3
I ncl usi o n of met h o ds of c o ntrace pti o n i n t his list of per mitte d met h o ds d oes n ot i m pl y t hat t he 
met h o d is a p pr o ve d i n a n y c o u ntr y or re gi o n. Met h o ds s h o ul d o nl y be use d if l ocall y a p pr o ve d.
Fe male patie nts m ust als o refrai n fr o m e g g d o nati o n, cr y o preser vati o n of cells, a n d i n vitr o 
fertilizati o n d uri n g treat me nt a n d u ntil t he e n d of c o ntrace pti o n re q uire me nt. If nee de d, fe male 
patie nts s h o ul d be a d vise d t o see k a d vice a b o ut e g g d o nati o n a n d cr y o preser vati o n pri or t o 
treat me nt.
3)   
C o ntr ace pti o n Re q uire me nts f or M ale P atie nts
It is t he oreticall y p ossi ble t hat a rele va nt s yste mic c o nce ntrati o n of st u d y dr u g ma y be ac hie ve d 
i n a fe male part ner fr o m e x p os ure t o t he patie nt’s se mi nal fl ui d a n d p ose a p ote ntial ris k t o a n 
e m br y o/fet us. Male patie nts wit h fe male part ners of c hil d beari n g p ote ntial m ust use c o n d o ms 
d uri n g treat me nt a n d u ntil 6 m o nt hs after last d ose of t he latest a d mi nistere d st u d y dr u g. If t he 
fe male part ner of c hil d beari n g p ote ntial is n ot pre g na nt, use of a n y hi g hl y effecti ve l ocall y 
a p pr o ve d c o ntrace pti ve meas ure s h o ul d als o be c o nsi dere d.
Male patie nts m ust als o refrai n fr o m s per m d o nati o n a n d cr y o preser vati o n of cells d uri n g 
treat me nt a n d u ntil t he e n d of c o ntrace pti o n re q uire me nt. If nee de d, male patie nts s h o ul d be 
a d vise d t o see k a d vice a b o ut s per m d o nati o n a n d cr y o preser vati o n pri or t o treat me nt.
4)   
U n acce pt a ble Birt h C o ntr ol Met h o ds
Birt h c o ntr ol met h o ds t hat are u nacce pta ble i ncl u de peri o dic a bsti ne nce (e g, cale n dar, o v ulati o n, 
s y m pt ot her mal, p ost o v ulati o n met h o ds), wit h dra wal (c oit us i nterr u pt us), s per mici des o nl y, a n d 
lactati o nal a me n orr hea met h o d. A fe male c o n d o m a n d a male c o n d o m s h o ul d n ot be use d 
t o get her.
5)  
Pr oce d ures t o be F oll o we d i n t he E ve nt of Pre g n a nc y
Fe male patie nts will be i nstr ucte d t o n otif y t he i n vesti gat or if t he y bec o me pre g na nt or s us pect 
t he y are pre g na nt at a n y ti me fr o m start of t he st u d y t o 6 m o nt hs after last st u d y dr u g d ose. St u d y 
dr u g m ust be disc o nti n ue d i m me diatel y.
Male patie nts w h ose part ner has bec o me pre g na nt or s us pects s he is pre g na nt fr o m start of st u d y 
t o 6 m o nt hs after last st u d y dr u g d ose m ust als o re p ort t he i nf or mati o n t o t he i n vesti gat or. 
Part ner pre g na nc y i nf or mati o n will n ot be c ollecte d i n t his st u d y; h o we ver, t he i n vesti gat or 
s h o ul d rei nf orce pr o per c o ntrace pti o n use wit h t he st u d y patie nt if a part ner pre g na nc y is 
re p orte d. I nstr ucti o ns f or re p orti n g pre g na nc y a n d pre g na nc y o utc o me are o utli ne d i n 
Secti o n 7. 4. 2. 3 .


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 1 0
2 4 Oct o ber 2 0 2 3
A p pe n di x 7.  
E aster n C o o per ati ve O nc ol o g y Gr o u p ( E C O G) Perf or m a nce St at us
Gr a de
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
{ O ke n 1 9 8 2 }


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 1 1
2 4 Oct o ber 2 0 2 3
A p pe n di x 8.   
Res p o nse E v al u ati o n Criteri a i n S oli d T u m ors ( R E CI S T, Versi o n 1. 1)
Eise n ha uer E A, T herasse P, B o gaerts J, Sc h wartz L H, Sar ge nt D, F or d R, et al. Ne w res p o nse 
e val uati o n criteria i n s oli d t u m o urs: re vise d R E CI S T g ui deli ne ( Versi o n 1. 1). E ur 
J C a ncer. 2 0 0 9; 4 5: 2 2 8- 2 4 7 f or f ull R E CI S T g ui deli nes.


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 1 2
2 4 Oct o ber 2 0 2 3
A p pe n di x 9.   
C o u ntr y- S pecific Re q uire me nts
N ot a p plica ble. 


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 1 3
2 4 Oct o ber 2 0 2 3
A p pe n di x 1 0.   
A me n d me nt Hist or y
Hi g h-le vel s u m maries of t he hist or y of t his st u d y’s a me n d me nts are pr o vi de d i n ta b ular f or m i n 
t he s u bsecti o ns bel o w (fr o m m ost rece nt a me n d me nt t o ol dest), wit h c ha n ges liste d i n eac h ta ble 
i n or der of i m p orta nce. Mi n or c ha n ges s uc h as t he c orrecti o n of t y p o gra p hic err ors, gra m mar, or 
f or matti n g are n ot detaile d.
Se parate s u m mar y of c ha n ge d oc u me nts f or earlier a me n d me nts are a vaila ble u p o n re q uest.
A se parate trac ke d c ha n ge (re d-li ne d) d oc u me nt c o m pari n g A me n d me nt 4 t o t his a me n d me nt 
will be ma de a vaila ble u p o n t he p u blicati o n of t his pr ot oc ol.
A me n d me nt 5 ( 2 4 Oct o ber 2 0 2 3)
R ati o n ale f or Ke y C h a n ges I ncl u de d i n A me n d me nt 5
Affecte d Secti o ns
C ollecti o n peri o d f or treat me nt-e mer ge nt a d verse e ve nts clarifie d.
Secti o n 8. 6. 4
C ollecti o n peri o d f or i nci de nce of treat me nt-e mer ge nt la b orat or y a b n or malities 
clarifie d. 
Secti o n 8. 6. 5
U p dates ma de t o ali g n wit h c urre nt safet y rec o m me n dati o ns. 
Secti o ns 1. 2. 3, 1. 7, 5. 6 
Ti mi n g of pri mar y a nal ysis f or P hase 2 C o h ort 1 clarifie d. 
Secti o n 8. 2. 2
U p date d t he t o xicit y ma na ge me nt re gar di n g he m o gl o bi n m o nit ori n g t o ali g n 
wit h c urre nt rec o m me n dati o ns. 
Secti o n 7. 8. 1
Re m o ve circ ulati n g t u m or cell sa m ple c ollecti o n as n ot perf or me d.
Secti o n 3. 8; A p pe n di x 
Ta bles 1 a n d 2
Sa m ple size f or ur ot helial ca ncer c o h ort u p date d. 
S y n o psis; Sc he ma; 
Secti o ns 3. 1, 4. 1, a n d 8. 1 0
Ma gr oli ma b a d mi nistrati o n la n g ua ge u p date d t o clarif y vital si g ns will be 
assesse d pri or t o a d mi nistrati o n. 
Secti o ns 5. 4
La n g ua ge a d de d t o all o w l ocal s o urci n g of d oceta xel.
Secti o n 5. 3. 2
U p date d g ui da nce pr o vi de d f or t he ma na ge me nt of i nf usi o n-relate d reacti o ns. 
Secti o n 7. 8. 1. 2 ( Ta ble 1 1)
Ne w secti o ns pr o vi de d f or g ui da nce o n ma na ge me nt of se vere ne utr o pe nia a n d 
seri o us i nfecti o ns.
Secti o ns 7. 8. 1. 5 a n d 7. 8. 1. 6
Te xt a d de d t o ali g n wit h E U- C T R re q uire me nts. 
Secti o ns 1. 4, 7. 2. 1, a n d 9. 2. 2; 
A p pe n dices 2 a n d 9
Te xt u p date d t o clarif y t hat ‘ uri ne or ser u m pre g na nc y tests will be c o n d ucte d 
fr o m C ycle 1 Da y 1’ wit h res pect t o pre g na nc y test.
A p pe n di x Ta ble 1 – 
f o ot n ote ‘e’ a n d A p pe n di x 
Ta ble 2
A nal ysis sets u p date d.
Secti o n 8. 3
G ui da nce o n C O VI D- 1 9 vacci nati o n pr o vi de d.
Secti o n 5. 7. 1. 1
La n g ua ge u p date d t o clarif y t hat a fi nal a nal ysis ma y be c o n d ucte d after t he 
pri mar y a nal ysis.
Secti o n 8. 2. 3
I ncl usi o n criteria were u p date d f or clarificati o n. 
S y n o psis; Secti o n 4. 2
Te xt was u p date d t o re place ‘ partici pa nts’ wit h ‘ patie nts’ t o mai ntai n 
c o nsiste nc y. 
A p pe n di x 3


Ma gr oli ma b
Pr ot oc ol G S- U S- 5 4 8- 5 9 1 8 
Gilea d Scie nces, I nc.
A me n d me nt 5
C O N FI D E N TI A L
Pa ge 1 1 4
2 4 Oct o ber 2 0 2 3
R ati o n ale f or Ke y C h a n ges I ncl u de d i n A me n d me nt 5
Affecte d Secti o ns
C ha n ges fr o m a d mi nistrati ve a me n d me nt 1 were a d de d t o t he pr ot oc ol.
Secti o n 6. 2. 1
C ha n ges fr o m a d mi nistrati ve a me n d me nt 2 were a d de d t o t he pr ot oc ol.
S y n o psis; Secti o n 6. 6; 
A p pe n di x Ta bles 1 a n d 2 
Mi n or c ha n ges t o c orrect t y p o gra p hic err ors.
T hr o u g h o ut, as nee de d


pr ot  G S- U S- 5 4 8- 5 9 1 8  a m d- 5
E L E C T R O NI C  SI G N A T U R E S
Si g n e d  b y
M e a ni n g  of  Si g n at ur e 
S er v er  D at e
( d d- M M M-
y y y y  h h: m m: s s)
Cli ni c al  D e v el o p m e nt
e Si g n e d
2 5- O ct- 2 0 2 3
1 5: 2 8: 2 8
P P D

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 2, Multi-Arm Study of Magrolimab in Patients 
With Solid Tumors 
Plain Language Short
Title:
Study of Magrolimab in Patients With Solid Tumors
Name of Test Drug:
Magrolimab (GS-4721)  
Study Number:
GS-US-548-5918
Protocol Version (Date):
Amendment 5 (24 October 2023)
Analysis Plan Version:
1.0
Analysis Plan Date:
06 March 2024
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
[r) GILEAU 


Magrolimab
GS-US-548-5918
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 2
06 March 2024
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN ...............................................................................................................................1
TABLE OF CONTENTS................................................................................................................................................2
LIST OF IN-TEXT TABLES .........................................................................................................................................4
LIST OF IN-TEXT FIGURES........................................................................................................................................4
LIST OF ABBREVIATIONS.........................................................................................................................................5
1.
INTRODUCTION..................................................................................................................................................7
1.1.
Study Objectives and Endpoints................................................................................................................7
1.2.
Study Design .............................................................................................................................................8
1.2.1.
Study Design ...........................................................................................................................8
1.2.2.
Safety Run-in Cohort 1............................................................................................................9
1.2.3.
Phase 2 Cohort 1......................................................................................................................9
1.2.4.
Study Treatments.....................................................................................................................9
1.3.
Sample Size and Power ...........................................................................................................................11
2.
TYPE OF ANALYSIS .........................................................................................................................................12
2.1.
Dose Determination Analysis..................................................................................................................12
2.2.
Informal Interim Analyses.......................................................................................................................12
2.3.
Primary Analysis .....................................................................................................................................12
2.4.
Final Analysis..........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................13
3.1.
Analysis Sets ...........................................................................................................................................13
3.1.1.
All Enrolled Analysis Set ......................................................................................................13
3.1.2.
Modified ITT Analysis Set....................................................................................................13
3.1.3.
Safety Analysis Set................................................................................................................13
3.1.4.
Dose-Limiting Toxicity (DLT) Evaluable Analysis Set .......................................................13
3.1.5.
Pharmacokinetic Analysis Set ...............................................................................................14
3.1.6.
Immunogenicity Analysis Set................................................................................................14
3.1.7.
Biomarker Analysis Set.........................................................................................................14
3.2.
Subject Grouping.....................................................................................................................................14
3.3.
Strata and Covariates...............................................................................................................................14
3.4.
Examination of Subject Subgroups .........................................................................................................14
3.5.
Adjustment for Multiplicity.....................................................................................................................14
3.6.
Missing Data and Outliers.......................................................................................................................15
3.6.1.
Missing Data..........................................................................................................................15
3.6.2.
Outliers ..................................................................................................................................15
3.7.
Data Handling Conventions and Transformations ..................................................................................15
3.8.
Analysis Visit Windows..........................................................................................................................17
3.8.1.
Definition of Study Day ........................................................................................................17
3.8.2.
Analysis Visit Windows........................................................................................................17
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window .................................................................................................................................18
3.9.
Assessment of COVID-19 Impact...........................................................................................................18
4.
PROTOCOL DEVIATIONS................................................................................................................................19
5.
SUBJECT INFORMATION ................................................................................................................................20
5.1.
Patient Enrollment and Disposition.........................................................................................................20
5.2.
Extent of Study Treatment Exposure ......................................................................................................21


Magrolimab 
GS-US-548-5918 
Statistical Analysis Plan 
Version 1.0 
5.2.1. 
Duration of Exposw·e ............................................................................................................ 21 
5.2.2. 
Relative Dose Intensity .......................................................................................................... 21 
5. 3. 
Demographics and Baseline characteristics ............................................................................................ 22 
5.4. 
Medical Histo1y ....................................................................................................................................... 22 
5.5. 
Prior and Concomitant Medications ........................................................................................................ 22 
5.5.1. 
Prior Medications .................................................................................................................. 22 
5.5.2. 
Conco1nitant Medica.tions ...................................................................................................... 23 
5.6. 
Prior Anti-cancer Therapy ....................................................................................................................... 23 
5.7. 
On Study or Post Study Anti-cancer Therapies ....................................................................................... 23 
5.8. 
Prior and On Study Radiation Therapy ................................................................................................... 24 
5.9. 
Prior and On Study Sw-geries and Procedw-es ........................................................................................ 24 
6. 
EFFICACY ANALYSES ..................................................................................................................................... 25 
6.1. 
Pri1nruy Efficacy Endpoints .................................................................................................................... 25 
6.1. 1. 
Definition of the Prima1y Efficacy Endpoints ....................................................................... 25 
6.1.2. 
Analysis of the Prima1y Efficacy Endpoint ........................................................................... 25 
6.1.3. 
Sensitivity Analysis of the Primruy Efficacy Endpoint.. ....................................................... 25 
6.2. 
Secondruy Efficacy Endpoints ................................................................................................................ 25 
6.2.1. 
Definition of Seconda1y Efficacy Endpoints ......................................................................... 25 
6.2.2. 
Anal sis Methods for Secondru Efficac End oints ........................................................... 26 
6.3. 
6.4. 
Changes From Protocol-Specified Efficacy Analyses ............................................................................ 28 
7. 
SAFETY ANALYSES ......................................................................................................................................... 29 
7.1. 
Adverse Events and Deaths ..................................................................................................................... 29 
7.1. 1. 
Adverse Event Dictiona1y ..................................................................................................... 29 
7.1.2. 
Adverse Event Severity ......................................................................................................... 29 
7.1.3. 
Relationship of Adverse Events to Study Treatment ............................................................ 29 
7.1.4. 
Serious Adverse Events ......................................................................................................... 29 
7.1.5. 
Treatinent-Emergent Adverse Events .................................................................................... 29 
7.1.6. 
SW'lllllaries of Adverse Events and Deaths ............................................................................ 31 
7.1.7. 
Additional Analysis of Adverse Events ................................................................................ 32 
7.2. 
Laborato1y Evaluations ........................................................................................................................... 33 
7.2.1. 
SW'lllllaries ofNwneric Labora.t01y Results .......................................................................... 33 
7.2.2. 
Graded Laborato1y Values .................................................................................................... 34 
7.2.3. 
Liver-related Laborat01y Evaluations .................................................................................... 35 
7.3. 
Body Weight and Vita.I Signs .................................................................................................................. 36 
7 .4. 
Electrocru·diogra1n (ECG) Results ........................................................................................................... 36 
7.5. 
Eastem Cooperative Oncology Group (ECOG) Perfonnance Sta.tus ...................................................... 36 
7.6. 
Pregnancy Test ........................................................................................................................................ 36 
7.7. 
Changes From Protocol-Specified Safety Analyses ................................................................................ 36 
8. 
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES .............................................................................. 37 
9. 
PHARMACOKINETIC (PK) AND IMMUNOGENICITY ANALYSES .......................................................... 38 
9.1. 
PKAna.lysis ............................................................................................................................................. 38 
9.2. 
Irmnunogenicity ana.lysis ......................................................................................................................... 38 
10. BIOMARKERANALYSIS ................................................................................................................................ .41 
11. REFERENCES .................................................................................................................................................... .42 
12. SOFTWARE ........................................................................................................................................................ .43 
CONFIDENTIAL 
Page3 
06 Mru·ch 2024 


Magrolimab
GS-US-548-5918
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 4
06 March 2024
13.
APPENDICES......................................................................................................................................................44
13.1.
Appendix 1. RECIST 1.1-based Assessments - Overall visit response ..................................................44
LIST OF IN-TEXT TABLES
Table 1-1.
Safety Run-in Cohort 1: Dose Level, Schedule, and De-escalation........................................10
Table 1-2.
Phase 2 Cohort 1: Dose Level and Schedule...........................................................................10
Table 1-3.
Sample Size Calculations ........................................................................................................11
Table 3-1.
Analysis Visit Windows for Lab By-visit Summaries ............................................................17
Table 6-1.
Censoring rules for analysis of PFS and DOR ........................................................................26
Table 7-1.
Treatment Emergent Adverse Events of Clinical Importance.................................................33
Table 13-1.
Overall Visit Response ............................................................................................................44
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Schema ............................................................................................................................8


Magrolimab
GS-US-548-5918
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 5
06 March 2024
LIST OF ABBREVIATIONS
ADA
anti-drug antibody
AE
adverse event
AECI
adverse events of clinical importance
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate transaminase
ATC
Anatomical Therapeutic Chemical
BMI
body mass index
BOR
best overall response
BSA
body surface area
CBR
clinical benefit rate
CI
confidence interval
CR
complete response
CRF
case report form
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
DOR
duration of response
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EOT
end of treatment
KM
Kaplan-Meier
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified intent to treat
NA
not applicable
NCI
National Cancer Institute
NE
not evaluable
NTLs
non-target lesions
ORR
objective response rate
OS
overall survival
PD
disease progression
PFS
progression-free survival
PK
pharmacokinetics
PR
partial response
PT
preferred term
Q1, Q3
first quartile, third quartile
RECIST
Response Evaluation Criteria in Solid Tumors (version 1.1)
SAE
serious adverse event
SAP
statistical analysis plan


Magrolimab
GS-US-548-5918
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 6
06 March 2024
SD
stable disease
SE
standard error
SMQ
Standard MedDRA Query
StD
standard deviation
SOC
system organ class
TLs
target lesions
ULN
upper limit of normal
WHO
World Health Organization


Magrolimab
GS-US-548-5918
Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 7
06 March 2024
1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and defines key 
elements including variable definitions for analysis of data of Study GS-US-548-5918 in support 
of the clinical study report (CSR). This SAP is based on the study protocol amendment 5.0 dated 
24 October 2023. Any changes made after the finalization of the SAP will be documented in the 
CSR.
The pharmacodynamics analysis will be described in a separate document.
Analysis methods specified in this document take precedence over those described in protocol 
should there be any difference.
1.1.
Study Objectives and Endpoints
Primary Objectives
Primary Endpoints
•
To evaluate the safety, tolerability, and 
recommended Phase 2 dose of magrolimab + 
docetaxel combination therapy in solid tumors 
(Safety Run-in Cohort 1, Phase 2 Cohorts 1a, 
1b, and 1c)
•
To evaluate the efficacy of magrolimab + 
docetaxel combination therapy in solid tumors 
as determined by investigator-assessed 
objective response rate (ORR) (Phase 2 
Cohorts 1a, 1b, and 1c)
•
Incidence of adverse events (AEs) and laboratory 
abnormalities according to the National Cancer 
Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE), Version 5.0 (Safety 
Run-in Cohort 1, Phase 2 Cohorts 1a, 1b, and 1c)
•
ORR, defined as the proportion of patients who 
achieve a complete response or partial response, as 
measured by Response Evaluation Criteria in Solid 
Tumors (RECIST), Version 1.1, as determined by 
investigator assessment (Phase 2 Cohorts 1a, 1b, and 
1c)
Secondary Objectives
Secondary Endpoints
•
To evaluate progression-free survival (PFS) by 
investigator assessment (Phase 2 Cohorts 1a, 
1b, and 1c)
•
To evaluate additional measures of efficacy of 
magrolimab + docetaxel combination therapy, 
including duration of response (DOR) and 
overall survival (OS) (Phase 2 Cohorts 1a, 1b, 
and 1c)
•
To evaluate the pharmacokinetics (PK) and 
immunogenicity of magrolimab when given 
with docetaxel as a combination therapy 
(Safety Run-in Cohort 1, Phase 2 Cohorts 1a, 
1b, and 1c)
•
PFS from date of dose initiation as determined by 
investigator assessment per RECIST, Version 1.1 
(Phase 2 Cohorts 1a, 1b, and 1c)
•
DOR, defined as time from first documentation of 
complete response or partial response to the earliest 
date of documented disease progression, per RECIST, 
Version 1.1, or death from any cause, whichever 
occurs first, as determined by investigator assessment 
(Phase 2 Cohorts 1a, 1b, and 1c)
•
OS, defined as date of dose initiation (Phase 2 
Cohorts 1a, 1b, and 1c) to death from any cause.
•
Magrolimab concentration versus time and antidrug 
antibodies to magrolimab (Safety Run-in Cohort 1; 
Phase 2 Cohorts 1a, 1b, and 1c)


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1.2.
Study Design
1.2.1.
Study Design
This Phase 2, open-label, multicenter, multi-arm study is evaluating magrolimab + docetaxel 
combination therapy for patients with solid tumors. This study will consist of the following 
Safety Run-in Cohort:
•
Safety Run-in Cohort 1: magrolimab + docetaxel combination in patients with solid tumors 
(mNSCLC, mUC, and mSCLC)
After completion of Safety Run-in Cohort 1, Phase 2 Cohort 1 will occur with Cohort 1a, 1b, and 
1c for mNSCLC, mUC, and mSCLC, respectively. 
Up to approximately 114 patients may be enrolled in the study, with up to approximately 
18 patients in Safety Run-in Cohort 1 and 96 patients in Phase 2 Cohort 1. 
The study schematic is presented in Figure 1-1.
Figure 1-1.
Study Schema
mNSCLC = metastatic non-small cell lung cancer; mSCLC = metastatic small cell lung cancer; mUC = metastatic urothelial 
cancer; RP2D = recommended Phase 2 dose
CCI
Safety Run-in Cohort 1 
mNSCLC, mUC, mSCLC 
Magrolimab + 
Docetaxel 
N = 18 
Safety Evaluation and RP2D 
Phase 2 Cohort 1 
(Magrolimab + Docetaxel) 
Phase 2 Cohort la 
(mNSCLC) 
N =30 
Phase 2 Cohort lb 
(mUC) 
N = 26 
Phase 2 Cohort le 
(mSCLC) 
N =40 


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1.2.2.
Safety Run-in Cohort 1
A dose‑limiting toxicity (DLT) evaluation period of 1 cycle (21 days) will occur. After 6 patients 
have completed the DLT evaluation period, decision will be made on further expansion or dose 
de-escalation.
Even though no dose-dependent toxicities have been observed with magrolimab, in order to 
preserve the efficacious doses of the combination partner drugs, dose de-escalation will take 
place for magrolimab.
Dose de-escalation decisions will be made as follows:
•
If 2 or fewer of 6 DLT-evaluable patients experience a DLT in Cycle 1, enrollment into 
Phase 2 Cohort 1 will begin at this dose level as the recommended Phase 2 dose.
•
If more than 2 patients experience at least 1 DLT during Cycle 1, enrollment at the current 
dose level will immediately stop and dose de-escalation will occur. Up to another 6 patients 
will then be enrolled and evaluated at a lower dose level in the same manner.
1.2.3.
Phase 2 Cohort 1
Once Safety Run-in Cohort 1 is completed and the recommended dose for Phase 2 Cohort 1 is 
determined, the sponsor will open Phase 2 Cohort 1. Phase 2 Cohort 1 will treat up to 30 patients 
with mNSCLC (Phase 2 Cohort 1a), up to 26 patients with mUC (Phase 2 Cohort 1b), and up to 
40 patients with mSCLC (Phase 2 Cohort 1c) to evaluate efficacy.
1.2.4.
Study Treatments
Table 1-1 shows the study treatments for Safety Run-in Cohort 1 and 1-2 shows the study 
treatments for Phase 2 Cohort 1.


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Table 1-1.
Safety Run-in Cohort 1: Dose Level, Schedule, and De-escalation
Dosing (Cycles Are 21 Days)
Drug
Dose Level
Cycle 1
Cycle 2
Cycle 3+ 
(maintenance 
dosing)
Starting dose
30 mg/kg
1 mg/kg IV (3 h ± 30 min) 
on Day 1 (priming dose), 
30 mg/kg IV (2 h ± 30 min) 
on Days 8 and 15
30 mg/kg IV (2 h ± 
30 min) on Days 1, 
8, and 15
60 mg/kg IV (2 h ± 
30 min) on Day 1
De-escalation
Level −1
20 mg/kg
1 mg/kg IV (3 h ± 30 min) 
on Day 1 (priming dose); 
20 mg/kg IV (2 h ± 30 min) 
on Days 8 and 15
20 mg/kg IV (2 h ± 
30 min) on Days 1, 
8, and 15
45 mg/kg IV (2 h ± 
30 min) on Day 1
Magrolimab
De-escalation
Level −2
15 mg/kg
1 mg/kg IV (3 h ± 30 min) 
on Day 1 (priming dose); 
15 mg/kg IV (2 h ± 30 min) 
on Days 8 and 15
15 mg/kg IV (2 h ± 
30 min) on Days 1, 
8, and 15
30 mg/kg IV (2 h ± 
30 min) on Day 1
Docetaxel
75 mg/m2
75 mg/m2 IV (1 h ± 5 min) 
on Day 1
75 mg/m2 IV (1 h ± 
5 min) on Day 1
75 mg/m2 IV (1 h ± 
5 min) on Day 1
IV = intravenous
Table 1-2.
Phase 2 Cohort 1: Dose Level and Schedule
Dosing (Cycles Are 21 Days)
Drug
RP2Da
Starting Dose
Cycle 1
Cycle 2
Cycle 3+ 
(maintenance 
dosing)
30 mg/kg
1 mg/kg IV (3 h ± 30 min) 
on Day 1 (priming dose); 
30 mg/kg IV (2 h ± 30 min) 
on Days 8 and 15
30 mg/kg IV (2 h ± 
30 min) on Days 1, 
8, and 15
60 mg/kg IV (2 h ± 
30 min) on Day 1
OR
20 mg/kg
1 mg/kg IV (3 h ± 30 min) 
on Day 1 (priming dose); 
20 mg/kg IV (2 h ± 30 min) 
on Days 8 and 15
20 mg/kg IV (2 h ± 
30 min) on Days 1, 
8, and 15
45 mg/kg IV (2 h ± 
30 min) on Day 1
Magrolimab
OR
15 mg/kg
1 mg/kg IV (3 h ± 30 min) 
on Day 1 (priming dose); 
15 mg/kg IV (2 h ± 30 min) 
on Days 8 and 15
15 mg/kg IV (2 h ± 
30 min) on Days 1, 
8, and 15
30 mg/kg IV (2 h ± 
30 min) on Day 1
Docetaxel
75 mg/m2 IV
75 mg/m2 IV (1 h ± 5 min) 
on Day 1
75 mg/m2 IV (1 h ± 
5 min) on Day 1
75 mg/m2 IV (1 h ± 
5 min) on Day 1
IV = intravenous; RP2D = recommended Phase 2 dose
a
RP2D as determined in Safety Run-in Cohort 1.


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1.3.
Sample Size and Power
Table 1-3 presents the sample size calculations. For Phase 2 Cohort 1, a sample size of 
30 patients in the mNSCLC cohort and 40 patients for the mSCLC cohort were calculated using 
one sample proportion test. The sample size of 26 patients for the mUC cohort was calculated 
using exact method instead of one sample test due to smaller sample size.
Table 1-3.
Sample Size Calculations
Tumor Type
Sample Size
Null ORR
Alternative ORR
1-sided 
alpha
Power
mNSCLC
30
13%
25%
0.2
81%
mUC
26
12.4%
28%
0.1
78%
mSCLC
40
9%
20%
0.15
84%
mNSCLC = metastatic non-small cell lung cancer; mSCLC = metastatic small cell lung cancer; mUC = metastatic urothelial 
cancer; ORR = objective response rate
The null ORR for each of the respective tumor cohorts are based on historical taxane efficacy 
data in the second line setting {Bellmunt 2017, Rittmeyer 2017, Smit 1998}. Power calculations 
were performed using EAST 6.5 and nQuery 8.0.


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2.
TYPE OF ANALYSIS
2.1.
Dose Determination Analysis
For the purposes of making any dose de-escalation decisions for Safety Run-in Cohort 1, dose 
determination analyses of relevant safety data focusing on DLTs and overall safety profile was 
conducted by the sponsor after all patients had completed required dosing cycles (21 days) and 
the follow-up period as defined in Section 1.2.2. Dose Determination Analyses has been 
completed and is not within the scope of this SAP.
2.2.
Informal Interim Analyses
No formal interim efficacy analysis, which may lead to early termination for efficacy or futility, 
is planned. 
For the purpose of potential Phase 3 planning, informal interim analyses may be conducted per 
cohort after at least 20 patients enrolled in each tumor type (i.e., including applicable patients 
from the combined Safety Run-in) and have been followed up for approximately 19 weeks. 
2.3.
Primary Analysis 
For each of the subcohorts in Phase 2 Cohort 1, the primary analysis of ORR will be conducted 
approximately 6 months after the last patient is enrolled, outstanding data queries have been 
resolved or adjudicated as unresolvable, and the data have been cleaned and finalized for the 
analysis.
2.4.
Final Analysis
The final analysis may be performed after all patients have completed the study or discontinued 
early, outstanding data queries have been resolved or adjudicated as unresolvable, and the data 
have been cleaned and finalized.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of patients in each category will be presented; for continuous variables, 
the number of patients (n), mean, standard deviation (StD) or standard error (SE), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
3.1.
Analysis Sets
For each analysis set, the number and percentage of patients eligible for inclusion, as well as the 
number and percentage of patients who were excluded and the reasons for their exclusion, will 
be summarized by cohort (Safety run-in cohort 1, Phase 2 cohort 1a, 1b, 1c, respectively).
A listing of reasons for exclusion from analysis sets will be provided by patient.
3.1.1.
All Enrolled Analysis Set
All Enrolled Analysis Set includes all patients who received a study subject identification 
number in the study after screening. 
3.1.2.
Modified ITT Analysis Set
The modified ITT Analysis Set (mITT) includes all enrolled patients who took at least 1 dose of 
any study drug. This is the primary analysis set for efficacy analyses of Phase 2 Cohort 1a, 1b 
and 1c, respectively.
3.1.3.
Safety Analysis Set
The Safety Analysis Set includes all patients who took at least 1 dose of any study drug. This is 
the primary analysis set for safety analysis (except for DLTs) of both Safety Run-in Cohort 1 and 
Phase 2 Cohort 1a, 1b, 1c, respectively.
3.1.4.
Dose-Limiting Toxicity (DLT) Evaluable Analysis Set
For Safety Run-in Cohort 1, the primary analysis set for the primary DLT analysis is the DLT 
Evaluable Analysis Set, defined as all patients who meet 1 of the following criteria in the DLT 
evaluable period (defined as 21 days of the first dosing cycle):
•
The patient experienced a DLT at any time after initiation of the first infusion of magrolimab.
•
The patient did not experience a DLT and completed at least 2 infusions of magrolimab 
(21-day cycle) and at least 1 dose of docetaxel in Safety Run-in Cohort 1.
For the 2nd criteria above, the 2 doses of magrolimab and 1 dose of docetaxel are infused within 
the 21-day cycle and patient is on study for at least 21 days after the first dose in Safety Run-in 
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3.1.5.
Pharmacokinetic Analysis Set
The PK analysis will be conducted on the PK Analysis Set, defined as all patients who received 
any amount of magrolimab and have at least 1 measurable posttreatment serum concentration of 
magrolimab.
3.1.6.
Immunogenicity Analysis Set
The immunogenicity analysis will be conducted on the Immunogenicity Analysis Set, defined as 
all patients who received any amount of magrolimab and have at least 1 evaluable 
anti-magrolimab antibody test result.
3.1.7.
Biomarker Analysis Set
The biomarker analysis will be conducted on the Biomarker Analysis Set, defined as all patients 
who received any study drug and have at least 1 evaluable biomarker measurement available.
3.2.
Subject Grouping
For primary analyses and final analysis based on the mITT or Safety Analysis Set, patients will 
be grouped according to the cohort they were enrolled in: Safety Run-in Cohort 1, Phase 2 
Cohort 1a (mNSCLC), Phase 2 cohort 1b (mUC), and Phase 2 cohort 1c (mSCLC).
For informal interim analysis based on the mITT or Safety Analysis Set, patients will be grouped 
according to the tumor type at enrollment as follows:
•
Safety Run-in cohort 1 with tumor type mNSCLC + Phase 2 cohort 1a (mNSCLC) 
•
Safety Run-in cohort 1 with tumor type mUC + Phase 2 cohort 1b (mUC) 
•
Safety Run-in cohort 1 with tumor type mSCLC + Phase 2 cohort 1c (mSCLC) 
Here the tumor type from safety run-in cohort 1 is determined by the type of cancer from 
medical history as collected in CRF. 
3.3.
Strata and Covariates
This study does not have randomization so no randomization strata is defined. 
No covariates will be included in efficacy and safety analyses.
3.4.
Examination of Subject Subgroups
There are no prespecified patient subgroupings for efficacy and safety analyses.
3.5.
Adjustment for Multiplicity
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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. 
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analysis.
3.7.
Data Handling Conventions and Transformations
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:
•
If only year of birth is collected, then “01 July” will be imputed as the day and month of birth
•
If year of birth is missing, then date of birth will not be imputed.
In general, age collected at the Study Day 1 (in years) will be used for analyses and presented in 
listings. If age at Day 1 is not available for a subject, then age derived based on date of birth and 
the date of Study Day 1 will be used instead. If an enrolled subject was not dosed with any study 
drug, the enrollment date will be used instead of the Day 1 visit date. For screen failures or patients 
who are not enrolled, the date the first informed consent was signed will be used for the age 
derivation. Age required for longitudinal and temporal calculations and analyses (eg, estimates of 
creatinine clearance, age at date of AE) will be based on age derived from date of birth and the 
date of the measurement or event, unless otherwise specified.
Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:
•
A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “< x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 
0.1,etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used 
to calculate summary statistics.
•
A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.
•
The lower or upper LOQ will be used to calculate descriptive statistics if the datum is 
reported in the form of “≤ x” or “≥ x” (where x is considered the lower or upper LOQ, 
respectively).


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If methods based on the assumption that the data are normally distributed are not adequate, 
analyses may be performed on transformed data or nonparametric analysis methods may be used, 
as appropriate.
PK Data Handling
Natural logarithmic transformation will be used for analyzing non-BLQ concentrations and PK 
parameters. Concentration values that are below the limit of quantitation (BLQ) will be presented 
as “BLQ” in the concentration data listing. Values that are BLQ will be treated as 0 at predose 
and postdose time points for summary purposes. The number of samples will be summarized to 
reflect the actual number of samples assessed at that time point.
At predose, if all concentration values are BLQ, then the mean, and order statistics (minimum, 
Q1, median, Q3, and maximum) will be displayed as 0 and the rest of the summary statistics (ie, 
SD and CV) will be missing. If any values are non-BLQ, then the number of samples, order 
statistics, and all summary statistics will be displayed. 
At any given postdose time point, if more than one-third of the participants have a concentration 
value of BLQ, then only the number of samples and order statistics will be displayed; otherwise, 
order statistics and summary statistics will be displayed.
The following conventions will be used for the presentation of order statistics for postdose time 
points: 
•
If at least 1 participant has a concentration value of BLQ for the time point, the minimum 
value will be displayed as “BLQ.”
•
If more than 25% of the participants have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.” 
•
If more than 50% of the participants have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.” 
•
If more than 75% of the participants have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.” 
•
If all participants have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
PK parameters that are BLQ will be excluded before log transformation or statistical model fitting 
and displayed as described above.


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3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of any study drug, which is the date of the 
first dose of magrolimab or the combination drug, whichever occurs first and derived as follows:
•
For postdose study days: Assessment Date – First Dosing Date + 1
•
For days prior to the first dose: Assessment Date – First Dosing Date
Therefore, study day 1 is the day of first dose of any study drug administration. If the subject is 
enrolled but not dosed, the enrollment date will be study day 1.
3.8.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for lab assessments are provided in Table 3-1. Post-infusion lab 
assessments for hemoglobin and hematocrit will use nominal visit and will be excluded when 
applying Table 3-1. Analyses windows will be applied to summary tables of lab results by visits 
and change from baseline if applicable.
Table 3-1.
Analysis Visit Windows for Lab By-visit Summaries
Visit Window Study Day
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
(none)
1a
Day 2b
2
1c
2
Week 1
8
3
11
Week 2
15
12
18
Week 3
22
19
25
Week 4
29
26
32
Week 5
36
33
39
Week 6
43
40
53
Week 9
64
54
74
Week xxd
(xx)*7 + 1
(xx)*7 - 9
(xx)*7 + 11
a
Prior to first dose date time
b
Day 2 visit not applicable to chemistry lab assessments. Chemistry labs assessed post first dose date time through study day 
2 will be assigned to “Week 1” visit
c
Post first dose date time
d
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3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
If multiple valid / nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:
•
For baseline, the last nonmissing value on or prior to the first dosing date of study drug will 
be selected, unless specified differently. If there are multiple records with the same time or 
no time recorded on the same day, the baseline value will be the average of the 
measurements for continuous data, or the measurement with the worst severity for 
categorical data.
•
For postbaseline values:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken for 
continuous data and the worst severity will be taken for categorical data, unless otherwise 
specified.
3.9.
Assessment of COVID-19 Impact
This study was ongoing during the novel coronavirus (COVID-19) pandemic which has an 
impact on the study conduct. Some patients were unable to attend onsite visits due to shelter in 
place guidelines, site closures, or other reasons. The following special situations due to 
COVID-19 may be handled in the analysis:
•
Study treatment or study discontinuation due to COVID-19
•
Protocol deviations due to COVID-19
•
Adverse events due to COVID-19
•
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4.
PROTOCOL DEVIATIONS 
Patients who did not meet at least one eligibility criterion for study entry, but enrolled in the 
study will be summarized by cohort regardless of whether they were exempted by the sponsor or 
not, based on the All Enrolled Analysis Set. The summary will also present the number and 
percentage of patients who did not meet specific criteria. 
Protocol deviations occurring after patients entered the study are documented during routine 
monitoring. The number and percentage of patients with important protocol deviations by 
deviation reason (e.g., eligibility criteria, informed consent) will be summarized by cohort for the 
All Enrolled Analysis Set. 


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5.
SUBJECT INFORMATION
In general, disposition tables and all listings will be based on All Enrolled Analysis Set. 
Summary of treatment exposure, prior and concomitant medications and post treatment anti-
cancer therapy will be based on Safety Analysis Set. All other table summaries in this section 
will be based on mITT Analysis Set, unless specified otherwise. 
5.1.
Patient Enrollment and Disposition
Key study dates (i.e., first patient screened, first patient enrolled, last patient enrolled, last patient 
last visit for the primary endpoint, and last patient last visit for the clinical study report) will be 
provided.
A summary of patient enrollment will be provided by cohort for each country, investigator and 
overall. 
A summary of patient disposition will be provided by cohort. This summary will present the 
number of patients who met all eligibility criteria but were not enrolled with reasons patients not 
enrolled, the number of patients enrolled, and the number of patients in each of the categories 
listed below:
•
mITT Analysis Set
•
Safety Analysis Set 
•
Continuing study treatment (magrolimab, docetaxel)
•
Discontinued study drug with reasons for discontinuation of study drug (magrolimab, 
docetaxel)  
•
On-going in study 
•
Discontinued the study with reasons for discontinuation of study
For the status of study drug and study completion and reasons for discontinuation, the number 
and percentage of patients in each category will be provided. The denominator for the percentage 
calculation will be the total number of patients in the All Enrolled Analyses Set corresponding to 
that column. 
The following by-patient listings will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:
•
Reasons for study drug discontinuation
•
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5.2.
Extent of Study Treatment Exposure 
Extent of exposure to study treatment will be summarized using descriptive statistics for total 
duration of exposure, total number of infusions received, total number of cycles received for 
each study drug, total cumulative dose administered for each study drug, relative dose intensity 
(%) of each study drug, and number (%) of patients with dose modifications (i.e., infusion 
interruption, dose delayed or not administered) and reasons for each study drug (Magrolimab and 
Docetaxel) by cohort.
5.2.1.
Duration of Exposure
Total duration of exposure to each study drug (Magrolimab and Docetaxel) will be defined for a 
subject as last dosing date minus first dosing date plus 1 day, regardless of any temporary 
interruptions in study drug administration, and will be expressed in weeks using up to 1 decimal 
place (e.g., 4.5 weeks).
The total duration of exposure to each study drug will be summarized using descriptive statistics 
for continuous variables, as well as using the number (i.e., cumulative counts) and percentage of 
patients exposed for at least the following time periods: 1 day, 3 weeks, 6 weeks, 9 weeks, 
18 weeks, and 27 weeks, etc.
5.2.2.
Relative Dose Intensity
Relative dose intensity (RDI) is the percentage of the total amount of study drug administered 
relative to the total amount of study drug expected to be administered during a patient’s actual 
on-treatment period based on the study drug regimen. 
Summary of relative dose intensity of magrolimab will be expressed as a percentage using the 
following formula:
𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝑑𝑜𝑠𝑒 𝑖𝑛𝑡𝑒𝑛𝑠𝑖𝑡𝑦 (%) =
𝐶𝑢𝑚𝑢𝑙𝑎𝑡𝑖𝑣𝑒 𝑑𝑜𝑠𝑎𝑔𝑒 𝑟𝑒𝑐𝑒𝑖𝑣𝑒𝑑 𝑚𝑔
𝑘𝑔
𝑇𝑜𝑡𝑎𝑙 𝑝𝑙𝑎𝑛𝑛𝑒𝑑 𝑑𝑜𝑠𝑎𝑔𝑒 𝑜𝑓 𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑑𝑟𝑢𝑔𝑚𝑔
𝑘𝑔
× 100
Cumulative dosage (mg/kg for Magrolimab or mg/m2 for Docetaxel) received for each subject is 
defined as the sum of all delivered dosages of all infusions the subject received. Delivered 
dosage will be calculated by the actual dose received (mg) as collected in CRF devided by the 
subjects’s weight (for Magrolimab) or BSA (for Docetaxel) collected on or before that visit. 
Total assigned dosage (mg/kg or mg/m2) for each subject is defined as the sum of the assigned 
dosage per protocol specified dose level and dosing schedule.
For each study drug, descriptive statistics for the relative dose intensity with the number and 
percentage of patients belonging to relative dose intensity categories (eg, < 75%, ≥ 75 to < 90%, 
≥ 90%) will be provided by cohort for the Safety Analysis Set.
( ___ 
(_/_)) 
( I ) 


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A by-patient listing of each study drug administration will be provided by subject ID number (in 
ascending order) and visit (in chronological order).
5.3.
Demographics and Baseline characteristics  
Subject demographic variables (i.e., age, sex at birth, race, ethnicity) and baseline characteristics 
include but are not limited to: body weight [in kg], height [in cm], body mass index [BMI; in 
kg/m2], Body Surface Area [BSA; in m2], type of cancer (Bladder, Non small cell lung, Small 
cell lung carcinoma) and disease stage at screening, Best response of the last prior anti-cancer 
therapy in metastatic setting before enrollment, and ECOG performance status, will be 
summarized using descriptive statistics for continuous variables and using number and 
percentage of patients for categorical variables. This analysis will be summarized with 
descriptive statistics by cohort for the mITT Analysis Set.
By-patient demographic and baseline characteristic listings, including the informed consent date, 
will be provided.
5.4.
Medical History
General medical history data will be collected at screening and will be coded using the current 
version of Medical Dictionary for Regulatory Activities (MedDRA). 
A by-patient listing including all the information collected in the medical history eCRF and the 
coded terms including SOC and PT will be provided.
5.5.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
5.5.1.
Prior Medications
Prior medications are defined as any medications taken before a patient took the first study drug.
Prior medications will be summarized by Anatomical Therapeutic Chemical (ATC) drug class 
Level 2 preferred name using the number and percentage of subjects by cohort and treatment 
group. A subject reporting the same medication more than once will be counted only once when 
calculating the number and percentage of subjects who received that medication. The summary 
will be ordered alphabetically by ATC medical class and then by preferred term in order of 
descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
For the purposes of analysis, any medication with a start date prior to the first dosing date of 
study drug will be included in the prior medication summary regardless of when the stop date is. 
If a partial start date is entered the medication will be considered prior unless the month and year 
(if day is missing) or year (if day and month are missing) of the start date are after the first 
dosing date. Medications with a completely missing start date will be included in the prior 
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Summaries will be based on the Safety Analysis Set and a by-patient listing will be provided. 
5.5.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a patient took study treatment. 
Use of concomitant medications will be summarized by Anatomical Therapeutic Chemical 
(ATC) drug class Level 2 and preferred name using the number and percentage of patients for 
each cohort. A patient reporting the same medication more than once within each ATC drug 
class will be counted only once when calculating the number and percentage of patients who 
received that medication. Medications may appear under multiple ATC drug classes. The 
summary will be ordered alphabetically by ATC medical class and then by preferred term in 
descending overall frequency within each ATC medical class. For drugs with the same 
frequency, sorting will be done alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study treatment and continued to be taken after the first dosing date, or started after the first 
dosing date but prior to or on the 30 days after last dosing date of study treatment will be 
considered concomitant medications. Medications started and stopped on the same day as the 
first dosing date or the last dosing date of study treatment will also be considered concomitant. 
Medications with a stop date prior to the date of first dosing date of study treatment or a start 
date after the last dosing date of study treatment plus 30 days will be excluded from the 
concomitant medication summary. Medications with partially or completely missing start and 
stop dates will be included in the concomitant medication summary, unless the partial missing 
date suggested otherwise. 
Summaries will be based on the Safety Analysis Set. 
All concomitant medications will be provided in a by-patient listing sorted by subject ID number 
and administration date in chronological order.
5.6.
Prior Anti-cancer Therapy
Prior anti-cancer therapy will be coded using the World Health Organization (WHO) Drug 
Dictionary and summarized by Preferred Drug Name. The number of prior regimans of anti-
cancer therapies in metastatic setting, therapy settings (neoadjuvant, adjuvant or metastatic), best 
response of the last prior anti-cancer therapy in metastatic setting before enrollment, and time 
from last disease progression to enrollment date will be summarized by cohort.
A by-patient listing will be provided.
5.7.
On Study or Post Study Anti-cancer Therapies
All subsequent anti-cancer therapies including flag for on-study and post study anti-cancer 
therapies as collected in CRF will be provided in a by-patient listing sorted by patient ID number 
and administration date in chronological order. Note that anti-cancer therapy is not allowed 
during the study drug treatment per protocol, which may be violated and lead to important 
protocol deviation. The analysis will be performed for Safety Analysis Set.


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5.8.
Prior and On Study Radiation Therapy
A by-patient listing including information collected in eCRF and the flag for prior and on study 
radiation therapy will be provided.
5.9.
Prior and On Study Surgeries and Procedures
A by-patient listing including information collected in eCRF and  the flag for prior and on study 
surgery and procedure will be provided.


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6.
EFFICACY ANALYSES
In general, summary of efficacy endpoints in this section will be based on mITT Analyses Set for 
each of the phase 2 cohort 1a, 1b and 1c, unless specified otherwise. Listing will be based on All 
Enrolled Analysis Set. Safety run-in cohort 1 subjects will only be listed for efficacy related 
endpoints.
6.1.
Primary Efficacy Endpoints
6.1.1.
Definition of the Primary Efficacy Endpoints
The primary efficacy endpoint of this study is objective response rate (ORR) defined as the 
proportion of patients who achieve the best overall response of complete response (CR) or partial 
response (PR) that is confirmed at least 4 weeks after initial documentation of response. The 
responses are measured by response evaluation criteria in solid tumors (RECIST), Version 1.1, 
as determined by investigator assessment (Phase 2 cohorts 1a, 1b, and 1c). Tumor response 
assessments after the date of patients receiving new anticancer therapy will be excluded from the 
analysis. Patients who do not have baseline or on-study response status assessment, or who 
received subsequent anticancer therapy prior to achieving CR or PR, will be considered as non-
responders.
6.1.2.
Analysis of the Primary Efficacy Endpoint
For each of Phase 2 cohorts 1a, 1b and 1c, the primary analysis of ORR will be conducted 
approximately 6 months after the last patient is enrolled. ORR along with the 2-sided 95% exact 
confidence interval (CI) of ORR based on Clopper-Pearson method will be provided for each 
cohort. 
6.1.3.
Sensitivity Analysis of the Primary Efficacy Endpoint
There is no sensitivity analysis is planned.
6.2.
Secondary Efficacy Endpoints
6.2.1.
Definition of Secondary Efficacy Endpoints
Progression-Free Survival (PFS)
PFS is defined as the interval from the first dosing date of any study drug to the earlier date of 
the first documentation of objective disease progression by investigator assessment per RECIST, 
Version 1.1, or death from any cause. 


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Duration of Response (DOR) 
DOR is defined for confirmed responders as duration of time from the date of initial response 
(first confirmed CR or PR) to the date of first documentation of disease progression per RECIST, 
Version 1.1, or the date of death due to any cause, whichever occurs first.
DOR = Date of disease progression/death or censoring – Date of first confirmed CR/PR + 1.
Date of initial response is the date of first response achieved and then confirmed by a subsequent 
disease assessment conducted prior to or at the initiation of the next line of subsequent anticancer 
therapy. 
Date of disease progression (PD) used to calculate DOR is the first PD date prior to or on the 
date of initiation of subsequent anticancer therapy.  
Overall Survival (OS) 
OS is defined as the interval from first dosing date of any study drug to death from any cause. 
For patients who were not known to have died at the time of the analysis, OS data will be 
censored at the last date that they were known to be alive. In the event that the patient has 
withdrawn consent, the vital status of the patient can be obtained by site personnel from publicly 
available resources under applicable local laws. 
6.2.2.
Analysis Methods for Secondary Efficacy Endpoints
Analysis of PFS, OS and DOR (confirmed responders only) will be performed using the Kaplan-
Meier method for the mITT Analysis Set. Medians, Q1, Q3, and the proportion of patients who 
are progression-free (for PFS only) will be provided along with corresponding 95% CIs 
calculated by the Brookmeyer and Crowley method with log-log transformation for each of the 
Phase 2 cohorts. Kaplan-Meier curves will be provided by each of the Phase 2 cohorts. 
Censoring rules for PFS and DOR are listed in Table 6-1.
Table 6-1.
Censoring rules for analysis of PFS and DOR
Situation
Censoring Rule for Analysis
Documented Progressive Disease (PD)
Progressed at date of earliest sign of PD
Death before first PD 
Progressed at date of death  
Death within 2 disease assessments window 
Progressed at date of death  
Alive and progression-free
Censored at date of last evaluable disease assessment
No PD or death before or on the initiation date of 
subsequent anticancer therapy
Censored at date of last evaluable assessment on or 
prior to subsequent anticancer therapy
PD or death after ≥ 2 consecutively missed or not 
evaluable (NE) disease assessments
Censored at date of last evaluable assessment prior to 
missed or NE assessments
No disease assessment at baseline or post-baseline 
assessment* for PFS
Censored at the first dosing date for PFS 
*Baseline tumor assessment should be performed no more than 28 days before the start of study drug, unless otherwise specified 
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The scheduled visit assessment scheme is every 9 weeks in a 21-day dosing cycle during the 
study starting from C1D1 with the on-treatment imaging window of ± 7 days. The definition of 
2 missed visits are 2 * (9 weeks + 7 days).
A by-patient listing of DOR will be provided by patient ID number in ascending order.
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6.4.
Changes From Protocol-Specified Efficacy Analyses
There are no deviations from the protocol-specified Efficacy analyses.
CCI


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7.
SAFETY ANALYSES
In general, safety analysis will be performed in the Safety Analysis Set for each cohort (Safety 
run-in cohort 1, Phase 2 cohort 1a, 1b and 1c respectively) and listings will be provided on the 
All Enrolled analysis set unless specified otherwise. Analysis of DLT was performed using the 
DLT evaluable analysis set for Safety Run-in evaluations which is not under the scope of this 
SAP.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of Medical 
Dictionary for Regulatory Activities (MedDRA). 
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to CTCAE 
Version 5.0. 
7.1.3.
Relationship of Adverse Events to Study Treatment
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Summary of relationship will also be applied based on 
“Related to Study Treatment Magrolimab” and “Related to Study Treatment Docetaxel” 
separately. 
Relatedness will always default to the investigator’s choice, not that of the medical monitor. 
Events for which the investigator did not record relationship to study drug will be considered 
related to study drug for summary purposes. However, by-patient data listings will show the 
relationship as missing.
7.1.4.
Serious Adverse Events 
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Global Patient Safety 
Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any events not present prior to the 
study treatment, or any events already present but worsening in either intensity or frequency 
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The TEAE reporting period is defined as the period from the date of the first dose of study 
treatment up to 30 days after the date of the last dose of study treatment or the day before 
initiation of subsequent antineoplastic therapy, whichever comes first. 
If the AE onset date is on or before the last dose date, the AE is considered as TEAE, regardless 
of the initiation of subsequent anti-cancer therapy.
7.1.5.2.
Missing or incomplete Dates
If there was a missing or incomplete date for the start date or stop date of an AE, the most 
conservative approach was used for analysis. 
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:
•
The AE onset date is the same as or after the month and year (or year alone if month is not 
recorded) of the first dosing date of any study drug, and
•
The AE onset date is the same as or before the month and year (or year alone if month is not 
recorded) of the date corresponding to the cutoff date of TEAE period, which is defined as 
the 30 days after the any study drug last dosing date or the day before the initiation of new 
anticancer therapy (whichever is earlier)
An AE with completely missing onset and stop dates, or with the onset date missing and the stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. 
In addition, an AE with the onset date missing and incomplete stop date with the same month 
and year (or year alone if month is not recorded) or later as the first dosing date of study drug 
will be considered treatment emergent.
In case when the AE onset date is incomplete and needs to be imputed, the following algorithm 
will be followed:
•
If the day is missing but the month and year are available, then the imputed day will be the 
first dosing date if they have the same month and year, or the first day of the month 
otherwise.
•
If the day and month are missing but year is available, then the imputed day and month will 
be the first dosing date if they have the same year, or 01Jan otherwise.


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7.1.6.
Summaries of Adverse Events and Deaths
A brief, high-level summary of the number of percentage of patients who experienced at least 
1 TEAE in the endpoints described below will be provided by cohort in Safety Analysis Set. The 
number and percentage of patients who experienced at least 1 TEAE will also be summarized by 
SOC and PT or by PT only, by cohort.
•
TEAEs
•
TEAEs with Grade 3 or higher
•
Treatment-related TEAEs for study drug (with indication of which study drug)
•
Treatment-related AEs with grade 3 or higher for study drug (with indication of which study 
drug)
•
TE SAEs 
•
TE Treatment-related SAEs for study drug (with indication of which study drug)
•
TEAEs leading to discontinuation for study drug (with indication of which study drug)
•
TEAEs leading to dose reduction for Docetaxel
•
TEAEs leading to dose interruption or dose delay (including not administered) for study drug 
(with indication of which study drug)
•
TEAEs leading to death
Multiple events will be counted only once per subject in each summary. Adverse events of all 
TEAEs, TEAEs of Grade 3 or higher, TE SAEs and TEAEs leading to death will be summarized 
by SOC and PT and listed first in alphabetic order of SOC and then by PT within each SOC in 
the descending order of overall frequency (or otherwise specified). For summaries by severity, 
the most severe severity will be used for those AEs that occurred more than once in a given 
subject during the study.
In addition to the above summary tables, all other AEs listed above will be summarized by PT 
only in descending order of overall frequencies (or otherwise specified).
By-patient listings for the following endpoints will also be provided in All Enrolled Analyses 
Set:
•
All AEs indicating whether the event is treatment emergent
•
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•
All Deaths
•
All SAEs leading to death
•
All AEs with severity of Grade 3 or higher
•
All AEs leading to discontinuation of study drug (with indication of which study drug)
•
All AEs leading to dose reduction of Docetaxel
•
All AEs leading to dose interruption or dose delay (including not administered) of study drug 
(with indication of which study drug)
A summary (number and percentage of patients) of deaths for the endpoints listed below will be 
provided by cohort. Summary will include the following categories:
•
All deaths
•
Deaths within 30 days of the last dosing of study treatment
•
Deaths beyond 30 days of the last dosing of study treatment
7.1.7.
Additional Analysis of Adverse Events
7.1.7.1.
Dose Limiting Toxicity (DLT)
In Safety run-in Cohort, a summary of DLT by PT among the DLT evaluable patients will be 
provided. DLT-type AEs will also be summarized in the same way, where DLT-type AEs are 
toxicities that met protocol specified criteria of DLTs and occurred beyond the protocol-specified 
DLT assessment period (onset date beyond the 21 days period).
By-patient listing of the DLT AEs and DLT-type AEs will also be provided.
7.1.7.2.
Treatment-Emergent Adverse Events of Clinical Importance 
The TEAE of clinical importance are defined in Table 7-1. Number and percentage of subjects 
with the following TEAE of clinical importance will be summarized by PT by cohort in Safety 
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Table 7-1.
Treatment Emergent Adverse Events of Clinical Importance
TEAE of Clinical Importance
Search Strategy
Anaemia
Medical Search Term (MST) Anemia Extravascular 
transient hemolysis
Infusion related reactions
Standardized MedDRA Queries (SMQ) Hypersensitivity 
(narrow) + within one day of latest infusion of any study 
drug
Severe Neutropenia
PT: Grade 3+ Febrile neutropenia, Grade 3+ Neutrophils 
count decreased, Grade 3+ Neutropenia
Serious Infections
SAE within SOC: Infections and infestations
Transfusion reactions due to magrolimab 
interference with RBC typing
MST Transfusion reactions due to magrolimab interference 
with RBC typing
Thromboembolic events
SMQ Embolic and thrombotic events (broad)
Pneumonitis
SMQ Interstitial lung disease (broad)
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to 30 days plus the last dose date OR the 
initiation of subsequent anti-cancer therapy. If the lab data collected on or before the last dose 
date, data will be included regardless of the initiation of subsequent anti-cancer therapy. The 
analysis will be based on values reported in conventional units. When values are below the LOQ, 
they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7.
A by-patient listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology and serum chemistry separately. Values falling outside of the 
relevant reference range and/or having a severity grade of 1 or higher on the CTCAE severity 
grade will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by cohort for selected laboratory test specified in the study 
protocol as follows:
•
Baseline values 
•
Postbaseline maximum value
•
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•
Change and percentage change from baseline to postbaseline maximum value
•
Change and percentage change from baseline to postbaseline minimum value
Plots of lab parameters may include (but not limited to) hemoglobin, hematocrit, platelet, and 
absolute neutrophil counts over time.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
7.2.2.
Graded Laboratory Values
The CTCAE Version 5.0 will be used to assign toxicity grades (0 to 4) to laboratory results for 
analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of at least 
Grade 1. For laboratory tests with criteria for both increased and decreased levels, analyses for 
each direction (i.e., increased, decreased) will be presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days and prior to the day of initiation of subsequent anti-cancer 
therapy. If the relevant postbaseline lab is assessed on or before the last dose date, the laboratory 
abnormality is considered as treatment-emergent laboratory abnormality, regardless of the 
initiation of subsequent anti-cancer therapy. If the relevant baseline laboratory value is missing, 
any abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent.
7.2.2.2.
Treatment-Emergent Marked Laboratory Abnormalities
Treatment-emergent marked laboratory abnormalities are defined as values that increase from 
baseline by at least 3 toxicity grades at any postbaseline time point up to and including the date 
of last dose of study drug plus 30 days and prior to the day of initiation of subsequent anti-cancer 
therapy. If the relevant postbaseline lab (with at least 3 toxicity grades increasing from baseline) 
is assessed on or before the last dose date, the laboratory abnormality is considered as treatment-
emergent marked laboratory abnormality, regardless of the initiation of subsequent anti-cancer 
therapy. If the relevant baseline laboratory value is missing, any Grade 3 or 4 values observed 
within the timeframe specified above will be considered treatment-emergent marked 
abnormalities.
7.2.2.3.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of patients) for treatment-emergent (TE) 
laboratory abnormalities will be provided by lab test by cohort. Patients will be categorized 
according to the most severe postbaseline abnormality grade for a given lab test:


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•
TE Laboratory abnormalities (Grade 1 to 4 separately)
•
Grade 3 or 4 TE laboratory abnormalities
•
Marked TE laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of patients in the 
correponding nonmissing postbaseline laboratory values up to 30 days after the last dosing date 
or the day before initiation of new anticancer therapy, whichever is earlier. 
By-patients listings of treatment-emergent Grade 3 or 4 laboratory abnormalities and treatment 
emergent marked laboratory abnormalities will be provided by subject ID number and visit in 
chronological order. This listing will include all test results that were collected throughout the 
study for the lab test of interest, with all applicable severity grades displayed. 
By-patient listing for post-infusion hematology will also be provided. Laboratory abnormalities 
that occur before the first dose of study drug or after the patient has been discontinued from 
treatment for at least 30 days will also be included in a data listing.
7.2.3.
Liver-related Laboratory Evaluations
Liver-related abnormalities after the first dose of any study drug will be examined and 
summarized by cohort using the number and percentage of patients who were reported to have 
the following laboratory test values for postbaseline measurements:
•
Aspartate aminotransferase (AST): >= 3 times of the upper limit of reference range (ULN)
•
Alanine aminotransferase (ALT): >= 3 x ULN
•
AST or ALT: >= 3 x ULN
•
Total bilirubin: > 2 x ULN
•
AST or ALT >= 3 x ULN and total bilirubin > 2 x ULN
•
AST or ALT >= 3 x ULN and total bilirubin > 2 x ULN and alkaline phosphatase (ALP) 
< 2 x ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
study drug or the day before initiation of new anticancer therapy, whichever is earlier. For 
individual laboratory tests, patients will be counted once based on the most severe postbaseline 
values. For the composite endpoints of AST or ALT and total bilirubin and ALP, patients will be 
counted once when the criteria are met at the same postbaseline visit date. The denominator is 
the number of patients in the Safety Analysis Set who have at least one postbaseline visit, at 
which all the relevant tests are nonmissing at the same postbaseline visit date.


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A listing of patients who met at least 1 of the above criteria will be provided.
7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by cohort for body weight, height, BMI, systolic and 
diastolic blood pressure, heart rate, temperature and respiratory rate.
•
Baseline values 
•
Values at each postbaseline time point 
•
Change and percentage change from baseline at each postbaseline time point
A baseline value will be defined as the last available value collected on or prior to the first dose 
of any study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. Vital signs measured at unscheduled visits will be 
included for the baseline value selection.
A by-patient listing of vital signs will be provided by subject ID number and time point in 
chronological order. 
7.4.
Electrocardiogram (ECG) Results
A by-patient listing of ECG results will be provided by subject ID number in ascending order.
7.5.
Eastern Cooperative Oncology Group (ECOG) Performance Status
A by-patient listing of ECOG performance status will be provided by subject ID number in 
ascending order.
7.6.
Pregnancy Test
A by-patient listing of the pregnancy test results as collected in CRF will be provided.
7.7.
Changes From Protocol-Specified Safety Analyses
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8.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
There is no deviation from protocol defined analysis.


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9.
PHARMACOKINETIC (PK) AND IMMUNOGENICITY 
ANALYSES
9.1.
PK Analysis
The PK Analysis Set will be used for summaries of PK concentration of magrolimab versus time. 
Serum concentrations will be listed and summarized for magrolimab using descriptive statistics 
by sampling timepoint and treatment. Graphical plots of individual serum concentration versus 
time and mean concentration versus time by treatment will be generated. PK data from this study 
might be combined with PK data from other Magrolimab studies and analyzed using a 
population PK model. Such an analysis would be reported separately.
9.2.
Immunogenicity analysis
Serum samples for antidrug antibody (ADA) assessments will be conducted utilizing a tiered 
approach (screen, confirmatory and titer), and ADA data will be collected at scheduled visits 
shown in the protocol. ADA result from each sample will be reported as either positive or 
negative. If the sample is positive, the ADA titer will be reported as well. In addition, the 
presence of neutralizing antibody (nAb) will be tested for all ADA positive samples using a 
ligand-binding assay. The nAb results will be reported as positive or negative. 
Patients for ADA prevalence are defined as patients who had at least one positive ADA sample 
at any time, including baseline and post-baseline, in Immunogenicity Analysis Set.
Patients for ADA incidence are defined as patients with at least one baseline ADA sample and at 
least one post-treatment ADA sample in Immunogenicity Analysis Set. 
Patients for nAb prevalence are defined as patients who had at least one positive nAB sample at 
any time, including baseline and post-baseline, in Immunogenicity Analysis Set
Among patients for ADA incidence, patients who had Treatment-Induced ADA or Treatment-
Boosted ADA are categorized as ADA positive by incidence, where
•
Treatment-Induced ADA is defined as patients who had negative baseline ADA sample and 
at least one positive post-treatment ADA sample. 
•
Treatment-Boosted ADA is defined as patients who had positive baseline ADA sample and 
at least one positive post-treatment ADA sample and the (max titer of the post-treatment 
ADA) / (titer of baseline ADA) ≥ 4.
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Transient ADA is defined as:
•
Treatment-Induced ADA detected only at one sampling time point during the treatment or 
follow-up observation period (excluding the last sampling time point, which ought to be 
considered persistent unless shown to be undetectable at a later time) 
or
•
Treatment-Induced ADA detected at two or more sampling time points during the treatment 
(including follow-up period if any), where the first and last ADA-positive sample 
(irrespective of any negative samples in between) are separated by a period less than 
16 weeks, and the patient’s last sampling time point is ADA-negative.
ADA Transience Rate: the proportion of patients who had transient among patients for ADA 
incidence.
Persistent ADA is defined as 
•
Treatment-Induced ADA detected at two or more sampling time points during the treatment 
(including follow-up period if any), where the first and last ADA-positive sample 
(irrespective of any negative samples in between) are separated by a period of 16 weeks or 
longer.
or
•
Treatment-Induced ADA incidence (i.e. Treatment-induced ADA) only in the last sampling 
time point of the treatment study period or at a sampling time point with less than 16 weeks 
before an ADA-negative last sample. 
•
ADA Persistence Rate: the proportion of patients who had persistent ADA among patients 
for ADA incidence.
The following ADA categories will be summarized by cohorts. 
•
ADA prevalence
•
ADA positive post-baseline and positive at baseline
•
ADA not detected post-baseline and positive at baseline
•
ADA incidence
•
Treatment-induced ADA
•
Treatment-boosted ADA


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•
Persistent ADA
•
Transient ADA
•
nAb prevalence 
ADA titer and nAb data will be listed for samples confirmed positive for the presence of ADA to 
study drug. The effect of ADA on PK, safety and efficacy may be examined by descriptive 
summaries if data allow. 


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10. 
BIOMARKER ANALYSIS 
Version 1.0 
The baseline level, absolute level, and change from baseline level over time will be summarized 
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11.
REFERENCES
Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as Second-
Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376 
(11):1015-26.
Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab 
versus docetaxel in patients with previously treated non-small-cell lung cancer 
(OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 
2017;389 (10066):255-65.
Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel 
in heavily pretreated patients with small-cell lung cancer. Br J Cancer 1998;77 
(2):347-51.


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Statistical Analysis Plan
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12.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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13.
APPENDICES
13.1.
Appendix 1.
RECIST 1.1-based Assessments - Overall visit response
The RECIST tumour response data will be used to determine each patient’s visit response 
according to RECIST version 1.1. At each visit, patients will be assigned a RECIST 1.1 visit 
response of CR, PR, SD or PD, using the information from target lesions (TLs), non-target 
lesions (NTLs) and new lesions and depending on the status of their disease compared with 
baseline and previous assessments. If a patient has had a tumour assessment which cannot be 
evaluated, then the patient will be assigned a visit response of not evaluable (NE). For patients 
with no disease at baseline (i.e. no TLs and no NTLs), evaluation of overall visit responses will 
be based on absence/presence of new lesions.  If no TLs and no NTLs are recorded at a visit, 
both the TL and NTL visit response will be recorded as NA and the overall visit response will be 
no evidence of disease (NED). If a new lesion is observed then the overall visit response will be 
PD. Table 13-1 summarizes overall visit response given the visit responses from TL and NTL 
arecombined with new leision.
Table 13-1.
Overall Visit Response
Target lesions
Non-target lesions
New lesions
Overall response
CR
CR or NA
No
CR
CR
Non CR/Non PD or NE
No
PR
PR
Non PD or NE or NA
No
PR
SD 
Non PD or NE or NA
No
SD
NE
Non PD or NE or NA
No
NE
PD
Any
Any
PD
Any
PD
Any
PD
Any
Any
Yes
PD
NA
CR
No
CR
NA
Non CR/Non PD
No
SD
NA
NE
No
NE
NA
NA
No
NED
CR  Complete response, NA  Not applicable, PR  Partial response, SD  Stable disease, PD  Progression of disease, NE  Not 
evaluable, NED No evidence of disease.