Randomized, OpEn-Label, Active-ContrOl Trial of SPI-2012 (Eflapegrastim) Versus Pegfilgrastim in the Management of Chemotherapy-Induced Neutropenia in Early-Stage BReast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) (RECOVER)
Phase: PHASE3
Conditions: Neutropenia, Breast Cancer
Sponsor: Spectrum Pharmaceuticals, Inc

Offici al Titl e:  
R a n d o miz e d, O p E n -L a b el, Acti v e-C o ntr Ol Tri al of S PI -2 0 1 2 ( Efl a p e gr asti m) 
V ers us P e gfil gr asti m i n t h e M a n a g e m e nt of C h e m ot h er a p y -I n d uc e d 
N e utr o p e ni a i n E arl y -St a g e B R e ast C a nc er P ati e nts R ec ei vi n g D oc et a x el a n d 
C ycl o p h os p h a mi d e ( T C) ( R E C O V E R)  
N C T 0 2 9 5 3 3 4 0  
N C T  Nu m b er: 
D oc u m e nt  D at e : 
A m e n d m e nt 1 : 2 8 J ul 2 0 1 7 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1  
C O N FI D E N TI A L  
C LI NI C A L S T U D Y P R O T O C O L  
Title P a ge  
St u d y Title: 
St u d y N u m ber:  
St u d y P h ase:  
St u d y Dr u g:  
I N D N u m ber: 
S p o ns or:  
R a n d o mize d, O p E n- L a bel, Acti ve- C o nt r O l Tri al of S PI- 2 0 1 2 
( Efl a pe gr asti m) V ers us Pe gfil gr asti m i n t he M an a ge me nt of 
C he m ot her a p y- I n d uced Ne utr o pe ni a i n E arl y- S t a ge B R e ast C a ncer 
P ati e nts Recei vi n g D ocet a xel a n d C yc l o p h os p h a mi de ( T C) 
(R E C O V E R ) 
S PI- G C F- 3 0 2
P h ase 3  
S PI- 2 0 1 2 (efl a pe gr asti m)  
1 0 3, 4 6 1  
S pectr u m P h ar m ace uti c als, I nc. 
1 5 7 Tec h n ol o g y Dri ve 
Ir vi ne, C A, U S A 
Pr ot oc ol V ersi o n/ D ate:  
A me n d me nt 1 /2 8  J U L 2 0 1 7 
T his st u d y is t o be c o n d u cte d acc or di n g t o U S a n d i nter nati o nal sta n dar ds of G o o d Cli nical 
Practice ( F D A Title 2 1 part 3 1 2 a n d I nter nati o nal C o nfere nce o n Har m o nizati o n g ui deli nes), 
a p plica ble g o ver n me nt re g ulati o ns a n d I nstit uti o nal researc h p olicies a n d pr oce d ures.  
C o nfi de nti alit y St ate me nt  
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 d ata, is t he pr o per t y or 
u n der c o ntr ol of S pe ctr u m P har mace uticals, I n c. 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 v esti 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/ Et hics C o m mittee. T he i nf or mati o n is o nl y t o b e 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 d escri 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 
S pectr u m P har mace uticals , I nc. e x ce pt t o t he e xte nt necessar y t o o btai n Inf 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. 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2  
I N V E S TI G A T O R SI G N A T U R E  
 
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
R a n d o mize d, O p E n -L a bel, Acti ve -C o nt r O l Tri al of S PI-2 0 1 2 ( Efl a pe gr asti m) V ers us 
Pe gfil gr asti m i n t he M a n a ge me nt of C he m ot her a p y -I n d uce d Ne utr o pe ni a i n E arl y -St a ge 
B R e ast C a ncer P ati e nts Recei vi n g D ocet a xel a n d C ycl o p h os p h a mi de ( T C) ( R E C O V E R ) 
I h a ve rea d t his pr ot oc ol a n d a gree t hat it c o ntai ns all t he necess ar y details f or perf or mi n g t he 
st u d y i n acc or da n ce wit h t he Declarati o n of Helsi n ki a n d t he I nter n ati o nal C o nfere n ce o n 
Har m o ni z ati o n (I C H) f or G o o d Cli nical Practice ( G C P).  
I will pr o vi de c o pies of t he pr ot oc ol a n d of t h e cli nical a n d precli nical i nf or mati o n o n t he 
i n vesti gati o nal pr o d uct, w hic h was f ur nis he d t o me b y t he S p o ns or  ( S pectr u m P har mace uticals, 
I n c.), t o all me m bers of t he st u d y te a m res p o nsi bl e t o me w h o partici pat e i n t he st u d y. I will 
disc uss t his material wit h t he m t o ass ure t hat t he y are f ull y i nf or m e d re gar di n g t he  st u d y dr u g 
a n d t he c o n d uct of t h e st u d y.  
I will perf or m t he st u d y acc or di n g t o s pecifi cati o ns o utli ne d i n t he pr ot oc ol a n d a gree t o 
i m ple me nt pr ot oc ol re q uire me nts o nl y after t he pr ot oc ol a n d patie nt i nf or m ati o n/Inf or me d 
C o nse nt f or m ha ve bee n a p pr o ve d b y  t he I nstit uti o nal Re vie w B o ar d/ Et hics C o m mittee 
(I R B/ E C). I will s u b mit a n y pr ot oc ol m o dificati o ns (a me n d me nts) a n d/ or a n y Inf or me d C o nse nt 
f or m m o dificati o ns t o t he I R B/ E C, a n d a p pr o val will be o btai ne d bef ore a n y m o dificati o ns are 
i m ple me nte d. 
I u n d ersta n d t hat t he i nf or mati o n prese nte d i n t his st u d y pr ot oc ol is c o nfi d e ntial, a n d I h ere b y 
ass ure t hat n o i nf or mati o n base d o n t he c o n d u ct of t he st u d y will be releas e d wit h o ut pri or 
c o nse nt fr o m S pectr u m P har mace uticals, I nc.,  u nl ess t his re q uire me nt is s u pe rse de d b y a 
re g ulat or y a ut h orit y (e g, F D A ). 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
I n vesti g at or N a me ( P L E A S E P RI N T):  
 
Si g n at ure: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ D ate _ _ _ _ _ _ _ _ _ _ _ _ _ _  
 
 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3  
S Y N O P SI S  
Title of St u d y: R a n d o mize d, O p E n -L a bel, Acti ve -C o ntr O l Tri al of S PI-2 0 1 2 ( Efl a pe gr asti m) V ers us 
Pe gfil gr asti m i n t he M a n a ge me nt of C he m ot her a p y -I n d u ce d Ne utr o pe ni a i n E arl y -St a ge B R e ast C a ncer 
P atie nts Recei vi n g D ocet a xel a n d C ycl o p h os p h a mi de ( T C) ( R E C O V E R ) 
N a me of S p o ns or:  S pectr u m P har mace uticals, I nc.  
N a me of I n vesti g ati o n al Pr o d uct: S PI -2 0 1 2   
Pl a n ne d N u m ber of P atie nts:  A p pr o xi matel y 2 1 8  patie nts  
St u d y Ce nters:  A p pr o xi matel y 8 0  st u d y ce nters 
D ur ati o n of St u d y : A p pr o xi matel y 2 8  m o nt hs  wit h 1 6  m o nt hs f or 
e nr oll me nt a n d treat me nt  a n d 1 2 m o nt hs f or safet y f oll o w -u p.   
Cli nic al P h ase:  3  
O bjecti ves:  
Pri m ar y O bjecti ve : 
T o c o m pare t he efficac y of  a si n gle d ose of  S PI -2 0 1 2  wit h p e gfil grasti m i n patie nts wit h e arl y-sta ge breast 
ca ncer recei vi n g d oceta xel a n d c ycl o p h os p ha mi de ( T C), as meas ure d b y t he D ur ati o n of S e vere N e utr o pe ni a  
(D S N ) i n C ycle 1  
Ke y Sec o n d ar y O bjecti ves:  
•  
T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m i n:  
1.  Ti me t o A bs ol ute Ne utr o p hil C o u nt  ( A N C) Rec o ver y i n C ycle 1  
2.  De pt h of A N C N a dir , defi ne d as t he patie nt’s l o west A N C i n C ycle 1  
3.  I nci de nce of Fe brile Ne utr o p e ni a  (F N ) i n patie nts d uri n g C ycle 1  
A d diti o n al Sec o n d ar y O bjecti ve s: 
•  
T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m  i n: 
1.  D ur ati o n of Se vere Ne utr o pe ni a  i n C ycles 2 , 3 , a n d 4  
2.  I nci de nce of Ne utr o pe nic C o m plicati o ns, i ncl u di n g a nti -i nfecti ve use a n d h os pitalizati o ns i n patie nts 
d uri n g C ycle 1   
3.  I nci de nce of F N  i n C ycles 2 , 3 , a n d 4  
4.  Rel ati ve D ose I nte nsit y  (R DI ) of T C i n C ycles 1  t o 4  
5.  Safet y  
St u d y Desi g n  a n d Tre at me nt Pl a n : 
T his is a P hase 3, ra n d o mize d, o pe n -la bel, acti ve-c o ntr olle d, m ultice nter  st u d y t o c o m pare t he efficac y a n d 
safet y of S PI -2 0 1 2  wit h pe gfil grasti m  i n breast ca ncer patie nts treate d wit h T C c he m ot hera p y.  
A p pr o xi matel y 2 1 8  patie nts will be e nr olle d a n d ra n d o mize d i n a 1: 1 rati o t o 2 treat me nt ar ms:  
•  
Tre at me nt Ar m 1  ( n = a p pr o xi matel y 1 0 9 ): S PI -2 0 1 2  (1 3. 2 m g/ 0. 6 m L fi xe d d ose S PI -2 0 1 2  e q ui vale nt 
t o 3. 6  m g  G -C S F ) 
•  
Tre at me nt Ar m 2  ( n = a p pr o xi matel y 1 0 9 ): P e gfil grasti m ( 6 m g/ 0. 6 mL )  
Pri or t o T C c he m ot hera p y a d mi nistrati o n, patie nts ma y  rec ei ve pre me dicati o n acc or di n g t o i nstit uti o nal sta n dar d 
of care . I ntra ve n o us (I V) a d mi nistrati o n of T C o n Da y 1 of e ac h c ycle will be as f oll o ws:  
•  
D oceta xel 7 5 m g/ m 2 I V i nf usi o n per i nstit ute ’s sta n dar d of care 
•  
C ycl o p h os p ha mi de 6 0 0 m g/ m 2 I V i nf usi o n per i nstit ute ’s sta n dar d of care  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4  
Eac h c ycle will be 2 1 da ys. O nl y 4 c ycles will be e val uate d f or t his st u d y After C ycle 1 , patie nts m ust ha ve 
A N C  ≥1. 5 × 1 0 9/ L a n d platelet c o u nt ≥1 0 0 × 1 0 9/ L t o be gi n ea ch of t he ne xt c ycles of c he m ot hera p y .  
T he st u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m ) will be a d mi nistere d o n D a y 2  of eac h c ycle, a p pr o xi matel y 2 4 t o 
2 6  h o urs after t he last d ose of T C c he m ot hera p y is gi ve n.  St u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m) d ose 
m o dificati o ns are n ot all o we d.  
O n D a y 1  of eac h c ycle, patie nts will recei ve T C c he m ot her a p y , a n d safet y a n d efficac y assess me nts will be 
perf or me d as o utli ne d i n t he pr ot oc ol. O n D a y 2  of eac h c ycle, patie nts will recei ve st u d y dr u g ( S PI -2 0 1 2  or 
pe gfil grasti m) , a n d  t he s pecifi e d assess me nts will be perf or me d .  
A bs ol ute ne utr o p hil c o u nt will be m o nit ore d  o n D a y 1  a n d D a ys 4  t o 1 5  i n C ycle 1 . I n C ycles 2  t o 4 , all patie nts 
m ust ha ve bl o o d sa m ples dra w n o n D a y 1  ( pri or t o c he m ot hera p y a d mi nistrati o n), o n D a ys 4 , 7 , 1 0 , a n d 1 5  
( ± 1 da y f or eac h c ollecti o n), a n d at t he E n d -of -Tre at me nt Visit . If t he partici pati n g site is n otifie d t hat t he  A N C 
is ≤1. 0 × 1 09/ L at a n y ti me d uri n g C ycles 2  t o 4 , t he n dail y C B Cs will be req uire d u ntil t he A N C is ≥1. 5 × 1 0 9/ L, 
after reac hi n g na dir, b ut bl o o d sa m ples m ust still be dra w n o n D a ys 4 , 7 , 1 0 , a n d 1 5 .  
A fter C ycle 1 , as a p plica ble, patie nts w h o ha ve recei ve d at l east o ne d ose of st u d y dr u g will  be  f oll o we d f or 
1 2  m o nt h s after t he last d ose of st u d y treat me nt f or safet y f oll o w-u p .  
D ur ati o n of St u d y:  A p pr o xi matel y 2 8  m o nt hs wit h 1 6  m o nt hs f or e nr oll me nt a n d treat me nt a n d 1 2 m o nt hs f or 
safet y f oll o w-u p.  
T he d urati o n of t he st u d y f or eac h patie nt i n S PI -G C F -3 0 2  will be a p pr o xi matel y 1 6  m o nt hs i ncl u di n g:  
•  
Scree ni n g Peri o d : 3 0  da ys  
•  
Tre at me nt Peri o d : 4 c ycles, 2 1 da ys per c ycle  
•  
E n d -of -Tre at me nt Visit:  3 5( ± 5) da ys  after last d ose of st u d y treat me nt 
•  
S afet y F oll o w -u p  Peri o d : 1 2 m o nt hs  after t he  last d ose of st u d y treat me nt 
•  
E n d -of -St u d y Visit:  At t he 1 2 M o nt h Visit  or 3 5 ( ± 5)  da ys after t he date of earl y disc o nti n uati o n   
P atie nt Re pl ace me nt Str ate g y:  P atie nts w h o disc o nti n ue fr o m t he st u d y pri or t o ra n d o mi zati o n will be 
re place d. 
I ncl usi o n & E xcl usi o n Crite ri a:  
I ncl usi o n Criteri a: 
1.  P atie nt or le gall y a ut h orize d re prese ntati ve m ust be willi n g a n d ca pa ble of gi vi n g writte n I nf or me d 
C o nse nt a n d m ust b e a ble t o a d here t o d osi n g a n d visit sc he d ules a s well as meet all st u d y re q uire me nts.   
2.  P atie nt m ust ha ve  ne w l y dia g n os e d , hist ol o gicall y c o nfir me d earl y-sta ge breast ca ncer ( E S B C) defi ne d 
as o pera ble S ta ge I t o S ta ge III A breast ca ncer.  
3.  P atie nt m ust  be a ca n di date t o recei ve a dj u va nt or ne oa dj u va nt  T C c he m ot hera p y.  
4.  P atie nt ( male or fe male) m ust be at least 1 8 years of a ge.  
5.  P atie nt m ust ha ve  a d e q uate he mat ol o gical, re nal a n d he patic f u ncti o n as defi ne d b y : 
•  
A N C ≥1. 5 × 1 0 9/ L 
•  
Platelet c o u nt ≥1 0 0 × 1 0 9/ L 
•  
He m o gl o bi n > 9 g/ d L  
•  
Calc ulate d creati ni ne cleara nc e > 5 0 m L/ mi n  
•  
T otal bilir u bi n ≤1. 5 m g/ d L  
•  
As partate a mi n otra nsferase ( A S T)/ser u m gl uta mic -o xal oacetic tra nsa mi nase ( S G O T) a n d ala ni ne 
a mi n otra nsferase (A L T )/ser u m gl uta mic-p yr u vic tra nsa mi nase ( S G P T) ≤2. 5 × U L N, a n d al kali ne 
p h os p hatase ≤2. 0 × U L N  
6.  P atie nt 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 ≤2.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
5  
7.  P atie nt m ust b e  willi n g t o practice t w o f or ms of c o ntrace pti o n, o ne of w hic h m ust be a barrier met h o d, 
fr o m st u d y e ntr y t hr o u g h 3 0 da ys after t he last d ose of st u d y dr u g a d mi nistrati o n or 3 0 da ys after date of 
patie nt earl y  disc o nti n uati o n.  
8.  Fe males of c hil d beari n g p ote ntial m ust ha ve a ne gati ve uri ne  pre g na nc y test wit hi n 3 0 da ys  pri or t o 
ra n d o mizati o n. Fe males w h o are p ost me n o pa usal f or at least 1 year ( defi ne d as m ore t ha n 1 2 m o nt hs 
si nce last me nses) or are s ur gi call y sterilize d d o n ot re q uire t his test. 
E xcl usi o n Criteri a:  
1.  P atie nt wit h a n acti ve c o nc urre nt mali g na nc y (e xce pt n o n mela n o ma s ki n ca ncer or carci n o ma i n sit u of 
t he cer vi x) or life-t hreate ni n g disease. If t here is a hist or y of pri or mali g na ncies or c o ntralatera l breast 
ca ncer, t he patie nt m ust b e dis ease free f or at least 5 years. 
2.  P atie nt wit h k n o w n se nsiti vit y or pre vi o us reacti o n t o Esc heric hi a c oli  (E. c oli ) deri ve d pr o d ucts (e g, 
fil grasti m, rec o m bi na nt i ns uli n [ H u m uli n ®], L-as para gi nas e, s o matr o pi n [ H u matr o p ®] gr o wt h h or m o ne, 
rec o m bi na nt i nterfer o n alfa-2 b [I ntr o n ® A]), or a n y of t he pr o d ucts t o be a d mi nistere d d uri n g st u d y 
partici pati o n.  
3.  P atie nt wit h c o nc urre nt a dj u va nt ca ncer t hera p y (c he m ot hera p y, ra diati o n t hera p y, i m m u n ot hera p y, 
bi ol o gic t hera p y ot her t ha n t he trial -s pecifie d t hera pies).  
4.  P atie nt has l ocall y rec urre nt/metastatic breast ca ncer . 
5.  P atie nt wit h pre vi o us e x p os ur e t o fil grasti m, pe gfil grasti m, or ot her G -C S F pr o d ucts i n cli nical 
de vel o p me nt wit hi n 1 2 m o nt hs pri or t o t he a d mi nistrati o n of st u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m) .  
6.  P atie nt wit h a n acti ve i nfecti o n  or recei vi n g a nti -i nfecti ves, a n u n derl yi n g me dical c o n diti o n, or a not her 
seri o us ill ness t hat w o ul d i m p air t he a bilit y of t he patie nt t o recei ve pr ot oc ol -s pecifie d treat me nt. 
7.  P atie nt has use d a n y i n vesti gati o nal dr u gs, bi ol o gics, or de vices wit hi n 3 0  da ys pri or t o st u d y treat me nt 
or pla ns t o use a n y of t hese d uri n g t he c o urse of t he st u d y.  
8.  P atie nt has ha d pri or b o ne marr o w or he mat o p oietic ste m cell tra ns pla nt. 
9.  P atie nt has ha d pri or ra diat i o n t hera p y wit hi n 3 0 da ys  pri or t o  e nr oll me nt . 
1 0.  P atie nt has ha d maj or s ur ger y wit hi n 3 0 da ys pri or t o e nr oll me nt. P atie nts w h o ha ve breast s ur ger y 
relate d t o t he breast ca ncer dia g n osis or ha ve ha d a p ort-a-cat h place me nt ma y be e nr olle d pri or t o 
3 0  da ys o nce t he y ha ve f ull y rec o vere d fr o m t he pr oce d ure.  
1 1.  P atie nt is pre g na nt or breast -fe e di n g. 
I n vesti g ati o n al Pr o d uct, D ose, a n d R o ute of A d mi nistr ati o n:  
S PI -2 0 1 2  ( 0. 6 m L) is s u p plie d i n a prefille d , si n gle-use s yri n ge f or s u bc uta ne o us i nj ecti o n. Eac h prefille d  
s yri n ge of S PI -2 0 1 2  c o ntai ns 1 3. 2 m g S PI -2 0 1 2 , w hic h is e q ui vale nt t o a  d ose of 3. 6 m g of G -C S F.  
T he d ose of S PI -2 0 1 2  is t o be a d mi nistere d s u bc uta ne o usl y o n Da y 2, a p pr o xi matel y 2 4 t o 2 6 h o urs  after T C 
a d mi nistrati o n. 
Refere nce T her a p y, D ose, a n d R o ute of A d mi nistr ati o n:  
O nl y pe gfil grasti m ( Ne ulasta), ma n ufact ure d b y A m ge n i n t he U nite d States ( N D C 5 5 5 1 3 -1 9 0 -0 1) will be use d 
i n t his st u d y; n o ot her G -C S Fs, i ncl u di n g bi osi mil ars, are t o be use d i n t his st u d y.  
P e gfil grasti m will b e s u p plie d b y S p ectr u m t o all sites ( U S a n d e x-U S) i n 6 m g/ 0. 6 m L prefille d  si n gle-use 
s yri n ges f or s u bc uta ne o us i nj ecti o n. Eac h s yri n ge c o ntai ns 6 m g G -C S F  i n a sterile s ol uti o n. 
P e gfil grasti m s h o ul d be a d mi nistere d s u bc uta ne o usl y o nce per c he m ot hera p y c ycle o n D a y 2 , a p pr o xi matel y 2 4 
t o 2 6 h o urs after T C a d mi nistrati o n , acc or di n g t o t he ma n ufa ct urer’s prescri bi n g i nf or mati o n. 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
6  
Effic ac y Assess me nts:  
Pri m ar y E n d p oi nt:  
•  
C o m paris o n of t he D ur ati o n of S e vere N e utr o pe ni a  (D S N ) i n C ycle 1  bet wee n t he S PI -2 0 1 2 
Tre at me nt Ar m  a n d  t he Pe gfil gr asti m Tre at me nt Ar m .  
D S N  is defi ne d as t he n u m ber of da ys of se vere ne utr o pe nia ( A N C < 0. 5 × 1 0 9/ L) fr o m t he first occ urre nce of a n 
A N C bel o w t he t hres h ol d . T he assess me nt of A N C will be perf or me d o n D a y 1  a n d D a ys 4  t o 1 5  i n C ycle 1 . 
T he e n d p oi nt will b e meas ure d i n all patie nts  i n an  Inte nt -t o-T re at P o p ul ati o n  (I T T P o p ul ati o n). F or patie nts 
w h o d o n ot meet se vere ne utr o pe nia criteria , t he e n d p oi nt meas ureme nt  will be defi ne d as D S N = 0.  
Ke y Sec o n d ar y E n d p oi nts:  
•  
T o c o m pare S PI -2 0 1 2  wit h pe gf il grasti m i n: 
1.  Ti me t o A N C Rec o ver y  i n C ycle 1   
2.  De pt h of A N C N a dir , defi ne d as t he patie nt’s l o west A N C i n C ycle 1  
3.  I nci de nce of F N  i n patie nts d uri n g C ycle 1  
T he a nal yses of t he Ke y Sec o n dar y E n d p oi nts will e m pl o y a hierarc hical , cl ose d testi n g pr oce d ure . 
A d diti o n al Sec o n d ar y E n d p oi nts:  
•  
T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m i n:  
1.  D ur ati o n of Se vere Ne utr o pe ni a  i n C ycles 2 , 3 , a n d 4  
2.  I nci de nce of Ne utr o pe nic Co m plicati o ns, i ncl u di n g use of a nti -i nfecti ves a n d h os pitalizati o ns, i n 
patie nts d uri n g C ycle 1  
3.  I nci dences of F N  i n C ycles 2 , 3 , a n d 4  
4.  R DI  of T C i n C ycles 1  t o 4  
5.  Safet y  
P h ar m ac o ki netic Assess me nts:  
All patie nts i n t he S PI -2 0 1 2  treat me nt ar m will ha ve bl o o d sa m ples dra w n f or s parse P K sa m pli n g at 6 ti me 
p oi nts d uri n g t he st u d y peri o d f or P K a nal ysis. T he sa m pli n g ti me p oi nts will be: 
•  
C ycle 1 :  
•  
D a y 2  ( 1 t o 4 h o urs after S PI -2 0 1 2  a d mi nistrati o n)  
•  
D a y 4  (at t he sa me ti me as C B C bl o o d dra w) 
•  
D a y 5  (at t he sa me ti me as C B C bl o o d dra w) 
•  
C ycle 3 : 
•  
D a y 2  ( 1 t o 4 h o urs p ost-d ose)  
•  
D a y 4  (± 1 da y, at t he sa me ti me as C B C bl o o d dra w ) 
•  
D a y 7  (± 1 da y, at t he sa me ti me as C B C bl o o d dra w)  
S afet y Assess me nts:  
Safet y (sec o n dar y e n d p oi nt) will be assesse d b y re p orte d/elicite d  a d verse e ve nts  (A Es ), la b orat or y assess me nts, 
a n d p h ysical e xa mi nati o ns.  I n a d diti o n, as a p plica ble, patie nts w h o recei ve at least o ne d ose of st u d y dr u g will 
be f oll o we d f or 1 2 m o nt hs aft er t he  last d ose of st u d y treat me nt t o assess l o n g-ter m safet y; patie nts w h o recei ve 
S PI -2 0 1 2  will b e teste d f or a nti b o dies t o S PI -2 0 1 2 , t he Fc re gi o n of t he S PI -2 0 1 2  m o lec ule, t he P E G m oiet y, 
a n d G-C S F . P atie nts  w h o recei ve pe gfil grasti m will be teste d f or a nti b o dies t o S PI -2 0 1 2 , P E G a n d G -C S F. All 
sera sa m ples p ositi ve f or G-C S F -bi n di n g a nti b o dies will be f urt her teste d f or G -C S F ne utr alizi n g a nti b o dies.   
A d verse E ve nt a n d Seri o us A d verse E ve nt Re p orti n g:  
All A Es t hat occ ur fr o m t he first d ose of st u d y treat me nt t hr o u g h at least 3 5( ± 5) da ys after t he date of last st u d y 
treat me nt or date of patie nt earl y disc o nti n uati o n  are t o be rec or de d o n t he A E C R F . A d diti o nall y, as ap plica ble  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
7  
patie nts w h o recei ve at least o ne d ose of st u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m ) will be f oll o we d f or 1 2 m o nt hs  
after t he  last d ose of st u d y treat me nt t o e val uate t he l o n g-ter m safet y a n d i m m u n o ge nicit y of S PI -2 0 1 2 . All A Es 
d uri n g t his ti me peri o d will be rec or de d. Fr o m t he ti me t he st u d y I nf or me d C o nse nt is si g ne d t hr o u g h t he first 
d ose of st u d y dr u g a d mi nistrati o n, o nl y S A Es t hat are relate d t o st u d y pr oce d ures are t o be rec or de d.  
St atistic al M et h o ds:  
F or  t he pri mar y efficac y a nal ysis, t he mea n D S N  i n C ycle 1  will be c o m pare d bet wee n t he S PI -2 0 1 2  a n d 
Pe gfil gr asti m Tre at me nt Ar m s usi n g a b o otstra p resa m pli n g met h o d wit h n o n -i nferi orit y h y p ot hesis. A 
2 -si de d 9 5 % co nfi de nce inter val  ( CI) of t he differe nce bet we e n  t he mea n D S N  of t he S PI -2 0 1 2  Tre at me nt A r m 
a n d t he mea n D S N  of t he Pe gfil gr asti m Tre at me nt Ar m  will be calc ulate d usi n g b o otstra p resa m pli n g  wit h 
treat me nt as t he o nl y stratificati o n fact or. T he st u d y will use a n o n -i nferi orit y mar gi n of 0. 6 2  da y f or t he a b o ve 
c o m paris o n.  
T he n o n -i nferi orit y of S PI -2 0 1 2  t o pe gfil grasti m will be declare d if t he u p per b o u n d of 9 5 % CI of t he differe nce 
i n mea n D S N  bet wee n t he treat me nt ar ms is < 0. 6 2 da y s. Pri mar y a nal ysis f or t he  n o n -i nferi orit y h y p ot hesis will 
be base d o n  t he I T T Po p ul ati o n . An a nal ysis base d o n t he P er P r ot oc ol P o p ul ati o n  will be perf or me d as  a 
se nsiti vit y a nal ysis.  
F or t he sec o n dar y efficac y a nal yses, t he res ults will eac h be s u m marize d b y T reat me nt Ar m a n d C ycle . The t w o -
si de d 9 5 % CI f or t he differe nc e bet wee n t he treat me nt ar ms will be calc ulate d.  
F or safet y a nal ysis, t he n u m ber a n d perce nta ge of patie nts wit h a n y treat me nt-e mer ge nt A Es ( T E A Es ), a n y 
seri o us A Es (S A Es ), T E A Es relate d t o st u d y dr u gs, a n d T E A Es ca usi n g treat me nt disc o nti n uati o n  will be 
s u m marize d. A d verse E ve nts of S pecial I nterest ( A E SI) ( m usc ul os keletal pai n, i nj ecti o n site reacti o ns, a n d 
h y perse nsiti vit y reacti o ns ) will b e assesse d a n d s u m marize d b y Preferre d T er m.  A n e x p os ure -res p o nse a nal ysis 
will b e perf or me d base d o n s p ar se P K sa m pli n g. 
Sa m ple size esti mates are base d o n a n o n -i nferi orit y desi g n. T he mar gi n of n o n-i nferi orit y is 0. 6 2 da ys. T he tr ue 
differe nce bet wee n t he mea ns is ass u me d t o be 0. 0 da ys. Sa m ple sizes of 1 0 9  per treat me nt ar m will pr o vi de 
9 0 %, 8 6 %, a n d 8 1 % p o wer t o detect n o n -i nferi orit y usi n g a o ne-si de d, t w o-sa m ple t-test at 2. 5 % le vel of 
si g nifica nce, w he n t he p o ole d sta n dar d de viati o n ( S D) of t he D S N  is 1.4 , 1.5 , or 1.6  da ys, res pecti vel y. T he 
p o ole d S D will be m o nit ore d i n t he o n g oi n g sister st u d y S PI -G C F -3 0 1 . If t he p o ole d S D i n t he sister st u d y is 
esti mate d t o be greater t ha n 1. 4  da ys, t he sa m ple size ma y b e i ncrease d t o reflect t he p ote ntial e xtra varia bilit y 
f or t he c urre nt st u d y. Si nce t he i nf or mati o n t hat ma y be use d is i n de p e n de nt of t he c urre nt stu d y res ults, t he 
n o mi nal t y pe I err or is preser ve d f or t he c urre nt st u d y.   
T he st u d y will e nr oll a n d ra n d o mize a p pr o xi matel y 1 0 9  patie nts per ar m f or a t otal of a p pr o xi matel y 
2 1 8  patie nts.  
Versi o n/ D ate : 2 8  J ul 2 0 1 7  
 
 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1 1  
T A B L E O F C O N T E N T S  
I N V E S TI G A T O R SI GN A T U R E  ..................................................................................................2  
T A B L E O F C O N T E N T S  ............................................................................................................1 1  
List of T a bles  ..........................................................................................................................1 4  
List of Fi g ures  .........................................................................................................................1 4  
LI S T O F A B B R E VI A TI O N S  .....................................................................................................1 5  
1  
I N T R O D U C TI O N ................................................................................................................1 7  
1. 1  
B ac k gr o u n d  ................................................................................................................1 7  
1. 1. 1  
Bre ast C a ncer a n d R ole of Gr a n ul oc yte C ol o n y Sti m ul ati n g F a ct or  ...........1 7  
1. 1. 2  
S PI -2 0 1 2 ( Efl a pe gr asti m [ R ol o nti s ™]) ............................................................1 9  
1. 1. 2. 1  
N o ncli nic al St u dies  ........................................................................................1 9  
1. 1. 2. 2  
Cli nic al E x perie nce  .......................................................................................2 0  
1. 1. 2. 3  
P h ase 1 St u dies  ..............................................................................................2 0  
1. 2  
R ati o n ale f or t he C urre nt St u d y  ...............................................................................2 4  
2  
S T U D Y O B J E C TI V E S  ........................................................................................................2 5  
2. 1  
Pri m ar y O bjecti ve  ......................................................................................................2 5  
2. 2  
Ke y Sec o n d ar y O bjecti ves  .........................................................................................2 5  
2. 3  
A d diti o n al Sec o n d ar y O bjecti ves  .............................................................................2 5  
3  
I N V E S TI G A TI O N A L P L A N ..............................................................................................2 6  
3. 1  
St u d y Desi g n a n d Tre at me nt Pl a n ............................................................................2 6  
3. 2  
St u d y a n d Tre at me nt D ur ati o n  ................................................................................2 8  
4  
P A TI E N T P O P U L A TI O N  ...................................................................................................2 9  
4. 1  
I ncl usi o n Criteri a .......................................................................................................2 9  
4. 2  
E xcl usi o n Criteri a  ......................................................................................................2 9  
4. 3  
P a ti e nt Disc o nti n u ati o n/ Wit h dr a w al Criteri a .........................................................3 0  
5  
S T U D Y P R O C E D U R E S  ......................................................................................................3 1  
5. 1  
Scree ni n g  .....................................................................................................................3 1  
5. 2  
P ati e nt Assi g n me nt  ....................................................................................................3 1  
5. 3  
Ti mi n g of Assess me nts a n d Pr oce d ures  ...................................................................3 1  
5. 3. 1  
Scree ni n g ( D a ys -3 0 t o -1)  .................................................................................3 1  
5. 3. 2  
Tre at me nt Peri o d –  C ycle 1, D a y 1 ( B aseli ne)  ................................................3 2  
5. 3. 3  
Tre at me nt Peri o d –  C ycle 1, D a y 2  ..................................................................3 2  
5. 3. 4  
Tre at me nt Peri o d –  C ycle 1, D a ys 4 t o 2 1  .......................................................3 3  
5. 3. 5  
Tre at me nt Peri o d –  C ycles 2 t o 4, D a y 1  .........................................................3 3  
5. 3. 6  
Tre at me nt Peri o d –  C ycles 2 t o 4, D a y 2  .........................................................3 3  
5. 3. 7  
Tre at me nt Peri o d –  C ycles 2 t o 4, D a ys 3 t o 2 1  ..............................................3 3  
5. 3. 8  
E n d -of -Tre at me nt Visit ( At t he e n d o f C ycle 4 or A p pr o xi m atel y 3 5 ( ± 5) 
d a ys After D ate of E arl y Disc o nti n u ati o n) ....................................................3 4  
5. 3. 9  
1 2 M o nt h S afet y F oll o w -u p  ...............................................................................3 4  
5. 3. 9. 1  
Tele p h o ne C o nt act  .........................................................................................3 4  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1 2  
5. 3. 9. 2  
Cli nic Visit  .....................................................................................................3 4  
5. 3. 1 0  
E n d of St u d y Visit ( M o nt h 1 2 Visit or 3 5 ( ± 5) d a ys after e arl y 
disc o nti n u ati o n)  ...............................................................................................3 5  
5. 4  
Descri pti o n of St u d y Assess me nts a n d Pr o ce d ures .................................................3 5  
5. 4. 1  
E x pl a n ati o n of St u d y a n d O bt ai ni n g Writte n I nf or me d C o nse nt  ................3 5  
5. 4. 2  
Me dic al Hist or y  .................................................................................................3 5  
5. 4. 3  
Re vie w I ncl usi o n/ E xcl usi o n Criteri a  ...............................................................3 5  
5. 4. 4  
R a n d o miz ati o n  ...................................................................................................3 5  
5. 4. 5  
P h ysic al E x a mi n ati o n  ........................................................................................3 5  
5. 4. 6  
E C O G Perf or m a nce St at us  ..............................................................................3 6  
5. 4. 7  
Vit al Si g n Assess me nts  ......................................................................................3 6  
5. 4. 8  
B o d y Te m per at ure  .............................................................................................3 6  
5. 4. 9  
C o m plete Bl o o d C o u nt  ......................................................................................3 6  
5. 4. 1 0  
C he mistr y  ...........................................................................................................3 7  
5. 4. 1 1  
P h ar m a c o ki netic Assess me nts  ..........................................................................3 7  
5. 4. 1 2  
A nti -I nfecti ve Use ..............................................................................................3 7  
5. 4. 1 3  
I m m u n o ge nicit y Testi n g ...................................................................................3 7  
5. 4. 1 4  
A d verse E ve nt  ....................................................................................................3 8  
5. 4. 1 5  
C o nc o mit a nt Me dic ati o ns  .................................................................................3 8  
6  
S T U D Y D R U G A N D P H A R M A C E U TI C A L I N F O R M A TI O N  .....................................3 8  
6. 1  
S PI -2 0 1 2  ......................................................................................................................3 8  
6. 1. 1  
S PI -2 0 1 2 C o m p ositi o n  .......................................................................................3 8  
6. 1. 2  
S PI -2 0 1 2 St or a g e a n d H a n dli n g  .......................................................................3 8  
6. 1. 3  
S PI -2 0 1 2 A d mi nistr ati o n  ..................................................................................3 8  
6. 2  
Pe gfil gr asti m  ...............................................................................................................3 9  
6. 2. 1  
Pe gf il gr asti m C o m p ositi o n ...............................................................................3 9  
6. 2. 2  
Pe gfil gr asti m S u p pl y  .........................................................................................3 9  
6. 2. 3  
Pe gfil gr asti m St or a g e a n d H a n dli n g  ................................................................3 9  
6. 2. 4  
Pe gfil gr asti m A d mi nist r ati o n  ...........................................................................3 9  
6. 3  
Bli n di n g of St u d y Tre at me nts  ...................................................................................3 9  
6. 4  
R a n d o miz ati o n of St u d y Tre at me nts  .......................................................................3 9  
6. 5  
N o n -st u d y Tre at me nts ...............................................................................................3 9  
6. 5. 1  
Pri o r a n d C o nc o mit a nt Me dic ati o ns  ...............................................................3 9  
6. 5. 2  
Pr o hi bite d T her a pies or Me dic ati o ns  ..............................................................4 0  
7  
S A F E T Y A S S E S S M E N T  .....................................................................................................4 0  
7. 1  
S afet y Me as ures  .........................................................................................................4 0  
7. 2  
A d verse E ve nts  ...........................................................................................................4 0  
7. 3  
G ui del i nes f or Rec or di n g a n d Attri b uti o n Sc ori n g of A d verse E ve nts ................4 1  
7. 3. 1  
Rec or di n g of A d verse E ve nts  ...........................................................................4 1  
7. 3. 2  
Gr a di n g of A d verse E ve nts  ...............................................................................4 2  
7. 4  
F oll o w -u p of A d verse E ve nts  ....................................................................................4 2  
7. 5  
Rel ati o ns hi p  ................................................................................................................4 2  
7. 6  
E x pecte d ness  ...............................................................................................................4 3  
7. 7  
Seri o us A d verse E ve nts  .............................................................................................4 3  
7. 7. 1  
Seri o us A d verse E ve nt Re p orti n g  ....................................................................4 4  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1 3  
7. 7. 2  
E xcl usi o ns t o Seri o us A d verse E ve nt Re p orti n g Re q uire me nts  ....................4 5  
7. 8  
Re pr o d ucti ve Ris ks  ....................................................................................................4 5  
8  
S T A T I S TI C A L P L A N..........................................................................................................4 5  
8. 1  
S a m ple Size  .................................................................................................................4 5  
8. 2  
Met h o d of Tre at me nt Assi g n me nt, R a n d o miz ati o n, a n d/ or Str atific ati o n  ..........4 6  
8. 3  
A n al ysis P o p ul ati o ns  ..................................................................................................4 6  
8. 4  
Ge ner al St atistic al Met h o ds  ......................................................................................4 6  
8. 5  
Effic ac y A n al yses  .......................................................................................................4 6  
8. 5. 1  
Pri m ar y E n d p oi nt  ..............................................................................................4 6  
8. 5. 2  
Ke y Sec o n d ar y E n d p oi nts  .................................................................................4 8  
8. 5. 3  
A d diti o n al Sec o n d ar y E n d p oi nts  .....................................................................4 8  
8. 6  
A n al ysis of S afet y  .......................................................................................................4 8  
8. 7  
Cli nic al L a b or at or y a n d Vit al Si g ns E v al u ati o ns  ...................................................4 9  
9  
A D MI NI S T R A TI V E P R O C E D U R E S A N D S T U D Y M A N A G E M E N T  ........................4 9  
9. 1  
I n vesti g at or Res p o nsi bilities .....................................................................................4 9  
9. 1. 1  
G o o d Cli nic al Pr a ctice  ......................................................................................4 9  
9. 1. 2  
I nstit uti o n al Re vie w B o ar d/ Et hics C o m mittee A p pr o v al ..............................5 0  
9. 1. 3  
I nf or me d C o nse nt ..............................................................................................5 0  
9. 1. 4  
St u d y Files a n d Rete nti o n of Rec or ds  ..............................................................5 0  
9. 2  
Rec or di n g a n d C ollecti n g of D at a  ............................................................................5 0  
9. 2. 1  
C ase Re p ort F or ms  ............................................................................................5 0  
9. 2. 2  
Dr u g Acc o u nt a bilit y  ..........................................................................................5 0  
9. 3  
Pr ot oc ol C o m pli a nce  ..................................................................................................5 1  
9. 4  
S p o ns or Res p o nsi bilities  ............................................................................................5 1  
9. 4. 1  
St u d y M o nit ori n g  ...............................................................................................5 1  
9. 4. 2  
S afet y M o nit ori n g  ..............................................................................................5 1  
9. 5  
J oi nt I n vesti g at or/ S p o ns or Res p o nsi bilities  ............................................................5 1  
9. 5. 1  
Access t o I nf or m ati o n f or M o nit ori n g a n d A u diti n g  .....................................5 1  
9. 5. 2  
Ter mi n ati o n of t he St u d y  ..................................................................................5 1  
9. 5. 3  
P u blic ati o n P olic y  ..............................................................................................5 2  
9. 6  
C o nfi de nti alit y  ............................................................................................................5 2  
1 0  R E F E R E N C E S  .....................................................................................................................5 3  
A P P E N DI X 1  
S C H E D U L E O F A S S E S S M E N T S A N D P R O C E D U R E S - C Y C L E 1  ......5 6  
A P P E N DI X 2  
S C H E D U L E O F A S S E S S M E N T S A N D P R O C E D U R E S - C Y C L E S 2 T O 
4  
5 7  
 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1 4  
List of T a bles  
T a ble 1  
Re p orte d I nci de nce of Fe brile Ne utr o pe ni a Ass oci ate d wit h T C as A dj u v a nt 
T her a p y wit h a n d wit h o ut G -C S F Pr o p h yl a xis i n P atie nts wit h E arl y -St a ge 
Bre ast C a ncer  ............................................................................................................1 8  
T a ble 2  
S u m m ar y of Tre at me nt -Rel ate d Tre at me nt -E mer ge nt A d verse E ve nts ( ≥5 %) 
b y Preferre d Ter m -P h ase 2 St u d y S PI -G C F -1 2 -2 0 1  .............................................2 3  
T a ble 3  
S u m m ar y of Seri o us Tre at me nt -E mer g e nt A d v erse E ve nts b y Preferre d Ter m -
P h ase 2 St u d y - S PI -G C F -1 2 -2 0 1  .............................................................................2 4  
T a ble 4  
E aster n C o o per ati ve O nc ol o g y Gr o u p St at us  ........................................................3 6  
T a ble 5  
I n vesti g at or Assess me nt of A d verse E ve nt C a us alit y ............................................4 2  
 
List of Fi g ures  
Fi g ure 1  
Me di a n A bs ol ute Ne utr o p hil C o u nt O ver Ti me - C ycle 1 - S PI -G C F -1 2 -2 0 1  .....2 2  
Fi g ure 2  
St u d y Des i g n Di a gr a m ..............................................................................................2 7  
 
 
 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1 7  
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  Bre ast C a ncer  a n d R ole of Gr a n ul oc yte C ol o n y Sti m ul ati n g F a ct or  
Acc or di n g t o t he A merica n Ca ncer S ociet y ( A C S), breast c a ncer is o ne of t he m ost c o m m o n 
f or ms of ca n cer a n d t he s ec o n d hi g hest ca us e of ca ncer deat hs i n w o me n [1 ]. I n 2 0 1 4 i n t he 
U nite d States ( U S) , a n esti mate d 2 3 2,6 7 0 ne w cas es of i n vasi ve breast ca n cer a n d 6 2, 5 7 0  
a d diti o nal cases of i n sit u breast c a ncer occ urre d, a n d a p pr o xi matel y 4 0, 4 3 0  U S w o me n were 
e x pecte d t o die fr o m breast c a ncer. I n a d diti o n, breast ca ncer is als o see n i n males, wit h  a n 
esti mate d 2 3 6 0  me n bei n g dia g n os e d wit h breast c a ncer a n d 4 1 0 d yi n g  fr o m t he disease i n 2 0 1 3. 
Data s h o w t hat m ortalit y rates fr o m breast c a ncer i ncreas e wit h a ge, reac hi n g a p ea k w he n 
patie nts are i n t heir 7 0s  [1 ].  
T he Nati o na l C o m pre he nsi ve Ca ncer Net w or k ( N C C N) cli nical g ui deli nes rec o m me n d t hat m ost 
patie nts wit h earl y -sta ge breast c a ncer ( E S B C) recei ve a dj u va nt c h e m ot hera p y after t he y ha v e 
u n der g o ne c o m plet e s ur gical e x cisi o n of t he pri mar y t u m or b y l u m pect o m y a n d a xillar y 
dissecti o n or m o difie d ra dical mastect o m y  [2 ]. C urre nt N C C N g ui deli nes f or a dj u va nt 
c he m ot hera p y re gi me ns t o treat E S B C  i ncl u de d o ceta xel, d o x or u bici n, a n d c ycl o p h os p ha mi de 
( T A C); d ose de nse d o x or u bici n pl us c ycl o p h os p h a mi de ( A C), wit h or wit h o ut s u bse q ue nt 
wee kl y or se mi w ee kl y paclita x el; a n d d oceta xel pl us c ycl o p h os p ha mi de ( T C).  
T he use of a dj u v a nt c he m ot hera p y t o i m pr o ve s ur vi val i n patie nts wit h E S B C has bee n wi del y 
a d o pte d [3 ]. T h e T C re gi me n is a n attracti ve t hera pe utic o pti o n beca use it h as de m o nstrate d 
effic ac y [4 ] a n d re d uce d ris k o f car di ot o xicit y c o m pare d wit h ot her t hera pies t hat c o ntai n 
a nt hrac ycli n es  [5 ]. U S O 9 7 3 5  was a pi v otal P hase 3 trial t hat c o m pared  T C vs. A C a m o n g 
patie nts wit h o pera ble E S B C  [6 ]. Trial res ults s h o we d t hat after 7 years of f oll o w -u p, 4 c ycles of 
T C were ass o ciate d wit h si g nifica ntl y i m pr o ve d Disease Free S ur vi v al (D F S ) a n d O verall 
S ur vi val ( O S ) c o m pare d wit h 4 c ycl es of A C. S pecificall y, t he  D F S  was 8 1 % a n d 7 5 % f or T C 
a n d A C, res pecti vel y, a n d t he O S  was 8 7 % a n d 8 2 %, res pecti vel y. Alt h o u g h t he T C re gi me n has 
n ot bee n ass ociat e d wit h car di ot o xicit y  [4 , 6 , 7 ], it has bee n ass o ciate d wit h ot her a d verse e v e nts, 
partic ularl y he mat ol o gic t o xicities  [4 , 6 ].  
I n U S O 9 7 3 5 , the re p orte d rates  of F e brile N e utr o pe ni a  (F N ) were 4 % i n w o me n y o u n ger t ha n 
6 5  years a n d 8 % i n t h ose 6 5 years or ol d er , alt h o u g h F N  was n ot a pre -pla n ne d e val ua bl e 
e n d p oi nt i n t he trial [4 ]. N o d ose re d u cti o ns were per mitte d, a n d patie nts w ere ta ke n off 
treat me nt if a n y st u d y dr u g a d mi nistrati o n was d ela ye d b y m ore t ha n 2 wee ks beca us e of dr u g-
relate d t o xicities. Pr o p h ylactic use of q ui n olo ne a nti bi otics was rec o m me n de d at t he discreti o n of 
t he treati n g p h ysicia n. Pr o p h yla ctic gra n ul oc yt e c ol o n y-sti m ulati n g fact or (G -C S F ) was n ot 
all o we d, a n d reacti ve G -C S F  s u p p ort f or c he m ot h era p y-i n d u ce d ne utr o p e nic c o m plicati o ns was 
n ot s pecifie d  [4 ]. 
S u bse q ue nt re p orts ha v e s u g geste d t h at T C is ass ociate d wit h  hi g h er rates of  F N  t ha n t h ose 
re p orte d i n U S O 9 7 3 5 , ra n gi n g fr o m 2 5 % t o 5 0 % i n t he a bse nce of G -C S F  s u p p ort a n d 
decreasi n g t o 0 % t o 6. 3 % wit h pri mar y G -C S F pr o p h yla xis (T a ble 1 ) [8 -1 2 ]. 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
1 9  
De vel o p me nt of F N  i n creases dia g n ostic a n d treat me nt c osts, a n d ofte n lea ds t o pr ol o n ge d 
h os pitaliz ati o ns. I n a d diti o n, c ha n ges i n ne utr o p hil c o u nts ha ve bee n c o rrelate d wit h q ualit y of 
life, as meas ur e d b y p h ysical f u ncti o ni n g, vitalit y, a n d me ntal healt h  [1 8 ].  
Fil grasti m, t b o -fil grasti m, a n d pe gfil grasti m are G -C S Fs c urre ntl y a p pr o ve d b y t he U S F o o d a n d 
Dr u g A d mi nistrati o n ( F D A) f or t he pre ve nti o n of c he m ot hera p y -i n d uce d n e utr o pe nia [1 5 ]. W hile 
t he E ur o pea n g ui d eli nes als o i ncl u de le n o grasti m as a rec o m me n de d G -C S F i n s oli d t u m ors a n d 
n o n -m yel oi d mali g na n cies, it is n ot a p pr o ve d f or use i n t he U S.  
St u dies ha ve de m o nstrate d t hat t he use of G -C S F ca n re d uce t he ris k, se v erit y, a n d d urati o n of 
F N  [1 5 ]. G ui deli nes fr o m t he A merica n S ociet y of Cli nical O nc ol o g y ( A S C O), t he E ur o pea n 
Or ga niz ati o n f or Researc h a n d Treat me nt of Ca ncer ( E O R T C) G ui d eli nes , as well as  N C C N 
rec o m me n d t he us e of G-C S F as pri mar y pr o p h yla xis w he n t he a ntici pate d ris k of F N  f or a 
patie nt i nitiati n g c he m ot hera p y is hi g h  [1 5 , 1 9 , 2 0 ].  
1. 1. 2  S PI -2 0 1 2  (Efl a pe gr asti m [R ol o ntis ™]) 
S pectr u m P har mace uticals, I nc. ( S pectr u m) is de v el o pi n g a n o v el, l o n g -acti n g f or m of G -C S F, 
S PI -2 0 1 2  (als o k n o w n as H M 1 0 4 6 0 A, L o n g Acti n g Pr otei n/ Pe pti de Disc o v er y Platf or m 
Tec h n ol o g y -G -C S F  [ L A P S-G -C S F ]), a c he micall y c o nj u gate d f or m  of a m o difie d G -C S F , f or 
t he i n dicati o n of t he re d u cti o n i n t he D ur ati o n of Se vere Ne utr o pe ni a  (D S N ) a n d i nci de nce of 
i nfecti o n, as ma nifest e d b y F N  i n p atie nts wit h s oli d t u m ors a n d n o n-m yel oi d mali g na nci es 
recei vi n g m yel os u p pressi ve a nti-ca n cer t hera p y. S PI -2 0 1 2  is a n o v el bi ol o gic a n d n ot a 
bi osi milar t o eit her fil grasti m or pe gfil grasti m.  
S PI -2 0 1 2  is pr o d uce d b y c o nj u gati n g a n o vel, m o difie d rec o m bi na nt h u ma n G -C S F ( wit h n o 
a d diti o nal N-ter mi nal Met, referre d t o as H M 1 0 4 1 1), a n d t he h u ma n i m m u n o gl o b uli n G 4 Fc 
fra g me nt (referre d t o as H M C 0 0 1) vi a a 3. 4 k Da p ol yet h yle ne gl yc ol ( P E G) li n ker t o pr o d uce  a 
ne w, l o n g -acti n g G -C S F . 
H M 1 0 4 1 1 a n d H M C 0 0 1 are eac h ma n ufact ure d usi n g rec o m bi na nt -D N A tec h n ol o g y i n E.  c oli. 
S pecificall y, H M 1 0 4 1 1 is pr o d uce d b y fer me ntati o n of tra nsf or m e d E. c oli i n t he peri plas mic 
s pace f oll o w e d b y har vesti n g a n d p urifi cati o n. W hereas H M C 0 0 1 is pr o d uce d b y fer m e ntati o n of 
tra nsf or me d E. c oli as a n i ncl usi o n b o d y f oll o we d b y har vesti n g, ref ol di n g, a n d p urificati o n.  
T he h u ma n i m m u n o gl o b uli n G 4 F c fra g me nt ( H M C 0 0 1) was s pecificall y c h ose n as t he 
c o nj u gati o n part ner f or t his n o vel G-C S F  beca use it has a l o n g i n viv o h alf -life of se veral wee ks. 
Details of t he pr o d uct’s c haract eristics ca n b e f o u n d i n t he In v esti gat or’s  B r oc h ure (I B).  
1. 1. 2. 1  N o ncli nic al St u dies  
T he  bi ol o gical  res p o nse t o r h-G -C S F  is n ot  s pecies s pecific, a n d t heref ore t he bi ol o gical  
res p o nse of r h-G -C S F h as bee n e x a m i ne d i n m ice, rats, d o gs, a n d m o n ke ys i n si n gle - a n d re peat -
d ose st u die s.  M o use  b o n e  marr o w  cells, c hem ot hera p y -i n d uce d ne utr o pe nic  m o use  a n d rat 
m o dels, n or m al a n d n e p hrect o m ize d rats, a n d c y n om ol g us  m o n ke ys  ha ve  all bee n  use d  t o 
st u d y t he e ffects of S PI -2 0 1 2 . All t o xic ol o g y stu dies w ere pe rf orm e d u n der G o o d La b orat or y 
Practice ( G L P)  c o n diti o ns.  
T he ki netics of ne utr o p hil pr oliferati o n i n ne utr o p e nic mice a n d rats sti m ulate d wit h S PI -2 0 1 2 , 
pe gfil grasti m, a n d f il grasti m were als o c o m pare d. S PI -2 0 1 2  was s h o w n t o ha ve a n 
a p pr o xi matel y 2 -f ol d hi g her Area U n d er t he Ti me -C o nce ntrati o n c ur ve ( A U C)  f or A bs ol ute 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2 0  
Ne utr o p hil C o u nt ( A N C) w he n c o m pare d t o pe gfil grasti m at si milar d oses (ie, w he n c o m pari n g 
e q ui vale nt G -C S F c o n ce ntrati o ns of t he c o m p o u n ds). Bas e d o n t hese res ults, S PI -2 0 1 2  was 
esti mate d t o ha ve t wice t he i n viv o p ote nc y as pe gfil grasti m. T he p ote ntial c li nical be nefit of t he 
i ncreas e d p ote nc y of S PI -2 0 1 2  was a n al yze d b y c o m pari n g t he D S N  i n ne utr o pe nic rats t o t he 
D S N  res p o nse t o pe gfil grasti m a n d fil grasti m i n t his sa me m o del. S PI -2 0 1 2  was f o u n d t o be 
m ore p ote nt i n s h orte ni n g t he D S N  wit h a l o wer G -C S F  e q ui vale nt d ose w he n c o m pare d t o 
eit her pe gfil grasti m or fil grasti m. T he D S N  was 0. 2 da ys w he n S PI -2 0 1 2  was c o -a d mi nistere d or 
se q ue ntiall y a d mi nistere d as a si n gl e d ose at 8 8 µ g/ k g (as G-C S F e q ui val e nt) wit h c he m ot hera p y 
dr u gs i n r ats. I n c o ntr ast, t he D S N  was 3. 0 4 da ys wit h fil grasti m a d mi nistere d at d ose of 
2 0  µ g/ k g f or 5 da ys a n d was 2. 8 da ys wit h pe gfil grasti m a d mi nistere d as a si n gle d ose of 
1 0 0  µ g/ k g.  
I n c y n o m ol g us m o n ke ys, ne utr o p hil c o u nts i ncrease d as S PI -2 0 1 2  d ose le vels i ncreas e d ( 1 6 1. 4 8 
t o 3 2 2. 9 6 μ g/ k g S PI -2 0 1 2 ,) b ut were n ot d os e -pr o p orti o nal. Ma xi m u m ne utr o p hil le vels pea ke d 
o n D a y 1  p ost -d ose, decrease d b y D a y 7  f oll o wi n g I V a d mi nistrati o n, pea k e d o n D a y 3  p ost -
d ose, a n d t he n decrease d b y D a y 1 6  f oll o wi n g S C a d mi nistrati o n of S PI -2 0 1 2 . S PI -2 0 1 2  als o 
s h o we d a n a p pr o xi matel y 3-f ol d hi g h er A U C f or A N C c o m pare d t o p e gfil grasti m at t he sa me 
G -C S F e q ui vale nt d osi n g le vel.  
1. 1. 2. 2  Cli nic al E x perie nce  
1. 1. 2. 3  P h ase 1 St u dies  
T w o P hase 1  st u dies of S PI -2 0 1 2  (0 8 -H M 1 0 4 6 0 -1 0 1 , N = 6 0; 0 9 -H M 1 0 4 6 0 -1 0 1 , N = 3 0) were 
c o n d ucte d i n he alt hy  v ol u nteers t o e val u ate t he safet y a n d t he p har mac o ki n etic ( P K) a n d 
p har mac o d y n a mic pr o perties of S PI -2 0 1 2 . M ost a d verse e v e nts ( A Es) re p orte d i n t hese st u dies 
were mil d a n d c o m p ara bl e t o t h ose re p orte d i n ot h er cli nical trials wit h pe gfil grasti m. C o m m o n 
treat me nt-relate d A Es i n cl u de d b o ne pai n, b ac k p ai n, a n d hea d ac h e. N o cli nicall y si g nifica nt 
c ha n ges w ere f o u n d i n el ectr ocar di o gra m ( E C G), vit al si g ns, or s ple nic e v al uati o n.  Is olate d cases 
of tac h ycar dia , p al pitati o n , a n d tra nsie nt ele vati o ns of li ver e nz y mes were s ee n i n s o me patie nts . 
O verall i n t he P hase 1 st u dies i n healt h y v ol u nteers, d oses of  S PI -2 0 1 2  bet wee n  1. 1 µ g/ k g a n d 
3 5 0 µ g/ k g were ge n erall y w ell -t olerate d a n d i ncrease d w hite bl o o d cell ( W B C) a n d ne utr o p hil  
c o u nts  i n a pro n o u nce d a n d d ose -de pe n d e nt ma n n er.  
1. 1. 2. 3. 1  P h ase 2 St u d y - S PI -G C F -1 2 -2 0 1  
A P hase 2, o pe n -la b el, d ose-ra n gi n g, st u d y (S PI -G C F -1 2 -2 0 1 , N = 1 4 8) has als o bee n c o m plete d. 
T his st u d y c o m pare d t hree wei g ht -bas e d d oses of S PI -2 0 1 2  ( 4 5, 1 3 5, a n d 2 7 0 µ g/ k g) vers us 
pe gfil gr asti m ( 6 m g) f or t he ma na ge m e nt of ne utr o pe nia i n breast ca ncer patie nts recei vi n g T C 
c he m ot hera p y, a n d pr o vi des safet y a n d effi cac y d ata s u p p orti n g a d va n ce m e nt t o P hase 3 a n d t he 
basis f or t he fi x e d d ose rec o m me n dati o n. Brief res ults are prese nte d bel o w a n d a d diti o nal res ults 
are prese nte d i n t he I n vesti gat or’s Br oc h ure (I B).  
1. 1. 2. 3. 1. 1  St u d y Desi g n  
S PI -G C F -1 2 -2 0 1  wa s a P hase 2, o pe n-la bel st u d y t o assess t he effect of test d oses of S PI -2 0 1 2  
o n t he D S N  d uri n g C ycle 1  i n patie nts wit h breast ca ncer w h o were ca n di dates f or a dj u va nt or  
ne oa dj u va nt c h e m ot hera p y wit h t he d oceta xel a n d c ycl o p h os p ha mi de ( T C).  
T he st u d y i ncl u d e d 4 si n gle -d os e treat me nt ar ms:  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2 1  
•  Ar m 1 : S PI -2 0 1 2  ( 4 5 μ g/ k g) 
•  Ar m 2 : S PI -2 0 1 2  ( 1 3 5 μ g/ k g) 
•  Ar m 3 : S PI -2 0 1 2  ( 2 7 0 μ g/ k g) 
•  Ar m 4 : Pe gfil grasti m ( 6 m g) 
A d mi nistrati o n of T C o n D a y 1  of eac h c ycl e I V was:  
•  D oceta x el at 7 5 m g/ m 2 I V i nf usi o n o ver 1 h o ur 
•  C ycl o p h os p ha mi de 6 0 0 m g/ m 2 I V i nf usi o n o ver 3 0 t o 6 0 mi n utes 
Eac h treat me nt c ycle was 2 1 da ys wit h u p t o a ma xi m u m of 4 c ycl es of c h e m ot hera p y. T o be gi n 
f ull-d ose c he m ot hera p y o n D a y 1  of t he ne xt c ycl e ( D a y 2 2  of t he pre vi o us c ycle), p atie nts m ust 
ha ve rec o vere d t o a n A N C greater t ha n 2. 0 × 1 0 9/ L a n d a platelet c o u nt ≥1 0 0 × 1 0 9/ L. 
S PI -2 0 1 2  w as a d mi nistere d o n D a y 2  of eac h c ycl e, a p pr o xi matel y 2 4 t o 2 6 h o urs  after T C 
c he m ot hera p y. T he d ose of S PI -2 0 1 2  a d mi nistere d de pe n de d o n t he tr eat m e nt ar m t o w hic h eac h 
patie nt was assi g ne d. Pe gfil grasti m was t o be a d mi nistere d acc o r di n g t o t he ma n ufact ur er’s 
Prescri bi n g I nf or m ati o n ( 6 m g s u bc uta ne o usl y o n ce per c h e m ot hera p y c ycl e).  
1. 1. 2. 3. 1. 2  Dis p ositi o n a n d De m o g r a p hics  
I n S PI -G C F -1 2 -2 0 1 , 1 4 8 patie nts were ra n d o mize d i nt o t he 4 treat me nt ar ms. M ost patie nts 
( 1 4 7 patie nts [ 9 9 %]) c o m plete d at least 1 c ycl e of treat me nt. Te n  p atie nts ( 7 %) disc o nti n ue d 
fr o m t he st u d y. T hree p atie nts ( 2 %) wit h dre w c o nse nt, t w o patie nts ( 1 %) disc o nti n ue d d ue t o 
a d verse e ve nts, a n d fi ve patie nts disc o nti n ue d f or ot her reas o ns. F o ur patie nts ( 2 patie nts eac h i n 
t he 13 5 μ g/ k g  S PI -2 0 1 2  gr o u p [ o ne patie nt wit h dre w c o nse nt a n d o ne patie nt i nitiate d a n o n -
pr ot oc ol t hera p y]  a n d 2 7 0 μ g/ k g S PI -2 0 1 2  d os e gr o u p  [ b ot h patie nts wit h dre w c o ns e nt]) 
disc o nti n ue d pri or t o be gi n ni n g C ycle 2  a n d 1 3 8 p atie nts ( 9 3 %) were tr eate d f or all 4 c ycl es.  
T he mea n a ge of all patie nts i n S PI -G C F -1 2 -2 0 1  was 5 8. 2 years a n d ra n ge d fr o m 3 2 years t o 
7 7  years acr oss all gr o u ps. M ost patie nts were less t ha n 6 5 years of a ge ( n = 1 0 0 [ 6 8 %]), fe male 
(n = 1 4 4 [ 9 8 %]), a n d W hite ( n = 1 3 9 [ 9 5 %]). T here were 3 mal e patie nts i n t he st u d y, t w o i n t he 
2 7 0 µ g/ k g S PI -2 0 1 2  gr o u p a n d o ne i n t he 1 3 5  µ g/ k g S PI -2 0 1 2  gr o u p.  
D uri n g C ycle 1 , m ost patie nts ( ≥6 4 %) i n all t hree S PI -2 0 1 2  d ose gr o u ps a n d t he pe gfil grasti m 
gr o u p di d n ot de v el o p ne utr o pe nia ; at S PI -2 0 1 2  d oses ≥1 3 5 µ g/ k g, t he pr o p orti o n of patie nts n ot 
e x perie nci n g n e utr o pe ni a was c o m para ble or hi g h er t o t he i nci de nce wit h p e gfil grasti m.  
1. 1. 2. 3. 1. 3  D ur ati o n of Se vere Ne utr o pe ni a  
I n t he 2 7 0 µ g/ k g S PI -2 0 1 2  gr o u p, n e utr o pe nia was re p orte d i n o nl y o ne pati e nt ( 3 %), w hic h 
laste d o nl y 1 da y. I n t he 1 3 5 µ g/ k g S PI -2 0 1 2  gr o u p, se ve n patie nts ( 1 9 %) e x perie nce d 
ne utr o pe nia, w hic h l aste d f or 1  da y i n t hree patie nts ( 8 %), 2 da ys i n t hree patie nts ( 8 %), a n d 
7  da ys i n o n e patie nt ( 3 %). A p pr o xi matel y o ne -t hir d of patients i n t he 4 5 µ g/ k g S PI -2 0 1 2  gr o u p 
e x perie nce d ne utr o pe nia t hat laste d bet wee n 1 t o 5 da ys. I n t he pe gfil grasti m gr o u p, fi v e patie nts 
( 1 4 %) e x perie n ce d ne utr o pe nia, w hic h laste d f or 1 da y i n o n e patie nt ( 3 %), 2 da ys i n t w o 
patie nts ( 6 %), a n d 3 d a ys i n t w o patie nts ( 6 %). T h e ma g nit u de of D S N  a n d t he mea n val ues i n 
t he vari o us treat me nt ar ms ma y be m uc h l o wer i n t his st u d y as c o m pare d t o t hat i n t he literat ure 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2 5  
cli nical be nefits of t he pr o p h yla ctic use of G -C S F  f or patie nt safet y, t o ma xi mize treat me nt 
i nte nsit y a n d o utc o mes, a n d c ost -effi cie nc y.  
P har mac ol o gical a n al ysis  of S PI -2 0 1 2  i n vi v o re v eale d a 2- t o 3-f ol d i ncrease i n t he A U C of t he 
A N C at G -C S F -e q ui v ale nt d oses si milar t o pe gfil grasti m. Cli nical e x perie nce fr o m t he P has e 2 
trial (S PI -G C F -1 2 -2 0 1) i n breast c a ncer patie nts h as s h o w n t hat S PI -2 0 1 2  is n o n-i nferi or t o 
pe gfil grasti m an d has a si milar safet y pr ofile. All d oses of S PI -2 0 1 2  a d mi nistere d i n 
S PI -G C F --1 2 -2 0 1  w ere well t olerate d. N o si g nifi ca nt d ose -relate d t o xicities were o bser ve d. T he 
D S N  i n t he 1 3 5 µ g/ k g S PI -2 0 1 2  ar m was n o n -i nf eri or t o pe gfil grasti m i n C ycle 1  a n d t he D S N  
i n t he 2 7 0 µ g/ k g S PI -2 0 1 2  Treat me nt A r m was s u peri or t o t he Pe gfil gr asti m Tre at me nt Ar m . 
N o n -i nferi orit y i n D S N  was als o o bser ve d i n C ycles 2  t o 4  i n b ot h t he 1 3 5 µ g/ k g a n d 2 7 0 µ g/ k g 
treat me nt ar ms w h e n c o m pare d t o pe gfil grasti m. 
T he c urre nt P hase  3 st u d y  is desi g ne d t o e x pa n d o n t he i nf or mati o n o btai ne d i n t he P hase 2 trial 
a n d e val uat e t he efficac y, a n d safet y of S PI -2 0 1 2 , as c o m pare d wit h pe gfil grasti m (Ne ulasta 
[ N D C 5 5 5 1 3-1 9 0 -0 1 ] ma n ufact ur e d b y A m ge n i n t he U nite d States), i n breast ca ncer patie nts 
recei vi n g T C.  
T he d ose of S PI -2 0 1 2  t o be st u die d i n t his trial is 1 3. 2 m g S PI -2 0 1 2  e q ui v ale nt t o 3 . 6 m g 
G -C S F, a p pr o xi matel y h alf of t he G -C S F e q ui val e nt d ose i n 6 m g pe gfil grasti m. T his d ose was 
selecte d o n t he b asis of t he p har mac ol o gi cal a n d p har mac o d yn a mic data fr o m t he P hase  2 trial 
(S PI -G C F -1 2 -2 0 1 ).  
As a p plica ble, p atie nts w h o ha ve recei ve d at least o ne d ose of st u d y dr u g ( S PI -2 0 1 2  or 
pe gfil grasti m) will be f oll o we d f or 1 2 m o nt hs after t he last d ose of st u d y tr eat me nt f or safet y 
f oll o w-u p. P atie nts will visit t he cli nic at a p pr o xi matel y 6 m o nt hs a n d 1 2 m o nt hs f or a bl o o d 
dra w f or e val uati o n of i m m u n o ge nicit y a n d f or e v al uati o n of A Es, s u bse q ue nt a nti -ca n cer 
t hera p y, use of ot her m yel oi d  gr o wt h f act ors, a n d partici pati o n i n a n y ot her s u bse q ue nt cli nical 
trials. I n a d diti o n, patie nts  will als o be c o ntacte d b y tele p h o n e at a p pr o xi matel y 3  m o nt hs a n d 
9  m o nt hs f or e val uati o n of A Es, s u bse q ue nt a nti-ca ncer t hera p y, use of ot her m yel oi d gr o wt h 
fact ors, a n d p artici pati o n i n a n y ot her s u bse q ue nt cli nical trials.  
2  S T U D Y O B J E C TI V E S   
2. 1  Pri m ar y O bjecti ve  
•  T o c o m pare t h e efficac y of S PI -2 0 1 2  wit h pe gfil grasti m  i n patie nts wit h earl y-sta ge 
breast c a ncer recei vi n g d oceta xel a n d c ycl o p h os p ha mi de ( T C), as me a s ure d b y t he D S N  
i n C ycle 1  
2. 2  Ke y Sec o n d ar y O bjecti ves  
•  T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m i n:  
•  
Ti me t o A N C Rec o ver y i n C ycle 1  
•  
De pt h of A N C N a dir , defi ne d as t he p atie nt’s l o west A N C i n C ycle 1  
•  
I n ci de nce of F N  i n patie nts d uri n g C ycl e 1   
2. 3  A d diti o n al Sec o n d ar y O bjecti ves  
•  T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m i n:  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2 6  
•  
D S N  i n C ycles 2 , 3 , a n d 4  
•  
I nci de nce of Ne utr o pe nic C o m plic ati o ns, i ncl u di n g a nti-i nf ecti ve use a n d 
h os pitaliz ati o ns i n patie nts d uri n g C ycl e 1   
•  
I n ci de nce of F N  i n C y cle s 2 , 3 , a n d 4  
•  
Rel ati ve D ose I nte nsit y  (R DI ) of T C i n C ycl es 1  t o 4  
•  
Safet y  
3  I N V E S TI G A TI O N A L P L A N 
3. 1  St u d y Desi g n  a n d Tre at me nt Pl a n  
T his is a P hase 3, ra n d o mize d, o pe n -la bel, acti ve -c o ntr olle d, m ultice nter  st u d y t o c o m pare t he 
effic ac y a n d s afet y of S PI -2 0 1 2  wit h pe gfil grasti m i n breast ca n cer patie nts treate d wit h T C 
c he m ot hera p y.  
A p pr o xi matel y 2 1 8  p atie nts will be e nr olle d a n d ra n d o mize d i n a 1: 1 rati o t o 2 treat me nt ar ms 
(Fi g ure 2 ):  
•  Tre at me nt Ar m 1  ( n = a p pr o xi matel y 1 0 9 ): S PI -2 0 1 2  (1 3. 2 m g/ 0. 6 m L fi x e d d ose 
S PI -2 0 1 2  e q ui v ale nt t o 3. 6  m g  G -C S F ) 
•  Tre at me nt Ar m 2  ( n =a p pr o xi matel y 1 0 9 ): Pe gfil grasti m ( 6 m g G -C S F / 0. 6 m L)  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2 8  
Pri or t o T C c he m ot hera p y a d mi nistrati o n, patie nts ma y recei ve pre -me dicati o n s acc or di n g t o 
i nstit uti o nal sta n dar d of care. I ntr a ve n o us (I V) a d mi nistrati o n of T C o n D a y 1  of eac h c ycle will 
be as f oll o ws:  
•  D oceta x el 7 5 m g/ m 2 I V i nf usi o n per i nstit ute ’s sta n dar d of care 
•  C ycl o p h os p ha mi de 6 0 0 m g/ m 2 I V i nf usi o n per i nstit ute ’s sta n dar d of care 
Eac h c ycl e will be 2 1 da ys. O nl y 4 c ycles will be e val uate d f or t his st u d y. After C y cle 1, patie nts 
m ust ha ve A N C ≥1. 5  ×  1 0 9/ L a n d platelet c o u nt ≥1 0 0  ×  1 0 9/ L t o be gi n t he eac h of n e xt c ycl e s of 
c he m ot hera p y.  
T he st u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m) will be a d mi nistere d o n D a y 2 of eac h c ycle, 
a p pr o xi matel y 2 4 t o 2 6 h o urs  after t h e last d ose of T C c he m ot hera p y is gi v e n.  St u d y dr u g 
(S PI -2 0 1 2  or pe gfil grasti m) d ose m o dificati o ns are n ot all o we d.  
O n D a y 1  of eac h c ycle, patie nts will recei ve T C c he m ot hera p y, a n d safet y a n d effi cac y 
assess me nts will be perf or me d as o utli ne d i n  Secti o n 5. 3 . O n D a y 2  of eac h c ycle, patie nts will 
recei v e st u d y dr u g (S PI -2 0 1 2  o r pe gfil grasti m), a n d t he s pecifie d assess me nts will be perf or m e d. 
Patie nts will be m o nit ore d o n D a y 1 a n d D a ys 4 t o 1 5 i n C ycle 1 . If t he p artici pati n g site is 
n otifie d t hat t he  A N C is ≤1. 0  ×  1 0 9/ L at a n y ti me d uri n g C ycle 1 , t he n dail y C B Cs will be 
re q uire d u ntil A N C is ≥1. 5  ×  1 0 9/ L, after reac hi n g na dir. I n C ycl es 2 t o 4 , all patie nts m ust ha ve 
bl o o d sa m ples dra w n o n D a y 1  ( pri or t o c h e m ot hera p y a d mi nistrati o n), o n D a ys 4 , 7 , 1 0 , a n d 1 5  
( ± 1 da y f or eac h c ollecti o n ), a n d at t he E n d -of -Tre at me nt Visit . If t h e partici pati n g site is 
n otifie d t hat t he  A N C is ≤1. 0  ×  1 0 9/ L at a n y ti me d uri n g C ycles 2  t o 4 , t he n dail y C B Cs will be 
re q uire d u ntil t he A N C is ≥1. 5  ×  1 0 9/ L, after reac hi n g na dir, b ut bl o o d sa m ples m ust still be 
dra w n o n D a ys 4 , 7 , 1 0 , a n d 1 5 . A s a p plica ble, p atie nts w h o ha ve recei ve d at least o ne d ose of 
st u d y dr u g will be f oll o w e d f or a p pr o xi matel y 1 2  m o nt hs after t he last d ose of st u d y tr eat me nt 
f or safet y f oll o w-u p .  
3. 2  S t u d y a n d Tre at me nt D ur ati o n  
T he d urati o n of t he S PI -G C F -3 0 2  st u d y is a p pr o xi matel y 2 8  m o nt hs ( 1 6  m o nt hs f or e nr oll me nt 
a n d 1 2 m o nt hs of treat me nt/f oll o w -u p). T he t otal d urati o n of t he st u d y f or eac h patie nt i n 
S PI -G C F -3 0 2  will be f or a p pr o xi matel y 1 6 m o nt hs i ncl u di n g:  
•  Scree ni n g Peri o d : 3 0 da ys  
•  Tre at me nt Peri o d : 4 c ycles, 2 1 da ys per c ycle 
•  E n d -of -Tre at me nt Visit : 3 5  ( ± 5) d a ys after last d ose of st u d y tr eat me nt 
•  S afet y F oll o w -u p : 1 2 m o nt hs after t he last d ose of st u d y tr eat me nt  
•  E n d -of -St u d y Visit : At t he 1 2 M o nt h Visit  or 3 5  ( ± 5) da ys after earl y disc o nti n uati o n  
A s a p plica ble, patie nts w h o recei v e at least o ne d ose of st u d y dr u g will be f oll o we d f or safet y f or 
1 2 m o nt hs  after t he last d ose of st u d y tr eat ment f or safet y f oll o w-u p . 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
2 9  
4  P A TI E N T P O P U L A TI O N  
4. 1  I ncl usi o n Criteri a  
1.  Patie nt or le gall y a ut h orize d re prese nt ati ve m ust be willi n g a n d ca pa bl e of gi vi n g writte n 
I nf or me d C o nse nt a n d m ust be a ble t o a d here t o d osi n g a n d visit sc he d ules as well as 
meet all st u d y re q uire me nts.  
2.  Patie nt m ust ha ve a ne w l y dia g n os e d, hist ol o gicall y c o nfir me d earl y -sta ge breast c a ncer 
( E S B C), defi n e d as o pera ble Sta ge I t o Sta ge III A breast c a ncer.  
3.  Patie nt m ust be a ca n di date t o recei v e a dj u va nt or ne oa dj u va nt T C c he m ot h era p y.  
4.  Patie n t ( male or fe m ale) m ust be at least 1 8 years of a ge.  
5.  Patie nt m ust ha ve a de q uate he mat ol o gi cal, re n al a n d he patic f u ncti o n as d efi ne d b y : 
•  
A N C ≥1. 5  ×  1 0 9/ L 
•  
Platelet c o u nt ≥1 0 0  ×  1 0 9/ L 
•  
He m o gl o bi n > 9 g/ d L  
•  
Calc ulate d creati ni ne cle ara nce > 5 0 m L/ mi n  
•  
T otal bil ir u bi n ≤1. 5 m g/ d L  
•  
As partate a mi n otra nsferase ( A S T)/ser u m gl uta mic -o x al oacetic tra nsa mi nas e ( S G O T) 
a n d ala ni ne a mi n otra nsferase A L T/ser u m gl uta mic -p yr u vic tr a nsa mi nase ( S G P T) 
≤2. 5  ×  U L N, a n d al kali ne p h os p hatase ≤2. 0  ×  U L N  
6.  Patie nt 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 ≤2.  
7.  Patie nt m ust be willi n g t o practice t w o f or ms of c o ntrace pti o n, o ne of w hic h m ust be a 
barrier m et h o d, fr o m st u d y e ntr y t hr o u g h 3 0 da ys after t he l ast d ose of st u d y dr u g 
a d mi nistrati o n or 3 0 da ys aft er d ate of patie nt earl y disc o nti n uati o n.  
8.  Fe males of c hil d beari n g p ote ntial m ust ha ve a ne gati ve uri ne pre g na nc y t est wit hi n 
3 0  da ys pri or t o ra n d o mi zati o n. Fe males w h o are p ost me n o pa usal f or at least 1 year 
( defi ne d as m ore t ha n 1 2 m o nt hs si nce last me nses) or are s ur gicall y sterilize d d o n ot 
re q uire t his test.  
4. 2  E xcl usi o n Criteri a   
1.  Patie nt wit h a n acti ve c o nc urre nt mali g na n c y (e x ce pt n o n mela n o ma s ki n ca ncer or 
carci n o ma i n sit u of t he cer vi x) or life -t hreate ni n g disease. If t h ere is a hist or y of pri or 
mal i g na n cies or c o ntr alat eral br east ca n cer , t he patie nt m ust be disease free f or at least 
5  years.  
2.  Patie nt wit h k n o w n se nsiti vit y or pre vi o us reacti o n t o Esc heric hi a c oli  (E. c oli ) deri ve d 
pr o d ucts (e g, fil grasti m, rec o m bi na nt i ns uli n [ H u m uli n ®], L -as para gi n ase, s o matr o pi n 
[ H u matr o p ®] gr o wt h h or m o ne, rec o m bi na nt i nterfer o n alf a-2 b [I ntr o n ® A]), or a n y of 
t he pr o d ucts t o be a d mi nistere d d uri n g st u d y partici pati o n.  
3.  Patie nt wit h c o nc urre nt a dj u va nt ca ncer t hera p y (c he m ot hera p y, ra diati o n t hera p y, 
i m m u n ot hera p y, bi ol o gic t hera p y ot her t h a n t he tri al s pecifie d t hera pies).  
4.  Patie nt has l ocall y rec urre nt/metastatic breast ca n cer.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 0  
5.  Patie nt wit h pre vi o us e x p os ure t o fil grasti m, pe gfil grasti m, or ot her G -C S F pr o d ucts i n 
cli nical de vel o p me nt wit hi n 1 2 m o nt hs pri or t o t he  a d mi nistrati o n of st u d y dr u g ( S PI-
2 0 1 2  or pe gfil grasti m) .  
6.  Patie nt wit h a n acti ve i nf ecti o n  or o n a nti -i nfecti ves, a n u n derl yi n g me dical c o n diti o n or 
a not her seri o us ill ness t h at w o ul d i m pair t he a bilit y of t he p atie nt t o recei ve pr ot oc ol -
s pecifie d treat me nt.  
7.  Patie nt has use d a n y i n vesti gati o nal dr u gs, bi ol o gi cs, or de vices wit hi n 3 0 da ys pri or t o 
st u d y treat me nt or pla ns t o use a n y of t hes e d uri n g t he c o urse of t h e st u d y.  
8.  Patie nt has ha d pri or b o n e marr o w or he mat o p oietic ste m cell tra ns pla nt.  
9.  Patie nt has  ha d pri or ra diati o n t hera p y wit hi n 3 0 da ys pri or t o e nr oll me nt.  
1 0.  Patie nt has ha d maj or s ur ger y wit hi n 3 0 da ys pri or t o e nr oll me nt. Patie nts w h o ha ve 
breast s ur ger y rel ate d t o t he breast ca ncer dia g n osis or ha ve ha d a p ort -a-cat h place me nt 
ma y b e e nr olle d pri or t o 3 0 da ys o n ce t he y h a ve f ull y rec o vere d fr o m t he pr oce d ure.  
1 1.   Patie nt is pre g n a nt or breast -fee di n g. 
4. 3  P ati e nt  Disc o nti n u ati o n/ Wit h dr a w al Criteri a   
P atie nts ca n wit h dra w fr o m partici pati o n i n t his st u d y at a n y ti me, f or a n y reas o n, s pecifi e d or 
u ns pecifie d, a n d wit h o ut prej u dice.  
•  Patie nts m ust  be wit h dra w n fr o m st u d y dr u g treat me nt f or a n y of t he f oll o wi n g reas o ns, 
b ut will c o nti n ue i n t he 1 2 -M o nt h S afet y F oll o w -u p :  
•  
De vel o p me nt of a n a d verse e ve nt ( A E) t hat i nterferes wit h t he patie nt’s partici pati o n  
•  
Disc o nti n uati o n of T C  
•  
Disc o nti n uati o n of S PI -2 0 1 2  or pe gfil grasti m  
•  
Dela y of T C a d mi nistrati o n f or > 4 2 da ys si nce last st u d y dr u g a d mi nistrati o n  
•  
I n v esti gat or decisio n  
•  
S p o ns or decisi o n  
•  
Pre g n a nc y  
•  Patie nts m ust be wit h dra w n fr o m t he st u d y, treat me nt p hase or 1 2 -M o nt h Safet y  F oll o w -
u p f or a n y of t h e f oll o wi n g reas o ns:  
•  
I nitiati o n of n o n-pr ot oc ol s yste mic c h e m ot hera p y or bi ol o gical t hera p y f or t he 
treat me nt of breast ca n cer 
•  
Patie nt w it h dra wal of i nf or me d c o nse nt  
•  
Treat me nt wit h a d diti o nal m yel oi d gr o wt h f act ors d uri n g f oll o w -u p  
•  
L ost t o f oll o w -u p  
•  
Deat h  
T he reas o n f or a p atie nt’s disc o nti n uati o n of st u d y treat me nt or disc o nti n uati o n fr o m t he st u d y is 
t o be rec or de d o n t he  ele ctr o nic  cas e re p ort  f or m (C R F ). A s a p plica ble, p atie nts w h o recei ve at 
least o ne d ose of st u d y dr u g (S PI -2 0 1 2  or pe gfil grasti m ) will be f oll o we d f or 1 2 m o nt hs  after t he 
last d ose of st u d y tr eat me nt f or safet y. All A Es d uri n g t his ti me peri o d will be rec or de d.   

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 1  
5  S T U D Y P R O C E D U R E S   
T he st u d y d esi g n dia gra m is prese nte d i n Fi g ure 2  a n d t he Sc he d ule s of St u d y Assess me nts a n d 
Pr oce d ures is pr ese nte d i n A p pe n di x 1  a n d A p pe n di x 2 . 
5. 1  Scree ni n g  
I nf or me d c o ns e nt is t o be o btai ne d pri or t o t he start of a n y pr ot oc ol-s pecifie d assess me nts or 
pr oce d ures. T he pr oce d ures a n d e v al uati o ns re q uire d f or e nr oll me nt i nt o t he st u d y are 
s u m marize d bel o w. All p ote ntial st u d y patie nts will be scree n e d a n d eli gi bi lit y d eter mi ne d pri or 
t o e nr oll me nt. Scree ni n g assess me nts perf or me d pri or t o t he si g ni n g of i nf or me d c o nse nt as p art 
of t he site’s r o uti ne sta n d ar d of practice will be all o we d at t he discreti o n of S pectr u m. T his 
i nf or mati o n s h o ul d be disc usse d wit h t he Medical M o nit or.  
5. 2  P ati e nt Assi g n me nt  
C o nfir mati o n of eli gi bilit y is t o be recei v e d b y t he i n vesti gati o nal site fr o m S pectr u m pri or t o 
e nr ollme nt of  a patie nt. After a p atie nt has si g ne d t he I C F, t he I n v esti gat or or site staff s h o ul d 
l o g i nt o I W R S a n d o btai n a Patie nt I D. T he Patie nt I D will i ncl u de t w o parts: t he site n u m ber 
c o m prise d of 5 di gits wit h a 2 -di git al p h a betic c o u ntr y c o d e [ Refere nce I S O 3 1 6 6] f oll o we d b y a 
3 -di git site s pecifi c n u meri c c o de a n d a 3-di git patie nt se q ue ntial n u m ber, u ni q ue t o a site, 
se parat e d b y a h y p he n (ie, 
). O nce t h e I n vesti gat or or site staff h a ve c o m plete d t he 
re q uire d C R F s, a n d a p pr o val f or ra n d o mizati o n has bee n recei ve d fr o m S p ectr u m,  t he site will 
ra nd o mize t he patie nt usi n g a pre -s p ecifie d ra n d o mizati o n sc he me. Please refer t o t he st u d y 
bi n der f or det aile d i nstr ucti o ns re gar di n g e nr oll me nt.  
5. 3  Ti mi n g of Assess me nts  a n d Pr oce d ures  
5. 3. 1  Scree ni n g ( D a ys -3 0  t o -1)  
T he f oll o wi n g s cree ni n g assess me nts a n d pr oce d u res are t o be perf or me d wit hi n 3 0 da ys of t he 
first da y of st u d y dr u g a d mi nistrati o n. Scree ni n g assess me nts perf or me d pri or t o t he si g ni n g of 
t he I C F as p art of t he site’s r o uti ne sta n dar d of practice (i ncl u di n g, b ut n ot li mite d t o i ma gi n g 
pr oce d ures, pat h ol o g y bi o ps y res ults) will be all o we d at t he discreti o n of t he S p o ns or. T his 
i nf or mati o n s h o ul d be disc usse d wit h t he Me dical M o nit or. 
•  Inf or me d C o nse nt  
•  C o m plete me dical hist or y  
•  De m o gra p hic d ata  
•  C o m plete p h ysical e x a mi nati o n   
•  Hei g ht a n d wei g ht  
•  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  
•  Vital si g ns  
•  C o m plete bl o o d c o u nt ( C B C) wit h 5 -part differe ntial  ( Ma y be o btai ne d wit hi n  3 da ys 
pri or t o C ycle 1 , D a y  1  wit h o ut re peati n g o n C ycle 1, D a y 1 ) 
•  C he mistr y  ( Ma y b e o btai ne d wit hi n  3 da ys pri or t o C ycle 1 , D a y  1  wit h o ut re peati n g o n 
C ycle 1, D a y 1 ) 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 2  
•  Pre g n a nc y test ( uri ne bet a h u ma n c h ori o nic g o n a d otr o pi n [ β -h C G]) i n w o me n of 
c hil d beari n g p ote ntial )  
•  A d verse e ve nts usi n g N CI C T C A E Versi o n 4. 0 3 , rec or d Seri o us A d verse E ve nts ( S A Es ) 
relate d t o a st u d y pr oce d ure o nl y 
•  H or m o ne rece pt or stat us, i ncl u di n g estr o ge n rece pt or ( E R), pr o gester o ne rece pt or ( P R) 
a n d h u ma n e pi der m al gr o wt h fact or 2 ( H E R 2 ), n u m ber of n o des , a n d sta ge. 
•  Ra n d o mizati o n (t he patie nt ca n be ra n d o mize d at a n y ti me bet wee n t h e ti me t he patie nt is 
a p pr o ve d f or st u d y p artici pati o n a n d C ycle 1 , D a y 1 ) 
5. 3. 2  Tre at me nt Peri o d  –  C y cle 1, D a y 1  ( B aseli ne) 
T he f oll o wi n g pr oce d ures a n d Bas eli ne assess me nts are t o be perf or me d b ef ore t he 
a d mi nistrati o n of T C c he m ot hera p y:  
•  Eli gi bilit y c o nfir m ati o n  
•  Patie nt I D assi g n me nt  
•  P h ysical e x a mi nati o n ( Ma y b e perf or me d wit hi n  3 da ys pri or t o C ycle 1 , D a y  1  wit h o ut 
re peati n g o n C y cle 1, D a y 1 ) 
•  Wei g ht  
•  E C O G perf or ma nce stat us  
•  Vital si g ns  
•  B o d y te m perat ure 
•  C o m plete bl o o d c o u nt  ( C B C) wit h 5 -part differe ntial  (Ma y be o btai ne d wit hi n  3 da ys 
pri or t o C ycle 1 , D a y  1  wit h o ut re peati n g o n C ycle 1, D a y 1 )  
•  C he mistr y  (o nce wit hi n 3 da ys pri or t o C ycle 1 , D a y 1  wit h o ut re peati n g o n C ycle 1, 
D a y  1 )  
•  Bl o o d dra w f or i m m u n o ge nicit y testi n g (all patie nts) 
•  C o nc o mita nt me dicati o ns   
•  A d verse e ve nts usi n g N CI C T C A E Versi o n 4. 0 3  
D oceta x el a n d c ycl o p h os p ha mi de  are t o b e a d mi nistere d as des cri be d i n  Secti o n 3. 1 . 
•  D oceta x el 7 5 m g/ m 2 I V i nf usi o n per i nstit ute ’s sta n dar d of care  
•  C ycl o p h os p ha mi de 6 0 0 m g/ m 2 I V i nf usi o n per i nstit ute ’s sta n dar d of care  
5. 3. 3  Tre at me nt Peri o d –  C y cle 1, D a y 2  
•  Vital si g ns (rec or de d pri or t o treat me nt, as w ell as a p pr o xi matel y 3 0 a n d 6 0 mi n utes after 
dr u g (S PI -2 0 1 2  or pe gfil grasti m ) a d mi nistrati o n  
•  B o d y te m perat ure  
•  C o nc o mita nt me dicati o ns  
•  A d vers e e ve nts  
•  St u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m ) a d mi nistrati o n  acc or di n g t o ra n d o mizati o n  
assi g n me nt  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 3  
•  Bl o o d sa m ple f or P K a nal ysis ( S PI -2 0 1 2 Tre at me nt A r m o nl y)  
5. 3. 4  Tre at me nt Peri o d –  C y cle 1, D a y s 4  t o 2 1  
•  T wice d ail y b o d y te m perat ure  
•  C o m plete bl o o d c o u nt wit h 5 -part differe ntial  o n D a ys 4  t o 1 5  o nl y . If t h e partici pati n g 
site is n otifie d t hat t he A N C is ≤1. 0 × 1 09/ L o n D a y 1 5 , t he n dail y C B Cs will be re q uire d 
u ntil t heir A N C is ≥1. 5 × 1 0 9/ L p ost-n a dir.  
•  Bl o o d sa m ple f or P K  a nal ysis (S PI -2 0 1 2 Tre at me nt A r m o nl y) ( D a ys 4  a n d 5  o nl y , at 
t he sa me ti me as C B C bl o o d dra w) 
5. 3. 5  Tre at me nt Peri o d –  C y cle s 2  t o 4, D a y 1  
T he f oll o wi n g pr oce d ures are t o be p erf or m e d bef ore t he a d mi nistrati o n of T C c he m ot hera p y:  
•  P h ysical e x a mi nati o n ( Ma y b e perf or me d wit hi n  3 da ys pri or t o D a y 1  of a n y treat me nt 
c ycle)  
•  Wei g ht  
•  E C O G perf or ma nce stat us  
•  Vital si g ns  
•  B o d y te m perat ure 
•  C o m plete bl o o d c o u nt wit h 5 -part differe ntial  ( Ma y be o bt ai ne d wit hi n 3 da ys pri or t o 
D a y  1  of a n y treat me nt c ycl e)  
•  C he mist r y ( Ma y b e o btai ne d wit hi n 3 da ys pri or t o D a y 1  of a n y treat me nt c ycle)  
•  A d verse e ve nts  
•  Bl o o d dra w f or i m m u n o ge nicit y testi n g (all patie nts) 
•  C o nc o mita nt me dicati o ns  
D oceta x el a n d c ycl o p h os p ha mi de are t o b e a d mi nistere d as des cri be d i n  Secti o n 3. 1 . 
5. 3. 6  Tre at me nt Peri o d –  C y cles 2 t o 4, D a y 2  
•  Vital si g ns rec or de d pri or t o treat me nt, as w ell as a p pr o xi matel y 3 0 a n d 6 0 mi n utes after 
st u d y dr u g (S PI -2 0 1 2  or pe gfil grasti m ) a d mi nistrati o n  
•  T wice dail y b o d y  te m perat ure 
•  C o nc o mita nt me dicati o ns  
•  A d verse e ve nts  
•  St u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m ) a d mi nistrati o n  
•  Bl o o d sa m ple f or P K a nal ysis ( S PI -2 0 1 2 Tre at me nt A r m o nl y) ( D a y 2  of C ycle 3  o nl y)  
5. 3. 7  Tre at me nt Peri o d –  C y cles 2 t o 4, D a ys 3 t o 2 1   
•  T wice dail y b o d y t e m perat ure  
•  C o m plete bl o o d c o u nt wit h 5 -part differe ntial  o nl y o n D a ys 4 , 7 , 1 0 , a n d 1 5  ( ±1  da y  f or 
eac h c ollecti o n ) or u ntil patie nts’ A N C is ≥1. 5 × 1 0 9/ L p ost-n a dir, w hic h e v er occ urs first.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 4  
If t he partici p ati n g site is n otifie d t hat t he A N C is ≤1. 0 × 1 09/ L at a n y ti me, t he n dail y 
C B Cs will be re q uire d u ntil A N C is ≥1. 5 × 1 0 9/ L p ost -na dir . 
•  Bl o o d sa m ple f or P K a nal ysis ( S PI -2 0 1 2 Tre at me nt A r m o nl y) ( D a ys 4  a n d 7  of 
C ycle  3  o nl y , ± 1 da y, at t he sa me ti me as C B C bl o o d dra w ) 
5. 3. 8  E n d -of -Tre at me nt Visit ( At t he e n d of C ycle 4  or  A p pr o xi m atel y 3 5  ( ± 5) d a ys After  
D ate of E arl y D isc o nti n u ati o n) 
•  P h ysical e x a mi nati o n  
•  Wei g ht  
•  E C O G perf or ma nce stat us  
•  Vital si g ns  
•  B o d y te m perat ure  
•  C B C wit h 5 -part differe ntial  
•  C he mistr y  
•  Bl o o d dra w f or i m m u n o ge nicit y testi n g  (all patie nts) 
•  C o nc o mita nt me dicati o ns  
•  A d verse e ve nts usi n g N CI C T C A E Versi o n 4. 0 3  
5. 3. 9  1 2 M o nt h  S afet y F oll o w -u p  
All ra n d o mize d patie nts w h o ha ve recei v e d at least o ne d ose of st u d y dr u g ( S PI -2 0 1 2  or 
pe gfil grasti m ) will c o nti n ue t o be f oll o we d f or 1 2  m o nt h s after t he last d ose of st u d y tr eat me nt 
f or e val u ati o n of l o n g-ter m safet y, i ncl u di n g i m m u n o ge ni cit y.  
5. 3. 9. 1  Tele p h o ne C o nt act  
At a p pr o xi matel y 3 m o nt hs ( ± 2 wee ks ) a n d 9 m o nt hs ( ±2 wee ks ) after t he l ast d ose of st u d y dr u g 
(S PI -2 0 1 2  or pe gfil grasti m) i n S PI -G C F -3 0 2  (t hr o u g h t he e n d of C ycle 4  or earl y 
disc o nti n uati o n), patie nts will be c o ntacte d b y tele p h o ne f or:  
•  M yel oi d gr o wt h fact or us e (i ncl u di n g t h e t y p e of G -C S F, t he sc he d ul e of a d mi nistrati o n 
a n d reas o n f or use)  
•  S u bse q ue nt t y pes of a nti -ca ncer t hera p y, i ncl u di n g d oses a n d n u m ber of c ycles recei ve d   
•  A d verse e ve nts usi n g N CI C T C A E Versi o n 4. 0 3  
•  Partici pati o n i n a n y ot her s u bse q ue nt cli nical trial, w here i n vesti gati o nal pr o d uct is 
a d mi nistere d  
5. 3. 9. 2  Cli nic Visit  
At a p pr oxi matel y 6 m o nt hs ( ± 2 wee ks ) a n d 1 2 m o nt hs ( ±2 wee ks ) after t he last d ose of st u d y 
dr u g ( S PI -2 0 1 2  or pe gfil grasti m) i n S PI -G C F -3 0 2  (t hr o u g h t h e e n d of C ycle 4  or earl y 
disc o nti n uati o n), patie nts will visit t he cli nic f or:  
•  Bl o o d dra w f or i m m u n o ge nicit y tes ti n g ( patie nts w h o ha ve use d a d diti o nal G-C S F 
pr o d ucts d uri n g t he f oll o w -u p will be e x cl u de d)  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 5  
•  M yel oi d gr o wt h fact or us e (i ncl u di n g t h e t y p e of G -C S F, t he sc he d ul e of a d mi nistrati o n 
a n d reas o n f or use)  
•  S u bse q ue nt t y pes of a nti -ca ncer t hera p y, i ncl u di n g d ose s a n d n u m ber of c ycles recei ve d   
•  A d verse e ve nts usi n g N CI C T C A E Versi o n 4. 0 3  
•  Partici pati o n i n a n y ot her s u bse q ue nt cli nical trial, w here i n vesti gati o nal pr o d uct is 
a d mi nistere d  
5. 3. 1 0  E n d of St u d y Visit ( M o nt h 1 2 Visit or 3 5  ( ± 5) d a ys after e arl y disc o nti n u ati o n)  
•  Bl o o d dra w f or i m m u n o ge nicit y testi n g if disc o nti n ue d pri or t o M o nt h 1 2  
•  C o nc o mita nt me dicati o ns li mite d t o G -C S F a n d ot her a nti -ca ncer t hera p y 
•  A d verse e ve nts usi n g N CI C T C A E Versi o n 4. 0 3  
5. 4  Descri pti o n of St u d y Assess me nts a n d Pr o ce d ures   
5. 4. 1  E x pl a n ati o n of  St u d y a n d O bt ai n i n g Writte n I nf or me d C o nse nt  
I nf or me d C o nse nt is t o be o btai ne d pri or t o t he start of a n y pr ot oc ol -s p ecifi e d assess me nts or 
pr oce d ures (i ncl u di n g re q uire d was h o ut of a n y pr o hi bite d me dicati o ns). T he Pri nci pal 
I n v esti gat or or desi g nee is t o disc uss t he st u d y f ull y wit h t he patie nt a n d o btai n writte n I nf or m e d 
C o nse nt. T he writte n I C F is t o be si g ne d b y t he patie nt a n d t he Pri nci pal I n v esti gat or or 
desi g nee. A c o p y of t he si g ne d I C F is t o be gi ve n t o t he patie nt. 
5. 4. 2  Me dic al Hist or y  
Me dical hist or y i n cl u des t he hist or y of t he n e o plastic disease, its pre vi o us t hera p y a n d 
i n vesti gati o ns as well as si g nifica nt p ast a n d all c o-e xisti n g diseases a n d c urre nt me dicati o ns f or 
t he pre vi o us 5 years. 
5. 4. 3  Re vie w I ncl usi o n/ E xcl usi o n Criteri a  
At Scree ni n g  a n d pri or t o e nr oll me nt, t he i ncl usi o n a n d e x cl usi o n criteria will be re vie we d b y 
t he Pri nci pal I n vesti gat or or ot her q ualifie d h ealt h care pr ofessi o nal t o e ns ure t hat t he patie nt 
q ualifies f or t he st u d y.  
5. 4. 4  R a n d o miz ati o n  
O nce it has bee n c o nfir m e d t hat a patie nt is e li gi ble f or e nr oll me nt, as assesse d b y S pectr u m, t he 
patie nt will be ra n d o mize d a n d recei ve a ra n d o mizati o n n u m ber acc or di n g t o t he i nf or mati o n i n 
Secti o n 8. 2 . 
5. 4. 5  P h ysic al E x a mi n ati o n  
A c o m plete p h ysical e x a mi nati o n, i ncl u di n g a des cri pti o n of e xter nal si g ns of t he ne o plastic 
disease a n d c o -m or bi dities is perf or me d at  t he Scree ni n g  Visit , D a y 1  of eac h c ycl e, a n d at t he 
E n d -of -Tre at me nt  Visit . Brief p h ysi cal e xa mi nati o ns are c o n d u cte d at all ot her visits. P h ysic al 
e x a m i nati o ns are t o be c o m plete d b y a p h ysi cia n or ot her healt h pr ofessi o nal lice nse d t o perf or m 
s uc h e x a mi nati o ns. Fi n di n gs will be d oc u me nt e d i n t he patie nt’s me dical r ec or d a n d o n t he 
a p pr o priate C R F . A n y a b n or malities are t o be rec or de d o n t he A E C R F .  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 7  
≤1. 0 × 1 0 9/ L at a n y ti me d uri n g C y cles 2  t o 4 , t he n dail y C B Cs will be re q uire d u ntil t he A N C is 
≥1. 5 × 1 0 9/ L, after reac hi n g na dir, b ut bl o o d sa m ples m ust still be dra wn o n D a ys 4 , 7 , 1 0 , a n d 1 5 .  
If t he patie nt c o nti n ues t o be ne utr o pe nic , t h e In vesti gat or will c o ns ult wit h S pectr u m  t o 
deter mi ne w het h er st u d y treat me nt s h o ul d be disc o nti n ue d. A h o me healt h care a ge n c y will be 
ma de a vaila ble f or t he c o n ve nie nce of patie nt s w h o d o n ot wis h t o ma ke m ulti ple tri ps t o t he 
st u d y site. 
5. 4. 1 0  C he mistr y  
Bl o o d c he mistr y a n al ysis will be perf or me d b y t h e ce ntral la b orat or y. Bl o o d sa m ples will be 
dra w n f or ser u m c h e mistr y p a nel, i ncl u di n g cal ci u m, s o di u m, p otassi u m, creati ni ne, t otal 
bilir u bi n, A S T, A L T, al k ali ne p h os p hatase, will b e dra w n at Scree ni n g , D a y 1  of eac h treat me nt 
c ycle a n d at t he E n d -of -Tre at me nt Visit . A uri n e b eta-h C G pre g na n c y test nee ds t o be 
perf or me d at S cree ni n g f or patie nts of c hil d beari n g p ote ntial.  
5. 4. 1 1  P h ar m a c o ki netic Assess me nts  
P har mac o ki netic sa m ples will be a nal yze d  b y a ce ntral la b orat or y. All patie nts i n t he S PI -2 0 1 2 
T re at me nt A r m will ha ve bl o o d sa m p les dra w n f or s parse P K sa m pli n g at 6 ti me p oi nts d uri n g 
t he st u d y peri o d f or p o p ulati o n P K a nal ysis. T he s a m pli n g ti me p oi nts will be: 
•  C ycle 1 :  
•  
D a y 2  ( 1 t o 4 h o urs after S PI -2 0 1 2  a d mi nistrati o n)  
•  
D a y 4  (at t he sa me ti me as C B C bl o o d dra w ) 
•  
D a y 5  (at t he same ti me as C B C bl o o d dra w ) 
•  C ycle 3 : 
•  
D a y 2  ( 1 t o 4 h o urs p ost-d ose)  
•  
D a y 4  (± 1 da y, at t he sa me ti me as C B C bl o o d dra w ) 
•  
D a y 7  (± 1 da y, at t he sa me ti me as C B C bl o o d dra w ) 
A h o me healt hcare a ge nc y will be ma d e a vaila ble f or t he c o n v e nie nce of patie nts w h o d o n ot 
wis h t o ma ke m ulti ple tri ps t o t he st u d y site.  
5. 4. 1 2  A nti -Infecti ve Use  
All a nti -i nfecti ves prescri be d b y  t h e In vesti gat or or patie nts’ ot her h ealt h care pr o vi ders d uri n g 
t he st u d y peri o d will be rec or de d o n t h e C R F .  
5. 4. 1 3  I m m u n o ge nicit y Testi n g  
I m m u n o ge nicit y sa m ples will be a nal yze d b y a ce ntral la b orat or y. T o assess i m m u n o ge nicit y, 
bl o o d sa m ples will be c ollecte d o n D a y 1  of C ycles 1  t o 4 , bef ore t he a d mi nistrati o n of 
c ortic oster oi ds, at t he E n d -of -Tre at me nt Visit , a n d als o at a p pr o xi matel y 6  m o nt hs a n d 1 2 
m o nt hs after C ycle 4 , D a y 2  or after t h e date of earl y disc o nti n uati o n . Patie nts w h o recei v e d 
S PI -2 0 1 2  will be teste d f or a nti b o dies t o S PI -2 0 1 2 , t he Fc re gi o n of t he S PI -2 0 1 2  m olec ule, t he 
P E G m oiet y, a n d G -C S F , a n d t h ose patie nts w h o recei ve d pe gfil grasti m will be teste d f or 
a nti b o dies t o S PI -2 0 1 2 , P E G a n d G -C S F. All sera sa m ples p ositi ve f or G -C S F -bi n di n g 
a nti b o dies will be f urt her teste d f or G -C S F n e utralizi n g a nti b o dies.   

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 8  
Details of bl o o d sa m ple c ollecti o n, pr ocessi n g, a n d s hi p p i n g i nstr ucti o ns are descri be d i n t he 
st u d y bi n der/la b orat or y ma n ual.  
5. 4. 1 4  A d verse E ve nt  
At e ver y visit, t he I n vesti gat or or desi g nee will i n q uire a b o ut a d verse e v e nts a n d i nterc urre nt 
ill nesses si nce t he last visit, w hic h 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) Scale Versi o n 4. 0 3 f or A E 
gra di n g, a n d will rec or d t he perti ne nt i nf or mati o n o n t he C R F . 
At a p pr o xi matel y 3 m o nt hs a n d 9 m o nt hs, t he I n v esti gat or or desi g nee will c o ntact t h e patie nt b y 
tele p h o ne a n d i n q uire a b o ut a d verse e ve nts a n d i nterc urre nt ill nesses si nce t he last visit, w hic h 
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 T er mi n ol o g y Criteri a 
f or A d verse E ve nts ( C T C A E) Scale Versi o n 4. 0 3 f or A E gra di n g, a n d will rec or d t h e perti ne nt 
i nf or mati o n o n t he C R F . At a p pr o xi matel y 6 m o nt hs a n d 1 2 m o nt hs A Es will be assesse d at t he 
st u d y site. 
5. 4. 1 5  C o nc o mit a nt Me dic ati o ns  
All me dicati o ns a d mi nistere d fr o m t he ti me t he I C F is si g ne d t hr o u g h 3 5 ( ± 5)  da ys after t he last 
d ose of st u d y dr u g a d mi nistrati o n will be rec or de d o n t he C R F . Start a n d st o p dates a n d reas o ns 
f or me dicati o n use will als o be n ote d.  A n y h os pitalizati o ns will als o be rec or de d o n t he C R F. 
After 3 5 ( ± 5)  da ys , a n d d uri n g t he 1 2 -m o nt h f oll o w -u p peri o d, o nl y a d diti o nal treat me nt wit h 
m yel oi d gr o wt h f act ors, i ncl u di n g fil grasti m, pe gfil grasti m or bi osi milars, a n d a d diti o nal ca ncer 
t hera p y will be rec or de d .  
6  S T U D Y D R U G A N D P H A R M A C E U TI C A L I N F O R M A TI O N  
6. 1  S PI -2 0 1 2  
S PI -2 0 1 2  will be s u p plie d b y S pectr u m .  
6. 1. 1  S PI -2 0 1 2  C o m p ositi o n  
S PI -2 0 1 2  ( 0. 6 m L) is s u p plie d i n prefille d  si n gle-use s yri n ges f or s u b c uta ne o us i njecti o n. Eac h 
prefille d  s yri n ge of S PI -2 0 1 2  c o ntai ns 1 3. 2 m g S PI -2 0 1 2,  e q ui vale nt t o 3. 6 m g G -C S F.  
6. 1. 2  S PI -2 0 1 2 St or a g e a n d H a n dli n g  
S PI -2 0 1 2  s h o ul d be st ore d u n der refri gerati o n wit h te m perat ur e c o ntr olle d bet wee n  2 º C a n d 8º C 
( 3 6º F t o 4 6º F) a n d pr ot ecte d fr o m li g ht . D o n ot s h a ke prefille d s yri n ges. If S PI -2 0 1 2  is 
acci de nt all y fr oze n, d o n ot use. S PI -2 0 1 2  prefille d  s yri n ges ca n b e left at r o o m te m perat ure f or 
u p t o 7 2 h o urs.  
6. 1. 3  S PI -2 0 1 2 A d mi nistr ati o n  
T he d ose of S PI -2 0 1 2  t o be a d mi nistere d is 1 3. 2 m g/ 0. 6 m L fi x e d d ose S PI -2 0 1 2  e q ui vale nt t o 
3. 6  m g  G -C S F  p er c ycle. S PI -2 0 1 2  s h o ul d be a d mi nistere d s u bc uta ne o usl y o n D a y 2 , 
a p pr o xi matel y 2 4 t o 2 6 h o urs  after T C a d mi nistrati o n.  T he e ntire c o nt e nt of t he prefille d s yri n ge 
s h o ul d be a d mi nistere d. N o d ose m o dificati o ns are all o we d. 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
3 9  
6. 2  Pe gfil gr asti m  
6. 2. 1  Pe gfil gr asti m  C o m p ositi o n  
Pe gfil grasti m will be s u p plie d b y S pectr u m  i n 0. 6 m L prefille d  si n gl e-use s yri n ges f or 
s u bc uta ne o us i njecti o n. Eac h s yri n ge c o ntai ns 6 m g pe gfil grasti m i n a sterile s ol uti o n.  
6. 2. 2  Pe gfil gr asti m  S u p pl y  
O n l y pe gfil grasti m ( Ne ul asta  [ N D C 5 5 5 1 3-1 9 0 -0 1]  ma n ufact ure d b y A m ge n i n t he U nite d 
States ) a n d s u p plie d b y S pectr u m  will be use d ; n o o t her G-C S Fs , i ncl u di n g bi osi mil ars , are  t o 
be use d i n t his st u d y .  
6. 2. 3  Pe gfil gr asti m St or a g e a n d H a n dli n g  
Pe gfil grasti m s h o ul d be st ore d a n d h a n dle d i n acc or da nce wit h t he Ne ulast a U nite d States 
Pac ka ge I ns ert ( U S PI ).  
6. 2. 4  Pe gfil gr asti m A d mi nist r ati o n  
Pe gfil grasti m 6  m g s h o ul d be a d mi nistere d s u bc ut a ne o usl y o nc e p er c h e m ot hera p y c ycl e o n 
D a y  2 , a p pr o xi matel y 2 4 t o 2 6 h o urs  after T C a d mi nistrati o n, acc or di n g t o t he ma n ufact urer’s 
prescri bi n g i nf or mati o n.  
T he e ntire c o nte nt of t he prefille d  s yri n ge s h o ul d be a d mi nistere d. N o d ose m o dificati o ns are 
all o we d.  
6. 3  Bli n di n g of St u d y Tre at me nts  
T his is a n o pe n -la bel st u d y. N o bli n di n g will be a p plie d.  
6. 4  R a n d o miz ati o n of St u d y Tre at me nts  
Patie nts w h o meet all eli gi bilit y criteria will be c o nsi dere d f or ra n d o mizati o n. Eli gi bilit y of all 
patie nts will be re vie we d a n d a p pr o ve d f or ra n d o mizati o n b y t he S p o ns or’s Me dical M o nit or, or 
desi g nee. Patie nts a p pr o v e d f or ra n d o mizati o n will be ra n d o mize d 1: 1 t o recei ve eit her S PI -2 0 1 2  
or pe gfil grast i m. T he det ail of t he ra n d o mizati o n sc he me is pr o vi de d i n Secti o n 8. 2 . 
6. 5  N o n -st u d y Tre at me nts 
6. 5. 1  Pri o r a n d C o nc o mit a nt Me dic ati o ns  
A c o nc o mita nt me dicati o n is a n y me dicati o n a patie nt e nteri n g t he trial is usi n g fr o m D a y 1  of 
C ycle 1  t o t he E n d -of -Tre at me nt  Visit . T he st u d y dr u gs are n ot c o nsi dere d c o nc o mita nt 
me dicati o ns.  
All c o nc o mita nt me dicati o ns rec or de d at trial e ntr y m ust ha ve a rel ate d, o n g oi n g c o n c o mita nt 
ill ness liste d u n der t he me dical hist or y at t he ti me of patie nt e ntr y i nt o t he trial u nless t he 
me dicati o n is use d f or pr o p h yla xis. Patie nts ma y c o nti n ue t o use a n y o n g oi n g me dicati o ns n ot 
pr o hi bite d b y t he pr ot oc ol.  
All prescri pti o n a n d o ver -t he-c o u nter me dicati o ns at trial e ntr y as w ell as a n y ne w me dicati o ns 
starte d d uri n g t he trial m ust be d oc u me nte d o n t he C R F  a n d i n t he s o urce d oc u me nts. T he 
d oc u me ntati o n s h o ul d c o nti n ue t hr o u g h t he e n d of t he 1 2 -M o nt h S afet y F oll o w -u p Peri o d  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 0  
(a p pr o xi matel y 1 2 m o nt hs  after t he last d ose of st u d y treat me nt) or 3 5  ( ± 5) da ys after t h e date of 
patie nt earl y disc o nti n uati o n.  D uri n g t he st u d y treat me nt peri o d a n d t he s u bse q ue nt 1 2 -m o nt h 
f oll o w-u p peri o d, a d diti o nal c o nc o mita nt treat me nt wit h m yel oi d gr o wt h fact ors, i ncl u di n g 
fil grasti m, pe gfil grasti m or its bi osi milars, a n d ot her  a nti-ca ncer t hera pies are pr o hi bite d wit h t he 
e x ce pti o n of h or m o nal t hera p y a n d H E R -2 tar gete d t hera p y f or t h e patie nts w h o nee d s uc h a 
tar gete d t hera p y.  
Pre me dicati o ns (s uc h as a ntie metics) use d f or s u p p orti ve care are all o we d as per i nstit uti o nal 
sta n dar ds or g ui deli nes.  
C ortic oster oi ds as pre me dicati o n f or d oceta xel are all o we d d uri n g st u d y tr eat me nt. Ot her use of 
s yste mic ster oi ds m ust b e a p pr o ve d b y t h e Me dical M o nit or.  
6. 5. 2  Pr o hi bite d T her a pies or Me dic ati o ns  
N o ot her a nti -ca ncer t hera p y i n cl u di n g c he m o t hera p y, ra diati o n t hera p y, i m m u n ot hera p y, or 
e x peri me ntal me dicati o ns are per mitte d d uri n g t h e st u d y, e x ce pt t hat r a diati o n t hera p y is all o we d 
d uri n g t he 1 2 -M o nt h Safet y F oll o w -u p Peri o d . A n y diseas e pr o gressi o n t hat re q uires a nti-t u m or 
t hera p y, ot her t h an T C, will be ca use f or disc o nti n uati o n fr o m t he trial.  
N o m yel oi d gr o wt h fact ors ot her t ha n st u d y dr u gs  (S PI -2 0 1 2  or pe gfil grasti m)  are t o be 
a d mi nistere d t o patie nts at a n y ti me d uri n g t h e treat me nt p hase or f oll o w -u p.  
N o w hite bl o o d cell  or w h ole bl o o d tra nsf usi o ns are all o we d. 
7  S A F E T Y A S S E S S M E N T  
7. 1  S afet y Me as ures  
It is t he res p o nsi bilit y of t he Pri nci pal I n vesti gat or t o o versee t he s afet y of t he patie nt s at t heir 
site a n d t o re p ort all A Es/ S A Es t hat are o bser ve d or re p orte d d uri n g t he st u d y, re gar dl ess of 
relati o ns hi p t o st u d y dr u g or cli nical si g nifi ca nce.  
Safet y d ata will  als o be re vie we d o n a re g ular basis b y S pectr u m’s  st u d y m o nit ori n g tea m, w hic h 
incl u des a Cli nical Researc h Ass ociate ( C R A ), Me dical M o nit or, a n d ot her pers o n nel fr o m t he 
c o m pa n y or its desi g n ee .  
A d verse e ve nts will be c haract erize d b y i nte nsit y (se verit y), ca usalit y, a n d seri o us ness b y t he 
I n v esti gat or base d o n t h e re g ulat or y defi ni ti o ns i ncl u de d bel o w. 
T his st u d y will utilize 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 v e nts ( C T C A E) Scale Versi o n 4 .0 3  f or A E gra di n g. 
7. 2  A d verse E ve nts  
A n A E is defi ne d as a n y u nt o war d  me dical o cc urre nce i n a patie nt or c li nical i n vesti gati o n 
patie nt, te m p orall y ass ociate d wit h t he use of a m e dici nal pr o d uct  or st u d y pr oce d ure , w het h er or 
n ot c o nsi dere d relate d t o t he me dici nal pr o d uct . T heref ore, a n A E ca n be a n y u nfa v ora bl e a n d 
u ni nte n de d si g n (i n cl u di n g a n a b n or mal la b o rat or y fi n di n g), s y m pt o m, or disease ( ne w or 
e x acer bate d) te m p orall y ass ociate d wit h t he use of a me dici nal pr o d u ct.  A treat me nt -e mer ge nt 
A E ( T E A E) is a n y A E t h at occ urs fr o m t he first d ose of st u d y tr eat me nt t hr o u g h 1 2 m o nt hs after 
t he last d ose of st u d y tr eat me nt or 3 5 ( ± 5)  da ys after t he date of patie nt earl y disc o nti n uati o n. 
A d diti o nall y, as a p plica ble, patie nts w h o recei ve at least o ne d ose of st u d y dr u g ( S PI -2 0 1 2  or 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 1  
pe gfil grasti m) will be f oll o we d f or safet y f or 1 2 m o nt hs after t he last d ose of st u d y tr eat me nt or 
date of patie nt e arl y disc o nti n uati o n . All A Es d uri n g t his ti me peri o d will be rec or de d. 
T he st u d y will rec or d all A Es acc or di n g t o t he i nf or mati o n i n  Secti o n 7. 3 . 
E x a m ples of A E s i ncl u de: 
•  E x acer bat i o n of a c hr o ni c or i nter mitte nt pre -e xisti n g c o n diti o n i ncl u di n g eit her a n 
i ncreas e i n fre q u e nc y a n d/ or i nte nsit y of t he c o n diti o n. 
•  Ne w c o n diti o ns detect e d or dia g n os e d after i n vesti gati o nal pr o d u ct a d mi nistrati o n . 
•  Si g ns, s y m pt o ms, or t he cli nical se q uela e of a s us pecte d dr u g i nteracti o n.  
•  Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her 
i n vesti gati o nal pr o d u ct or a c o nc urre nt me di cati o n. 
•  A Es ma y i n cl u de pre -treat me nt or p ost-treat me nt e ve nts t hat occ ur as a res ult of pr ot oc ol-
ma n date d pr oce d ures , ie, i n vasi ve pr oce d ures. 
A b n or mal la b orat or y res ults are t o be rec or de d as A Es, if a n y of t he f oll o wi n g c o n diti o ns are 
met:  
•  T he a b n or mal la b orat or y val ue lea ds t o a t hera p e utic i nter ve nti o n.  
•  T he a b n or mal la b orat or y val ue is c o nsi dere d t o b e cli nicall y si g nifica nt b y t he 
I n v esti gat or. 
•  T he a b n or mal la b orat or y val ue is pre defi ne d as a n A E i n t he pr ot oc ol or i n a n ot her 
d oc u me nt c o m m u nicate d t o t he I n v esti gat or b y S pectr u m  or desi g nee.  
•  T he a b n or mal  la b orat or y val ue is ≥Gra de 3 b ase d o n C T C A E V ersi o n 4. 0 3 . 
E x a m ples of e ve nts t hat  d o n ot c o nstit ute A Es i ncl u de : 
•  Me dical or s ur gic al pr oce d ure s (e g, e n d osc o p y, a p pe n dect o m y); t he c o n diti o n t hat lea ds 
t o t he pr oce d ure is a n A E. 
•  Sit uati o ns w here a n u nt o war d  me dical occ urre n ce d oes n ot occ ur ( e g, s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).  
•  A ntici pate d da y -t o-d a y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) prese nt or 
detecte d at t he start of t h e st u d y t hat d o n ot w ors e n.   
•  Pla n ne d a n d pres c h e d ule d h os pitalizati o ns a n d pr oce d ures.  
•  Pr o gressi ve disease . 
7. 3  G ui deli nes f or Rec or di n g a n d Attri b uti o n Sc ori n g of A d verse E ve nts  
Ti mel y a n d c o m plete re p orti n g of all A Es is re q uire d f or all patie nts. M o nit ori n g a n d 
d oc u me ntati o n of all A Es all o ws f or i de nt ificati o n of p ote ntial st u d y-dr u g or d ose -relate d A Es, 
a n d f or a d h ere n ce t o r e g ulat or y re q uire m e nts . Please refer t o t he C R F  C o m pleti o n G ui deli nes 
l ocate d i n t he st u d y bi n d er f or detaile d i nstr ucti o ns f or A E re p orti n g . 
7. 3. 1  Rec or di n g of A d verse E ve nts  
All A Es t hat occ ur fr o m t he first d ose of st u d y treat me nt t hr o u g h 3 5 ( ± 5)  d a ys after last d ose of 
st u d y treat me nt (S PI -2 0 1 2  or pe gfil grasti m) or 3 5 ( ± 5)  da ys after t he date of patie nt earl y 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 4  
•  I n cl u des i m p orta nt me dic al e ve nts t hat ma y n ot be i m me diatel y life-t hreat e 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 uir e i nter ve nti o n t o 
pre ve nt o ne  of t he o utc o mes liste d i n t his defi niti o n.  
A d verse e ve nts t hat d o n ot meet a n y of t he a b o v e criteria f or seri o us will b e re gar de d as n ot 
seri o us. 
7. 7. 1  Seri o us A d verse E ve nt Re p orti n g  
All S A Es t hat occ ur fr o m t he ti me t he st u d y I nf or me d C o nse nt  is o btai ne d a n d t hr o u g h 3 5 ( ± 5)  
da ys after l ast d ose of st u dy dr u g a d mi nistrati o n or 3 5 ( ± 5)  da ys after t he date of patie nt earl y 
disc o nti n uati o n  are t o be re p orte d t o S pectr u m  wit hi n 2 4 h o urs of k n o wle d ge of t he e v e nt. Fr o m 
t he ti me t he st u d y I C F is si g ne d t hr o u g h t he first d ose of st u d y dr u g a d mi nistrati o n, o nl y S A Es 
t hat are relate d t o st u d y pr oce d ures are t o be rec or de d. A d diti o nall y, all patie nts w h o recei ve at 
least o ne d ose of st u d y dr u g will ha ve all A Es rec or de d t hr o u g h t he e n d of t he 1 2  M o nt h S afet y 
F oll o w -u p Peri o d . 
S A Es (re gar dless of t heir relati o ns hi p t o st u d y treat me nt) are t o be re p ort e d a n d t he Seri o us 
A d verse E v e nt Re p ort (S A E R ) fa x e d or e -m aile d wit hi n 2 4 h o urs of k n o wle d ge of t he e ve nt t o:  
S pectr u m P h ar m ace uti c als, I nc . 
Pri m ar y C o nt a ct: P h ar m a c o vi gil a nce De p art me nt  
F a x: 
 
E -m ail: 
 
S pectr u m  ma y re q u est a d diti o nal i nf or mati o n fr o m t he I n v esti gat or t o e ns ure t he ti mel y 
c o m pleti o n of acc urate s afet y re p orts . Safet y dat a t hat are critical t o t he re p orta bilit y of a n S A E, 
s uc h as ca us alit y ass ess me nt a n d seri o usness  criteria, s h o ul d be i ncl u de d i n t he i nitial fa xe d or 
e-maile d S A E R . If o mitte d, a ti mel y res p o nse t o dr u g s afet y dat a q ueri es recei ve d fr o m S pectr u m  
or desi g n ee is e x pecte d.  
T he I n vesti gat or is t o ta k e all a p pr o pri ate t hera pe utic meas ures necessar y f or res ol uti o n of S A Es. 
A n y me di cati o ns necessar y f or treat me nt of t he S A E are t o b e rec or de d i n t he c o nc o mita nt 
me dicati o n secti o n of t he patie nt’s C R F . 
S A Es t hat are st u d y treat me nt -relate d will be f oll o we d u ntil res ol uti o n or u ntil t he y ha ve ret ur n e d 
t o Gra de 1, w hi c he ver is l o n ger, or u ntil it is deter mi ne d t hat t he o utc o me will n ot c ha n ge wit h 
f urt her f oll o w-u p.  
A d diti o nall y, t he S A E is t o be e ntere d i n t he A E C R F . F oll o w-u p S A E Rs n ee d t o be s u b mitte d t o 
S pectr u m wit hi n 2 4 h o urs o nce a d diti o nal i nf or mati o n re g ar di n g t he e v e nt bec o mes a v aila ble 
(e g, fi nal dia g n osis is ma de, la b orat or y or test res ults, e ve nt c o urse, o utc o m e, etc).  
S pectr u m  or desi g nee will be res p o nsi ble f or re p orti n g S A Es t o t he re g ulat or y a ut h orities i n 
acc or da nce wit h a p plica ble e x pe dite d re p orti n g re g ulat or y g ui deli nes. T he I n v esti gat or is 
res p o nsi ble f or s u b mitti n g S A Es t o his/ her l ocal I nstit uti o nal Re vie w B oar d (I R B)/ Et hics 
C o m mittee ( E C). C o pies of eac h S A E R , a n d d oc u me ntati o n of I R B/ E C n otificati o n a n d 
ac k n o wle d ge me nt of recei pt, will be ke pt i n t he Site’s Re g ulat or y Bi n der.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 5  
7. 7. 2  E xcl usi o ns t o Seri o us A d verse E ve nt Re p orti n g Re q uire me nts  
T he f oll o wi n g are n ot c o nsi dere d S A Es : 
•  Sit uati o ns w here a n u nt o war d me dical occ urre n ce di d n ot occ ur (e g, s o cial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital , h os pitalizati o n f or dia g n ostic tests s uc h as C T 
sca ns). 
•  A ntici pate d da y -t o-d a y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) p rese nt or 
detecte d pri or t o first st u d y treat me nt a d mi nistrati o n t hat d o n ot w orse n.  
•  Pla n ne d a n d p res c he d ule d h os pitalizati o ns a n d pr oce d ures.  
•  Pr o gressi ve disease . 
7. 8  Re pr o d ucti ve Ris ks  
N o a de q uat e a n d w ell -c o ntr olle d st u dies of S PI -2 0 1 2  ha ve bee n c o n d uct e d i n pre g n a nt w o me n. 
T he effect s of S PI -2 0 1 2  o n  fertilit y a n d fetal de v el o p me nt ha ve n ot bee n st u die d i n pre g na nt 
w o me n. S PI -2 0 1 2  is n ot rec o m me n de d f or use d uri n g pre g na n c y. 
Pre g n a ncies i n v ol vi n g a st u d y patie nt or a patie nt’s part ner, t hat occ ur fr o m t he first d ose of 
st u d y treat me nt t hr o u g h 3 5  ( ± 5) da ys after last d ose of st u d y dr u g a d mi nistrati o n or 3 5 ( ± 5)  da ys 
after t he d ate of p atie nt e arl y dis c o nti n uati o n, will  be re p ort e d wit hi n 2 4 h o urs after t h e 
I n v esti gat or has gai n e d k n o wle d ge of t he e ve nt vi a f a x or e-mail (see c o ntact i nf or mati o n i n  
Secti o n 7. 7. 1 ). Pre g na n cies s h o ul d be f oll o we d u p u ntil o utc o me a n d f oll o w -u p i nf or mati o n 
re gar di n g t he o ut c o me of t he pre g na n c y s h o ul d be fa x e d or e -maile d t o S pectr u m ’s 
P h ar mac o vi gila nce De part me nt.  
All patie nts w h o bec o me pre g na nt d uri n g partici pati o n i n t his st u d y are t o be wit h dra w n fr o m t he 
st u d y. 
8  S T A TI S TI C A L P L A N  
T his secti o n c o ntai ns a brief o ver vie w of t he statistical a nal yses  pla n ne d f or t his st u d y.  A f or mal 
statistical a nal ysis pla n ( S A P) will be fi nalize d pri or t o first patie nt e nr olle d .  
8. 1  S a m ple Size  
A p pr o xi matel y 2 1 8  p atie nts will be e nr olle d i n t his st u d y. T he pri mar y e n d p oi nt a nal ysis is base d 
o n t he test of n o n-i nferi orit y of S PI -2 0 1 2  as c o m p are d t o pe gfil grasti m.  
F or t he test of n o n -i nferi orit y h y p ot hesis, t he mar gi n of n o n-i nferi orit y t o be use d i n t he st u d y is 
0. 6 2 da y. T he tr ue differe nce bet w ee n t he mea ns is ass u me d t o be 0. 0 da ys. Sa m ple siz es of 
1 0 9  per treat me nt ar m will pr o vi de 9 0 %, 8 6 % , a n d 8 1 % p o wer t o det ect n o n -i nferi orit y usi n g a 
o ne -si de d, t w o-sa m ple t-t est at 2. 5 % le vel of si g nifica nce, w he n t he p o ole d sta n dar d de viati o n 
( S D) of t he D S N  is 1.4 , 1.5 , or 1.6  da ys, res p ecti vel y. T he p o ole d S D will be m o nit ore d i n t he 
o n g oi n g sister s t u d y S PI -G C F -3 0 1 . If t he p o ole d S D i n t he sister st u d y is esti mate d t o be greater 
t ha n 1.4  da ys, t he sa m ple siz e ma y be i ncreas e d t o reflect t he p ote ntial e xtra varia bilit y f or t he 
c urre nt st u d y. Si nce t he i nf or mati o n t hat ma y be use d is i n de pe n de nt of t he c urre nt st u d y res ults, 
t he n o mi nal t y pe I err or is preser ve d f or t he c urre nt st u d y. T he stu d y will e nr oll a n d ra n d o mize 
1 0 9  patie nts per ar m f or a t otal of a p pr o xi matel y 2 1 8  patie nts.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 6  
T he n o n -i nferi orit y of S PI -2 0 1 2  t o pe gfil grasti m will be declare d if t he u p per b o u n d of 9 5 % CI 
of t he differe nce i n mea n D S N  bet wee n t he treat m e nt ar ms is < 0. 6 2 da ys.   
8. 2  Met h o d of Tre at me nt Assi g n me nt, R a n d o miz ati o n, a n d/ or Str atific ati o n  
T he patie nts e nr olle d i n t his st u d y will be ra n d o mi ze d at a 1: 1 rati o t o  t he S PI -2 0 1 2  a n d 
Pe gfil gr asti m Tre at me nt Ar m s a n d stratifie d b y st u d y site. A ra n d o mizati o n sc he me usi n g a 
per m ute d bl oc k desi g n will be de vel o pe d. A n i nteracti ve we b res p o nse s yst e m will be use d t o 
assi g n a ra n d o mizati o n i de ntificati o n (I D) o nce p atie nts meet eli gi bilit y criteria a n d are rea d y t o 
be ra n d o mize d. T he ra n d o mizati o n I D will be differe nt t ha n t he Patie nt I D, a n d a ma p pi n g of 
ra n d o mizati o n I D t o Pati e nt I D will be ke pt i n a s ec ure d d ata bas e.  
8. 3  A n al ysis P o p ul ati o ns  
•  I nte nt-t o-Tre at P o p ul ati o n  (I T T): will c o nsist of all patie nts w h o are ra n d o mize d . 
Patie nts will be a nal yze d as ra n d o mize d  if t he act u al treat me nt assi g n me nts de viate fr o m 
t he ra n d o mizati o n sc he me.  
•  Per Pr ot oc ol ( P P) P o p ul ati o n:  will  i ncl u de all patie nts i n t he I T T p o p ul ati o n wit h n o 
maj or pr ot oc ol de viati o n  i n C ycle 1 . Patie nts will be a nal yz e d as tr eate d if t he act ual 
treat me nt assi g n me nts de viate fr o m t he ra n d o mizati o n sc he me.  
•  S afet y A n al ysis P o p ul ati o n  (S A F ): will c o nsist of all patie nts w h o recei ve at least o ne 
d ose of a n y pr ot o c ol -s pecifie d dr u g ( T C or S PI -2 0 1 2  o r pe gfil grasti m) 
Patie nts w h o disc o nti n ue fr o m t he st u d y pri or t o ra n d o mizati o n will be re place d  as t he y are n ot 
c o nsi dere d t o be t h e I T T patie nts .  
8. 4  Ge ner al St atistic al Met h o ds  
S pectr u m’s Bi ostatistics a n d Data Ma n a ge me nt ( B D M) gr o u p  ( or a c o ntracte d data ma na ge me nt 
ve n d or) will be res p o nsi ble f or data m a na ge me nt a n d statistical a nal ysis of t his st u d y. All 
statistical a nal ys es will be perf or me d usi n g S A S f or Wi n d o ws ( versi o n 9. 3  or hi g her). Patie nt 
data listi n gs a n d ta b ular prese ntati o ns of res ults will be pr o vi de d. F urt her details of t he criteri a 
a n d c o n d uct of t he st atistical a nal yses will be i ncl u de d i n t he Statistical A nal ysis Pla n f or t his 
st u d y t o be fi naliz e d pri or t o first patie nt e nr olle d. 
8. 5  Effic ac y A n al yses  
8. 5. 1  Pri m ar y E n d p oi nt  
T he pri mar y a n al ysis of t he c o m paris o n of t he D S N  i n C ycle 1  bet w ee n t he S PI -2 0 1 2 
Tre at me nt Ar m a n d t he Pe gfil gr asti m Tre at me nt Ar m will be c o n d ucte d usi n g t he I T T 
P o p ul ati o n . 
D S N  i n C ycle 1  is defi ne d  as t he n u m ber of d a ys of se vere ne utr o p e nia ( A N C < 0. 5 × 1 0 9/ L) fr o m 
t he first occ urre nce of a n A N C bel o w t he t hres h ol d. T he assess me nt of A N C will be perf or me d 
o n D a y 1  a n d D a ys 4 -1 5  i n C ycle  1 . T he e n d p oi nt will be meas ure d i n all p atie nts i n t he I T T 
P o p ul a ti o n. F or patie nts w h o d o n ot meet se vere ne utr o pe nia criteria, t he e n d p oi nt meas ure me nt 
will be defi ne d as  D S N = 0.  
F or t he pri mar y efficac y a nal ysis, t he m ea n D S N  i n C ycle 1  will be c o m pare d bet wee n t he 
S PI -2 0 1 2 Tre at me nt Ar m  a n d t he P e gfil gr asti m T re at me nt A r m usi n g a b o otstra p resa m pli n g 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 7  
met h o d wit h n o n -i nferi orit y h y p ot hesis. A 2-si de d 9 5 % c o nfi de n ce i nter val ( CI) of t he differe nce 
bet wee n t he m ea n D S N  of t he S PI -2 0 1 2 T re at me nt A r m a n d t he m ea n D S N  of t he 
P e gfil gr asti m Tre at me nt A r m will be calc ul at e d usi n g b o otstra p resa m pli n g  wit h treat me nt as 
t he o nl y stratificati o n fact or. T he st u d y will use n o n i nferi orit y m ar gi n of 0. 6 2 da y s f or t he a b o ve 
c o m paris o n. T he n o n -i nf eri orit y of S PI -2 0 1 2  t o pe gfil grasti m will be declare d if t he u p per b o u n d 
of 9 5 % C I of t he differe n ce i n mea n D S N  b et wee n t he treat me nt ar ms is < 0. 6 2  da y s.  
Pri mar y a nal ysis f or t he n o n -i nferi orit y h y p ot hesis will be base d o n  t he I T T p o p ulati o n. A n 
anal ysis b ase d o n t he P P  P o p ul ati o n  will be perf or me d as a se nsiti vit y a nal ysis .  
I n a d diti o n t o b o otstra p resa m pli n g met h o d t o calc ulate 9 5 % CI of t h e differe nce i n mea n D S N  
bet wee n tr eat me nt ar ms, t he test of t he differe nce i n mea n D S N  bet wee n tr eat me nt ar ms will be 
c o n d ucte d usi n g P oiss o n distri b uti o n  as a n ot her se nsiti vit y a n al ysis. If t he data is o ver dis perse d, 
a ne gati ve bi n o mial distri b uti o n will be i nc or p orat e d f or t he test. F or t he P oiss o n a n d ne gati ve 
bi n o mial re gressi o n, t he i de ntical li n k will be use d a n d treat me nt will be t he o nl y c o v ariate i n t he 
m o del. T he differe nce i n me a n D S N  bet wee n S PI -2 0 1 2  a n d p e gfil grasti m will be calc ulate d 
al o n g wit h 2 -si de d 9 5 % CI, bas e d o n P oiss o n or ne gati ve bi n o mial re gressi o n. Base d o n t h e 
i nitial re vie w of t he effici e nc y of t he esti mates of b o otstra p, P oiss o n a n d ne gati ve bi n o mial 
distri b uti o ns, 9 5 % CI cal c ulate d usi n g b o otstr a p resa m pli n g met h o d a p p ear t o be r o b ust a n d 
t heref ore is pr o p ose d t o b e t he pri mar y a nal ysis  met h o d f or t he pri mar y e n d p oi nt.  D etaile d 
si m ulati o n res ults will be pr o vi de d al o n g wit h S A P.  
A d diti o nal se nsiti vit y a n al yses will als o be use d t o e x a mi ne  t he: 
•  T reat me nt effect, a dj usti n g f or t he vari o us st u d y sites. T his a nal ysis will be carri e d o ut 
usi n g t he sa me m et h o d ol o g y as t h e pri mar y a n al ysis ( b o otstra p resa m pli n g met h o d) , a n d 
st u d y site will be use d as a n a d diti o nal stratificati o n fact or i n t he resa m pli n g.  
•  T reat me nt effect, a dj usti n g f or disease st at us at ra n d o mizati o n (a dj u va nt or ne oa dj u va nt). 
T his a nal ysis will be t he sa me as t he pri mar y a nal ysis ( b o otstra p resa m pli n g met h o d) a n d 
disease stat us will be use d as a d diti o nal stratificati o n fact or i n t he resa m pli n g.  
•  I m pa ct of missi n g d ata, usi n g a w orst case s ce n ari o. W he n A N C data are missi n g o n or 
after D a y 5 , a n d bef ore p atie nts’ A N C i ncrease t o ≥1. 5 × 1 0 9/ L after t he e x pecte d na dir i n 
C ycle 1 , missi n g A N C val ues will be i m p ute d as < 0. 5 × 1 0 9/ L f or S PI -2 0 1 2  a n d ≥0. 5 ×
1 0 9/ L f or pe gfil grasti m, f or t he p ur p ose of D S N  calc ulati o n. T he met h o d of a nal ysis of 
i m p ute d D S N  data usi n g w orst case s ce nari o will be t he sa me as t h e pri mar y a n al ysis 
( b o otstra p res a m pli n g met h od).  
I n a d diti o n, t he f oll o wi n g s u b gr o u ps will be e x a mi ne d f or D S N  i n C ycl e 1 :  
•  A ge : < 6 5 y ears, ≥6 5 y ea rs 
•  Ge n der ( Male, Fe male)  
•  Race  
•  Disease Stat us ( A dj u va nt, Ne oa dj u va nt) at ra n d o mizati o n  
•  Ge o gra p hic R e gi o n  
•  Wei g ht : < 6 5 k g, 6 5 t o 7 5 k g, or > 7 5 k g  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 8  
8. 5. 2  Ke y Sec o n d ar y E n d p oi nts  
•  T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m i n:  
 Ti me t o A N C Rec o v er y i n  C ycle 1 , defi ne d as t h e ti me fr o m c he m ot hera p y 
a d mi nistrati o n u ntil t he patie nt ’s A N C i ncreases t o ≥1. 5 × 1 0 9/ L after t he e x pecte d 
na dir. F or patie nts wit h A N C val ue ≥1. 5 × 1 0 9/ L at all ti mes, T i me t o A N C R ec o ver y 
will be assi g ne d t o a val u e of 0 . 
 De pt h of A N C N a dir , defi ne d as t he p atie nt’s l o west A N C i n C ycle 1  
 I nci de nce of F N i n patie nts d uri n g C ycl e 1 , i n w hic h F N  is d efi ne d as a n oral 
te m perat ur e > 3 8. 3° C ( 1 0 1. 0° F) or t w o c o nsec uti v e rea di n gs of > 3 8. 0° C ( 1 0 0. 4° F) f or 
2 h o urs a n d A N C < 1. 0 × 1 0 9/ L 
8. 5. 3  A d diti o n al Sec o n d ar y E n d p oi nts  
•  T o c o m pare S PI -2 0 1 2  wit h pe gfil grasti m i n:  
 D S N  i n C ycles 2 , 3 , a n d 4  
 I nci de nce of Ne utr o pe nic C o m plic ati o ns, i ncl u di n g use of a nti-i nfecti ves a n d 
h os pitaliz ati o ns, i n patie nts d uri n g C ycl e 1  
 I n ci de nce of F N  i n C y cles 2 , 3 , a n d 4  
 R DI  of T C i n C ycles 1  t o 4  
 Safet y  
T he a nal yses of Ke y Sec o n dar y E n d p oi nts will e m pl o y a hierarc hical cl os e d testi n g pr oce d ure 
[2 9 ], w here e n d p oi nts are ra n ke d wit h t he pri mar y e n d p oi nt first a n d t he n t he Ke y Sec o n d ar y 
E n d p oi nts i n t he or der liste d a b o ve. S pecifi call y, t he or der of testi n g is:  
1.  D S N  i n C ycle 1  
2.  Ti me t o A N C Rec o v er y  i n C ycle 1  
3.  De pt h of A N C Na dir i n C ycle 1  
4.  I n ci de nce of F N  i n C y cle 1  
F or t he sec o n dar y efficac y a n al ys es, t he res ults will eac h be s u m marize d b y Treat me nt Ar m a n d 
C ycle a n d will use t he I T T p o p ulati o n. T w o -si de d 9 5 % CI f or t he differe nce bet wee n t he 
treat me nt ar ms will be calc ulate d. 
N o a dj ust me nt t o al p ha will be necessar y o nce t h e prece di n g e n d p oi nt c o m paris o n is si g nifica nt 
f or t he s u bse q ue nt e n d p oi nts i n t he a b o ve or der of e n d p oi nts, with eac h test at t he sa me 
si g nifica n ce le v el of α = 0. 0 5. 
8. 6  A n al ysis of S afet y  
T he o verall i nci de nce of treat me nt -e mer ge nt A Es ( T E A E) (i e, A Es occ urri n g fr o m t he ti me t he 
first d ose of t he st u d y dr u g t hr o u g h 1 2 m o nt hs  aft er t he last d ose of st u d y dr u g a d mi nistrati o n or 
3 5 ( ± 5)  da ys after t he d ate of patie nt earl y disc o nti n uati o n) a n d t he pr o p orti o n of patie nts w h o 
disc o nti n ue beca us e of a T E A E are t he pri mar y s afet y o ut c o me meas ures.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
4 9  
T he n u m ber a n d p erce nt of patie nts wit h ne w -o ns et T E A Es will be s u m marize d b y t he Me d D R A 
S yste m -Or ga n -Class ( S O C) le vel a n d P referre d T er m ( P T) f or all treate d patie nts. T he s u m mar y 
of T E A Es will be pres e nte d i n t he f oll o wi n g cate g ories:  
•  N u m ber a n d p erce nta ge of patie nts wit h a n y T E A Es b y S O C  a n d P T . 
•  N u m ber a n d p erce nta ge of patie nt s wit h a n y S A Es b y S O C  a n d P T . 
•  N u m ber a n d p erce nta ge of patie nts wit h relate d T E A Es b y S O C  a n d P T . 
•  
Relate d t o T C  
•  
Relate d t o S PI -2 0 1 2  
•  
Relate d t o pe gfil grasti m   
•  N u m ber a n d p erce nta ge of patie nts wit h T E A Es ca usi n g disc o nti n uati o n of t he st u d y b y 
S O C  a n d P T . 
•  N u m ber a n d p erce nta ge of patie nts wit h A Es of S pecial I nterest  b y P T  
•  
M usc ul os keletal p ai n  
•  
I nje cti o n site reacti o ns 
•  
H y p erse nsiti vit y reacti o ns   
I n a d diti o n, t he n u m ber a n d perce nt of patie nts wit h T E A Es b y gra d e will be s u m marize d. 
A d verse e ve nts re p orte d pri or t o treat me nt b ut aft er I nf or me d C o nse nt will be pr o vi de d i n a 
listi n g. A n e x p os ure -res p o nse a nal ysis will be perf or me d base d o n s p arse P K sa m pli n g. 
8. 7  Cli nic al L a b or at or y  a n d  Vit al Si g ns  E v al u ati o ns  
Ke y la b orat or y para meters  a n d vital si g ns  will be s u m m arize d usi n g s hift ta bles, w hic h will 
dis pla y a cr oss -ta b ulati o n of t he B aseli ne  gra de v ers us t he hi g h est o n -st u d y gra de f or eac h 
la b orat or y para meter.  
All a b n or malities will be classifie d acc or di n g t o N CI C T C A E Versi o n 4. 0 3  a n d s u m marize d b y 
w orst gra de s e verit y per patie nt b y c ycle a n d b y tr eat me nt wit hi n c ycle.  
9  A D MI NI S T R A TI V E P R O C E D U R E S A N D S T U D Y M A N A G E M E N T   
9. 1  I n vesti g at or Res p o nsi bilities  
9. 1. 1  G o o d Cli nic al Pr a ctice  
It is t he res p o nsi bilit y of t he Pri nci pal I n vesti gat or t o o versee t he s afet y of t he patie nts at t heir 
site. 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 f ull c o m plia nce wit h t he 
pri nci ples of t he “ D eclarati o n of Helsi n ki” (as a me n de d i n T o k y o, Ve nice, H o n g K o n g, a n d 
S o ut h Africa), I C H g ui d eli nes, or wit h t he la ws a n d re g ulati o ns of t he c o u ntr y i n w hi c h t he 
researc h is c o n d u cte d. B y si g ni n g t he U S F or m F D A 1 5 7 2, “ State me nt of I n v esti gat or,” t he 
I n v esti gat or c o m mits t o a d here t o a p plica ble secti o ns of t he U S C F R parts 5 0 “ Pr otecti o n of 
H u ma n Patie nts ,” 5 4 “ Fi na ncial Discl os ure b y Cli nical I n vesti gat ors ,” 5 6 "I nstit uti o nal Re vie w 
B oar ds ,” a n d 3 1 2 s u b part D “ Res p o nsi bilities of S p o ns ors a n d I n vesti gat ors .” All I n v esti gat ors 
will e ns ure a d here nce t o I C H g ui deli nes f or G C P a n d Cli nical Safet y Data Ma na ge me nt . 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
5 0  
9. 1. 2  I nstit uti o n al Re vie w B o ar d/ Et hics C o m mittee A p pr o v al 
T he I n vesti gat or s hall ass ure t hat t he I R B/ E C will pr o vi de i nitial a n d c o nti n ui n g re vi e w of t he 
st u d y. Pri or t o scree ni n g a n d e nr oll me nt of st u d y patie nts, d oc u me nte d I R B/ E C a p pr o val of t h e 
pr ot oc ol, I C F a n d a n y patie nt materials m ust be o btai ne d a n d pr o vi de d t o S pectr u m or its 
desi g nee.  
9. 1. 3  I nf or me d C o nse nt  
T he i n vesti gat or will e ns ure t hat t he met h o d of o btai ni n g a n d d o c u me nti n g t he Inf or me d C o nse nt 
c o m plies wit h I C H -G C P a n d all a p plica ble re g ulat or y re q uire m e nt(s). I nf or me d C o nse nt m ust be 
o btai ne d bef ore st u d y pr oce d ures are p erf or me d, u nless perf or m e d as sta n dar d of care. T he 
s u bject’s s o urce d oc u me nts s hall d oc u me nt t he i nf or me d c o nse nt pr ocess a n d t hat I nf or me d 
C o nse nt was o btai ne d pri or t o st u d y par tici pati o n. A c o p y of eac h si g ne d I C F m ust be pr o vi de d 
t o t he patie nt or t he patie nt’s le gall y a ut h orize d re prese ntati ve. All si g ne d IC F s m ust re mai n i n 
eac h p atie nt’s st u d y file a n d m ust be a vaila ble f or verificati o n at a n y ti me.  
9. 1. 4  St u d y Files a n d Rete nti o n  of Rec or ds  
T he I n vesti gat or will ret ai n all st u d y rec or ds u ntil at least 2 years after t he l ast a p pr o val of a 
mar keti n g a p plicati o n or at least 2 years ha ve ela pse d si nce t he f or mal disc o nti n uati o n of cli nical 
de vel o p me nt of t he i n vesti gati o nal pr o d uct. T h ese d oc u me nts will be retai n e d f or a l o n ger 
peri o d, h o we v er, if re q uire d b y t he a p plica ble re g ulat or y re q uire m e nts or b y a n a gree me nt wit h 
S pectr u m. If t he I n v esti gat or rel oc ates, or f or a n y reas o n desir es t o dis p ose of t he rec or ds, t he 
st u d y rec or ds ma y b e tra nsferre d t o a n ot her i nstit uti o n, a n ot her i n vesti gat or, or t o S pectr u m u p o n 
writte n a gree me nt bet w ee n t he I n vesti gat or a n d S pectr u m.  
9. 2  Rec or di n g a n d C ollecti n g of D at a  
I n acc or da n ce wit h I C H a n d G C P g ui deli nes, t he I n v esti gat or will mai ntai n c o m plete, acc urat e, 
le gi ble, a n d easil y retrie v a ble data, a n d will all o w pers o n nel a ut h orize d b y S pectr u m access t o all 
st u d y data at a n y ti me. S uc h data s hall als o be s ec ure d i n or der t o pre ve nt l oss of data.  
9. 2. 1  C ase Re p ort F or ms  
At sc he d ule d m o nit ori n g visits, C R F s will be verifie d a gai nst s o urce d o c u m e ntati o n a n d 
s u b mitte d as fi nal data. A n y s u bse q u e nt c ha n ges t o t he C R F s are t o be perf or me d i n acc or da n ce 
wit h S pectr u m’s sta n dar d o perati n g pr oce d ures f or e diti n g a n d clarif yi n g C R F s. Data e ntr y will 
be perf or me d b y  t he sites usi n g a n electr o nic d ata ca pt ure ( E D C) s yste m.  
9. 2. 2  Dr u g Acc o u nt a bilit y  
I n acc or da n ce wit h all a p plica ble re g ulat or y re q uir e me nts, t he I n vesti gat or or desi g n ate d site 
staff is t o mai ntai n st u d y treat me nt acc o u nta bilit y rec or ds t hr o u g h o ut t he c o urse of t he st u d y. 
T his pers o n(s) will d oc u me nt t he a m o u nt of t he st u d y dr u g ( S PI -2 0 1 2  or pe gfil grasti m  
a d mi nistere d t o patie nts. T he C R A will re vie w i n v e nt or y a n d acc o u nta bilit y d oc u me ntati o n 
d uri n g m o nit ori n g visits.  
T he I n vesti gat or will n ot s u p pl y i n vesti ga ti o nal st u d y dr u gs t o ot her i n vesti gat ors n ot liste d o n 
t he U S F or m F D A 1 5 7 2 or e q ui vale nt. I n v esti gati o nal st u d y dr u g us e, ot her t ha n as directe d b y 
t his pr ot oc ol, is n ot all o we d. 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
5 1  
All u n use d s yri n ges of S PI -2 0 1 2  are t o b e acc o u nte d f or at t he site a n d m ai ntai ne d i n a sec ure d, 
l oc ke d st ora ge area wit h access li mite d t o a ut h orize d st u d y p ers o n nel o nl y. Use d S PI -2 0 1 2  
s yri n ges will be destr o ye d per i nstit uti o n, l ocal, a n d all a p plica ble p olicies a n d pr oce d ures. After 
st u d y c o n cl usi o n, all u n use d s yri n ges of S PI -2 0 1 2  ma y b e destr o ye d at t he site, f oll o wi n g 
verificati o n of acc o u nt a bilit y b y a S pectr u m re prese ntati ve.  
9. 3  Pr ot oc ol C o m pli a nce  
T he Pri nci pal 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 uct e d i n acc or da nce wit h 
t he pr oce d ures a n d e val u ati o ns descri be d i n t his pr ot oc ol. 
9. 4  S p o ns or Res p o nsi bilities  
9. 4. 1  St u d y M o nit ori n g  
T he st u d y will be m o nit ore d b y e m pl o yees or re prese ntati ves of S pectr u m. C R As will m o nit or 
eac h site o n a p eri o dic b asis a n d perf or m v erificati o n of s o urce d o c u me ntati o n f or eac h patie nt as 
well as ot her r o uti ne c o m plia nce re vi e ws. S pectr u m’s Me dical M o nit or a n d P har mac o vi gila nce 
De part me nt will re vi e w s afet y data a n d be res p o nsi ble f or e ns uri n g ti mel y re p orti n g of e x pe dite d 
S A E Rs t o re g ulat or y a ge ncies a n d I n v esti gat ors.  
9. 4. 2  S afet y M o nit or i n g 
T he cli nical dr u g safet y of st u d y tr eat me nt will be c o nti n u o usl y e val u ate d b y t he st u d y Me dical 
M o nit or or desi g n ee o n a n o n g oi n g basis d uri n g t h e c o urse of t his cli nical st u d y. All S A Es 
relate d t o st u d y treat me nt i n t his st u d y a n d all ot her o n g oi n g cli nical st u dies wit h st u d y treat me nt 
will be pr ocesse d i n c o m plia nce wit h c urre nt re g ulat or y g ui deli nes b y S pectr u m’s 
P har mac o vi gila nce De part me nt. T his pr ocessi n g will i ncl u de a f or mal ass ess me nt of eac h S A E 
b y dr u g s afet y. I n a d diti o n, a c u m ulati ve re vi e w  of all S A Es fr o m all s o urces will be assesse d 
peri o dicall y  
9. 5  J oi nt I n vesti g at or/ S p o ns or Res p o nsi bilities  
9. 5. 1  Access t o I nf or m ati o n f or M o nit ori n g a n d A u diti n g  
I n acc or da n ce wit h I C H G C P g ui deli nes a n d 2 1 C F R 3 1 2, t he C R A/a u dit or is t o ha ve direct 
access t o t he  patie nt’s s o urce d oc u m e ntati o n i n or der t o verif y t he data rec or de d i n t he C R F s. 
T he C R A is res p o nsi ble f or r o uti ne re vie w of t he C R F s at re g ular i nter vals t hr o u g h o ut t he st u d y 
a n d t o verif y a d h ere n ce t o t he pr ot oc ol, as well as t he c o m plete ness, c o nsist e nc y, a n d acc urac y of 
t he data bei n g rec or de d. T he C R A/a u dit or is t o ha ve access t o a n y patie nt r ec or ds nee de d t o 
verif y t he e ntri es o n t he C R F s, as well as access t o all ot her st u d y-relat e d d oc u me ntati o n a n d 
materials. T he I n v esti gat or a grees t o pr o vi de t h e m o nit or wit h s ufficie nt ti me a n d facilities t o 
c o n d uct m o nit ori n g.  
9. 5. 2  Ter mi n ati o n of t he St u d y  
F or reas o na bl e ca us e, eit her t he I n v esti gat or or S pectr u m ma y ter mi nate t h e I n vesti gat or’s 
partici pati o n i n t his st u d y. I n a d diti o n, S pectr u m P har mace uticals I nc.  m a y ter mi nate t he st u d y at 
a n y ti me u p o n i m me diate n otice f or a n y reas o n, i n cl u di n g b ut n ot li mite d t o, S pectr u m’s belief 
t hat ter mi nati o n is necess ar y f or t he s afet y of patie nts. 

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
5 2  
9. 5. 3  P u blic ati o n P olic y  
T o c o or di nate t he disse mi nati o n of data fr o m t his st u d y,  S pectr u m e n c o ura ges t he f or mati o n of a 
p u blicati o n c o m mittee c o nsisti n g of t he Pri nci pal I n vesti gat or a n d a p pr o priate S pectr u m staff. 
T he c o m mittee is e x pecte d t o s olicit i n p ut a n d assista nce fr o m ot her In vesti gat ors a n d S p o ns or 
staff as a p pr o priate. M e m bers hi p o n t he c o m mittee ( b ot h f or In vesti gat ors a n d S taff) d o es n ot 
g uara nte e a ut h ors hi p - t he criteria d escri be d b el o w s h o ul d be met f or e ver y p u blicati o n. 
A ut h ors hi p of a n y p u blicati o ns res ulti n g fr o m t his st u d y will be deter mi ne d o n t he basis of t he 
U nif or m Re q uire me nts f or Ma n uscri pt S u b mitte d t o Bi o me dical J o ur nals (I nter nati o nal 
C o m mittee of Me dical J o ur nal E dit ors, 2 0 0 5), w hi c h states:  
•  A ut h ors hi p cre dit s h o ul d be base d o n t he f oll o wi n g; a ut h ors s h o ul d meet all t hree 
c o n diti o ns:  
1.  S u bsta ntial c o ntri b uti o ns t o c o nce pti o n a n d desi g n, ac q uisiti o n of data, or a n al ysis 
a n d i nter pret ati o n of data;  
2.  Drafti n g t he article or re visi n g it criticall y f or i m p orta nt i ntellect ual c o nte nt; a n d  
3.  Fi nal a p pr o val of t he versi o n t o be p u blis he d.  
•  W he n a lar ge, m ultice nter gr o u p has c o n d u cte d t h e w or k, t he gr o u p s h o ul d i de ntif y t he 
i n di vi d uals w h o acce pt direct res p o nsi bilit y f or t h e ma n uscri pt. T hes e i n di vi d uals s h o ul d 
f ull y meet t he criteri a f or a ut h ors hi p defi ne d a b o v e.  
•  Ac q uisiti o n of f u n di n g, c ollecti o n of data, or ge neral s u per visi o n of t he res earc h gr o u p 
al o ne d oes n ot c o nstit ute a ut h ors hi p.  
•  All pers o ns desi g n ate d as a ut h ors s h o ul d q ualif y f or a ut h ors hi p, a n d all t h ose w h o q ualif y 
s h o ul d be liste d. 
•  Eac h a ut h or s h o ul d ha v e partici pate d s ufficie ntl y i n t he w or k t o ta ke p u blic res p o nsi bilit y 
f or a p pr o priate p orti o ns of t he c o nte nt. 
All p u blicati o ns (e g, m a n uscri pts, a bstracts, or al/sli de prese ntati o ns, b o o ks c ha pters) base d o n 
t his st u d y m ust be s u b mitte d t o S pectr u m wit hi n 3 0 da ys ( b ut n o less t ha n 1 0 da ys) pri or t o 
s u b missi o n or p u blicati o n f or c or p orate re vie w.  
9. 6  C o nfi de nti alit y  
All i nf or mati o n pr o vi de d t o t he I n v esti gat or b y S pectr u m, i ncl u di n g n o n cli nical data, pr ot oc ols, 
C R F s, a n d ver bal a n d writte n i nf or mati o n, will be ke pt strictl y c o nfi de ntial a n d c o nfi ne d t o t he 
cli nical pers o n nel i n v ol v e d i n c o n d ucti n g t his st u d y, a n d n o dis cl os ure s hall be ma de e x ce pt i n 
acc or da nce wit h a n y ri g ht of p u blicati o n gra nte d t o t he I n v esti gat or. All pers o n nel will ha n dle 
patie nt data i n a c o nfi de ntial ma n ner i n  acc or da n ce wit h a p plica ble re g ulati o ns g o ver ni n g cli nical 
researc h. U p o n re q uest b y a re g ulat or y a ut h orit y s uc h as t he U S F D A a n d ot her re g ulat or y 
a ut h orities w orl d wi de, t h e I n vesti gat or/i nstit uti o n is t o ma ke a vaila ble f or direct access all 
re q ueste d st ud y -relate d rec or ds or re p orts ge n erate d as a res ult of a patie nt’s partici pati o n i n t his 
st u d y. T his i nf or mati o n ma y b e relat e d i n c o nfi de nce t o t he I R B/ E C or ot h er c o m mittee 
f u ncti o ni n g i n a si milar ca pacit y. I n a d diti o n, n o r e p orts or i nf or mati o n a b o ut the st u d y or its 
pr o gress will be pr o vi de d t o a n y o n e n ot i n v ol ve d i n t he st u d y ot her t h a n t o S pectr u m, or i n 
c o nfi de nce t o t he I R B/ E C or si milar c o m mittee, e x ce pt if re q uire d b y la w.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
5 3  
1 0  R E F E R E N C E S  
1.  
A merica n Ca n cer S oci et y - Ca n cer Facts a n d  Fi g ures 2 0 1 4.  
2.  
Nati o nal C o m pre he nsi ve Ca ncer Net w or k. Breast Ca ncer ( Versi o n 3, 2 0 1 4) [ Se pte m ber 
2, 2 0 1 4]. A vaila ble fr o m: w w w. ncc n. or g/ pr ofessi o nals/ p h ysicia n _ gls/ p df/ breast. p df.  
3.  
Harla n L C, A bra ms J, Warre n J L, Cle g g L, Ste ve ns J, Ballar d -Bar bas h R.  A dj u va nt 
T hera p y f or Breast Ca ncer: Practice Patter ns of C o m m u nit y P h ysicia ns. J Cli n O nc ol. 
2 0 0 2; 2 0( 7): 1 8 0 9 -1 7.  
4.  
J o nes S, H ol mes F A, O' S ha u g h n ess y J, Bl u m J L, V u kelja SJ, McI nt yre KJ, et al. 
D oceta x el wit h C ycl o p h os p ha mi de Is Ass ociate d wit h a n O verall  S ur vi val Be nefit 
C o m pare d wit h D o x or u bici n a n d C ycl o p h os p h a mi de: 7 -Year F oll o w -u p of Us O nc ol o g y 
Researc h Trial 9 7 3 5. J Cli n O nc ol. 2 0 0 9; 2 7( 8): 1 1 7 7 -8 3.  
5.  
C ortes -F u nes H, C or o na d o C. R ole of A nt hrac ycli nes i n t he Era of Tar get e d T hera p y. 
Car di o vasc T o xic o l. 2 0 0 7; 7( 2): 5 6-6 0.  
6.  
J o nes S E, Sa vi n M A, H ol mes F A, O' S ha u g h ness y J A, Bl u m J L, V u kelja S, et al. P hase 
Iii Trial C o m pari n g D o x or u bici n Pl us C ycl o p h os p ha mi de wit h D oceta xel Pl us 
C ycl o p h os p ha mi de as A dj u va nt T hera p y f or O pera ble Breast Ca ncer. J Cli n O nc ol. 
2 0 0 6; 2 4( 3 4): 5 3 8 1 -7.  
7.  
Tre nt J C, Valer o V, B o os er DJ, Es parza -G uerra L T, I bra hi m N, Ra h ma n Z, et al. A P hase 
I St u d y of D o ceta x el Pl us C ycl o p h os p ha mi de i n S oli d T u m ors F oll o we d b y a P hase Ii 
St u d y as First -Li n e T hera p y i n M etastatic Breast Ca ncer. Cli n C a ncer Res. 
2 0 0 3; 9( 7): 2 4 2 6 -3 4.  
8.  
B or d o ni R, Haisli p S, Gil m ore J, S har pe J, A bella E, C h oi M. P 5 -2 0 -0 7: Esti mati o n of 
Fe brile Ne utr o pe ni a  i n W o me n Recei vi n g D ocet a x el Pl us C ycl o p h os p ha mi de as 
A dj u va nt T hera p y f or Earl y Sta ge Breast Ca ncer: A Retr os pecti ve A nal ysis. Ca ncer 
Researc h. 2 0 1 1; 7 1( 2 4 S u p ple me nt 3).  
9.  
C ha n A, F u W H, S hi h V, C o y uc o J C, Ta n S H, N g R. I m pact of C ol o n y -Sti m ulati n g 
Fact ors t o Re d u ce Fe bril e Ne utr o pe ni c E ve nts i n Breast Ca ncer Patie nts Recei vi n g 
D oceta x el Pl us C ycl o p h os p ha mi de C he m ot hera p y. S u p p ort Care Ca ncer. 
2 0 1 1; 1 9( 4): 4 9 7 -5 0 4.  
1 0.  
M yers R, Hi g gi ns B, M yers J, Le u n g M, Raja g o p al S, J o nes G, et al. C he m ot hera p y 
I n d u ce d Fe brile Ne utr o pe ni a  of D oceta xel wit h C ycl o p h os p ha mi de ( Tc) f or A dj u va nt 
T hera p y of Breast Ca ncer i n t he C o m m u nit y: Rea lit y C hec k. Ca n cer Res earc h. 
2 0 0 9; 6 9( 2 4 S u p pl): A bstract nr 2 0 9 2.  
1 1.  
S o o n g D, Haj R, Le u n g M G, M yers R, Hi g gi ns B, M yers J, et al. Hi g h Rat e of Fe brile 
Ne utr o pe ni a  i n Patie nts wit h O pera ble Breast Ca ncer Recei vi n g D oceta xel a n d 
C ycl o p h os p ha mi de. J Cli n O nc ol. 2 0 0 9; 2 7( 2 6):e 1 0 1 -2.  
1 2.  
Va n de n ber g T, Y o u n us J, Al -K ha y yat S. Fe brile Ne utr o pe ni a  Rates wit h A dj u va nt 
D oceta x el a n d C ycl o p h os p ha mi de C he m ot hera p y i n Earl y Breast Ca ncer: Discre pa n c y 
bet wee n P u blis he d Re p orts a n d C o m m u nit y Practice -a R etr os pecti ve A nal y sis. C urr 
O nc ol. 2 0 1 0; 1 7( 2): 2 -3.  

S pectr u m P h ar m ace utic als, I nc . 
Cli nic al  St u d y Pr ot oc ol  
Efl a pe gr asti m  
Pr ot oc ol N u m ber: S PI -G C F -3 0 2  
Pr ot oc ol  A me n d me nt 1: 2 8  J ul 2 0 1 7  
C o nfi de nti al  
5 4  
1 3.  
K u derer N M, Dal e D C, Cra wf or d J, L y ma n G H. I m pact of Pri mar y Pr o p h yl a xis wit h 
Gra n ul oc yte C ol o n y -Sti m ulati n g Fact or o n Fe brile Ne utr o pe ni a  a n d M ortalit y i n A d ult 
Ca ncer Patie nts Recei vi n g C he m ot hera p y: A S yst e matic Re vi e w. J Cli n O nc ol. 
2 0 0 7; 2 5( 2 1): 3 1 5 8 -6 7.  
1 4.  
L y m a n G H, Mic hels S L, Re y n ol ds M W, Barr o n R, T o mic K S, Y u J. Ris k of M ortalit y i n 
Patie nts wit h Ca ncer W h o E x perie nce Fe brile Ne utr o pe ni a . Ca ncer. 2 0 1 0; 1 1 6( 2 3): 5 5 5 5-
6 3.  
1 5.  
Nati o nal C o m pre he nsi ve Ca ncer Net w or k. M yel oi d Gr o wt h Fact ors ( Versi o n 2, 2 0 1 4). 
A vaila ble fr o m: w w w. ncc n. or g/ pr ofessi o n als/ p h ysicia n _ gls/ p df/ m yel oi d _ gr o wt h. p df.  
1 6.  
Dale D C, Mc Cart er G C, Cra wf or d J, L y ma n G H. M yel ot o xicit y a n d D os e I nte nsit y of 
C he m ot hera p y: Re p orti n g Practices fr o m Ra n d o mize d  Cli nical Trials. J Natl C o m pr Ca nc 
Net w. 2 0 0 3; 1( 3): 4 4 0 -5 4.  
1 7.  
L y m a n G H, K u derer N M, Cra wf or d J, W olff D A, C ula k o va E, P o nie wiers ki M S, et al. 
Pre dicti n g I n di vi d ual Ris k of Ne utr o pe ni c C o m plicati o ns i n Patie nts Recei vi n g Ca ncer 
C he m ot hera p y. Ca ncer. 2 0 1 1; 1 1 7( 9): 1 9 1 7 -2 7.  
1 8.  
F ort ner B V, Sc h wartz ber g L, T a uer K, H o uts A C, Hac kett J, St ols he k B S. I m pact of 
C he m ot hera p y -I n d u ce d Ne utr o pe nia o n Q ualit y of Lif e: A Pr os pecti ve Pil ot 
I n v esti gati o n. S u p p ort Care Ca n cer. 2 0 0 5; 1 3( 7): 5 2 2-8.  
1 9.  
Aa pr o M S, B o hli us J, Ca m er o n D A, Dal La g o L, D o n nell y J P, Kear ne y N, et al. 2 0 1 0 
U p date of E ort c G ui deli n es f or t he Us e of Gra n ul o c yt e -C ol o n y Sti m ulati n g Fact or t o 
Re d uce t he I n ci de nce of C he m ot hera p y -I n d u ce d Fe brile Ne utr o pe ni a  i n A d ult Patie nts 
wit h L y m p h o pr oliferati v e Dis or der s a n d S oli d T u m o urs. E ur J Ca ncer. 2 0 1 1; 4 7( 1): 8-3 2.  
2 0.  
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