A Phase 2, Single-Arm, Open-Label Study of Trilaciclib Administered Prior to Sacituzumab Govitecan-hziy in Patients With Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer Who Received at Least Two Prior Treatments, at Least One in the Metastatic Setting
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Sponsor: G1 Therapeutics, Inc.

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Pr ot oc ol Title: A P has e 2, Si n gle- Ar m, O p e n- La bel St u d y of Trilacicli b A d mi nistere d Pri or t o 
Sacit uz u ma b G o viteca n- hzi y i n Patie nts wit h U nresecta ble L ocall y A d va n ce d or 
Metastatic Tri ple- N e gati ve Breast Ca nc er W h o Recei ve d at Least T w o Pri or 
Treat me nts, at Least O ne i n t he Metastatic Setti n g   
Pr ot oc ol N u m ber: G 1 T 2 8- 2 1 3  
C o m p o u n d: Trilacicli b  
St u d y P h ase:  2 
S p o ns or N a me: G 1 T hera pe utics, I nc. 
Le g al Re gistere d A d dress:  G 1 T hera p e utics, I nc. 
7 0 0 Par k Offices Dr. S uite 2 0 0 
P O B o x 1 1 0 3 4 1  
Researc h Tria n gle Par k, N C 2 7 7 0 9  
 
Re g ul at or y A ge nc y I de ntifier N u m bers:  
I N D: 1 4 5 0 9 1  
 
A p pr o v al D ate: 1 5 N o v 2 0 2 1 ( Versi o n 2. 0) 
Pre vi o us Versi o n:  2 9 J u n 2 0 2 1 ( Versi o n 1. 0) 
 
 
T his d oc u me nt c o ntai ns c o nfi de ntial a n d/ or tra de secret i nf or mati o n t hat is discl ose d o nl y i n c o n necti o n 
wit h t he lice nsi n g a n d/ or re gistrati o n of pr o d ucts f or G 1 T hera pe utics, I nc. T his d oc u me nt s h o ul d n ot be 
discl ose d or use d, i n w h ole or i n part, f or a n y ot her p ur p os e wit h o ut t he pri or writte n c o nse nt of 
G 1 T hera pe utics, I nc. 

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P R O T O C O L SI G N A T U R E P A G E 
S p o ns or’s A p pr o v al  
I h a ve rea d a n d u n dersta n d t he c o nte nts of t his cli nical pr ot oc ol, Versi o n 2. 0 f or 
St u d y G 1 T 2 8- 2 1 3 dat e d 1 5 N o v 2 0 2 1 a n d I a gree t o meet all o bli gati o ns of t he S p o ns or as 
detaile d i n all a p plica ble re g ulati o ns a n d g ui deli nes. I n a d diti o n, I will i nf or m t he Pri nci pal 
I n v esti gat or a n d all ot her I n v esti gat ors of all rele va nt i nf or mati o n t hat bec o mes a vaila ble d uri n g 
t he c o n d uct of t he st u d y. 
 
 
 
 
  
 
 
 
G 1 T hera pe utics, I nc.  
 
 
 
Date 
 
 
 
P P D
P P D
P P D
P P D
P P D

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I N V E S TI G A T O R’ S A G R E EM E N T 
 
Cli nic al St u d y Pr ot oc ol G 1 T 2 8- 2 1 3:  A P has e 2, Si n gle- Ar m, O p e n- La bel St u d y of Trilaci cli b 
A d mi nistere d Pri or t o Sacit uz u ma b G o viteca n- hzi y i n Patie nts wit h U nresecta ble L ocall y 
A d va nce d or Metastatic Tri ple- Ne gati ve Breast  C a ncer W h o Recei ve d at Least T w o Pri or 
Treat me nts, at Least O ne i n t he Metastatic Setti n g   
 
Versi o n 2. 0 Iss ue D ate: 1 5 N o v 2 0 2 1 
 
I h a ve rea d t he G 1 T 2 8- 2 1 3 pr ot oc ol a n d a gree t o c o n d uct t he st u d y as o utli ne d. I a gree t o 
mai ntai n t he c o nfi de ntialit y of all i nf or mati o n r ecei ve d or de v el o pe d i n c o n necti o n wit h t his 
pr ot oc ol.  
 
 
 
 
 
 
Pri nci pal I n vesti gat or Si g nat ure 
 
Date 
 
 
 
 
 
 
 
 
Pri nci pal I n vesti gat or Na me 
 
I nstit uti o n 
 
 

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1.  
S Y N O P SI S 
N a me of S p o ns or/ C o m p a n y: G 1 T hera pe utics, I nc. 
N a me of I n vesti g ati o n al Pr o d uct: Trilacicli b f or I njecti o n, 3 0 0 m g/ vial  
N a me of Acti ve I n gre die nt: trilacicli b ( G 1 T 2 8) 
P r ot oc ol N u m ber: G 1 T 2 8- 2 1 3  P h ase: 2  
Re gi o n: U nite d States  
Title of St u d y:  
A P hase 2, Si n gle - Ar m, O p e n- La bel St u d y of Trilacicli b A d mi nistere d Pri or t o Sacit uz u ma b 
G o viteca n - hzi y i n Patie nts wit h U nresecta ble L ocally A d va nce d or Metastatic Tri ple- Ne gati ve 
Breast Ca ncer W h o Recei ve d at Least T w o Pri or Treat me nts , at Least O ne i n t he Metastatic Setti n g  
St u d y ce nters: A p pr o xi matel y 2 0 ce nters  
St u d y peri o d ( m o nt hs): A p pr o xi matel y 3 0 m o nt hs  
Esti mate d date first patie nt e nr olle d: Q 4 2 0 2 1 
Esti mate d date last patie nt c o m plete d: Q 2 2 0 2 4 
O bjecti ves: 
Pri m ar y:  
T o e val uate t he a nti-t u m or efficac y of trilacic li b w he n a d mi nistere d pri or t o sacit uz u ma b 
g o viteca n - hzi y as meas ure d b y pr o gressi o n-free s ur vi val ( P F S).  
Sec o n d ar y:  
T o e val uate t he a nti-t u m or efficac y of trilacicli b  a d mi nistere d pri or t o sacit uz u ma b g o viteca n-hzi y 
as meas ure d b y t he o bjecti ve res p o nse rate ( O R R), d urati o n of o bjecti ve res p o nse ( D O R), cli nical 
be nefit rate ( C B R), a n d o verall s ur vi val ( O S); e val uate t he m yel o pr otecti ve effects of trilacicli b; 
a n d assess  t he safet y a n d t olera bilit y of trilacicli b a d mi nistere d pri or t o sacit uz u ma b g o viteca n-hzi y  
St u d y Desi g n:  
T his is a P hase 2, m ultice nter, o pe n -la bel, si n gle ar m st u d y e val uati n g t he safet y a n d efficac y of 
trilacicli b a d mi nistere d pri or t o sacit uz u ma b g o viteca n- hzi y i n patie nts wit h u nresecta ble, l ocall y 
a d va nce d or metastatic tri ple- ne gati ve breast ca ncer ( T N B C) w h o recei ve d at least 2 pri or 
treat me nts, at least 1 i n t he metastatic setti n g.  
A p pr o xi matel y 4 5  patie nts will be e nr olle d. Trilacicli b a n d sacit uz u ma b g o viteca n-h zi y will be 
a d mi nistere d i ntra ve n o usl y (I V) i n 2 1 - da y c ycles as i n dicate d i n t he res pecti ve d osa ge a n d 
a d mi nistrati o n secti o ns of t he s y n o psis.  
A Safet y M o nit ori n g C o m mittee ( S M C) will m o nit or acc u m ulati n g safet y a n d dis p ositi o n data wit h 
t he first meeti n g pla n ne d w he n a p pr o xi matel y 1 0 patie nts ha ve c o m plete d at least 2 c ycles of st u d y 
treat me nt. T he meeti n gs will c o nti n ue w he n a p pr o xi matel y 2 5 e nr olle d patie nts ha ve c o m plete d at 
least 2 c ycles of st u d y treat me nt a n d a gai n w he n all e nr olle d patie nts ha ve c o m plete d at least 
2 c ycles of st u d y treat me nt or as defi ne d i n t he S M C c harter. A d diti o nal re vie ws ma y occ ur. 
T he st u d y will i ncl u de 3 st u d y p hases: Scree ni n g P hase, Treat me nt P hase, a n d S ur vi val F oll o w- u p 
P hase. T he Treat me nt P hase be gi ns o n t he da y of t he first d ose of st u d y treat me nt a n d c o m pletes at 
t he Safet y F oll o w- u p Visit. T he first S ur vi val F oll o w-u p assess me nt s h o ul d occ ur a p pr o xi matel y 
3 m o nt hs after t he Safet y F oll o w- U p Visit.  
St u d y dr u g a d mi nistrati o n will c o nti n ue u ntil pr o gressi ve disease per Res p o nse E val uati o n Criteria 
i n S oli d T u m ors ( R E CI S T) v 1. 1 or cli nical pr o gressio n as deter mi ne d b y t he I n vesti gat or, 
u nacce pta ble t o xicit y, wit h dra wal of c o nse nt, I n vesti gat or decisi o n, or t he e n d of t he st u d y, 
w hic he ver occ urs first. Treat me nt c ycles will occ ur c o nsec uti vel y wit h o ut i nterr u pti o n, e xce pt 

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w he n necessar y, t o ma na ge t o xicities or f or a d mi nistrati ve reas o ns. A 3- wee k del a y fr o m t he 
sc he d ule d d ose of sacit uz u ma b g o viteca n- hzi y is per mitte d. As e xa m ples, if at t he sc he d ule d 
C ycle  X Da y 1 visit (e. g., C ycle 2 Da y 1) a d ose dela y is nee de d f or t o xicit y reas o ns, a dela y u p t o 
3 wee ks fr o m C ycle X Da y 1 f or sacit uz u ma b g o viteca n - h zi y is per mitte d; if at t he sc he d ule d 
C ycle X Da y 8 visit (e. g., C ycle 1 Da y 8) a d ose dela y is nee de d f or t o xicit y reas o ns, a dela y u p t o 
3 wee ks fr o m C ycle X Da y 1 f or sacit uz u ma b g o viteca n - h zi y is per mitte d. A d osi n g dela y 
> 3  wee ks fr o m t he sc he d ule d d ose of sacit uz u ma b g o viteca n- hzi y ma y be per mitte d o n a 
case- b y-case basis wit h t he a p pr o val of t he I n vesti gat or a n d Me dical M o nit or. Criteria t hat patie nts 
m ust meet i n or der t o  recei ve st u d y treat me nt are pr o vi de d i n t he f ull pr ot oc ol. 
A n E n d of Treat me nt Visit will occ ur a p pr o xi matel y 1 4 da ys f oll o wi n g a patie nt’s last d ose of 
st u d y treat me nt. A Safet y F oll o w- u p visit ( w hic h ma y be a p h o ne call) will occ ur 3 0 da ys after t he 
last d ose of st u d y dr u g. F oll o wi n g t he Safet y F oll o w-u p Visit, patie nts will be f oll o we d f or s ur vi val 
a p pr o xi matel y e ver y 3 m o nt hs. T hese s ur vi val f oll o w -u ps ma y be d o ne via tele p h o ne, e mail, or 
cli nic visit. U nless ot her wise deci de d b y t he S p o ns or, t he st u d y will c o nti n ue u ntil at least 
a p pr o xi matel y 7 0 % of patie nts e nr olle d i n t he st u d y ha ve die d. 
Met h o d ol o g y:  
S a m ple Size J ustific ati o n:   
T he sa m ple size is calc ulate d t o s u p p ort t he pri mar y o bjecti ve of t he st u d y, t hat is, t o e val uate  
trilacicli b’s effect on P F S w he n a d mi nistere d pri or t o sacit uz u ma b g o viteca n- h zi y i n patie nts wit h 
u nresecta ble  l ocall y a d va nce d or metastatic T N B C w h o recei ve d at least 2 pri or treat me nts wit h at 
least 1 i n t he metastatic setti n g.  
T his si n gle -ar m st u d y pla ns t o e nr oll 4 5 patie nts d uri n g a 1 0- m o nt h accr ual peri o d wit h a n 
a p pr o xi mate 3 0 - m o nt h t otal st u d y d urati o n. Wit h 4 5 patie nts a n d 1 4 m o nt hs of f oll o w- u p after t he 
last patie nt is d ose d, t he f oll o wi n g ta ble prese nts t he re q uire d n u m ber of P F S eve nts a n d statistical 
p o wer t o detect hazar d rati os  of 0. 7 a n d 0. 8 at a 2-si de d si g nifica nce of 0. 2 f or a me dia n P F S of t he 
hist oric al c o ntr ol gr o u p of 5. 6 m o nt hs, w hic h was o bser ve d i n patie nts wit h o ut brai n metastases 
treate d wit h sacit uz u ma b g o viteca n- hzi y i n t he P hase 3 A S C E N T trial (Bar dia, 2 0 2 1 ). T he 
calc ulati o n is base d o n a o ne-sa m ple l o g-ra n k test ( W u, 2 0 1 5 ) wit h t he ass u m pti o n t hat t he s ur vi val 
ti me distri b uti o ns f or b ot h st u d y treat me nt a n d hist orical c o ntr ol gr o u p f oll o w t he Wei b ull 
distri b uti o n wit h a s ha pe para meter of 1. 0 0 (i.e., e x p o ne ntial di stri b uti o n).  
H az ar d 
R ati o 
Me di a n P F S f or tril acicli b + 
s acit uz u m a b g o vitec a n-hzi y 
( M o nt hs) 
E x pecte d n u m ber of 
e ve nts i n t he st u d y 
St atistic al P o wer 
0. 7 0 
8. 0 
3 6 
8 0 % 
0. 8 0 
7. 0 
3 8 
5 4 % 
 
N u m ber of p atie nts ( pl a n ne d):  
A p pr o xi matel y 4 5  patie nts are pla n ne d i n t his st u d y.  
Di a g n osis a n d m ai n criteri a f or i ncl usi o n:  
Patie nts ≥1 8 years of a ge at t he ti me of si g ni n g t he i nf or me d c o nse nt wit h meas ura ble l ocall y 
a d va nce d, u nresecta ble, or metastatic T N B C ( defi ne d as < 1 % estr o ge n rece pt or a n d  pr o gester o ne 
rece pt or b y i m m u n o hist oc he mistr y [I H C], h u ma n e pi der mal gr o wt h fact or rece pt or 2-ne gati ve b y 
I H C or i n sit u h y bri dizati o n) a n d wit h a n Easter n C o o perati ve O nc ol o g y Gr o u p perf or ma nce stat us 
of 0 or 1. Patie nts m ust ha ve meas ura ble disease as d efi ne d b y R E CI S T v 1. 1 a n d c o nsi dere d 
eli gi ble t o recei ve sacit uz u ma b g o viteca n - hzi y treat me nt. Patie nts wit h k n o w n brai n metastasis at 
t he ti me of e nr oll me nt are n ot eli gi ble. Patie nts m ust ha ve recei ve d 2 or m ore pri or li nes of 
s yste mic t hera p y, at least o ne of t he m i n t he metastatic setti n g. Pri or ra diati o n t hera p y is per mitte d 

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f or rec urre nt disease as l o n g as t he patie nt has at least 1 meas ura ble lesi o n t hat has n ot bee n 
irra diate d. Patie nts m ust als o ha ve a de q uate or gan f u ncti o n as de m o nstrate d b y la b or at or y val ues. 
I n vesti g ati o n al pr o d uct, d os a ge, a n d m o de of a d mi nistr ati o n:  
Trilacicli b  
I n eac h 2 1- da y c ycle at Da y 1 a n d Da y 8, a d ose of trilacicli b 2 4 0 m g/ m 2 rec o nstit ute d a n d dil ute d 
i n 2 5 0 m L of s o di u m c hl ori de s ol uti o n 0. 9 % ( n or mal sali ne) or de xtr ose 5 % i n water ( D 5 W) will 
be a d mi nistere d as a 3 0 -mi n ute I V i nf usi o n c o m plete d wit hi n 4 h o urs pri or t o start of sacit uz u ma b 
g o viteca n - hzi y eac h da y sacit uz u ma b g o viteca n- hzi y is a d mi nistere d. If a d mi nistrati o n of 
sacit uz u ma b g o viteca n- h zi y is s ki p pe d or disc o nti n ue d, trilacicli b will als o be s ki p pe d or 
disc o nti n ue d.   
D ur ati o n of tre at me nt:  
St u d y treat me nt a d mi nistrati o n will c o nti n ue f or eac h patie nt u ntil pr o gressi ve disease per R E CI S T 
v 1. 1 or cli nical pr o gressi o n as deter mi ne d b y t he I n vesti gat or, u nacce pta ble t o xicit y, wit h dra wal of 
c o nse nt, I n vesti gat or decisi o n, or t he e n d of t he trial, w hic he ver occ urs first.   
Ref ere nce t her a p y, d os a ge, a n d m o de of a d mi nistr ati o n:  
I n eac h 2 1- da y c ycle at Da y 1 a n d Da y 8, a d ose of sacit uz u ma b g o viteca n- hzi y 1 0 m g/ k g 
rec o nstit ute d a n d dil ute d i n s o di u m c hl ori de s ol uti o n 0. 9% ( n or mal sali ne) t o a c o nce ntrati o n of 
1. 1  m g/ m L t o 3. 4 m g/ m L; t otal v ol u me s h o ul d n ot e xcee d 5 0 0 m L. O nl y s o di u m c hl ori de s ol uti o n 
0. 9 % ( n or mal sali ne) s h o ul d be use d. Pr otect i nf usi o n ba g fr o m li g ht. A d mi nister t he first i nf usi o n 
o ver 3 h o urs a n d o bser ve patie nts d uri n g t he i nf usi o n a n d f or at least 3 0 mi n utes f oll o wi n g t he 
i nitial d ose f or si g ns or s y m pt o ms of i nf usi o n-relate d reacti o ns. S u bse q ue nt i nf usi o ns ma y be 
a d mi nister e d o ver 1 t o 2 h o urs if pri or i nf usi o ns were t olerate d, a n d patie nts s h o ul d be o bser ve d 
d uri n g t he i nf usi o n a n d f or at least 3 0 mi n utes after i nf usi o n.  
Pri or t o eac h i nf usi o n of sacit uz u ma b g o viteca n -hzi y, pre me dicati o n f or t he pre ve nti o n of i nf usi o n 
reacti o ns a n d c he m ot hera p y-i n d uce d na usea a n d v o miti n g is rec o m me n de d. 
 
Pre me dicate wit h a nti p yretics, hista mi ne rece pt or 1 a n d hista mi ne rece pt or 2 bl oc kers pri or 
t o i nf usi o n, a n d c ortic oster oi ds ma y be use d f or patie nts w h o ha d pri or i nf usi o n reacti o ns. 
 
Pre me dicate wit h a t w o or t hree dr u g ( preferre d) c o m bi nati o n re gi me n (e. g., 
de xa met has o ne wit h eit her a 5- H T 3 rece pt or a nta g o nist or a ne ur o ki ni n 1 rece pt or 
a nta g o nist, as well as ot her dr u gs as i n dicate d). 
Criteri a f or e v al u ati o n:  
Effic ac y:  
A nti -t u m or efficac y assess me nts i ncl u de P F S, O R R, C B R, D O R a n d O S. T u m or res p o nse criteria 
will be base d o n R E CI S T v 1. 1. M yel os u p pressi o n e n d p oi nts will be base d o n re p orte d he mat ol o g y 
assess me nts, m yel os u p pressi o n-relate d a d verse e ve nt ( A E) details, d ose re d ucti o ns/ dela ys, a n d 
s u p p orti ve care i nter ve nti o ns (i ncl u di n g tra nsf usi o ns). 
S af et y:  
Safet y will be e val uate d b y m o nit ori n g A Es, cli nic al la b orat or y test res ults ( he mat ol o g y, cli nical 
c he mistr y), vital si g n meas ure me nts ( bl o o d press ure, heart rate, a n d oral b o d y te m perat ure), 
1 2 -lea d safet y electr ocar di o gra m ( E C G) res ults, d ose m o dificati o ns, a n d p h ysical e xa mi nati o n 
fi n di n gs. 
St atistic al met h o ds:  
T he f oll o wi n g a nal ysis p o p ulati o ns are defi ne d f or t he st u d y.  

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S u m mar y statistics will be pr o vi de d f or all e n d p oi nt s. T he cate g orical varia bles will be s u m marize d 
b y c o u nts a n d perce nta ges, t he c o nti n u o us varia bles will be s u m marize d b y mea n, me dia n, sta n dar d 
de viati o ns, 2 5 % a n d 7 5 % perce ntiles, a n d mi ni m u m a n d ma xi m u m val ues. 
A n al ysis p o p ul ati o n  
T he f ull a nal ysis set ( F A S) i ncl u des all e nr olle d patie nts w h o were a d mi nistere d at least 1 d ose of 
st u d y dr u g. U nless ot her wise s pecifie d, t he F A S is t he pri mar y a nal ysis set f or all efficac y 
a nal yses. 
T he res p o nse e val ua ble ( R E) p o p ulati o n i ncl u des all patie nts w h o are i n t he F A S a n d w h o ha ve 
meas ura ble (tar get) t u m or lesi o n(s) at baseli ne t u m or assess me nt a n d eit her (i) ha ve at least 1 p ost-
baseli ne t u m or assess me nt, or (ii) d o n ot ha ve p ost - d ose t u m or assess me nt b ut ha ve cli nical 
pr o gressi o n as n ote d b y t he I n vesti gat or, or (iii) die d d ue t o disease pr o gressi o n pri or t o t heir first 
p ost -baseli ne t u m or sca n. T he R E p o p ulati o n will be t he pri mar y a nal ysis set f or t u m or res p o nse 
a nal yses. 
T he safet y p o p ulati o n i ncl u des all e nr olle d patie nts w h o recei ve d at least 1 d ose of st u d y dr u g. All 
safet y a nal yses will be e val uate d usi n g t he safet y p o p ulati o n. 
St atistic al a n al ysis met h o ds f or pri m ar y a n d sec o n d ar y e n d p oi nts  
A n alysis f or pri m ary effic acy e n d p oi nt  
T he pri mar y e n d p oi nt, P F S, is defi ne d as t he ti me ( m o nt hs) fr o m t he date of first d ose of st u d y 
dr u g  u ntil t he date of d oc u me nte d ra di o gra p hic disease pr o gressi o n ( P D) per R E CI S T v 1. 1 or deat h 
d ue t o a n y ca use, w hic he ver c o mes first. F or patie nts w h o d o n ot e x perie nce P D or are ali ve at t he 
ti me of perf or mi n g t he a nal ysis, P F S will be calc ulate d per ce ns ori n g r ules detaile d i n t he 
Statistical A nal ysis Pla n. T he pri mar y a nal ysis f or P F S will be c o n d ucte d at t he ti me w he n 
3 6  patie nts ha ve ra di o gra p hicall y- deter mi ne d disease pr o gressi o n or ha ve die d. A Ka pla n-Meier 
pl ot will be pr o d uce d . T he me dia n, 2 5t h perce ntile, a n d 7 5t h perce ntile of P F S will be esti mate d 
usi n g t he Ka pla n -Meier met h o d wit h t heir c orres p o n di n g 9 5 % c o nfi de nce i nter nal ( CI) calc ulate d 
base d o n t he met h o d b y Br o o k me yer a n d Cr o wle y ( 1 9 8 2) . P F S will be a nal yze d o n t he F A S 
p o p ulati o n.  
A n alysis f or sec o n d ary a nti -t u m or effic acy e n d p oi nts: 
T u m or res p o nse : 
O bjecti ve re s p o nse rate is defi ne d as t he pr o p orti o n of patie nts wit h best o verall res p o nse ( B O R) of 
eit her c o nfir me d c o m plete res p o nse ( C R) or c o nfir me d partial res p o nse ( P R) per R E CI S T v 1. 1. 
O R R , al o n g wit h its 9 5 % t w o-si de d CI usi n g t he Cl o p per- Pears o n met h o d, will be c o m p ute d. O R R 
will be a nal yze d o n t he R E p o p ulati o n.  
C B R is defi ne d as t he pr o p orti o n of patie nts wit h a B O R of c o nfir me d C R, c o nfir me d P R, or sta ble 
disease lasti n g 2 4 wee ks or l o n ger fr o m t he first date of st u d y dr u g a d mi nistrati o n. C B R will be 
a nal yze d si milarl y as O R R base d o n t he R E p o p ulati o n. 
D O R is t he ti me ( m o nt hs) bet wee n t he date of ac hie vi n g first o bjecti ve res p o nse ( C R or P R), 
c o nfir me d at t he ne xt t u m or sca n, a n d t he date of d oc u me nte d disease pr o gressi o n per 
R E CI S T  v 1. 1 or deat h, w hic he ver c o mes first. Patie nts w h o d o n ot e x perie nce o bjecti ve C R or P R 
will n ot be i ncl u de d i n t he a nal ysis. F or patie nts wit h o bj ecti ve res p o nse w h o d o n ot reac h 
ra di o gra p hicall y deter mi ne d P D or die at t he ti me of a nal ysis, ce ns ore d ti me will be calc ulate d 
f oll o wi n g t he r ules detaile d i n Secti o n 1 2. 4. 6. 2 . T he me dia n, 2 5t h perce ntile a n d 7 5t h perce ntile will 
be esti mate d usi n g t he Ka pla n- Meier met h o d wit h t heir c orres p o n di n g 9 5 % CI calc ulate d base d o n 
t he met h o d b y Br o o k me yer a n d Cr o wle y ( 1 9 8 2) . 
O S:  
O S is defi ne d as t he ti me ( m o nt hs) fr o m t he date of first d ose of st u d y dr u g t o t he date of deat h f or 
patie nts w h o die d i n t he st u d y d ue t o a n y ca use, a n d t he ti me t o t he last c o ntact date k n o w n t o be 

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ali ve f or t h ose patie nts w h o s ur vi ve d as of t he date f or fi nal data base l oc k (ce ns ore d cases). O S will 
be c o n d ucte d at t he ti me w he n a p pr o xi matel y 7 0 % of patie nts ( ~ 3 2 patie nts) ha ve die d. 
Ka pla n - Meier pl ots will be pr o d uce d. T he me dia n, 2 5t h perce ntile, a n d 7 5t h perce ntile of O S will be 
esti mate d usi n g t he Ka pla n- Meier met h o d wit h t heir c orres p o n di n g 9 5 % CI calc ulate d base d o n t he 
met h o d b y Br o o k me yer a n d Cr o wle y ( 1 9 8 2) . O S will be a nal yze d o n t he F A S. 
A n alysis f or myel os u p pressi o n e n d p oi nts: 
T he m yel os u p pressi o n e n d p oi nts i ncl u de t he occ urre nce of se vere ne utr o pe nia ( S N). S N is defi ne d 
as t he a bs ol ute ne utr o p hil c o u nt ( A N C) la b orat or y val ue t hat meets t he Nati o nal Ca ncer I nstit ute 
C o m m o n T er mi n ol o g y Criteria f or  A d verse E ve nts ( N CI-C T C A E) v 5. 0 criteria f or ≥ Gra de 4 
t o xicit y (i.e., A N C < 0. 5 x 1 09/ L i n SI U nit). T he n u m ber a n d perce nta ge of patie nts wit h at least 
o ne occ urre nce of S N d uri n g t he treat me nt peri o d will be s u m marize d. F or c o u nti n g 
m yel os u p pressi o n e n d p oi nts (e. g., t he n u m ber of re d bl o o d cell [ R B C] tra nsf usi o ns o n/after 
Wee k  5, a n d t he n u m ber of d ose re d ucti o ns d uri n g t he treat me nt peri o d), t he t otal n u m ber of t he 
e ve nt, t he t otal d urati o n of treat me nt peri o d (eit her i n t he u nit of wee ks or c ycles), a n d e ve nt rate 
per 1 0 0 wee ks or c ycles will be s u m marize d. F o r e xa m ple, t he e ve nt rate f or R B C tra nsf usi o ns 
o n/after Wee k 5 will be re p orte d per 1 0 0 wee ks a n d t hat f or d ose re d ucti o n will be re p orte d per 
1 0 0  c ycles. F or a gi ve n e ve nt, patie nts wit h o ut a n y e ve nts d uri n g t he treat me nt peri o d will be 
assi g ne d a val ue 0 t o be i ncl u de d i n t he a nal ysis.   
A n alysis f or s afety e n d p oi nts  
Safet y a n d t olera bilit y will be assesse d b y A Es, d ose m o dificati o ns, la b orat or y tests, vital si g ns, 
a n d E C G. Safet y data will be s u m marize d usi n g descri pti ve statistics base d o n t he safet y 
p o p ulati o n. A Es are defi ne d as t h ose e ve nts occ urr i n g or w orse ni n g after treat me nt has be g u n o n 
t his st u d y. A E data will be c o de d t o s yste m or gan class a n d preferre d ter m usi n g t he latest versi o n 
of  Me dical Dicti o nar y f or Re g ulat or y Acti vities. T he se verit y (t o xicit y gra des 1-5) of A Es will be 
gra de d b y I n vesti gat ors acc or di n g t o N CI- C T C A E Versi o n 5. 0. A n y A E, A Es relate d t o st u d y dr u g 
(trilacicli b or sacit uz u ma b g o viteca n- hzi y), A Es lea di n g t o st u d y dr u g disc o nti n uati o n, d ose 
m o dific ati o n, trilacicli b a d verse e ve nts of s pecial i nterest will be s u m marize d b y s yste m or ga n 
class, preferre d ter m, a n d C T C A E gra de, as a p pr o priate.   
F or la b orat or y assess me nts, vital si g ns, a n d E C G i nter vals, o bser ve d val ues  a n d c ha n ges fr o m 
baseli ne will be s u m marize d. F or  c he mistr y a n d he mat ol o g y la b orat or y para meters, cli nical la bs 
will be c haracterize d acc or di n g t o C T C A E t o xicit y gra de 1 t o 5, v 5. 0 w he n p ossi ble, a n d t he 
n u m ber a n d perce nta ge of patie nts wit hi n eac h C T C A E  gra de will be s u m marize d f or t he o verall 
treat me nt peri o d as well as f or eac h c ycle. Safet y data c ollecte d t hr o u g h sc he d ule d or u nsc he d ule d 
visits will all be i ncl u de d i n t he safet y e val uati o n.  

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2.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
T A B L E O F C O N T E N T S 
P R O T O C O L SI G N A T U R E P A G E ................................................................................................. 2  
I N V E S TI G A T O R’ S A G R E EM E N T ............................................................................................... 3  
1.  
S Y N O P SI S ................................................................................................................... 4  
2.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F FI G U R E S ................. 9  
3.  
LI S T O F A B B R E VI A TI O N S..................................................................................... 1 4  
4.  
I N T R O D U C TI O N ...................................................................................................... 1 8 
4. 1.  
Tri ple- Ne gati ve Breast C a ncer ................................................................................... 1 8  
4. 2.  
St u d y R ati o nale ........................................................................................................... 1 9  
4. 2. 1.  
Rati o nale f or I m pr o vi n g A nti-t u m or Efficac y wit h Trilacicli b .................................. 2 0  
4. 2. 2.  
Rati o nale f or I m m u ne M ec ha nis m of Trilacicli b ....................................................... 2 2  
4. 2. 3.  
Rati o nale f or M yel o pr otecti o n .................................................................................... 2 3  
4. 3.  
Bac k gr o u n d ................................................................................................................. 2 4  
4. 3. 1.  
S u m mar y of N o n cli nical Data .................................................................................... 2 4  
4. 3. 1. 1.  
P har mac ol o g y St u dies ................................................................................................ 2 5  
4. 3. 1. 2.  
P har mac o ki netic St u dies ............................................................................................. 2 7  
4. 3. 2.  
S u m mar y of Cli nical Dat a .......................................................................................... 2 8  
4. 3. 2. 1.  
Efficac y ...................................................................................................................... . 2 8 
4. 3. 3.  
Ris ks ......................................................................................................................... .. 3 3 
4. 3. 3. 1.  
Trilacicli b ................................................................................................................... . 3 3 
4. 3. 3. 2.  
Sacit uz u ma b g o viteca n- h zi y ....................................................................................... 3 5  
4. 4.  
Be nefit/ Ris k Assess me nt ............................................................................................ 3 5  
5.  
O BJ E C TI V E S A N D E N D P OI N T S ............................................................................ 3 7  
6.  
I N V E S TI G A TI O N A L P L A N ..................................................................................... 3 9 
6. 1.  
O verall St u d y Desi g n .................................................................................................. 3 9  
6. 2.  
Rati o nale f or Pri mar y a n d Sec o n dar y E n d p oi nts ........................................................ 4 1  
6. 2. 1.  
A nti-t u m or Efficac y .................................................................................................... 4 1  
6. 2. 2.  
M yel o pr ot ecti o n .......................................................................................................... 4 1  
6. 2. 3.  
Safet y ........................................................................................................................ .. 4 1 
6. 3.  
Rati o nale f or D ose a n d Sc he d ule of St u d y Treat me nt ................................................ 4 1  

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6. 4.  
Rati o nale f or Patie nt P o p ulati o n ................................................................................. 4 2  
6. 5.  
Rati o nale f or Sacit uz u ma b G o viteca n- hzi y T hera p y .................................................. 4 3  
6. 6.  
Rati o nale f or S u p p orti ve Care I nter ve nti o ns ( Gr o wt h Fact ors a n d 
Tra nsf usi o ns) .............................................................................................................. 4 4  
7.  
S T U D Y P O P U L A TI O N ............................................................................................. 4 5  
7. 1.  
I n cl usi o n Criteria ........................................................................................................ 4 5 
7. 2.  
E x cl usi o n Criteria ....................................................................................................... 4 6  
8.  
P R O T O C O L S C H E D U L E O F A S S E S S M E N T S ...................................................... 4 9  
9.  
S T U D Y T R E A T M E N T .............................................................................................. 5 2  
9. 1.  
St u d y Dr u gs A d mi nistere d ......................................................................................... 5 2  
9. 1. 1.  
D ose, D osi n g R e gi me n, a n d R o ute ............................................................................. 5 2  
9. 1. 1. 1.  
Trilacicli b –  I n vesti gati o nal Pr o d uct .......................................................................... 5 2 
9. 1. 1. 2.  
Sacit uz u ma b G o viteca n- hzi y –  C he m ot hera p y .......................................................... 5 3 
9. 1. 2.  
Pre parati o n, H a n dli n g, St ora ge, a n d Acc o u nta bilit y .................................................. 5 4  
9. 1. 3.  
Treat me nt C o m plia nce ................................................................................................ 5 4  
9. 2.  
Criteria f or Starti n g C ycl e 1 a n d Eac h S u bse q ue nt D ose ........................................... 5 4  
9. 3.  
T o xicit y Ma n a ge me nt a n d D ose M o dificati o ns ......................................................... 5 5  
9. 3. 1.  
Rec o m me n de d Acti o ns wit h Sacit uz u ma b G o viteca n- hzi y f or A d verse 
E ve nts ........................................................................................................................ . 5 6 
9. 3. 2.  
Rec o m me n de d Acti o ns wit h Trilacicli b f or A d verse E ve nts of S pecial 
I nterest ( A E SI) ............................................................................................................ 5 7 
9. 3. 3.  
H y’s La w Ma n a ge me nt  ............................................................................................... 5 9 
9. 4.  
S u p p orti ve Care I nter v e nti o ns .................................................................................... 6 0  
9. 4. 1.  
C ol o n y Sti m ulati n g Fact or Usa ge ............................................................................... 6 0  
9. 4. 2.  
Er yt hr o p oiesis- Sti m ulati n g A ge nt Usa ge ................................................................... 6 0  
9. 4. 3.  
Tra nsf usi o ns ................................................................................................................ 6 1  
9. 5.  
Pri or/ C o nc o mita nt Me dicati o ns a n d Pr oce d ures ........................................................ 6 1  
9. 6.  
Meas ures t o Mi ni mize Bias ........................................................................................ 6 2  
9. 7.  
I nter ve nti o n aft er E n d of St u d y Treat me nt ................................................................. 6 2 
1 0.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A TI E N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L .................................................................. 6 3  
1 0. 1.  
Disc o nti n uati o n of St u d y Treat me nt ........................................................................... 6 3  
1 0. 2.  
Disc o nti n uati o n/ Wit h dra wal fr o m t he St u d y .............................................................. 6 3  
1 0. 3.  
L ost t o F oll o w U p ....................................................................................................... 6 4  

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1 0. 4.  
St u d y a n d Site Start a n d Cl os ure ................................................................................ 6 4  
1 1.  
S T U D Y A S S E S S M E N T S .......................................................................................... 6 6  
1 1. 1.  
Scree ni n g Assess me nts ............................................................................................... 6 6  
1 1. 1. 1.  
E R-, Pr o gest er o ne Rece pt or-, H E R 2- Ne gati ve Stat us ................................................ 6 6  
1 1. 1. 2.  
E nr oll me nt .................................................................................................................. 6 6  
1 1. 1. 3.  
De m o gra p hics ............................................................................................................. 6 6  
1 1. 1. 4.  
Me dical Hist or y a n d Breast Ca ncer Dis ease Hist or y ................................................. 6 7  
1 1. 2.  
Efficac y Assess me nts ................................................................................................. 6 7  
1 1. 2. 1.  
A nti-t u m or Efficac y Ass ess me nt ................................................................................ 6 7  
1 1. 2. 2.  
M yel o pr ot ecti o n Assess me nts .................................................................................... 6 8  
1 1. 3.  
Safet y Assess me nts ..................................................................................................... 6 8  
1 1. 3. 1.  
Vital Si g ns .................................................................................................................. 6 8  
1 1. 3. 2.  
P h ysical E x a mi nati o n ................................................................................................. 6 8  
1 1. 3. 3.  
E C O G Perf or ma n ce Stat us ......................................................................................... 6 9  
1 1. 3. 4.  
Electr ocar di o gra m ....................................................................................................... 6 9  
1 1. 3. 5.  
Cli nical Safet y La b orat or y Assess me nts .................................................................... 6 9  
1 1. 3. 6.  
A d verse a n d Seri o us A d verse E ve nts ......................................................................... 7 0  
1 1. 3. 6. 1.  
Ti me Peri o d a n d Fre q ue n c y f or C ollecti n g A d verse a n d Seri o us A d verse 
E ve nt I nf or mati o n ....................................................................................................... 7 0  
1 1. 3. 6. 2.  
Met h o d of Dete cti n g A d verse a n d Seri o us A d verse E ve nts ....................................... 7 1  
1 1. 3. 6. 3.  
F oll o w- u p of A d v erse a n d Seri o us A d verse E v e nts ................................................... 7 1  
1 1. 3. 6. 4.  
Re g ulat or y Re p orti n g Re q uire me nts f or Seri o us A d verse E ve nts ............................. 7 1  
1 1. 3. 6. 5.  
Pre g n a nc y ................................................................................................................... 7 2  
1 1. 4.  
Safet y M o nit ori n g C o m mittee .................................................................................... 7 2  
1 1. 5.  
E n d of Treat me nt Visit ............................................................................................... 7 2  
1 1. 6.  
Safet y F oll o w- u p Visit ................................................................................................ 7 2  
1 1. 7.  
S ur vi val F oll o w- u p P has e ........................................................................................... 7 2  
1 2.  
S T A TI S TI C A L C O N SI D E R A TI O N S ....................................................................... 7 4  
1 2. 1.  
Sa m ple Siz e Deter mi nati o n ........................................................................................ 7 4  
1 2. 2.  
A nal ysis P o p ulati o n .................................................................................................... 7 4  
1 2. 3.  
Ti mi n g of Pla n ne d A n al ysis ....................................................................................... 7 5  
1 2. 3. 1.  
First Pla n ne d A nal ysis –  A nal ys es f or Pr o gressi o n- Free S ur vi val, T u m or 
Res p o nse E n d p oi nts, a n d M yel os u p pressi o n E n d p oi nts ............................................ 7 5  

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1 2. 3. 2.  
Fi nal Pla n ne d A nal ysis –  A nal ysis f or O verall S ur vi val ............................................ 7 5 
1 2. 4.  
Statistical A nal ysis Met h o ds....................................................................................... 7 5  
1 2. 4. 1.  
Ge neral C o nsi derati o ns ............................................................................................... 7 5  
1 2. 4. 2.  
Patie nt Dis p ositi o n ...................................................................................................... 7 5  
1 2. 4. 3.  
De m o gra p hic a n d Baseli ne  C haracteristics ................................................................ 7 5 
1 2. 4. 4.  
Pri or a n d S u bse q ue nt A ntica ncer T hera pies ............................................................... 7 5  
1 2. 4. 5.  
St u d y Dr u g E x p os ure, M o dificati o n a n d D ose I nt e nsit y ............................................ 7 6  
1 2. 4. 6.  
Efficac y A nal yses ....................................................................................................... 7 6  
1 2. 4. 6. 1.  
A nal ys es of Pri mar y Effi cac y E n d p oi nt – Pr o gressi o n- Free S ur vi val ....................... 7 6  
1 2. 4. 6. 2.  
A nal ys es f or Sec o n dar y A nti-t u m or Efficac y E n d p oi nts ........................................... 7 7  
1 2. 4. 6. 3.  
A nal ysis of M yel os u p pressi o n E n d p oi nts .................................................................. 7 8  
1 2. 4. 7.  
Safet y A nal yses .......................................................................................................... 7 8  
1 2. 4. 7. 1.  
A d verse E v e nts ........................................................................................................... 7 9  
1 2. 4. 7. 2.  
Ot her Safet y E n d p oi nts ............................................................................................... 7 9  
1 3.  
E T HI C S ...................................................................................................................... 8 0  
1 3. 1.  
Et hics Re vie w ............................................................................................................. 8 0  
1 3. 2.  
Et hical C o n d uct of t he St u d y ...................................................................................... 8 0  
1 3. 3.  
Writte n I nf or m e d C o nse nt .......................................................................................... 8 0  
1 4.  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G ....................................................... 8 1  
1 4. 1.  
Data Pr otecti o n ........................................................................................................... 8 1  
1 4. 2.  
Data Q ualit y Ass ura nce .............................................................................................. 8 1  
1 4. 3.  
Disse mi nati o n of Cli nical St u d y Data ........................................................................ 8 2  
1 4. 4.  
S o urce D oc u m e nts ...................................................................................................... 8 2  
1 4. 5.  
A u dits a n d I ns p ecti o ns ................................................................................................ 8 2  
1 5.  
P U B LI C A TI O N P O LI C Y .......................................................................................... 8 3  
1 6.  
R E F E R E N C E S ........................................................................................................... 8 4  
1 7.  
A P P E N DI C E S ............................................................................................................ 8 9  
1 7. 1.  
Cli nical La b orat or y Tests ........................................................................................... 8 9  
1 7. 2.  
A d verse E v e nts: Defi niti o ns a n d Pr oce d ures f or R ec or di n g, E val u ati n g, a n d 
F oll o w- u p .................................................................................................................... 9 0  
1 7. 2. 1.  
Defi niti o n of A E ......................................................................................................... 9 0  
1 7. 2. 2.  
Defi niti o n of S A E ....................................................................................................... 9 1  
1 7. 2. 3.  
Rec or di n g a n d F oll o w- U p of A E a n d/ or S A E ............................................................ 9 2  

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1 7. 2. 4.  
Re p orti n g of S A Es ...................................................................................................... 9 4  
1 7. 3.  
C o ntrace pti ve G ui da n ce a n d C ollect i o n of Pre g na nc y I nf or mati o n ........................... 9 5 
1 7. 4.  
Defi niti o ns of T u m or Res p o nse a n d Diseas e Pr o gressi o n ( per R E CI S T v 1. 1) .......... 9 8  
 
LI S T O F T A B L E S 
Ta ble 1:  
A b bre viati o ns .............................................................................................................. 1 4  
Ta ble 2:  
I nte grate d A nal ysis f or M yel o pr ot ecti o n Efficac y i n S C L C ( St u dies 
G 1 T 2 8- 0 2, G 1 T 2 8- 0 3, a n d G 1 T 2 8- 0 5) ...................................................................... 2 4  
Ta ble 3:  
G 1 T 2 8- 0 4: S u m mar y of O verall S ur vi val a n d Pr o gressi o n- Free S ur vi val 
(I T T A nal ysis Set) ...................................................................................................... 3 0 
Ta ble 4:  
G 1 T 2 8- 0 4: T u m or Res p o nse Acc or di n g t o P D- L 1 Stat us .......................................... 3 2  
Ta ble 5:  
O bjecti ves a n d E n d p oi nts ........................................................................................... 3 7  
Ta ble 6:  
Sc he d ule of Assess me nts ............................................................................................ 5 0  
T a ble 7:  
St u d y Dr u gs  ............................................................................................................... 5 2 
Ta ble 8:  
Rec o m me n de d D ose M o dificati o ns f or Sacit uz u ma b G o viteca n- hzi y ....................... 5 7 
Ta ble 9:  
Rec o m me n de d Acti o ns wit h Trilacicli b F oll o wi n g A E SIs ........................................ 5 8  
Ta ble 1 0:  Patie nt Ris k Fact ors f or P o or Cli nica l O utc o mes Res ulti n g fr o m Fe brile 
Ne utr o pe nia or I nfecti o n ............................................................................................. 6 0  
Ta ble 1 1:  E C O G Perf or ma n ce Stat us ......................................................................................... 6 9  
Ta ble 1 2:  Statistical P o wer ......................................................................................................... 7 4  
Ta ble 1 3:  Pr ot oc ol- S pecifie d Safet y La b orat or y Assess me nts ................................................... 8 9  
 
LI S T O F FI G U R E S 
Fi g ure 1:  
Trilacicli b Tra nsie ntl y Arrests N or mal Cells t o Pre ve nt 
C he m ot hera p y-I n d u ce d M yel os u p pressi o n a n d I m pr o ve A nti- T u m or 
Efficac y ...................................................................................................................... . 2 0 
Fi g ure 2:  T he A d diti o n of Trilacicli b t o C he m ot hera p y/I m m u ne C hec k p oi nt I n hi bit or 
Treat me nt E n ha n ces Effi cac y T hr o u g h T Cell Acti vati o n ......................................... 2 6  
Fi g ure 3:  Trilacicli b A u g me nts A nti- P D- 1 A nti b o d y-I n d u ce d A ntit u m or Acti vit y .................. 2 7  
Fi g ure 4:  
G 1 T 2 8- 0 4: O verall S ur vi val –  Ka pla n- M eier C ur ve (I T T A n al ysis Set) ................... 3 1 
Fi g ure 5:  
St u d y Sc h e ma ............................................................................................................. 3 9  

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3.  
LI S T O F A B B R E VI A TI O N S  
T he f oll o wi n g a b bre vi ati o ns a n d s pecialist ter ms are use d i n t his st u d y pr ot oc ol. 
T a ble 1:  
A b bre vi ati o ns  
A b bre vi ati o n  
Defi niti o n  
5- F U 
5-fl u or o uracil 
5- H T 3 
5- h y dr o x ytr y pta mi ne or C ys-l o o p s u perfa mil y of li ga n d- gate d i o n c ha n nels 
A E 
a d verse e ve nt 
A E SI 
a d verse e ve nt of s pecial i nterest 
A L T 
ala ni ne a mi n otra nsferase 
A N C 
a bs ol ute ne utr o p hil c o u nt 
A S C O 
A merica n S ociet y of Cli nical O nc ol o g y 
A S T 
as partate a mi n otra nsferase 
β - h C G 
beta h u ma n c h ori o nic g o na d otr o pi n  
B O R 
best o verall res p o nse 
B R C A 
breast ca ncer ge ne 
B S A 
b o d y s urface area 
C A P 
C olle ge of A merica n Pat h ol o gists 
C B C 
c o m plete bl o o d c o u nt 
C B R 
cli nical be nefit rate 
C D 
cl uster of differe ntiati o n 
C D K 
c ycli n- de pe n de nt ki nase  
C F R 
C o de of Fe deral Re g ulati o ns 
CI 
c o nfi de nce i nter val 
CI N V 
c he m ot hera p y-i n d uce d na usea a n d v o miti n g 
C N S 
ce ntral ner v o us s yste m 
C P S 
c o m bi ne d p ositi ve sc ore 
C R 
c o m plete res p o nse 
C T 
c o m p ute d t o m o gra p h y  
C T C A E 
C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts 
C Y P 
c yt oc hr o me P 4 5 0 
D 5 W 
de xtr ose 5 % i n water 
D DI 
dr u g- dr u g i nteracti o n 

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A b bre vi ati o n  
Defi niti o n  
D N A 
de o x yri b o n ucleic aci d 
D O R 
d urati o n of o bj ecti ve res p o nse 
D S N 
d urati o n of se ver e ne utr o pe nia 
E C G 
electr ocar di o gra m 
E C O G 
Easter n C o o perati ve O nc ol o g y Gr o u p  
e C R F 
electr o nic case re p ort f or m 
E D C 
electr o nic data ca pt ure 
E/ P 
et o p osi de pl us car b o plati n 
E/ P/ A 
et o p osi de pl us car b o plati n pl us atez oliz u ma b 
E R 
estr o ge n rece pt or 
E S A 
er yt hr o p oiesis sti m ulati n g a ge nt 
E S- S C L C 
e xte nsi ve-sta ge s mall cell l u n g ca ncer 
F A S 
f ull a nal ysis set 
F D A 
F o o d a n d Dr u g A d mi nistrati o n 
F D G 
[1 8F]-fl u or o de o x y gl uc ose 
F N 
fe brile ne utr o pe nia 
F S H 
f ollicle sti m ulati n g h or m o ne 
G 1 
ga p 1 p hase of t he cell c ycle 
G 1 T 2 8 
trilacicli b; f or merl y G 1 T 2 8- 1 
G C 
ge mcita bi ne a n d car b o plati n 
G C P 
G o o d Cli nical Practice 
G- C S F 
gra n ul oc yte c ol o n y-sti m ulati n g fact or 
G M- C S F 
gra n ul oc yte- macr o p ha ge c ol o n y-sti m ulati n g fact or 
H 1/ H 2 
hista mi ne rece pt or 1/ 2 
H E R 2 
h u ma n e pi der mal gr o wt h fact or rece pt or 2 
HI V 
h u ma n i m m u n o deficie nc y vir us 
H R 
hazar d rati o 
H R T 
h or m o ne re place me nt t hera p y 
H S P C 
he mat o p oietic ste m a n d pr o ge nit or cell 
I B 
I n vesti gat or’s Br oc h ure 
I C 
t u m or-i nfiltrati n g i m m u ne cells 

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A b bre vi ati o n  
Defi niti o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
I CI 
i m m u ne c hec k p oi nt i n hi bit ors 
I D 
i de ntificati o n 
I E C 
i n de pe n de nt et hics c o m mittee  
I F N 
i nterfer o n 
I H C 
i m m u n o hist oc he mistr y 
I L 
i nterle u ki n 
I N R 
I nter nati o nal N or malize d Rati o 
I R B 
i nstit uti o nal re vie w b oar d 
I V 
i ntra ve n o us 
L F T 
li ver f u ncti o n test 
M A T E 1 or 2- K 
m ulti dr u g a n d t o xi n e xtr usi o n 1 or 2- K  
M B C 
metastatic breast ca ncer 
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
M O A 
mec ha nis m of acti o n 
M RI 
ma g netic res o na nce i ma gi n g 
Na F 
s o di u m fl u ori de 
N CI 
Nati o nal Ca ncer I nstit ute 
N K 1 
ne ur o ki ni n 1 
O A T 1 or 3  
or ga nic a ni o n tra ns p orter 1 or 3  
O A T P 1 B 1 or 1 B 3 
or ga nic a ni o n tra ns p orti n g p ol y pe pti de 1 B 1 or 1 B 3   
O C T 1 or 2  
or ga nic cati o n tra ns p orter 1 or 2 
O R R 
o bj ecti ve res p o nse rate 
O S 
o verall s ur vi val 
P A R P 
p ol y a de n osi ne di p h os p hate-ri b ose p ol y merase 
P C S 
p ote ntiall y cli nicall y si g nifica nt 
P D 
pr o gressi ve disease 
P D- 1 
pr o gra m me d cell deat h pr otei n 1  
P D- L 1 
pr o gra m me d deat h-li ga n d 1 
P E S 
p ol yet her s ulf o ne 

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A b bre vi ati o n  
Defi niti o n  
P E T 
p ositr o n e missi o n t o m o gra p h y 
P F S 
pr o gressi o n-free s ur vi val 
P K 
p har mac o ki netic(s) 
P R 
partial res p o nse 
P T F E 
p ol ytetrafl u oret h yle ne 
P V G 
p har mac o vi gila nce 
Q T c F 
Q T c orrecte d i nter val usi n g Fri dericia’s f or m ula  
R B C 
re d bl o o d cell 
R E 
Res p o nse E val ua ble 
R E CI S T 
Res p o nse E val uati o n Criteria i n S oli d T u m ors  
S A E 
seri o us a d verse e ve nt 
S A P 
statistical a nal ysis pla n 
S C L C 
s mall cell l u n g ca ncer 
S D 
sta ble disease 
S M C 
Safet y M o nit ori n g C o m mittee 
S N 
se vere ne utr o pe nia 
S U S A R 
s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
T C R 
T cell rece pt or 
TI L 
t u m or i nfiltrati n g l y m p h oc yte 
T N B C 
tri ple- ne gati ve breast ca ncer 
Tr o p- 2 
tr o p h o blast cell s urface a nti ge n 2 
U L N 
u p per li mit of n or mal 
U S 
U nite d States 

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1 8 
 
 
  
 
4.  
I N T R O D U C TI O N 
4. 1.  
Tri ple- Ne g ati ve Bre ast C a ncer  
Tri ple- ne gati ve breast ca ncer ( T N B C) h as bee n c h aract erize d b y se veral a g gressi ve 
cli nic o pat h ol o gic feat ur es, i ncl u di n g o nset at a y o u n ger a ge, l ar ge, hi g h- gra de t u m ors, a n d a 
pr o pe nsit y f or visceral m etastasis ( C hea n g , 2 0 0 8 ; F o ul kes , 2 0 1 0 ). T h e esti mate d me dia n s ur vi val 
fr o m t he ti me of dia g n osis is a p pr o xi matel y 1 3- 1 8 m o nt hs a n d t he me dia n a ge at dia g n osis is 
a p pr o xi matel y 5 0 years ( Kassa m, 2 0 0 9; Yar dl e y, 2 0 1 8 ). Treat me nts w hi c h are effecti ve f or 
h or m o ne rece pt or- p ositi v e breast ca ncer a n d h u m a n e pi der mal gr o wt h f act or rece pt or 2 
( H E R 2)- p ositi ve breast c a ncer, s u c h as e n d ocri ne t hera p y or H E R 2-tar get e d t hera pies 
(e. g., trast uz u ma b) are n ot effecti ve i n T N B C, w hi c h lac ks t hese m ar kers. I n partic ular, 
c he m ot hera pi es t hat tar get de o x yri b o n ucleic aci d  ( D N A) re pair (e. g., plati n u m c o m p o u n ds) a n d 
cell pr oliferati o n (e. g., ta x a nes a n d a nt hrac ycli n es, li ke d o x or u bici n) ha ve bee n f o u n d t o be t he 
m ost effecti ve i n T N B C; h o we ver, t hes e treat me n ts are li mite d b y t o xicit y a n d e ve nt uall y all 
patie nts de vel o p dr u g resista nce. 
T he c o m bi nati o n of i m m u ne c hec k p oi nt i n hi bit ors (I CIs) wit h c he m ot hera p y ha v e pr o vi de d a 
mea ni n gf ul ste p f or w ar d f or t he treat me nt of pati e nts wit h pr o gra m me d deat h-li ga n d 1 ( P D- L 1) 
p ositi ve l ocall y a d v a nce d u nresect a ble/ metastati c T N B C, b ut d ue t o t he p ot e ntial treat me nt 
t o xicities ass ociate d wit h I CIs, n ot all patie nts wit h P D- L 1 p ositi ve T N B C are a p pr o priate 
ca n di dates f or I CI treat me nt a n d, as w o ul d be  e x pecte d, t he p atie nt p o p ulati o n wit h P D- L 1 
ne gati ve T N B C di d n ot deri ve be n efit. A d diti o nal a vaila ble tar gete d t hera pi es a p pr o ve d b y t h e 
F D A are p ol y a d e n osi ne di p h os p hate-ri b ose p ol y mera se ( P A R P) i n hi bit ors s uc h as ola pari b f or 
t he treat me nt of p atie nts wit h ger mli ne breast c a n cer ge n e ( B R C A)- p ositi ve, H E R 2- ne gati ve 
metastatic breast ca ncer ( M B C) w h o ha v e pre vi o usl y recei ve d c he m ot hera p y a n d t alaz o pari b f or 
patie nts wit h deleteri o us or s us pecte d deleteri o us ger mli ne B R C A- m utate d, H E R 2- ne gati ve 
l ocall y a d va nce d or metastatic breast c a ncer. W hile t hese t w o tar gete d t hera pies offer be nefit t o 
patie nts wit h T N B C, t he y are li mite d t o t h ose wit h ger mli ne B R C A m utati o ns ( ~ 9- 1 8 % of 
T N B C patie nts; Ha h n e n, 2 0 1 7 ). Alt h o u g h I CIs a n d P A R P i n hi bit ors ha ve s h o w n pr o misi n g first-
li ne be nefits, si n gle-a ge nt c he m ot hera p y re mai ns t he sta n dar d of care f or pre vi o usl y treate d 
( be y o n d first-li ne) m etastatic T N B C (Bar dia, 2 0 2 1 ). 
I n 2 0 2 0, accelerate d a p pr o val was gra nt e d b y F D A f or sacit uz u ma b g o viteca n- hzi y ( Tr o del v y® ) 
f or t he treat me nt of a d ult patie nts wit h metastatic T N B C w h o ha v e recei ve d at least t w o pri or 
t hera pies f or metastatic disease. Sacit uz u ma b go viteca n- hzi y is a tr o p h o blast cell s urface a nti ge n 
2 ( Tr o p- 2)- direct e d a nti b o d y- dr u g c o nj u gate li n ke d t o S N- 3 8, t he acti ve meta b olite of iri n oteca n, 
a t o p ois o merase I i n hi bit or (f or m or e i nf or mati o n, refer t o Secti o n 6. 5 ). T h e accelerate d a p pr o val 
was base d o n res ults fr o m t he P hase 2 I M M U- 1 3 2- 0 1 trial w here patie nts ( N = 1 0 8) tr eate d wit h 
sacit uz u ma b g o viteca n- h zi y h a d a n o bjecti ve res p o nse rate ( O R R) of 3 3. 3 %, me dia n d urati o n of 
res p o nse ( D O R) of 7. 7 m o nt hs ( 9 5 % CI: 4. 9- 1 0. 8 m o nt hs), a n d 5 5. 5 % a n d 1 6. 7 % of patie nts 
ha vi n g a D O R of ≥6 m o nt hs a n d ≥1 2  m o nt hs, res pecti vel y (Bar dia, 2 0 1 9 ). I n 2 0 2 1, f ull a p pr o val 
was gra nte d b y F D A b as e d o n t he res ults fr o m t he P hase 3 A S C E N T trial ( Bar di a, 2 0 2 1 ). 
Me dia n P F S f or patie nts recei vi n g sacit u z u ma b g o viteca n- hzi y was 4. 8 m o nt hs ( 9 5 % CI: 
4. 1- 5. 8 m o nt hs) c o m pare d wit h 1. 7 m o nt hs ( 9 5 % CI: 1. 5- 2. 5 m o nt hs) i n t h ose recei vi n g 
p h ysicia n’s c h oice of si n gle- a ge nt c h e m ot hera p y ( hazar d rati o n [ H R] 0. 4 3, 9 5 % CI: 0. 3 5- 0. 5 4, 
P < 0. 0 0 0 1) a n d me dia n o verall s ur vi val ( O S) wa s 1 1. 8 m o nt hs ( 9 5 % CI: 1 0. 5- 1 3. 8 m o nt hs) a n d 

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6. 9 m o nt hs ( 9 5 % CI: 5. 9- 7. 6 m o nt hs), res pec ti vel y ( H R 0. 5 1, 9 5 % CI: 0. 4 1- 0. 6 2, P < 0. 0 0 0 1) 
(Tr o del v y Pac k a ge I ns ert, 2 0 2 1 ). I n t hat sa me st u d y, i n a s u bset of patie nts wit h o ut brai n 
metastasis at baseli ne ( 8 8 % of t he f ull st u d y p o p ul ati o n), me dia n P F S f or p atie nts recei vi n g 
sacit uz u ma b g o viteca n- h zi y w as 5. 6 m o nt hs ( 9 5 % CI: 4. 3- 6. 3 m o nt hs) c o m pare d wit h 1. 7 
m o nt hs ( 9 5 % CI: 1. 5- 2. 5 m o nt hs) i n t h ose recei vi n g p h ysicia n’s c h oice of si n gle -a ge nt 
c he m ot hera p y ( H R 0. 4 1, 9 5 % CI: 0. 3 2- 0. 5 2, P < 0. 0 0 1) a n d me dia n O S w as 1 2. 1 m o nt hs ( 9 5 % 
CI: 1 0. 7- 1 4. 0 m o nt hs) a n d 6. 7 m o nt hs ( 5. 8- 7. 7 m o nt hs), res pecti vel y ( H R 0. 4 8, 9 5 % CI: 0. 3 8-
0. 5 9, P < 0. 0 0 1) ( Bar dia, 2 0 2 1 ). 
O verall, patie nts wit h T N B C ha ve fe w treat me nt o pti o ns be y o n d sta n dar d c he m ot hera p y. E v e n 
t h o u g h t here are n o w a v aila ble tar gete d t hera pies f or T N B C, t hes e t hera pi es are li mite d t o t h ose 
eli gi ble patie nts e x pressi n g P D- L 1- p ositi ve diseas e (I CIs) a n d/ or t h ose t hat carr y a ger mli ne 
B R C A m utati o n ( P A R P i n hi bit ors) a n d i n t he case of I CIs, c o me wit h a d diti o nal t o xicit y. I n 
a d diti o n t o t hese li mitati o ns, c he m ot hera p y -i n d u ce d i m m u n os u p pressi o n ma y als o affect 
a nti-t u m or effic ac y d u e t o a n i na bilit y of t h e h ost i m m u ne s yste m t o effecti vel y m o u nt a 
res p o nse a gai nst t he ca n cer. T heref ore, preser vi n g t he b o ne marr o w a n d i m m u ne s yste m fr o m 
t he c yt ot o xic effects of c he m ot hera p y has t h e p ote ntial t o ma xi mize t he a nti-t u m or acti vit y of t he 
c he m ot hera p y w hile mi ni mizi n g m yel ot o xicit y. N o ve l t hera pe utic o pti o ns t hat ca n offer si milar 
or i m pr o ve d a ntit u m or efficac y wit h o ut t he ass o c iate d hi g h- gra d e t o xicities are cl earl y n ee de d 
f or all T N B C patie nts, re gar dless of P D- L 1 or B R C A stat us. 
4. 2.  
St u d y R ati o n ale  
Trilacicli b is a hi g hl y p ot e nt a n d selecti ve, re versi ble, c ycli n- de p e n de nt ki n ase ( C D K) 4/ 6 
i n hi bit or t hat preser ves h e mat o p oietic ste m a n d pr o ge nit or cells ( H S P Cs) as well as i m m u ne 
s yste m f u n cti o n d uri n g c he m ot hera p y ( m yel o pr otecti o n) i n a d diti o n t o directl y e n h a nci n g 
a nti-t u m or i m m u nit y (a nti-ca ncer efficac y) ( Fi g ure 1 ). B ot h H S P C a n d l y m p h oc yt e pr oliferati o n 
are de p e n de nt o n C D K 4/ 6 acti vit y ( K ozar , 2 0 0 4; Mal u m bres, 2 0 0 4; Ra mse y , 2 0 0 7; 
H orsle y , 2 0 0 8 ) a n d b ec o me arreste d i n t he ga p 1 ( G1) p hase of t he cell c ycl e u p o n e x p os ure t o 
trilacicli b (He , 2 0 1 7 ). T his trilacicli b-i n d uce d tra nsie nt cell c ycle arrest has bee n de m o nstrat e d t o 
pr o vi de resista nce t o c he m ot hera p y-i n d uce d cell d a ma ge b y pre ve nti n g H S P Cs fr o m 
pr oliferati n g i n t he prese nce of c yt ot o xic c he m ot h era p y a n d fa v ora bl y alteri n g t he t u m or i m m u ne 
micr oe n vir o n me nt t hr o u g h tra nsi e nt T cell i n hi biti o n w he n c o m bi ne d wit h c he m ot hera p y 
(He , 2 0 1 7; Bisi , 2 0 1 6; Lai , 2 0 1 8; S orre nti n o , 2 0 1 7 ). I n Fe br uar y 2 0 2 1, t he F D A a p pr o ve d 
trilacicli b ( C O S E L A ™) as a treat me nt t o decreas e t he i nci de nce of c h e m ot hera p y-i n d uce d 
m yel os u p pressi o n i n a d ult patie nts w he n a d mi ni stere d pri or t o a plati n u m/et o p osi de-c o ntai ni n g 
re gi me n or t o p oteca n-c o ntai ni n g re gi me n f or e xte nsi ve-sta ge s mall cell l u n g ca ncer ( E S- S C L C). 

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Fi g ure 1:  
Tril acicli b Tr a nsie ntl y Arrests N or m al C ells t o Pre ve nt 
C he m ot her a p y-I n d uce d M yel os u p pre ssi o n a n d I m pr o v e A nti- T u m or 
Effic ac y 
 
4. 2. 1.  
R ati o n ale f or I m pr o vi n g A nti-t u m o r Effic ac y wit h Tril acicli b 
T he use of trilacicli b f or patie nts wit h T N B C was e val uate d i n St u d y G 1 T 2 8- 0 4, a gl o bal, 
m ultice nter, ra n d o mize d, o pe n-la bel, P hase 2 cli nical trial t o e val uat e t he safet y, effi cac y, a n d 
p har mac o ki netics ( P K) of trilac icli b a d mi nistere d pri or t o ge mcita bi ne/car b o plati n ( G C) t hera p y 
f or patie nts wit h l ocall y a d va nce d u nresecta ble/ metastatic T N B C w h o ha d pre vi o usl y b ee n 
treate d wit h 0 t o 2 li nes of t hera p y i n t he met astatic setti n g. Patie nts were ra n d o mize d 1: 1: 1 t o 
o ne of t w o differe nt trila cicli b + G C treat me nt re gi me ns or G C al o ne. Base d o n its mec ha nis m of 
acti o n ( M O A), it w as h y p ot hesize d t hat trilacicli b a d mi nistere d bef ore c h e m ot hera p y c o ul d 
pr otect t he b o ne marr o w fr o m t he c yt ot o xic effects of c he m ot hera p y, w hile als o e n ha nci n g 
i m m u ne acti vit y i n patie nts wit h T N B C, t h us p ote ntiall y i m pr o vi n g b ot h safet y a n d a nti-t u m or 
acti vit y.  
T he G 1 T 2 8- 0 4 st u d y was t he first e val uati o n of trilacicli b i n a t u m or t y p e ot her t ha n S C L C 
w here trilacicli b de vel o p me nt f oc use d o n m yel o pr otecti o n be nefits ( Secti o n 4. 3. 2. 1 ). T hree 
ra n d o mize d, d o u ble- bli n d, P hase 2 cli nical trials e val uati n g trilacicli b/ place b o a d mi nistere d pri or 
t o c he m ot hera p y i n patie nts wit h S C L C ha ve d e m o nstrate d i n a vari et y of cli nical setti n gs (first-, 
sec o n d-, t hir d-li ne S C L C treate d wit h se v eral differe nt classes of c he m ot hera p y) t hat trilacicli b 
ca n pre v e nt c he m ot hera p y-i n d uc e d m yel os u p pressi o n as meas ure d b y m ulti ple e n d p oi nts 
(Weiss, 2 0 1 9; Hart, 2 0 2 1; Da niel, 2 0 1 9 ). I n a d diti o n, t hese m yel o pr otecti o n be nefits were 
o bser ve d i n t he setti n g of mi n or i m pr o ve me nts i n P F S a n d O S as e vi de nce d b y H Rs < 1. 0 i n 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
2 1 
 
 
  
 
al m ost all cli nical setti n gs f or trilacicli b c o m pare d wit h place b o. F or m ore detaile d i nf or mati o n, 
refer t o t he trilacicli b I n v esti gat or’s Br oc h ure (I B).  
I n c o ntrast t o t he pre vi o usl y o bser ve d S C L C res ults, t he a d diti o n of trilacicli b t o c he m ot hera p y 
f or patie nts wit h T N B C i n G 1 T 2 8- 0 4 di d n ot res ult i n statisticall y si g nifica nt i m pr o ve me nts i n 
m yel os u p pressi o n e n d p oi nts b ut i nstea d res ult e d i n a s u bsta ntial i m pr o ve me nt i n a nti-t u m or 
effic ac y as me as ure d b y O S ( me dia n O S d urati o n i n c o ntr ol 1 2. 6 m o nt hs vs. n ot e val ua ble or 
1 7. 8 m o nt hs i n t he t w o trilacicli b gr o u ps, H R 0. 3 1 [ 9 5 % CI: 0. 1 5- 0. 6 3] a n d H R 0. 4 0 [ 9 5 % CI: 
0. 2 2- 0. 7 4], res pecti vel y) a n d b y P F S ( me dia n P F S i n c o ntr ol 5. 7 m o nt hs vs. 9. 4 m o nt hs or 7. 3 
m o nt hs i n t he t w o trilacicli b gr o u ps H R 0. 6 2 [ 9 5 % CI: 0. 3 2- 1. 2 0] a n d 0. 6 3 [ 9 5 % CI: 0. 3 2- 1. 2 2], 
res pecti vel y a n d O R R ( 2 9. 2 % i n t he c o ntr ol gr o u p vs. 5 0. 0 % a n d 3 8. 7 % i n t he t w o trilacicli b 
gr o u ps, res pecti vel y; n ot statisticall y si g nifica nt) ( Ta n, 2 0 1 9; O ’ S ha u g h ness y, 2 0 2 0). T h e 
cli nicall y me a ni n gf ul a nti-t u m or effic ac y res ults o bser ve d i n G 1 T 2 8- 0 4 were n ote d acr oss b ot h 
of t he trilacicli b treat me nt gr o u ps a n d i n p atie nts  wit h b ot h P D- L 1 p ositi ve a n d ne gati ve t u m ors, 
a n d t hese be n efits were o bser ve d f or m ulti ple a n ti-t u m or efficac y e n d p oi nts, wit h O R R, P F S, a n d 
O S e n d p oi nts all s h o wi n g n u meri cal i m pr o ve me nt wit h t he a d diti o n of trilacicli b t o G C 
c o m pare d wit h G C al o n e. T hese res ults w ere o bs er ve d i n t he c o nte xt of a c o ntr ol gr o u p t hat is 
reflecti ve of p u blis he d literat ur e f or t his patie nt p o p ulati o n (refer t o Secti o n 4. 3. 2. 1  f or a d diti o nal 
i nf or mati o n). A c o nfir m at or y P hase 3 st u d y is c urre ntl y o n g oi n g ( St u d y G 1 T 2 8- 2 0 8, 
N C T 0 4 7 9 9 2 4 9).  
T he differe nces bet wee n t he o bser ve d a nti-t u m or efficac y res ults i n t he S C L C trials a n d t h ose i n 
t he T N B C trial are h y p ot hesiz e d t o res ult fr o m differe n ces i n t he ke y v aria bles bet wee n t he t w o 
cli nical sit uati o ns. U nli ke c he m ot hera p y-i n d uce d m yel os u p pressi o n, t he effects of trilacicli b o n 
a nti-t u m or effic ac y are pre dicte d t o be pri maril y dri ve n b y t h e t u m or t y p e, c he m ot hera p y t y p e, 
a n d h ost, i.e., ( 1) t he t u m or t y pe m ust be s ufficie ntl y res p o nsi v e t o c he m ot h era p y s uc h t h at 
mai nte na nce of c he m ot h era p y d ose i nte nsit y is be neficial, ( 2) t h e t u m or m ust be s ufficie ntl y 
i m m u n o ge nic a n d s e nsiti ve t o t he h ost c yt ol ytic eff orts as t o see i m pr o ve m e nt i n a nti-t u m or 
e n d p oi nts li ke O S, ( 3) t he c he m ot hera p y s h o ul d pr o m ote i m m u ne acti vati o n, ( 4) t he h ost m ust be 
a ble t o t olerate t he sta n d ar d of care c h e m ot hera p y d ose i nte nsit y, a n d ( 5) t h e h ost m ust be a ble t o 
m o u nt a n effecti ve c yt ol ytic res p o nse a gai nst t he t u m or. I n t he S C L C trials, t he a d diti o n of 
trilacicli b t o t he sta n dar d of care t hera pies pr o vi ded m o dest i m pr o ve me nt, t o ne utral effects, o n 
meas ures of a nti-t u m or efficac y i ncl u di n g O R R, P F S, a n d O S. T hese res ults are n ot s ur prisi n g 
c o nsi deri n g t hat S C L C is o ne of t he m ost a g gressi ve s oli d t u m ors, rela pses q uic kl y after 
c o m pleti o n of c he m ot hera p y, h as bee n s h o w n t o be  relati vel y i nse nsiti ve t o m ulti ple atte m pts t o 
i nte nsif y t he c he m ot hera p y re gi me n be y o n d t he c urre nt sta n dar d of care, a n d is n ot partic ularl y 
i m m u n o ge nic or s e nsiti ve t o i m m u ne m o d ulati o n. I n c o ntrast, T N B C has b ee n s h o w n t o be 
i m m u n o ge nic a n d m or e s e nsiti ve t o i m m u ne m o d ulati o n c o m pare d t o S C L C (Se me n o va, 2 0 1 5; 
He, 2 0 1 7; Car vajal- Ha us d orf, 2 0 1 9; Li u, 2 0 1 8) . 
I n a d diti o n, t he G 1 T 2 8- 0 4 res ults were ge nerall y c o nsiste nt acr oss patie nt s u b gr o u ps, i ncl u di n g 
C D K 4/ 6 stat us. Patie nt t u m ors were c haract erize d as C D K 4/ 6 i n de pe n de nt, de pe n de nt, or 
i n deter mi nate usi n g t w o esta blis he d si g nat ures ( Pr osi g na Breast Ca ncer Pr o g n ostic Ge ne 
Si g nat ure Assa y [ P A M 5 0] a n d Le h ma n n tri ple- ne gati ve breast ca ncer t y pe) ( Prat, 2 0 1 4; 
Le h m a n n, 2 0 1 6; As g har, 2 0 1 7 ). As e x pecte d, t hes e data s u g gest trilaci cli b d oes n ot a nta g o nize 
c he m ot hera p y effi cac y re gar dless of C D K 4/ 6 st at us, i ncl u di n g t u m ors t hat are C D K 4/ 6 
i n deter mi nate or d e pe n de nt (Ta n, 2 0 1 9; O ’ S ha u g h ness y, 2 0 2 0). T hese d ata are c o nsiste nt t hat 
T N B C is pre d o mi na ntl y C D K 4/ 6 i n de pe n de nt a n d t h eref ore n ot se nsiti ve t o C D K 4/ 6 i n hi biti o n. 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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T he c o m bi nati o n of trilacicli b pl us sacit uz u ma b g o viteca n- hzi y i n patie nts wit h T N B C is 
pre dicte d t o de m o nstrat e i m pr o ve me nt i n a nti-t u m or efficac y si milar t o t he res ults o bser ve d i n 
St u d y G 1 T 2 8- 0 4. As n ot e d a b o ve, T N B C has b ee n s h o w n t o be i m m u n o ge nic a n d m ore se nsiti ve 
t o i m m u ne m o d ulati o n a n d sacit uz u ma b g o viteca n- hzi y i n d u ces D N A da ma ge lea di n g t o 
a p o pt osis a n d cell deat h t hr o u g h u pt a ke of t u m or cells (see Secti o n 6. 5 ). T his mec ha nis m of 
acti o n c o m pli me nts trilacicli b’s p ositi ve i m pact o n a nti-t u m or i m m u ne m o d ulati o n (see 
Secti o n 4. 2. 2 ). T heref ore, t he c o m bi nati o n of trilacicli b pl us sacit uz u ma b g o viteca n- hzi y i n 
patie nts wit h T N B C f ulfills t he ke y varia bles  des cri be d a b o ve t hat are i n dicati ve of a n 
i m pr o ve me nt i n a nti-t u m or effic ac y. 
4. 2. 2.  
R ati o n ale f or I m m u ne Mec h a nis m of Tril acicli b 
I n t he G 1 T 2 8- 0 5 st u d y e val uati n g trilacicli b pri or t o cis plati n, et o p osi de, a n d atez oliz u ma b 
( E/ P/ A) i n patie nts wit h e xte nsi ve sta ge S CL C, fl o w c yt o m etr y a n d T cell rece pt or ( T C R) 
i m m u n ose q ue nci n g d ata re veal e d t hat patie nts recei vi n g trilaci cli b ha d a n i ncreas e d rati o of t otal 
a n d acti vate d cl uster of differe ntiati o n ( C D) 8 +  T cells t o Tre gs a n d i ncrease d peri p heral T cell 
cl o nal e x pa nsi o n s u g gesti n g e n h a nce d T cell ac ti vati o n. F urt her m ore, t here was si g nifi ca nt 
e n ha nce me nt i n ne wl y detecte d e x pa n de d cl o nes a m o n g patie nts r ecei vi n g trilacicli b c o m pare d 
wit h place b o, w hic h w as str o n ger a m o n g patie nts wit h a n a nti-t u m or res p o nse t o et o p osi de pl us 
car b o plati n pl us atez oliz u ma b ( E/ P/ A), s u g gest i n g t hat trilaci cli b ma y e n h a nce t u m or a nti ge n 
prese ntati o n, a p h e n o me n o n t hat has bee n o bser ve d i n precli nical st u dies wit h ot her C D K 4/ 6 
i n hi bit ors (Da niel, 2 0 2 0 ). 
T hese o bser vati o ns are c o nsiste nt wit h t h ose fr o m t he G 1 T 2 8- 0 2 P hase 2 st u d y of patie nts wit h 
e xte nsi ve sta ge S C L C recei vi n g trilacicli b pri or t o et o p osi de pl us car b o plati n ( E/ P). I n 
G 1 T 2 8- 0 2, a hi g her pr o p orti o n of acti vate d or effect or C D 8 +  a n d C D 4+  T cells was o bser ve d i n 
patie nts recei vi n g trila cicli b c o m pare d wit h place b o. I n a d diti o n, hi g h le vels of T cell cl o nal 
e x pa nsi o n were ass oci ate d wit h i m pr o ve d P F S a n d n u mericall y l o n ger me di a n O S. Ta ke n 
t o get her, t he data s u g gest t hat t he a d diti o n of trilacicli b at least preser ves, if n ot e n ha nces, T cell 
f u ncti o n d uri n g tr eat me nt wit h E/ P or E/ P/ A (Lai, 2 0 2 0 ). 
Lastl y, t o e val uate t he effect of trilacicli b o n T cell acti vati o n, peri p heral bl o o d was c ollecte d a n d 
t he T C R was e val uate d. Si m ps o n cl o nalit y decrease d o ver ti me i n patie nts t hat recei v e d 
trilacicli b i n a d diti o n t o G C w he n c o m pare d t o G C al o ne. F urt her m ore, aft er stratificati o n a b o ve 
or bel o w me dia n Si m ps o n cl o nalit y at b aseli ne, a n e x pl orat or y a n al ysis s h o we d patie nts a b o ve 
t he me dia n de m o nstrate d a great er O S be n efit wit h t he a d diti o n of trilacicli b t o G C t ha n patie nts 
bel o w t he me dia n. I n a d diti o n t o a decreas e i n Si m ps o n cl o nalit y, res p o n ders recei vi n g trilaci cli b 
pri or t o G C ha d m ore ne wl y de t ecte d e x pa n de d cl o nes c o m pare d wit h res p o n ders recei vi n g G C 
al o ne. T hese d ata s u g gest trilacicli b e n ha nces a nti-t u m or i m m u nit y t hr o u g h T cell acti vati o n 
lea di n g t o a n a nti-t u m or res p o nse (O ’ S ha u g h n ess y, 2 0 2 0).  
Des pite t he c o m pelli n g cli nical efficac y of I CIs, t he maj orit y of patie nts e v e nt uall y d e vel o p 
t hera pe utic resista nce l ea di n g t o disease pr o gressi o n after a n i nitial res p o nse. Mec ha nis ms of I CI 
resista nce i ncl u d e ge neti c, e pi ge netic, a n d cell ular si g nali n g alterati o ns t hat d ysre g ul ate 
ne oa nti ge n pres e ntati o n/ pr ocessi n g a n d disr u pt c yt o t o xic T cells acti vit y as well as mec ha nis ms 
i n w hic h n o n-ca n cer o us str o mal or i m m u ne cells pr o m ote gr o wt h a n d resista nce t o I CIs (Li u, 
2 0 1 8; Barr uet o, 2 0 2 0 ; J e n ki ns, 2 0 1 8; Fares, 2 0 1 9; B orc h er di n g, 2 0 1 8 ; Gi de, 2 0 1 8 ). I nteresti n gl y, 
ma n y of t h e mec h a nis ms t o o verc o me I CI-i n d u ce d resista nce h a ve bee n ass ociate d wit h t he 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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i m m u ne acti vati n g effects of C D K 4/ 6 i n hi biti o n, i ncl u di n g i ncreasi n g a nti ge n prese nt ati o n 
( maj or hist oc o m pati bilit y c o m ple x class I), e n han ci n g T cell cl o nalit y a n d t u m or i nfiltrati o n, 
i n hi biti n g re g ulat or y T cell pr oliferati o n, decreasin g T cell e x ha usti o n mar kers ( pr o gra m me d cell 
deat h pr otei n 1 [ P D- 1], c yt ot o xic T-l y m p h oc yte ass ociate d pr ot ei n 4, a n d T cell i m m u n o gl o b uli n 
a n d m uci n d o mai n 3), sta bilizi n g e x pressi o n of P D- L 1 o n t u m or cells, pr o m oti n g de n dritic cell 
mi grati o n, a n d i ncreasi n g T effect or cell f u ncti o n t hr o u g h hi g h i nterfer o n (I F N) ga m ma 
pr o d ucti o n.  T hese dat a s u g gest patie nts m a y b e nefit fr o m trilacicli b after pr o gressi n g o n I CI 
treat me nt (C hai k o vs k y  a n d Sa ge, 2 0 1 8; De n g, 2 0 1 8; G oel, 2 0 1 7; Sc haer, 2 0 1 8; Lai, 2 0 2 0 ; 
B o nelli, 2 0 1 9 ; Te h  a n d A pli n, 2 0 1 9 ).   
Ta ke n t o get her, t hese dat a fr o m cli nical trials e v al uati n g trilaci cli b i n a vari et y of cli nical 
c o nte xts s u g gest t hat trilacicli b has a c o nsiste nt p ositi ve i m pact o n a nti-t u m or i m m u ne 
m o d ulati o n. F urt her m ore, t here a p p ears t o be s e veral i m m u ne- base d mec ha nis ms t hr o u g h w hic h 
t his effect c a n be me di ate d i ncl u di n g ne o a nti ge n prese ntati o n a n d T cell acti vati o n a n d f u ncti o n.  
T heref ore, it is p ossi ble t hat trilacicli b ma y i m pr o ve a nti-t u m or o utc o mes, s uc h as P F S a n d O S, 
i n T N B C patie nts treat e d wit h sacit uz u ma b g o viteca n- hzi y. 
4. 2. 3.  
R ati o n ale f or M yel o pr otecti o n 
Trilacicli b has s h o w n w ell- d oc u me nte d i m pr o ve m e nt i n m yel os u p pressi o n o utc o mes t hat c o ul d 
pr o vi de be nefit t o patie nts recei vi n g sacit uz u ma b g o viteca n- hzi y. I n t he P hase 3 A S C E N T trial, 
5 2 % of patie nts wit h T N B C treate d wit h saci t uz u ma b g o viteca n- hzi y e x perie nce d Gra d e 3/ 4 
ne utr o pe nia ( 1 4 % Gra de 4) wit h 6 % e x perie nci n g  fe brile ne utr o p e nia. I n A S C E N T, t he me dia n 
ti me t o o nset of t he first e ve nt of Gra de ≥3 ne utr o pe nia i n patie nts treate d wit h sacit uz u ma b 
g o viteca n- hzi y w as 2 1 da ys ( R u g o, 2 0 2 0 ). I n a d diti o n, 9 % of patie nts treat e d wit h sacit uz u ma b 
g o viteca n- hzi y e x perie nce d Gra d e 3/ 4 a ne mia ( Bar dia, 2 0 2 1; Tr o del v y Pac ka ge I nsert, 2 0 2 1 ). 
Patie nts treate d f or S C L C wit h trilacicli b ha d mar ke d re d u cti o ns i n t he occ urre n ce of t h ese 
o utc o mes ( Ta ble 2 ), re q uiri n g less s u p p orti ve care a n d e x perie nce d e n ha n ce d q ualit y of life.  T he 
e x pl orat or y patie nt-re p orte d o utc o me e n d p oi nts i n t hese patie nts s u g geste d t hat trilacicli b 
a d mi nistere d pri or t o c h e m ot hera p y ma y offer p ot e ntial be nefit i n m ulti ple as pects of healt h-
relate d q ualit y of life wit h a great er ma g nit u de of effect o bser v e d f or fati g u e a n d a n e mia 
s y m pt o ms a n d f u ncti o nal li mitati o ns (Weiss, 2 0 1 9 ). A n a nal ysis of i nte grate d fati g ue s u bscale 
data fr o m F u ncti o nal Ass ess me nt of Ca ncer T hera p y –  A ne mia i n t he t hree st u dies s h o we d t hat 
trilacicli b dela ye d t he m e dia n ti m e t o deteri orati o n b y a p pr o xi matel y 5 m o nt hs f or fati g ue 
( 7. 0 3 m o nt hs i n t he trilacicli b gr o u p vs. 2. 3 3 m o nt hs i n t he place b o gr o u p, H R 0. 5 6, 9 5 % CI: 
0. 3 7, 0. 8 5) ( Weiss, 2 0 2 1 ). F or m ore d etaile d i nf or mati o n, refer t o t he trilacicli b I B.  Gi ve n t hat 
t he rate of Gra d e 3/ 4 ne utr o pe nia i n T N B C p atie nts treate d wit h sacit uz u ma b g o viteca n- hzi y is 
hi g her t h a n t hat o bser ve d i n T N B C patie nts fr o m St u d y G 1 T 2 8- 0 4 tr eate d wit h 
ge m cita bi ne/car b o plati n ( 5 2 % vs. 2 6. 5 %), it is p ossi ble t hat t he m yel o pr ot ecti ve be n efits of 
trilacicli b ma y als o be o bser ve d i n T N B C patie nts treate d wit h sacit uz u ma b g o viteca n- hzi y. 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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T a ble 2:  
I nte gr ate d A n al ysis f or M yel o pr otecti o n Effic ac y i n S C L C ( St u dies 
G 1 T 2 8- 0 2, G 1 T 2 8- 0 3, a n d G 1 T 2 8- 0 5) 
 
Pl ace b o + 
C he m o 
Tril acicli b + 
C he m o 
2 -si de d p-v al ue 
I T T Set 
1 1 9 
1 2 3 
 
Ne utr o p hils  
D S N [ da ys] i n C ycle 1 –  Mea n ( S D)a 
4 ( 5. 1) 
0 ( 1. 8) 
< 0. 0 0 0 1 
Occ urre nce of S N ( Yes, %) b 
6 4 ( 5 2. 9) 
1 4 ( 1 1. 4) 
< 0. 0 0 0 1 
R B Cs  
Occ urre nce of Gra de 3/ 4 he m o gl o bi n decrease d 
(a ne mia) ( Yes, %)b 
3 8 ( 3 1. 9) 
2 5 ( 2 0. 3) 
0. 0 2 7 9 
Occ urre nce of R B C tra nsf usi o n o n/after 5 wee ks 
( Yes, %)b 
3 1 ( 2 6. 1) 
1 8 ( 1 4. 6) 
0. 0 2 5 2 
C u m ulati ve i nci de nce of R B C tra nsf usi o n o n/after 5 
wee ks - E ve nt rate ( per 1 0 0 wee ks)c 
3. 1  
1. 5  
0. 0 0 2 7 
Pl atelets  
Occ urre nce of Gra de 3/ 4 platelet c o u nt decrease d 
(t hr o m b oc yt o pe nia) ( Yes, %)b 
4 3 ( 3 6. 1) 
2 4 ( 1 9. 5) 
0. 0 0 6 7 
Occ urre nce of platelet tra nsf usi o n ( Yes, %) b 
1 1 ( 9. 2) 
1 0 ( 8. 1) 
0. 9 5 6 4 
C u m ulati ve i nci de nce of platelet tra nsf usi o n –  E ve nt 
rate ( per 1 0 0 wee ks)c 
1. 7  
1. 1  
0. 5 1 6 9 
A N C =a bs ol ute ne utr o p hil c o u nt; C he m o =c he m ot hera p y; D S N = d urati o n of se vere ( Gra de 4) ne utr o pe nia; 
E C O G = Easter n C o o perati ve Gr o u p; R B C =re d bl o o d cells; S C L C =s mall cell l u n g ca ncer; S D =sta n dar d de viati o n; 
S N =se vere ( Gra de 4) ne utr o pe nia w hic h is defi ne d as A N C < 5 0 0/ m m 3; I T T =i nte nt t o treat. 
C he m o =et o p osi de + plati n u m i n G 1 T 2 8- 0 2, et o p osi de + p lati n u m + atez oliz u ma b i n G 1T 2 8- 0 5, a n d t o p oteca n i n 
G 1 T 2 8- 0 3. Sta n dar d s u p p orti ve care i nter ve nti o ns were all o we d f or all ar ms. 
a p- val ue was o btai ne d fr o m a n o n para metric a nal ysis of c o varia nce ( A N C O V A). 
b p- val ue was o btai ne d fr o m a m o difie d P oiss o n m o del. 
c p- val ue was o btai ne d fr o m a ne gati ve bi n o mial m o del. All t hree m o dels c o ntai ne d fi xe d effect of treat me nt, E C O G 
perf or ma nce stat us ( 0- 1 vers us 2), Prese nce of brai n metastases ( Y/ N), a n d st u d y ( G 1 T 2 8- 0 2, G 1 T 2 8- 0 3, or 
G 1 T 2 8- 0 5). C orres p o n di n g baseli ne assess me nt was als o i ncl u de d as a c o variate. 
4. 3.  
B ac k gr o u n d 
I n Fe br uar y 2 0 2 1, t h e U S F D A a p pr o ve d trila cicli b ( C O S E L A ™) as a tr eat me nt t o decrease t he 
i nci de nce of c he m ot hera p y-i n d uc e d m yel os u p pressi o n i n a d ult patie nts w he n a d mi nistere d pri or 
t o a plati n u m/et o p osi de-c o ntai ni n g re gi me n or t o p oteca n-c o ntai ni n g re gi me n f or E S- S C L C. 
4. 3. 1.  
S u m m ar y of N o ncli nic al D at a 
A s u m mar y of t he trilaci cli b n o ncli nical data is pr ese nte d i n t he trilacicli b I B.  
N o ncli nical data relate d t o sacit uz u ma b g o viteca n- hzi y are pr o vi de d i n t he l ocal pres cri bi n g 
i nf or mati o n. 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
2 5 
 
 
  
 
4. 3. 1. 1.  
P h ar m a c ol o g y St u dies 
T hr o u g h a str uct ur e- bas e d desi g n a p pr oac h t o  o pti mize p ote nc y, selecti vit y, a n d dr u g 
meta b olis m a n d P K pr o perties, trilacicli b was i de ntifi e d as a hi g hl y p ot e nt i n hi bit or of C D K 4 
a n d C D K 6 ( half m a xi mal i n hi bit or y c o nce ntrati o n va l ues of 1 n M a n d 4 n M, res pecti vel y) t h at is 
hi g hl y selecti ve f or C D K 4/ C ycli n D 1 vers us C D K 2/ C ycli n E ( > 2 5 0 0-f ol d s electi vit y). Trilacicli b 
als o de m o nstrate d re versi ble i n hi biti o n of C D K 4/ C ycli n D 1, wit h a n i n hi biti o n c o nsta nt val ue of 
0. 7 8 n M. 
T he trilacicli b-i n d uc e d G 1 arrest of H S P Cs has bee n s h o w n t o be tra nsie nt a n d rea dil y re versi ble 
i n b ot h i n vitr o a n d i n vi v o m o dels. I n vi v o a n al ysis has de m o nstrate d t hat trilacicli b 
a d mi nistere d pri or t o m yel os u p pressi ve c h e m ot hera p y lea ds t o i m pr o ve d c o m plete bl o o d c o u nt 
( C B C) rec o ver y of all bl o o d li nea ges a n d i ncreas e d s ur vi val. S pecificall y, i n a m o del usi n g t he 
hi g hl y m yel os u p pressi ve c he m ot hera p y 5-fl u or o ur acil ( 5- F U), w hile t he e xte nt a n d d urati o n of 
na dir i n C B Cs w orse n e d after eac h c ycle of 5- F U a d mi nistere d al o ne, trilacicli b a d mi nistere d 
pri or t o 5- F U a meli orate d t his w orse ni n g effect a n d t he a ni mals t hat recei ve d trilacicli b + 5- F U 
de m o nstrate d a faster rat e of rec o ver y of C B Cs  c o m pare d wit h t he 5- F U al o ne gr o u p f oll o wi n g 
C ycle 4 ( He, 2 0 1 7 ).  
Precli nical data h a ve s h o w n trilacicli b e n ha n c es i m m u ne acti vati o n a n d pr o m otes a nti-t u m or 
i m m u nit y b y differe ntiall y arresti n g c yt ot o xic a n d re g ulat or y T cell s u bsets f oll o we d b y a faster 
rec o ver y of c yt ot o xic T l y m p h oc ytes t ha n re g ulat or y T cells i n t u m ors. S pecificall y, t he a d diti o n 
of trilacicli b t o vari o us c he m ot hera p y/I CI tr eat me nt c o m bi nati o ns res ulte d i n e n ha nce d t u m or 
gr o wt h dela y a n d d ura bilit y of t he a ntit u m or res p o nse. Trilacicli b fa v ora bl y m o d ulate d t he 
pr oliferati o n of T cell s u bsets i n t he t u m or mi cr oe n vir o n me nt, c o nsiste nt wit h a n e n ha nce d 
c yt ot o xic T cell res p o ns e ( Fi g ure 2 ; Lai, 2 0 2 0 ). T his differe ntial alterati o n of cell c ycl e ki netics 
bet wee n c yt ot o xic T l y m p h oc yt es a n d re g ulat or y T cells res ults i n a hi g h er pr o p orti o n of 
c yt ot o xic T l y m p h oc ytes t ha n re g ulat or y T cells, e n ha nce me nt of T cell acti vati o n, a n d a 
decrease i n r e g ulat or y T cell- me diate d i m m u n os u p pressi ve f u ncti o ns ( C hai k o vs k y  a n d Sa ge, 
2 0 1 8; De n g, 2 0 1 8; G o el, 2 0 1 7; Sc haer, 2 0 1 8 ). T o get her, t hese e ve nts pr o m ote t he c yt ot o xic 
T l y m p h oc yte- me diate d cleara nce of t u m or cells. T heref ore, t hes e data s u p p ort t he h y p ot hesis 
t hat trilacicli b- me diate d tra nsie nt pr oliferati ve arrest of T cells ( pr otecti n g t he m fr o m 
c he m ot hera p y-i n d uce d d a ma ge), f oll o we d b y acti vati o n of c yt ot o xic T l y m p h oc yt es i n t he 
c o nte xt of fe wer re g ulat or y T cells, le d t o t he a nti-t u m or res p o nse o bser ve d. 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
2 6 
 
 
  
 
Fi g ure 2:   
T he A d diti o n of Tril acicli b t o C he m ot her a p y/I m m u ne C hec k p oi nt I n hi bit or 
Tre at me nt E n h a nces Effic ac y T hr o u g h T Cell Acti v ati o n 
 
 
C D =cl uster of differe ntiati o n; P D- 1 = pr o gra m me d cell de at h pr otei n 1; P D- L 1 = pr o gra m me d deat h-li ga n d 1; 
Tre g =re g ulat or y T cell 
E x vi v o a n d i n vi v o st u dies re veale d t hat t he i n hi biti o n of C D K 4/ 6 b y trilacicli b res ulte d i n 
i ncreas e d a ntit u m or acti vit y, partic ularl y i n c o nju ncti o n wit h P D- 1 bl oc ka de, a n d t his effect was 
lar gel y de pe n d e nt o n T cells (De n g, 2 0 1 8 ). I n vi v o P D- 1 bl oc ka de i n d uce d partial t u m or gr o wt h 
i n hi biti o n i n t he m uri ne c ol o n carci n o ma M C 3 8 m o del a n d t he a d diti o n of i nter mitte nt e x p os ure 
t o trilacicli b nearl y eli mi nate d t u m or gr o wt h (Fi g ure 3, L E F T ). Pr ofili n g of t u m or i nfiltrati n g 
l y m p h oc ytes ( TI Ls) fr o m M C 3 8 t um ors re veale d t hat a nti- P D- 1 al o ne i ncrease d C D 8 + I F N γ 
pr o d ucti o n b ut n ot C D 4 + I L 2 pr o d ucti o n ( Fi g ure 3, RI G H T a n d MI D D L E ). T h us, i n t his m o del, 
P D- 1 bl oc ka de i ncreas e d t he c yt ot o xicit y of C D 8 + T cells b ut di d n ot i ncrease T cell 
pr oliferati o n t hr o u g h i nterle u ki n (I L)- 2. A d diti o n of  trilacicli b t o P D- 1 bl oc ka de res ulte d i n a n 
a p pr o xi matel y 1 0- f ol d i n creas e i n t he le vels of I F Nγ i n C D 8 + TI Ls a n d a p pr o xi matel y 2-f ol d 
i ncreas e i n C D 4 + I L- 2 pr o d ucti o n. T hese data de m o nstrate t hat trilacicli b a u g m e nte d a nti-t u m or 
i m m u nit y, w hic h tr a nslat e d t o a n i m pr o ve d a ntit u m or res p o nse t hat w as lar gel y d e pe n de nt o n t he 
acti vit y of T cells, t here b y se nsitizi n g t u m ors t o i m m u ne c hec k p oi nt bl oc ka de.  

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
2 7 
 
 
  
 
Fi g ure 3:   
Tril acicli b A u g me nts A nti- P D- 1 A nti b o d y-I n d uce d A ntit u m o r Acti vit y 
 
C D =cl uster of differe ntiati o n; I F N =i nterfer o n; I L =i nterle u ki n; P D- 1 = pr o gra m me d cell deat h pr otei n 1; N S = n ot 
si g nifica nt 
C o m bi nati o n treat me nt of trila cicli b s y ner gize a nti – P D- 1 a nti b o d y – i n d uce d a ntit u m or i m m u nit y t hr o u g h T cells. 
( L E F T) T u m or gr o wt h c ur ves of M C 3 8 cells treate d wit h tril acicli b or P D- 1 a nti b o d y al o ne or i n c o m bi nati o n. 
M C 3 8 m uri ne ca ncer cells were i nj ecte d s u bc uta ne o us l y i nt o C 5 7 B L/ 6 mice. T he mice were treate d wit h 
trilacicli b 1 0 0 m g/ k g i nter mitt e ntl y ( 3 da ys o n, 4 da ys off) wit h or wit h o ut P D-1 a nti b o d y ( 2 0 0 μ g/ m o use, 3 ti mes 
a wee k) as i n dicate d starti n g fr o m da y 3 ( M C 3 8). T u m or v ol u mes were m o nit ore d e ver y 2 – 3 da ys. T he gra p h 
s h o ws re prese ntati ve res ults fr o m t w o i n de p e n de nt e x peri me nts ( n = 8; *, P < 0. 0 5; * *, P < 0. 0 1; * * *, P < 0. 0 0 1). 
( MI D D L E a n d RI G H T) Q ua ntificati o n of c yt o ki ne pr o d ucti o n pr o d uce d b y M C 3 8 t u m or-i nfiltrati n g T 
l y m p h oc ytes. At t he e n d of t he treat me nt ( da y 1 7), mice wer e sacrifice d a n d t u m or i nfiltrati n g l y m p h oc ytes were 
is olate d fr o m t he t u m or f or c yt o ki ne a nal ysis f or I L-2 fr o m C D 4 + T cells ( MI D D L E) a n d I F N γ fr o m C D 8 + T cells 
( RI G H T) ( *, P < 0. 0 5; * *, P < 0. 0 1; * * *, P < 0. 0 0 1).  
N o ncli nical data h a ve s h o w n t hat i n a hi g hl y C D K 4/ 6 de pe n de nt estr o ge n rece pt or ( E R) + breast 
ca ncer m o del, i nter mitte nt trilaci cli b d osi n g d uri n g t he ti me of c he m ot hera p y treat me nt di d n ot 
ne gati vel y affect c h e m ot hera p y tr eat me nt. T he la c k of a nta g o nis m w he n trilacicli b was a d d e d t o 
c he m ot hera p y treat me nt was o bser v e d i n m ulti ple C D K 4/ 6 de pe n de nt m o d els ( S orre nti n o, 2 0 1 8 ). 
W hile trilacicli b is n ot e x pecte d t o directl y i m pa ct t u m or pr oliferati o n, it has t he p ote ntial t o 
greatl y i m pr o ve t he c urre nt sta n dar d of care i n T N B C b y pr otecti n g t he b o ne marr o w a n d 
i m m u ne s yste m f u ncti o n d uri n g sacit uz u ma b g o vit eca n- hzi y t hera p y i n a d diti o n t o acti vati n g 
T cell me diate d i m m u nit y a n d p ot e ntiall y e n ha nci n g a nti-t u m or acti vit y.  
4. 3. 1. 2.  
P h ar m a c o ki netic St u dies 
P har mac o ki netic st u dies i n rats a n d d o gs s h o we d t hat t he relati o ns hi p bet wee n d ose le vel a n d 
plas ma e x p os ure t o trilacicli b was ge nerall y si milar bet wee n males an d fe males a n d di d n ot 
c ha n ge wit h r e peat e d dail y d osi n g. E x p os ure t o trilacicli b i ncrease d wit h d ose le vel, b ut n ot 
al wa ys pr o p orti o nall y.  
I n vitr o a nal yses of direct a n d ti me- de pe n d e nt i n hi biti o n s u g gest t hat dr u g i nteracti o ns base d o n 
i n hi biti o n of c yt o c hr o me P 4 5 0 ( C Y P) 1 A 2-, 2 B 6-, 2 C 8-, 2 C 9-, 2 C 1 9-, a n d 2 D 6- me diate d 
meta b olic pat h wa ys are u nli kel y at cli nical d os es ; h o we ver, t he st u dies d o s u g gest t hat dr u g- dr u g 
i nteracti o ns ( D DI) bas e d o n trilacicli b- me diate d i n hi biti o n of C Y P 3 A 4- me diate d meta b olic 
pat h wa ys are p ossi ble (see Secti o n 4. 3. 2. 1. 1  f or a d diti o nal details). A d diti o nall y, i n vitr o 
i n d ucti o n st u dies of t he 3 maj or i n d uci ble CY P e nz y m es ( C Y P 1 A 2, C Y P 3 A 4, a n d C Y P 2 B 6) i n 
h u ma n he pat oc ytes s u g gest t hat trilac icli b- me diat e d i n d ucti o n is u nli kel y.  
I n vitr o i n hi biti o n st u dies wit h me m bra ne tra ns p orter m o del s yste ms als o s u g gest trilacicli b is 
u nli kel y t o ca us e a D DI base d o n i n hi biti o n of breas t ca n cer resista nce pr otei n-, bile salt e x p ort 
p u m p-, or ga nic a ni o n tra ns p orter 1 ( O A T 1)-, or ga nic a ni o n tra ns p orter 3 ( O A T 3)-, or ga nic a ni o n 
tra ns p orti n g p ol y pe pti de 1 B 1 ( O A T P 1 B 1)-, p- gl yc o pr otei n-, m ulti dr u g resista nce pr otei n 1-, 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
2 8 
 
 
  
 
m ulti dr u g resista nce pr ot ei n 2-, or or ga nic a ni o n tra ns p orti n g p ol y pe pti de 1 B 3 ( O A T P 1 B 3)-
me diate d tra ns p ort.  
H o we ver, i n vitr o, trilacicli b is a p ote nt i n hi bit or of m ulti dr u g a n d t o xi n e xtr usi o n 1 ( M A T E 1), 
m ulti dr u g a n d t o xi n e xtr usi o n 2- K ( M A T E 2- K), or ga nic cati o n tra ns p orter 1 ( O C T 1), a n d 
or ga nic cati o n tra ns p orter 2 ( O C T 2) (s ee Secti o n 4. 3. 2. 1. 1  f or a d diti o nal d etails).  
4. 3. 2.  
S u m m ar y of Cli nic al D at a 
A brief s u m mar y of t he trilacicli b cli nical data is pr o vi de d i n t he f oll o wi n g secti o ns. Detaile d 
i nf or mati o n is prese nte d i n t he trilacicli b I B.  
4. 3. 2. 1.  
Effic ac y 
T he safet y a n d efficac y of a d mi nisteri n g tril acicli b pri or t o c he m ot hera p y was teste d i n o ne 
c o m plete d a n d o ne o n g oi n g P hase 1 b/ 2 st u d y ( G 1 T 2 8- 0 2 a n d G 1 T 2 8- 0 3) a n d o ne o n g oi n g a n d 
o ne c o m plete d P hase 2 st u d y ( G 1 T 2 8- 0 5 a n d G 1 T 2 8- 0 4) i n patie nts wit h S C L C or T N B C. T he 
P hase 2 p orti o ns of St u dies G 1 T 2 8- 0 2, G 1 T 2 8- 0 3, a n d St u d y G 1 T 2 8- 0 5 were ra n d o mize d, 
d o u ble- bli n d a n d place b o-c o ntr olle d. St u d y G 1 T 2 8- 0 4 was ra n d o mize d a n d i ncl u de d a c o ntr ol 
ar m b ut was n ot d o u ble- bli n de d. 
 St u d y G 1 T 2 8- 0 2 e x a mi ne d o nce- d ail y i ntra ve n o us (I V) a d mi nistrati o n of eit her 
trilacicli b or place b o o n Da ys 1 t o 3 of eac h 2 1- d a y E/ P c h e m ot hera p y c ycle i n 
patie nts wit h treat me nt naï ve E S- S C L C.  
 St u d y G 1 T 2 8- 0 3 e x a mi ne d o nce- d ail y I V a d mi nistrati o n of tril acicli b or pl ace b o o n 
Da ys 1 t o 5 of eac h 2 1- d a y t o p oteca n c he m ot hera p y c ycle i n patie nts wit h pre vi o usl y 
treate d E S- S C L C.  
 St u d y G 1 T 2 8- 0 5 e x a mi ne d o nce- d ail y I V a d mi nistrati o n of trilacicli b or pl ace b o o n 
Da ys 1 t o 3 f or a m a xi m u m of f o ur 2 1- da y c ycles of E/ P a n d atez oliz u ma b, f oll o we d 
b y m o n ot hera p y atez oliz u ma b, i n patie n ts wit h treat me nt naï ve E S- S C L C.  
 St u d y G 1 T 2 8- 0 4 e x a mi ne d o nce- d ail y I V a d mi nistrati o n of trilacicli b pri or t o G C i n 
patie nts wit h metastatic T N B C w h o ha d rece i ve d 0 t o 2 li nes of pre vi o us t hera p y i n 
t he metastatic setti n g. Patie nts recei v e d eit her 1) G C t hera p y o nl y o n Da ys 1 a n d 8 of 
a 2 1- da y c ycle, 2) trilacicli b a n d G C o nce dail y o n Da ys 1 a n d 8 of eac h 2 1- da y 
c ycle, O R 3) trilacicli b o n Da ys 1, 2, 8 a n d 9 wit h G C o n Da ys 2 a n d 9 of eac h 2 1-
da y c ycle (f urt her n ote d as Gr o u p 1, 2, or 3, res pecti vel y).  
At t he U S F D A a p pr o ve d d ose of 2 4 0 m g/ m 2, acr oss all t hree S C L C st u dies, trilacicli b 
a d mi nistere d pri or t o c h e m ot hera p y statisticall y si g nifica ntl y re d uce d t he d urati o n of se vere 
ne utr o pe nia ( D S N) i n C ycle 1 a n d occ urre nce of s e vere n e utr o pe ni a ( S N) ( pri mar y e n d p oi nts) 
c o m pare d wit h place b o. A n i nte grate d dat a a nal ysis of t he t hree S C L C st u dies ( G 1 T 2 8- 0 2, 
G 1 T 2 8- 0 3, a n d G 1 T 2 8- 0 5) f or 8 of t he m ost rele va nt m yel os u p pressi o n e n d p oi nts ( ne utr o p hils, 
re d bl o o d cells [ R B Cs] a n d platelets) de m o nstrate d statisticall y si g nifica nt, a n d cli nicall y 
mea ni n gf ul, i m pr o ve me nts f or trilacicli b o ver a vaila ble t hera pies i n 6 of 8 e n d p oi nts acr oss 
m ulti ple li nea ges. I m p ort a ntl y, t hese m yel o pr otecti o n be nefits c o me wit h a n o verall i m pr o ve d 
safet y pr ofile c o m pare d wit h a vaila ble t hera p y, as e vi de nce d b y re d uce d hi g h gra de 
treat me nt-e mer ge nt a d v erse e ve nts ( A Es) acr oss all S C L C st u dies, a n d n o detri me nt t o 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
2 9 
 
 
  
 
a nti-t u m or effic ac y res ults. F or a m or e detaile d desc ri pti o n of t he res ults, refer t o t he trilaci cli b 
I B. 
Res ults fr o m t he T N B C St u d y G 1 T 2 8- 0 4 de m o nstrate d t hat alt h o u g h t he a d diti o n of trilacicli b at 
t he U S F D A a p pr o ve d d ose of 2 4 0 m g/ m2 t o G C di d n ot statisticall y si g nifi ca ntl y i m pr o ve 
c he m ot hera p y-i n d uce d m yel os u p pressi o n as meas ure d b y t he ne utr o p hil- b ase d e n d p oi nts of D S N 
i n C ycle 1 a n d o cc urre n ce of S N, t here were tre n ds t o war d i m pr o ve me nt i n R B C a n d 
platelet- base d me as ures . I n a d diti o n, a nti-t u m or efficac y res ults de m o nstrat e d a cli nicall y 
mea ni n gf ul i m pr o ve me nt i n P F S a n d O S ( Fi g ure 4; Ta ble 3 ). T his mea ni n gf ul a nti-t u m or 
effic ac y w as o bser ve d acr oss m ulti ple s u b gr o u ps, i ncl u di n g b ot h P D- L 1 p ositi ve a n d ne gati ve 
t u m or t y pes (T a ble 4 ), a n d i n b ot h trilacicli b gr o u ps c o m pare d wit h t he c o ntr ol gr o u p. 
As me nti o ne d i n Secti o n 4. 3. 1. 1 , t here is a h y p ot h etical ris k t hat a d mi nistrati o n of trilacicli b 
pri or t o c he m ot hera p y c o ul d decrease c h e m ot hera p y  efficac y. T his h y p ot hetical ris k is c o u ntere d 
b y t he res ults o bser ve d i n St u d y G 1 T 2 8- 0 4 w hic h s u g geste d t h at t he a d diti o n of trilacicli b 
i m pr o ves t he a nti-t u m or effic ac y of G C re gar dless of t he C D K 4/ 6 stat us of t he T N B C t u m or. 
Alt h o u g h T N B C t u m ors are pre d o mi na ntl y classifie d as C D K 4/ 6 i n de pe n d e nt (i.e., t heir 
re plicati o n is n ot se nsiti ve t o C D K 4/ 6 i n hi biti o n), t here is a s mall s u bset of patie nts w h ose 
t u m ors are classifi e d as eit her C D K 4/ 6 i n deter mi nate or C D K 4/ 6 de pe n de nt. W he n t he T N B C 
p o p ulati o n e nr olle d i n St u d y G 1 T 2 8- 0 4 is di vi de d i nt o t hese s u bsets, e val u ati o n of t he a nti-t u m or 
effic ac y i n patie nts w h os e t u m ors are classifie d as C D K 4/ 6 i n deter mi nate or C D K 4/ 6 de pe n de nt 
s u g gests t hat trilaci cli b d oes n ot a nta g o nize t he a nti-t u m or effects of G C. S pecificall y, P F S a n d 
O S di d n ot decreas e w he n trilacicli b was a d d e d t o  G C i n t he m ost C D K 4/ 6- de pe n de nt p o p ulati o n 
(see trilaci cli b I B). 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 0 
 
 
  
 
T a ble 3:  
G 1 T 2 8- 0 4: S u m m ar y of O ver all S ur vi v al a n d Pr o gressi o n- Free S ur vi v al 
(I T T A n al ysis Set) 
C ate g or y 
Gr o u p 1  
Ge m/ C ar b o 
( D a y 1 + 8) 
( N = 3 4) 
Gr o u p 2  
Ge m/ C ar b o + 
Tri l acicli b 
( D a y 1 + 8)  
( N = 3 3) 
Gr o u p 3  
Ge m/ C ar b o + 
Tril acicli b 
( D a y 1/ 2 + 8/ 9)  
( N = 3 5) 
Gr o u ps 2 + 3 
( N = 6 8) 
O ver all s ur vi v al ( m o nt hs) ( 9 5 %  CI)a, b 
2 5 % 
5. 8 ( 2. 8, 9. 7) 
9. 4 ( 3. 4, 1 9. 6) 
8. 8 ( 6. 0, 1 5. 3) 
8. 8 ( 6. 0, 1 4. 0) 
Me dia n 
1 2. 6 ( 6. 3, 1 5. 6) 
N R ( 1 0. 2, N R) 
1 7. 8 ( 1 2. 9, 3 2. 7) 
1 9. 8 ( 1 4. 0, N R) 
7 5 % 
1 7. 8 ( 1 2. 8, 2 5. 0) 
N R ( N R, N R) 
3 2. 7 ( 1 9. 8, N R) 
N R ( 3 2. 7, N R) 
C o m p aris o n (tre at me nt gr o u p vers us Gr o u p 1)  
A dj uste d H R ( S E) c 
N A 
0. 3 1 ( 0. 1 1 1) 
0. 4 0 ( 0. 1 2 5) 
0. 3 7 ( 0. 1 0 1) 
9 5 % CI c 
N A  
0. 1 5, 0. 6 3 
0. 2 2, 0. 7 4 
0. 2 1, 0. 6 3 
2-si de d p- val ue d 
N A  
0. 0 0 1 6 
0. 0 0 0 4 
< 0. 0 0 0 1 
Pr o gressi o n-free s ur vi v al ( m o nt hs) ( 9 5 % CI) a, b 
2 5 % 
2. 2 ( 1. 2, 5. 4) 
5. 3 ( 1. 2, 7. 9) 
6. 2 ( 1. 2, 7. 1) 
5. 9 ( 2. 1, 6. 5) 
Me dia n 
5. 7 ( 3. 3, 9. 9) 
9. 4 ( 6. 1, 1 1. 9) 
7. 3 ( 6. 2, 1 3. 9) 
9. 0 ( 6. 4, 1 1. 3) 
7 5 % 
9. 9 ( 8. 3, 1 8. 8) 
1 3. 0 ( 9. 7, 2 4. 1) 
1 3. 9 ( 9. 0, N R) 
1 3. 9 ( 1 0. 9, 1 5. 6) 
C o m p aris o n ( Tre at me nt Gr o u p vers us Gr o u p 1)  
A dj uste d H R ( S E) c 
N A 
0. 6 2 ( 0. 2 0 9) 
0. 6 3 ( 0. 2 1 2) 
0. 6 2 ( 0. 1 8 0) 
9 5 % CI c 
N A 
0. 3 2, 1. 2 0 
0. 3 2, 1. 2 2 
0. 3 6, 1. 1 0 
2-si de d p- val ue d 
N A 
0. 2 0 9 9 
0. 1 8 1 6 
0. 1 2 9 1 
CI =c o nfi de nce i nter val; Ge m/ Car b o = ge mcita bi ne/car b o plati n; H R = hazar d rati o; I T T =i nte nt-t o-treat; N =t otal 
n u m ber of patie nts i n eac h tre at me nt gr o u p; N A = n ot a p plica ble; N R = n ot reac he d; O S = o verall s ur vi val; 
S E =sta n dar d err or. 
a  Calc ulate d usi n g t he Ka pla n- Meier met h o d 
b  O S re p orte d fr o m fi nal data b ase; P F S re p orte d fr o m earlier data c ut off o n 1 5 Ma y 2 0 2 0. 
c  T he H R a n d its 9 5 % CI were calc ulate d usi n g t he C o x regressi o n m o del c o ntr olli n g f or t he stratificati o n fact ors, 
na mel y, n u m ber of pri or li nes of t hera p y ( 0 vers us 1 or 2) a n d li ver i n v ol ve me nt. 
d  P- val ue was calc ulate d usi n g t he stratifie d l o g-ran k test c o ntr olli n g f or t he t w o stratificati o n fact ors. 
 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 1 
 
 
  
 
Fi g ure 4:  
G 1 T 2 8- 0 4: O ver all S ur vi v al –  K a pl a n- Meier C ur ve (I T T A n al ysis Set) 
 
CI =c o nfi de nce i nter val; G C = ge mcita bi ne a n d car b o plati n; H R = hazar d r ati o; I T T =i nte nt-t o-treat; N R = n ot reac he d; O S = o verall s ur vi v al. 
Gr o u p 1: G C a d mi nistere d o n Da ys 1 a n d 8 of 2 1- da y c ycles; Gr o u p 2: Trilacicli b a n d G C a d mi nistere d o n Da ys 1 a n d 8 of 2 1- da y c ycles; Gr o u p 3: Trilacicli b 
a d mi nistere d o n Da ys 1, 2, 8, a n d 9 a n d G C a d mi nistere d o n Da ys 1 a n d 8 of 2 1- da y c ycles. 
N ote: T he H R a n d its 9 5 % CI c o m pari n g Gr o u p 1 a n d 2 a n d Gr o u p 1 a n d 3 were calc ulate d usi n g t he C o x re gressi o n m o del wit h tre at me nt a n d stratificati o n 
fact ors of n u m ber of pri or li nes of t hera p y ( 0 vers us 1 or 2) a n d li ver i n v ol ve me nt. 
N ote: P- val ues c o m pari n g Gr o u p 1 a n d 2 a n d Gr o u p 1 a n d 3 were calc ulate d usi n g t he stratifie d l o g-ra n k test t o acc o u nt f or t he n u m ber of pri or li nes of t hera p y 
( 0 vers us 1 or 2) a n d li ver i n v ol ve ment as t he stratificati o n fact ors.  
N ote: data ge nerate d fr o m fi nal d ata b ase. 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 2 
 
 
  
 
T a ble 4:  
G 1 T 2 8- 0 4: T u m or R es p o nse Acc or di n g t o P D- L 1 St at us 
 
P D- L 1 P ositi ve 
P D- L 1 Ne g ati ve 
 
Gr o u p 1 
Gr o u p 2 
Gr o u p 3 
Gr o u p 2 + 3 
Gr o u p 1 
Gr o u p 2 
Gr o u p 3 
Gr o u p 2 + 3 
P atie nts a nal yze d 
1 7 
1 6 
1 6 
3 2 
1 0 
1 0 
1 6 
2 6 
Me dia n P F S, m o nt hs 
( 9 5 % CI)a 
5. 4           
( 3. 3-N R) 
7. 9           
( 6. 1-N R) 
1 0. 9         
( 6. 2-N R) 
9. 7           
( 6. 2-1 5. 5) 
9. 2         
( 8. 3-N R) 
1 1. 9         
( 8. 8-N R) 
9. 0           
( 6. 4-N R) 
9. 4           
( 6. 5-1 4. 6) 
H R ( 9 5 % CI) 
- 
0. 7 4         
( 0. 3-1. 7) 
0. 4 1         
( 0. 2-1. 1) 
0. 5 7         
( 0. 3-1. 2) 
- 
0. 6 0         
( 0. 2-1. 9) 
1. 4 7         
( 0. 5-4. 3) 
0. 9 7         
( 0. 4-2. 5) 
Me dia n O S, m o nt hs 
( 9 5 % CI)a 
1 0. 5         
( 6. 3-1 8. 8) 
2 0. 1       
( 1 0. 2-N R) 
3 2. 7        
( 1 5. 3-N R) 
3 2. 7       
( 1 7. 7-N R) 
1 3. 9      
( 1 2. 6-N R) 
N R          
( 9. 4-N R) 
1 7. 8       
( 1 2. 9-N R) 
1 7. 8       
( 1 3. 1-N R) 
H R ( 9 5 % CI) 
- 
0. 3 8         
( 0. 2-1. 0) 
0. 3 0         
( 0. 1-0. 8) 
0. 3 4         
( 0. 2-0. 7) 
- 
0. 3 5         
( 0. 1-1. 2) 
0. 5 5         
( 0. 2-1. 4) 
0. 4 8         
( 0. 2-1. 2) 
CI =c o nfi de nce i nter val; H R = hazar d rati o; N R = n ot reac he d; O S = o verall s ur vi val; P D- L 1 = pr o gra m me d deat h li ga n d- 1; P F S = pr o gressi o n- free s ur vi val. 
Gr o u p 1: c he m ot hera p y o n Da ys 1 a n d 8; Gr o u p 2: trilacicli b a n d c he m ot hera p y o n Da ys  1 a n d 8; Gr o u p 3: trilacicli b al o n g o n Da ys 1 a n d 8 wit h c he m ot hera p y 
o n Da ys 2 a n d 9. H R val ues are c o m paris o ns bet wee n Gr o u p 2 a n d Gr o u p 1, Gr o u p 3 a n d Gr o u p 1, a n d bet wee n c o m bi ne d Gr o u ps 2 a n d 3 a n d Gr o u p 1. 
a  O S re p orte d fr o m fi nal data b ase; P F S re p orte d fr o m earlier data c ut off o n 1 5 Ma y 2 0 2 0.

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 3 
 
 
  
 
4. 3. 2. 1. 1.  P h ar m a c o ki netics 
A cli nical D DI st u d y i n h ealt h y s u bjects usi n g t he i n de x C Y P 3 A s u bstrate mi daz ola m i n dicate d 
t hat trilacicli b ha d n o i m pact o n C Y P 3 A acti vit y a n d t hat t he str o n g C Y P 3 A i n d ucer rif a m pi n 
ha d n o cli nicall y mea ni n gf ul effect o n trilacicli b P K. T w o cli nical D DI st u dies usi n g a str o n g 
C Y P 3 A i n hi bit or itrac o naz ole were als o c o n d ucte d. N o cli nicall y si g nifica nt c ha n ges i n e x p os ure 
were o bs er ve d f or trilaci cli b w he n c o- a d mi nistere d wit h itrac o naz ole. 
I n a n a d diti o nal cli nical D DI assess me nt i n healt h y s u bjects, trilacicli b i ncrease d metf or mi n 
( M A T E 1, M A T E 2- K a n d O C T 2 s u bstrate) e x p os ure b y 6 5 % c o m p are d wit h a d mi nistrati o n of 
metf or mi n al o ne. H o w e v er, d ue t o t he i nter mitte nt sc he d ule of trilacicli b a d mi nistrati o n a n d t he 
o bser vati o n t hat t he effect of trilacicli b o n metf or mi n was si milar t o mil d t o m o derate re d ucti o ns 
i n re nal f u ncti o n, t he cli nical si g nifica nce of t he m etf or mi n plas ma c o nce ntr ati o n i ncreas e is n ot 
e x pecte d t o be hi g h.  
C o-a d mi nistrati o n of trilacicli b ma y i ncrease t he c o nce ntrati o n or n et acc u m ulati o n of O C T 2, 
M A T E 1, a n d M A T E- 2 K s u bstrates i n t he ki d ne y (e. g., d ofetili de a n d dalfa m pri di ne).   
4. 3. 3.  
Ris ks 
4. 3. 3. 1.  
Tril acicli b 
Re pr o d ucti ve/e m br y o-fet al effects are a n i m p orta n t p ote ntial ris k of trilacicli b. B ot h n o ncli nical 
t o xic ol o g y st u dies wit h trilacicli b, a n d cli nical st u dies wit h ot her c o m p o u n ds wit h a si milar 
M O A, re p ort effects o n eit her t he re pr o d ucti ve s yste m or e m br y o/fet us. Si nce t his cli nical st u d y 
will f oc us o n trilacicli b a d mi nistere d pri or t o sa cit uz u ma b g o viteca n- hzi y ( w hic h carries its o w n 
ris k of re pr o d ucti ve/e m br y o-fetal t o xicit y), t he ris ks s pecific t o trilacicli b are c o nsiste nt wit h 
t h ose e x perie nce d wit h s acit uz u ma b g o viteca n- hzi y. I n a d diti o n, f e male patie nts will be 
m o nit ore d f or pre g n a nc y a n d eli gi bilit y criteria d escri bi n g s p ecific birt h c o ntr ol met h o ds are 
i nc or p orate d. D ose disc o nti n uati o n rec o m m e n datio ns f or fe mal e patie nts w h o bec o me pre g na nt 
w hile recei vi n g trilacicli b are als o pr o vi de d i n t he pr ot oc ol ( Secti o n 1 1. 3. 6. 5 ). Detaile d 
i nf or mati o n re gar di n g all i m p orta nt i de ntifie d a n d i m p orta nt p ote ntial ris ks of trilacicli b 
a d mi nistrati o n ca n be f o u n d i n t he trilacicli b I B. 
At t he U S F D A a p pr o ve d d ose of 2 4 0 m g/ m 2 bei n g use d i n t his st u d y, trila cicli b di d n ot ha ve a 
cli nicall y rele va nt effect o n Q Tc (i.e., > 1 0 msec). 
I n a n i nte grat e d safet y a n al ysis fr o m t he f o ur P has e 2 o nc ol o g y st u dies c o n d ucte d wit h trilacicli b 
t o date ( G 1 T 2 8- 0 2 [c o m plete], G 1 T 2 8- 0 3 [ data c ut off: 3 1 Ma y 2 0 1 9], G 1 T 2 8- 0 5 [ data c ut off: 
2 8 J u n 2 0 1 9], a n d G 1 T 2 8- 0 4 [c o m plete]), t he m ost  c o m m o n treat me nt-e m er ge nt a d verse e ve nts 
( T E A Es) ( ≥1 0 %) t hat oc c urre d m or e fre q ue ntl y i n patie nts recei vi n g trilacicli b c o m pare d t o 
place b o w ere n a usea, fati g ue, h ea d ac he, d ys p n ea, c o u g h, h y p o k ale mia, a n d i nf usi o n relate d 
reacti o n. Trilacicli b-related T E A Es occ urri n g i n ≥5 % of patie nts wit h at least a ≥2 % hi g her 
i nci de nce i n trilaci cli b c o m pare d t o place b o were na usea, fati g u e, a n e mia, hea dac he, i nf usi o n 
relate d reacti o n, ne utr o p hil c o u nt decrease d, decrease d a p p etite, v o miti n g, a n d c o nsti pati o n. 
A d verse e ve nts of s pecial i nterest ( A E SIs) i de ntifi e d f or trilaci cli b i n t he i nte grate d safet y 
s u m mar y are d escri be d b el o w. S o me A E SIs h a ve bee n i nfre q ue ntl y re p orte d ( or n ot re p ort e d) i n 
t he trilacicli b cli nical pr o gra m t o date b ut are c o nsi dere d t o be p ote ntial cl ass effects of C D K 4/ 6 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 4 
 
 
  
 
i n hi bit ors. H o we ver, as trilacicli b is gi ve n I V a n d o nl y w he n c he m ot hera p y is a d mi nistere d, t he 
safet y pr ofile of trilacicli b a p pears t o b e differe nt fr o m t hat of t he oral, c hr o nicall y- d os e d 
me m bers of its p har mac ol o gic cl ass. All patie nts will be m o nit ore d f or t hese e ve nts a n d d os e 
m o dificati o n a n d disc o nti n uati o n g ui deli nes are pr o vi de d i n Secti o n 9. 3 . 
Tril acicli b A E SIs : 
1.  I njecti o n Site Re acti o n/ P hle bitis/ T hr o m b o p hle bitis: I nf usi o n of trilacicli b ca n ca us e 
i njecti o n-site reacti o ns i ncl u di n g p hle bitis a n d t hr o m b o p hle bitis. I njecti o n-site reacti o ns 
i ncl u di n g p hle bitis a n d t hr o m b o p hle bitis occ urre d i n 5 6 ( 2 1 %) of 2 7 2 patie nts recei vi n g 
trilacicli b i n cli nical trials, i ncl u di n g Gra de 2 ( 1 0 %) a n d Gra de 3 ( 0. 4 %) A Es. T he 
me dia n ti me t o o nset fr o m start of trilacicli b  was 1 5 da ys (ra n ge 1 t o 5 4 2) a n d fr o m t he 
prece di n g d os e of trilaci cli b was 1 da y ( 1 t o 1 5). T he me dia n d urati o n was 1 da y (ra n ge 1 
t o 1 5 1 f or t he res ol ve d cases). I njecti o n-site reacti o ns i ncl u di n g p hle bitis a n d 
t hr o m b o p hle bitis res ol ve d i n 4 9 ( 8 8 %) of t he 5 6 patie nts a n d le d t o disc o nti n uati o n of 
treat me nt i n 3 ( 1 %) of t he 2 7 2 patie nts. 
M o nit or patie nts f or si g ns a n d s y m pt o ms of i njecti o n-site reacti o ns, p hle bitis, a n d 
t hr o m b o p hle bitis, i ncl u di n g i nf usi o n-site pai n a n d er yt h e ma d uri n g i nf usi o n. F or mil d 
( Gra d e 1) t o m o derate ( Gra de 2) i njecti o n-site reacti o ns, fl us h li ne/ca n n ula wit h at least 
2 0 m L of sterile 0. 9 % S o di u m C hl ori de I njecti o n, U S P or 5 % De xtr ose I nj ecti o n, U S P 
after e n d of i nf usi o n. F or se vere ( Gra de 3) or  life-t hreate ni n g ( Gra d e 4) i njecti o n-site 
reacti o ns, st o p i nf usi o n a n d per ma ne ntl y disc o nti n ue trilacicli b. 
2.  Ac ute D r u g H y perse nsiti vit y Re acti o n:  Trilacicli b ca n ca us e ac ut e dr u g 
h y perse nsiti vit y reacti o ns, i ncl u di n g facial e d e ma a n d urticari a. Ac ute dr u g 
h y perse nsiti vit y reacti o ns occ urre d i n 1 6 ( 6 %) of 2 7 2 patie nts recei vi n g trilacicli b i n 
cli nical trials, i ncl u di n g Gra de 2 reacti o ns  ( 2 %). O ne patie nt e x perie nce d a Gra d e 2 
a na p h ylactic reacti o n 4 da ys after recei vi n g tr ilaci cli b, w hic h res ol ve d wit h e pi ne p hri ne, 
a n d treat me nt wit h trilaci cli b was c o nti n ue d. T he me dia n ti me t o o nset fr o m start of 
trilacicli b was 7 7 da ys (ra n ge 2 t o 2 5 6) a n d fr o m t he prece di n g d ose of trilacicli b was 
1 da y (ra n ge 1 t o 2 8). T h e me dia n d urati o n was 6 da ys (ra n ge 1 t o 6 9 f or t h e res ol ve d 
cases). Ac ute dr u g h y p erse nsiti vit y reacti o ns res ol ve d i n 1 2 ( 7 5 %) of t h e 1 6 patie nts. 
M o nit or patie nts f or si g ns a n d s y m pt o ms of ac ute dr u g h y p erse nsiti vit y reacti o ns 
i ncl u di n g facial, e ye, a n d t o n g ue e de ma, urticaria, pr urit us, a n d a na p h ylactic reacti o ns. 
F or m o derate ( Gra d e 2) ac ute dr u g h y perse nsiti vit y rea cti o ns, st o p i nf usi o n a n d h ol d 
trilacicli b u ntil t he a d verse reacti o n rec o v ers t o Gra de ≤1. F or se v ere ( Gra de  3) or 
life-t hreat e ni n g ( Gra de 4) ac ute dr u g h yperse nsiti vit y reacti o ns, st o p i nf usi o n a n d 
per ma ne ntl y disc o nti n ue trilacicli b. 
3.  P ne u m o nitis/I nterstiti al L u n g Dise ase : Se vere, life-t hreate ni n g, or fatal i nterstitial l u n g 
disease a n d/ or p n e u m o nitis ca n occ ur i n pati e nts treate d wit h C D K 4/ 6 i n hi bit ors, t he 
sa me dr u g class as trilaci cli b. I nterstitial l u n g dise ase/ p ne u m o nitis occ urre d i n 1 ( 0. 4 %) 
of 2 7 2 patie nts recei vi n g trilacicli b i n cli nica l trials. T he e ve nt w as Gra d e 3 a n d re p ort e d 
2 m o nt hs after disc o nti n ui n g trilacicli b, i n a p atie nt recei vi n g a c o nf o u n di n g me dicati o n. 
T he e ve nt di d n ot res ol ve. 
M o nit or patie nts f or p ul m o nar y s y m pt o ms i n dicati ve of i nterstitial l u n g 
disease/ p ne u m o nitis s uc h as c o u g h, d ys p nea, a n d h y p o xia. F or rec urre nt m o derate 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 5 
 
 
  
 
( Gra d e 2) i nterstitial l u n g disease/ p ne u m o nitis, per ma ne ntl y disc o nti n ue tril acicli b. F or 
se vere ( Gra de 3) or life-t hreate ni n g ( Gra d e 4) i nterstitial l u n g disease/ p ne u m o nitis, 
per ma ne ntl y disc o nti n ue trilacicli b.  
4.  He p at ot o xicit y:  B ot h n o ncli nical t o xic ol o g y st u di es wit h trilacicli b, a n d cli nical st u dies 
wit h ot her c o m p o u n ds wit h a si milar M O A, re p ort re versi ble ele vati o ns i n tr a nsa mi nases 
wit h c o nti n u o us d osi n g. T here h as bee n o nl y 1 i nsta nce of Gra de 4 ala ni ne 
a mi n otra nsferase ( A L T) i ncreas e i n a patie nt r ecei vi n g trilacicli b, n o Gra de 4 as partate 
a mi n otra nsferase ( A S T) i ncreas es, a n d n o cases of H y’s l a w re p orte d i n patie nts 
recei vi n g trilaci cli b. H o we ver, g e nerall y l o w grade a n d tra nsie nt i ncreas es i n A S T, A L T, 
or bilir u bi n ha ve bee n o bser ve d i n a s mall n u m ber of patie nts ( ~ 5 %) recei vi n g trilaci cli b 
pri or t o c he m ot hera p y. Patie nts wit h mil d he patic i m pair me nt ha ve bee n treate d wit h 
trilacicli b wit h o ut a cli nicall y si g nifica nt i ncrease i n e x p os ure or t he fre q u e nc y/se v erit y 
of A Es.  
5.  E m b olic a n d T hr o m b otic E ve nts, Ve n o us:  T he C D K 4/ 6 i n hi bit or a be macicli b has bee n 
ass ociate d wit h a n i ncrease d ris k f or ve n o us t hr o m b oe m b olis m w he n c o m bi ne d wit h 
e n d ocri ne t hera p y i n pati e nts wit h breast ca n cer. T his sa me ris k has n ot bee n re p ort e d f or 
t he ot her a p pr o ve d oral C D K 4/ 6 i n hi bit ors (ri b ocicli b a n d pal b ocicli b); t heref ore, it is n ot 
clear if t his is a cl ass effe ct. A p pr o xi matel y 3 % of ca ncer patie nts t hat r ecei ve d trilacicli b 
pri or t o c he m ot hera p y e x perie nce d a ve n o us t hr o m b oe m b olic e ve nt a n d half of t h ose 
e ve nts ( 3/ 6) were Gra d e 3 or 4. N o Gra d e 5 e v e nts were re p orte d. A p pr o xi matel y 2 % of 
patie nts recei vi n g c he m ot hera p y al o ne or wit h  place b o re p orte d a n e m b olic or t hr o m b oti c 
e ve nt, 1 of 3 s uc h e ve nts was Gra d e 3.  
4. 3. 3. 2.  
S acit uz u m a b g o vitec a n- hzi y 
Per War ni n gs a n d Preca uti o ns i n t he prescri b i n g i nf or mati o n f or sacit uz u ma b g o viteca n- hzi y 
(Tr o del v y Pac k a ge I ns ert, 2 0 2 1 ), t he f oll o wi n g are i m p orta nt ris ks relate d t o sacit uz u ma b 
g o viteca n- hzi y us e: 
 Se vere or lif e-t hreate ni n g ne utr o pe nia ( b o x e d war ni n g)  
 Se vere diarr hea ( b o xe d war ni n g) 
 H y p erse nsiti vit y a n d i nf usi o n-relate d reacti o ns, i ncl u di n g se v ere a na p h ylactic 
reacti o ns  
 Na usea a n d v o miti n g 
 Patie nts wit h Re d uce d U G T 1 A 1 Acti vit y: I n di vi d uals w h o are h o m oz y g o us f or t he 
uri di ne di p h os p h ate- gl uc ur o n osyl tr a nsfer ase 1 A 1 ( U G T 1 A 1) * 2 8 allele are at 
i ncreas e d ris k f or ne utr o pe nia, fe brile ne utr o pe ni a, a n d a n e mia 
 E m br y o-fetal t o xicit y 
4. 4.  
Be nefit/ Ris k Assess me nt 
Trilacicli b (a C D K 4/ 6 i n hi bit or) is bei n g e v al uate d f or a nti-t u m or effi cac y, m yel o pr otecti o n, as 
well as its a bilit y t o i m pr o ve t he patie nt e x peri e nce w hile recei vi n g c he m ot hera p y. I n a d diti o n t o 
t he si de effects of c h e m ot hera p y, c h e mot hera p y-i n d uce d i m m u n os u p pressi o n ma y li mit 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 6 
 
 
  
 
a nti-t u m or effic ac y d u e t o a n i na bilit y of t h e h ost i m m u ne s yste m t o effecti vel y m o u nt a 
res p o nse a gai nst t he ca n cer. T heref ore, a d mi nistrati o n of trilacicli b t o preser ve t he b o ne marr o w 
a n d t he i m m u ne s yste m fr o m t he c yt ot o xic effects of c he m ot hera p y has t he p ote ntial t o 
ma xi mize a nti-t u m or acti vit y of t he c h e m ot hera p y. As state d i n Secti o n 4. 3. 2,  t he F D A a p pr o ve d 
d ose of 2 4 0 m g/ m 2 trilaci cli b esta blis he d i n P hase 1 b/ 2a S C L C st u dies a n d i n t he P hase 2 T N B C 
st u d y will be use d i n t his st u d y a n d a d mi nistere d pri or t o t he F D A a p pr o ve d d ose f or 
sacit uz u ma b g o viteca n- h zi y i n T N B C.  
St u dies t o date wit h trilacicli b ha ve de m o nstrate d a ma na gea ble safet y pr ofile (see 
Secti o n  4. 3. 3. 1). I n St u d y G 1 T 2 8- 0 4, t he rates of o verall t o xicit y were c o m para ble i n T N B C 
patie nts w h o recei ve d tril acicli b wit h G C vers us G C al o ne des pite t he 1. 5-f ol d i ncrease i n t he 
me dia n n u m ber of c ycles a n d 5 0 % i ncrease i n t he c u m ulati ve d ose of b ot h ge m cita bi ne a n d 
car b o plati n i n patie nts w h o recei v e d trilacicli b. R ates of disc o nti n uati o n d ue t o a n A E were n ot 
differe nt b et wee n t h e trilacicli b gr o u ps a n d t he G C al o ne gr o u p. Si milarl y, i n patie nts wit h S C L C 
a d mi nistere d trilacicli b wit h E/ P/ A i n St u d y G 1 T 2 8- 0 5, t he rates of o verall t o xicit y pr ofile were 
c o m para ble i n p atie nts w h o recei v e d trilacicli b pl us E/ P/ A vers us place b o pl us E/ P/ A des pite t he 
l o wer rel ati ve d ose i nte nsit y of E/ P/ A bei n g l o wer i n patie nts i n t he place b o gr o u p c o m pare d 
wit h t he trilacicli b gr o u p, wit h t he trilacicli b gr o u p ha vi n g a l o wer n u m ber of d ose 
dela ys/re d ucti o n. I n a d diti o n, patie nts recei vi n g tr ilacicli b ha d l o wer rates of disc o nti n uati o n d ue 
t o a n A E a n d atez oliz u ma b A E SIs as c o m pare d wit h patie nts recei vi n g place b o. Fi n all y, 
trilacicli b is c urre ntl y bei n g i n vesti gate d i n c o m bi nati o n wit h iri n oteca n as part of a 
F O L F O XI RI/ be v aciz u ma b treat me nt r e gi me n i n  patie nts wit h metastatic c ol orectal ca ncer 
( St u d y G 1 T 2 8- 2 0 7, N C T 0 4 6 0 7 6 6 8). N o ne w safet y si g nals ha v e bee n i d e ntifie d t o date a n d t here 
are n o k n o w n ris ks of p ote ntial D DI bet w ee n trila cicli b a n d S N- 3 8.  
I n c o ncl usi o n, t he c o m bi nati o n treat me nt of trilaci cli b wit h sacit uz u ma b g o viteca n- hzi y offers 
t he p ote ntial f or cli nical be nefit wit h a fa v ora ble s afet y pr ofile. 

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5.  
O B J E C TI V E S A N D E N D P OI N T S 
T he pri mar y, sec o n dar y, a n d e x pl orat or y o bj ecti ves of t his st u d y, a n d t heir ass ociate d e n d p oi nts, 
f or patie nts w h o recei v e d at least 2 pri or treat me nts, at least 1 i n t he metastatic setti n g f or 
u nresect a ble, l ocall y a d v a nce d or m etastatic T N B C bei n g a d mi nistere d trilacicli b wit h 
sacit uz u ma b g o viteca n- h zi y, are prese nte d i n T a bl e 5 . 
T a ble 5:   
O bjecti ves a n d E n d p oi nts 
O bjecti ves 
E n d p oi nts 
Pri mar y O bjecti ve 
 
T o e val uate t he a nti-t u m or 
acti vit y of trilacicli b w he n 
a d mi nistere d pri or t o sacit uz u ma b 
g o viteca n- hzi y 
 
P F S defi ne d as ti me fr o m t he date of first d ose  of 
st u d y dr u g t o ra di o gra p hic disease pr o gressi o n 
usi n g R E CI S T v 1. 1 or deat h d ue t o a n y ca use, 
w hic he ver occ urs first; f or patie nts wit h o ut 
disease pr o gressi o n or deat h, P F S will be 
calc ulate d per ce ns ori n g r ules. 
Sec o n dar y O bj ecti ve: Efficac y 
 
T o e val uate t he a nti-t u m or 
acti vit y of trilacicli b w he n 
a d mi nistere d pri or t o sacit uz u ma b 
g o viteca n- hzi y 
 
O R R defi ne d as t he perce nta ge of patie nts wit h 
B O R of c o nfir me d C R or c o nfir me d P R per 
R E CI S T v 1. 1 
 
C B R defi ne d as t he perce nta ge of patie nts wit h a 
B O R of c o nfir me d C R, c o nfir me d P R, or S D 
lasti n g 2 4 wee ks or l o n ger si nce t he first date of 
st u d y dr u g a d mi nistrati o n per R E CI S T v 1. 1 
 
D O R defi ne d as d urati o n of o bj ecti ve res p o nse  
 
O S defi ne d as ti me fr o m t he date of first d ose of 
st u d y dr u g t o deat h d ue t o a n y ca use f or t h ose 
w h o die d; or ti me t o last c o ntact k n o w n as ali ve 
f or t h ose w h o s ur vi ve d i n t he st u d y (ce ns ore d 
cases) 
Sec o n dar y O bj ecti ve: T o e val uate t he m yel o pr otecti ve effects of trilacicli b 
 
T o e val uate t he m yel o pr otecti ve 
effects of trilacicli b w he n 
a d mi nistere d pri or t o sacit uz u ma b 
g o viteca n- hzi y 
 
Occ urre nce of S N ( d uri n g C ycles 1/ 2 a n d o verall 
st u d y) 
 
Occ urre nce of fe brile ne utr o pe nia 
 
Occ urre nce of G- C S F a d mi nistrati o n  
 
Occ urre nce of Gra de 3/ 4 decrease of he m o gl o bi n 
 
Occ urre nce a n d n u m ber of R B C tra nsf usi o ns 
o n/after Wee k 5 
 
Occ urre nce of E S A a d mi nistrati o n 
 
Occ urre nce of Gra de 3/ 4 decrease of platelets  
 
Occ urre nce a n d n u m ber of p latelet tra nsf usi o ns  
 
Occ urre nce of seri o us i nfecti o ns 
 
Use of I V a nti bi otics 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
3 8 
 
 
  
 
O bjecti ves 
E n d p oi nts 
Sec o n dar y Safet y O bj ecti ves 
 
T o e val uate t he safet y a n d 
t olera bilit y of trilacicli b w he n 
a d mi nistere d pri or t o sacit uz u ma b 
g o viteca n- hzi y 
 
Occ urre nce a n d se verit y of A Es b y N CI C T C A E 
v 5. 0  
 
Trilacicli b A E SIs 
 
C ha n ges i n la b orat or y para meters ( he m at ol o g y 
a n d c he mistr y), vital si g ns a n d E C G para meters 
 
Gra de 3 or 4 a b n or malities i n c he mistr y 
la b orat or y para meters  
 
Trilacicli b i nf usi o n i nterr u pti o ns  
 
Sacit uz u ma b g o viteca n- hzi y i nf usi o n i nterr u pti o ns 
 
Sacit uz u ma b g o viteca n- hzi y d ose re d ucti o n a n d 
c ycle dela y 
A E =a d verse e ve nt; A E SI =a d verse e ve n t of s pecial i nterest; B O R = best o verall res p o nse; C B R =cli nical be nefit rate; 
C R =c o m plete res p o nse; C T C A E = C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts; D O R = d urati o n of res p o nse; 
E C G =electr ocar di o gra m; E S A =er yt hr o p oiesis sti m ulati n g a ge nt; G- C S F = gra n ul oc yte c ol o n y-sti m ulati n g fact or; 
I V =i ntra ve n o us; N CI = Nati o nal Ca ncer I nstit ute; OR R = o bj ecti ve res p o nse rate; O S = o verall s ur vi val; 
P F S = pr o gressi o n-free s ur vi val; P R = p artial res p o nse; R B C =r e d bl o o d cell; R E CI S T = Res p o nse E val uati o n Criteria i n 
S oli d T u m ors; S D =sta ble dise ase; S N =se vere ne utr o pe nia 

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6.  
I N V E S TI G A TI O N A L P L A N 
6. 1.  
O ver all St u d y Desi g n 
T his is a n e x pl orat or y P hase 2, m ultice nter, o p e n-l a bel st u d y e val uati n g t he safet y a n d efficac y 
of trilacicli b a d mi nistere d wit h sacit u z u ma b g o vi teca n- hzi y i n patie nts wit h u nresect a ble l ocall y 
a d va nce d or metastatic T N B C w h o recei v e d at leas t 2 pri or treat me nts, at least 1 i n t he metastatic 
setti n g. I ncl usi o n/e x cl usi o n criteria are o utli ne d i n Secti o n 7. 1  a n d Secti o n 7. 2 , res pecti vel y. 
A p pr o xi matel y 4 5 p atie nts will be e nr olle d.   
Trilacicli b pl us sacit uz u ma b g o viteca n- hzi y will be a d mi nistere d I V i n 2 1- da y c ycl es as f oll o ws: 
 Trilacicli b 2 4 0 m g/ m 2 a d mi nistere d as a 3 0- mi n ut e I V i nf usi o n c o m plete d wit hi n 
4 h o urs pri or t o t he start of sacit uz u ma b g o viteca n- hzi y o n Da y 1 a n d Da y 8 of eac h 
2 1- da y treat me nt c ycle. 
 Sacit uz u ma b g o viteca n- h zi y 1 0 m g/ k g a d mi nistere d I V o n Da y 1 a n d Da y 8 of eac h 
2 1- da y treat me nt c ycle. A d mi nister t he first i nf usi o n o ver 3 h o urs a n d o bs er ve 
patie nts d uri n g t he i nf usi o n a n d f or at least 3 0 mi n utes f oll o wi n g t he i nitial d ose f or 
si g ns or s y m pt o ms of i nf usi o n-relate d reacti o ns. S u bse q ue nt i nf usi o ns ma y be 
a d mi nistere d o ver 1 t o 2 h o urs if pri or i nf usi o ns were t olerate d, a n d p atie nts s h o ul d 
be o bser ve d d uri n g t he i nf usi o n a n d f or at least 3 0 mi n utes after i nf usi o n. Pri or t o 
eac h i nf usi o n of s acit uz u ma b g o viteca n- hzi y, pre me dicati o n f or t he pre ve nti o n of 
i nf usi o n reacti o ns a n d c h e m ot hera p y-i n d u ce d na usea a n d v o miti n g ( CI N V) is 
rec o m me n de d. 
 Pre me dicate wit h a nti p yretics, hista mi ne rece pt or 1 ( H 1) a n d hist a mi ne rece pt or 2 
( H 2) bl oc kers pri or t o i nf usi o n, a n d c orticoster oi ds ma y be use d f or p atie nts w h o 
ha d pri or i nf usi o n reacti o ns. 
 Pre me dicate wit h a t w o or t hree dr u g ( preferre d) c o m bi nati o n re gi me n (e. g., 
de x a met has o ne wit h eit her a 5- h y dr o x ytr y pta mi ne ( 5- H T 3) rece pt or a nta g o nist or 
a ne ur o ki ni n 1 ( N K 1) rece pt or a nta g o nist, as  well as ot her dr u gs as i n dicate d). 
T he st u d y will i ncl u de 3 st u d y p hases: Scr ee ni n g P hase, Treat me nt P has e, a n d S ur vi val 
F oll o w- u p P hase ( Fi g ure 5 ). T he Treat me nt P hase be gi ns o n t he da y of e nr oll me nt a n d c o m pletes 
at t he E n d of Treat me nt Visit. S ur vi val F oll o w- u p assess me nts s h o ul d occ ur e ver y 3 m o nt hs after 
t he E n d of Treat me nt Visit. 
Fi g ure 5:  
St u d y Sc he m a 
 
D C = dic o nti n ue d; P D = pr o gressi ve disease; PI = Pri nci pal I n vesti gat or; W D = wit h dra w  

Pr ot oc ol A me n d me nt 1 
 
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Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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Patie nts e nr olle d i n t he st u d y will be eli gi b le t o recei ve treat me nt u ntil disease pr o gressi o n, 
u nacce pta ble t o xicit y, wit h dra wal of c o nse nt, I n vesti gat or decisi o n, or t he e n d of t he trial, 
w hic he ver c o mes first. Treat me nt c ycl es will occ ur c o nsec uti vel y wit h o ut i nterr u pti o n, e x ce pt 
w he n necessar y, t o ma n a ge t o xicities or f or a d mi nistrati ve reas o ns. T h ere s h o ul d be n o m ore 
t ha n a 3- wee k dela y fr o m t he ne xt sc he d ule d d ose of sacit uz u ma b g o viteca n- hzi y. A d osi n g 
dela y > 3 w ee ks fr o m t he ne xt sc he d ule d d ose ma y be per mitte d o n a case- b y-case b asis wit h t he 
a p pr o val of t he I n vesti gat or a n d Me dical M o nit or.  
Criteria w hic h patie nts m ust meet i n or der t o recei ve st u d y dr u g o n Da y 1 a n d o n Da y 8 d uri n g 
treat me nt are pr o vi de d i n Secti o n 9. 2. 
A n E n d of Treat me nt Visit will occ ur a p pr o xi ma tel y 1 4 da ys f oll o wi n g a p atie nt’s last d ose of 
st u d y treat me nt. Safet y F oll o w- u p visits ( w hic h ma y b e a p h o n e call) will o cc ur 3 0 da ys after t he 
last d ose of st u d y tr eat me nt. Patie nts will be f oll o we d f or s ur vi v al a p pr o xi matel y e ver y 3 m o nt hs 
after t he E n d of Treat me nt Visit. S ur vi val F oll o w- u p Visits ma y be d o n e via tele p h o ne, e mail, or 
cli nic visit. U nless ot her wise deci de d b y t he S p o n s or, t he st u d y will c o nti n ue u ntil a p pr o xi matel y 
7 0 % of patie nts e nr olle d i n t he st u d y ha ve di e d. 
A Safet y M o nit ori n g C o m mittee ( S M C) will m o ni t or acc u m ulati n g safet y a n d dis p ositi o n data 
wit h t he first meeti n g pla n ne d w he n a p pr o xi matel y 1 0 patie nts ha v e c o m pl ete d at least 2 c ycles 
of st u d y tr eat me nt. T he meeti n gs will c o nti n ue w he n a p pr o xi matel y 2 5 e nr olle d patie nts ha ve 
c o m plete d at least 2 c ycl es of st u d y tr eat me nt  a n d a gai n w he n all e nr olle d patie nts ha ve 
c o m plete d at least 2 c ycl es of st u d y tr eat me n t or as defi ne d i n t he S M C c harter. A d diti o nal 
re vie ws ma y o cc ur. F or m ore i nf or mati o n, refer t o Secti o n 1 1. 4 .  
T he st u d y will be c o m plete d w he n t he criteria o utli ne d i n Secti o n 1 0. 4  ha ve bee n met or u p o n 
s p o ns or ter mi nati o n of t he st u d y. 

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6. 2.  
R ati o n ale f or Pri m ar y a n d Sec o n d ar y E n d p oi nts 
6. 2. 1.  
A nti-t u m o r Effic ac y 
Meas ure me nts of a nti-t u m or effic ac y as m eas ure d b y P F S a n d O S, as well as a nti-t u m or 
res p o nse rates b y Res p o nse E val uati o n Criteria i n S oli d T u m ors ( R E CI S T) v 1. 1, O R R, cli nical 
be nefit rat e ( C B R), a n d D O R, are sta n d ar d ass ess me nts use d i n o nc ol o g y s oli d t u m or st u dies t o 
meas ure t he effects of st u d y treat me nt o n t he u n derl yi n g mali g na nt diseas e. A d diti o nall y, cli nical 
be nefit i n o nc ol o g y s h o ul d be base d o n dir ect e v i d e nce, s uc h as i m pr o ve me nt i n d urati o n of P F S 
or O S, i m pr o ve me nt i n a patie nt’s q ualit y of life, i m pr o ve d p h ysi cal f u ncti o ni n g, or i m pr o ve d 
t u m or-relate d s y m pt o ms, w hic h ma y n ot be a d e q u atel y m eas ure d b y res p o nse rates al o n e. 
T heref ore, i m pr o ve m e nt i n s ur vi val is c o nsi dere d o ne of t he m ost relia ble meas ures i n pr o vi di n g 
direct e vi de n ce of cli nical be nefit t o patie nts a n d is a preferre d cli nical e n d p oi nt. S ur vi val is 
c o nsi dere d eas y t o meas ure via d oc u me nt ati o n of t he date of d eat h a n d is n ot pr o ne t o bias ( F D A, 
2 0 0 8 ).  
6. 2. 2.  
M yel o pr otecti o n 
Patie nts e x perie nci n g c he m ot hera p y-i n d uce d m yel os u p pressi o n ofte n face s e vere cli nical 
c o nse q ue nces (e. g., fe brile ne utr o pe nia [ F N] pre dis p oses patie nts t o seri o us i nfecti o ns a n d e v e n 
deat h). F or t h ose patie nts wit h ne utr o pe nia re q uiri n g h os pitalizati o n, t he esti mate d i n patie nt 
m ortalit y rates ra n ge d fr o m 3. 4 % t o 1 0. 5 % de pe n di n g o n t u m or t y p e i n 1 st u d y, wit h a n o verall 
m ortalit y rate of 6. 8 % ( C a g gi a n o, 2 0 0 5 ). I n a n ot her a nal ysis, t he o verall rate of deat h w as 9. 5 %, 
wit h rates f or s oli d t u m or ca ncer patie nts r a n gi n g fr o m 3. 6 % f or breast c a ncer patie nts t o 1 3. 4 % 
f or l u n g ca n cer patie nts (K u derer, 2 0 0 6 ). Beca use b ot h t he se verit y a n d d urati o n of ne utr o pe nia 
c orrel ate wit h t he ris k of F N a n d i nf ecti o ns ( B o de y, 1 9 6 6; G usti netti, 2 0 1 6; Li, 2 0 1 6 ), a 
re d ucti o n i n its occ urre nce a n d d urati o n will decrease t he ris k of t hes e e ve nts a n d pr o vi de a n 
i m pr o ve d patie nt e x perie nce w hile recei vi n g c h e m ot hera p y (Pa dilla, 2 0 0 5 ).  
6. 2. 3.  
S afet y 
Assess me nt of A Es, c h a n ges i n la b orat or y para met ers, electr ocar di o gra ms ( E C Gs), vital si g ns, 
a n d 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 are all sta n dar d 
assess me nts use d i n o nc ol o g y trials t o meas ure patie nt safet y.  
6. 3.  
R ati o n ale f or D ose a n d Sc he d ule of St u d y Tre at me nt 
Pre vi o us st u dies de m o nstrate d t he rec o m m e n de d P hase 2 d ose of trilacicli b was 2 4 0 m g/ m 2; t he 
d ose a p pr o ve d b y t h e F D A f or E S- S C L C. W he n  trilacicli b was a d mi nistere d pri or t o 
c he m ot hera p y t o ca ncer patie nts, d oses of 2 0 0 m g/ m 2 (r o u n de d u p fr o m 1 9 2 m g/ m2), 2 4 0 m g/ m2, 
a n d 2 8 0 m g/ m 2 were e val uate d. Trilacicli b e x p os ures i n ca n cer patie nts were sli g htl y l o w er 
c o m pare d wit h he alt h y s u bjects, s uc h t hat t he d os e of 2 4 0 m g/ m 2 (rat her t h a n 2 0 0 m g/ m2) m ore 
cl osel y mat c he d t he bi ol o gic all y effecti ve d ose of 1 9 2 m g/ m 2. I n a d diti o n, t he d ose of 2 4 0 m g/ m2 
de m o nstrate d ma xi mal m yel o pr ot ecti o n effica c y b e nefits (c o m pare d wit h 2 0 0 m g/ m 2 a n d 
2 8 0 m g/ m 2) as meas ur e d b y a v ariet y of m yel os u p pressi o n e n d p oi nts. T he m yel o pr otecti ve effect 
at 2 4 0 m g/ m 2 was f urt her e val uate d a n d c o nfir m e d i n t hree ra n d o mize d c o ntr oll e d P hase 2 
st u dies i n S C L C patie nts. I n a d diti o n, b ot h t he pla n ne d sc he d ule an d t he pl a n ne d d oses of 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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trilacicli b were us e d i n t he pre vi o us T N B C st u d y ( G 1 T 2 8- 0 4) a n d d e m o nstr ate d cli nicall y 
mea ni n gf ul be nefits i n O S d urati o n. See t he trilaci cli b I B f or details.  
T he 1 0 m g/ k g d ose a n d s c he d ule of s acit uz u ma b g o viteca n- hzi y tr eat me nt is base d o n t he 
i nstr ucti o ns pr o vi de d i n t he prescri bi n g i nf or mati o n (Tr o del v y Pac k a ge I ns ert, 2 0 2 1 ). 
Trilacicli b is al wa ys a d mi nistere d pri or t o s y st e mic a nti-ca n cer t hera p y o n eac h d a y of a nti-
ca ncer t hera p y a d mi nistrati o n. Trilacicli b s hall n ot be a d mi nistere d as m o n ot hera p y (i.e., o n d a ys 
t hat sacit uz u ma b g o viteca n- hzi y will be dela ye d or s ki p pe d). 
6. 4.  
R ati o n ale f or P atie nt P o p ul ati o n 
Metastatic T N B C is i nc ura ble. Hist oricall y, T N B C patie nts u n der g oi n g s ec o n d-li ne t hera p y ha ve 
ha d a ver y p o or pr o g n osis ( P F S d urati o n of 2 t o 3 m o nt hs a n d O S d urati o n of 9 t o 1 2 m o nt hs). 
C he m ot hera p y is t he mai nsta y of treat me nt of T N B C a n d t here is n o preferre d or sta n dar d 
re gi me n use d.  W hile tar get e d t hera pi es ha ve greatl y i m pr o ve d o utc o mes f or h or m o ne- p ositi ve 
a n d H E R 2- p ositi ve breast ca ncer, t here re mai n p a tie nts wit h T N B C w h o d o n ot be nefit fr o m 
t hese t hera pi es. F or e x a m ple, alt h o u g h t he P D- 1/ P D- L 1 i n hi bit ors i n metastatic T N B C patie nts 
wit h P D- L 1- p ositi ve t u m ors de m o nstrate d s u peri or efficac y lea di n g t o accelerate d a p pr o val, t his 
be nefit d oes n ot e xte n d t o patie nts w h o ha ve P D- L 1 ne gati ve diseas e or w h o are P D- L 1 p ositi ve, 
b ut f or w h o m a P D- 1/ P D- L 1 t ar gete d treat me nt is n ot a p pr o priate ( Tece ntri q ®  Pac ka ge I ns ert, 
2 0 2 0 ). A d diti o nal a vaila ble tar gete d t hera pies rece ntl y a p pr o ve d b y t he F D A are P A R P 
i n hi bit ors s uc h as ola pari b f or t he treat me nt of patie nts wit h ger mli ne B R C A- p ositi ve, 
H E R 2- ne gati ve metast atic breast ca ncer w h o h a ve pre vi o usl y recei ve d c h e m ot hera p y (a p pr o ve d 
i n J a n uar y 2 0 1 8) a n d talaz o pari b f or patie nts wit h deleteri o us or s us pecte d deleteri o us ger mli ne 
B R C A- m utate d, H E R 2- n e gati ve l ocall y a d v a nce d or metastatic breast ca n cer (a p pr o ve d i n 
Oct o ber 2 0 1 8). W hile t hese t w o tar gete d t h era pies off er be nefit t o patie nts wit h T N B C, t he y are 
li mite d t o t h ose wit h ger mli ne B R C A m utati o ns ( ~ 9- 1 8 % of T N B C patie nts; Ha h ne n, 2 0 1 7 ). 
Treat me nt o pti o ns are e v e n m ore li mite d f or patie nts w h o ha ve recei ve d t w o or m ore r e gi me ns i n 
t he metastatic setti n g. Trilacicli b ma y pr o vi de a n o vel t hera pe utic o pti o n f or t hese patie nts w h o 
ha ve mi ni mal o pti o ns a vaila ble. Offeri n g T N B C patie nts a n alter nati ve t h era pe utic o pti o n t hat 
ma y pr o vi d e a cli nic all y mea ni n gf ul e xte nsi o n of t he d urati o n of P F S or O S i n t he c o nte xt of a 
ma na gea bl e safet y pr ofil e w o ul d be a n i m p orta nt ste p f or war d f or p atie nts wit h l ocall y a d v a nce d 
or metastatic T N B C w h o ha ve recei ve d at least 2 pri or treat me nts, at least 1 i n t he metastatic 
setti n g, re gar dless of P D- L 1 stat us.  
Trilacicli b e n ha n ces i m m u ne acti vati o n a n d pr o m otes a nti-t u m or i m m u nit y b y differe ntiall y 
arresti n g c yt ot o xic a n d re g ulat or y T cell s u bsets f oll o we d b y a faster rec o ver y of c yt ot o xic T 
l y m p h oc ytes t ha n re g ulat or y T cells i n t u m ors (Lai, 2 0 2 0 ). T his differe ntial alterati o n of cell 
c ycle ki netics bet w ee n c yt ot o xic T l y m p h o c ytes a n d re g ulat or y T cells res ults i n a hi g her 
pr o p orti o n of c yt ot o xic T l y m p h oc ytes t ha n re g ulat or y T cells, e n ha n ce me nt of T cell acti vati o n, 
a n d a decrease i n re g ul at or y T cell- me diat e d i m m u n os u p pressi ve f u ncti o ns ( C hai k o vs k y a n d 
Sa ge, 2 0 1 8; D e n g, 2 0 1 8; G oel, 2 0 1 7; Sc haer, 2 0 1 8 ). T o get her, t hes e e v e nts pr o m ote t he 
c yt ot o xic T l y m p h oc yte- me diate d cleara n ce of t u m o r cells. T heref ore, t he a nti-t u m or effects of 
trilacicli b mi g ht res ult fr o m t he tra nsie nt pr oliferati ve arrest of T cells, f oll o we d b y acti vati o n of 
c yt ot o xic T l y m p h oc ytes i n t he c o nte xt of fe wer re g ulat or y T cells.  
Base d o n t h e p ositi ve i m pact o n O S d urati o n o bser ve d i n St u d y G 1 T 2 8- 0 4 ( Ta ble 3  a n d T a ble 4 ), 
i n t he c o nte xt of trilacicli b’s ma na gea ble safet y pr ofile, t he a d diti o n of trilacicli b t o sacit uz u ma b 

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g o viteca n- hzi y c o ul d pr o vi de a mea ni n gf ul treat me nt o pti o n f or patie nts wit h l ocall y a d v a nce d or 
metastatic T N B C w h o h a ve recei ve d at least 2 pri or treat me nts, at least 1 i n t he metastatic setti n g 
a n d f urt her e val uati o n of trilacicli b i n t his area of hi g h u n met me dical nee d is warra nte d. 
6. 5.  
R ati o n ale f or S acit uz u m a b G o vitec a n- hzi y T her a p y 
As disc usse d i n Secti o n 4. 1 , w hile s o me breast c a n cer patie nts h a ve tar gete d t hera pies a v aila ble 
t o t he m, se q ue ntial si n gle-a ge nt c h e m ot hera p y re m ai ns t he sta n dar d of care f or patie nts wit h 
metastatic T N B C ( C ar d os o, 2 0 1 7; N C C N, 2 0 2 0 ). Sacit uz u ma b g o viteca n- h zi y is a n 
a nti b o d y- dr u g c o nj u gate c o m p ose d of a h u ma nize d a nti – Tr o p- 2 m o n ocl o nal a nti b o d y a n d a 
clea va bl e li n ker c o u ple d t o t he c yt ot o xic c he m ot hera p y S N- 3 8, a n acti ve m eta b olite of t he 
t o p ois o merase I i n hi bit or iri n oteca n a n d pre ve nts r e-li gati o n of t o p ois o merase I-i n d uce d si n gle 
stra n d brea ks (Star o d u b, 2 0 1 5 ). T he res ulti n g D N A da ma ge lea ds t o a p o pt osis a n d cell deat h. 
Tr o p- 2 (tr o p h o blast cell-s urface a nti ge n) is a calci u m si g nal tra ns d ucer o vere x presse d i n ma n y 
e pit helial ca ncers a n d i m plicate d i n t he pr o m oti o n of cell ular pr oliferati o n, s ur vi val, a n d i n vasi o n 
(Barr os o- S o usa, 2 0 2 1 ). Tr o p- 2 is e x presse d i n breast ca ncer cells, i ncl u di n g t h ose i n T N B C 
(Bar dia, 2 0 1 9 ), a n d hi g h le vels of Tr o p- 2 e x pressi o n are ass o ciate d wit h p o or pr o g n osis a n d 
w orse s ur vi val i n breast c a ncer ( A m br o gi, 2 0 1 4 ). Sacit uz u ma b g o viteca n- h zi y c o ntai ns o n 
a vera ge 7 t o 8 m olec ules of S N- 3 8 per a nti b o d y m olec ule ( Tr o d el v y Pac ka ge I nsert, 2 0 2 1 ). U p o n 
bi n di n g t o Tr o p- 2 e x pressi n g ca n cer cells, it is  i nter nalize d a n d s u bse q ue ntiall y rel eases S N- 3 8 
b ot h i ntracell ularl y a n d i n t he t u m or micr oe n vir o n me nt ( Bar dia, 2 0 1 9; Tr o del v y Pac ka ge I nsert, 
2 0 2 1 ). T his res ults i n t u m or cells rec o g nize d b y s acit uz u ma b g o viteca n- hzi y bei n g kille d b y 
i ntracell ular u pta k e of S N- 3 8, a n d a dj ace nt t u m or cells bei n g kille d b y t he e xtracell ular rel ease 
of S N- 3 8 ( Bar dia, 2 0 1 9 ). 
I n 2 0 2 0, accelerate d a p pr o val was gra nt e d b y t he F D A f or sacit uz u ma b g o viteca n- hzi y f or t he 
treat me nt of a d ult patie nts wit h metastatic T N B C w h o ha ve recei v e d at least t w o pri or t hera pies 
f or metastatic disease. T h e accelerate d a p pr o val w as base d o n res ults fr o m t he P hase 2 
I M M U- 1 3 2- 0 1 trial w h ere patie nts ( N = 1 0 8) treated wit h sacit uz u ma b g o viteca n- hzi y ha d a n 
O R R of 3 3. 3 %, me dia n D O R of 7. 7 m o nt hs ( 9 5 %  CI: 4. 9- 1 0. 8 m o nt hs), a n d 5 5. 5 % a n d 1 6. 7 % of 
pati e nts ha vi n g a D O R of ≥6 m o nt hs a n d ≥1 2 m o nt hs, res pecti vel y ( Bar dia, 2 0 1 9 ). I n 2 0 2 1, f ull 
a p pr o val was gra nte d b y F D A bas e d o n t he res ults fr o m t he P hase 3 A S C E N T trial (Bar dia, 
2 0 2 1 ). Me dia n P F S f or p atie nts recei vi n g sacit uz u ma b g o viteca n- hzi y was 4. 8 m o nt hs ( 9 5 % CI: 
4. 1- 5. 8 m o nt hs) c o m pare d wit h 1. 7 m o nt hs ( 9 5 % CI: 1. 5- 2. 5 m o nt hs) i n t h ose recei vi n g 
p h ysicia n’s c h oice of si n gle - a ge nt c h e m ot hera p y ( H R 0. 4 3, 9 5 % CI: 0. 3 5- 0. 5 4, P < 0. 0 0 0 1) a n d 
me dia n O S was 1 1. 8 m o nt hs ( 9 5 % CI: 1 0. 5- 1 3. 8 m o nt hs) a n d 6. 9 m o nt hs ( 9 5 % CI: 5. 9- 7. 6 
m o nt hs), res pecti vel y ( H R 0. 5 1, 9 5 % CI: 0. 4 1- 0. 6 2, P < 0. 0 0 0 1) ( Tr o del v y Pac ka ge I ns ert, 2 0 2 1 ). 
I n t hat s a me st u d y, i n a s u bset of patie nts wit h o ut brai n m etastasis at baseli ne ( 8 8 % of t h e f ull 
st u d y p o p ulati o n), me dia n P F S f or patie nts recei vi n g sacit uz u ma b g o viteca n- hzi y was 5. 6 
m o nt hs ( 9 5 % CI: 4. 3- 6. 3 m o nt hs) c o m pare d wit h  1. 7 m o nt hs ( 9 5 % CI: 1. 5- 2. 5 m o nt hs) i n t h ose 
recei vi n g p h ysicia n’s c h oice of si n gle-a ge nt c he m ot hera p y ( H R 0. 4 1, 9 5 % CI: 0. 3 2- 0. 5 2, 
P < 0. 0 0 1) a n d me dia n O S was 1 2. 1 m o nt hs ( 9 5 % CI: 1 0. 7- 1 4. 0 m o nt hs) a n d 6. 7 m o nt hs ( 5. 8- 7. 7 
m o nt hs), res pecti vel y ( H R 0. 4 8, 9 5 % CI: 0. 3 8- 0. 5 9, P < 0. 0 0 1) ( Bar dia, 2 0 2 1 ).  
Sacit uz u ma b g o viteca n- h zi y h as pr o vi de d a n i m p orta nt ne w treat me nt o pti o n t o patie nts wit h 
metastatic T N B C b ut is ass ociate d wit h s o me si g nif ica nt ris ks. Sacit uz u ma b g o viteca n- hzi y ma y 
ca use se v ere di arr h ea a n d se vere or life-t hr eate ni n g ne utr o pe nia ( Tr o del v y Pac ka ge I ns ert, 2 0 2 1 ). 

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T he a d diti o n of trilacicli b t o sacit uz u ma b g o viteca n- hzi y ma y offer t h e p ote ntial f or cli nical 
be nefit (i ncreas e d s ur vi v al) a n d a n i m pr o ve d t o lera bilit y pr ofile ( m yel o pr otecti o n) t o patie nts 
wit h metastatic T N B C w h o ha ve recei ve d at leas t 2 pri or t hera pies, at least 1 i n t he metastatic 
setti n g. 
6. 6.  
R ati o n ale f or S u p p orti ve C are I nter ve nti o ns ( Gr o wt h F act ors a n d 
Tr a nsf usi o ns) 
I n or der t o facilitate a n u n biase d e val uati o n of tril acicli b effects o n t he he mat ol o gic e n d p oi nts, 
pri mar y pr o p h ylactic gra n ul oc yte c ol o n y-sti m ulati n g fact or ( G- C S F) will b e pr o hi bite d i n 
C ycle 1; h o w e ver t h era p e utic G- C S F (a d mi nistere d i n res p o nse t o a n e utr o pe nic e ve nt) i n 
C ycle 1 a n d sec o n d ar y pr o p h yla ctic G- C S F be gi n ni n g i n C ycl e 2 a n d f or all s u bse q ue nt c ycles 
(i.e., after a preci pitati n g e ve nt i n a pri or c ycle of t hera p y) will be all o we d p er gr o wt h 
fact or/ ne utr o p e nia ma n a ge m e nt g ui d eli nes i n Secti o n 9. 4. 1  a n d I n v esti gat or discreti o n (Aa pr o, 
2 0 1 0 ; S mit h, 2 0 1 5 ).  
Er yt hr o p oiesis-sti m ulati n g a ge nt ( E S A) a d mi nistrati o n a n d R B C or platelet tra nsf usi o ns will be 
all o we d per I n vesti gat or discreti o n base d o n g ui deli nes detaile d i n Secti o n 9. 4. 2  a n d 
Secti o n 9. 4. 3 . W hile t hese i nter ve nti o ns ma y c o nf o u n d a nal ysis of t he m yel os u p pressi o n 
e n d p oi nts, all o wi n g p h ysicia ns t o pr o vi de a p pr o priate s u p p orti ve care t o patie nts will facilitate 
patie nt safet y.  
T he N C C N H u ma n Gr o wt h Fact or S u p p orte d Care G ui deli nes ( N C C N, 2 0 2 1 ) f or patie nts 
recei vi n g c yt ot o xic c he m ot hera p y (i ncl u di n g th ose i n cli nical trials) i ncl u des t he f oll o wi n g 
g ui da n ce f or t he use of trilacicli b as a s u p p orti ve ca re i nter ve nti o n f or patie nts wit h E S- S C L C. 
Trilacicli b as a s u p p orti v e care i nter ve nti o n is bei n g f urt her i n vesti gate d i n t his trial i n patie nts 
wit h T N B C recei vi n g sacit uz u ma b g o viteca n- hzi y treat me nt. 
 Trilacicli b ma y be use d as a pr o p h yl actic  o pti o n t o decrease t he i n ci de nce of 
c he m ot hera p y-i n d uce d m yel os u p pressi o n w he n a d mi nistere d bef ore ( or G- C S F ma y 
be a d mi nistere d after) pl ati n u m/et o p osi de ± i m m u ne c hec k p oi nt i n hi bit or-c o ntai ni n g 
re gi me ns or a t o p oteca n- c o ntai ni n g re gi me n f or E S- S C L C. 
 Trilacicli b ma y be use d as a pr o p h yl actic o pti o n t o decrease t he i n ci de nce of 
c he m ot hera p y-i n d uce d m yel os u p pressi o n w he n a d mi nistere d bef ore ( pr o p h yl actic  
G- C S F ma y be a d mi nistere d aft er  Cycl e 1) plati n u m/et o p osi de ± i m m u ne c hec k p oi nt 
i n hi bit or-c o ntai ni n g re gi mes or a t o p oteca n-c o ntai ni n g re gi me n f or E S- S C L C. 
 Trilacicli b ma y be use d as a pr o p h yl actic o pti o n t o decrease t he i n ci de nce of a ne mi a 
a n d R B C tr a nsf usi o ns  w he n a d mi nistere d bef ore plati n u m/et o p osi de ± i m m u ne 
c hec k p oi nt i n hi bit or-c o nt ai ni n g re gi me ns or a t o p oteca n-c o ntai ni n g re gi me n f or 
E S- S C L C. 

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7.  
S T U D Y P O P U L A TI O N 
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as 
a pr ot oc ol wai ver or e x e m pti o n, is n ot per mitte d. 
7. 1.  
I ncl usi o n Criteri a 
Patie nt eli gi bilit y s h o ul d be re vie we d a n d d o c u me nte d b y a n a p pr o priatel y q ualifi e d me m ber of 
t he I n v esti gat or st u d y tea m bef ore p atie nts are i n cl u de d i n t he st u d y. Patie nts m ust meet all  of 
t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i nt o t he st u d y: 
1.  A ge ≥1 8 years . 
2.  Fe male or male patie nt wit h meas ura ble, u nresect a ble l ocall y a d va nce d or metastatic 
T N B C. 
3.  D oc u me ntati o n of hist ol o gic all y or c yt ol o gi call y c o nfir me d h or m o ne (estr o ge n a n d 
pr o gester o ne) rece pt or n e gati ve t u m or b y i m m u n o hist oc he mistr y (I H C) ass ess me nt 
( defi ne d as < 1 % n u clei stai ni n g) a n d H E R 2- ne gati ve, n o n- o vere x pressi n g ( b y I H C [ 0 or 
1 +] O R i n sit u h y bri dizati o n [rati o < 2. 0] O R a vera ge H E R 2 ge ne c o p y n u m ber of 
< 4 si g n als/ n ucle us) per 2 0 1 8 A merica n S oc iet y of Cli nical O nc ol o g y ( A S C O) a n d t he 
C olle ge of A merica n Pat h ol o gists ( A S C O/ C A P) criteria. Patie nts wit h “estr o ge n rece pt or 
( E R) or pr o gest er o ne rece pt or ( P R) l o w p ositi ve” as per u p dat e d A S C O/ C A P 2 0 2 0 
g ui deli nes ca n be c o nsi dere d after a p pr o val b y t h e Me dical M o nit or. 
4.  Meas ura ble dis ease as defi ne d b y R E CI S T v 1. 1. 
5.  C o nsi dere d t o be eli gi ble t o recei ve s acit uz u ma b g o viteca n- hzi y tr eat me nt, i n t he 
In v esti gat or’s j u d g me nt . 
6.  Patie nts m ust ha ve recei v e d 2 or m ore pri o r li nes of s yste mic t hera p y, at least o ne of 
t he m i n t he metastatic setti n g.  
7.  Ra diati o n t hera p y f or m etastatic disease is per m itt e d as l o n g as t he patie nt has at least 
1 meas ura ble l esi o n t hat has n ot bee n irra diate d. P atie nts s h o ul d be s ufficie ntl y rec o vere d 
fr o m t he effects of ra diati o n as deter mi ne d b y t he I n vesti gat or b ut m ust ha v e c o m plete d 
ra di ot hera p y at least 2 w ee ks pri or t o e nr oll me nt. 
8.  E C O G perf or ma nce stat us of 0 or 1. 
9.  A de q uate or ga n f u ncti o n as de m o nstrate d b y t he f oll o wi n g la b orat or y val u es: 
a. He m o gl o bi n ≥9. 0 g/ d L i n t he a bse nce of R B C tr a nsf usi o n or E S A a d mi nistrati o n 
wit hi n 7 da ys pri or t o t he first d ose of trilacicli b; 
b.  A bs ol ute ne utr o p hil c o u nt ( A N C) ≥1. 5 × 1 0 9/ L;  
c. Platelet c o u nt ≥1 0 0 × 1 0 9/ L;  
d.  Esti mate d gl o mer ular filtrati o n rate ≥3 0 m L/ mi n ute/ 1. 7 3 m 2;  
e. T otal bilir u bi n ≤1. 5 × u p per li mit of n or mal ( U L N) ;  
f. A L T a n d A S T ≤3 × U L N i n t he a bse nce of li ver m etastasis or ≤5 × U L N i n t he 
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1 0.  Res ol uti o n of n o n he mat ol o gic t o xicities fr o m pri or s yste mic t hera p y, ra diati o n t hera p y, 
or s ur gical pr o ce d ures t o 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) 
≤ Gra de 1 (e x ce pt al o pecia or peri p heral ne ur o pat h y t hat ma y b e Gra d e 2 or less). 
1 1.  Pre dicte d life e x pecta n c y of ≥3 m o nt hs . 
1 2.  C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal g ui deli nes re gar di n g 
t he met h o ds of c o ntrace pti o n f or t h ose partici pati n g i n cli nical st u dies . Please see Secti o n 
1 7. 3  f or detaile d i nstr ucti o ns o n met h o ds of c o ntrace pti o n re q uir e me nts. 
1 3.  Ca pa ble of gi vi n g si g n e d i nf or me d c o nse nt, w hic h i ncl u des c o m plia nce wit h t he 
re q uire me nts a n d restricti o ns liste d i n t he i nf or me d c o nse nt f or m a n d i n t his pr ot oc ol. 
7. 2.  
E xcl usi o n Criteri a  
A patie nt will n ot be eli gi ble f or partici pati o n i n t his st u d y if a ny  of t he f oll o wi n g criteria a p pl y: 
1.  Pri or treat me nt wit h trilacicli b, sacit uz u ma b g o vit eca n- hzi y, iri n oteca n, Tr o p- 2 a nti b o d y 
dr u g c o nj u gate, or a n y t h era p y wit h a t o p ois o merase- 1 pa yl oa d. 
2.  Patie nts wit h k n o w n brai n metastasis at e nr oll me nt. 
3.  Patie nts wit h k n o w n Gil bert’s disease or k n o w n h o m oz y g o us f or t he U G T 1 A 1 * 2 8  allele. 
4.  Patie nts wit h b o ne- o nl y disease. 
5.  Mali g na n cies ot her t ha n T N B C wit hi n 3 years pri or t o e nr oll me nt. Patie nts wit h 
mali g na n cies of a n e gli gi ble ris k of metastasis or deat h (e. g., ris k of metast asis or deat h 
< 5 % at 5 years as d eter mi ne d b y t h e I n vesti gat or) are eli gi ble pr o vi d e d t he y meet all of 
t he f oll o wi n g criteria: 
a. Mali g na n c y treate d wit h e x pecte d c urati ve i nte nt ( e. g., a de q u atel y treat e d carci n o ma 
i n sit u of t he cer vi x, basal or s q ua m o us cell s ki n ca ncer, or d uctal carci n o ma i n sit u 
treate d s ur gic all y wit h c urati ve i nte nt); 
b.  N o e vi de nce of rec urre nce or metastasis b y f oll o w- u p i ma gi n g a n d a n y dise ase-
s pecific t u m or mar kers. 
6.  Hist or y of cli nicall y si g nifica nt gastr oi ntesti nal blee di n g, i ntesti nal o bstr ucti o n, or 
gastr oi ntesti nal perf orati o n wit hi n 6 m o nt hs of e nr oll me nt. 
7.  Recei pt of a n y i n vesti gati o nal me dicati o n wit hi n 4 wee ks, or at least 5 half-li ves, 
w hic he ver is greater, pri or t o t he first d ose of st u d y treat me nt. 
8.  Recei pt of a n y c yt ot o xic c he m ot hera p y wit hi n 2 wee ks or a nti b o d y treat me nt f or ca n cer 
wit hi n 3 wee ks pri or t o t he first d ose of st u d y treat me nt. 
9.  Recei pt of a n y hi g h d ose s yste mic c ortic oster oi ds  wit hi n 2 wee ks pri or t o t he first d ose of 
st u d y treat me nt: 
a. L o w d os e c ortic oster oi ds ( ≤2 0 m g pre d nis o ne or e q ui vale nt dail y) are per mitte d  if t he 
d ose is sta ble f or 4 w ee ks, or if me dicall y i n dicate d as part of t heir pre- m e dicati o ns 
f or i nf usi o ns. 
b.  T o pical ster oi ds a n d c ortic os ter oi d i n halers are all o we d. 
1 0.  C urre nt use of i m m u n os u p pressi ve me dicati o n, E X C E P T f or t he f oll o wi n g: 

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a. I ntr a nasal, i n hal e d, t o pical ster oi ds, or l ocal ster oi d i njecti o n (e. g., i ntra-artic ular 
i njecti o n); 
b.  S yste mic c ortic oster oi ds at p h ysi ol o gical d oses ≤1 0 m g/ da y of pre d nis o ne or 
e q ui vale nt; 
c. Ster oi ds as pre me dicati o n f or h y perse nsiti vit y reacti o ns (e. g., C T sca n 
pre me dicati o n). 
1 1.  Use of oral or I V a nti bi otics wit hi n 2 wee ks pri or t o e nr oll me nt. 
1 2.  Q T c orrecte d i nter val usi n g Fri deri cia’s f or m ula ( Q Tc F) > 4 8 0 msec at scree ni n g 
(c o nfir me d o n re peat). F or patie nts wit h ve ntric ul ar pace ma kers, Q Tc F > 5 0 0 msec. 
1 3.  U nc o ntr olle d isc he mic h eart diseas e or u nc o nt r oll e d s y m pt o matic c o n gesti ve heart fail ure 
( Class III or I V as defi ne d b y t he Ne w Y or k Heart Ass ociati o n f u ncti o nal classificati o n 
s yste m). 
1 4.  K n o w n hist or y of str o ke or cere br o vas c ular acci d e nt wit hi n 6 m o nt hs pri or t o first d ose of 
st u d y treat me nt. 
1 5.  K n o w n seri o us acti ve i nf ecti o n s uc h as, b ut n ot li mite d t o, h u ma n i m m u n o deficie nc y 
vir us ( HI V) (e. g., vir al l oa d i n dicati ve of HI V, HI V 1/ 2 a nti b o dies), He patitis B (e. g., 
He patitis B s urface a nti ge n reacti ve or He pa titis B D N A detecte d), He patitis C (e. g., 
He patitis C ri b o n ucleic aci d [ q ua ntitati v e] is detecte d) or t u berc ul osis. 
1 6.  Se vere i nf ecti o ns wit hi n 4 wee ks pri or t o  e nr oll me nt, i ncl u di n g b ut n ot li mite d t o 
h os pitaliz ati o n f or c o m plicati o ns of i nfecti o n, bactere mia, or s e vere p ne u m o nia. 
1 7.  Ot her u nc o ntr olle d seri o us c hr o nic diseas e or ps yc hiatric c o n diti o n t hat i n t he 
In v esti gat or’s o pi ni o n c o ul d affect patie nt safet y, c o m plia nce, or f oll o w - u p i n t he 
pr ot oc ol. 
1 8.  K n o w n h y p erse nsiti vit y or aller g y t o iri n oteca n, S N- 3 8, trilacicli b, or sacit uz u ma b 
g o viteca n- hzi y or a n y e x ci pie nts of t he af ore me nti o ne d me dicati o ns. 
1 9.  Pri or he mat o p oietic ste m cell or b o ne marr o w tra ns pla ntati o n. 
2 0.  Pre g n a nt or lact ati n g w o me n: 
a. W o me n of c hil d beari n g p ote ntial m ust ha ve ne gati ve ser u m pre g na n c y test res ult 
wit hi n 7 da ys pri or t o i nitiati n g st u d y treat me nt. 
2 1.  Maj or s ur gical pr o ce d ure, o pe n bi o ps y, or si g nifica nt tra u matic i nj ur y wit hi n 4 wee ks 
pri or t o st u d y treat me nt start, or a ntici pati o n of t he nee d f or m aj or s ur gical pr oce d ure 
d uri n g t he c o urse of t he st u d y. 
2 2.  Recei ve d a li ve, atte n uat e d vacci ne wit hi n 4 wee ks pri or t o t he first d ose of st u d y 
treat me nt or a ntici pati o n t hat s uc h a vacci ne will b e re q uir e d d uri n g t he st u d y treat me nt 
peri o d: 
a. I nfl ue nza vacci nati o n s h o ul d be gi ve n d urin g i nfl ue nza seas o n o nl y (a p pr o xi matel y 
Oct o ber t hr o u g h M a y i n t he N ort her n He mis p here). 
2 3.  Le gal i nca p acit y or li mite d le gal ca pacit y. 

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2 4.  Patie nts w h o are i n vesti gati o nal site staff me m bers directl y i n v ol ve d i n t he c o n d uct of t he 
st u d y a n d t heir fa mil y m e m bers, site staff m e m bers ot her wise s u per vise d b y t he 
I n v esti gat or, or patie nts w h o are e m pl o yees of G 1 T hera p e utics, I nc. dir ectl y i n v ol ve d i n 
t he c o n d uct of t he st u d y. 

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8.  
P R O T O C O L S C H E D U L E O F A S S E S S M E N T S 
T he pr oce d ures a n d assess me nts t o be perf or me d d uri n g t he st u d y are o utli ne d i n Ta ble 6 . W he n 
t here are m ulti ple pr oce d ures at t he sa me or o verl a p pi n g ti me p oi nts, or der of e ve nts s h o ul d be: 
E C Gs, vitals, bl o o d dra w. 
U nless ot her wise s pecifie d, assess me nts are t o b e c o m plete d wit hi n ± 1 da y of t he sc he d ule d visit 
date. U nsc he d ule d assess me nts a n d visits t o ma na ge p atie nt safet y m a y occ ur at t he 
I n v esti gat or’s discreti o n. St u d y pr oce d ures p erf orme d at u nsc he d ule d visits s h o ul d be rec or d e d 
i n t he a p pr o priate electr o nic case re p ort f or m (e C R F). 
 

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T a ble 6:   
Sc he d ule of Assess me nts 
Assess me nt 
Scree ni n g  
Tre at me nt P h ase ( 1 c ycle = 2 1 d a ys) 
F oll o w- U p 
P h ase 
See Pr ot oc ol 
Secti o n f or 
A d diti o n al 
Det ails 
E ver y C ycle  
E n d of 
Tre at me nt Visit 
S afet y 
F oll o w- u p   
S ur vi v al  
F oll o w- U p  
3 0 d a ys 
pri or t o 
e nr oll me nt 
D a y 1 
D a y 8 
1 4 d a ys after l ast 
d ose of st u d y 
tre at me nt ( ± 7 d) 
3 0 d a ys 
after l ast 
d ose ( + 7 d) 
E ver y 3 
m o nt hs 
p ost -S afet y 
F oll o w- u p 
I nf or me d C o nse nt 
X 
 
 
 
 
 
Secti o n  1 3. 3  
E nr oll me nt  
 
X 
[ C ycle 1 (-7 d)] 
 
 
 
 
 
Secti o n  1 1. 1. 2   
I ncl usi o n/ E xcl usi o n Criteria 
X 
 
 
 
 
 
Secti o n  7  
De m o gra p hics 
X 
 
 
 
 
 
Secti o n 1 1. 1. 3   
Me dical Hist or y a n d S ur gical Hist or y 
X 
 
 
 
 
 
Secti o n 1 1. 1. 4   
C o nc o mita nt Me dicati o ns 
X 
X 
 
 
Secti o n 1 1. 1. 4   
C o m plete P h ysical E xa mi nati o n (i ncl u de 
wei g ht a n d hei g ht)  
X 
 
 
 
 
 
Secti o n  1 1. 3. 2   
S y m pt o m- directe d P h ysical 
E xa mi nati o n ( wit h wei g ht o nl y)  
 
X 
 
 
 
 
Secti o n  1 1. 3. 2   
Vital Si g ns 
X 
X 
 
X 
 
 
Secti o n 1 1. 3. 1   
E C O G Perf or ma nce Stat us 
X 
X 
 
X 
 
 
Secti o n 1 1. 3. 3   
A d verse E ve nt Re p orti n g 
 
X 
X 
 
Secti o n 1 1. 3. 6   
L a b or at or y Assess me nts a n d Pr oce d ures 
He mat ol o g y 
X 
X 
X 
X 
 
 
Secti o n 1 1. 3. 5   
C he mistr y 
X 
X a 
 
X 
 
 
Secti o n 1 1. 3. 5   
Pre g na nc y T est ( W O C B P o nl y) 
X 
X 
 
X 
 
 
Secti o n 1 1. 3. 5   
1 2 -lea d Electr ocar di o gra m (i n tri plicate) 
X 
X 
[ C ycle 1] 
X 
[ C ycle 1] 
 
 
 
Secti o n  1 1. 3. 4   

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Assess me nt 
Scree ni n g  
Tre at me nt P h ase ( 1 c ycle = 2 1 d a ys) 
F oll o w- U p 
P h ase 
See Pr ot oc ol 
Secti o n f or 
A d diti o n al 
Det ails 
E ver y C ycle  
E n d of 
Tre at me nt Visit 
S afet y 
F oll o w- u p   
S ur vi v al  
F oll o w- U p  
3 0 d a ys 
pri or t o 
e nr oll me nt 
D a y 1 
D a y 8 
1 4 d a ys after l ast 
d ose of st u d y 
tre at me nt ( ± 7 d) 
3 0 d a ys 
after l ast 
d ose ( + 7 d) 
E ver y 3 
m o nt hs 
p ost -S afet y 
F oll o w- u p 
St u d y Tre at me nt 
Trilacicli b 
 
X 
X 
 
 
 
Secti o n 9. 1   
Sacit uz u ma b g o viteca n- hzi y 
 
X 
X 
 
 
 
Secti o n 9. 1   
Dise ase Assess me nt 
T u m or Assess me nts ( C T/ M RI)  
X 
X b 
 
 
Secti o n  1 1. 2. 1   
S ur vi val F oll o w U p a n d S u bse q ue nt 
A nti - Ca ncer Treat me nts 
 
 
 
 
 
X  
Secti o n 1 1. 7   
C R =c o m plete res p o nse; C T =c o m p ute d t o m o gra p h y; d = da y; E C G =elec tr ocar di o gra m; E C O G = Easter n C o o perati ve O nc ol o g y Gr o u p; 
F D G =[ 1 8F]-fl u or o de o x y gl uc os e; M RI = ma g netic res o na nce i ma gi n g; Na F =s o di u m fl u ori de; P E T = p ositr o n e missi o n t o m o gra p h y; M RI = ma g netic res ona nce 
i ma gi n g; Q 6 =e ver y si x; Q 9 =e ver y 9; W O C B P = w o me n of c hil d beari n g p ote ntial 
a C he mistr y sa m ples will be c ollecte d e ver y c ycle d uri n g C ycl es 1- 4 a n d e ver y ot her c ycle ( C ycle 6, C ycle 8, etc.) if res ults are  sta ble, per I n vesti gat or 
discreti o n. 
b C T/ M RI of c hest/a b d o me n/ pel vis Q 6 wee ks ( ± 7 d) t hr o u g h Wee k 3 6 relati ve t o C ycle 1 D a y 1 a n d Q 9 wee ks ( ± 7 d) t hereafter relati ve t o C ycle 1 Da y 1 u ntil 
d oc u me nte d disease pr o gressi o n or s u bse q ue nt a ntica ncer t hera p y. Brai n sca n ( M RI preferre d) d uri n g scree ni n g is n ot re q uire d a n d s h o ul d be perf or me d per 
I n vesti gat or discreti o n base d o n cli nical si g ns a n d s y m pt o ms. A d diti o nal brai n M RI s h o ul d be c o n d ucte d if t here are ne w cli nic al si g ns a n d s y m pt o ms 
s u g gesti ve of brai n metastases. B o ne metastases i de ntifie d at baseli ne via a b o ne sca n or P E T (s uc h as F D G- P E T, Na F- P E T, or ot h er l ocall y a vaila ble P E T 
o pti o ns) t o be f oll o we d at sc h e d ule d visits usi n g l ocalize d C T or M RI as cli nicall y i n dicat e d. If b o ne metastases ca n n ot be see n o n C T or M RI sca ns, b o ne 
sca ns or P E T s h o ul d be re p eate d, usi n g t he sa me dia g n ostic pr oce d ure b o ne metastases were at baseli ne, w he n C R is i de ntifie d i n  tar get disease or w he n 
pr o gressi o n i n b o ne is s us pect e d. 

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9.  
S T U D Y T R E A T M E N T 
9. 1.  
St u d y Dr u gs A d mi nistere d 
St u d y dr u gs are defi n e d as a n y i n v esti gati o nal pr o d uct or c he m ot hera p y i nt e n de d t o be 
a d mi nistere d t o a st u d y p atie nt acc or di n g t o t he st u d y pr ot o c ol. St u d y dr u gs use d i n t his 
pr ot oc ol are d escri b e d i n  Ta ble 7. 
T a ble 7:  
St u d y Dr u gs 
N a me 
Tril acicli b  
S acit uz u m a b G o vitec a n- hzi y 
T y pe  
I n vesti gati o nal Pr o d uct 
C he m ot hera p y 
D ose F or m ul ati o n 
Si n gle- use, sterile p o w der t o be 
rec o nstit ute d a n d f urt her dil ut e d wit h 
2 5 0 m L of n or mal sali ne (s o di u m 
c hl ori de s ol uti o n 0. 9 %) or de xtr ose 
5 % i n water ( D 5 W) per t he 
P har mac y Ma n ual  
See c urre nt prescri bi n g i nf or mati o n 
(Tr o del v y  Pac ka ge I nsert, 2 0 2 1) 
U nit D ose Stre n gt h(s) 
3 0 0 m g/ 2 0 m L  
See c urre nt prescri bi n g i nf or mati o n 
D os a ge Le vel(s) 
2 4 0 m g/ m 2 a d mi nistere d o n D a y 1 
a n d Da y 8  of eac h 2 1- da y c ycl e  
1 0 m g/ k g rec o nstit ute d t o a 
c o nce ntrati o n of 1. 1 m g/ m L t o 
3. 4  m g/ m L i n n or mal sali ne; t otal 
v ol u me s h o ul d n ot e xcee d 5 0 0 m L 
a d mi nistere d o n Da y 1 a n d Da y 8 of 
eac h 2 1 - da y c ycle. Pr otect fr o m li g ht. 
R o ute of A d mi nistr ati o n 
I V 
I V 
I nf usi o n Ti me 
3 0 mi n utes 
3 h o urs f or first i nf usi o n; 1 t o 2 h o urs 
f or s u bse q ue nt i nf usi o ns if pri or 
i nf usi o ns were t olerate d 
I V =i ntra ve n o us  
9. 1. 1.  
D ose, D osi n g Re gi me n, a n d R o ute 
Trilacicli b m ust be a d mi nistere d be f ore sacit uz u ma b g o viteca n- hzi y. 
9. 1. 1. 1.  
Tril acicli b –  I n vesti g ati o n al Pr o d uct 
Trilacicli b f or I nj ecti o n, 3 0 0 m g/ vial (als o r eferre d t o as “Trilacicli b Steril e P o w der f or 
c o nce ntr ate f or s ol uti o n f or I V i nf usi o n, 3 0 0 m g/ vial”)  is s u p plie d as a sterile, 
preser vati ve-free, yell o w, l y o p hiliz e d ca ke i n a si n gle- d os e vial ( 3 0 0 m g/ 2 0 m L). 
Trilacicli b m ust be rec o nstit ute d a n d f urt her dil ute d pri or t o I V i nf usi o n as o utli ne d i n t he 
P har mac y Ma n u al. Ase ptic tec h ni q ue m ust be  use d f or rec o nstit uti o n a n d dil uti o n. U p o n 
rec o nstit uti o n, t he s ol uti o n m ust t he n be dil ute d t o t he calc ulate d d os e bas e d o n t he b o d y 
s urface area ( B S A) of t he patie nt. Act ual b o d y wei g ht s h o ul d be utilize d f or d ose 
calc ulati o ns. If t here is a c ha n ge i n b o d y wei g ht ≥1 0 % relati ve t o t he wei g ht at t he ti me of 
t he last d ose calc ul ati o n, d ose s h o ul d be recalc ulat e d. Recalc ul ati o n of d ose m ore fre q u e ntl y 
per l ocal i nstit uti o nal g ui deli nes is per mitte d. D ose recalc ulati o n t o a dj ust f or c ha n ges i n 
b o d y w ei g ht will n ot be c o nsi dere d a d os e re d u cti o n a n d will be ma de at t he discreti o n of t he 

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I n v esti gat or. N o trilacicli b d ose re d ucti o ns f or t o xicit y ma na ge me nt will be all o we d d uri n g 
t he st u d y. 
9. 1. 1. 1. 1.  A d mi nistr ati o n of Tril acicli b 
 A d mi nister dil ute d trilacicli b s ol uti o n as a 3 0- mi n ute I V i nf usi o n n o m ore t ha n 
4 h o urs pri or t o sacit uz u ma b g o viteca n- hzi y. D o n ot a d mi nister trilacicli b as a 
b ol us. 
 Trilacicli b is al wa ys a d mi nistere d first.  Res ults fr o m he mat ol o g y la bs s h o ul d be 
re vie we d pri or t o a d mi nistrati o n of trilacicli b. If a d mi nistrati o n of sacit uz u ma b 
g o viteca n- hzi y t hera p y is s ki p pe d or disc o nti n ue d, trilacicli b will als o be s ki p pe d 
or disc o nti n ue d. 
 Dil ute d trilacicli b s ol uti o n m ust be a d mi nistere d wit h a n i nf usi o n set, i ncl u di n g a n 
i n-li ne filter ( 0. 2 or 0. 2 2 micr o n). C o m pati ble i n-li ne filters i ncl u de p ol yet her 
s ulf o ne ( P E S), p ol y vi n yli de ne fl u ori de, a n d cell ul ose acet ate.  
 D o n ot a d mi nister dil ute d trilacicli b s ol uti o n wit h a p ol ytetrafl u oret h yl e ne ( P T F E) 
i n-li ne filter. P T F E i n-li ne filters are n ot c o m pati ble wit h dil ute d trilacicli b 
s ol uti o n. 
 D o n ot c o-a d mi nister ot h er dr u gs t hr o u g h t he s a me i nf usi o n li ne.  
 D o n ot c o-a d mi nister ot h er dr u gs t hr o u g h a ce ntr al access d e vice u nless t he 
de vice s u p p orts c o-a d mi nistrati o n of i nc o m pati ble dr u gs.  
If t here is a n y st u d y dr u g re mai ni n g i n t he i nf usi o n ba g at t he e n d of t h e 3 0 mi n utes, t he 
i nf usi o n s h o ul d be c o nti n ue d at t he sa me rate u ntil t he e ntire c o nte nts of t h e ba g h a ve b ee n 
a d mi nistere d t o e ns ure p atie nts recei ve t he f ull d ose. U p o n c o m pleti o n of i nf usi o n of dil ute d 
trilacicli b s ol uti o n, t he i nf usi o n li ne/ca n n ula m ust be fl us he d wit h at least 2 0 m L sterile 5 % 
de xtr ose ( D 5 W) or 0. 9 % n or mal sali ne. 
T he i nf usi o n rate ma y b e decrease d t o ma n a ge a n i nf usi o n-relate d A E; f or e x a m ple, if a 
patie nt e x perie nces a b ur ni n g se nsati o n d uri n g i nf usi o n, t he d urati o n of i nf usi o n ma y be 
i ncreas e d t o 4 5 mi n utes ( or l o n ger if cli nicall y i n dicate d) t o alle viat e t he s y m pt o ms. T he 
act ual start/st o p ti me of i nf usi o n will be d oc u me nte d a n d e ntere d i n t he e C R F. 
9. 1. 1. 2.  
S acit uz u m a b G o vitec a n- hzi y –  C he m ot her a p y 
Descri pti o ns of t he f or m ulati o ns of c o m merciall y-a vaila ble s acit uz u ma b g o viteca n- hzi y ca n 
be f o u n d i n t he res p ecti v e c urre nt pres cri bi n g  i nf or mati o n. Pr ot oc ol-s pecifi e d d oses of 
sacit uz u ma b g o viteca n- h zi y will be a d mi nistere d I V i n acc or da nce wit h i nstit uti o nal 
g ui deli nes acc or di n g t o t he st u d y site’s sta n d ar d pr actice. De viati o n fr o m t he 
rec o m me n dati o ns pr o vi d e d i n t his pr ot oc ol i n or der t o f oll o w i nstit uti o nal g ui deli nes m ust 
recei v e pri or a p pr o val fr o m t he Me dical M o nit or or S p o ns or. 
Act ual b o d y wei g ht ( n ot i deal b o d y wei g ht) s h o ul d be utilize d f or d ose cal c ulati o ns. At a 
mi ni m u m, if t here is a c ha n ge i n b o d y wei g ht of > 1 0 % relati ve t o t he wei g ht at t he ti me of 
t he last d ose calc ul ati o n, d oses s h o ul d be recalc ulate d. Recalc ulati o n of t he d ose m ore 
fre q ue ntl y per l ocal i nstit uti o nal g ui deli nes is per mitte d. D ose recalc ulati o n t o a dj ust f or 
c ha n ges i n b o d y w ei g ht will n ot be c o nsi dere d a d ose re d ucti o n. 

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Pri or t o eac h i nf usi o n of sacit uz u ma b g o viteca n- h zi y, pre me dicati o n f or t h e pre ve nti o n of 
i nf usi o n reacti o ns a n d CI N V is rec o m me n d e d. 
 Pre me dicate wit h a nti p yretics, H 1 a n d H 2 bl oc k ers pri or t o i nf usi o n, a n d 
c ortic oster oi ds ma y be us e d f or patie nts w h o h a d pri or i nf usi o n reacti o ns. 
 Pre me dicate wit h a t w o or t hree dr u g ( preferre d) c o m bi nati o n re gi me n (e. g., 
de x a met has o ne wit h eit her a 5- H T 3 rece pt or a nta g o nist or a n N K 1 rece pt or 
a nta g o nist, as well as ot h er dr u gs as i n dicate d). 
A d mi nister t he first i nf usi o n o ver 3 h o urs a n d o bs er ve patie nts d uri n g t he i nf usi o n a n d f or at 
least 3 0 mi n utes f oll o wi n g t he i nitial d ose f or si g ns or s y m pt o ms of i nf usi o n-relate d 
reacti o ns. S u bse q ue nt i nf usi o ns ma y be a d mi nistere d o ver 1 t o 2 h o urs if pri or i nf usi o ns were 
t olerate d, a n d p atie nts s h o ul d be o bser ve d d urin g t he i nf usi o n a n d f or at least 3 0 mi n utes 
after i nf usi o n. Pr otect i nf usi o n ba g fr o m li g ht. D o n ot a d mi nister as a n I V p us h or b ol us. T he 
act ual start/st o p ti me of i nf usi o n will be d oc u me nte d a n d e ntere d i n t he e C R F. 
Trilacicli b is al wa ys a d mi nistere d first, f oll o we d b y sacit uz u ma b g o viteca n- hzi y. A d mi nister 
dil ute d trilacicli b s ol uti o n as a 3 0- mi n ute I V i n f usi o n t o be c o m plete d wit hi n 4 h o urs pri or t o 
t he start of sacit uz u ma b g o viteca n- hzi y. If a d mi nistrati o n of trilacicli b is dela ye d or 
disc o nti n ue d, sacit uz u ma b g o viteca n- hzi y will al s o be dela ye d or disc o nti n ue d. Li k e wise, if 
sacit uz u ma b g o viteca n- h zi y is dela ye d or disco nti n ue d, trilacicli b will als o be dela ye d or 
disc o nti n ue d. 
9. 1. 2.  
Pre p ar ati o n, H a n dli n g, St or a ge, a n d Acc o u nt a bilit y 
T he I n vesti gat or or d esi g nee is res p o nsi ble f or st u d y dr u g acc o u nta bilit y, rec o nciliati o n, a n d 
rec or d m ai nte na nce (i.e., recei pt, rec o n ciliatio n, a n d fi nal dis p ositi o n rec or ds).  T he 
I n v esti gat or/i nstit uti o n ma y assi g n s o m e or all of t he I n vesti gat or’s/i nstit uti o n’s d uties f or 
i n vesti gati o nal pr o d u ct(s) acc o u nt a bilit y t o a n a p pr o priate p har macist or a n ot her a p pr o pri ate 
i n di vi d ual w h o is u n der t he s u per visi o n of t he I n v esti gat or/i nstit uti o n. 
F urt her g ui d a nce a n d i nf or mati o n are pr o vi d e d i n t he P har mac y M a n u al. 
9. 1. 3.  
Tre at me nt C o m pli a nce 
T he I n vesti gat or or d esi g nee will dis pe nse t h e st u d y dr u gs, via a P har macist/ Desi g nee, o nl y 
f or use b y patie nts e nr olle d i n t he st u d y as d escri b e d i n t his pr ot oc ol. T he st u d y dr u gs are n ot 
t o be use d f or reas o ns ot her t ha n t h ose des cri be d i n t his pr ot oc ol. T he cli nical st u d y site will 
mai ntai n rec or ds of st u d y dr u gs’ recei pt, pre p arati o n, a n d dis pe nsi n g, i ncl u di n g t he 
a p plica ble l ot n u m bers; p atie nt’s hei g ht, b o d y wei g ht, a n d b o d y s urface area; date a n d ti me 
of t he start of eac h trila cicli b a n d sacit uz u ma b g o viteca n- hzi y i nf usi o n; a n d t otal dr u g 
a d mi nistere d. A n y discre pa nc y bet w ee n t he ca lc ul ate d d ose a n d d os e a d mi nistere d a n d t he 
reas o n f or t he discre pa nc y (e. g., i nterr u pti o n of i nf usi o n wit h o ut restarti n g) will be rec or de d 
o n e C R F a n d i n t he s o urce d oc u me nts. 
9. 2.  
Criteri a f or St arti n g C ycle 1 a n d E ac h S u bse q ue nt D ose  
Patie nts m ust meet all t he f oll o wi n g criteria t o recei ve st u d y tr eat me nt o n C ycle 1 Da y 1:  
 A N C ≥1. 5 × 1 0 9/ L  
 Platelet c o u nt ≥1 0 0 × 1 0 9/ L 

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 T otal bilir u bi n ≤1. 5 × U L N  
 A S T/ A L T ≤3 × U L N or ≤5 × U L N i n t he pres e nce of li ver metastasis 
 Ot her n o n he mat ol o gic dr u g- relate d t o xicities m ust be ≤ Gra d e 1 (e x ce pt al o pecia or 
peri p heral ne ur o pat h y t h at ma y b e Gra de 2 or l ess).  
Patie nts m ust als o ha ve A N C ≥1. 5 × 1 0 9/ L t o recei ve a n y C ycle Da y 1 d ose of st u d y 
treat me nt a n d A N C ≥1. 0 × 1 0 9/ L t o recei ve a n y C ycl e Da y 8 d os e of st u d y treat me nt.  
9. 3.  
T o xicit y M a n a ge me nt a n d D ose M o dific ati o ns 
T he d ose of trilacicli b will n ot be m o difie d a n d will re mai n at 2 4 0 m g/ m 2 t hr o u g h o ut t he 
st u d y. If a d mi nistrati o n of sacit uz u ma b g o viteca n- hzi y is disc o nti n ue d, trilacicli b will als o be 
disc o nti n ue d.  
T he d ose of sacit uz u ma b g o viteca n- hzi y ca n be re d uce d, w he n n ecessar y, as descri be d 
bel o w. T he rec o m me n de d d ose m o dificati o n pr oce d ures f or he mat ol o gic a n d 
n o n- he mat ol o gi c t o xicities are d escri b e d i n Ta ble 8 . If a s u bse q ue nt c ycle is dela ye d f or 
t o xicit y, t he patie nt s h o ul d still c o m plete t he cli nical la b orat or y assess me nts o n t he sc he d ule d 
Da y 1 (e ntere d as a n U ns c he d ule d ass ess me nt i n electr o nic data ca pt ur e [ E D C]) as well as o n 
t he act ual first d osi n g da y of t hat c ycle. If t he del a y is sec o n dar y t o h e mat ol o gic t o xicit y, 
wee kl y re p eat he m at ol o g y ass ess me nts s h o ul d c o nti n ue u ntil t he fi n di n g meets criteria f or 
res u m pti o n of d osi n g. 
Treat me nt wit h sacit uz u ma b g o viteca n- hzi y will be per ma n e ntl y disc o nti n ue d f or a p atie nt i n 
t he e ve nt of a n y Gra d e 4 i nf usi o n reacti o ns w hic h occ ur after pre- me di cati o n wit h 
a nti hista mi nes, H 2 bl oc kers, a n d ster oi ds. 
Rec o m me n dati o n f or ma na ge me nt of trilaci cli b A E SIs are pr o vi d e d i n Ta ble 9 . 
Rec o m me n dati o ns f or he pa t o biliar y t o xicit y ma na ge m e nt are i n Secti o n 9. 3. 3.  
F or d ose d ela ys d ue t o t o xicit y, t he patie nt s h o ul d be f oll o we d (at least) wee kl y, i ncl u di n g 
C B Cs if t he A E is he mat ol o gic, t o m o nit or t he t o xicit y u ntil treat me nt criteria are met or u ntil 
t he y disc o nti n ue tr eat me nt. A 3- wee k d ela y fr o m t he sc he d ule d d ose of sacit uz u ma b 
g o viteca n- hzi y is per mitte d f or t o xicit y a n d/ or a d mi nistrati ve reas o ns. As e x a m ples, if at t he 
sc he d ule d C ycle X Da y 1 visit (e. g., C ycle 2 Da y 1) a d ose del a y is nee de d f or t o xicit y 
reas o ns, a d ela y u p t o 3 wee ks fr o m C ycl e X Da y 1 f or sacit uz u ma b g o viteca n- hzi y is 
per mitte d; if at t he sc he d ule d C ycle X Da y 8 visit (e. g., C ycle 1 Da y 8) a d ose dela y is 
nee de d f or t o xicit y reas o ns, a dela y u p t o 3 wee ks fr o m C ycl e X Da y 1 f or sacit uz u ma b 
g o viteca n- hzi y is per mitte d. D osi n g d ela ys > 3 wee ks fr o m t he sc h e d ule d d ose of 
sacit uz u ma b g o viteca n- h zi y ma y b e per mitte d o n a case b y-case basis wit h t he d oc u me nte d 
a p pr o val of t he I n vesti gat or a n d Me dical M o nit or. 
All rec o m me n dati o ns are i nte n de d as a mi ni m u m g ui deli ne f or t o xicit y ma na ge me nt a n d are 
n ot a re place me nt f or i n d e pe n de nt  me dical j u d g m e nt tail ore d t o s pecific cir c u msta nces wit h 
a n i n di vi d ual patie nt. Please als o re fer t o t he i n di vi d ual pac ka ge i nsert (Tr o del v y Pac ka ge 
I ns ert, 2 0 2 1) f or a d diti o nal i nf or mati o n a n d rec o m me n dati o ns. 
St u d y dr u g a d mi nistrati o n will c o nti n ue u ntil pr o gressi ve diseas e per R E CI S T v 1. 1 or 
cli nical pr o gressi o n as d eter mi ne d b y t h e I n ve sti gat or, u nacce pta ble t o xicit y, wit h dra wal of 
c o nse nt, I n vesti gat or d ecisi o n, or t he e n d of t he st u d y, w hic h e ver occ urs first. 

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9. 3. 1.  
Rec o m me n de d Acti o ns wit h S acit uz u m a b G o vitec a n- hzi y f or A d verse E ve nts 
Rec o m me n de d d ose le v els f or re d ucti o n of s acit uz u ma b g o viteca n- hzi y d os e are d escri b e d 
bel o w. Sacit uz u ma b g o viteca n- hzi y d os e re d u cti o ns f or he mat ol o gic t o xicities are bas e d o n 
val ues o btai ne d wit hi n 2 4 h o urs pri or t o Da y 1 or Da y 8 of a gi v e n c ycle p er I n vesti gat or 
discreti o n a n d i nstit uti o nal g ui deli nes; rec o m me n dati o ns are pr o vi de d i n T a ble 8 . All d ose 
re d ucti o ns f or a n i n di vi d ual patie nt are p er ma n e nt; a n d t he d ose, w hic h has bee n re d u ce d f or 
t o xicit y, m ust n ot be re- escalate d. U p t o a m a xi m u m of 2 d ose re d u cti o ns will be all o we d per 
patie nt. If a t hir d d ose re d ucti o n is re q uire d pe r t he m o dificati o ns bel o w, t h e patie nt s h o ul d 
disc o nti n ue st u d y treat me nt. 
 Starti n g d ose: 1 0 m g/ k g 
 First d ose re d u cti o n: 2 5 % fr o m ori gi nal d ose 
 Sec o n d d ose re d u cti o n: 5 0 % fr o m ori gi nal d ose 
 T hir d d ose re d u cti o n: disc o nti n ue all st u d y dr u gs 
N ote t hat d ose m o dificati o ns (s pecificall y d ose re d ucti o ns/ disc o nti n uati o ns) are 
rec o m me n de d f or t h ose e ve nts c o nsi dere d relate d t o dr u g (i.e., t o xicities) s uc h t hat 
decreasi n g t he d ose or st o p pi n g t he dr u g will lea d t o i m pr o ve d patie nt safet y. If a n e v e nt is 
n ot t h o u g ht t o be relat e d t o st u d y dr u g b y t he I n v esti gat or, d ose re d ucti o n/ disc o nti n uati o n is 
n ot re q uire d si nce d ecreasi n g t he d ose or st o p pi n g t he dr u g w o ul d n ot be e x pecte d t o alter t h e 
ris k of t he e ve nt oc c urri n g a gai n; rat her, t he I n vesti gat or s h o ul d c o nsi der if treat me nt s h o ul d 
be dela ye d u ntil t he e v e nt rec o vers t o ≤Gra de 1 or ba seli ne bef ore res u m pti o n of treat me nt. 
Decrease d n e utr o p hil, platelet c o u nts or he m o gl o bi n val ues t hat occ ur i n is olati o n (e. g., at 
na dir) t hat d o n ot res ult i n a d osi n g d ela y, fe brile ne utr o pe nia, seri o us a d verse e ve nt ( S A E) or 
ot her c o nse q u e nce, d o n ot re q uire d ose m o dificati o n. 
If dr u g-relate d t o xicit y re q uires disc o nti n uati o n of sacit uz u ma b g o viteca n- h zi y or trilacicli b 
t he n t he patie nt m ust per ma ne ntl y disc o nti n ue all st u d y dr u gs a n d s h o ul d c o m plete t he 
P ost- Treat me nt Visit a n d e nter S ur vi val F oll o w- u p. 

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T a ble 8:  
Rec o m me n de d D ose M o dific ati o ns f or S acit uz u m a b G o vit ec a n- hzi y  
A d verse E ve nt 
Occ urre nce 
D ose M o dific ati o n 
Se vere Ne utr o pe ni a  
Gra de 4 ne utr o pe nia ≥7 da ys 
O R  
Gra de 3 fe brile ne utr o pe nia  ( A N C < 1 0 0 0/ m m3 a n d fe ver 
≥3 8. 5° C) 
O R  
At ti me of sc he d ule d treat me nt, Gra de 3 - 4 ne utr o pe nia 
w hic h dela ys d osi n g  b y 2 or 3 wee ks f or rec o ver y t o 
≤Gra de 1 
First 
2 5 % d ose re d ucti o n 
a n d a d mi nister 
G- C S F 
Sec o n d 
5 0 % d ose re d ucti o n 
T hir d 
Disc o nti n ue treat me nt 
At ti me of sc he d ule d treat me nt, Gra de 3- 4 ne utr o pe nia 
w hic h dela ys d osi n g be y o n d 3 wee ks f or rec o ver y t o 
≤Gra de 1 
First 
Disc o nti n ue treat me nt 
Se vere N o n- Ne utr o pe nic T o xicit y 
Gra de 4 n o n- he mat ol o gic t o xicit y of a n y d urati o n 
O R  
A n y Gra de 3 - 4 na usea, v o miti n g, or diarr hea d ue t o 
treat me nt t hat is n ot c o ntr olle d wit h a ntie metics a n d 
a nti - diarr heal a ge nts 
O R  
Gra de 3 - 4 n o n-he mat ol o gic t o xicit y persisti n g > 4 8 h o urs 
des pite o pti mal me dical ma na ge me nt  
O R  
At ti me of sc he d ule d treat me nt, Gra de 3 - 4 n o n-ne utr o pe nic 
he mat ol o gic or n o n -he mat ol o gic t o xicit y, w hic h dela ys 
d ose b y 2 or 3 wee ks f or rec o ver y t o ≤Gra de 1 
First 
2 5 % d ose re d ucti o n 
Sec o n d 
5 0 % d ose re d ucti o n 
T hir d 
Disc o nti n ue treat me nt 
I n t he e ve nt of Gra de 3- 4 n o n- ne utr o pe nic he mat ol o gic or 
n o n - he mat ol o gic t o xicit y, w hic h d oes n ot rec o ver t o 
≤Gra de 1 wit hi n 3 wee ks 
First 
Disc o nti n ue treat me nt 
A N C =a bs ol ute ne utr o p hil c o u nt; G- C S F = gra n ul oc yte c ol o n y-sti m ulati n g fact or 
S o urce: T a ble recreate d fr o m Tr o del v y Pac ka ge I nsert, 2 0 2 1  
9. 3. 2.  
Rec o m me n de d Acti o ns wit h Tril acicli b f or A d verse E ve nts of S peci al 
I nterest ( A E SI) 
S u g geste d acti o ns t o be ta ke n wit h trilacicli b f oll o wi n g A E SI are pr o vi de d i n Ta ble 9 . 

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T a ble 9:   
Rec o m me n de d Acti o ns wit h Tril acicli b F oll o wi n g A E SIs 
A E SI 
Se verit y  
Rec o m me n de d Acti o n 
I nj ecti o n site 
reacti o ns i ncl u di n g 
p hle bitis a n d 
t hr o m b o p hle bitis 
Gra de 1: T e n der ness wit h or 
wit h o ut s y m pt o ms (e. g. war mt h, 
er yt he ma, itc hi n g)  
I nterr u pt or sl o w i nf usi o n of trilacicli b. 
If 0. 9 % n or mal sali ne is bei n g use d as a 
dil ue nt/fl us h, c o nsi der c ha n gi n g t o 5 % 
de xtr ose as a p pr o priate f or s u bse q ue nt 
i nf usi o ns. 
Gra de 2: Pai n; li p o d ystr o p h y; 
e de ma; p hle bitis 
I nterr u pt i nf usi o n of trilacicli b. If pai n 
n ot se vere, f oll o w i nstr ucti o ns f or 
Gra de  1. Ot her wise, st o p i nf usi o n i n 
e xtre mit y a n d r otate site of i nf usi o n t o 
site i n alter nati ve e xtre mit y. If 0. 9 % 
n or mal sali ne is bei n g use d as a 
dil ue nt/fl us h, c o nsi der c ha n gi n g t o 5 % 
de xtr ose as a p pr o priate f or s u bse q ue nt 
i nf usi o ns. Ce ntral access ma y als o be 
c o nsi dere d. 
Gra de 3: Ulcerati o n or necr osis; 
se vere tiss ue da ma ge; o perati ve 
i nter ve nti o n i n dicate d.  
Gra de 4: Life t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o ns i n dicate d. 
St o p i nf usi o n a n d per ma ne ntl y 
disc o nti n ue trilacicli b.  
Ac ute dr u g 
h y perse nsiti vit y 
reacti o ns  
Gra de 2: M o derate; mi ni mal, 
l ocal or n o ni n vasi ve i nter ve nti o n 
i n dicate d; li miti n g A D L 
St o p i nf usi o n a n d h ol d trilacicli b u ntil 
rec o ver y t o Gra de ≤1 or baseli ne, t he n 
c o nsi der res u mi n g trilacicli b. If Gra de 2 
rec urs, per ma ne ntl y disc o nti n ue 
trilacicli b. 
Gra de 3: Se vere or me dicall y 
si g nifica nt b ut 
n ot i m me diatel y life -t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of 
h os pitalizati o n i n dicate d; 
disa bli n g; li miti n g self -care A D L 
O R  
Gra de 4: Life -t hreate ni n g 
c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d 
Per ma ne n tl y disc o nti n ue trilacicli b. 
I L D/ p ne u m o nitis 
Gra de 2 (s y m pt o matic)  
H ol d trilacicli b u ntil rec o ver y t o 
Gra de  ≤1 or baseli ne, t he n c o nsi der 
res u mi n g trilacicli b. 
If Gra de 2 rec urs, per ma ne ntl y 
disc o nti n ue trilacicli b.  

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A E SI 
Se verit y  
Rec o m me n de d Acti o n 
Gra des 3: Se vere s y m pt o ms; 
li miti n g self-care A D L; o x y ge n 
i n dicate d  
O R  
Gra de 4: Life -t hreate ni n g 
res pirat or y c o m pr o mise; ur ge nt 
i nter ve nti o n i n dicate d (e. g., 
trac he ot o m y or i nt u bati o n) 
Per ma ne ntl y disc o nti n ue trilacicli b.  
A E SI =a d verse e ve nt of s pecial i nterest; A D L =acti vities of dail y li vi n g; I L D =i nterstitial l u n g disease 
9. 3. 3.  
H y’s L a w  M a n a ge me nt 
A b n or mal val ues i n A S T a n d/ or A L T c o n c urre nt wit h a b n or mal ele vati o ns i n t otal bilir u bi n 
t hat meet t he criteri a o utli ne d bel o w i n t he a bse n ce of ot her ca uses of li ver i nj ur y are 
c o nsi dere d p ote ntial cases of dr u g-i n d uce d li ver i nj ur y ( p ot e ntial H y’s La w cases) a n d s h o ul d 
al wa ys be c o nsi d ere d i m p orta nt me dical e ve nts.  
T he t hres h ol d of la b orat or y a b n or malities f or a p ote ntial case of dr u g-i n d uce d li ver i nj ur y 
de pe n ds o n t he patie nt’s i n di vi d ual baseli ne val ues  a n d u n derl yi n g c o n diti o ns. Patie nts w h o 
prese nt wit h t he f oll o wi n g la b orat or y a b n or malit ies s h o ul d be e val uate d f urt her t o deter mi ne 
t he eti ol o g y of t he a b n or mal la b orat or y val u es: 
 Baseli ne A S T or A L T a n d t otal bilir u bi n val ues are wit hi n t he n or mal ra n ge a n d 
t he patie nt s u bse q ue ntl y prese nts wit h A S T or A L T ≥3 × U L N c o n c urre nt wit h a 
t otal bilir u bi n ≥2 × U L N wit h n o e vi de nce of he m ol ysis a n d a n al kali ne 
p h os p hatase ≤2 × U L N or n ot a v aila ble. 
 Pree xisti n g A L T O R A S T O R t otal bilir u bi n val ues a b o ve t he u p per li mit of 
n or mal, a n d t he patie nt s u bse q ue ntl y prese nts wit h:  
- 
A S T or A L T ≥2 ti mes t he baseli ne val u es a n d ≥3 × U L N, or ≥8 × U L N 
( w hic he ver is s maller)  
- 
C o nc urre nt wit h t otal bilir u bi n i ncreas e d  b y o ne ti me t he baseli ne val u e O R 
≥3 × U L N ( w hi c he ver is s maller).  
T he patie nt s h o ul d ret ur n t o t he i n vesti gati o nal site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware n ess of t he a b n or mal res ults. T his e v al uati o n s h o ul d 
i ncl u de la b orat or y t ests, detaile d hist or y, a n d p h ysical assess me nt. I n a d diti o n t o re peati n g 
A S T a n d A L T, la b orat or y tests s h o ul d i ncl u de al b u mi n, creati ne ki nas e, t otal bilir u bi n, direct 
a n d i n direct bilir u bi n, ga m ma- gl uta m yl tr a nsferas e, pr ot hr o m bi n ti me/I nter nati o nal 
N or maliz e d Rati o (I N R), a n d al kali ne p h os p hatas e. A detaile d hist or y, i ncl u di n g rel e va nt 
i nf or mati o n, s uc h as re vi e w of et ha n ol, acet a mi n o p he n, recreati o nal dr u g a n d s u p ple me nt 
c o ns u m pti o n, fa mil y hist or y, o cc u pati o nal e x p os ure , se x ual hist or y, tra v el hist or y, hist or y of 
c o ntact wit h a ja u n dice d patie nt, s ur ger y, bl o o d tra nsf usi o n, hist or y of li ver or aller gic 
disease, a n d w or k e x p os ure, s h o ul d be c ollecte d. F urt her testi n g f or ac ute he patitis A, B, or C 
i nfecti o n a n d li ver i ma gi n g (e. g., biliar y tract) ma y be warra nte d.  

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All cases c o nfir me d o n re peat testi n g as me et i n g t he la b orat or y criteria d efi ne d a b o ve, wit h 
n o ot her ca us e f or li ver f u ncti o n test ( L F T) a b n or malities i de ntifie d at t he ti me s h o ul d be 
c o nsi dere d p ote ntial H y’s La w cas es irres p ecti ve of a vaila bilit y of all t he res ults of t he 
i n vesti gati o ns perf or me d t o deter mi ne eti ol o g y of t he a b n or mal L F Ts. S uc h p ote ntial H y’s 
La w cas es s h o ul d be pr o m ptl y re p ort e d as S A Es via t he E D C. 
9. 4.  
S u p p orti ve C are I nter ve nti o ns 
9. 4. 1.  
C ol o n y Sti m ul ati n g F act or Us a ge 
Use of pr o p h yla ctic c ol o n y sti m ulati n g fact ors ( e. g., G- C S F; gra n ul oc yte- macr o p ha ge 
c ol o n y-sti m ulati n g fact or [ G M- C S F]) d uri n g C ycl e 1 (i.e., pri or t o t he act u al C ycle 2 Da y 1 
d osi n g visit) is n ot all o we d. I n s u bse q ue nt c ycles ( C ycl e 2 a n d be y o n d), pr o p h ylactic 
c ol o n y-sti m ulati n g fact ors are all o we d as o utli ne d i n Ta ble 8 , w hic h are bas e d o n t he A S C O 
g ui deli nes f or ne utr o p e nia ( S mit h, 2 0 1 5 ) a n d pac k a ge i nserts. If i n a n y c ycl e (i ncl u di n g 
C ycle 1), a patie nt e x perie nces se v ere n e utr o pe ni a ( Gra d e 4) or fe brile n e utr o pe nia a n d is at 
hi g h ris k f or i nfecti o n- ass ociate d c o m plicati o ns, or has pr o g n ostic fact ors t hat are pre dicti ve 
of p o or cli nical o utc o mes ( Ta ble 1 0 ), G- C S F/ G M- C S F ma y b e use d t o treat t he se vere 
ne utr o pe nia or fe brile n e utr o pe nia e ve nt p er A S C O g ui deli nes a n d pac k a ge i nserts.  
S h ort-acti n g G- C S F pr o d ucts (i.e., Ne u p o ge n or bi osi milars) ma y b e a d mi nistere d starti n g 
2 4 t o 4 8 h o urs after s acit uz u ma b g o viteca n- hzi y a n d m ust be st o p pe d 4 8 h o urs pri or t o st u d y 
dr u g a d mi nistrati o n i n t he ne xt c ycl e. Si milarl y, Ne ulasta ( or bi osi milars) or ot her l o n g 
half-life G- C S F pr o d ucts (e. g., maca pe gfil grasti m) ma y b e a d mi nistere d 2 4 t o 4 8 h o urs after 
sacit uz u ma b g o viteca n- h zi y b ut d ue t o its pr ol o n ge d half-life s h o ul d n ot be re peat e d wit hi n 
t hat c ycle. 
T a ble 1 0:   
P ati e nt Ris k F a ct ors f or P o o r Cli nic al O utc o mes Res ulti n g fr o m Fe brile 
Ne utr o pe ni a or I nf ecti o n 
Ris k F act or 
Se psis s y n dr o me 
A ge > 6 5 years 
Pr of o u n d ne utr o pe nia (a bs ol ute ne utr o p hil c o u nt < 0. 1 × 1 0 9/ L) 
Ne utr o pe nia e x pecte d t o last > 1 0 da ys 
P ne u m o nia 
I n v asi ve f u n gal i nfecti o n 
Ot her cli nicall y d oc u me nte d i nfecti o ns 
H os pitalizati o n at ti me of fe ver 
Pri or e pis o de of fe brile n e utr o pe nia 
A S C O = A meric a n S ociet y of Cli nical O nc ol o g y  
S o urce: Ta ble recreate d fr o m Ta ble 2 of t h e A S C O g ui d eli nes ( S mit h, 2 0 1 5 ; S mit h, 2 0 0 6). 
9. 4. 2.  
Er yt hr o p oiesis- Sti m ul ati n g A ge nt Us a ge 
If a patie nt e x perie nces c he m ot hera p y-i n d u ce d a n e mia ( he m o gl o bi n le vel < 1 0 g/ d L) after 
recei vi n g t he first d ose of st u d y treat me nt, E S As ma y b e use d per A S C O g ui deli nes a n d t he 
c urre nt pr escri bi n g i nf or mati o n ( B o hli us, 2 0 1 9 ) (Pr ocrit ® , 2 0 1 7; Ara nes p ® , 2 0 1 1 ). 

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9. 4. 3.  
Tr a nsf usi o ns 
Re d Bl o o d Cells 
Base d o n t h e N C C N Cli nical Practice G ui deli nes i n O nc ol o g y f or He mat o p oietic Gr o wt h 
Fact ors Versi o n 2. 2 0 2 0 a n d t he A A B B Cli nical Practice G ui d eli nes, t he f oll o wi n g R B C 
tra nsf usi o n t hres h ol ds are rec o m me n d e d (Cars o n, 2 0 1 6 ; G oel, 2 0 1 8); h o we ver, t he p atie nt’s 
cli nical sit uati o n s h o ul d al wa ys be t he pri mar y g ui di n g fact or w he n d eci di n g t o tra nsf use. 
 Tra nsf usi o n is n ot i n dicate d u ntil t he he m o gl o bi n le vel is ≤7 g/ d L f or h os pitalize d 
a d ult patie nts w h o are h e m o d y na micall y sta ble. 
 A n R B C tra nsf usi o n t hres h ol d of ≤8 g/ d L is rec o m me n de d f or patie nts 
u n der g oi n g ort h o pe dic s ur ger y, car diac s ur ger y, a n d t h ose wit h pree xisti n g 
car di o vas c ular dise ase.  
 Patie nts wit h s y m pt o mati c a ne mia s h o ul d be tr a nsf use d per t he I n vesti gat or 
discreti o n re gar dless of h e m o gl o bi n le vels. 
Pl atelets 
Platelet tra nsf usi o n is rec o m me n de d at a t hres h ol d of ≤1 0 x 1 0 9/ L. Platel ets s h o ul d als o be 
tra nsf use d i n a n y p atie nt w h o is blee di n g wit h a platelet c o u nt < 5 0 x 1 09/ L ( 1 0 0 x 1 09/ L f or 
ce ntral ner v o us s yste m or oc ular blee di n g) ( Ka uf ma n, 2 0 1 5 ; Sc hiffer, 2 0 0 1). 
9. 5.  
Pri or/ C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures 
All pri or a n d c o nc o mita nt me dicati o ns i ncl u di n g prescri pti o n me dicati o ns, o ver-t he-c o u nter 
pre parati o ns, s u p ple me nts, her bal re m e dies , gr o wt h fact ors, a n d bl o o d pr o d ucts fr o m 
i nf or me d c o nse nt t hr o u g h 3 0 da ys after t he last d ose of st u d y tr eat me nt ( S afet y F oll o w- u p 
Visit) will be d oc u me nte d, w here p ossi ble. 
A v oi d c o nc o mit a nt use of tril acicli b wit h cert ai n O C T 2, M A T E 1, a n d M A T E- 2 K 
s u bstr ates (e. g., d ofetili de, d alf a m pri di ne) w here mi ni mal c o nce ntrati o n c ha n ges ma y lea d 
t o seri o us or life-t hreate ni n g t o xicities. Refer t o t he prescri bi n g i nf or mati o n f or t hese 
c o nc o mita nt me dicati o ns f or assessi n g t he be n ef it a n d ris k of c o n c o mita nt use of trilacicli b. 
A v oi d a d mi nisteri n g U G T 1 A 1 i n hi bit ors wit h s acit uz u m a b g o vitec a n- hzi y . C o nc o mita nt 
a d mi nistrati o n of sacit uz u ma b g o viteca n- hzi y wit h i n hi bit ors of U G T 1 A 1 ma y i ncreas e t he 
i nci de nce of a d verse reacti o ns d ue t o p ote ntial i ncrease i n s yste mic e x p os ure t o S N- 3 8.  
A v oi d a d mi nisteri n g U G T 1 A 1 i n d ucers wit h  s acit uz u m a b g o vit ec a n- hzi y. E x p os ure t o 
S N- 3 8 ma y b e s u bsta ntiall y re d u ce d i n patie nts c o nc o mita ntl y recei vi n g U G T 1 A 1 e nz y m e 
i n d ucers.   
A d mi nistrati o n of ot her c o nc o mita nt i n vesti gat i o n al a ge nts f or a n y i n dicati o n or a n y li ve 
atte n uate d vacci nes is n ot per mitte d w hile o n t his st u d y. Necessar y s u p p orti ve care 
(a ntie metics, a nti diarr heals, c he m ot hera p y pre me dicati o n, etc.) per t he sta n dar d of care at t he 
st u d y ce nt er will be per mitte d. See Secti o n 9. 4 f or g ui da nce o n t he use of gr o wt h fact ors 
(c ol o n y-sti m ulati n g fact ors a n d E S As) d uri n g t he st u d y. 
A d mi nistrati o n of ot her s yste mic c o n c o mita nt n o n- pr ot oc ol a ntica n cer t h era pies pri or t o 
pr o gressi o n is n ot per mitte d w hile o n t his st u d y. Palliati ve treat me nt of a s y m pt o matic 

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lesi o n(s) is per mitte d t o c o ntr ol disease s y m pt o ms b ut n ot t o ai d i n t he res p o nse of t he t u m or. 
If t he lesi o n(s) treate d is bei n g f oll o w e d f or e val u ati o n b y R E CI S T v 1. 1 (t ar get or n o ntar get 
lesi o n), t he n “ n ot e val u a ble” s h o ul d be re p orte d i n E D C f or t his lesi o n at s u bse q ue nt disease 
assess me nts f oll o wi n g p alliati ve treat me nt. Patie n ts re q uiri n g palliati ve t hera p y m a y c o nti n ue 
recei vi n g st u d y dr u g u ntil d oc u me nte d disease pr o gressi o n (ra di o gra p hic or cli nical) if, i n t he 
I n v esti gat or’s o pi ni o n, t he patie nt is c o nti n ui n g t o recei v e cli nical be nefit a n d t he y meet t he 
re q uire me nts des cri be d i n Secti o n 9. 2. H o we ver, f or patie nts w h o ha v e n ot ha d disease 
pr o gressi o n at t he ti me of t he nee d f or palliati ve ra diati o n t hera p y or s ur ger y, t he re q uire m e nt 
f or i nter ve nti o n will be re gar de d as disease pr o gressi o n i n t he st u d y’s a n al ys es a n d will be 
e ntere d as s uc h i n t he E D C.  
A n y dia g n ostic, t hera p e utic, or s ur gical pr o ce d ures perf or me d d uri n g t he st u d y peri o d will be 
d oc u me nte d. D oc u m e ntati o n will i ncl u de i nf or mati o n re gar di n g t he dat e(s), i n dicati o n(s), 
descri pti o n of t he pr oce d ure(s), a n d a n y cli nical or pat h ol o gical fi n di n gs, if a vaila ble.  
9. 6.  
Me as ures t o Mi ni mize Bi as 
T he st u d y will be si n gle- ar m a n d o pe n-la bel.  
Patie nts t hat are e nr olle d, recei v e d at least o ne d ose of st u d y dr u g, a n d disc o nti n ue fr o m t he 
st u d y will n ot be re pla ce d. Patie nts t hat are e nr oll e d b ut di d n ot recei ve a n y st u d y dr u g ma y 
be re pla ce d u p o n a p pr o val of t he Me dical M o nit or a n d S p o ns or. 
9. 7.  
I nter ve nti o n after E n d of St u d y Tre at me nt 
F oll o wi n g c o m pleti o n of st u d y treat me nt o n t he st u d y, patie nts will recei ve treat me nt as 
deter mi ne d b y t heir h ealt hcare pr o vi der. D uri n g  S ur vi val F oll o w- u p, t he p atie nt ( or le gall y 
a ut h orize d re pres e ntati ve w here all o we d b y l ocal re g ul ati o n) will be c o ntact e d t o rec or d t heir 
stat us (ali ve or dea d) as well as details of a n y s u bse q ue nt s yst e mic a nti-ca ncer t hera p y 
i nitiate d (see Secti o n 1 1. 7 ). 

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1 0.  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D 
P A TI E N T DI S C O N TI N U A TI O N/ WI T H D R A W A L  
1 0. 1.  
Disc o nti n u ati o n of St u d y Tre at me nt 
St u d y dr u gs will be disc o nti n ue d if a n y of t he f oll o wi n g e v e nts occ ur d uri n g t he st u d y: 
 A patie nt s uffers a n A E t hat, i n t he j u d g me nt of t h e I n vesti gat or, S p o ns or, or 
Me dical M o nit or, prese nts a n u nacce pta ble ris k t o t he patie nt 
 Ge neral or s pecific c h a n ges i n t he p atie nt’s c o n diti o n (e . g., a si g nifi ca nt 
i nterc urre nt ill ness or c o m plicati o n) t hat, i n t he j u d g me nt of t he I n vesti gat or, are 
u nacce pta ble f or f urt her a d mi nistrati o n of st u d y dr u g 
 Occ urre nce of pre g na n c y i n a fe male p atie nt d uri n g t he st u d y 
 Si g nifica nt n o nc o m plia n ce wit h pr ot oc ol r e q uire me nts 
 T he S p o ns or or le gal r e prese ntati ve of t he S p o ns or re q uests t he patie nt t o 
wit h dra w 
 Patie nt has d oc u me nte d disease pr o gressi o n (ra di o gra p hic or cli nical pr o gressi o n). 
See Secti o n 9. 5  f or det ails re gar di n g palliati ve t hera p y. 
 If t he t otal ti me fr o m a sc he d ule d sacit uz u ma b g o viteca n- hzi y d os e e x cee ds a t otal 
of > 3 wee ks, u nless a gree d t o b y t he treati n g I n v esti gat or a n d M e dical M o nit or. 
 W here per ma n e nt disc o nti n uati o n of a n y st u d y dr u g is i n dicate d i n t he t o xicit y 
ma na ge me nt rec o m me n d ati o ns ( Secti o n 9. 3 ).  
At t he ti me of st u d y dr u g disc o nti n uati o n, a n E n d of Treat me nt Visit s h o ul d be c o m plete d 
wit h assess me nts perf or me d as s h o w n i n t he Sc h e d ule of Assess me nts ( T a ble 6 ). T he 
I n v esti gat or or D esi g n ee will d oc u me nt t he reas o n f or st u d y dr u g disc o nti n uati o n o n t he 
a p plica ble e C R F. W he n disc o nti n uati o n is d ue t o a S A E or a Gra de 3 or 4 t o xicit y c o nsi dere d 
t o be relate d t o st u d y dr u g, t he I n v esti gat or s h o ul d f oll o w t he e ve nt u ntil res ol uti o n, ret ur n t o 
baseli ne, or it is dee me d t hat f urt her rec o v er y is u nli kel y. Dat a o n t hese e v e nts s h o ul d be 
c ollecte d o n t he A E e C R F. I n t he e ve nt a patie nt disc o nti n ues d ue t o pre g na nc y, t h e 
I n v esti gat or or desi g nee s h o ul d n otif y t he Medical M o nit or b y tele p h o ne wit hi n 2 4 h o urs of 
pre g na nc y c o nfir mati o n (see Secti o n 1 7. 3 ). 
F or t h ose patie nts w h o h a ve n ot pr o gresse d cli nicall y or ra di ol o gicall y at t he ti me of st u d y 
dr u g disc o nti n uati o n, e v er y eff ort s h o ul d be ma de t o c o nti n ue ra di ol o gi cal t u m or assess me nts 
e ver y 1 2 w ee ks ( ± 7 d a ys) d uri n g s ur vi val f oll o w- u p, utilizi n g t he sa me i m a gi n g m o dalit y as 
use d at Scree ni n g as o utli ne d i n t he Sc he d ule of Assess me nts ( Ta ble 6 ), u ntil pr o gressi ve 
disease, i nitiati o n of s u bse q ue nt a nti-ca ncer t hera p y, wit h dr a wal of c o nse nt, or st u d y 
c o m pleti o n, w hic he ver occ urs first. Res u lts of t hese sca ns s h o ul d be ass esse d b y 
R E CI S T v 1. 1 a n d data e ntere d i n E D C i n t h e c orres p o n di n g t u m or ass ess me nt f or ms. 
1 0. 2.  
Disc o nti n u ati o n/ Wit h dr a w al fr o m t he St u d y 
A patie nt ma y wit h dra w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest or ma y b e 
wit h dra w n at a n y ti me at t he discreti o n of t he I n v esti gat or f or safet y, b e ha vi oral, c o m plia nce, 

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or a d mi nistrati ve reas o ns. At t he ti me of disc o nti n ui n g fr o m t he st u d y, if t h e patie nt has n ot 
alrea d y disc o nti n ue d st u d y i nter ve nti o n, a n E n d of  Treat me nt Visit s h o ul d be c o m plete d wit h 
assess me nts perf or me d as s h o w n i n t he Sc he d ule of Assess me nts ( Ta ble 6 ).  
If t he patie nt wit h dra ws c o nse nt f or discl os ure of f ut ure i nf or mati o n, t he S p o ns or ma y retai n 
a n d c o nti n ue t o use a n y d ata c ollecte d bef ore s uc h a wit h dra wal of c o nse nt. 
If a patie nt wit h dr a ws fr o m t he st u d y, he/s he ma y re q uest destr u cti o n of a n y sa m ples ta k e n 
a n d n ot teste d, a n d t he I n vesti gat or or desi g nee m ust d oc u me nt t his i n t he site st u d y rec or ds. 
If a patie nt wit h dra ws c o nse nt f or f urt h er st u d y pr oce d ures, t h e site s h o ul d clarif y if t he 
patie nt ( or le gall y a ut h ori ze d re prese nt ati ve w here all o we d b y l ocal r e g ulati o n) re mai ns o pe n 
t o s ur vi val c o ntact a n d ass ociate d data c ollecti o n. P u blic rec or ds ma y be us e d t o verif y 
s ur vi val stat us if per mitte d b y i nstit uti o nal or c o u ntr y g ui deli nes. 
1 0. 3.  
L ost t o F oll o w U p 
A patie nt will be c o nsi dere d l ost t o f oll o w- u p if he or s he re peat e dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site. 
I n ge neral, a patie nt is c o nsi dere d l ost t o f oll o w- u p after t here are at least 3 d oc u me nte d 
atte m pts t o c o ntact t he patie nt. It is rec o m m e n de d t hat 1 atte m pt is via certifie d letter t o t he 
patie nt. 
1 0. 4.  
St u d y a n d Site St art a n d Cl os ure 
T he o verall st u d y be gi ns w he n t he first patie nt si g ns t he i nf or me d c o nse nt f or m. T he o verall 
st u d y e n ds w h e n t he last patie nt c o m pletes t he last st u d y-relate d p h o ne-call or visit, 
disc o nti n ues fr o m t he trial or is l ost t o f oll o w- u p (i.e., t he patie nt is u na ble t o be c o ntacte d b y 
t he I n v esti gat or).   
A st u d y site is c o nsi dere d eli gi ble t o start partici pati o n i n t he st u d y o nce all re g ul at or y 
a p pr o vals are i n place, site a gree me nt c o ntr act is f ull y e x ec ute d, a n d a n y ot her re q uir e d 
d oc u me nts are i n place as re q uire d b y S p o ns or.  
T he e n d of st u d y is e ve nt dri ve n. T hat is, u nless ot her wise deci de d b y t he S p o ns or, t he st u d y 
will c o nti n ue u ntil a p pr o xi matel y 7 0 % of patie nts e nr olle d i n t he st u d y h a v e die d, w hic h is 
esti mate d t o be a p pr o xi matel y 3 0 m o nt hs after t he first patie nt is e nr olle d.  
T he S p o ns or reser ves t he ri g ht t o cl ose a st u d y site(s) or ter mi nate t h e st u d y at a n y ti me f or 
a n y reas o n. St u d y sites will be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is c o nsi dere d 
cl ose d w he n all re q uire d d oc u me nts a n d st u d y s u p plies ha ve bee n c ollecte d, a st u d y-site 
cl os ure visit has bee n p erf or me d, a n d t he site h as cl ose d all re g ulat or y acti vities wit h t he 
I nstit uti o nal Re vie w B oar d (I R B)/In de p e n de nt Et hics C o m mittee (I E C). 
T he I n vesti gat or ma y b e re q ueste d t o i nitiate st u d y-site cl os ure at a n y ti me, pr o vi de d t here is 
reas o na bl e ca us e a n d s ufficie nt n otice is gi ven i n a d va nce of t he i nte n de d t er mi nati o n. 
S h o ul d t his occ ur wit h patie nts recei vi n g st u d y dr u g, t he patie nts will tra nsiti o n t o recei ve 
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Reas o ns f or t he earl y cl os ure of a st u d y site b y t he S p o ns or or I n v esti gat or ma y i ncl u d e b ut 
are n ot li mite d t o: 
 Fail ure of t he I n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uir e me nts of t he 
I R B/I E C or l ocal h ealt h a ut h orities, t he S p o ns or's pr oce d ures, or G o o d Cli nical 
Practice ( G C P) g ui deli nes 
 I n a de q uat e recr uit me nt of patie nts b y t h e I n vesti gat or 
 Disc o nti n uati o n of f urt her de vel o p me nt of trilacicli b 
If t he st u d y is pre mat urel y ter mi nat e d or s us pe n d e d, t he S p o ns or s hall pr o m ptl y i nf or m t he 
I n v esti gat ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y c o ntr act r esearc h 
or ga niz ati o n(s) use d i n t he st u d y of t h e reas o n f or t er mi nati o n or s us pe nsi o n, as s pecifie d b y 
t he a p plica ble re g ulat or y re q uire me nts. T h e I n vesti gat or s h all pr o m ptl y i nf or m t he patie nt 
a n d s h o ul d ass ure a p pr o priate patie nt t hera p y a n d/ or f oll o w- u p. 

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1 1.  
S T U D Y A S S E S S M E N T S  
St u d y pr oce d ures a n d t heir ti mi n g are s u m m arize d i n t he Sc he d ule of Assess me nts ( Ta ble 6 ). 
A d here n ce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he Sc he d ule of 
Assess me nts, is esse ntial a n d re q uir e d f or st u d y c o n d uct. I m me di ate safet y c o ncer ns s h o ul d 
be disc usse d wit h t he st u d y Me dic al M o nit or u p o n occ urre nce or a ware ness t o deter mi ne if 
t he patie nt s h o ul d c o nti n ue or disc o nti n ue st u d y i nter ve nti o n. 
T he I n vesti gat or or Desi g nee will mai ntai n a scree ni n g l o g t o rec or d details of all patie nts 
scree n e d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or scree ni n g fail ure, as a p plica ble.  
Pr oce d ures c o n d ucte d as part of t he patie nt’s r o uti ne cli nical ma na ge me nt (e . g., h e mat ol o g y, 
c he mistr y) a n d o btai ne d bef ore si g ni n g of t he i nf or me d c o nse nt f or m (I C F) ma y b e utilize d 
f or scree ni n g or baseli ne p ur p oses pr o vi de d t he proce d ures m et t he pr ot oc ol-s pecifie d criteria 
a n d are p erf or me d wit hi n t he per mitte d 3 0- da y Scree ni n g peri o d.  
1 1. 1.  
Scree ni n g Assess me nts 
T he f oll o wi n g i nf or mati o n f or scree ni n g fail ures s h o ul d be rec or de d i nt o a p pr o priate e C R Fs: 
patie nt i de ntificati o n (I D), de m o gra p hic data, i ncl usi o n/e x cl usi o n criteria, eli gi bilit y stat us, 
a n d S A Es (if a n y). Patie nts ma y o nl y be re scree n e d o ne ti me at t he discreti o n of t he 
I n v esti gat or. F or a b n or m al la b orat or y v al ues, a sec o n d test t o c o nfir m t he first is per mitte d.   
1 1. 1. 1.  
E R-, Pr o gest er o ne R ece pt or-, H E R 2- Ne g ati ve St at us 
Eli gi bilit y will be base d o n l ocal E R- ne gati ve, pr o gester o ne rece pt or- ne gati ve, 
H E R 2- ne gati ve stat us fr o m t he m ost rece nt t u m or bi o ps y re p ort o btai ne d pri or t o Scree ni n g.  
Estr o ge n rece pt or/ pr o gester o ne rece pt or n e gati ve stat us s h o ul d be hist ol o gicall y or 
c yt ol o gic all y c o nfir me d b y l oc al pat h ol o g y I H C assess me nt ( defi ne d as < 1 % n uclei stai ni n g) 
a n d H E R 2 n o n- o vere x pressi n g stat us s h o ul d be c o nfir me d b y l ocal ass ess me nt of I H C ( 0 or 
1 +), b y i n sit u h y bri dizati o n (rati o < 2. 0), or b y a vera ge H E R 2 ge ne c o p y n u m ber of < 4 
si g nals/ n ucle us) p er 2 0 1 8 A S C O C A P criteria. 
1 1. 1. 2.  
E nr oll me nt 
Eli gi bilit y will be deter mi ne d pri or t o e nr oll me nt a n d t he start of st u d y tr eat me nt. All eli gi ble 
patie nts will recei ve a u ni q ue patie nt I D n u m ber. O nce a p atie nt I D is assi g ne d t o p atie nt, it 
ca n ne v er be reassi g ne d t o a n ot her patie nt.  
Eli gi ble patie nts will be i nstr ucte d o n all pr ot oc ol re q uire me nts, i ncl u di n g a n y restricti o ns o n 
c o nc o mita nt me dicati o n usa ge.  
E nr oll me nt will be perf or me d via I nteracti ve We b Res p o nse S yste m f oll o wi n g c o nfir mati o n 
t hat t he patie nt is eli gi ble f or t he st u d y. 
1 1. 1. 3.  
De m o gr a p hics  
A ge, ge n der, race, a n d et h nicit y will b e c ollect e d d uri n g t he Scree ni n g p eri o d. 

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1 1. 1. 4.  
Me dic al Hist or y a n d Bre ast C a ncer Dise ase Hist or y 
Me dical a n d s ur gic al hist or y, i ncl u di n g past a n d c urre nt c o n diti o ns, will be c ollecte d. 
C o nc o mita nt me dicati o ns ta ke n wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g t hr o u g h 
t he E n d of Treat me nt Visit will be rec or de d.  
D oc u me ntati o n of T N B C hist or y, i ncl u di n g date of dia g n osis as well as B R C A classificati o n 
(if a vaila ble), will be c oll ecte d.  
Pri or ra diati o n, s ur ger y, a n d s yste mic c he m ot hera p y f or T N B C will als o be rec or de d.  
1 1. 2.  
Effic ac y Assess me nts 
1 1. 2. 1.  
A nti-t u m o r Effic ac y Assess me nt 
All sites of meas ura ble a n d n o n- meas ura ble di sease m ust be d oc u me nte d at Scree ni n g a n d 
re-ass esse d at e ac h s u bse q ue nt t u m or e val uatio n. T u m or assess me nt will be perf or me d at t he 
ti me p oi nts relati ve t o C ycle 1 Da y 1, as s pecifie d i n t he Sc he d ule of Assess me nts (Ta ble 6 ), 
re gar dl ess of dr u g (c ycle) dela ys, s ki ps, or i nterr u pti o ns. T u m or assess me nts will c o nti n ue 
u ntil disease pr o gressi o n, wit h dra wal of c o nse nt, i nitiati o n of s u bse q ue nt a nti-ca ncer t hera p y, 
or st u d y c o m pleti o n, w hi c he ver occ urs first.  
Baseli ne i ma gi n g m ust i ncl u de C T or ma g net ic res o na nce i ma gi n g ( M RI) of t he c hest, 
a b d o me n, a n d pel vis. C T sca ns wit h I V c o ntr ast are t he preferre d met h o d u nless 
c o ntrai n dicate d (i.e., pati e nts wit h c o ntrast  aller g y or i m paire d re n al cleara nce) a n d oral 
c o ntrast ma y be use d p er I n v esti gat or’s discreti o n. M RIs of t he c hest, a b d o me n, a n d pel vis 
wit h a n o nc o ntrast C T sca n of t he c h est ma y be us e d i n patie nts f or w h o m C T sca ns wit h 
c o ntrast are c o ntr ai n dicat e d. B o ne s ca n or p os itr o n e missi o n t o m o gra p h y ( P E T) sca n (s uc h as 
[1 8F]-fl u or o de o x y gl uc os e [ F D G]- P E T, s o di u m fl u ori de [ Na F]- P E T, or ot her l ocall y a vaila ble 
P E T o pti o ns) m ust als o be perf or me d i n all patie nts t o e val uate f or b o n e metastases at 
baseli ne. At t he I n v esti gat or’s discreti o n, ot her met h o ds of assess me nt of  m eas ura bl e disease 
per R E CI S T v 1. 1 ma y b e use d. A n y C T, M RI, or b o ne i ma gi n g ( b o ne sca n or P E T sca n) 
o btai ne d as sta n dar d of care pri or t o Scree ni n g vi sit will n ot nee d t o be re peate d as l o n g as 
t h ose i ma gi n g tests were o btai ne d wit hi n 3 0 da ys pri or t o t he date of e nr oll me nt. 
After bas eli ne t u m or assess me nts, e val uati o n of t u m or res p o nse per R E CI S T v 1. 1 will be 
perf or me d e ver y 6 wee ks f or t he first 3 6 wee ks f oll o wi n g C ycle 1 Da y 1 ( ± 7 da ys) a n d e v er y 
9 wee ks t hereaft er ( ± 7 d a ys), wit h a d diti o nal sca ns perf or me d as cli nicall y i n dicate d.  
P ost- baseli ne t u m or assess me nts s h o ul d use t he sa me i ma gi n g m o dalit y ( C T or M RI) as at 
baseli ne. Patie nts wit h b o ne metastases i de ntifie d o n t he baseli ne b o ne s ca n or P E T sca n 
s h o ul d be f oll o we d at sc h e d ule d visits usi n g l ocali ze d C T or M RI as cli nicall y i n dicate d. If 
t he patie nt has b o ne metastases o n t he baseli ne b o ne sca n or P E T s ca n b ut are n ot vis ualize d 
o n C T or M RI, t he s a me b o ne i ma gi n g m o dalit y ( b o ne sca n or P E T s ca n) s h o ul d be re peate d 
w he n a c o m plet e res p o ns e is i de ntifie d i n tar get disease or w he n pr o gressi o n i n b o ne is 
s us pecte d (T a ble 6 ). 
T u m or res p o nse criteria will be base d o n R E CI S T v 1. 1 ( Eise n ha uer, 2 0 0 9 ) as cite d i n 
Secti o n 1 7. 4 . A partial or c o m plete res p o nse s h o ul d be c o nfir me d b y a re p eat sca n n ot less 
t ha n 4 wee ks fr o m t he date t he res p o nse was first d oc u me nte d per R E CI S T v 1. 1.  

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F or t h ose patie nts w h o h a ve n ot pr o gresse d cli nicall y or ra di ol o gicall y at t he ti me of st u d y 
dr u g disc o nti n uati o n, e v er y eff ort s h o ul d be ma de t o c o nti n ue ra di ol o gi cal t u m or 
assess me nts, utilizi n g t he sa me i ma gi n g m o dalit y as use d at Scree ni n g. 
1 1. 2. 2.  
M yel o pr otecti o n Assess me nts 
T he m yel o pr otecti ve effects of trilacicli b w h e n a d mi nistere d pri or t o sacit u z u ma b 
g o viteca n- hzi y will be e v al uate d base d o n t h e f oll o wi n g: occ urre nce of S N; he mat ol o gic 
t o xicities, i ncl u di n g fe brile ne utr o pe nia; R B C a n d platelet tra nsf usi o ns; he mat o p oietic 
gr o wt h fact or utilizati o n; i nfecti o ns a n d s y ste mic a nti bi otic use; d ose re d ucti o ns/ dela ys. All 
of t hese vari a bles will be assesse d as d escri be d i n t he safet y ass ess me nts ( m o nit ori n g of A Es, 
cli nical la b orat or y assess me nts, a n d c o nc o mita nt me dicati o ns).  
1 1. 3.  
S afet y Assess me nts  
U nless s pecifie d ot her wise, safet y ass ess me n ts s h o ul d be c o n d ucte d pri or t o st u d y dr u g 
a d mi nistrati o n. 
1 1. 3. 1.  
Vit al Si g ns 
T he f oll o wi n g will be c ollecte d per t h e Sc he d ule of Assess me nts ( Ta ble 6 ) wit hi n 1 0 mi n utes 
pri or t o t he start of sacit uz u ma b g o viteca n- hzi y i nf usi o n, 3 0 mi n utes after t he start of t he 
sacit uz u ma b g o viteca n- h zi y i nf usi o n ( ± 5 mi n utes), a n d at t he e n d of t h e sacit uz u ma b 
g o viteca n- hzi y i nf usi o n: 
 B o d y te m perat ure, p ulse rate, bl o o d press ure ( diast olic a n d s yst olic) 
Hei g ht i n ce nti meters ( Scree ni n g visit o nl y) a n d b o d y wei g ht i n kil o gra ms will als o be 
c ollecte d.  
Assess me nts ma y b e perf or me d b y a p h ysicia n, re gistere d n urse, or ot her q ualifie d healt h 
care pr o vi der.  
1 1. 3. 2.  
P h ysic al E x a mi n ati o n 
F ull p h ysic al e x a mi nati o n e val uati o ns at Scree ni n g s h o ul d i ncl u de all maj or b o d y s yste ms, 
i ncl u di n g ge n eral a p p eara nce, s ki n, nec k, e yes, ears, n ose, t hr oat, l u n gs, heart, a b d o me n, 
bac k, l y m p h n o d es, e xtre mities, a n d ne ur ol o gi cal e x a mi nati o ns. S u bse q ue nt s y m pt o m-
directe d p h ysic al e x a ms s h o ul d i ncl u de b o d y s y st e ms as a p pr o pri ate (e. g., li mite d p h ysici a n 
e x a m base d o n s y m pt o ms) a n d wei g ht. 
I nf or mati o n a b o ut t he p h ysical e x a mi nati o n m ust be prese nt i n t he s o urce d oc u me ntati o n at 
t he st u d y site. Cli nicall y rele va nt fi n di n gs o bser v e d pri or  t o t he start of st u d y dr u g, s h o ul d be 
rec or de d as me dical hist or y. Cli nicall y rel e va nt fi n di n gs o bser ve d after  t he start of st u d y 
dr u g, w hic h meet t he d efi niti o n of a n A E, m ust be rec or de d o n t he A E e C R F. 
Assess me nts ma y b e perf or me d b y a p h ysicia n, re gistere d n urse, or ot her q ualifie d healt h 
care pr o vi der. 

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1 1. 3. 3.  
E C O G Perf or m a nce St at us 
T he I n vesti gat or or q u alifie d desi g nee will  assess E C O G perf or ma nce stat us d uri n g t he 
Scree ni n g Peri o d t o assess f or eli gi bilit y ac c or di n g t o t he i ncl usi o n a n d e x cl usi o n criteria 
(Ta ble 1 1 ) as well as t o m o nit or perf or ma n ce t hr o u g h o ut t he st u d y (Ta bl e 6 ).  
T a ble 1 1:  
E C O G Perf or m a nce St at us 
Gr a de 
E C O G 
0 
F ull y acti ve, a ble t o carr y o n all pre- disease perf or ma nce wit h o ut restricti o n 
1 
Restricte d i n p h ysicall y stre n u o us acti vit y b ut a m b ulat or y a n d a ble t o carr y o ut 
w or k of a li g ht or se de ntar y nat ure, e . g., li g ht h o use w or k, office w or k 
2 
A m b ulat or y a n d ca pa ble of all selfcare b ut u na ble t o carr y o ut a n y w or k acti vities. 
U p a n d a b o ut m ore t ha n 5 0 % of wa ki n g h o urs 
3 
Ca pa ble of o nl y li mite d selfcare, c o nfi ne d t o be d or c hair m ore t ha n 5 0 % of wa ki n g 
h o urs  
4 
C o m pletel y disa ble d. Ca n n ot carr y o n a n y selfcare. T otall y c o nfi ne d t o be or c hair 
5 
Dea d 
E C O G = E aster n C o o perati ve O nc ol o g y Gr o u p  
S o urce: O ke n, 1 9 8 2. 
1 1. 3. 4.  
Electr oc a r di o gr a m 
Sta n dar d 1 2-lea d E C Gs will be perf or me d i n tr i plicate at Scree ni n g a n d o n Da y 1 a n d Da y 8 
of C ycl e 1 at t he f oll o wi n g ti me p oi nts: pre- d ose ( a n y ti me pri or t o trilacicli b o n t he da y of 
d osi n g), at t he e n d of tril acicli b i nf usi o n ( b ut pri or t o i nitiati o n of sacit uz u ma b g o viteca n-
hzi y i nf usi o n), a n d at t he e n d of sacit uz u ma b g o viteca n- hzi y i nf usi o n ( Ta bl e 6 ). A d diti o nal 
E C Gs ma y b e perf or me d as cli nicall y i n dicate d at a n y ti me d uri n g t he st u d y. All 1 2-lea d 
E C Gs will be o btai ne d after t he patie nt has b ee n  resti n g f or at least 1 0 mi n utes a n d s h all be 
rec or de d at 2 5 m m/sec. All E C Gs f or a n i n di vi d ual patie nt s hall be rec or de d wit h t he patie nt 
i n t he sa me p h ysi cal p ositi o n.  
A n y E C G wit h a Q Tc v al ue of > 5 0 0 msec s hall ha ve t he Q Tc v al ue c o nfir me d via ma n ual 
rea d. T h e I n vesti gat or or q ualifie d desi g nee s h o ul d re vie w t he E C Gs f or a n y a b n or malities as 
c o m pare d wit h t he b aseli ne E C G. F oll o wi n g c o nfir mati o n, t he I n vesti gat or s h o ul d e val uate 
f or a n y ot her p ote ntial ca uses of t he pr ol o n gati o n (e. g., c o nc o mita nt me dicati o ns) a n d 
deter mi ne t he a p pr o priat e cli nical c o urs e. 
T he I n vesti gat or or q u alifie d desi g nee s h all re vie w t he E C Gs f or a n y a b n or malities as 
c o m pare d wit h t he b aseli ne E C G. 
1 1. 3. 5.  
Cli nic al S afet y L a b or at or y Assess me nts 
He mat ol o g y, c he mistr y, a n d pre g na n c y tests will be perf or me d at t he site’s l ocal certifie d 
la b orat or y per t he sc h e d ule o utli ne d i n t he Sc he d ule of Assess me nts (T a ble 6 ). Cli nical 
la b orat or y sa m ples ma y be c ollecte d fr o m patie nts at a differe nt l ocati o n t ha n I n vesti gat or’s 
cli nic f oll o wi n g a p pr o val b y t he M e dical M o nit or. A list of cli nical la b orat or y tests t o be 
perf or me d is pr o vi de d i n Secti o n 1 7. 1 .  

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He mat ol o g y m a y be o btai ne d u p t o 2 4 h o urs a n d c he mistr y ma y b e o btai ne d u p t o 7 2 h o urs 
pri or t o eac h ti me p oi nt o n Sc he d ule of Assess m e nts. F or w o me n of c hil d beari n g p ot e ntial, 
pre g na nc y t ests will be perf or me d as f oll o ws: ser u m beta h u ma n c h ori o nic g o na d otr o pi n ( ß-
h C G) at Scree ni n g a n d ser u m or uri ne ß- h C G o n Da y 1 of eac h treat me nt c ycle, a n d at t he 
E n d of Treat me nt Visit. A pre g na n c y test s h o ul d be perf or me d wit hi n 2 4 h o urs of t he C ycle 1 
Da y 1 visit a n d m ust be ne gati ve t o i nitiate treat me nt.   
C he mistr y a n d he m at ol o g y res ults s hall be re v ie we d bef ore d osi n g. La b orat or y t o xicities will 
be assesse d usi n g t he N ati o nal Ca ncer I nstit ute ( N CI)- C T C A E v 5. 0. 
A n a b n or mal la b orat or y val ue is n ot a n A E u nless it is c o nsi dere d t o be cli nicall y si g nifica nt 
b y t he I n vesti gat or. La b orat or y para meters f or w hi c h cli nicall y si g nifica nt v al ues are n ote d 
will be re- me as ure d o n t h e a p pr o pri ate cli nical f oll o w- u p arra n ge d b y t h e I n vesti gat or. A n y 
la b orat or y val u e t hat re m ai ns a b n or mal at t he e n d of t he st u d y a n d t hat is c o nsi dere d 
cli nicall y si g nifica nt s h o ul d be  f oll o we d acc or di n g t o acce pt e d me dical sta n dar ds f or u p t o 
3 0 da ys or u ntil t he val ues ret ur n t o n or mal or bas eli ne or are n o l o n ger c o nsi dere d cli nicall y 
si g nifica nt b y t he I n vesti gat or. If s uc h v al ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d 
of ti me j u d ge d reas o n a ble b y t h e I n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d, a n d t he 
Me dical M o nit or n otifie d.  
If a s u bse q u e nt c ycle is d ela ye d/s ki p pe d f or t o xicit y, t he patie nt s h o ul d still c o m plete t he 
cli nical la b orat or y assess me nts o n t he sc he d ule d Da y 1 (e ntere d as a n U ns c he d ule d 
assess me nt i n t he e C R F) as well as o n t he act ual first d osi n g da y of t h at c ycle. If t he del a y is 
sec o n dar y t o h e mat ol o gi c t o xicit y, wee kl y rep eat he mat ol o g y assess me nts s h o ul d c o nti n ue 
u ntil t he fi n di n g meets criteria f or res u m pti o n of d osi n g (see Secti o n 9. 2 ; Ta ble 8 ). 
1 1. 3. 6.  
A d verse a n d Seri o us A d verse E ve nts 
T he I n vesti gat or a n d a n y q ualifie d desi g nees ar e res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or 
f oll o wi n g u p, as a p plica ble, A Es t hat are s eri o us, c o nsi dere d rel ate d t o t he st u d y dr u gs or 
st u d y pr oce d ures, or t hat ca use d t he patie nt t o dis c o nti n ue t he st u d y or st u d y dr u gs (see 
Secti o n 1 0. 1 ). Patie nts s h o ul d be e nc o ura ge d t o r e p ort A Es freel y or i n res p o nse t o ge neral, 
n o n directe d q uesti o ni n g. A d verse e ve nts (seri o us a n d n o n-seri o us) s h o ul d be re p ort e d o n t he 
a p pr o priate p a ge of t h e e C R F. T o xicit y will be assesse d b y I n vesti gat ors usi n g 
N CI- C T C A E v 5. 0. 
1 1. 3. 6. 1.  Ti me Peri o d a n d Fre q ue nc y f or C ollec ti n g A d verse a n d Seri o us A d verse 
E ve nt I nf or m ati o n 
A Es will be c ollecte d starti n g fr o m t he first d ose of st u d y dr u g t hr o u g h t h e Safet y F oll o w- u p 
Visit. A n y S A E occ urri n g bet w ee n t he date t he p atie nt si g ns i nf or me d c o ns e nt a n d t he first 
d ose of a n y st u d y dr u g, a n d w hic h t he I n vesti gat or feels is relat e d t o a st u d y s pecific 
pr oce d ure (i.e., w o ul d n ot ha ve occ urre d u nl ess t he patie nt was o n t he st u d y), s h o ul d als o b e 
re p orte d. A n y A Es t hat o cc ur bet w ee n t he date of si g ni n g i nf or me d c o ns e nt a n d t he first d ose 
of st u d y dr u g s h o ul d be rec or de d as Me dical Hist or y. 
All S A Es will be rec or de d a n d re p ort e d t o G 1 T hera pe utics p har mac o vi gila nce ( P V G) or 
desi g nee i m me diatel y a n d s h o ul d n ot e xcee d 2 4 h o urs after bec o mi n g a ware of t he e v e nt, as 
i n dicate d i n Secti o n 1 7. 2 .  

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I n v esti gat ors are n ot o bli gat e d t o acti vel y see k A E or S A E i nf or mati o n after 3 0 da ys 
f oll o wi n g t he last d ose of st u d y dr u gs o n t his st u d y. H o we ver, if t he I n v esti gat or l ear ns of 
a n y S A E, i n cl u di n g a d eat h, at a n y ti me after a patie nt has bee n disc h ar ge d fr o m t he st u d y, 
a n d he/s he c o nsi ders t he e ve nt t o be reas o na bl y relate d t o t he st u d y i nter ve nti o n or st u d y 
partici pati o n, t he I n vesti gat or or desi g nee m ust pr o m ptl y n otif y G 1 T hera p e utics P V G or 
desi g nee. 
1 1. 3. 6. 2.  Met h o d of Detecti n g A d verse a n d Seri o us A d verse E ve nts 
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g ca usalit y of A E a n d S A E a n d t he 
pr oce d ures f or c o m pleti n g a n d tr a ns mitti n g S A E re p orts are pr o vi de d i n Secti o n 1 7. 2 . 
Care s h o ul d be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es a n d/ or S A Es. O pe n-e n d e d 
a n d n o nlea di n g ver bal q u esti o ni n g of t he p atie n t is t he preferre d met h o d t o i n q uire a b o ut A E 
occ urre nces. 
1 1. 3. 6. 3.  F oll o w- u p of A d verse a n d Seri o us A d verse E ve nts 
After t he i nitial A E/ S A E re p ort, t he I n v esti gat or is  re q uire d t o pr o acti vel y f oll o w eac h patie nt 
at s u bse q ue nt visits/c o ntacts.  All A Es ( b ot h seri o us a n d n o nseri o us) will be f oll o we d i n 
acc or da nce wit h g o o d m e dical practice u ntil re s ol uti o n, ret ur n t o baseli ne, or it is dee me d 
t hat f urt her rec o v er y is u nli kel y. All meas ures re q uire d f or A E m a na ge m e nt a n d t he ulti mate 
o utc o me of t he A E will b e rec or de d i n t he s o urce d oc u me nt a n d re p orte d t o G 1 T hera p e utics 
P V G or desi g n ee. 
All S A Es will be f oll o we d u ntil res ol uti o n, s ta bilizati o n, t he e ve nt is ot her wise e x plai ne d, or 
t he patie nt is l ost t o f oll o w- u p (as d efi ne d i n Secti o n 1 0. 3 ). F urt her i nf or mati o n o n f oll o w- u p 
pr oce d ures is pr o vi de d i n Secti o n 1 7. 2 . 
1 1. 3. 6. 4.  Re g ul at or y Re p orti n g Re q uire me nts f or Seri o us A d verse E ve nts 
Pr o m pt n otificati o n of G 1 T hera p e utics P V G or desi g nee b y t he I n v esti gat or ( or desi g nee) of 
a n S A E is esse ntial s o t hat le gal o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of 
patie nts a n d t he safet y of a st u d y i nter ve nti o n u n d er cli nical i n vesti gati o n are met. 
G 1 T hera p e utics has a l e gal r es p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d 
ot her re g ulat or y a ge n cies a b o ut t he safet y of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. 
G 1 T hera p e utics will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire m e nts relati n g t o safet y 
re p orti n g t o t he re g ulat or y a ut h orit y, Ce ntr al I R B/I E C, a n d I n vesti gat ors. F or all st u dies, 
e x ce pt t h ose utilizi n g me dical de vices, I n vesti gat or safet y re p orts m ust be pre pare d f or 
s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A R) acc or di n g t o l ocal re g ul at or y 
re q uire me nts a n d G 1 T hera pe utics p olic y a n d f or war de d t o I n v esti gat ors, as necessar y. 
A n I n vesti gat or w h o recei ves a n I n vesti gat or safet y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or mati o n ( e. g., s u m mar y or listi n g of S A Es) fr o m G 1 T hera p e utics or desi g n ee will 
re vie w a n d t h e n file it al o n g wit h t he I n v esti gat or’s Br oc h ure a n d will n otif y t he I R B/I E C, if 
a p pr o priate acc or di n g t o l ocal re q uir e me nts. 

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1 1. 3. 6. 5.  Pre g n a nc y 
Details of all pre g n a ncies i n fe male patie nts a n d fe male part ners of male p atie nts will be 
c ollecte d after t he start of st u d y i nter ve nti o n a n d u ntil 3 0 a n d 1 2 0 da ys res p ecti vel y, after t he 
last d ose of st u d y dr u g. 
If a pre g na nc y is r e p orte d, t he I n v esti gat or or d esi g nee s h o ul d i nf or m G 1 T hera pe utics P V G 
or desi g n ee wit hi n 2 4 h o urs of lear ni n g of t he pre g na n c y a n d s h o ul d f oll o w t he pr oce d ures 
o utli ne d i n Secti o n 1 7. 3 . 
A b n or mal pre g n a nc y o ut c o mes (e. g., s p o nta n e o us a b orti o n, fetal deat h, still birt h, c o n ge nital 
a n o malies, ect o pic pre g n a nc y) are c o nsi dere d S A Es. 
1 1. 4.  
S afet y M o nit ori n g C o m mittee 
A n i n de pe n de nt S M C will m o nit or acc u m ulati n g safet y a n d dis p ositi o n data wit h t he first 
meeti n g pla n n e d f or w he n a p pr o xi matel y 1 0 patie nts ha ve c o m plete d at least 2 c ycl es of 
st u d y treat me nt. T he meeti n gs will c o nti n ue w he n a p pr o xi matel y 2 5 e nr olle d patie nts ha ve 
c o m plete d at least 2 c ycl es of st u d y tr eat me n t a n d a gai n w he n all e nr olle d patie nts ha ve 
c o m plete d at least 2 c ycl es of st u d y tr eat me nt or as defi ne d i n t he S M C c harter. A d diti o nal 
re vie ws ma y o cc ur. 
A si n gle S M C c hart er will defi ne t he r oles a n d res p o nsi bilities of t he S M C a n d its me m bers. 
A d diti o nal details re gar di n g t he c o m mitt ee ’s c o m p ositi o n, sc o pe, o bjecti ves, pr oce d ures, a n d 
p olicies, i ncl u di n g data t o be re vie we d are des cri b e d i n t he S M C c harter. T he S M C will 
m o nit or acc u m ulati n g s afet y a n d dis p ositi o n data a n d will be c o m prise d of st u d y tea m 
me m bers a n d i n de p e n de nt me m bers. 
1 1. 5.  
E n d of Tre at me nt Visit 
W he n a patie nt per ma n e ntl y disc o nti n ues st u d y tr eat me nt, t he patie nt s h o ul d c o m plete a n 
E n d of Treat me nt Visit 1 4 da ys ( ± 7 da ys) fr o m last d ose of st u d y dr u g as o utli ne d i n  Ta ble 6.  
1 1. 6.  
S afet y F oll o w- u p Visit 
T he patie nt s h o ul d c o m plete a Safet y F oll o w- u p Visit 3 0 da ys ( + 7 d a ys) fr o m last d ose of 
st u d y dr u g as o utli ne d i n Ta ble 6. T his visit ma y o cc ur at t he st u d y site, or ca n be via 
tele p h o ne, e mail, or b y recei vi n g i nf or mati o n fr o m a fa mil y m e m ber or h ealt hcare pr o vi der.    
1 1. 7.  
S ur vi v al F oll o w- u p P h ase 
After c o m pleti o n of t he S afet y F oll o w- u p Visit, t he patie nt will be f oll o we d a p pr o xi matel y 
e ver y 3 m o nt hs f or s ur vi val. S ur vi val F oll o w- u p Visits ca n be via tele p h o ne, e mail, or cli nic 
visits.    
I nf or mati o n will be c ollecte d u ntil t he e n d of t he st u d y ( or d eat h) t o rec or d t he patie nt’s 
stat us (ali ve or dea d). I n a d diti o n, details of a n y s u bse q ue nt s yst e mic a nti-ca ncer t hera p y 
i nitiate d, i ncl u di n g na me(s) of a ge nt(s), dat es (start/st o p) a d mi nistere d, best res p o nse t o t he 
treat me nt, a n d dat e of pr o gressi o n s h o ul d als o be re p orte d t o t he best of t heir a bilit y.  

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If a patie nt wit h dra ws c o nse nt f or f urt h er st u d y pr oce d ures, t h e site s h o ul d clarif y if t he 
patie nt ( or le gall y a ut h ori ze d re prese nt ati ve w here all o we d b y l ocal r e g ulati o n) re mai ns o pe n 
t o s ur vi val c o ntact a n d ass ociate d data c ollecti o n. Pr o vi de d t hat t he patie nt has n ot wit h dra w n 
c o nse nt f or f oll o w u p c o ntact, i nf or mati o n fr o m  me dical rec or ds ma y be s u bstit ute d f or 
p h o ne or ot her c o ntact, pr o vi de d t hat rec or ds are a vaila ble as s o urce d oc u m e ntati o n. P u blic 
rec or ds ma y b e use d t o v erif y s ur vi val status if per mitte d b y i nstit uti o nal or c o u ntr y 
g ui da n ces. 

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1 2.  
S T A TI S TI C A L C O N SI D E R A TI O N S 
F ull details o n t he statistical a nal yses t o b e perf or me d will be pr o vi de d i n a se parate 
statistical a nal ysis pla n ( S A P).  
1 2. 1.  
S a m ple Size Deter mi n ati o n 
T he sa m ple siz e is calc ul ate d t o s u p p ort t he pri mar y o bjecti ve of t he st u d y, t hat is, t o e val uate 
trilacicli b’s effect o n P F S w he n a d mi nistere d pri or t o sacit uz u ma b g o viteca n- hzi y i n patie nts 
wit h l ocall y a d v a nce d or metastatic T N B C w h o re cei ve d at least 2 pri or treat me nts wit h at 
least 1 i n t he metastatic s etti n g.  
T his si n gle-ar m st u d y pla ns t o e nr oll 4 5 patie nts d uri n g t he 1 0- m o nt h accr ual peri o d wit h a n 
a p pr o xi mate 3 0- m o nt h t otal st u d y d urati o n. Wit h  4 5 patie nts a n d 1 4 m o nt hs of f oll o w- u p 
after t he l ast patie nt is d ose d, Ta ble 1 2 prese nts t he re q uir e d n u m ber of P F S e ve nts a n d 
statistical p o wers t o dete ct H Rs of 0. 7 a n d 0. 8 at a 2-si de d si g nifica n ce of 0. 2 f or a me dia n 
P F S of t he hist orical c o ntr ol gr o u p of 5. 6 m o nt hs , w hic h was defi ne d f or p atie nts wit h o ut 
brai n metastases tr eate d wit h sacit uz u ma b g o viteca n- hzi y i n t he P hase 3 A S C E N T trial 
(Bar dia, 2 0 2 1 ). T h e cal c ulati o n is base d o n o ne-s a m ple l o g-ra n k test (W u, 2 0 1 5 ) wit h t he 
ass u m pti o n t hat t he s ur vi val ti me distri b uti o ns f or b ot h st u d y treat me nt a n d hist oric c o ntr ol 
gr o u p f oll o w t he Wei b ull distri b uti o n wit h a s ha pe para meter of 1. 0 0 (i. e., e x p o ne ntial 
distri b uti o n).  
T a ble 1 2:  
St atistic al P o w er 
H az ar d 
R ati o 
Me di a n P F S f or tril acicli b + 
s acit uz u m a b g o vitec a n-hzi y 
( M o nt hs) 
E x pecte d n u m ber of 
e ve nts i n t he st u d y 
St atistic al P o wer 
0. 7 0 
8. 0 
3 6 
8 0 % 
0. 8 0 
7. 0 
3 8 
5 4 % 
1 2. 2.  
A n al ysis P o p ul ati o n 
T he f oll o wi n g a nal ysis p o p ulati o ns are defi n e d f or t he st u d y.  
T he f ull a nal ysis set ( F A S) i ncl u des all e nr olle d p atie nts w h o were a d mi nistere d at least 1 
d ose of st u d y dr u g. U nless ot her wise s pecifi e d, t he F A S is t he pri mar y a nal ysis set f or all 
effic ac y a n al ys es. 
T he res p o nse e val ua bl e ( R E) p o p ulati o n i ncl u des all patie nts w h o are i n t h e F A S a n d w h o 
ha ve meas ura ble (t ar get) t u m or lesi o n(s) at t he bas eli ne t u m or assess me nt a n d eit her (i) ha v e 
at least 1 p ost- baseli ne t u m or assess me nt, or ( ii) d o n ot ha ve p ost- d ose t u m or assess me nt b ut 
ha ve cli nical pr o gressi o n as n ote d b y t he I n vesti gat or, or (iii) die d d ue t o disease pr o gressi o n 
pri or t o t heir first p ost- baseli ne t u m or sca n. T he R E p o p ulati o n will be t he pri mar y a nal ysis 
set f or t u m or res p o ns e a n al yses.  
T he safet y p o p ulati o n i ncl u des all e nr olle d patie nts w h o recei ve d at least 1 d ose of st u d y 
dr u g. All safet y a n al ys es will be e val uate d usi n g t he safet y p o p ulati o n.  

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1 2. 3.  
Ti mi n g of Pl a n ne d A n al ysis  
1 2. 3. 1.  
First Pl a n ne d A n al ysis –  A n al yses f or Pr o gressi o n- Free S ur vi v al, T u m or 
Res p o nse E n d p oi nts, a n d M y el os u p pressi o n E n d p oi nts 
T he first pla n ne d a nal ysis will be c o n d ucte d f or t h e pri mar y e n d p oi nt, P F S, at t he ti me w he n 
3 6 patie nts ha ve ra di o gra p hicall y- d eter mi ne d dise ase pr o gressi o n or ha ve die d. St u d y 
data base will be l oc k e d t o s u p p ort t he a nal ysis . I n a d diti o n, t he f oll o wi n g s pecifie d a n al yses 
will be perf or me d: 
 A nal ysis of t u m or res p o nse e n d p oi nts ( O R R, C B R, a n d D O R). 
 A nal ysis of m yel os u p pressi o n e n d p oi nts. 
 A nal ysis of s afet y d ata. 
1 2. 3. 2.  
Fi n al Pl a n ne d A n al ysis –  A n al ysis f or O ver all S ur vi v al 
A nal ysis f or O S will be c o n d ucte d w he n a p pr o xi matel y 7 0 % of patie nts ha v e die d (i.e., 
3 2 deat hs). St u d y d ata bas e will be l oc ke d t o s u p p ort t he fi nal O S a nal ysis.  
1 2. 4.  
St atistic al A n al ysis Met h o ds 
A n S A P will be de vel o pe d a n d fi nalize d pri or t o t he first data bas e l oc k a n d will i ncl u de m ore 
details relate d t o t he statistical a nal ysis of t his st u d y’s data. T his secti o n is a s u m mar y of t he 
ke y as pects of t he pla n ne d statistical a nal ys es. 
1 2. 4. 1.  
Ge ner al C o nsi der ati o ns 
All statistical a nal yses will be perf or me d usi n g S A S ®  v 9. 4 or hi g h er. Cate g orical vari a bles 
will be s u m mariz e d b y c o u nts a n d perce nta ges, w hile c o nti n u o us varia bles will be 
s u m marize d b y mea n, sta n dar d de viati o ns, me dia n, 2 5 % a n d 7 5 % perce ntiles, a n d mi ni m u m 
a n d ma xi m u m val ues. 
1 2. 4. 2.  
P ati e nt Dis p ositi o n 
Patie nt dis p ositi o n will be s u m marize d. T he s u m mar y will i ncl u de n u m ber of all scree ne d 
patie nts, a n d n u m ber a n d perce nt a ge of patie nts w h o were e nr olle d , recei v e d st u d y dr u g, 
disc o nti n ue d fr o m eac h st u d y dr u g a n d t he re as o ns, a n d disc o nti n ue d fr o m t he st u d y a n d 
reas o ns. 
1 2. 4. 3.  
De m o gr a p hic a n d B aseli ne C h ar acteristics 
De m o gra p hics a n d baseli ne c haracteristics will  be s u m marize d f or t he F A S. T he s u m mar y 
will i ncl u de a ge, a ge gr o u ps, ge n d er, race, et h nicit y, scree ni n g vital si g ns ( b o d y wei g ht, 
hei g ht, b o d y mass i n de x, B S A), E C O G stat us ( 0- 1), n u m ber of pre vi o us c h e m ot hera p y 
re gi me ns or a d v a nce d dis ease.  
1 2. 4. 4.  
Pri o r a n d S u bse q ue nt A ntic a ncer T her a pies 
Pri or a n d s u bse q ue nt a nti ca ncer t hera p y ver bati m ter ms will be c o de d t o A n at o mical 
T hera p e utic Classificati o n a n d preferre d ter m usi n g t he lat est versi o n of W orl d Healt h 

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Or ga niz ati o n- Dr u g Dicti o nar y. F or t he F A S, s u m mar y st atistics will be pr o vi de d f or pri or 
a n d s u bse q ue nt s yste mic a nti-ca ncer t hera pies. F or t he s u bse q ue nt s yst e mic a nti-ca ncer 
t hera pies, t he li nes of t h era p y, best resp o ns e t o eac h treat me nt r e gi me n, a n d disease 
pr o gressi o n stat us will als o be s u m marize d. 
1 2. 4. 5.  
St u d y Dr u g E x p os ure, M o dific ati o n a n d D ose I nte nsit y  
T he s u m mar y descri be d bel o w will be base d o n t he safet y p o p ulati o n. 
D urati o n of st u d y dr u g e x p os ure will be de fi ne d f or sacit uz u ma b g o viteca n- hzi y a n d f or 
trilacicli b a n d s u m marize d. T he n u m ber of c ycles t hat patie nts ha ve recei v e d will be 
s u m marize d b y descri pti ve statistics as a c o nti n u o us varia ble, w hile t he n u m ber of c ycl es t hat 
are c o m plet e d will be s u m marize d as a cate g orical varia ble.  
St u d y dr u g m o dificati o ns will be s u m marize d i n t hree cate g ori es: sacit uz u ma b 
g o viteca n- hzi y d os e re d u cti o ns, sacit uz u ma b g o viteca n- hzi y c ycl e dela y, a n d i nf usi o n 
i nterr u pti o n. T he n u m ber a n d perce nta ge of patie nts w h o ha ve a n y sacit uz u ma b 
g o viteca n- hzi y d os e re d u cti o ns will be s u m m arize d; t he n u m ber a n d perce nta ge of patie nts 
w h o ha ve at least o ne c ycle dela y will be s u m marize d al o n g wit h a s u m mar y of t he n u m ber 
of c ycles t hat h a ve bee n dela ye d; t he n u m ber a n d perce nt a ge of patie nts w h o ha ve at least 
o ne i nf usi o n i nterr u pti o n f or trilacicli b or sacit uz u ma b g o viteca n- hzi y will be s u m marize d 
al o n g wit h a s u m mar y of t he n u m ber of i nterr u pti o ns. Lastl y, t he pri mar y reas o n f or eac h 
f or m of st u d y dr u g m o dificati o n (sacit uz u ma b g o viteca n- hzi y d os e re d u cti o ns, c ycl e dela y, 
a n d i nf usi o n i nterr u pti o n) will als o be s u m marize d. 
F or trilaci cli b a n d sacit uz u ma b g o viteca n- hzi y, c u m ulati ve d ose, d ose i nte nsit y, relati ve d os e, 
a n d relati ve d os e i nte nsit y will be deri ve d a n d s u m marize d. 
1 2. 4. 6.  
Effic ac y A n al yses  
1 2. 4. 6. 1.  A n al yses of Pri m ar y Effic ac y E n d p oi nt –  Pr o g ressi o n- Free S ur vi v al 
T he pri mar y effic ac y e n d p oi nt of P F S d uri n g t he st u d y is defi ne d as t he ti me ( m o nt hs) fr o m 
t he date of first d ose of st u d y dr u g t o t he d ate of d oc u me nte d ra di o gra p hic disease 
pr o gressi o n per R E CI S T v 1. 1 or deat h d ue t o a n y ca use, w hic h e ver c o mes first. P F S will be 
deter mi ne d usi n g all data u ntil t he last e val ua ble visit pri or t o or o n t he date of (i) 
ra di o gra p hic disease pr o gressi o n per R E CI S T v 1. 1; (ii) wit h dra wal of c o nse nt t o o btai n 
a d diti o nal sca ns o n st u d y; or (iii) i nitiati o n of s u bse q ue nt a ntica n cer t h era p y, w hic h e ver is 
earlier. Deat h (i n a bse nce of pr o gressi ve dise ase [ P D]) is al wa ys cate g orize d as a n e ve nt i n 
t he P F S a nal ysis. Ce ns ori n g r ules f or patie nts w h o d o n ot e x perie nce P D or deat h at t he data 
c ut off date will be descri be d i n t he st u d y S A P. 
T he pri mar y a n al ysis f or P F S will be c o n d ucte d at t he ti me w he n 3 6 patie nts ha ve 
ra di o gra p hic all y- deter mi ne d disease pr o gressi o n or ha ve die d. A Ka pla n- Meier pl ot will be 
pr o d uce d. T h e me dia n, 2 5 %, a n d 7 5 % perce ntile of  P F S will be esti mate d usi n g t he Ka pla n-
Meier met h o d wit h t heir c orres p o n di n g 9 5 % CI calc ulate d usi n g t he m et h o d b y Br o o k me yer  
a n d Cr o wle y ( 1 9 8 2) .  
A nal ysis of P F S d uri n g t he st u d y will be bas e d o n t he F A S. 

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1 2. 4. 6. 2.  A n al yses f or Sec o n d ar y A nti-t u m o r Effic ac y E n d p oi nts 
Sec o n dar y a nti-t u m or e n d p oi nts i ncl u de t he f oll o wi n g: 
 T u m or res p o nse relate d e n d p oi nts 
- O bjecti ve res p o nse rate ( O R R)  
- Cli nical be nefit rate ( C B R) 
- D urati o n of o bje cti ve res p o nse ( D O R)  
 O verall s ur vi val ( O S)  
A nal ysis f or T u m or Res p o nses 
At eac h t u m or ass ess me nt visit, a n o verall ti me p oi nt res p o nse b y R E CI S T v 1. 1 will be 
deri ve d pr o gra m maticall y usi n g t he meas ure me nts pr o vi de d b y t h e I n vesti gat or f or tar get 
lesi o ns, n o n-tar get lesi o ns, a n d ne w lesi o ns c ollect e d i n t he e C R F. Best o verall res p o nse 
( B O R) will be d eter mi ne d usi n g all visit res p o nses pri or t o or o n t he date of (i) ra di o gra p hic 
disease pr o gressi o n; (ii) wit h dra wal of c o nse nt t o o bt ai n t u m or sca ns; (iii) deat h; (i v) l ost t o 
f oll o w- u p; or ( v) i nitiati o n of s u bse q ue nt a ntican cer t hera p y, w hic he v er is earlier.  
T he n u m ber a n d p erce nta ge of patie nts i n eac h cate g or y of deri ve d B O R (c o nfir me d 
c o m plete res p o nse ( C R), c o nfir me d  partial res p o ns e ( P R), sta ble disease ( S D), P D, or N ot 
E val ua ble) will be s u m m arize d.  
O R R is defi ne d as t he pr o p orti o n of patie nts wit h B O R of c o nfir me d C R or c o nfir me d P R. 
O R R, al o n g wit h its e x act 9 5 % t w o-si de d CI usi n g t he Cl o p per- Pears o n met h o d, will be 
c o m p ute d. O R R will be a nal yze d bas e d o n t he R E p o p ulati o n. 
C B R is defi ne d as t he pr o p orti o n of patie nts wit h a B O R of c o nfir me d C R or c o nfir me d P R 
or S D lasti n g 2 4 wee ks or l o n ger fr o m t he first dat e of st u d y dr u g a d mi nistrati o n. T he 
a nal ysis of C B R will be perf or m e d usi n g t he m et h o ds si milarl y t o O R R. 
D O R is t he ti me bet wee n first o bjecti ve res p o ns e of C R or P R (c o nfir me d) a n d t he first date 
t hat pr o gressi ve diseas e is d oc u me nte d or deat h, w hic he ver c o mes first. D O R will o nl y b e 
a nal yze d f or t he p atie nts w h o ha ve a c hie ve d o bj ecti ve res p o nse. F or patie nts wit h o bjecti ve 
res p o nse b ut di d n ot reac h ra di o gra p hicall y d eter mi ne d P D or die d, t he last a de q uate t u m or 
assess me nt date pri or t o t he earliest ti me of t he f oll o wi n g will be use d t o calc ulate ce ns ore d 
ti me: (i) wit h dre w c o nse nt t o o btai n sca ns; (ii) l ost t o f oll o w- u p; (iii) i nitiate d s u bse q ue nt 
a ntica ncer t hera p y. T he Ka pla n- Mei er met h o d wi ll be use d t o esti mate t he me dia n, 2 5 %, a n d 
7 5 % perce ntile of D O R, al o n g wit h t he 9 5 % CI, w hic h is calc ulate d usi n g t he met h o d b y 
Br o o k me yer  a n d Cr o wle y ( 1 9 8 2) .  
A nal ysis f or O S 
O verall s ur vi val is defi n e d as t he ti me ( m o nt hs) fr o m t he date of first d ose of st u d y dr u g t o 
t he date of deat h f or p atie nts w h o die d i n t he st u d y d ue t o a n y ca us e or t he ti me t o t he last 
c o ntact date k n o w n t o be ali ve f or t h ose patie nts w h o s ur vi ve d as of t he d ata c ut off d ate f or 
t he pla n ne d O S a nal ysis (ce ns ore d cases). F or pati e nts w h o dr o p o ut of t he st u d y ri g ht after 
e nr oll me nt, t heir s ur vi val ti me is ce ns ore d at t he d ate of e nr oll me nt. O S will be c o n d ucte d at 
t he ti me w he n a p pr o xi matel y 7 0 % of patie nts ( ~3 2 patie nts) ha ve die d. S ur vi val distri b uti o n 

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of O S will be base d o n K a pla n- Meier met h o d use d f or t he a n al ysis f or P F S.  I n a d diti o n, t he 
n u m ber a n d perce nt a ge of patie nts w h o die d or ce ns ore d will be s u m marize d al o n g wit h t he 
e C R F c ollecte d reas o ns f or deat h. T he t otal d ur at i o n of f oll o w- u p will als o be s u m marize d.  
T he a nal ysis f or O S will be base d o n t he F A S.    
T he a nal ysis f or O R R, D C R a n d D O R will be base d o n t he R E p o p ulati o n.  
1 2. 4. 6. 3.  A n al ysis of M yel os u p pressi o n E n d p oi nts 
M yel os u p pressi o n e n d p oi nts are gr o u pe d b y li nea ge a n d c o nse q ue nce as f oll o ws:  
 Ne utr o p hils relate d (i ncl u di n g occ urre nce of S N [ d uri n g C ycles 1/ 2 a n d t h e o verall 
st u d y], occ urre nce of F N, a n d occ urre n ce of G- C S F a d mi nistrati o n) 
 R B C relate d (i n cl u di n g o cc urre nce of Gra d e 3/ 4 d ecrease of he m o gl o bi n, occ urre nce 
a n d n u m ber of R B C tra nsf usi o ns o n/after Wee k 5, a n d occ urre n ce of E S A 
a d mi nistrati o n) 
 Platelet relate d (i ncl u di n g occ urre nce of Gra d e 3/ 4 decrease of pl atelets, o cc urre nce 
a n d n u m ber of plat elet tr a nsf usi o ns) 
 E n d p oi nts relate d t o trilacicli b’s effect o n d osi n g or h os pitalizati o ns d ue t o 
c he m ot hera p y-i n d uce d m yel os u p pressi o n (i ncl u di n g occ urre nce a n d n u m b er of d ose 
re d ucti o ns, or d ose d ela y) 
T he a nal ysis of m yel os u p pressi o n e n d p oi nts will be base d o n t he F A S. 
Bi n ar y M yel os u p pressi o n E n d p oi nts:  
F or t he bi nar y m yel os u p pressi o n e n d p oi nts (e. g., t he occ urre nce of S N a n d t he occ urre nce of 
R B C tra nsf usi o ns o n/after Wee k 5), t he n u m ber a n d perce nt a ge of patie nts wit h at least o ne 
occ urre nce d uri n g t he treat me nt peri o d wi ll be s u m marize d b y treat me nt gr o u p.  
C o u nti n g M yel os u p pressi o n E n d p oi nts: 
F or c o u nti n g m yel os u p pressi o n e n d p oi nts (e. g., t he n u m ber of R B C tra nsf usi o ns o n/after 
Wee k 5, a n d t he n u m ber of d ose re d u cti o ns d uri n g t he treat me nt peri o d), t he t otal n u m ber of 
t he e ve nt, t he t otal d urati o n of treat me nt peri o d (eit her i n t he u nit of wee ks or c ycles), a n d 
e ve nt rate p er 1 0 0 w ee ks or c ycles will be s u m marize d. F or e x a m ple, t he e v e nt rate f or R B C 
tra nsf usi o ns o n/after Wee k 5 will be re p ort e d per 1 0 0 wee ks a n d t h at f or d ose re d ucti o n will 
be re p ort e d per 1 0 0 c ycles. F or a gi ve n e ve nt, pati e nts wit h o ut a n y e v e nts d uri n g t he 
treat me nt peri o d will be assi g ne d a val ue 0 t o b e i ncl u de d i n t he a nal ysis.  
1 2. 4. 7.  
S afet y A n al yses  
Safet y a n d t olera bilit y will be assesse d b y A Es, la b orat or y tests, vital si g ns, a n d E C G. All 
safet y data will be s u m mariz e d usi n g des cri pti ve statistics base d o n t he safet y p o p ulati o n. 
Data c ollecte d t hr o u g h sc he d ule d or n o n-s c he d ule d visits will all be i ncl u de d i n t he safet y 
a nal ys es. 

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1 2. 4. 7. 1.  A d verse E ve nts  
A Es are d efi ne d as t h ose e ve nts occ urri n g or w orse ni n g after treat me nt has be g u n o n t his 
st u d y. A d verse e v e nt dat a will be c o de d t o s yste m or ga n class a n d preferre d ter m usi n g t he 
latest versi o n of t he Me di cal Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A). T he se v erit y 
(t o xicit y gra des 1- 5) of A Es will be gra de d b y I n v esti gat ors acc or di n g t o t he N CI- C T C A E 
Versi o n 5. 0. T he n u m ber a n d perce nta ge of patie nts e x perie nci n g a n y A E, A Es relate d t o 
st u d y dr u g (trilacicli b or sacit uz u ma b g o viteca n-h zi y) as assess e d b y t he i n vesti gat or, A Es 
lea di n g t o st u d y dr u g dis c o nti n uati o n, d ose m o dificati o n, a n d trilacicli b A E SIs will be 
s u m marize d b y s yste m or ga n class, preferre d t er m, a n d N CI- C T C A E gra d e, w he n 
a p pr o priate. I n t he ta b ulati o n of t o xicit y gra d e a n d ca usalit y, if t he sa me A E occ urre d o n 
m ulti ple occasi o ns f or a patie nt, t he hi g h est gra de a n d str o n gest relati o ns hi p t o st u d y dr u g 
will be use d i n a s u m mar y. Trilacicli b A E SI cate g ories ha ve b ee n rec o g nize d, refl ecti n g 
eit her t he fi n di n gs i n t he A Es fr o m t he pre v i o us st u dies of trilacicli b or class effects f or 
C D K 4/ 6 i n hi bit ors. A E SI f or trilacicli b t hat will be re p ort e d fr o m t his st u d y will be i de ntifie d 
b y searc hi n g M e d D R A preferre d t er ms base d o n t he C ust o mize d Me d D R A Q ueries t hat will 
be detaile d i n t he st u d y S A P.  
1 2. 4. 7. 2.  Ot her S afet y E n d p oi nts 
O bser ve d v al ues a n d c ha n ges fr o m baseli ne i n  E C G, vital si g ns a n d la b orat or y assess me nts 
of he mat ol o g y, c he mistr y, a n d li ver f u ncti o n para meters will be s u m marize d f or eac h 
sc he d ule d visit, ma xi m u m a n d mi ni m u m p ost- baseli ne b y c ycle, o verall m a xi m u m a n d 
mi ni m u m p ost- baseli ne d uri n g tr eat me nt pe ri o d, a n d last o n-treat me nt assess me nt.  
C he mistr y a n d he m at ol o g y la b orat or y para meters will be c haracterize d acc or di n g t o C T C A E 
t o xicit y gra d e fr o m 1 t o 5, Versi o n 5. 0, w he n p ossi ble. T he n u m ber a n d p erce nta ge of 
patie nts wit hi n eac h C T C A E gra de will be s u m marize d f or t he o verall treat me nt peri o d as 
well as f or eac h c ycle. If a patie nt has m u lti ple la b orat or y assess me nts i n a n i nter val of 
i nterest, t he ma xi m u m gra de will be re p orte d.  
F or E C G a n d vital si g ns, p ote ntiall y cli nicall y si g nifica nt ( P C S) fi n di n gs will be s u m marize d. 
T he p ote ntiall y cli nicall y si g nifica nt E C G a n d vita l si g ns are defi ne d eit her b y p ost- bas eli ne 
assess me nt or b y t he c h a n ge fr o m baseli ne wit h  res pect t o t he pre-s p ecifie d t hres h ol ds. T he 
criteria d efi ni n g P C S f or E C G a n d vital si g ns will be detaile d i n t he st u d y S A P.  

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1 3.  
E T HI C S 
1 3. 1.  
Et hics Re vie w 
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C F, I B, a n d ot her rele va nt d oc u me nts (e. g., 
a d vertise me nts) m ust be s u b mitte d t o a n I R B/I E C b y t he I n vesti gat or a n d re vie we d a n d 
a p pr o ve d b y t he I R B/I E C bef ore t he st u d y is i nitiate d.  
A n y a me n d me nts t o t he pr ot oc ol will re q uire  I R B/I E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma d e t o t he st u d y desi g n, e x ce pt f or c ha n ges n ecess ar y t o eli mi nat e a n i m me diate 
hazar d t o st u d y patie nts. 
T he I n vesti gat or will be res p o nsi ble f or t he f oll o wi n g: 
 Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y t o t he I R B/I E C a n n uall y or 
m ore fre q u e ntl y i n acc or da nce wit h t he re q uire m e nts, p olicies, a n d pr oce d ures 
esta blis he d b y t h e I R B/I E C 
 N otif yi n g t he I R B/I E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y 
I R B/I E C pr oce d ures 
 Pr o vi di n g o versi g ht of t h e c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C o de of Fe d eral Re g ulati o ns ( C F R), I nter n ati o nal C o u ncil f or 
Har m o nisati o n (I C H) g ui deli nes, t he I R B/I E C, E ur o pea n re g ulati o n 5 3 6/ 2 0 1 4 f or 
cli nical st u dies (if a p plica ble), a n d all ot her a p plica ble l ocal r e g ulati o ns 
1 3. 2.  
Et hic al C o n d uct of t he St u d y 
T his st u d y will be c o n d u cte d i n acc or da n ce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g: 
 C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declarati o n of Helsi n ki a n d C o u ncil f or  I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces I nter nati o nal Et hical G ui deli nes 
 A p plica ble I C H G C P G ui deli nes 
 A p plica ble la ws a n d re g ulati o ns 
1 3. 3.  
Writte n I nf or me d C o nse nt 
T he Pri nci pal I n vesti gat or(s) at e ac h ce nter will e ns ure t hat t he patie nt is gi ve n f ull a n d 
a de q uate oral a n d writte n i nf or mati o n a b o ut t he na t ure, p ur p ose, p ossi ble ris k a n d be nefit of 
t he st u d y. Patie nts m ust als o be n otifie d t hat t he y are free t o disc o nti n ue fr o m t he st u d y at 
a n y ti me. T h e patie nt s h o ul d be gi ve n t h e o p p or t u nit y t o as k q uesti o ns a n d all o we d ti me t o 
c o nsi der t he i nf or m ati o n pr o vi de d. 
T he patie nt’s si g ne d a n d date d i nf or me d c o nse nt m ust be o bta i ne d bef ore c o n d ucti n g a n y 
st u d y pr oce d ures. 
T he Pri nci pal I n vesti gat or(s) m ust mai ntai n t he ori gi nal, si g ne d I C F. A c o p y of t he si g n e d 
I C F m ust be gi ve n t o t he patie nt or t he patie nt’s le gall y a ut h orize d re pres e ntati ve  w here 
all o we d b y l ocal r e g ulati o n. 

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1 4.  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G 
1 4. 1.  
D at a Pr otecti o n 
Patie nts will be assi g ne d a u ni q ue i de ntifier b y t he S p o ns or. A n y patie nt rec or ds or datasets 
t hat are tr a nsferre d t o t he S p o ns or will c o ntai n t he i de ntifier o nl y; p atie nt na mes or a n y 
i nf or mati o n w hic h w o ul d ma ke t he patie nt i de ntifi a ble will n ot be tra nsferre d.  
T he patie nt m ust be i nf or me d t hat his/ her pers o nal st u d y-relate d dat a will be use d b y t he 
S p o ns or i n acc or da nce wit h l ocal data pr otecti o n l a w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he patie nt w h o will be re q uire d t o gi ve c o nse nt f or t heir data t o be use d as 
descri be d i n t he i nf or me d c o nse nt.  
T he patie nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y b e e x a mi ne d b y Cli nical 
Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t h e S p o ns or, b y 
a p pr o priate I R B/I E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities. 
1 4. 2.  
D at a Q u alit y Ass ur a nce 
 All patie nt data relati n g t o t he st u d y will be rec or de d o n e C R F u nless tra ns mitte d 
t o t he S p o ns or or Desi g n ee electr o nicall y. T he I n v esti gat or is r es p o nsi ble f or 
verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysic all y or electr o nicall y 
si g ni n g t he e C R F.  
 T he I n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce dat a) t hat 
s u p p orts t he i nf or mati o n e ntere d i n t he e C R F.  
 T he I n vesti gat or m ust per mit st u d y-rel ate d m o nit ori n g, a u dits, I R B/I E C re vie w, 
a n d re g ulat or y a ge n c y i ns pecti o ns a n d pr o vi de direct access t o s o urce data 
d oc u me nts.  
 M o nit ori n g details descri bi n g strate g y (e. g., ris k- b ase d i nitiati ves i n o perati o ns 
a n d q ualit y s uc h as Ris k Ma na ge me nt a n d Miti gati o n Strate gies a n d A nal ytical 
Ris k Base d M o nit ori n g), met h o ds, res p o nsi bilities, a n d re q uir e me nts, i ncl u di n g 
ha n dli n g of n o n c o m plia nce iss ues a n d m o nit ori n g tec h ni q ues (ce ntral, r e m ote, or 
o n-site m o nit ori n g) are pr o vi de d i n t he M o nit ori n g Pla n. 
 T he S p o ns or or Desi g nee is res p o nsi ble f or t he dat a ma na ge m e nt of t his st u d y 
i ncl u di n g q ualit y c hec ki n g of t he d ata.  
 St u d y M o nit ors will perf or m o n g oi n g s o urce data verificati o n at t he fre q u e ncies 
a n d e xte nt as o utli ne d i n t he M o nit ori n g Pla n t o c o nfir m t hat data e ntere d i nt o t he 
e C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifi a ble fr o m 
s o urce d oc u m e nts; t hat t he safet y a n d ri g hts of patie nts are bei n g pr otecte d; a n d 
t hat t he st u d y is bei n g c o n d ucte d i n acc or da n ce wit h t he c urre ntl y a p pr o ve d 
pr ot oc ol a n d a n y ot her st u d y a gree m e nts, I C H G C P, a n d all a p plica ble re g ulat or y 
re q uire me nts.  
 T he I n vesti gat or m ust mai ntai n all d oc u me ntati o n relati n g t o t he st u d y f or a 
peri o d of 2 years after t h e last mar keti n g  a p plicati o n a p pr o val, or if n ot a p pr o ve d 
2 years f oll o wi n g t he dis c o nti n ua nce of t h e i n vesti gati o n of trilacicli b. If it 

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bec o mes necessar y f or t h e S p o ns or or t he Re g ulat or y A ut h orit y t o r e vie w a n y 
d oc u me ntati o n relati n g t o t he st u d y, t he I n v esti gat or m ust per mit access t o s uc h 
rec or ds. N o rec or ds ma y be destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he 
writte n a p pr o val of t h e S p o ns or. N o rec or ds  ma y b e tra nsferre d t o a n ot her l ocati o n 
or part y wit h o ut writte n n otificati o n t o t h e S p o ns or. T he I n vesti gat or m ust e ns ure 
t hat t he rec or ds c o nti n ue t o be st ore d sec urel y f or as l o n g as t h e y are mai ntai ne d. 
1 4. 3.  
Disse mi n ati o n of Cli nic al St u d y D at a 
T he S p o ns or f ulfills its c o m mit me nt t o p u blicl y discl ose cli nical st u d y res ults t hr o u g h 
p osti n g t he res ults of st u dies o n w w w.cli nicaltrials. g o v, t he E u dra C T, a n d ot her p u blic 
re gistries i n acc or da n ce wit h ap plia ble l ocal la ws/re g ul ati o ns.  
Data res ults are p oste d i n a n o bjecti ve, acc ura te, bala nce d, a n d c o m plete m a n ner. Res ults are 
p oste d re gar dl ess of o utc o me of t he st u d y. 
1 4. 4.  
S o urce D oc u me nts 
S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste nce of t he p atie nt a n d s u bsta ntiate t he 
i nte grit y of t he d ata c ollecte d. S o urce d o c u me nts are file d at t he In vesti gat or’s site. All data 
re p orte d i n t he e C R F s h o ul d be s u p p orte d b y s o urce d oc u me nts; direct e ntr y of data i nt o t he 
e C R F is n ot per mitte d i n t his st u d y. 
Data re p orte d o n t he C R F or e ntere d i n t he e C R F t hat are tr a nscri be d fr o m s o urce d oc u m e nts 
m ust be c o nsiste nt wit h t he s o urce d o c u me nts or t he discre p a ncies m ust be e x plai ne d. T he 
I n v esti gat or ma y nee d t o re q uest pre vi o us me di cal rec or ds or tra nsfer rec or ds, de pe n di n g o n 
t he st u d y. Als o, c urre nt me dical rec or ds m ust be a vaila ble. 
1 4. 5.  
A u dits a n d I ns pecti o ns 
A ut h orize d re pres e ntati ves of G 1 T hera pe utics, a re g ulat or y a ut h orit y, a n I E C, or I R B ma y 
visit t he site t o perf or m a u dits or i ns pecti o ns, i ncl u di n g s o urce data verificati o n. T he p ur p ose 
of a n a u dit or i ns pecti o n is t o s yst e maticall y a n d i n de pe n de ntl y e x a mi ne all st u d y-rel ate d 
acti vities a n d d oc u me nts t o deter mi ne w het her t hese acti vities were c o n d ucte d, a n d data were 
rec or de d, a n al yze d, a n d acc urat el y re p ort e d accor di n g t o t he pr ot oc ol, G C P g ui deli nes of t h e 
I C H, a n d a n y a p plica ble re g ulat or y re q uire me nts. T he I n vesti gat or s h o ul d c o ntact 
G 1 T hera p e utics i m me diatel y if c o ntact e d b y a re g ulat or y a ge nc y a b o ut a n i ns pecti o n. 

Pr ot oc ol A me n d me nt 1 
 
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Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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1 5.  
P U B LI C A TI O N P O LI C Y 
B y si g ni n g t he st u d y pr ot oc ol, t he I n vesti gat or a n d his or her i nstit uti o n a gree t hat t he res ults 
of t he st u d y ma y b e use d b y G 1 T h era p e utics f or t he p ur p oses of nati o nal a n d i nter nati o nal 
re gistrati o n, p u blicati o n, a n d i nf or mati o n f or me di cal a n d p har mace utical pr ofessi o nals. If 
necessar y, t he a ut h orities will be n otifie d of t he I n vesti gat or’s na me, a d dress, q ualificati o ns, 
a n d e xte nt of i n v ol ve me nt. 
I nitial p u blicati o n of t he res ults of t his st u d y will b e of a c o o p erati ve nat ur e t hat ma y i ncl u de 
a ut h ors re prese nti n g t he S p o ns or, I n v esti gat or(s ), a n d c olla b orati n g sci e ntists. I n de p e n de nt 
p u blicati o ns b y i n v ol ve d i n di vi d uals ma y f oll o w. I n vesti gat ors a n d t heir i nstit uti o ns a gree n ot 
t o p u blis h or p u blicl y prese nt a n y i nteri m res ults of st u dies wit h o ut t he pri or writte n c o nse nt 
of G 1 T hera pe utics. G 1 T hera p e utics reser ve s t he ri g ht t o re q u est m o dificati o n of a n y 
p u blicati o n, prese ntati o n or use b y t he I n v esti gat or if s uc h acti vit y m a y je o par dize a pate nt 
a p plicati o n, a n e xisti n g pate nt, or ot her pr o prie tar y ri g hts. G 1 T h era p e utics s hall deter mi ne 
or der of a ut h ors hi p of a n y p u blicati o n c o m bi ni n g all cli nical res ults of t his st u d y. 

Pr ot oc ol A me n d me nt 1 
 
G 1 T 2 8- 2 1 3 
Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
8 4 
 
 
  
 
1 6.  
R E F E R E N C E S 
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gra n ul oc yte- c ol o n y sti m ulati n g fact or t o re d u ce t he i nci de nce of c h e m ot hera p y-i n d u ce d 
fe brile ne utr o p e nia i n a d ult patie nts wit h l y m p h o pr oliferati ve dis or d ers a n d s oli d t u m ors. E ur 
J Ca ncer. 2 0 1 1; 4 7: 8- 3 2. 
A m br o gi F, F or nili M, B oracc hi P, et al. Tr o p- 2 is a deter mi na nt of breast ca ncer s ur vi val 
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2 0 1 4; 9( 5):e 9 6 9 9 3. 
Ara nes p ®  ( dar be p o eti n al p ha) Prescri bi n g I nf or mati o n. A m ge n. 2 0 1 1. 
As g h ar U S, Barr A R, C utts R, et al. Si n gle- cell d y na mics deter mi nes res p o nse t o C D K 4/ 6 
i n hi biti o n i n tri ple- ne gati ve breast ca ncer. Cli n Ca ncer Res. 2 0 1 7; 2 3: 5 5 6 1- 7 2. 
Bar di a A, H ur vitz S A, T ola ne y S M, et al. Sacit uz u ma b G o viteca n i n Metastatic Tri ple-
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Barr uet o L, Ca mi ner o F, Cas h L. Resis ta nce t o c hec k p oi nt i n hi biti o n i n ca ncer 
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3 7. 
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1 9 8 2; 2 9- 4 1. 
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Car d os o F, Pal uc h- S hi m o n S, Se n k us E, et al. 5t h E S O- E S M O i nter nati o nal c o nse ns us 
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Pr ot oc ol A me n d me nt 1 
 
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8 5 
 
 
  
 
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C hea n g M C, V o d u c D, Baj di k C, et al. Basal-li ke breast c a ncer defi n e d b y fi ve bi o mar kers 
has s u peri or pr o g n ostic v al ue t ha n tri ple- ne gati ve p he n ot y p e. Cli n Ca ncer Res. 
2 0 0 8; 1 4( 5): 1 3 6 8- 7 6. 
Da niel D, K uc h a va V, B o n dare n k o I, et al. Trilacicli b decreases m yel os u p pressi o n i n 
e xte nsi ve-sta ge s m all cell l u n g ca n cer patie nts  recei vi n g first-li ne c he m ot h era p y pl us 
atez oliz u ma b. E S M O A n n ual Meeti n g 2 0 1 9; Barcel o na, S pai n; Se p 2 0 1 9 (a bstr 1 7 4 2 P D).  
Da niel D, K uc h a va V, B o n dare n k o I, et al. Trilacicli b pri or t o c he m ot hera p y a n d 
atez oliz u ma b i n patie nts wit h ne wl y dia g n os e d  e xte nsi ve-sta ge s mall cell l u n g ca ncer: A 
m ultice ntre, ra n d o mise d, d o u ble- bli n d, place b o-c o ntr olle d P hase II trial [ p u blis he d o nli ne 
a hea d of pri nt, 2 0 2 0 Dec 2 1]. I nt J Ca ncer. 2 0 2 0; 1 4 8( 1 0): 2 5 5 7- 7 0. 
De n g J, Wa n g E S, J e n ki ns R W, et al. C D K 4/ 6 i n hi biti o n a u g me nts a ntit u m or i m m u nit y b y 
e n ha nci n g T- cell acti vati o n. Ca ncer Dis c o v. 2 0 1 8; 8: 2 1 6- 3 3. 
Eise n ha uer E A, T herasse P, B o gaerts J, et al. Ne w res p o nse e v al uati o n criteria i n s oli d 
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Fares C M, Va n Alle n E M, Dra ke C G, et al. Mec ha nis ms of resista nce t o i m m u ne c hec k p oi nt 
bl oc ka de: W h y d o es c hec k p oi nt i n hi bit or i m m u n ot hera p y n ot w or k f or all patie nts? 2 0 1 9 
A S C O E d ucati o nal B o o k. 
F o o d a n d Dr u g A d mi nistrati o n ( F D A) G ui da n ce f or I n d ustr y, Cli nical Trial E n d p oi nts f or t he 
A p pr o val of Ca n cer Dr u gs a n d Bi ol o gics. 2 0 0 8. 
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Nat ure 2 0 1 7; 5 4 8( 7 6 6 8): 4 7 1- 5. 
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Recei vi n g T o p oteca n f or S mall Cell L u n g Ca n cer: Res ults fr o m  a Ra n d o mize d, D o u ble-
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Pr ot oc ol A me n d me nt 1 
 
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He S, R o berts PJ, S orre nti n o J A, et al. Tra nsie nt C D K 4/ 6 i n hi biti o n pr otects he mat o p oietic 
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2 0 1 7 b; 1 1 2: 7 5- 8 0. 
H orsle y V, Ali pra ntis A O, P ola k L, et al.  N F A Tc 1 bala nces q uies ce n ce a n d pr oliferati o n of 
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2 0 0 9; 9( 1): 2 9- 3 3.  
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Ke ytr u da ®  ( pe m br oliz u ma b) Prescri bi n g I nf or mati o n. Merc k. 2 0 2 0. 
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Breast Ca ncer. Versi o n 5. 2 0 2 0. N C C N, F ort Was hi n gt o n, P A. 

Pr ot oc ol A me n d me nt 1 
 
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Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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Nati o nal C o m pre he nsi ve Ca ncer Net w or k. N C C N Cli nical Practice G ui deli nes f or 
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2 0 2 0; Sa n A nt o ni o, T X; Dece m b er 8- 1 1, 2 0 2 0. 
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N O A H st u d y. Cli n Ca ncer Res. 2 0 1 4; 2 0: 5 1 1- 2 1 
Pr ocrit ®  (e p oeti n al p ha) Prescri bi n g I nf or m ati o n. J a nsse n Pr o d ucts L P. 2 0 1 7. 
Ra mse y M R, Kris h na m urt h y J, Pei X H, et al. E x pressi o n of p 1 6I n k 4a C o m pe nsates f or 
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2 0 0 7; 6 7: 4 7 3 2- 4 1. 
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sacit uz u ma b g o viteca n i n t he p hase 3 A S C E NT st u d y i n patie nts wit h metastatic tri ple-
ne gati ve breast ca n cer. A bstract P S 1 1- 0 9. 8- 1 1 Dec 2 0 2 0 Breast Ca ncer S y m p osi u m. Sa n 
A nt o ni o, Te x as. 
Sc haer D A, Bec k ma n n R P, De m pse y J A, et al. T h e C D K 4/ 6 i n hi bit or a be macicli b i n d uces a 
T cell i nfla me d t u m or micr oe n vir o n me nt a n d e n ha nces t he efficac y of P D- L 1 c h ec k p oi nt 
bl oc ka de. Cell Re p. 2 0 1 8; 2 2: 2 9 7 8- 9 4. 
Sc hiffer C A, A n d ers o n K C, Be n nett C L, et al. Platelet tra nsf usi o n f or p atie nts wit h ca ncer: 
cli nical practice g ui deli n es of t he A merica n S ociet y of Cli nical O nc ol o g y. J Cli n O nc ol. 
2 0 0 1; 1 9( 5): 1 5 1 9- 3 8. 
Se me n o va E A, N a gel R, Ber ns A. Ori gi ns, ge netic la n dsca pe, a n d e mer gi n g t hera pies of 
s mall cell l u n g ca ncer. Ge nes De v 2 0 1 5; 2 9: 1 4 4 7– 6 2. 
S mit h R E. Tre n ds i n rec o m me n dati o ns f or m yel os u p pressi ve c h e m ot hera p y f or t he treat me nt 
of s oli d t u m ors. J Natl C o m pr Ca nc Net w. 2 0 0 6; 4: 6 4 9 – 5 8. 
S mit h TJ, B o hl ke K, L y ma n G H, et al. Rec o m me n dati o ns f or t he Use of W B C Gr o wt h 
Fact ors: A m erica n S oci et y of Cli nical O n c ol o g y Cli nical Practice G ui deli ne U p date. J Cli n 
O nc ol. 2 0 1 5; 3 3: 3 1 9 9- 2 1 2. 
S orre nti n o J, Lai A, Str u m J, R o berts PJ. Tr ilacicli b ( G 1 T 2 8), a C D K 4/ 6 i n hi bit or, e n ha nces 
t he effic ac y of c o m bi nati o n c he m ot hera p y a nd i m m u ne c hec k p oi nt i n hi bit or treat me nt i n 
precli nical m o dels. A merica n Ass ociati o n f or Ca n cer  Researc h A n n ual Me eti n g. Ca ncer Res. 
2 0 1 7; 7 7( 1 3): 5 6 2 8. 

Pr ot oc ol A me n d me nt 1 
 
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Versi o n 2. 0 date d 1 5 N o v 2 0 2 1 
 
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S orre nti n o J A, Bisi J E, T h o m ps o n D, et al. Tr ilaci cli b, a C D K 4/ 6 i n hibit or, d oes n ot i m pair 
t he effic ac y of c he m ot hera p y i n C D K 4/ 6- de p e n de nt t u m or m o dels. 3 0t h E O R T C- N CI- A A C R 
S y m p osi u m. 1 3- 1 6 N o v e m ber 2 0 1 8. D u bli n, Irela n d. 
Star o d u b A N, Ocea n AJ, S ha h M A, et al. First-i n- H u ma n Trial of a N o vel A nti- Tr o p- 2 
A nti b o d y- S N- 3 8 C o nj u gate, Sacit uz u ma b G o vit eca n, f or t h e Treat me nt of Di verse Metast atic 
S oli d T u m ors. Cli n Ca ncer Res. 2 0 1 5; 2 1( 1 7): 3 8 7 0- 8.  
Ta n A R, Wri g ht G S, T h u m mala A R, et al. Trilacicli b pl us c he m ot hera p y vers us 
c he m ot hera p y al o ne i n p atie nts wit h metastatic tri ple- ne gati ve breast c a ncer: a m ultice ntre, 
ra n d o mize d, o pe n-la bel, P hase 2 trial. La ncet O nc ol. 2 0 1 9; 2 0: 1 5 8 7- 6 0 1. 
Tece ntri q ®  (at ez oliz u ma b) Prescri bi n g I nf or mati o n. Ge ne ntec h, I nc. 2 0 2 0. 
Te h J L F, A pli n A E. Arreste d De vel o p me nts: C D K 4 / 6 I n hi bit or Resista nce a n d Alterati o ns i n 
t he T u m or I m m u n e Micr oe n vir o n me nt. Cli n Ca ncer Res. 2 0 1 9; 2 5( 3). 
Tr o del v y ®  (sacit uz u ma b g o viteca n- hzi y) Prescri bi n g I nf or mati o n. I m m u n o me dics, I nc. 2 0 2 1. 
Weiss J, G ol dsc h mi dt J, A n dric Z, et al. Effects of Trilacicli b o n C he m ot hera p y-I n d uce d 
M yel os u p pressi o n a n d Patie nt- Re p orte d O utc o m e s i n Patie nts wit h E xte nsi ve- Sta ge S mall 
Cell L u n g Ca ncer: P o ole d Res ults fr o m T hree P hase II Ra n d o mize d, D o u ble- Bli n d, Place b o-
C o ntr olle d St u dies [ p u blis he d o nli ne a hea d of pri nt, 2 0 2 1 Mar 2 6]. Cli n L u n g Ca ncer. 
2 0 2 1; S 1 5 2 5- 7 3 0 4( 2 1) 0 0 0 6 4- 4. 
Weiss J M, Cs oszi T, Ma gla k eli dze M, et al. M yel o preser vati o n wit h t he C D K 4/ 6 i n hi bit or 
trilacicli b i n patie nts wit h s mall-cell l u n g ca ncer recei vi n g first-li ne c he m ot hera p y: a p has e 
I b/r a n d o mize d p hase II trial. A n n O nc ol. 2 0 1 9; 3 0: 1 6 1 3- 2 1. 
W u, Jia nr o n g. Sa m ple siz e calc ulati o n f or t he o n e-sa m ple l o g-ra n k t est. P har mace utical 
Statistics. 2 0 1 5; V ol u me 1 4: 2 6- 3 3. 
Yar dle y D A, C ole ma n R, C o nte P, et al. na b- Paclita xel pl us car b o plati n or ge mcita bi ne 
vers us ge mcita bi ne pl us car b o plati n as first-li ne tr eat me nt of patie nts wit h tri ple- ne gati ve 
metastatic breast ca ncer: res ults fr o m t he t n Acit y trial. A n n O nc ol. 2 0 1 8; 2 9( 8): 1 7 6 3- 7 0.  

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1 7.  
A P P E N DI C E S 
1 7. 1.  
Cli nic al L a b or at or y Tests 
 T he ti mi n g a n d la b orat or y tests deta ile d i n Sc h e d ule of Assess me nts (Ta bl e 6 ) 
will be perf or me d b y a l o cal la b orat or y.  
 Pr ot oc ol-s pecific re q uire me nts f or i ncl usi o n or e x cl usi o n of patie nts are d etaile d 
i n Secti o n 7  of t he pr ot oc ol. 
 A d diti o nal tests ma y be p erf or me d at a n y ti me d uri n g t he st u d y as d eter mi ne d 
necessar y b y t he I n v esti gat or or re q uire d b y l ocal re g ulati o ns 
T a ble 1 3:  
Pr ot oc ol- S pecifie d  S afet y L a b or at or y Assess me nts 
L a b or at or y Assess me nt 
P ar a met ers 
He m at ol o g y 
W B C 
He m o gl o bi n 
A bs ol ute ne utr o p hil 
c o u nt 
Platelets 
L y m p h oc ytes 
He mat ocrit 
Ser u m C he mistr y 
Bl o o d Urea Nitr o ge n 
( B U N) or Urea 
Ser u m Creati ni ne 
Bicar b o nate 
As partate 
A mi n otra nsferase 
( A S T) 
Ala ni ne 
A mi n otra nsferase 
( A L T) 
Calci u m 
P otassi u m 
S o di u m 
C hl ori de 
Gl uc ose 
T otal Pr otei n 
Al b u mi n 
Al kali ne 
p h os p hatase  
T otal Bilir u bi n 
 
Ot her Tests 
Ser u m or uri ne h u ma n c h ori o nic g o na d otr o pi n ( h C G) pre g na nc y 
test (f or W O C B P o nl y) 
h C G = h u ma n c h ori o nic g o na d otr o pi n; W B C = w hite bl o o d cell; W O C B P = w o ma n of c hil d beari n g p ote ntial 
 
 

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1 7. 2.  
A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, a n d F oll o w- u p 
1 7. 2. 1.  
Defi niti o n of A E 
A E Defi niti o n 
 
A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y patie nt, te m p orall y 
ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or n ot c o nsi dere d relate d t o t he st u d y 
i nter ve nti o n. 
 
N O T E: A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he 
use of st u d y i nter ve nti o n. 
E ve nts Meeti n g t he A E Defi niti o n  
 
A n y a b n or mal la b orat or y test res ults ( e. g., he mat ol o g y, c he mistr y) or ot her safet y assess me nts 
(e. g., E C G, ra di ol o gical sca ns, vital si g ns meas ure me nts), i ncl u di n g t h ose t hat w orse n fr o m 
baseli ne, c o nsi dere d cli nicall y si g nifica nt a n d re q uire cli nical i nter ve nti o n or f urt her 
i n vesti gati o n ( be y o n d or deri n g a re peat [c o nfir mat or y] test) i n t he me dical a n d scie ntific 
j u d g me nt of t he I n vesti gat or (i.e., n ot relate d t o pr o gressi o n of u n derl yi n g disease) u nless t he y 
are ass ociate d wit h a n alrea d y re p orte d cli nical e ve nt, e. g., ele vate d li ver e nz y mes i n a patie nt 
wit h ja u n dice. 
 
E xacer bati o n of a c hr o nic or i nter mitte nt pre- e xisti n g c o n diti o n i ncl u di n g eit her a n i ncrease i n 
fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n. 
 
Ne w c o n diti o ns detecte d or dia g n ose d after st u d y i nter ve nti o n a d mi nistrati o n e ve n t h o u g h it 
ma y ha ve bee n prese nt bef ore t he start of t he st u d y. 
 
Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y i nter ve nti o n 
or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as a n A E/ S A E u nless it is a n 
i nte nti o nal o ver d ose ta ke n wit h p ossi ble s uici dal/self-har mi n g i nte nt. S uc h o ver d oses s h o ul d be 
re p orte d re gar dless of se q uelae. 
E ve nts N O T Meeti n g t he A E Defi niti o n  
 
A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safet y assess me nts 
w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y t he I n vesti gat or t o be m ore 
se vere t ha n e x pecte d f or t he patie nt’s c o n diti o n. 
 
T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
di sease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he patie nt’s c o n diti o n. 
 
Me dical or s ur gical pr oce d ure (e. g. , e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat lea ds t o t he 
pr oce d ure is t he A E. 
 
Sit uati o ns i n w hic h a n u nt o war d me dical occ urre n ce di d n ot occ ur (s ocial a n d/ or c o n ve nie nce 
a d missi o n t o a h os pital). 
 
A ntici pate d da y-t o- da y fl uct uati o ns of pre-e x isti n g disease(s) or c o n diti o n(s) prese nt or 
detecte d at t he start of t he st u d y t hat d o n ot w orse n. 

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1 7. 2. 2.  
Defi niti o n of S A E 
If a n e v e nt is n ot a n A E per defi niti o n a b o ve, t h e n it ca n n ot be a n S A E e v e n if seri o us 
c o n diti o ns are met (e. g., h os pitaliz ati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y, d eat h 
d ue t o pr o gressi o n of dis ease). 
A S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose: 
1.  Res ults i n de at h 
2.  Is life-t hre ate ni n g 
T he ter m 'life -t hreate ni n g' i n t he defi niti o n of 'seri o us' refers t o a n e ve nt i n w hic h t he patie nt was at 
ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n e ve nt, w hic h h y p ot heticall y mi g ht ha ve 
ca use d deat h, if it were m ore se vere.  
3.  Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n 
I n ge neral, h os pitalizati o n si g nifies t hat t he patie nt has bee n detai ne d ( us uall y i n v ol vi n g at least a n 
o ver ni g ht sta y) at t he h os pital or  e mer ge nc y war d f or o bser vati o n a n d/ or treat me nt t hat w o ul d n ot 
ha ve bee n a p pr o priate i n t he p h ysicia n’s office or o ut patie nt setti n g. C o m plicati o ns t hat occ ur 
d uri n g h os pitalizati o n are A Es. If a c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her  
seri o us criteria, t he e ve nt is seri o us. 
H os pitalizati o n f or electi ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot w orse n fr o m baseli ne 
is n ot c o nsi dere d a n A E. 
4.  Res ults i n persiste nt dis a bilit y/i nc a p acit y 
 
T he ter m disa bilit y mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct n or mal life 
f u ncti o ns. 
 
T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical si g nifica nce 
s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, i nfl ue nza, a n d acci de ntal tra u ma 
(e. g., s prai ne d a n kle) w hic h ma y i nterfere wit h or pre ve nt e ver y da y life f u ncti o ns b ut d o n ot 
c o nstit ute a s u bsta ntial disr u pti o n. 
5.  Is a c o n ge nit al a n o m al y/ birt h defect 
6.  Ot her sit u ati o ns: 
 
Me dical or scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w het her S A E re p orti n g is 
a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical e ve nts t hat ma y n ot be i m me diatel y 
life-t hreate ni n g or res ult i n deat h or h os pitalizati o n b ut ma y j e o par dize t he patie nt or ma y 
re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he 
a b o ve defi niti o n. T hese e ve nts s h o ul d us uall y be c o nsi dere d seri o us. 
 
E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt i n a n 
e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias or c o n v ulsi o ns t hat 
d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of dr u g de pe n de nc y or dr u g a b use.  
 

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1 7. 2. 3.  
Rec or di n g a n d F oll o w- U p of A E a n d/ or S A E 
A E a n d S A E Rec or di n g 
 
W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he I n vesti gat or t o re vie w all 
d oc u me ntati o n (e. g., h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostics re p orts) 
relate d t o t he e ve nt. 
 
T he I n vesti gat or will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t he e C R F. 
 
It is n ot acce pta ble f or t he In vesti gat or t o se n d p h ot oc o pies of t he patie nt’s me dical rec or ds t o 
G 1 T hera pe utics ( or desi g nee) i n lie u of c o m pleti o n of t he A E/ S A E e C R F pa ge or pa per S A E 
Re p ort F or m. 
 
T here ma y be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are re q ueste d b y 
G 1 T hera pe utics ( or desi g nee). I n t his case, all patie nt i de ntifiers, wit h t he e xce pti o n of t he 
patie nt n u m ber, will be re dacte d o n t he c o pies of t he me dical rec or ds bef ore s u b missi o n t o G 1 
T hera pe utics ( or desi g nee). 
 
T he I n vesti gat or will atte m pt t o es ta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis ( n ot t he i n di vi d ual 
si g ns/s y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 
 
All S A Es s h o ul d be re p orte d t o G 1 T hera pe utics P V G ( or desi g nee) wit hi n 2 4 h o urs of 
n otificati o n o n a S A E F or m i n t he e C R F. A n y rele va nt s o urce data relate d t o t he S A E t hat 
ca n n ot be e ntere d i n E D C s h o ul d be e maile d or fa xe d t o G 1 T hera pe utics P V G ( or desi g nee): 
G 1 T her a pe utics P h ar m ac o vi gil a nce 
E mail: safet yre p orti n g @ g 1t hera pe utics.c o m 
Fa x: + 1- 9 8 4- 2 8 5- 7 1 3 1 
Assess me nt of I nte nsit y 
I nte nsit y will be ass esse d usi n g N CI- C T C A E v 5. 0 criteria, as f oll o ws: 
 
Gra de 1: Mil d; as y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y; 
i nter ve nti o n n ot i n dicate d. 
 
Gra de 2: M o derate; mi ni mal, l ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g 
a ge-a p pr o priate i nstr u me ntal acti vities of dail y li vi n g. 
 
Gra de 3: Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life-t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitaliza ti o n i n dicate d; disa bli n g; li miti n g self-care 
acti vities of dail y li vi n g. 
 
Gra de 4: Life-t hreate ni n g c o nse q ue nces; ur ge nt i nter ve nti o n i n dicate d. 
 
Gra de 5: Deat h relate d t o A E. 

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A E a n d S A E Rec or di n g 
Assess me nt of C a us alit y 
 
T he I n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y i nter ve nti o n a n d eac h 
occ urre nce of eac h A E/ S A E ( Relate d or N ot Relate d); i.e., is t here a “reas o na ble p ossi bilit y” 
t he st u d y i nter ve nti o n ca use d t he e ve nt ( yes/ n o). 
 
A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot be r ule d o ut. 
 
T he I n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p. 
 
Alte r nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her ris k fact ors, 
as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u d y i nter ve nti o n a d mi nistrati o n will be 
c o nsi dere d a n d i n vesti gate d. 
 
T he I n vesti gat or will als o c o ns ult t he I B a n d/ or Pr o d uct I nf or mati o n, f or mar kete d pr o d ucts, i n 
his/ her assess me nt. 
 
F or eac h A E/ S A E, t he I n vesti gat or m ust  d oc u me nt i n t he me dical n otes t hat he/s he has 
re vie we d t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y. 
 
T here ma y be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he I n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o G 1 T hera pe utics P V G ( or desi g nee). H o we ver, it 
is ver y i m p orta nt t hat t he I n vesti gat or al wa ys ma ke a n assess me nt of ca usalit y f or e ver y e ve nt 
bef ore t he i nitial tra ns missi o n of t he S A E data t o G 1 T hera pe utics P V G ( or desi g nee). 
 
T he I n vesti gat or ma y c ha n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w- u p i nf or mati o n a n d 
se n d a S A E f oll o w- u p re p ort wit h t he u p date d ca usalit y assess me nt. 
 
T he ca usalit y assess me nt is o ne of t he criter ia use d w he n deter mi ni n g re g ulat or y re p orti n g 
re q uire me nts. 
F oll o w- u p of A Es a n d S A Es 
 
T he I n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d or as re q ueste d b y G 1 
T hera pe utics P V G ( or desi g nee; S A Es o nl y ) t o el uci date t he nat ure a n d/ or ca usalit y of t he 
A E or S A E as f ull y as p ossi ble. T his ma y i ncl u de a d diti o nal la b orat or y tests or 
i n vesti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her healt h care 
pr ofessi o nals. 
 
Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y c o m plete d e C R F. 
 
T he I n vesti gat or will s u b mit a n y ne w or u p date d S A E data t o G 1 T hera pe utics P V G ( or 
desi g nee) wit hi n 2 4 h o urs of recei pt of t he i nf or mati o n:  
G 1 T her a pe utics P h ar m ac o vi gil a nce 
E m ail: s afet yre p orti n g @ g 1t her a pe utics.c o m 
F a x: + 1- 9 8 4- 2 8 5- 7 1 3 1  

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1 7. 2. 4.  
Re p orti n g of S A Es 
S A E Re p orti n g t o G 1 T her a pe utics ( or desi g nee) vi a a n Electr o nic D at a C ollecti o n T o ol 
 
T he pri mar y mec ha nis m f or re p orti n g a n S A E t o G 1 T hera pe utics ( or desi g nee) will be t he 
electr o nic data c ollecti o n t o ol ( E D C). 
 
If t he electr o nic s yste m is u na vaila ble, t he n t he site will use t he pa per S A E Re p ort F or m i n 
or der t o re p ort t he e ve nt wit hi n 2 4 h o urs via e mail or fa x (see bel o w f or S A E re p orti n g 
c o ntact i nf or mati o n).  
 
T he site will e nter t he S A E data i nt o t he electr o nic s yste m as s o o n as it bec o mes a vaila ble. 
 
After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic data c ollecti o n t o ol will be ta ke n 
off-li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data. 
 
If a site recei ves a re p ort of a ne w S A E fr o m a st u d y patie nt or recei ves u p date d data o n a 
pre vi o usl y re p orte d S A E after t he electr o nic data c ollecti o n t o ol has bee n ta ke n off- li ne, t he n 
t he site s h o ul d re p ort t his i nf or mati o n o n a pa per S A E Re p ort f or m or n otif y t he Me dical 
M o nit or b y tele p h o ne. 
 
C o ntact f or S A E re p orti n g:  
G 1 T her a pe utics P h ar m ac o vi gil a nce 
E m ail: s afet yre p orti n g @ g 1t her a pe utics.c o m 
F a x: + 1- 9 8 4- 2 8 5- 7 1 3 1   
 
 
 
 

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1 7. 3.  
C o ntr ace pti ve G ui d a nce a n d C ollecti o n of Pre g n a nc y I nf or m ati o n 
W O C B P Defi niti o n 
W o m a n of C hil d be ari n g P ote nti al  
A w o ma n is c o nsi dere d fertile f oll o wi n g m e narc h e a n d u ntil bec o mi n g p ost- me n o pa usal 
u nless per ma ne ntl y steril e (see b el o w). 
If fertilit y is u nclear (e. g., a me n orr hea i n a d oles ce nts or at hletes), a d diti o nal e val uati o n 
s h o ul d be c o nsi dere d. 
W o me n i n t he f oll o wi n g c ate g ori es ar e n ot c o nsi dere d W o m a n of C hil d be ari n g 
P ote nti al 
1.  Pre me narc hal 
N ote: D oc u me ntati o n ca n c o me fr o m t he site pers o n nel’s re vie w of t he pati e nt’s 
me dical rec or ds, me dic al e xa mi nati o n, or me dical hist or y i nter vie w. 
2.  Pre me n o pa usal f e male wit h 1 of t he f oll o wi n g acce pta ble s ur gical steriliz ati o n 
tec h ni q ues: c o m plete or partial h yst erect o m y, bilateral t u bal li gati o n, or occl usi o n 
wit h s ur ger y at least 6 m o nt hs pri or t o d osi n g, or bilateral o o p h orect o m y wit h s ur ger y 
at least 2 m o nt hs pri or t o d osi n g. 
3.  P ost me n o pa usal fe male: defi ne d as s p o nta n e o us a me n orr hea f or > 1 2 m o nt hs pri or t o 
Scree ni n g wit h o ut alter nati ve ca use (e. g., i m pla nt a ble c o ntrace pti ve, si de effect of 
me dicati o n, etc.) a n d a ser u m f ollicle sti m ulati n g h or m o ne ( F S H) wit hi n t he 
la b orat or y’s refere n ce ra n ge f or p ost me n o pa us al f e males. 
 W o me n ta ki n g h or m o ne re place me nt t her a p y ( H R T) m ust disc o nti n ue H R T at 
least 2- 4 wee ks pri or t o Scree ni n g f or acc urate ass ess me nt of F S H (t h o u g h e x act 
i nter val will de pe n d o n t he t y p e a n d d osa ge of H R T a n d s h o ul d be deter mi ne d b y 
t he pri nci pal I n vesti gat or). 
C o ntr ace pti o n G ui d a nce 
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal re g ul ati o ns re gar di n g 
t he met h o ds of c o ntrace pti o n f or t h ose partici pati n g i n cli nical st u dies. 
 Male patie nts: Males m ust be s ur gi call y st erile pri or t o Scree ni n g wit h a p pr o priate 
d oc u me ntati o n (a bse n ce of s per m i n ejac ul ate 6 m o nt hs after pr o ce d ure) or ha ve a 
fe male part ner(s) w h o is eit her p ost me n o pa usal, s ur gicall y st erile, or usi n g 2 
f or ms of c o nc urre nt c o ntrace pti o n as d efi ned b el o w. I n a d diti o n, males m ust als o 
refrai n fr o m s per m d o n ati o n d uri n g t he st u d y a n d utilize a barrier met h o d wit h 
i nterc o urse d uri n g a n d f or 3 m o nt hs f oll o wi n g disc o nti n uati o n of treat me nt. 
 Fe male p atie nts: All fe males of c hil d beari n g p ote ntial m ust ha ve a ne gati v e ser u m 
β - h C G test res ult at Scree ni n g, o n Da y 1 of eac h c ycle, a n d at t he E n d of 
Treat me nt Visit.  
 Fe males m ust be eit her p ost me n o pa usal, s ur gicall y sterile, or a gree t o use 
2 c o nc urre nt f or ms of c o ntrace pti o n d uri n g t he st u d y a n d f or 6 m o nt hs f oll o wi n g 
last d ose of st u d y dr u g. Acce pt a ble f or ms of c o ntrace pti o n i ncl u de: 

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 Esta blis he d use of oral, i njecte d or i m pla nte d h or m o nal met h o ds of 
c o ntrace pti o n (sta ble d os e at least 3 m o nt hs pri or t o d osi n g) 
 I ntr a uteri ne d e vi ce or i ntra uteri ne s yste m 
 Barrier met h o ds of c o ntr ace pti o n: c o n d o m or occl usi ve ca p ( dia p hra g m or 
cer vical/ va ult ca ps) wit h s per mici dal f oa m/ gel/fil m/crea m/s u p p osit or y. Barrier 
met h o ds al o ne ( wit h o ut s per mici de) are n ot acce pta ble met h o ds. Li k e wise, 
s per mici de al o ne is n ot a n acce pta ble met h o d 
 Male steriliz ati o n pri or t o Scree ni n g wit h t he a p pr o priate p ost- vas ect o m y 
d oc u me ntati o n (a bse n ce of s per m i n t he ejac ulate 6 m o nt hs after pr oce d ure). 
F or fe male patie nts o n t h e st u d y, t he va sect o mize d male part ner s h o ul d be t he 
s ole part ner f or t hat patie nt 
 Tr ue a bsti ne nce w he n t his is i n li ne wit h t he preferre d a n d us ual lifest yle of 
t he patie nt. Peri o dic a bsti ne nce (e. g., cale n dar, o v ulati o n, s y m pt ot her mal, 
p ost- o v ulati o n met h o ds) a n d wit h dra wa l are n ot acce pta bl e met h o ds of 
c o ntrace pti o n 
 F or patie nts w h o are e x cl usi vel y i n sa me-s e x relati o ns hi ps, c o ntrace pti ve 
re q uire me nts d o n ot a p pl y. If a patie nt w h o is i n a sa me-se x relati o ns hi p at t he 
ti me of si g ni n g t he I C F b ec o mes e n ga ge d i n a heter ose x ual relati o ns hi p, t he y 
m ust a gree t o use c o ntrace pti o n as descri be d pre vi o usl y. If a patie nt w h o is 
a bsti ne nt at t he ti me of si g ni n g t he I C F bec o m es se x uall y acti ve, t he y m ust a gree 
t o use c o ntrace pti o n as d escri be d a b o ve. 
C ollecti o n of Pre g n a nc y I nf or m ati o n 
M ale p artici p a nts wit h p art ners w h o bec o me pre g n a nt 
 T he I n vesti gat or or d esi g nee will atte m p t t o c ollect pre g n a nc y i nf or mati o n o n a n y 
male patie nt’s fe m ale part ner w h o bec o m es pre g n a nt w hile t he male patie nt is i n 
t his st u d y. T his a p plies o nl y t o males w h o recei ve st u d y i nt er ve nti o n. 
 After o btai ni n g t he necessar y si g n e d i nf or me d c o nse nt fr o m t he pre g n a nt fe male 
part ner directl y, t he I n v esti gat or or d e si g n ee will rec or d pre g na n c y i nf or mati o n o n 
t he Pre g n a nc y –  I nitial Re p ort F or m a n d s u b mitte d t o G 1 T hera p e utics P V G or 
desi g nee wit hi n 2 4 h o urs of lear ni n g of t he p art ner’s pre g n a nc y. T h e fe mal e 
part ner will als o be f oll o we d t o deter mi ne t he o ut c o me of t he pre g na n c y. T he 
Pre g n a nc y –  F oll o w- u p Re p ort F or m s h o ul d be use d t o re p ort i nf or mati o n o n t he 
stat us of t he m ot her a n d c hil d a n d will be f or war de d t o G 1 T hera pe utics P V G or 
desi g nee. Ge n erall y, t he f oll o w- u p will be n o l o n ger t ha n 1 2 wee ks f oll o wi n g t he 
esti mate d deli ver y date. A n y ter mi nati o n of t he pre g n a nc y will be re p orte d 
re gar dl ess of fet al stat us ( prese n ce or a bse nce of a n o malies) or i n dicati o n f or t he 
pr oce d ure.  
C o ntact f or Pre g na n c y re p orti n g:  
G 1 T her a pe utics P h ar m ac o vi gil a nce
E m ail: s afet yre p orti n g @ g 1t her a pe utics.c o m
F a x: + 1- 9 8 4- 2 8 5- 7 1 3 1  

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Fe m ale P ati e nts w h o bec o me pre g n a nt 
 T he I n vesti gat or or d esi g nee will c ollect pr e g na nc y i nf or m ati o n o n a n y fe m ale 
patie nt w h o bec o mes pre g na nt w hile p artici pati n g i n t his st u d y. T he i nitial 
I nf or mati o n will be rec or de d o n t he Pre g na n c y Re p orti n g a n d O utc o me F or m 
( Pre g na nc y –  I nitial Re p ort F or m) a n d s u b mitte d t o G 1 P V G or desi g n ee wit hi n 
2 4 h o urs of lear ni n g of a patie nt’s pre g na n c y wit hi n 2 4 h o urs of lear ni n g of a 
patie nt’s pre g n a n c y.  
 T he patie nt will be f oll o we d t o deter mi ne t he o ut c o me of t he pre g na n c y. T he 
I n v esti gat or or desi g nee will c ollect f oll o w- u p i nf or mati o n o n t he patie nt a n d t he 
ne o nate a n d t h e i nf or mati o n will be c ollecte d o n t he Pre g na nc y –  F oll o w- u p 
Re p ort F or m a n d f or w ar de d t o G 1 T hera pe utics P V G or desi g nee. Ge n erall y, 
f oll o w- u p will n ot be re q uire d f or l o n ger t ha n 1 2 wee ks be y o n d t h e esti mate d 
deli ver y date. A n y t er mi nati o n of pre g na n c y will be re p ort e d, re gar dless of fetal 
stat us ( prese n ce or a bse n ce of a n o m alies) or i n dicati o n f or t he pr oce d ure. 
 W hile pre g na n c y itself is n ot c o nsi dere d t o be a n A E or S A E, a n y pre g na n c y 
c o m plicati o n or electi ve t er mi nati o n of a pre g na nc y f or me dical r eas o ns will be 
re p orte d as a n A E or S A E. A s p o nta ne o us a b orti o n ( occ urri n g at < 2 2 wee ks 
gestati o nal a ge) or still birt h ( occ urri n g at > 2 2 wee ks gestati o nal a ge) is al w a ys 
c o nsi dere d t o be a n S A E a n d will be re p ort e d as s uc h. A n y p ost-st u d y pre g na nc y 
relate d S A E c o nsi dere d reas o na bl y relate d t o t he st u d y i nter ve nti o n b y t he 
I n v esti gat or will be re p orte d t o G 1 T hera p e utics P V G or desi g nee. W hile t he 
I n v esti gat or is n ot o bli gate d t o acti vel y s ee k t his i nf or mati o n i n f or mer st u d y 
patie nts, he or s he ma y lear n of a n S A E t hr o u g h s p o nta ne o us re p orti n g. 
 A n y fe male p atie nt w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y will 
disc o nti n ue st u d y i nter ve nti o n. 
C o ntact f or Pre g na n c y re p orti n g:  
G 1 T her a pe utics P h ar m ac o vi gil a nce 
E m ail: s afet yre p orti n g @ g 1t her a pe utics.c o m 
F a x: + 1- 9 8 4- 2 8 5- 7 1 3 1 
 
 
 
 

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1 7. 4.  
Defi niti o ns of T u m or Res p o nse a n d Dise ase Pr o gressi o n ( per 
R E CI S T v 1. 1) 
T he deter mi nati o n of t u m or res p o nse a n d pr o gressi o n will be base d o n t he R E CI S T v 1. 1 
(Eise n ha uer, 2 0 0 9 ). Disease pr o gressi o n ma y als o be determi ne d cli nicall y b y t he I n vesti gat or.  
T u m or lesi o ns will be cat e g orize d as f oll o ws: 
Me as ur a ble lesi o ns : t u m or lesi o ns wit h a l o n gest dia meter ( meas ure d i n at least 1 di me nsi o n) 
wit h a mi ni m u m size as f oll o ws:  
 1 0 m m b y C T or M RI ( wit h a sca n sl ice t hic k ness of n o great er t ha n 5 m m) 
 Meas ura ble l y m p h n o des m ust be ≥1 5 m m o n t he s h ort a xis b y C T or M RI ( wit h a 
sca n slice t hic k ness of n o greater t ha n 5 m m); o nl y t he s h ort a xis is t o be meas ure d at 
baseli ne a n d f oll o w- u p.  
 B o ne lesi o ns: B o n e sca n, P E T sca n, or plai n fil ms are n ot c o nsi dere d a d e q u ate 
i ma gi n g tec h ni q u es t o meas ure b o n e lesi o ns. H o we ver, t hes e tec h ni q ues ca n be use d 
t o c o nfir m t he pres e nce or disa p peara nce of b o ne l esi o ns. L ytic b o ne l esi o ns or mi x e d 
l ytic- blastic lesi o ns, wit h i de ntifia ble s oft tiss ue c o m p o ne nts, t hat ca n be e val uate d b y 
cr oss-secti o nal i ma gi n g t ec h ni q ues s uc h as C T or M RI ca n be c o nsi dere d meas ura ble 
lesi o ns if t he s oft tiss ue c o m p o ne nt meets t he defi niti o n of meas ura bilit y d escri be d 
a b o ve. Bl astic b o ne lesi o ns are n o n- meas ura ble. 
 C ystic lesi o ns re prese nti n g c ystic met astases t hat meet t he defi niti o n of meas ura bilit y 
descri be d a b o ve ca n be c o nsi dere d meas ura b le lesi o ns. If prese nt, n o n c ysti c lesi o ns 
s h o ul d be selecte d as tar get lesi o ns f or t his st u d y. 
 A t u m or lesi o n t hat has bee n pre vi o usl y irra diate d ma y b e c o nsi dere d meas ura ble if 
u ne q ui v ocal gr o wt h of t h e lesi o n has bee n d e m o nstrate d.  
T ar get lesi o ns : At baseli ne, u p t o 5 meas ura bl e t u m or lesi o ns/l y m p h n o d es ( wit h a ma xi m u m of 
2 lesi o ns per or ga n) s h o ul d be i de ntifie d as tar get lesi o ns. Lesi o ns wit h t he l o n gest dia met er, t hat 
are re pres e ntati ve of all i n v ol ve d or ga ns, a n d f or w hic h re pr o d uci ble re p eate d meas ure m e nts ca n 
be o btai ne d s h o ul d be sel ecte d as t he t ar get lesi o ns. Mali g na nt l y m p h n o de is c o nsi dere d a n 
or ga n i n t his st u d y, t heref ore o nl y 2 mali g na nt l y m p h n o des (re gar dless of l ocati o n) ma y be 
selecte d as t ar get lesi o ns a n d all ot hers s h o ul d be e ntere d as n o ntar get lesi o ns. 
N o n- me as ur a ble Lesi o ns: t u m or lesi o ns wit h a l o n gest dia met er < 1 0 m m, l y m p h n o des wit h 
≥1 0 t o < 1 5 m m s h ort a xis, or n o n - meas ura ble lesi o ns s uc h as le pt o me ni n geal disease, ascites, 
ple ural or pericar dial eff usi o n, i nfla m mat or y brea st disease, l y m p ha n gitic i n v ol ve me nt of s ki n or 
l u n g, or a b d o mi nal masses/a b d o mi nal or ga n o me gal y i de ntifie d b y p h ysi cal e x a m t hat is n ot 
meas ura ble b y C T sca n or M RI.  
N o nt ar get lesi o ns : All ot her lesi o ns ( or sites of disease) i de ntifi e d at baseli ne s h o ul d be 
i de ntifie d as n o ntar get lesi o ns a n d rec or de d i n t he e C R F. Meas ure me nts of t hese lesi o ns are n ot 
re q uire d, b ut t he prese n ce, a bse nce, or u n e q ui v ocal pr o gressi o n of eac h n o ntar get lesi o n s h o ul d 
be rec or de d i n t he e C R F at eac h f oll o w u p ti me p oi nt. M ulti ple n o ntar get lesi o ns i n t he sa me 
or ga n ma y be n ote d as a si n gle ite m o n t he e C R F. 
 

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E v al u ati o n of T ar get Lesi o ns 
T he defi niti o ns f or t u m or res p o nse f or t he tar get lesi o n per R E CI S T v 1. 1 are as f oll o ws: 
C o m plete Res p o nse: Disa p peara nce of all tar get le si o ns. A n y p at h ol o gical l y m p h n o des ( w het her 
tar get or n o n-tar get) m ust ha ve re d u cti o n i n s h ort a xis t o < 1 0 m m ( < 1 c m). 
Partial Res p o nse: At least a 3 0 % decreas e i n t he s u m of t he dia meters of t ar get lesi o ns, ta ki n g as 
refere nce t he bas eli ne s u m dia meters. 
Pr o gressi ve Diseas e: At least a 2 0 % i ncreas e i n  t he s u m of t he dia meters of tar get lesi o ns, ta ki n g 
as refere n ce t he s mallest s u m o n st u d y (t his i ncl u des t he baseli ne s u m if t hat is t he s mallest o n 
st u d y). I n a d diti o n t o t he relati ve i ncrease of 2 0 %, t he s u m m ust als o de m o nstrate a n a bs ol ute 
i ncreas e of at least 5 m m ( 0. 5 c m). ( N ot e: t he a p peara nce of o ne or m ore n e w lesi o ns is als o 
c o nsi dere d pr o gressi o n). 
Sta ble Disease: Neit her s ufficie nt s hri n ka ge t o q ualif y f or P R n or s ufficie nt i ncrease t o q u alif y 
f or P D, ta ki n g as refere n ce t he s mallest s u m dia meters w hile o n st u d y. 
E v al u ati o n of N o n- T ar get Lesi o ns 
C o m plete Res p o nse: Disa p peara nce of all n o n-tar ge t lesi o ns a n d n or malizati o n of t u m or mar ker 
le vel. All l y m p h n o des m ust be n o n- pat h ol o gi cal i n size ( < 1 0 m m [ < 1 c m] s h ort a xis). 
N o n- C R/ N o n- P D: Persiste nce of o ne or m ore n o n-tar get lesi o n(s) a n d/ or mai nte na nce of t u m or 
mar ker le v el a b o ve t he n or mal li mits. 
Pr o gressi ve Diseas e: A p peara n ce of o ne or m ore  ne w lesi o ns a n d/ or u ne q ui v ocal pr o gressi o n of 
e xisti n g n o n- tar get lesi o ns. ‘ U ne q ui v ocal pr o gressi o n’ re pres e nts a s u bsta ntial i ncreas e i n o verall 
t u m or b ur de n s uc h t hat tr eat me nt s h o ul d be disc o nti n ue d e ve n i n t he setti n g of S D or P R i n t he 
tar get disease. Alt h o u g h a clear pr o gressi o n of “ n o n-tar get” l esi o ns o nl y is rare, t h e o pi ni o n of 
t he treati n g p h ysicia n s h o ul d pre vail i n s uc h circ u msta nces. 
A p pe ar a nce of Ne w Lesi o ns 
T he a p peara n ce of ne w l esi o n(s) is c o nsi dere d P D acc or di n g t o R E CI S T v 1. 1.  
Ti me p oi nt Res p o nse 
P ati e nts wit h Me as ur a ble Dise ase (i .e., T ar g et ± N o n- T ar get Dise as e) 
T ar get 
Lesi o ns 
N o n- T ar get Lesi o ns 
Ne w Lesi o ns 
O ver all Res p o nse 
C R 
C R 
N o 
C R 
C R 
N o n- C R/ N o n- P D 
N o 
P R 
C R 
N E 
N o 
P R 
P R 
N o n- C R/ N o n- P D/ N E 
N o 
P R 
S D 
N o n- C R/ N o n- P D/ N E 
N o 
S D 
N E 
N o n- P D 
N o 
N E 
P D 
A n y 
Yes or N o 
P D 
A n y 
P D a 
Yes or N o 
P D 
A n y 
A n y 
Yes 
P D 
C R =c o m plete res p o nse;  N E = n ot e val ua ble; P D: pr o gressi ve diseas e; P R = partial res p o nse; S D =sta ble disease. 

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N ote: P atie nts wit h a gl o bal d eteri orati o n of healt h stat us re q uiri n g disc o nti n uati o n of treat me nt wit h o ut o bj ecti ve 
e vi de nce of disease pr o gressi o n at t hat ti me s h o ul d be re p orte d as “sy m pt o m atic deteri or ati o n. ” E ver y eff ort s h o ul d 
be ma d e t o d oc u me nt t he o bj ecti ve pr o gressi o n e ve n after disc o nti n uati o n of treat me nt. 
a  U ne q ui v ocal pr o gressi o n i n n o n-tar get lesi o ns ma y be acce pte d as disease pr o gressi o n. 
 
P ati e nts wit h E v al u a ble or N o n- Me as ur a ble Dise ase O nl y (i.e., N o n- T ar get Dise as e) 
N o n- T ar get Lesi o ns 
Ne w Lesi o ns 
O ver all Res p o nse 
C R 
N o 
C R 
N o n- C R/ n o n- P D 
N o 
N o n- C R/ n o n- P D a 
N ot all e val uate d 
N o 
N E 
U ne q ui v ocal P D 
Yes or N o 
P D 
A n y 
Yes 
P D 
C R =c o m plete res p o nse;  N E = n ot e val ua ble; P D: pr o gressi ve disease; S D =sta ble disease. 
a  ‘N o n- C R/ n o n- P D’ is preferre d o ver ‘sta ble disease’ f or n o n -t ar get disease si nce S D is i ncreasi n gl y use d as a n 
e n d p oi nt f or assess me nt of efficac y i n s o me st u dies s o t o assi g n t his cate g or y w he n n o lesi o ns ca n be meas ure d is 
n ot a d vise d.